Effect of pH and oxalic acid on the reduction of Fe(3+) by a biomimetic chelator and on Fe(3+) desorption/adsorption onto wood: Implications for brown-rot decay

Fenton reaction is thought to play an important role in wood degradation by brown-rot fungi. In this context, the effect of oxalic acid and pH on iron reduction by a biomimetic fungal chelator and on the adsorption/desorption of iron to/from wood was investigated. The results presented in this work indicate that at pH 2.0 and 4.5 and in the presence of oxalic acid, the phenolate chelator 2,3-dihydroxybenzoic acid (2,3-DHBA) is capable of reducing ferric iron only when the iron is complexed with oxalate to form Fe mono-oxalate (Fe(C(2)O(4))(+)). Within the pH range tested in this work, this complex formation occurs when the oxalate:Fe(3+) molar ratio is less than 20 (pH 2.0) or less than 10 (pH 4.5). When aqueous ferric iron was passed through a column packed with milled red spruce (Picea rubens) wood equilibrated at pH 2.0 and 4.5. it was observed that ferric iron binds to wood at pH 4.5 but not at pH 2.0, and the bound iron could then be released by application of oxalic acid at pH 4.5. The release of bound iron was dependent on the amount of oxalic acid applied in the column. When the amount of oxalate was at least 20-fold greater than the amount of iron bound to the wood, all bound iron was released. When Fe-oxalate complexes were applied to the milled wood column equilibrated in the pH range of 2-4.5, iron from Fe-oxalate complexes was bound to the wood only when the pH was 3.6 or higher and the oxalate:Fe(3+) molar ratio was less than 10. When 2,3-DHBA was evaluated for its ability to release iron bound to the milled wood, it was found that 2,3-DHBA possessed a greater affinity for ferric iron than the wood as 2,3-DHBA was capable of releasing the ferric iron bound to the wood in the pH range 3.6-5.5. These results further the understanding of the mechanisms employed by brown-rot fungi in wood biodegradation processes. (C) 2009 Elsevier Ltd. 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.

Pimaradienoic acid inhibits vascular contraction and induces hypotension in normotensive rats

The present investigation was designed to investigate the effect of the diterpene ent-pimara-8(14),15-dien-19-oic acid (pimaradienoic acid, PA) on smooth muscle extracellular Ca2+ influx. To this end, the effect of PA on phenylephrine- and KCI-induced increases in cytosolic calcium concentration ([Ca2+](c)) measured by the variation in the ratio of fluorescence intensities (R340/ 380 nm) of Fura-2, was analysed. Whether bolus injection of PA could induce hypotensive responses in conscious normotensive rats was also evaluated. PA inhibited the contraction induced by phenylephrine (0.03 or 10 mu mol L-1) and KCI (30 or 90 mmol L-1) in endothelium-denuded rat aortic rings in a concentration dependent manner. Pre-treatment with PA (110, 100, 200 mu mol L-) attenuated the contraction induced by CaCl2 (0.5 nmol L(-)1 or 2.5 mmol L-1) in denuded rat aorta exposed to Ca2+- free medium containing phenylephrine (0.1 mu mol L-1) or KCI (30 mmol L-1). Interestingly, the inhibitory effect displayed by PA on CaCl2-induced contraction was more pronounced when KCI was used as the stimulant. Phenylephrine- and KCI-induced increases in (Ca2+,](c) were inhibited by PA. Similarly, verapamil, a Ca2+-channel blocker, also inhibited the increase in [Ca2+](c) induced by either phenylephrine or KCI. Finally, bolus injection of PA (1-15 mg kg(-1)) produced a dose-dependent decrease in mean arterial pressure in conscious normotensive rats. The results provide the first direct evidence that PA reduces vascular contractility by reducing extracellular Ca2+ influx through smooth muscle cellular membrane, a mechanism that could mediate the hypotensive response induced by this diterpene in normotensive rats.

