Greater Suppressive Effect Research Articles

Desflurane inhibits endothelium-dependent vasodilation more than sevoflurane with inhibition of endothelial nitric oxide synthase by different mechanisms

The effects of desflurane on endothelium-dependent vasodilation remain uncertain, whereas sevoflurane is known to inhibit it. Endothelium-dependent vasodilation is mainly mediated by endothelial nitric oxide synthase. The effects of desflurane on endothelium-dependent vasodilation were compared with those of sevoflurane, and inhibition mechanisms, including phosphorylation of endothelial nitric oxide synthase and the calcium pathway, were evaluated for the two anesthetics. We hypothesized that desflurane would inhibit endothelium-dependent vasodilation in a concentration-dependent manner more than sevoflurane, with inhibition of a calcium pathway.Isolated rat aortic rings were randomly assigned to treatment with desflurane or sevoflurane for measurements of the vasodilation ratio. To determine NO production with desflurane and sevoflurane, an in vitro assay was performed with cultured bovine aortic endothelial cells. These cells were also used for measurement of intracellular calcium or Western blotting.For endothelium-dependent vasodilation, the ratio of vasodilation was more significantly inhibited by 11.4% desflurane than by 4.8% sevoflurane. Inhibition did not between 5.7% desflurane and 2.4% sevoflurane. No inhibitory effect of desflurane or sevoflurane was observed in endothelium-denuded aorta. Desflurane inhibited nitric oxide production caused by stimulation of bradykinin significantly more than sevoflurane. Desflurane had a greater suppressive effect on the bradykinin-induced increase in intracellular calcium concentration than did sevoflurane. Sevoflurane, but not desflurane, inhibited phosphorylation of the serine 1177 residue by bradykinin stimulation.Desflurane inhibited endothelium-dependent vasodilation more than sevoflurane through inhibition of a calcium pathway. Sevoflurane inhibited endothelium-dependent vasodilation by inhibition of phosphorylation of the serine 1177 residue of endothelial nitric oxide synthase.

Tissue-specific seasonal changes in mitochondrial function of a mammalian hibernator.

Mammalian hibernators, such as golden-mantled ground squirrels (Callospermophilus lateralis; GMGS), cease to feed while reducing metabolic rate and body temperature during winter months, surviving exclusively on endogenous fuels stored before hibernation. We hypothesized that mitochondria, the cellular sites of oxidative metabolism, undergo tissue-specific seasonal adjustments in carbohydrate and fatty acid utilization to facilitate or complement this remarkable phenotype. To address this, we performed high-resolution respirometry of mitochondria isolated from GMGS liver, heart, skeletal muscle, and brown adipose tissue (BAT) sampled during summer (active), fall (prehibernation), and winter (hibernation) seasons using multisubstrate titration protocols. Mitochondrial phospholipid composition was examined as a postulated intrinsic modulator of respiratory function across tissues and seasons. Respirometry revealed seasonal variations in mitochondrial oxidative phosphorylation capacity, substrate utilization, and coupling efficiency that reflected the distinct functions and metabolic demands of the tissues they support. A consistent finding across tissues was a greater influence of fatty acids (palmitoylcarnitine) on respiratory parameters during the prehibernation and hibernation seasons. In particular, fatty acids had a greater suppressive effect on pyruvate-supported oxidative phosphorylation in heart, muscle, and liver mitochondria and enhanced uncoupled respiration in BAT and muscle mitochondria in the colder seasons. Seasonal variations in the mitochondrial membrane composition reflected changes in the supply and utilization of polyunsaturated fatty acids but were generally mild and inconsistent with functional variations. In conclusion, mitochondria respond to seasonal variations in physical activity, temperature, and nutrient availability in a tissue-specific manner that complements circannual shifts in the bioenergetic and thermoregulatory demands of mammalian hibernators.

