Effects of Protein-Energy Malnutrition on NF-KappaB Signalling in Murine Peritoneal Macrophages

Protein-energy malnutrition (PEM) is an important public health problem affecting millions of people worldwide. PEM decreases resistance to infection, impairing a number of physiological processes. In unstimulated cells, NF-kappa B is kept from binding to its consensus sequence by the inhibitor I kappa B alpha, which retains NF-kappa B in the cytoplasm. Upon various signals, such as lipopolysaccharide (LPS), I kappa B alpha is rapidly degraded and NF-kappa B is induced to translocate into the nucleus, where it activates expression of various genes that participate in the inflammatory response, including those involved in the synthesis of TNF-alpha. TRAF-6 is a cytoplasmic adapter protein that links the stimulatory signal from Toll like receptor-4 to NF-kappa B. The aim of this study was to evaluate the effect of malnutrition on induction of TNF-a by LPS in murine peritoneal macrophages. We evaluated peritoneal cellularity, the expression of MyD88, TRAF-6, IKK, I kappa B alpha and NF-kappa B, NF-kappa B activation and TNF-alpha mRNA and protein synthesis inmacrophages. Two-month-old male BALB/Cmice were submitted to PEM with a low-protein diet that contained 2% protein, compared to 12% protein in the control diet. When the experimental group had lost about 20% of the original body weight, it was used in the subsequent experiments. Malnourished animals presented anemia, leucopenia and severe reduction in peritoneal cavity cellularity. TNF-a mRNA and protein levels of macrophages stimulated with LPS were significantly lower in malnourished animals. PEM also decreased TRAF-6 expression and NF-kappa B activation after LPS stimulation. These results led us to conclude that PEM changes NF-kappa B signalling pathway in macrophages to LPS stimulus.

Protein-Energy Malnutrition Modifies the Production of Interleukin-10 in Response to Lipopolysaccharide (LPS) in a Murine Model

Malnutrition modifies resistance to infection by impairing a number of physiological processes including hematopoesis and the immune response. In this study, we examined the production of Interleukin-4 (IL-4) and IL-10 in response to lipopolysaccharide (LPS) and also evaluated the cellularity of the blood, bone marrow, and spleen in a mouse model of protein-energy malnutrition. Two-month-old male Swiss mice were subjected to protein-energy malnutrition (PEM) with a low-protein diet (4%) as compared to the control diet (20%). When the experimental group lost approximately 20% of their original body weight, the animals from both groups received 1.25 mu g of LPS intravenously. The Cells ill the blood, bone marrow, and spleen were counted, and circulating levels of IL-4 and IL-10 were evaluated in animals stimulated with LPS. Cells from the spleen, bone marrow, and peritoneal cavity of non-inoculated animals were collected for Culture to evaluate the production of IL-4 and IL-10 after stimulating these cells with 1.25 mu g of LPS in vitro. Malnourished animals presented leucopenia and a severe reduction in bone marrow, spleen, and peritoneal cavity cellularity before and after Stimulus with LPS. The circulating levels of IL-10 were increased in malnourished animals inoculated with LPS when compared to control animals, although the levels of IL-4 did not differ. In cells cultured with LPS, we observed high levels of IL-10 in the bone marrow cells of malnourished animals. These findings suggest that malnourished mice present a deficient immune response to LPS. These alterations may be partly responsible for the immunodeficiency observed in these malnourished mice.

Chiral Triphenylprolinol Ligands for the Efficient Catalytic Asymmetric Arylation of Aldehydes

The synthesis of new chiral amino alcohols by Heck arylation of an enecarbamate is described. These compounds were used as chiral ligands for the catalytic asymmetric arylation of aldehydes and can be easily recovered. Chiral, nonracemic diarylmethanols were obtained in high yields and enantioselectivities.

