Influence of Pluronic (R) F68 on Ceftazidime Biological Activity in Parenteral Solutions

beta-Lactam antimicrobials are known to have a low concentration/therapeutic response. However, extending the period in which beta-lactam are free in the plasma does directly influence therapeutic outcomes. The objective of this study was to evaluate the influence of Pluronic (R) F68 on the antimicrobial activity of ceftazidime when admixed with aminophylline in parenteral solutions by the evaluation of its minimal inhibitory concentration (MIC) within 24 h. Ceftazidime, aminophylline, and Pluronics (R) F68 were evaluated using the MIC method against Escherichia coli and Pseudomonas aeruginosa, with these compounds individually and associated in the same parenteral solutions. When Pluronics (R) F68 was admixtured with ceftazidime alone or with ceftazidime and aminophylline, it was possible to observe lower MIC values not only at 24 h but also at 0 h for both microorganisms. This indicates that Pluronics (R) F68 may be able to enhance ceftazidime antimicrobial activity in the presence or absence of aminophylline. This fact suggests that Pluronics (R) F68 can be applied to allow the administration of ceftazidime under continuous infusion in parenteral solutions, beneficiating hospital pharmacotherapy. It may also be possible to reduce ceftazidime doses in formulations achieving the same therapeutic results. (C) 2010 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 100:715-720, 2011

Characterization of Brazilian lager and brown ale beers based on color, phenolic compounds, and antioxidant activity using chemometrics

BACKGROUND: Epidemiological studies have shown that beer has positive effects on inhibiting atherosclerosis, decreasing the content of serum low-density lipoprotein cholesterol and triglycerides, by acting as in vivo free radical scavenger. In this research, the antioxidant activity of commercial Brazilian beers (n = 29) was determined by the oxygen radical absorbance capacity (ORAC) and 1,1 -diphenyl-2-picrylhydrazyl (DPPH(center dot)) assays and results were analyzed by chemometrics. RESULTS: The brown ale samples (n = 11) presented higher (P < 0.05) flavonoids (124.01 mg L(-1)), total phenolics (362.22 mg L(-1)), non-flavonoid phenolics (238.21 mg L(-1)), lightness (69.48), redness (35.75), yellowness (55.71), color intensity (66.86), hue angle (59.14), color saturation (0.9620), DPPH(center dot) values (30.96% inhibition), and ORAC values (3,659.36 mu mol Trolox equivalents L(-1)), compared to lager samples (n = 18). Brown ale beers presented higher antioxidant properties (P < 0.05) measured by ORAC (1.93 times higher) and DPPH (1.65 times higher) compared to lager beer. ORAC values correlated well with the content of flavonoids (r = 0.47; P = 0.01), total phenolic compounds (r = 0.44; P < 0.01) and DPPH (r = 0.67; P < 0.01). DPPH values also correlated well to the content of flavonoids (r = 0.69; P < 0.01), total phenolic compounds (r = 0.60; P < 0.01), and non-flavonoid compounds (r = 0.46; P = 0.01). CONCLUSION: The results suggest that brown ale beers, and less significantly lager beers, could be sources of bioactive compounds with suitable free radical scavenging properties. (C) 2010 Society of Chemical Industry

Phenolic compounds content and antioxidant activity in pomace from selected red grapes (Vitis vinifera L. and Vitis labrusca L.) widely produced in Brazil

The phenolic compounds content and antioxidant activity of pomace from the vinification of grape varieties widely produced in Brazil (Cabernet Sauvignon, Merlot, Bordeaux and Isabel) were investigated with a view to their exploitation as a potential source of natural antioxidants. Cabernet Sauvignon grape pomace was found to have the highest content of total phenolic compounds (74.75 mg gallic acid equivalent (GAE)/g), the highest antioxidant activity (determined using the 2,2`-azino-bis(3-ethylbenzothiazoline-6-sulfonate) (ABTS) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging methods; 485.42 and 505.52 mu Mol Trolox equivalent antioxidant capacity (TEAC)/g, respectively), and the highest reducing power (determined using the FRAP method; 249.46 mu Mol TEAC/g). The Bordeaux variety showed the highest oxidation inhibition power (41.13%), determined using the beta-carotene/linoleic acid method and the highest content of total anthocyanins (HPLC; 29.17 mg/g). Catechin was the most abundant non-anthocyanic compound identified in the grape pomace (150.16 mg/100 g) for all varieties. In this study, pomaces of the red wine vinification of Cabernet Sauvignon and Bordeaux varieties showed the highest potential as a source of antioxidant compounds and natural colourants, respectively. (C) 2011 Elsevier Ltd. All rights reserved.