Response of Vegetable Seedling Emergence to Mustard (Sinapis alba ‘IdaGold’ and Brassica juncea ‘Pacific Gold’) Seed Meal

Mustard Seed Meals (MSMs) are by-products of biodiesel and an alternative to conventional herbicides for organic farming. However, MSMs might also suppress the emergence of vegetable seedlings. The objective of this study was to determine the response of vegetable seedling emergence to different MSM types and rates applied as an alternative herbicide. Six types of vegetable seeds, onion (Allium cepa), two cultivars of lettuce (Lactuca sativa ‘Black Seeded Simpson’ and ‘Buttercrunch’), mustard (Brassica juncea), kale (Brassica oleracea), and Mizuna (Brassica rapa var. japonica), were sowed in petri dishes containing germination mix. MSMs (Sinapis alba ‘IdaGold’ and B. juncea ‘Pacific Gold’) were incorporated into the germination mix at 0, 88, 176, or 265 g·m−2. Petri dishes were sealed for 1, 3, 5, or 7 days after sowing. For onion, ‘Pacific Gold’ had a greater suppressive effect on seedling emergence than ‘IdaGold’. For kale and mustard, ‘IdaGold’ and ‘Pacific Gold’ had similar suppressive effects on seedling emergence, but ‘Pacific Gold’ delayed emergence of kale at 88 g·m−2 when sealed for 3, 5, and 7 days. For Mizuna, ‘IdaGold’ had more suppressive effects than ‘Pacific Gold’ on seedling emergence, while sealing delayed but did not decrease emergence percentage (EP) at the lower rate (88 g·m−2) compared with the control treatment. For ‘Buttercrunch’ lettuce, there were no differences in the suppressive effects between the two MSMs. For ‘Black Seeded Simpson’ lettuce, ‘Pacific Gold’ had more suppressive effects on seedling emergence than ‘IdaGold’ when sealed at the lower rate (88 g·m−2) for longer durations (7 days) or at higher rates (176 and 265 g·m−2) for shorter durations (1 and 3 days). These results suggest that MSMs might suppress vegetable seedling emergence when applied at high rates (176 and 265 g·m−2), and sealing for more than 7 days after sowing may strengthen the suppressive effect. Extending sealing duration at the medium rates could achieve similar weed control results to high rates without sealing.

Abstract B34: Inhibition of breast cancer cell metastasis with a non-cyclooxygenase inhibitory derivative of sulindac by suppressing TGFbeta/miR-21 signaling

Abstract Compelling efficacy on intervention of tumor occurrence and progression by nonsteroidal anti-inflammatory drugs (NSAIDs) has been intensively reported in numerous preclinical and clinical studies. However, the toxicities related to cyclooxygenase (COX) inhibition resulting in suppression of physiologically important prostaglandins limit their clinical use for human cancer chemoprevention. A novel derivative of the NSAID, sulindac sulfide (SS), referred as sulindac sulfide amide (SSA) was recently developed, which lacks COX inhibitory activity, yet shows greater suppressive effect than SS on growth of variable cancer cells. In this study, we focus on the inhibitory activity of SSA on breast tumor cell motility, which has not been studied previously. Our results showed that SSA could inhibit breast tumor cell invasion and migration at sub-cytotoxic concentrations; whereas we previously reported that SS has similar activity on breast and colon tumor cells but at a concentration (50 µM) over 10 times higher than SSA (4 µM). We found that miR-21, a well-documented oncogenic miRNA for promoting tumor cell metastasis, could be downregulated by SSA and involved in mediation of anti-invasive activity of SSA in breast tumor cells. When studying the mechanisms responsible for the regulation of miR-21 by SSA, we demonstrated that TGFbeta signaling suppressed by SSA could ultimately result in downregulation of miR-21 through the transcriptional control. Reduction of Smad2 and Smad3 phosphorylation was the direct response to SSA treatment in metastatic breast tumor MDA-MB-231 cells. By using ChIP assay, we demonstrated that phosphorylated Smad2/3 could bind to the promoter of miR-21 gene. Therefore, in this project, we demonstrate that a non-COX inhibitory derivative of sulindac can inhibit breast tumor metastasis through a new mechanism involving the TGFbeta/miR-21 signaling axis. This study is supported by the NIH/NCI R01 Grant (1R01CA192395) and the American Cancer Society Research Scholar Grant (RSG-13-265-01-RMC). Citation Format: Bin Yi, Hong Chang, Xiangling Feng, Ruixia Ma, Gary A Piazza, Yaguang Xi. Inhibition of breast cancer cell metastasis with a non-cyclooxygenase inhibitory derivative of sulindac by suppressing TGFbeta/miR-21 signaling. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Cancer Cell Cycle - Tumor Progression and Therapeutic Response; Feb 28-Mar 2, 2016; Orlando, FL. Philadelphia (PA): AACR; Mol Cancer Res 2016;14(11_Suppl):Abstract nr B34.