Highly efficient palladium-catalyzed Suzuki-Miyaura reactions of potassium aryltrifluoroborates with 5-iodo-1,3-dioxin-4-ones in water: an approach to alpha-aryl-beta-ketoesters

The high efficient palladium-catalyzed Suzuki-Miyaura reactions of potassium aryltrifluoroborates 3 with 5-iodo-1,3-dioxin-4-ones 2a-b in water as only solvent in the presence of n-Bu(4)NOH as base is reported. The respective 5-aryl-1,3-dioxin-4-ones 4a-n were obtained in good to excellent yields. The catalyst system provides high efficiency at low load using electronically diverse coupling partners. The obtained 2,2,6-trimethyl-5-aryl-1,3-dioxin-4-ones were transformed into corresponding alpha-aryl-beta-ketoesters 6 by reaction with an alcohol in the absence of solvent. (C) 2009 Elsevier Ltd. All rights reserved.

Electron beam irradiation of Matricaria chamomilla L. for microbial decontamination

Wild chamomile (Matricaria chamomilla L.) is one of the most popular herbal materials with both internal and external use to cure different health disturbances. As a consequence of its origin, chamomile could carry various microbial contaminants which offer different hazards to the final consumer. Reduction of the microbial load to the in force regulation limits represents an important phase in the technological process of vegetal materials, and the electron beam treatment might be an efficient alternative to the classical methods of hygienic quality assurance. The purpose of the study was to analyze the potential application of the electron beam treatment in order to assure the microbial safety of the wild chamomile. Samples of chamomile dry inflorescences were treated in electron beam (e-beam) of 6 MeV mean energy, at room temperature and ambient pressure. Some loss of the chemical compounds with bioactive role could be noticed, but the number of microorganisms decreased as a function on the absorbed dose. Consequently, the microbial quality of studied vegetal material inflorescences was improved by e-beam. irradiation. (C) 2008 Elsevier B.V. All rights reserved.

Copper salt-catalyzed homo-coupling reaction of potassium alkynyltrifluoroborates: a simple and efficient synthesis of symmetrical 1,3-diynes

The copper-catalyzed dimerization of alkynyltrifluoroborates proceeds readily with good yields. The homo-coupling reaction can be effected in DMSO, in the open air, using Cu(OAc)(2) as catalyst in the absence of any other additives. A variety of functional groups are tolerated. (C) 2008 Elsevier Ltd. All rights reserved.

Kinetic and thermodynamic investigation on clavulanic acid formation and degradation during glycerol fermentation by Streptomyces DAUFPE 3060

Clavulanic acid (CA) is a potent inhibitor of beta-lactamases, produced by some resistant pathogenic microorganisms, which allows efficient treatment of infectious diseases. The kinetic and thermodynamic parameters of CA production by a new isolate of Streptomyces DAUFPE 3060 and its degradation were evaluated. The effect of temperature on the system was investigated in the range 24-40 degrees C adopting an overall model accounting for (a) the Arrhenius-type formation of CA by fermentation, (b) the hypothetical reversible unfolding of the enzyme limiting the overall metabolism, and (c) the irreversible first-order degradation of CA. The higher rates of CA formation (k(CA) = 0,107 h(-1)) and degradation (k(d) = 0.062 h(-1)) were observed at 32 and 40 degrees C, respectively. The main thermodynamic parameters of the three above hypothesized events were estimated. In particular, the activation parameters of degradation (activation energy = 39.0 kJ/mol; Delta H(d)* = 36.5 kJ/mol; Delta S(d)* = -219.7 J/(mol K); Delta G(d)* = 103.5 kJ/mol) compare reasonably well with those reported in the literature for similar system without taking into account the other two events. (C) 2009 Elsevier Inc. All rights reserved.

Efficient sonochemical synthesis of novel 3,5-diaryl-4,5-dihydro-1H-pyrazole-1-carboximidamides

An Ultrasound-assisted preparation of a series of novel 3,5-diaryl-4,5-dihydro-1H-pyrazole-1-carboximidamides that proceeds via the efficient reaction of chalcones with aminoguanidine hydrochloride under clean conditions is described. (C) 2009 Elsevier B.V. All rights reserved.

