bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantitative Structure–Activity Relationships Study on the Ah Receptor Binding Affinities of Polybrominated Diphenyl Ethers Using a Support Vector Machine
Authors: Zheng Gang , Xiao Man , Lu Xiaohua
Published: December 2006

Polybrominated Diphenyl Ethers (PBDEs), which are widely distributed in the environment due to their use as flame retardant, may cause long‐term health problems in humans. Their structural similarity to Polychlorinated Biphenyls (PCBs) implies their possible dioxin‐like toxicity. By the use of Partial Least Square Regression (PLS ) with Leave‐One‐Out (LOO) Cross‐Validation (CV), seven net atomic charge descriptors have been extracted from more than 80 quantum descriptors for predicting the Aryl hydrocarbon Receptor Relative Binding Affinities (RBA) of PBDEs. Using Support Vector Machines (SVM) and Radial Basis Function Neural Networks (RBFNs), the RBAs of 15 PBDE congeners have been correlated with the extracted seven quantum chemical descriptors. The SVM models generalize better than the RBFN models. The CV correlation coefficients (q2) for the SVM models based on three‐ and five‐fold CVs are 0.889 and 0.896, respectively. The good performance of the QSAR models based on net atomic charges suggests that electrostatic interactions may play important roles in the Aryl hydrocarbon Receptor (AhR) binding of PBDEs.
Quantitative Structure–Activity Relationship Study on a Series of Novel Ligands Binding to Central Benzodiazepine Receptor By Using the Combination of Heuristic Method and Support Vector Machines
Authors: Qin Shen , Liu Huanxiang , Wang Jie , Yao Xiaojun , Liu Mancang , Hu Zhide , Fan Botao
Published: December 2006

In this study, Heuristic Method (HM) and Support Vector Machines (SVMs) were used for Quantitative Structure–Activity Relationship (QSAR) study of a series of 2‐aryl (heteroaryl)‐2,5‐dihydropyrazolo [4,3‐c] quinolin‐3‐(3H)‐ones, which have high affinity with central Benzodiazepine Receptor (BzR). Seven molecular descriptors selected by the HM in CODESSA were used as inputs for SVM. The prediction results are in good agreement with the experimental values. The correlation coefficients R2 of the nonlinear SVM model were 0.93 and 0.96 for the training and testing sets, respectively. This paper proposes a new and effective method to design new ligands of BzR based on QSAR study.
Estimation of Phosphate Ester Hydrolysis Rate Constants. II. Acid and General Base Catalyzed Hydrolysis
Authors: Whiteside Tad , Carreira Lionel , Hilal Said
Published: December 2006

SPARC (SPARC Performs Automated Reasoning in Chemistry) chemical reactivity models were extended to calculate acid and neutral hydrolysis rate constants of phosphate esters in water. The rate is calculated from the energy difference between the initial and transition states of the reactant molecule. This difference is a function of the reference rate and internal and external perturbations to the reference rate. The internal perturbations are comprised of electrostatic and resonance effects. The external perturbations quantify solute‐solvent interactions based on the dielectric constant of the solvent and the steric size of substituent groups. The neutral hydrolysis model has been tested against 89 observed hydrolysis rate constants at multiple temperatures. The RMS deviation of the calculated versus observed values was 1.08 log M−1 s−1. The acid hydrolysis model has been tested on 83 rate constants over a variety of temperatures. The RMS deviation of the acid hydrolysis model was 0.41 log M−1 s−1.
A Virtual Screening Filter for Identification of Cytochrome P450 2C9 (CYP2C9) Inhibitors
Authors: Byvatov Evgeny , Baringhaus Karl‐Heinz , Schneider Gisbert , Matter Hans
Published: December 2006

Cytochrome P450 2C9 (CYP2C9) is one of the most important phase 1 metabolizing enzymes in humans for therapeutically relevant pharmaceuticals. Any new compound inhibiting this membrane‐associated protein would notably affect the metabolism of physiologically important molecules and drugs, resulting in clinically significant drug‐drug interactions. In search for computational tools to identify potential CYP2C9 inhibitors early in discovery, we present here the construction of filters based on 1100 structurally diverse molecules tested for CYP2C9 inhibition under identical conditions. Their chemical structures were encoded using various 2D descriptors including Three‐Point Pharmacophoric (3PP) fingerprints, followed by generation of statistical models using Support Vector Machines (SVM) and Partial Least Squares (PLS). This consistently led to significant and predictive models for regression and classification of CYP2C9 inhibitors. Their predictive ability was underscored by successfully applying them to different test sets of 238 diverse and 344 GPCR‐targeted compounds. Even more important for early drug discovery is the ability of these models to correctly discriminate CYP2C9 inhibitors from inactive molecules. These models collectively are able to identify true CYP2C9 inhibitors with relatively low rates of false positives. The 3PP‐based filter also allows visualizing important substructures and functional groups, which are linked to protein‐ligand interactions for CYP2C9, as illustrated for selected structure‐activity series. The application of these models to the substrate S‐warfarin, recently co‐crystallized with CYP2C9, revealed that the important substructures are indeed involved in the interaction with the CYP2C9 binding site. For example, the model correctly indicated aromatic stacking interactions with Phe114 and Phe476 as well as a hydrogen bond with Phe100. Hence, these models consistently provide guidelines for reducing CYP2C9 inhibition in novel candidate molecules.
Conformational analysis and the binding sites of nitrilotriacetamide: A computational study
Authors: Singh Ajeet , Chakraborty Shampa , Ganguly Bishwajit
Published: December 2006