Different Effects of Eicosapentaenoic and Docosahexaenoic Acids on Atherogenic High-Fat Diet-Induced Non-Alcoholic Fatty Liver Disease in Mice.

Non-alcoholic fatty liver disease (NAFLD), the hepatic manifestation of metabolic syndrome, can progress to steatohepatitis (NASH) and advanced liver damage, such as that from liver cirrhosis and cancer. Recent studies have shown the benefits of consuming n-3 polyunsaturated fatty acids (PUFAs) for the treatment of NAFLD. In the present study, we investigated and compared the effects of the major n-3 PUFAs—eicosapentaenoic acid (EPA, C20:5) and docosahexaenoic acid (DHA, C22:6)—in preventing atherogenic high-fat (AHF) diet-induced NAFLD. Mice were fed the AHF diet supplemented with or without EPA or DHA for four weeks. Both EPA and DHA reduced the pathological features of AHF diet-induced NASH pathologies such as hepatic lobular inflammation and elevated serum transaminase activity. Intriguingly, EPA had a greater hepatic triacylglycerol (TG)-reducing effect than DHA. In contrast, DHA had a greater suppressive effect than EPA on AHF diet-induced hepatic inflammation and ROS generation, but no difference in fibrosis. Both EPA and DHA could be effective for treatment of NAFLD and NASH. Meanwhile, the two major n-3 polyunsaturated fatty acids might differ in a relative contribution to pathological intermediate steps towards liver fibrosis.

Abstract P1-07-25: SSA, a novel sulindac sulfide derivative, inhibits tumor cell growth and invasion in breast cancer

Abstract Nonsteroidal anti-inflammatory drugs (NSAIDs), such as sulindac sulfide (SS), have been reported for striking chemopreventive activities in various types of human malignances, including breast cancer. However, the toxicities related to cyclooxygenase (COX) inhibition resulting in suppression of physiologically important prostaglandins limit their clinical use for chemoprevention in human cancer. We recently developed a novel amine derivative of SS named as SSA, which lacks inhibitory effect on COX-1 or -2, yet shows 10 times greater suppressive effect than SS on growth of a panel of breast cells. Moreover, SSA treatment at sub-cytotoxic concentration (4μM) for 36 hr can significantly inhibit both migration and invasion of highly aggressive breast tumor MDA-MB-231cells. To understand the molecular mechanism accounting for this activity, we examined 4 oncogenic miRNAs, including mir-17-92, mir-9, mir-10b, and mir-21 that were previously reported by our group to be associated with SS anti-invasive activity in breast and colorectal cancer. We found SSA could significantly down-regulate these miRNAs; whereas their forced expression was able to counteract the anti-invasive activity of SSA in MDA-MB-231 cells. There results imply that significance of SSA with non-COX inhibitory properties in suppression of tumor cell invasion could provide novel insights into development of safer and more effective strategies for prevention of breast cancer progression and metastasis. In addition, after inducing mobility of non-invasive breast MCF-7 cells by using TGF-β1, we treated these invading cells with SSA and found that their mobility was significantly decreased. These results support anti-invasive activity of SSA in human breast cancer cells and inhibition of TGF-β1 as well as oncogenic miRNAs may be responsible for the mechanistic basis by which SSA prevents breast tumor cell invasion. This study is supported by an American Cancer Society Research Scholar Grant (RSG-13-265-01-RMC) and NIH/NCI R21 Grants (5R21CA160280 and 1R21CA182754) to Yaguang Xi. Citation Format: Bin Yi, Xiangling Feng, Hong Chang, Ruixia Ma, Xiaoguo Zhang, Gary A Piazza, Yaguang Xi. SSA, a novel sulindac sulfide derivative, inhibits tumor cell growth and invasion in breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-07-25.