Generation and Analysis of Interaction Energy Maps of p-Substituted Benzoic Acid [(5-Nitro-thiophen-2-yl)-methylene]-Hydrazides Active against MRSA

In this preliminary study eighteen p-substituted benzoic acid [(5-nitro-thiophen-2-yl)-methylene]-hydrazides with antimicrobial activity were evaluated against multidrug-resistant Staphylococcus aureus, correlating the three-dimensional characteristics of the ligands with their respective bioactivities. The computer programs Sybyl and CORINA were used, respectively, for the design and three-dimensional conversion of the ligands. Molecular interaction fields were calculated using GRID program. Calculations using Volsurf resulted in a statistically consistent model with 48 structural descriptors showing that hydrophobicity is a fundamental property in the analyzed biological response.

Mitochondrial energy metabolism and redox responses to hypertriglyceridemia

In this work we review recent findings that explain how mitochondrial bioenergetic functions and redox state respond to a hyperlipidemic in vivo environment and may contribute to the maintenance of a normal metabolic phenotype. The experimental model utilized to evidence these adaptive mechanisms is especially useful for these studies since it exhibits genetic hypertriglyceridemia and avoids complications introduced by high fat diets. Liver from hypertrigliceridemic (HTG) mice have a greater content of glycerolipids together with increased mitochondrial free fatty acid oxidation. HTG liver mitochondria have a higher resting respiration rate but normal oxidative phosphorylation efficiency. This is achieved by higher activity of the mitochondrial potassium channel sensitive to ATP (mitoK(ATP)). The mild uncoupling mediated by mitoK(ATP) accelerates respiration rates and reduces reactive oxygen species generation. Although this response is not sufficient to inhibit lipid induced extra-mitochondrial oxidative stress in whole liver cells it avoids amplification of this redox imbalance. Furthermore, higher mitoK(ATP) activity increases liver, brain and whole body metabolic rates. These mitochondrial adaptations may explain why these HTG mice do not develop insulin resistance and obesity even under a severe hyperlipidemic state. On the contrary, when long term high fat diets are employed, insulin resistance, fatty liver and obesity develop and mitochondrial adaptations are inefficient to counteract energy and redox imbalances.

Synthesis and evaluation of sesquiterpene lactone inhibitors of phospholipase A(2) from Bothrops jararacussu

Several sesquiterpene lactone were synthesized and their inhibitive activities on phospholipase A(2) (PLA(2)) from Bothrops jararacussu venom were evaluated. Compounds Lac01 and Lac02 were efficient against PLA(2) edema-inducing, enzymatic and myotoxic activities and it reduces around 85% of myotoxicity and around 70% of edema-inducing activity. Lac05-Lac08 presented lower efficiency in inhibiting the biological activities studied and reduce the myotoxic and edema-inducing activities around only 15%. The enzymatic activity was significantly reduced. The values of inhibition constants (K(1)) for Lac01 and Lac02 were approximately 740 mu M, and for compounds Lac05-Lac08 the inhibition constants were approximately 7.622-9.240 mu M. The enzymatic kinetic studies show that the sesquiterpene lactones inhibit PLA(2) in a non-competitive manner. Some aspects of the structure-activity relationships (topologic, molecular and electronic parameters) were obtained using ab initio quantum calculations and analyzed by chemometric methods (HCA and PCA). The quantum chemistry calculations show that compounds with a higher capacity of inhibiting PLA(2) (Lac01-Lac04) present lower values of highest occupied molecular orbital (HOMO) energy and molecular volume (VOL) and bigger values of hydrophobicity (LogP). These results indicate some topologic aspects of the binding site of sesquiterpene lactone derivatives and PLA(2). (C) 2010 Elsevier Ltd. All rights reserved.