The conformational analysis of nitrilotriacetamide has been carried out computationally, at both the semi‐empirical AM1 and density functional theory (DFT) (B3LYP/6‐31+G*) levels of theory. The lowest‐energy conformation predicted with the Monte Carlo search method, using the AM1 model, has two amide functionalities aligned on the same side; however, the DFT calculations at B3LYP/6‐31+G* predicted the global minimum with all three acetamide functionalities on the same side in the gas phase. In the aqueous phase, the DFT results predicted the orientations of amides similar to that of the reported crystal structure. The rotation barriers to transition to different low‐energy conformers of nitrilotriacetamide are lower in energy (5.0 kcal/mol) in water. The molecular electrostatic isopotentials (MESP) generated for the selected conformers at DFT level show that the nitrilotriacetamide could interact more effectively with the sodium chloride surface than that of its monomeric unit nitrilomonoacetamide. © 2006 Wiley Periodicals, Inc. Int J Quantum Chem, 2007
Is sluice gate management beneficial for spawning migrations? The case of the shark catfish (Helicophagus waandersii) in the Mun River below the Pak Mun Dam, Thailand
Authors: Jutagate Tuantong , Thapanand Thanitha , Tabthipwan Pratak
Published: December 2006

The reproductive ecology of shark catfish Helicophagus waandersii in the Mun River, the largest Mekong tributary in Thailand, was studied from July 2003 to December 2004. The aim of the study was to determine whether shark catfish, which contribute greatly to fish catches, benefits in terms of spawning, from the management regime of the Pak Mun Dam to open all sluice gates annually for 4 months during the rainy season. In total, 228 females were studied. The highest average gonadosomatic index (4.42% ± 1.90%) was observed in the rainy season in June 2004. Fecundity ranged from 21 550 to 191 540 eggs. Three hormonal profiles viz. testosterone (T), 17 β‐estradiol (E2), and 17, 20 β‐dihydroxy‐4‐pregnen‐3‐one (17, 20 βP) were determined by radioimmunoassay. The highest levels of T (0.96 ng ml−1), E2 (14.37 pg ml−1), and 17, 20 βP (0.81 ng ml−1) were respectively measured in April to May, July, and May. Changes in the maturity stage and the annual sex hormonal profiles revealed that the spawning period of H. waandersii is from May to June. There was no spatial statistical difference (p > 0.05) for each sex steroid profiles. The results indicated that H. waandersii spawn during the rainy season in the rapid areas, both downstream and upstream, and the sluice gates opening management regime for 4 months in the rainy season is of advantage for H. waandersii in terms of feeding and nursery grounds in the upstream area. Copyright © 2006 John Wiley & Sons, Ltd.
Sand deposition in shoreline eddies along five Wild and Scenic Rivers, Idaho
Authors: Andrews E. D. , Vincent Kirk R.
Published: December 2006

Sand bars deposited along the lateral margin of a river channel are frequently a focus of recreational activities. Sand bars are appealing sites on which to camp, picnic, fish and relax because they are relatively flat, soft, non‐cohesive sand, free of vegetation and near the water's edge. The lack of vegetation and cohesion make sand bars easily erodible. Without appreciable deposition of new material, number and size of bars through a given reach of river will decline substantially over a period of years. We studied 63 beaches and their associated eddies located throughout 10 selected reaches within the designated Wild and Scenic River sections of the Lochsa, Selway, Middle Fork Clearwater, Middle Fork Salmon and Salmon Rivers in Idaho to determine the relation of beaches to the frequency and magnitude of streamflows that deposit appreciable quantities of sand. At present, these rivers have been altered little, if at all, by flow regulation, and only the Salmon River has substantial diversion upstream of a study reach. The river reaches studied have an abundance of sand bar beaches of appreciable size, in spite of suspended sand concentrations that rarely exceeded a few hundred milligrams per litre even during the largest floods.

Calculated mean annual rates of deposition in an eddy vary from 5.8 to more than 100 cm depending primarily on: (1) the duration of streamflows that inundate the eddy sand bar depositions; (2) the rate of the flow exchange between the channel and an eddy and (3) the concentrations of suspended sand in the primary channel. The annual thickness of sand deposition in an eddy varies greatly from year to year depending on the duration of relatively large streamflows. Maximum annual sand depositions in an eddy are three to nine times the estimated long‐term mean values. Relatively large, sustained floods deposit an appreciable portion of total deposition over a period of years. For the period of record, 1930–2002, the seven largest annual depositions, which represent more than 40% of all material deposited over the Lochsa River 21.9 km eddy, occurred in the years with the seven largest instantaneous annual peak floods. Beach area and volume for most beaches, however, are less variable year‐to‐year than the variation in annual deposition would indicate. Accumulative 10‐year weighed deposition rate was computed to estimate the effective variability of beach deposition. Although less variable than the annual deposition, the cumulative 10‐year deposition calculated for the longest hydrologic records, 71 years, existing on the Idaho Wild and Scenic Rivers varied by more than an order of magnitude from less than 20 cm to more than 220 cm. Published in 2006 by John Wiley & Sons, Ltd.
Selection of river flow indices for the assessment of hydroecological change
Authors: Monk Wendy A. , Wood Paul J. , Hannah David M. , Wilson Douglas A.
Published: December 2006