Synergism on antioxidant activity between natural compounds optimized by response surface methodology

Despite the increase in the use of natural compounds in place of synthetic derivatives as antioxidants in food products, the extent of this substitution is limited by cost constraints. Thus, the objective of this study was to explore the synergism on the antioxidant activity of natural compounds, for further application in food products. Three hydrosoluble compounds (x(1) = caffeic acid, x(2) = carnosic acid, and x(3) = glutathione) and three liposoluble compounds (x(1) = quercetin, x(2) = rutin, and x(3) = genistein) were mixed according to a ""centroid simplex design"". The antioxidant activity of the mixtures was analyzed by the ferric reducing antioxidant power (FRAP) and oxygen radical absorbance capacity (ORAL) methodologies, and activity was also evaluated in an oxidized mixed micelle prepared with linoleic acid (LAOX). Cubic polynomial models with predictive capacity were obtained when the mixtures were submitted to the LAOX methodology ((y) over cap = 0.56 x(1) + 0.59 x(2) + 0.04 x(3) + 0.41 x(1)x(2) - 0.41 x(1)x(3) - 1.12 x(2)x(3) - 4.01 x(1)x(2)x(3)) for the hydrosoluble compounds, and to FRAP methodology ((y) over cap = 3.26 x(1) + 2.39 x(2) + 0.04 x(3) + 1.51 x(1)x(2) + 1.03 x(1)x(3) + 0.29 x(1)x(3) + 3.20 x(1)x(2)x(3)) for the liposoluble compounds. Optimization of the models suggested that a mixture containing 47% caffeic acid + 53% carnosic acid and a mixture containing 67% quercetin + 33% rutin were potential synergistic combinations for further evaluation using a food matrix.

Design, synthesis, antimicrobial activity and molecular modeling studies of novel benzofuroxan derivatives against Staphylococcus aureus

Molecular modi. cation is a quite promising strategy in the design and development of drug analogs with better bioavailability, higher intrinsic activity and less toxicity. In the search of new leads with potential antimicrobial activity, a new series of 14 4-substituted [N`-(benzofuroxan-5-yl) methylene] benzohydrazides, nifuroxazide derivatives, were synthesized and tested against standard and multidrug-resistant Staphylococcus aureus strains. The selection of the substituent groups was based on physicochemical properties, such as hydrophobicity and electronic effect. These properties were also evaluated through the lipophilic and electrostatic potential maps, respectively, considering the compounds with better biological pro. le. Twelve compounds exhibited similar bacteriostatic activity against standard and multidrug-resistant strains. The most active compound was the 4-CF(3) substituted derivative, which presented a minimum inhibitory concentration (MIC) value of 14.6-13.1 mu g/mL, and a ClogP value of 1.87. The results highlight the benzofuroxan derivatives as potential leads for designing new future antimicrobial drug candidates. (C) 2009 Elsevier Ltd. All rights reserved.

Gastric anti-ulcer activity of leaf fractions obtained of polar extract from Wilbrandia ebracteata in mice

Leaf fractions of Wilbrandia ebracteata were investigated for anti-ulcerogenic effects in ethanol and indomethacin-induced gastric ulcer assays in mice. Protective anti-ulcer effects were detected only in the ethanol-induced ulcer assay effects after pre-treatment with MeOH extract, MeOH chlorophyll-free, chlorophyll residue, HEX, DCM, aqueous MeOH fraction, ethyl acetate (EtOAc) and aqueous fractions. A potent anti-ulcerogenic effect was determined after pre-treatment of animals with EtOAc fraction, which was fractionated for isolation of active constituents. Seven flavonoids, 3`,4`,5,6,7,8-hexahydroxyflavonol, orientin, isoorientin, vitexin, isovitexin, luteolin, 6-methoxi-luteolin were isolated from the leaves of W. ebracteata (Cucurbitaceae) by chromatographic methods and identified by their spectral data. The data suggest that flavonoids are active anti-ulcerogenic compounds from leaves of W. ebracteata. The ability of scavenging free radicals was evaluated by DPPH reduction assay by TLC of flavonoids isolated.