Iontophoretic transport of zinc phthalocyanine tetrasulfonic acid as a tool to improve drug topical delivery

Phthalocyanines have been used as systemic photosensitizers because of their high affinity towards tumour tissue, and the high rates of reactive oxygen species produced when they are irradiated during photodynamic therapy. However, the topical administration of these compounds is limited by their large size, poor hydrosolubility and ionic character. This study aimed to investigate the iontophoretic delivery of charged zinc phthalocyanine tetrasulfonic acid (ZnPcS(4)) from a hydrophilic gel to different skin layers by means of in-vitro and in-vivo studies. Six hours of passive administration was insufficient for ZnPcS(4) to cross the stratum corneum (SC) and to reach the epidermis and dermis. No positive effect was reached when anodal iontophoresis was performed, showing that the drug-electrode attraction effect was higher than the electro-osmosis contribution at a pH of 5.5. Cathodal iontophoresis, however, was able to transport significant amounts of the drug to the viable epidermis. In addition, the absence of NaCl in the formulation significantly increased (by five-fold) the amount of ZnPcS(4) that crossed the SC and accumulated in the epidermis and dermis. It was possible to visualize the drug accumulation in the follicle openings and in the epidermis, even after SC removal. In-vivo experiments in rat skin showed that these results were maintained in an in-vivo model, even with only 15 min of iontophoresis. In addition, confocal analysis of the treated skin showed a homogeneous distribution of ZnPcS(4) in the viable epidermis after this short period of cathodal iontophoresis. Anti-Cancer Drugs 22:783-793 (C) 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Molecular cocrystals of carboxylic acids. XXVII - An investigation into the use of triphenylphosphine oxide cocrystals for non-linear optics: the crystal structure of the adduct of triphenylphosphine oxide with N-methylpyrrole-2-carboxylic acid

Four adducts of triphenylphosphine oxide with aromatic carboxylic acids have been synthesized and tested for second-order non-linear optical properties. These were with N-methylpyrrole-2-carboxylic acid (I), indole-2-carboxylic acid (2), 3-dimethylaminobenzoic acid (3), and thiophen-2-carboxylic acid (4). Compound (1) produced clear, colourless crystals (space group P2(1)2(1)2(1) With a 9.892(1), b 14.033(1), c 15.305(1) Angstrom, Z 4) which allowed the structure to be determined by X-ray diffraction.

Quantification of free mycophenolic acid by high-performance liquid chromatography-atmospheric pressure chemical ionisation tandem mass spectrometry

To facilitate the investigation of free mycophenolic acid concentrations we developed a high-performance liquid chromatography tandem mass spectrometry method using indomethacin as an internal standard. Free drug was isolated from plasma samples (500 mul) using ultrafiltration, The analytes were extracted from the ultrafiltrate (200 mul) using C-18 solid-phase extraction. Detection was by selected reactant monitoring of mycophenolic acid (m/z 318.9-->190.9) and the internal standard (m/z 356.0-->297.1) with an atmospheric pressure chemical ionisation interface. The total chromatographic analysis time was 12 min. The method was found to be linear over the range investigated, 2.5-200 mug/l (r>0.990, n=6). The relative recovery of the method for the control samples studied (7.5, 40.0 and 150 mug/l) ranged from 95 to 104%. The imprecision of the method, expressed in terms of intra- and inter-day coefficients of variation, was

Lipid content and fatty acid composition of 11 species of Queensland (Australia) fish