A wide range of ‘ecologically relevant’ hydrological indices (variables) have been identified as potential drivers of riverine communities. Recently, concerns have been expressed regarding index redundancy (i.e. similar patterns of variance) across the host of hydrological descriptors on offer to researchers and water resource managers. Some guiding principles are required to aid selection of the most statistically defensible and meaningful river flow indices for hydroecological analysis. In this short communication, we investigate the utility of a principal components analysis (PCA)‐based method that identifies 25 hydrological variables to characterize the major modes of statistical variation in 201 hydrological indices for 83 rivers across England and Wales. The emergent variables, and all 201 hydrological variables, are used to develop regression models [for the whole data set and three river flow regime shape (i.e. annual hydrograph form) classes] for an 11‐year macroinvertebrate community dataset (i.e. LIFE scores). The same ‘best’ models are produced using the PCA‐based method and all 201 hydrological variables for two of the three river flow regime groups. However, weaker models are yielded by the PCA‐based method for the remaining (flashy) river flow regime class and the whole data set (all 83 rivers). Thus, it is important to exercise caution when employing data reduction/index redundancy approaches, as they may reject variables of ecological significance due to the assumption that the statistically dominant sources of hydrological variability are the principal drivers of, perhaps more subtle (sensitive), hydroecological associations. © Crown copyright 2006. Reproduced with the permission of Her Majesty's Stationery Office. Published by John Wiley & Sons, Ltd.
Efficacy of training in stress and contingency management in cases of irritable bowel syndrome
Authors: Fernández Concepción , Amigo Isaac
Published: December 2006

Forty patients with irritable bowel syndrome were assigned at random to four treatment conditions (two experimental groups: training in stress management and training in contingency management; and two control groups: medical treatment and placebo). In each of the groups (N = 10), care was taken to ensure that half the cases were suitable for training in stress management due to the respondent nature of the illness in these cases and the other half suitable for training in contingency management due to the operant nature of their problem. The patients underwent six individual sessions of specific treatment according to the condition. All of the subjects completed symptom‐monitoring diaries. In the post‐treatment, a MANOVA of mixed factorial design was carried out to analyse the interaction between the suitability of the patient and the type of treatment for the global value of the symptomatology and for each symptom. The results showed that statistically significant changes occurred depending on the interaction between suitability‐treatment p < 0.1) and on the type of treatment (p < 0.05). The clinical changes recorded by the gastroenterologist were maintained after a year. An analysis is made of the behavioural predictors of the resolution of the patients according to suitability and the type of treatment. Copyright © 2006 John Wiley & Sons, Ltd.
Coping is not an ‘either’ ‘or’: the interaction of coping strategies in regulating affect, arousal and performance
Authors: Sideridis Georgios D.
Published: December 2006

The purpose of the present studies was to (a) examine the association between coping, affect, and stress during demanding, stressful tasks, and (b) examine the presence of a synergy between coping strategies towards regulating stress, affect and performance. In Study 1 participants were 53 first year undergraduate students at a state university. Student's coping strategies were assessed prior to a job interview. Results indicated that emotion‐focused coping was associated with significantly elevated negative affect compared to problem‐focused coping. Inclusion of an interaction term reflecting different levels of the two coping strategies showed enhanced adaptation compared to the use of either problem‐focused or emotion‐focused coping strategies. Study 2 aimed at replicating the findings of Study 1, and extend them with assessment of behavioral and physiological indices of stress. Participants were 48 undergraduate students and their coping, affect, and behavioral and physiological stress were assessed prior to an in‐class presentation. Results indicated that neither problem nor emotion‐focused coping were associated with stress levels. However, the interaction of problem‐focused and emotion‐focused strategies was associated with significantly lessened stress. It is concluded that the presence of more than one coping strategy at a given time may be more adaptive compared to the adoption of one type of strategy. Copyright © 2006 John Wiley & Sons, Ltd.
Effects of microenvironmental heterogeneity on the seed‐to‐seedling process and tree coexistence in a riparian forest
Authors: Masaki Takashi , Osumi Katsuhiro , Takahashi Kazunori , Hoshizaki Kazuhiko , Matsune Kenji , Suzuki Wajirou
Published: December 2006

In a temperate riparian forest, the effects of substrate types, canopy gaps and conspecific seedfall density were investigated on the seed‐to‐seedling process for the five dominant species (Aesculus turbinata, Fagus crenata, Acer mono, Pterocarya rhoifolia and Cercidiphyllum japonicum). Densities of seedfall and subsequent seedling recruits were measured in the stand over a period of 6 years. A model assuming that local density of seedling recruits is proportional to seedfall density in the preceding year significantly explained a spatial variation in seedling recruits for all species. Several environmental factors were then added. Substrate composition had a positive effect on P. rhoifolia and C. japonicum. P. rhoifolia was favored by gravel substrate, which also explained the adult distribution of this species in this forest. C. japonicum appeared to be facilitated by a mineral‐soil substrate. However, the distributions of this substrate and adults of C. japonicum did not follow each other closely. A. mono was negatively affected by gaps, and F. crenata was negatively affected by conspecific seedfall density. In contrast, A. turbinata was not significantly affected by any of the environmental factors tested. The microenvironmental heterogeneity in this forest explained species coexistence to a limited extent in the context of seed‐to‐seedling processes. Performances at later stages of the life‐cycle and/or catastrophic disturbances (e.g. landslides) might have a stronger influence on species coexistence in this forest.
n−3 Polyunsaturated fatty acids and inflammation: From molecular biology to the clinic
Authors: Calder Philip C.
Published: December 2006