Cytotoxic activity of a dichloromethane extract and fractions obtained from Eudistoma vannamei (Tunicata: Ascidiacea)

This study consists of the bioassay-guided fractionation of the dichloromethane extract from Eudistoma vannamei and the pharmacological characterization of the active fractions. The dried hydromethanolic extract dissolved in aqueous methanol was partitioned with dichloromethane and chromatographed on a silica gel flash column. The anti-proliferative effect was monitored by the MTT assay. Four of the latest fractions, numbered 14 to 17, which held many chemical similarities amongst each other, were found to be the most active. The selected fractions were tested for viability, proliferation and death induction on cultures of HL-60 promycloblastic leukemia cells. The results suggested that the observed cytotoxicity is related to apoptosis induction. (C) 2007 Elsevier Inc. All rights reserved.

Lercanidipine reduces matrix metalloproteinase-2 activity and reverses vascular dysfunction in renovascular hypertensive rats

Increased expression/activity of matrix metalloproteinases (MMPs), especially MMP-2, plays a role in the vascular alterations induced by hypertension, and increased oxidative stress is a major factor activating MMPs. Here, we hypothesized that lercanidipine, a calcium channel blocker, could attenuate the increases in oxidative stress and MMP-2 expression/activity in the two-kidney, one-clip (2K-1C) hypertensive rats. Sham-operated or 2K-1C hypertension rats were treated with lercanidipine 2.5 mg/kg/day (or vehicle) starting three weeks after hypertension was induced. Systolic blood pressure was monitored weekly. After five weeks of treatment, aortic rings were isolated to assess endothelium-dependent and independent relaxations. Quantitative morphometry of structural changes in the aortic wall were studied in hematoxylin/eosin sections. Aortic MMP-2 levels were determined by gelatin zymography. Aortic MMP-2/tissue inhibitor of metalloproteinases (TIMP)-2 mRNA levels were determined by quantitative real-time RT-PCR. Plasma thiobarbituric acid reactive substances concentrations were determined using a fluorometric method. Lercanidipine attenuated 2K-1C hypertension (224 12 versus 183 11 mm Hg in 2K-1C rats and 2K-1C + Lercandipine rats, respectively; P < 0.01) and prevented the reduction in endothelium-dependent vasorelaxation found in 2K-1C rats. Increased MMP-2 and Pro-MMP-2 levels were found in the aortas of 2K-1C rats (all P < 0.05). Lercandipine attenuated 2K-1C-induced increases in MMP-2 by more than 60% and blunted 2K-1C-induced increases in oxidative stress (both P < 0.001). While hypertension-induced significant aortic wall hypertrophy and approximately 9-fold increases in the ratio of MMP-2MMP-2 mRNA expression (both P < 0.05), lercandipine did not affect these changes. These results suggest that lercanidipine produces antihypertensive effects and reverses the endothelial dysfunction associated with 2K-1C hypertension, probably through mechanisms involving antioxidant effects leading to lower MMP-2 activation. (C) 2008 Elsevier B.V. All rights reserved.

Antioxidant activity of flavonoids in isolated mitochondria

Mitochondria are important intracellular sources and targets of reactive oxygen species (ROS), while flavonoids, a large group of secondary plant metabolites, are important antioxidants. Following our previous study on the energetics of mitochondria exposed to the flavonoids quercetin, taxifolin, catechin and galangin, the present work addressed the antioxidant activity of these compounds (1-50 mu mol/L) on Fe2+/citrate-mediated membrane lipid peroxidation (LPO) in isolated rat liver mitochondria, running in parallel studies of their antioxidant activity in non-organelle systems. Only quercetin inhibited the respiratory chain of mitochondria and only galangin caused uncoupling. Quercetin and galangin were far more potent than taxifolin and catechin in affording protection against LPO (IC50 = 1.23 +/- 0.27 and 2.39 +/- 0.79 mu mol/L, respectively), although only quercetin was an effective scavenger of both 2,2-diphenyl-1-picrylhydrazyl (DPPH) and superoxide radicals. These results, together with the previous study, suggest that the 2,3-double bond in conjugation with the 4-oxo function in the flavonoid structure are major determinants of the antioxidant activity of flavonoids in mitochondria, the presence of an o-di-OH structure on the B-ring, as occurs in quercetin, favours this activity via superoxide scavenging, while the absence of this structural feature in galangin, favours it via a decrease in membrane fluidity and/or mitochondrial uncoupling. Copyright (c) 2008 John Wiley & Sons, Ltd.