Synthesis and Study of the Photophysical Properties of a New Eu(3+) Complex with 3-Hydroxypicolinamide

This work reports on the synthesis and characterization of a new complex of Eu(3+) with the 3-hydroxypicolinamide ligand (Hhpa). Here we present an approach for obtaining bis[2-carbamoyl(kappa O)pyridin-3-olato(kappa O`)] lanthanide complexes, which were characterized through elemental analysis, thermal analysis, infrared and photoluminescence spectroscopies (emission, excitation, luminescence lifetimes, quantum efficiencies, Judd-Ofelt parameters and quantum yields). Although hpa can act as a bidentate ligand in different conformations, the results attest for the occurrence of a unique coordination site of low symmetry for the Eu(3+) ions, in which two anionic hpa ligands coordinate the cations through an O/O chelating system. The phosphorescence of the synthesized gadolinium complex provides the energy of the triplet state, which is determined to be at 20,830 cm(-1) over the ground state. This makes the Hhpa ligand very adequate for sensitizing the Eu(3+) luminescence, which leads to a very efficient antenna effect and opens a wide range of applications for the complex in light emitting organic-inorganic devices.

Fast and efficient synthesis of pyrano[3,2-c]quinolines catalyzed by niobium(V) chloride

A highly efficient two-step method for the synthesis of pyranoquinoline derivatives from imino-Diels-Alder reactions between aldimines and 3,4-dihydro-2H-pyran using niobium(V) chloride as catalyst under mild conditions is described.

Fermentative production of hydrogen from cassava processing wastewater by Clostridium acetobutylicum

This work reports on the effect of initial substrate concentration on COD consumption, pH, and H(2) production during cassava processing wastewater fermentation by Clostridium acetobutylicum ATCC 824. Five initial COD wastewater concentrations, namely 5.0, 7.5, 10.7, 15.0, and 30.0 g/L, were used. The results showed that higher substrate concentrations (30.0 and 15.0 COD/L) led to lower H(2) yield as well as less efficient substrate conversion into H(2). On the other hand, initial COD concentrations of 10.7, 7.5 and 5 g/L furnished 1.34, 1.2 and 2.41 mol H(2)/mol glucose, with efficiency of glucose conversion into H(2) of 34, 30, and 60% (mol/mol), respectively. These results demonstrate that cassava processing wastewater, a highly polluting effluent, can be successfully employed as substrate for H(2) production by C acetobutylicum at lower COD concentrations. (C) 2011 Elsevier Ltd. All rights reserved.

Resting energy expenditure in white and non-white severely obese women

This study aimed to compare the resting energy expenditure (REE) of white and non-white severely obese Brazilian women. REE was examined in 83 severely obese Brazilian women (n = 58 white and 25 non-white) with mean (+/- SD) age 42.99 +/- 11.35 and body mass index 46.88 +/- 6.22 kg/m(2) who were candidates for gastric bypass surgery. Body composition was assessed by air displacement plethysmography (ADP) BOD PODO body composition system (Life Measurement Instruments, Concord, CA) and REE was measured, under established protocol, with an open-circuit calorimeter (Deltatrac II MBM-200, Datex-Ohmeda, Madison, WI, USA). There was no significant difference between the REE of white and non-white severely obese women (1,953 +/- 273 and 1,906 +/- 271 kcal/d, respectively; p = 0.48). However, when adjusted for fat free mass (MLG), REE was significantly higher in non-white severely obese women (difference between groups of 158.4 kcal, p < 0.01). REE in white women was positively and significantly correlated to C-reactive protein (PCR) (r = 0.41.8; P < 0.001) and MLG (r = 0.771; P < 0.001). In the non-white women, REE was only significantly correlated to MLG (r = 0.753; P < 0.001). The multiple linear regression analysis showed that skin color, MLG and PCR were the significant determinants of REE (R(2) = 0.55). This study showed that, after adjustment for MLG, non-white severely obese women have a higher REE than the white ones. The association of body composition inflammation factors and REE in severely obese Brazilian women remains to be further investigated.