The immune system is involved in host defense against infectious agents, tumor cells, and environmental insults. Inflammation is an important component of the early immunologic response. Inappropriate or dysfunctional immune responses underlie acute and chronic inflammatory diseases. The n−6 PUFA arachidonic acid (AA) is the precursor of prostaglandins, leukotrienes, and related compounds that have important roles in inflammation and in the regulation of immunity. Feeding fish oil results in partial replacement of AA in cell membranes by EPA. This leads to decreased production of AA‐derived mediators, through several mechanisms, including decreased availability of AA, competition for cyclooxygenase (COX) and lipoxygenase (LOX) enzymes, and decreased expression of COX‐2 and 5‐LOX. This alone is a potentially beneficial anti‐inflammatory effect of n−3 FA. However, n−3 FA have a number of other effects that might occur down‐stream of altered eicosanoid production or might be independent of this effect. For example, dietary fish oil results in suppressed production of proinflammatory cytokines and can modulate adhesion molecule expression. These effects occur at the level of altered gene expression. Fish oil feeding has been shown to ameliorate the symptoms of some animal models of autoimmune disease and to protect against the effects of endotoxin. Clinical studies have reported that oral fish oil supplementation has beneficial effects in rheumatoid arthritis and among some asthmatics, supporting the idea that the n−3 FA in fish oil are anti‐inflammatory. There are indications that the inclusion of fish oil in enteral and parenteral formulae is beneficial to patients.
n−3 long‐chain FA decrease serum levels of TG and remnant‐like particle‐cholesterol in humans
Authors: Hamazaki Kei , Itomura Miho , Huan Mingming , Nishizawa Hiroto , Watanabe Shiro , Hamazaki Tomohito , Sawazaki Shigeki , Terasawa Katsutoshi , Nakajima Shuuji , Terano Takashi , Hata Yoshiya , Fujishiro Seiichi
Published: December 2006

A large number of papers have reported that administration of n−3 FA reduced serum TG concentrations in hypertriglyceridemic patients. However, few studies have examined the effect of n−3 FA on serum concentrations of remnant‐like particle (RLP) cholesterol. Volunteers (n=41) whose serum TG concentrations were 100–300 mg/dL were recruited and randomly assigned to either an n−3 FA group or a control group with stratification by sex, age, and serum TG level in a double‐blind manner. The subjects in the n−3 FA group were administered 125 ml of fermented soybean milk with fish oil containing 600 mg of EPA and 260 mg of DHA/d for 12 wk. The controls consumed control soybean milk with olive oil. Fasting blood samples were obtained before the start of administration and at 4, 8 and 12 wk. EPA concentrations in red blood cells increased significantly in all but one subject in the n−3 FA group, with no significant changes in the control group. TG levels decreased more in the n−3 FA group than in the control group at weeks 4 (P<0.05), 8 (P<0.01), and 12 (P<0.05) with their baseline as covariate. RLP cholesterol levels decreased more in the n−3 FA group than in the control at weeks 8 (P<0.01) and 12 (P<0.05) with their baseline as covariate. The groups did not differ in the other lipid levels. It is likely that n−3 long‐chain FA may exert anti‐atherosclerotic effects by lowering serum TG and RLP‐cholesterol levels even at the dose of 860 mg/d.
Phytosterols and human lipid metabolism: efficacy, safety, and novel foods
Authors: St‐Onge Marie‐Pierre , Jones Peter J. H.
Published: December 2006

Plant sterols have been known for several decades to cause reductions in plasma cholesterol concentrations. These plant materials have been granted a conditional health claim in the United States regarding their effects in the prevention of cardiovascular disease and are being sold in functional foods in several countries in Europe as well as in the United States and Australia. It is generally suggested that daily consumption of ∼2 g of plant sterols can lower cholesterol concentrations as part of a dietary prevention strategy. However, phytosterols have been added and tested for their cholesterol‐lowering effects mainly in spreads. Consumption of these high‐fat foods seemingly flies in the face of current recommendations for the promotion of heart health, which suggest lowering total fat and energy intake to maintain weight. Hence, new food formulations are being evaluated using phytosterols incorporated into low‐fat and reduced‐fat food items. The purpose of this review is to examine the cholesterol‐lowering efficacy of plant sterols, focusing on novel food applications, their mechanism of action, and safety. These novel food formulations include new solubilization processes that lead to improved uses for plant sterols, as well as new foods into which phytosterols have been incorporated, such as breads, cereals, and beef. Such new foods, and formulations should pave the way for greater use of phytosterols in heart health promotion, increasing the longer‐term potential for the creation of innovative functional foods containing plant sterols and their derivatives.
Modulation of body composition and immune cell functions by conjugated linoleic acid in humans and animal models: Benefits vs. risks
Authors: Kelley D. S. , Erickson K. L.
Published: December 2006

We have reviewed the published literature regarding the effects of CLA on body composition and immune cell functions in humans and in animal models. Results from studies in mice, hamsters, rats, and pigs generally support the notion that CLA reduced depot fat in the normal or lean strains. However, in obese rats, it increased body fat or decreased it less than in the corresponding lean controls. These studies also indicate that t10,c12‐CLA was the isomer that reduced adipose fat; however, it also increased the fat content of several other tissues and increased circulating insulin and the saturated FA content of adipose tissue and muscle. Four of the eight published human studies found small but significant reductions in body fat with CLA supplementation; however, the reductions were smaller than the prediction errors for the methods used. The other four human studies found no change in body fat with CLA supplementation. These studies also report that CLA supplementation increased the risk factors for diabetes and cardiovascular disease including increased blood glucose, insulin, insulin resistance, VLDL, C‐reactive protein, lipid peroxidation, and decreased HDL. Most studies regarding the effects of CLA on immune cell functions have been conducted with a mixture of isomers, and the results have been variable. One study conducted in mice with the purified c9,t11‐CLA and t10,c12‐CLA isomers indicated that the two isomers have similar effects on immune cell functions. Some of the reasons for the discrepancies between the effects of CLA in published reports are discussed. Although significant benefit to humans from CLA supplementation is questionable, it may create several health risks in both humans and animals. On the basis of the published data, CLA supplementation of adult human diets to improve body composition or enhance immune functions cannot be recommended at this time.
Docosapentaenoic acid does not completely replace DHA in n−3 FA‐deficient rats during early development
Authors: Greiner Rebecca S. , Catalan Janice N. , Moriguchi Toru , Salem Norman
Published: December 2006