The fatty acid composition of 11 species of fish caught off the northeast coast of Australia was determined. No fatty acid profiles have been previously published for fish from this area nor for nine of these species. Although the percentage of polyunsaturated fatty acid (PU FA) was the same as the calculated average for Australian fish (42.3%), the percentage of n-3 fatty acids was lower (24.4 +/- 5.4% vs. 30.7 +/- 10.1%) and the n-6 fatty acids higher (16.5 +/- 4.5% vs. 11.2 +/- 5.9%), P < 0.001 in each case. The major n-3 PUFA were docosahexaenoic (15.6 +/- 6.3%) and eicosapentaenoic acid (4.3 +/- 1.1%) while the major n-6 PUFA were arachidonic (8.3 +/- 3.2%) and n-6 docosatetraenoic acid (3.1 +/- 1.3%). The second-most abundant class of fatty acid was the saturates (31.6 +/- 3.5%) while the monounsaturates accounted for 17.4 +/- 4.3% of the total fatty acids. The monounsaturate with the highest concentration was octadecenoic acid (11.8 +/- 2.6%). There was a positive correlation between the total lipid content and saturated and monounsaturated fatty acids (r = 0.675 and 0.567, respectively) and a negative correlation between the total lipid content and PUFA(r = 0.774).

Chemistry of 5-oxodihydroisoxazoles .17. Acylation of 5-oxodihydroisoxazoles

2-Unsubstituted isoxazol-5(4H)-ones and -5(2N)-ones may be acylated by acid chlorides, anhydrides or carboxylic acids in the presence of carbodiimides, to give O- and N-acylated products, The solvent, the presence of base and the temperature are found to alter the product ratios dramatically, but the substituents present at C-3 have the greatest effect, Aliphatic acid anhydrides and chlorides generally react at nitrogen, but aroyl halides give significant proportions of O-acylated products, Limited success in converting O-aroyl to N-aroyl isoxazolones is reported.

Preoperative Gastric Acid Secretion and the Risk to Develop Barrett`s Esophagus After Esophagectomy for Chagasic Achalasia

The aim of this study was to determine the contribution of preoperative gastric secretory and hormonal response, to the appearance of Barrett`s esophagus in the esophageal stump following subtotal esophagectomy. Thirty-eight end-stage chagasic achalasia patients submitted to esophagectomy and cervical gastric pull-up were followed prospectively for a mean of 13.6 +/- 9.2 years. Gastric acid secretion, pepsinogen, and gastrin were measured preoperatively in 14 patients who have developed Barrett`s esophagus (Group I), and the results were compared to 24 patients who did not develop Barrett`s esophagus (Group II). In the group (I), the mean basal and stimulated preoperative gastric acid secretion was significantly higher than in the group II (basal: 1.52 vs. 1.01, p = 0.04; stimulated: 20.83 vs. 12.60, p = 0.01). Basal and stimulated preoperative pepsinogen were also increased at the Group I compared to Group II (Basal = 139.3 vs. 101.7, p = 0.02; stimulated = 186.0 vs. 156.5, p = 0.07. There was no difference in preoperative gastrin between the two groups. Gastritis was present during endoscopy in 57.1% of the Group I, while it was detected in 16.6% of the Group II, p = 0.014. Barrett`s esophagus in the esophageal stump was associated to high preoperative levels of gastric acid secretion, serum pepsinogen, and also gastritis in the transposed stomach.

Effects of Caffeoylquinic Acid Derivatives and C-Flavonoid from Lychnophora ericoides on in vitro Inflammatory Mediator Production

In this study we aimed at evaluating the effect of the major polar constituents of the medicinal plant Lychnophora ericoides on the production of inflammatory mediators produced by LPS-stimulated U-937 cells. The 6,8-di-C-beta-glucosylapigenin (vicenin-2) presented no effect on tumor necrosis factor (TNF)-alpha production, but inhibited, in a dose-dependent manner, the production of prostaglandin (PG) E(2) without altering the expression of cyclooxygenase (COX) -2 protein. 3,5-Dicaffeoylquinic acid and 4,5-dicaffeoylquinic acid, at lower concentrations, had small but significant effects on reducing PG E, levels; at higher doses these compounds stimulated PGE(2) and also TNF-alpha production by the cells. All the caffeoylquinic acid derivatives, in a dose-dependent fashion, were able to inhibit monocyte chemoattractant protein-3 synthesis/release, with 4,5-DCQ being the most potent at the highest tested concentration. These results add important information on the effects of plant natural polyphenols, namely vicenin-2 and caffeoylquinic acid derivatives, on the production of inflammatory mediators by cultured cells.