Neuropharmacological effects in mice of Lychnophora species (Vernonieae, Asteraceae) and anticonvulsant activity of 4,5-di-O-[E]-caffeoylquinic acid isolated from the stem of L-rupestris and L-staavioides

Aiming at contributing with the search for neuroactive substances from natural sources, we report for the first time antinociceptive and anticonvulsant effects of some Lychnophora species. We verify the protective effects of polar extracts (600 mg/kg, intraperitoneally), and methanolic fractions of L. staavioides and L. rupestris (100 mg/kg, intraperitoneally) in pentylenetetrazole-induced seizures on mice. Previously, a screening was accomplished, evaluating the antinociceptive central activity (hot plate test), with different extracts of L. rupestris, L. staavioides and L. diamantinana. It was possible to select the possible extracts of Lychnophora with central nervous system activity. Some of the active extracts were submitted to fractionation and purification process and the methanolic fractions of L. rupestris (stem) and L. staavioides (stem), with anticonvulsant properties (100 mg/kg, intraperitoneally), yielded 4,5-di-O-[E]-caffeoylquinic acid. This substance was injected intraperitoneally in mice and showed anticonvulsant effect against pentylenetetrazole-induced seizures at doses of 25 and 50 mg/kg. It has often been shown that seizures induced by pentylenetetrazole are involved in inhibition and/or attenuation of GABAergic neurotransmission. However, other systems of the central nervous system such as adenosinergic and glutamatergic could be involved in the caffeoylquinic acid effects. Further studies should be conducted to verify that the target receptor could be participating in this anticonvulsant property. Although other investigations have reported a series of biological activities from Lychnophora species, this is the first report of central analgesic and anticonvulsant activity in species of this genus.

Photocytotoxic activity of a nitrosyl phthalocyanine ruthenium complex - A system capable of producing nitric oxide and singlet oxygen

The synthesis, structural aspects, pharmacological assays, and in vitro photoinduced cytotoxic properties of [Ru(NO)(ONO)(pc)] (pc = phthalocyanine) are described. Its biological effect on the B16F10 cell line was studied in the presence and absence of visible light irradiation. At comparable irradiation levels, [Ru(NO) (ONO)(pc)] was more effective than [Ru(pc)] at inhibiting cell growth, suggesting that occurrence of nitric oxide release following singlet oxygen production upon light irradiation may be an important mechanism by which the nitrosyl ruthenium complex exhibits enhanced biological activity in cells. Following visible light activation, the [Ru(NO)(ONO)(pc)] complex displayed increased potency in B16F10 cells upon modifications to the photoinduced dose; indeed, enhanced potency was detected when the nitrosyl ruthenium complex was encapsulated in a drug delivery system. The liposome containing the [Ru(NO)(ONO)(pc)] complex was over 25% more active than the corresponding ruthenium complex in phosphate buffer solution. The activity of the complex was directly proportional to the ruthenium amount present inside the cell, as determined by inductively coupled plasma mass spectroscopy. Flow cytometry analysis revealed that the photocytotoxic activity was mainly due to apoptosis. Furthermore, the vasorelaxation induced by [Ru(NO)(ONO)(pc)], proposed as NO carrier, was studied in rat isolated aorta. The observed vasodilation was concentration-dependent. Taken together, the present findings demonstrate that the [Ru(NO)(ONO)(pc)] complex induces vascular relaxation and could be a potent anti-tumor agent. Nitric oxide release following singlet oxygen production upon visible light irradiation on a nitrosyl ruthenium complex produces two radicals and may elicit phototoxic responses that may find useful applications in photodynamic therapy. Crown Copyright (C) 2011 Published by Elsevier Inc. All rights reserved.

Iron chelating-mediated antioxidant activity of Plectranthus barbatus extract on mitochondria