The reciprocal replacement of DHA by docosapentaenoic acid (DPAn−6) was studied in rats that consumed an n−3 FA‐deficient or n−3 FA‐adequate diet. Dams were fed the two experimental diets from weaning and throughout pregnancy and lactation. Their pups were then fed the respective diets after weaning. Cortex FA analysis was performed at various times (0, 5, 10, 20, 50, and 91 d) after birth to determine whether DPAn−6 completely replaced DHA in the n−3‐deficient group. Cortical DHA levels were significantly lower (average 86%) in the n−3‐deficient rats. DPAn−6 increased significantly in the n−3‐deficient rats starting with a 6.5‐fold increase at day 0 up to a 54‐fold increase at day 91 compared with the n−3‐adequate group. However, this significant increase did not completely replace the loss of DHA at postnatal days 5, 10, and 20 in which there was still an 11.5, 10.3, and 8.0% deficit in the sum of DHA and DPAn−6, respectively, in the n−3‐deficient group. Once docosatetraenoic (DTA) and arachidonic acids (AA) were included in the sum (DHA+DPAn−6+DTA+AA), the levels between the two groups were similar, These results suggest that not only DPAn−6 but also other n−6 FA, including DTA and AA, replace DHA in n−3‐deficient rats. The lack of total 22‐carbon (22C) FA in the brain during the rapid membrane biogenesis that occurs during early development could be a factor in the nervous ystem functional deficits associated with n−3 FA deficiency.
Effects of docosapentaenoic acid on neuronal apoptosis
Authors: Kim Hee‐Yong , Akbar Mohammed , Lau Audrey
Published: December 2006

We previously established that n−3 FA status in membrane phospholipids influences the biosynthesis and accumulation of PS in neuronal tissues. We also demonstrated that neuronal apoptosis under adverse conditions is prevented by DHA enrichment in a PS‐dependent manner. In this study, we examined the effect of a structural analog of DHA, docosapentaenoic acid (22∶5n−6, DPA), which accumulates in neuronal membranes during n−3 FA deficiency. We observed that enrichment of neuronal cells with DPA increased the total PS content in comparison to nonenriched control. However, the increase was significantly less than that observed in DHA‐enriched cells, primarily due to the fact that the 18∶0,22∶5n−6 species was not accumulated as effectively as 18∶0,22∶6n−3 in PS. As was the case with DHA, DPA enrichment also protected against cell death induced by staurosporine treatment in Neuro 2A cells, but to a lesser extent. These data indicate that provision of DPA in place of DHA is sufficient neither for fully supporting PS accumulation nor for cell survival. The in vitro interaction between Raf‐1 and membrane was affected not only by the PS content but also by the fatty acyl composition in PS. The reduction of PS concentration as well as the substitution of 18∶0,22∶6 with 16∶0,18∶1 in the liposome considerably reduced the interaction with Raf‐1. These data suggest that depletion of DHA from neuronal tissues may have a compounding effect on Raf‐1 translocation in growth factor signaling. The fact that DPA cannot fully support the protective role played by DHA may provide a basis for the adverse effect of n−3 FA deficiency on neuronal development and function.
Increased blood pressure later in life may be associated with perinatal n−3 fatty acid deficiency
Authors: Armitage James A. , Pearce Adrian D. , Sinclair Andrew J. , Vingrys Algis J. , Weisinger Richard S. , Weisinger Harrison S.
Published: December 2006

Hypertension is a major risk factor for cardiovascular and cerebrovascular disease. Previous work in both animals and humans with high blood pressure has demonstrated the antihypertensive effects of n−3 polyunsaturated fatty acids (PUFA), although it is not known whether these nutrients are effective in preventing hypertension. The predominant n−3 PUFA in the mammalian nervous system, docosahexaenoic acid (DHA), is deposited into synaptic membranes at a high rate during the perinatal period, and recent observations indicate that the perinatal environment is important for the normal development of blood pressure control. This study investigated the importance of perinatal n−3 PUFA supply in the control of blood pressure in adult Sprague‐Dawley rats. Pregnant rat dams were fed semisynthetic diets that were either deficient in (DEF) or supplemented with (CON) n−3 PUFA. Offspring were fed the same diets as their mothers until 9 wk; then, half of the rats from each group were crossed over to the opposite diet, creating four groups, i.e., CON‐CON; CON‐DEF; DEF‐DEF, DEF‐CON. Mean arterial blood pressures (MAP) were measured directly, at 33 wk of age, by cannulation of the femoral artery. The phospholipid fatty acid profile of the hypothalamic region was determined by capillary gas‐liquid chromatography. The tissue phospholipid fatty acid profile reflected the diet that the rats were consuming at the time of testing. Both groups receiving DEF after 9 wk of age (i.e., DEF‐DEF and CON‐DEF) had similar profiles with a reduction in DHA levels of 30%, compared with rats receiving CON (i.e., CON‐CON and DEF‐CON). DEF‐DEF rats had significantly raised MAP compared with all other groups, with differences as great as 17 mm Hg. DEF‐CON rats had raised MAP compared with CON‐CON rats, and DEF‐DEF rats had higher MAP than CON‐DEF rats, despite the fact that their respective fatty acid profiles were not different. These findings indicate that inadequate levels of DHA in the perinatal period are associated with altered blood pressure control in later life. The way in which these long‐term effects are produced remains to be elucidated.
Effect of the Δ6‐desaturase inhibitor SC‐26196 on PUFA metabolism in human cellsinhibitor SC‐26196 on PUFA metabolism in human cells
Authors: Harmon Shawn D. , Kaduce Terry L. , Manuel Tony D. , Spector Arthur A.
Published: December 2006