Lercanidipine decreases vascular matrix metalloproteinase-2 activity and protects against vascular dysfunction in diabetic rats

Abnormal matrix metalloproteinases (MMPs) activity causes cardiovascular diseases. Because hyperglycemia increase MMPs activities through increased oxidative stress. we hypothesized that antioxidant effects produced by lercanidipine could attenuate the increases in MMP-2 expression/activity in diabetic rats. Control and diabetic (alloxan-induced diabetes) rats received lercanidipine 2.5 mg/kg/day (or tap water) starting three weeks after alloxan (or vehicle) injections. Blood pressure was monitored weekly. After six weeks of treatment, vascular reactivity and structural changes were assessed in aortic rings. MMP-2 levels were determined by gelatin zymography, and 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 by fluorimetry. Lercanidipine produced antihypertensive effects (201 +/- 5 vs. 163 +/- 7 mm Hg in diabetic rats untreated and treated with lercaniclipine, respectively; P < 0.01) and reversed the impairment in endothelium-dependent vasorelaxation in diabetic rats. Increased MMP-2 and Pro-MMP-2 levels were found in the aortas of diabetic rats (both P < 0.001). Lercandipine attenuated the increases in oxidative stress and in MMP-2 (both P < 0.05). While diabetes induced no major structural changes, it caused a 16-fold increase in the ratio of MMP-2/TIMP-2 mRNA expression, which was completely reversed by lercanidipine (both P < 0.001). These results show that antioxidant and beneficial vascular effects produced by lercanidipine in diabetic rats are associated with reversion of the imbalance in vascular MMP-2MMP-2 expression. (C) 2008 Published by Elsevier B.V.

A histone deacetylase inhibitor, azelaic bishydroxamic acid, shows cytotoxicity on Epstein-Barr virus-transformed B-cell lines - A potential therapy for posttransplant lymphoproliferative disease

Background. Posttransplant lymphoproliferative disease (PTLD), driven by the presence of Epstein-Barr virus (EBV), is becoming an increasingly important clinical problem after solid organ transplantation. The use of immunosuppressive therapy leads to the inhibition of the cytotoxic T cells that normally control the EBV latently infected B cells. The prognosis for many patients with PTLD is poor, and the optimal treatment strategy is not well defined. Method. This study investigates the use of a histone deacetylase inhibitor, azelaic bishydroxamic acid (ABRA), for its ability to effectively kill EBV-transformed lymphoblastoid cell lines. Results. In vitro treatment of lymphoblastoid cell lines with ABRA showed that they were effectively killed by low doses of the drug (ID50 2-5 mug/ml) within 48 hr. As well as being effective against polyclonal B-cell lines, ABHA was also shown to be toxic to seven of eight clonal Burkitt's lymphoma cell lines, indicating that the drug may also be useful in the treatment of late-occurring clonal PTLD. In addition, ABHA treatment did not induce EBV replication or affect EBV latent gene expression. Conclusion. These studies suggest that ABHA effectively kills both polyclonal and clonal B-cell lines and has potential in the treatment of PTLD.

Thiazolidinediones and type 2 diabetes: new drugs for an old disease

Thiazolidinediones are a new class of drugs for the treatment of type 2 diabetes, and act by improving insulin sensitivity in adipose tissue, liver and skeletal muscle. Rosiglitazone and pioglitazone are registered for use in monotherapy, and in combination with sulfonylureas and metformin. Pioglitazone is also licensed for use in combination with insulin. There is level II evidence that in patients with inadequate glycaemic control both drugs reduce the level of HbA(1c) and fasting plasma glucose (FPG) when used as monotherapy and in combination with sulfonylurea or metformin or insulin; and both drugs increase levels of HDL and LDL and lower free fatty acid levels, but only pioglitazone significantly lowers triglyceride levels. Both drugs lower fasting insulin and C-peptide levels. In monotherapy, they may be slightly less potent at reducing the level of HbA(1c) than sulfonylureas or metformin. The maximal effect of these agents may not be seen for 6-14 weeks after commencement. Both drugs are well tolerated but liver function must be checked at baseline every second month for the first year, and periodically thereafter. The drugs are currently contraindicated in patients with moderate to severe liver dysfunction and alanine aminotransferase levels more than 2.5 times normal, New York Heart Association III-IV cardiac status, pregnancy, lactation and in children. The main side effects include weight gain, oedema, and mild dilutional anaemia.