Effects of Soil Amendments on the Abundance of a Parasitic Weed, Yellow Rattle (Rhinanthus minor) in Hay Fields

Yellow rattle is a hemiparasitic weed that is becoming increasingly problematic in hay fields in the northeastern United States. The biomass of yellow rattle was assessed in two experiments in which commercially available soil amendments were applied to an infested hay field under no-till management. The amendments were applied in the fall of 2010 and 2011 and included wood ash, biochar, hardwood sawdust, lime, and K. Wood ash applied at a rate of 8,967 kg ha−1 (4 tons per acre) had the greatest suppressive effect and reduced yellow rattle biomass the following summer by 86 and 92% relative to the untreated control in Experiments 1 and 2, respectively. Two additional treatments included in Experiment 2, a doubled rate of wood ash and sawdust applied at a rate of 13,450 kg ha−1, also reduced yellow rattle biomass. No other treatments affected yellow rattle biomass. A partial least-squares regression (PLSR) analysis that included aboveground plant community and soil biochemical data explained only 42.4% of the variation in yellow rattle biomass, suggesting that the mechanisms responsible for the suppression of yellow rattle by wood ash and sawdust are complex. Amending hay fields with wood ash or sawdust may be an effective nonherbicide strategy for managing yellow rattle infestations. Additional research will be required to determine the mechanisms and generality of yellow rattle suppression by wood ash and sawdust amendments to the soil.

A meta-analysis of the effect of dietary fat on enteric methane production, digestibility and rumen fermentation in sheep, and a comparison of these responses between cattle and sheep

The objective of this study was to investigate the effect of dietary fat supplementation on methane production, digestibility and rumen fermentation in sheep by means of a meta-analysis, and subsequently to compare the results with response in cattle. A dataset was constructed compiling data from ten published publications containing 41 dietary treatments and 259 observations on sheep. Fat supplementation decreased methane production (expressed as g/day, g/kg dry matter (DM) intake, g/kg digestible DM intake, % of gross energy intake) linearly (P<0.05; R2=0.49 to 0.78). Inclusion of fat did not (P=0.21) affect DM intake. However, digestibilities of DM (P=0.04; R2=0.24) and neutral detergent fiber (P=0.09; R2=0.16) reduced linearly with increasing fat concentrations. Conversely, fat digestibility increased quadratically (P=0.03; R2=0.65) with increasing fat contents. Total volatile fatty acids and acetate percentage in rumen fluid were not altered (P>0.10) by dietary fat supplementation. Percentage of propionate increased linearly (P=0.06; R2=0.17), while butyrate percentage (P=0.06; R2=0.21), acetate to propionate ratio (P=0.05; R2=0.22) and ammonia concentration (P=0.02; R2=0.39) in rumen fluid decreased linearly with increasing fat concentrations. Supplementation of fat had greater suppressive effects on methane production expressed as digestible DM intake in sheep than cattle, but had similar responses on digestibility and rumen fermentation. In conclusion, low concentration of fat in the diet may decrease methane emission without adversely affecting rumen fermentation; but it may lower fiber digestibility at high concentrations.

Autophagy and cancer stem cells or tumor-initiating cells in human breast cancer

Autophagy and cancer stem cells or tumor-initiating cells in human breast cancer

Inhibition of the autophagic flux by salinomycin in breast cancer stem-like/progenitor cells interferes with their maintenance

Breast cancer tissue contains a small population of cells that have the ability to self-renew; these cells are known as cancer stem-like cells (CSCs). We have recently shown that autophagy is essential for the tumorigenicity of these CSCs. Salinomycin (Sal), a K+/H+ ionophore, has recently been shown to be at least 100 times more effective than paclitaxel in reducing the proportion of breast CSCs. However, its mechanisms of action are still unclear. We show here that Sal blocked both autophagy flux and lysosomal proteolytic activity in both CSCs and non-CSCs derived from breast cancer cells. GFP-LC3 staining combined with fluorescent dextran uptake and LysoTracker-Red staining showed that autophagosome/lysosome fusion was not altered by Sal treatment. Acridine orange staining provided evidence that lysosomes display the characteristics of acidic compartments in Sal-treated cells. However, tandem mCherry-GFP-LC3 assay indicated that the degradation of mCherry-GFP-LC3 is blocked by Sal. Furthermore, the protein degradation activity of lysosomes was inhibited, as demonstrated by the rate of long-lived protein degradation, DQ-BSA assay and measurement of cathepsin activity. Our data indicated that Sal has a relatively greater suppressant effect on autophagic flux in the ALDH+ population in HMLER cells than in the ALDH− population; moreover, this differential effect on autophagic flux correlated with an increase in apoptosis in the ALDH+ population. ATG7 depletion accelerated the proapoptotic capacity of Sal in the ALDH+ population. Our findings provide new insights into how the autophagy-lysosomal pathway contributes to the ability of Sal to target CSCs in vitro.