The objective of this study was to determine the effect of 2,2‐diphenyl‐5‐(4‐{[(1E)‐pyridin‐3‐yl‐methylidene]‐amino}piperazin‐1‐yl)pentanenitrile (SC‐26196), a Δ6‐desaturase inhibitor, on PUFA metabolism in human cells. SC‐26196 inhibited the desaturation of 2 μM [1‐14C] 18∶2n−6 by 87–95% in cultured human skin fibroblasts, coronary artery smooth muscle cells, and astrocytes. By contrast, SC‐26196 did not affect the conversion of [1‐14C]20∶3n−6 to 20∶4 in the fibroblasts, demonstrating that it is selective for Δ6‐desaturase. The IC50values for inhibition of the desaturation of 2 μM [1‐14C] 18∶3n−3 and [3‐14C]24∶5n−3 in the fibroblasts, 0.2–0.4 μM, were similar to those for the inhibition of [1‐14C] 18∶2n−6 desaturation, and the rates of recovery of [1‐14C] 18∶2n−6 and [3‐14C] 24∶5n−3 desaturation after removal of SC‐26196 from the culture medium also were similar. SC‐26196 reduced the conversion of [3‐14C] 22∶5n−3 and [3‐14C] 24∶5n−3 to DHA by 75 and 84%, respectively, but it had no effect on the retroconversion of [3‐14C] 24∶6n−3 to DHA. These results demonstrate that SC‐26196 effectively inhibits the desaturation of 18‐ and 24‐carbon PUFA and, therefore, decreases the synthesis of arachidonic acid, EPA, and DHA in human cells. Furthermore, they provide additional evidence that the conversion of 22∶5n−3 to DHA involves Δ6‐desaturation.
Chylomicron and VLDL TAG structures and postprandial lipid response induced by lard and modified lard
Authors: Yli‐Jokipii Kaisa M. , Schwab Ursula S. , Tahvonen Raija L. , Kurvinen Juha‐Pekka , Mykkänen Hannu M. , Kallio Heikki P. T.
Published: December 2006

Alterations in chylomicron and VLDL TAG and the magnitude of postprandial lipemia were studied in healthy volunteers after two meals of equal FA composition but different TAG‐FA positional distribution. Molecular level information of individual lipoprotein TAG regioisomers was obtained with a tandem MS method. The incremental area under the response curve of VLDL TAG was large (P=0.021) after modified lard than after lard. In plasma TAG, the difference did not quite reach statistical significance (P=0.086). In general, there were less TAG with palmitic acid in the sn‐2 position and more TAG with oleic acid in the sn‐2 position in chylomicrons than in fat ingested. From 1.5 to 8 h postprandially, the proportion of individual chylomicron TAG was constant or influenced by TAG M.W. VLDL TAG regioisomerism was similar regardless of the positional distribution of fat ingested. Significant alterations were seen in VLDL TAG FA, in M.W. fractions, and in individual regioisomers with respect to time. The TAG sn‐14∶0‐18∶1‐18∶1+sn‐18∶1‐18∶1‐14∶0, sn‐16∶0‐16∶1‐18∶1+sn‐18∶1‐16∶1‐16∶0, and sn‐16∶1‐18∶1‐18∶1+sn‐18∶1‐18∶1‐16∶1 decreased (P<0.05); and sn‐16∶0‐16∶0‐18∶2+sn‐18∶2‐16∶0‐16∶0, sn‐16∶0‐16∶0‐18∶1+sn‐18∶1‐16∶0‐16∶0, sn‐16∶0‐18∶1‐16∶0, and sn‐16∶0‐18∶1‐18∶2+sn‐18∶2‐18∶1‐16∶0 increased (P<0.05) after both meals. In conclusion, positional distribution of TAG FA was found to affect postprandial lipid metabolism in healthy normolipidemic subjects.
Phospholipids affect the intestinal absorption of carotenoids in mice
Authors: Baskaran Villikannan , Sugawara Tatsuya , Nagao Akihiko
Published: December 2006

Previously, we have shown that uptake of carotenoids solubilized with mixed micelles by human intestinal Caco‐2 cells is enhanced by lysophosphatidylcholine (lysoPC) and suppressed by PC. This study determined the effect of PC and lysoPC in mixed micelles on the accumulation of β‐carotene and lutein in mice in order to elucidate the roles of micellar phospholipid in the intestinal uptake of carotenoids in vivo. Mixed micelles were composed of 2.5 mM monooleoylglycerol, 7.5 mM oleic acid, 12 mM sodium taurocholate, 200 μM carotenoid, and 3 mM phospholipid in PBS. The mice were fed single doses of β‐carotene or lutein solubilized in PC (PC group), lysoPC (LPC group), and no phospholipid (NoPL group) micelles. The β‐carotene responses in the plasma and liver of the PC group were markedly lower than those of the other two groups, whereas no differences were noticed between the LPC and NoPL groups. The average level of lutein in the plasma of the PC group after administration was significantly (P<0.05) lower than those of the other groups. Moreover, the average level of lutein in the liver was significantly (P<0.05) different among the groups in the order of LPC>NoPL>PC. Thus, the results clearly indicate that PC suppressed the accumulation of β‐carotene and lutein in plasma and liver and that lysoPC enhanced the accumulation of lutein in liver. These results suggest that the hydrolysis of PC to lysoPC plays an important role in the intestinal uptake of carotenoids solubilized in mixed micelles.
Effects of dietary vegetable oil on atlantic salmon hepatocyte fatty acid desaturation and liver fatty acid compositions
Authors: Tocher Douglas R. , Bell J. Gordon , Dick James R. , Crampton Viv O.
Published: December 2006