Trans fatty acid intake among the population of the city of São Paulo, Brazil

OBJECTIVE: To analyze the monounsaturated and polyunsaturated trans fatty acid intake among the general population. METHODS: A cross-sectional study was conducted in São Paulo, Southeastern Brazil, in 2003, on a representative sample of 2,298 male and female subjects, including 803 adolescents (12 to 19 years), 713 adults (20 to 59 years) and 782 elderly people (60 years or over). Food intake was measured using 24-hour recall. Mean trans fatty acid intake was described according to gender and age group. RESULTS: The mean trans fatty acid intake was 5.0 g/day (SE = 0.1), accounting for 2.4% (SE = 0.1) of total energy and 6.8% (SE = 0.1) of total lipids. The adolescents had the highest mean intake levels (7.4 g/day; 2.9% of energy) while the adults and the elderly had similar intake (2.2% of energy for both; 6.4% of lipids and 6.5% of lipids, respectively). The mean trans fatty acid intake among adult and elderly women (approximately 2.5% of energy and 7.0% of lipids) was higher than among men in the same age group. The food item with the highest contribution towards trans fatty acids was margarine, accounting for more than 30% of total intake, followed by filled cookies among adolescents and meat among adults and the elderly. CONCLUSIONS: The trans fatty acid intake is above the level recommended by the World Health Organization. Replacement of the trans fatty acids in manufactured food items may be an effective measure for reducing trans fatty acid intake in Brazil.

Tris(2-Ethylhexyl) trimellitate (TOTM) a potential reference fluid for high viscosity. Part II: density measurements at temperatures from (293 to 373)K and pressures up to 85MPa

In Part I of the present work we describe the viscosity measurements performed on tris(2-ethylhexyl) trimellitate or 1,2,4-benzenetricarboxylic acid, tris(2-ethylhexyl) ester (TOTM) up to 65 MPa and at six temperatures from (303 to 373)K, using a new vibrating-wire instrument. The main aim is to contribute to the proposal of that liquid as a potential reference fluid for high viscosity, high pressure and high temperature. The present Part II is dedicated to report the density measurements of TOTM necessary, not only to compute the viscosity data presented in Part I, but also as complementary data for the mentioned proposal. The present density measurements were obtained using a vibrating U-tube densimeter, model DMA HP, using model DMA5000 as a reading unit, both instruments from Anton Paar GmbH. The measurements were performed along five isotherms from (293 to 373)K and at eleven different pressures up to 68 MPa. As far as the authors are aware, the viscosity and density results are the first, above atmospheric pressure, to be published for TOTM. Due to TOTM's high viscosity, its density data were corrected for the viscosity effect on the U-tube density measurements. This effect was estimated using two Newtonian viscosity standard liquids, 20 AW and 200 GW. The density data were correlated with temperature and pressure using a modified Tait equation. The expanded uncertainty of the present density results is estimated as +/- 0.2% at a 95% confidence level. Those results were correlated with temperature and pressure by a modified Tait equation, with deviations within +/- 0.25%. Furthermore, the isothermal compressibility, K-T, and the isobaric thermal expansivity, alpha(p), were obtained by derivation of the modified Tait equation used for correlating the density data. The corresponding uncertainties, at a 95% confidence level, are estimated to be less than +/- 1.5% and +/- 1.2%, respectively. No isobaric thermal expansivity and isothermal compressibility for TOTM were found in the literature. (C) 2014 Elsevier B.V. All rights reserved.