Plectranthus barbatus Andrews (Lamiaceae) is a popular medicinal plant used to treat gastrointestinal and hepatic ailments. In this work, we assessed the antioxidant activity of the aqueous extract of P. barbatus leaves on Fe(2+)-citrate-mediated membrane lipid peroxidation in isolated rat liver mitochondria, as well in non-mitochondrial systems: DPPH reduction, (center dot)OH scavenging activity, and iron chelation by prevention of formation of the Fe(2+)-bathophenanthroline disulfonic acid (BPS) complex. Within all the tested concentrations (15-75 mu g/ml), P. barbatus extract presented significant free radical-scavenging activity (IC(50) = 35.8 +/- 0.27 mu g/ml in the DPPH: assay and IC(50) = 69.1 +/- 0.73 mu g/ml in the (center dot)OH assay) and chelated iron (IC(50) = 30.4 +/- 3.31 mu g/ml). Over the same concentration range, the plant extract protected mitochondria against Fe(2+)/citrate-mediated swelling and malondialdehyde production, a property that persisted even after simulation of its passage through the digestive tract. These effects could be attributed to the phenolic compounds, nepetoidin - caffeic acid esters, present in the extract. Therefore, P. barbatus extract prevents mitochondrial membrane lipid peroxidation, probably by chelation of iron, revealing potential applicability as a therapeutic source of molecules against diseases involving mitochondrial iron overload. (C) 2010 Elsevier Ltd. All rights reserved.

Retention of the Enzymatic Activity and Product Properties During Spray Drying of Pineapple Stem Extract in Presence of Maltodextrin

The aim of this work was to investigate the effects of drying parameters on the retention of the enzymatic activity and on the physical properties of spray-dried pineapple stem extract. A Box and Behnken experimental design was used to investigate the effects of the processing parameters on the product properties. The parameters studied were the inlet temperature of drying gas (Tgi), the feed flow rate of the pineapple extract relative to evaporative capacity of the system (Ws /Wmax), and the concentration of maltodextrin added to the extract (MD). Significant effects of the processing parameters on the retention of the proteolytic activity of the powdered extract were observed. High processing temperatures lead to a product with a smaller moisture content, particle size, and lower agglomerating tendency. A product with insignificant losses of the proteolytic activity ( 10%) and low moisture content (less than 6.5%) is obtained at selected conditions.

Evaluation of ent-Kaurenoic Acid Derivatives for their Anticariogenic Activity

Ent-kaur-16(17)-en-19-oic acid (kaurenoic acid, KA) is a tetracyclic diterpene prototype for natural anticaries agents. Six KA derivatives were prepared and their antimicrobial activity against the main microorganisms involved in the caries process evaluated. The sodium salt of KA (KA-Na) was the most active, displaying very promising MIC values for most pathogens. Time-kill assays against the primary causative agent of caries (Streptococcus mutans) indicated that KA and KA-Na only inhibited growth in the first 12 h, suggesting a bacteriostatic effect. After this period (12-24 h), their bactericidal effect was clearly noted. KA and KA-Na showed no synergy when combined with the gold standard anticariogenic (chlorhexidine dihydrochloride, CHD) in the checkerboard assays against S. mutans.

Evaluation of antiulcer activity of the main phenolic acids found in Brazilian Green Propolis

Aim of the study: In a previous study, our group described the gastric protective effect of the hydroalcoholic extract of Brazilian green propolis. The main compounds found in Brazilian green propolis include phenolic acids, such as: caffeic, ferulic, p-coumaric and cinnamic acids. This study was therefore carried out to evaluate the antiulcerogenic property of the main phenolic acids found in Brazilian Green Propolis. Material and methods: The anti-ulcer assays were performed using the following protocols: nonsteroidal-antinflammatory drug (NSAID)-induced ulcer, ethanol-induced ulcer, and stress-induced ulcer. The effects of the phenolic acids on gastric content volume, pH and total acidity, using the pylorus ligated model, were also evaluated. Results: It was observed that treatment using doses of 50 and 250 mg/kg of caffeic, ferulic, p-coumaric and cinnamic acids and positive controls (omeprazol or cimetidine) significantly diminished the lesion index, the total area of the lesion and the percentage of lesion in comparison with the negative control groups. In addition, the percentage of ulcer inhibition was significantly higher in the groups treated with the different phenolic acids, cimetidine or omeprazol, in all the protocols used, compared with the negative control groups. In the model to determine gastric secretion, using ligated pylorus, treatment with phenolic acids and cimetidine reduced the volume of gastricjuice and total acidity and significantly increased the gastric pH (p < 0.05), compared with the control group, with the exception of the group treated with 50 mg/kg of p-coumaric acid, in which no significant difference was observed, compared with the control. In relation to the acute toxicity, none sign of toxicity was observed when phenolic acids, used in this study, were administered for rats in dose of 2000 mg/kg. Conclusions: In conclusion, the results of this study show that caffeic, ferulic, p-coumaric and cinnamic acids display antiulcer activity. (c) 2008 Elsevier Ireland Ltd. All rights reserved.