Fatty acyl desaturase activities, involved in the conversion of the C18EFA 18∶2n−6 and 18∶3n−3 to the highly unsaturated fatty acids (HUFA) 20∶4n−6, 20∶5n−3, and 22∶6n−3, are known to be under nutritional regulation. Specifically, the activity of the desaturation/elongation pathway is depressed when animals, including fish, are fed fish oils rich in n−3 HUFA compared to animals fed, vegetable oils rich in C18FFA. The primary aims of the present study were (i) to establish the relative importance of product inhibition (n−3 HUFA) vs. increased substrate concentration (C18EFA) and (ii) to determine whether 18∶2n−6 and 18∶3n−3 differ in their effects on the hepatic fatty acyl desaturation/elongation pathway in Atlantic salmon (Salmo salar). Smolts were fed 10 experimental diets containing blends of two vegetable oils, linseed (IO), and rapeseed oil (RO), and fish oil (FO) in a triangular mixture design for 50 wk. Fish were sampled after 32 and 50 wk, lipid and FA composition of liver determined, fatty acyl desaturation/elongation activity estimated in hepatocytes using [1‐14C]18∶3n−3 as substrate, and the data subjected to regression analyses. Dietary 18∶2n−6 was positively correlated, and n−3 HUFA negatively correlated, with lipid content of liver. Dietary 20∶5n−3 and 22∶6n−3 were positively correlated with liver FA with a slope greater than unity suggesting relative retention and deposition of these HUFA. In contrast, dietary 18∶2n−6 and 18∶3n−3 were positively correlated with liver FA with a slope of less than unity suggesting metabolismviaβ‐oxidation and/or desaturation/elongation. Consistent with this, fatty acyl desaturation/elongation in hepatocytes was significantly increased by feeding diets containing vegetable oils. Dietary 20∶5n−3 and 22∶6n−3 levels were negatively correlated with hepatocyte fatty acyl desaturation. At 32 wk, 18∶2n−6 but not 18∶3n−3 was positively correlated with hepatocyte fatty acyl desaturation, wheres the reverse was true at 50 wk. The data indicate that both feedback inhibition through increased n−3 HUFA and decreased C18fatty acyl substrate concentration are probably important in determining the level of hepatocyte fatty acyl desaturation and that 18∶2n−6 and 18∶3n−3 may differ in their effects on this pathway.
Desaturase activities in rat model of insulin resistance induced by a sucrose‐rich diet
Authors: Brenner Rodolfo R. , Rimoldi Omar J. , Lombardo Yolanda B. , González María S. , Bernasconi Ana M. , Chicco Adriana , Basabe Juan C.
Published: December 2006

A sucrose‐rich diet, as compared with a similar starch diet, induces a time‐dependent typical noninsulin‐dependent diabetes syndrome characterized by insulin resistance in rats. Within the first 3 wk, there was glucose intolerance associated with hyperinsulinemia, hypertriglyceridemia, and high plasma FFA. In this study, we examined the effect of the sucrose‐rich diet vs. the starch diet during short‐(3 wk) and long‐term treatment (6 mon) on hepatic Δ9, Δ6, and Δ5 desaturases. These enzymes modulate monounsaturated FA and PUFA biosynthesis, respectively. Sucrose feeding (3 wk) caused an initial hyperinsulinemia that was normalized within 6 mon. In the early period (3 wk), stearoyl‐CoA desaturase‐1 (SCD‐1) mRNA and activity were decreased, whereas Δ6 desaturase mRNA abundance and Δ6 and Δ5 desaturase activities remained unchanged. After 6 mon of sucrose feeding, activities of the Δ9, Δ6, and Δ5 desaturases were each increased. The SCD‐1 and Δ6 desaturase mRNA were also correspondingly higher. These increases were consistent with an increase in oleic acid, the 20∶4/18∶2 ratio, and 22∶4n−6 and 22∶5n−6 acids in liver and muscle lipids. On the other hand, the percentage of 22∶6n−3 acid was decreased. In conclusion, a sucrose‐rich diet after 6 mon induces an increase in rat liver SCD‐1 and Δ6 desaturase mRNA and enzymatic activities that are opposite to the changes reported in insulin‐dependent diabetes mellitus. It appears that neither blood insulin levels nor insulin resistance is a factor affecting the Δ9, Δ6, and Δ5 desaturase changes in mRNA and activity found with the sucrose‐rich diet.
Enterotoxigenic Escherichia coli strains bind bovine milk gangliosides in a ceramide‐dependent process
Authors: Martín María‐Jesús , Martín‐Sosa Samuel , Alonso Josefa M. , Hueso Pablo
Published: December 2006

Diarrhea caused by enterotoxigenic Escherichia coli (ETEC) is the main infectious disease of newborn calves. The first step of infection involves bacterial attachment to the intestinal mucosa. This adhesion is mediated by fimbriae that recognize some glycoconjugates on the host cell surface, in particular, several gangliosides. Because milk also contains gangliosides, these have been suggested to serve as ligands for bacterial fimbriae and thus prevent the bacterial attachment to mucosa. The most relevant ETEC strains in calves, including those with K99 and F41 fimbriae, were assayed to determine whether they are able to bind gangliosides isolated from several stages of bovine lactation. Both GM3 and GD3, the main gangliosides of milk, were recognized by ETEC strains, although the different fimbriae showed diverse levels of affinity. Unexpectedly, the adhesion to colostral gangliosides was considerably weaker than that to gangliosides from the other stages of lactation. Because the carbohydrate moiety did not change and because differences in the percentages of unsaturated FA and sphingosine between colostrum and other stages were observed, we conclude that the differences in adhesion could be due to a different composition of the ganglioside caramide.
FA determination in cold water marine samples
Authors: Budge Suzanne M. , Parrish Christopher C.
Published: December 2006

The determination of FA in cold water marine samples is challenging because of the presence of large proportions of a variety of labile PUFA. This study was undertaken to establish optimal methods for FA analysis in various sample types present in the marine environment. Several techniques used in FA analysis, including lipid fractionation, FAME formation, and picolinyl ester synthesis, were examined. Neutral lipids, acetone‐mobile polar lipids, and phospholipids (PL) were readily separated from each other on columns of activated silica gel, but recoveries of PL were reduced. Deactivation of the silica gel with 20% w/w water produced variable recoveries of PL (66±22%). FAME formation with BF3gave optimal recoveries, and a method to remove hydrocarbon contamination from these samples before GC analysis using column chromatography was optimized. Picolinyl derivatives of FA are useful in structural determinations with MS, and a new base‐catalyzed transesterification method of their synthesis from FAME was developed. Finally, a series of calculations, combining FA proportions with acyl lipid class concentrations, was designed to estimate FA concentrations. In algae and animal samples, these estimates were in good agreement with actual FA concentrations determined by internal standards.
Determination of c9,t11‐CLA in major human plasma lipid classes using a combination of methylating methodologies
Authors: Shahin Alam M. , McGuire Michelle K. , McGuire Mark A. , Ritzenthaler Kristin L. , Shultz Terry D.
Published: December 2006

Isomeric CLA exhibit several significant biological activities in animals and humans and are easily isomerized to their corresponding t,t‐CLA isomers during methylation with various acid‐catalyzed reagents. To minimize such isomerization and provide a valid quantification of human plasma CLA content, several methylation methods were tested. Plasma neutral lipid, nonesterified FA (NEFA), and polar lipid classes were separated into the following fractions: (i) cholesteryl ester (CE, 1.2 mg/12 mL, 37.5% lipids), (ii) TAG (0.8 mg/12 mL, 25% lipids), (iii) NFFA (0.2 mg/12 mL, 6.2% lipids), (iv) MAG/DAG/cholesterol (0.3 mg/12 mL, 9.4% lipids), and (v) phospholipid (PL, 0.5 mg/20 mL, 15.6% lipids). Data showed that c9,t11‐CLA found in TAG, MAG/DAG/cholesterol, and PL fractions were converted to methyl esters with sodium methoxide within 2 h at 55°C. However, the c9,t11‐CLA in the CE fraction could not be completely converted to methyl esters by sodium methoxide/acetylchloride in methanol or methanolic KOH; instead, CE was treated with sodium methoxide and methyl acetate in diethyl ether for 1 h. NEFA were converted to methyl esters with trimethylsilyldiazomethane (TMSDAM). All reaction mixtures were monitored by TLC prior to GLC analysis. The highest enrichment of c9,t11‐18∶2 (% FA) was in TAG (0.31%), followed by CE (0.14%) and PL (0.13%). The above methylation methods were then applied to a small subset (n=10) of nonfasting plasma lipid fractions to confirm the applicability of these data. Results from this subset of samples also indicated that the greatest enrichment of c9,t11‐CLA was present in the TAG fraction (0.39%), followed by CE (0.27%) and PL (0.22%). These data indicate that different plasma fractions have different c9,t11‐CLA contents.
Purification and some properties of galectin‐1 derived from water buffalo (Bubalus bubalis) brain
Authors: Ola M. Shamsul , Tabish M. , Khan F.H. , Banu Naheed
Published: December 2006

An increasing number of galectins have been found in various animal species, the most abundant of which is galectin‐1. The purpose of the present study was to purify and characterize galectin‐1 from buffalo brain. We purified the galectin using a combination of ammonium sulphate fractionation and affinity chromatography and the homogeneity was determined by both native polyacrylamide gel electrophoresis (PAGE) and denaturing SDS‐PAGE. The molecular weight of the galectin as determined by SDS‐PAGE under reducing conditions and by gel filtration column under native conditions was 13.8 and 24.5 kDa, respectively, suggesting a dimeric form of galectin. The most potent inhibitor of the galectin activity was lactose, giving complete inhibition of hemagglutination at 0.8 mM. Galectin showed higher specificity towards human blood group A. Free thiol groups were estimated at a molar ratio of 2.9. The effects of alkylating reagents (iodoacetate and iodoacetamide) on saccharide binding of the galectin were studied. Both alkylating reagents significantly inactivated the activity of the galectin within 20 min. The temperature and pH stability of the galectin were determined. Our findings based on physico‐chemical properties, carbohydrate and blood group specificities of the galectin may have future implications in biological and clinical applications.
First, Do No Harm: The Cure for Medical Malpractice
Authors: Herbein Nancy
Published: December 2006

First, Do No Harm: The Cure for Medical Malpractice Ira E. Williams 2004, 197 pages $14.95 softcover