Cytotoxic effects and changes in cytokine gene expression induced by microcystin-containing extract in fish immune cells – An in vitro and in vivo study

Blooms of cyanobacteria producing very toxic secondary metabolites (especially microcystins) are potent environmental stressors, hazardous not only to aquatic animals but also to public health. The purpose of this study was to investigate the effects of an extract containing microcystins on immune cells isolated from the common carp (Cyprinus carpio L.). In the present study it has been found that the extract induced apoptosis and inhibited in vitro lymphocyte proliferation. In addition, the results indicated the possible role of oxidative stress in this cytotoxicity and apoptosis. The in vivo investigations showed that the extract containing microcystins had greater suppressive effects on the essential functions of immune cells (intracellular reactive oxygen species production and lymphocyte proliferation) than the pure toxin alone. Moreover, immersion of fish in the toxic extract caused changes in the mRNA levels of various pro- and anti-inflammatory cytokines in carp leukocytes, while after exposure to the pure toxin, only IL1-β expression was markedly up-regulated. The observed modulatory effects on immune cells could have important implications for the health of planktivorous fish, which feed more frequently on toxic cyanobacteria.

Party Government and Variation in Corporate Influence on Agency Decision Making: OSHA Regulation, 1981–2006

ObjectiveTo understand how changes in the partisan control of the institutions of government may condition the effect of corporate political activities on bureaucratic decision making.MethodsI examine the variation in the effectiveness of corporate political expenditures in reducing workplace safety (Occupational Safety and Health Administration) violations across partisan contexts between 1981 and 2006 for a large number of corporations.ResultsCorporate expenditures have a greater suppressant effect on workplace safety violations (but not inspections) when the Republicans control the Congress or presidency.ConclusionsCorporations are able to influence bureaucratic decision making, but bureaucrats balance the demands of corporations against those of other party constituencies and their political principals. Thus, the partisan control of government importantly conditions corporate influence in the bureaucracy.

Decitabine Facilitates the Generation of Functional Regulatory γδT Cells Via Foxp3 Gene Demethylation and NF-κB up-Regulation

Abstract 3281Regulatory γδT cells (γδTregs) are capable of suppressing T-cell activation and proliferation (Rita et al Journal of immunology 2009). Our previous studies demonstrated the immunosuppressive features of γδTregs and further supported the use of γδTregs as a promising therapeutic strategy for the adoptive immunotherapy of allograft rejection, post-transplantation graft-versus-host disease (GVHD) and autoimmune diseases (Hu et al ASH abstract 2011). To this end, large-scale, efficient expansion of γδTregs represents a fundamentally important prerequisite for their clinical application. Here we explored the efficacy of decitabine (a DNA hypomethylating agent) for the generation of functional γδTregs and its underlying mechanisms.Human peripheral blood mononuclear cells (PBMCs) were cultured with interleukin (IL)-2, IL-15, TGF-β1 and zoledronic acid (ZOL). Decitabine was added to aliquots of PBMCs. Frequency and absolute number of γδTregs were investigated by flow cytometry (FACS) and trypan blue live-cell counts after cultivation. Our results showed a higher frequency (61.9±10.3% versus 38.4±7.8%, p<0.01) and absolute number of γδTregs [(3.1±0.1)×106 versus (5.9±0.2)×106, p<0.01] were seen in cells treated with decitabine plus ZOL/IL-2/IL-15/TGF-β1 (referred to as decitabine-induced γδTregs below) than in cell without decitabine induction (referred to as common γδTregs) as shown in Fig. 1. These data demonstrated that decitabine and ZOL/cytokines synergized to induce stable γδTregs via improved Foxp3 expression.Next we analyzed the underlying mechanisms of decitabine on γδTreg induction. Genomic DNA was isolated from γδTregs sorted by FACS. The Foxp3 gene methyaltion status of upstream enhancer CpG islands from −5995 to −5778 and from −5031 to −4792, proximal promoter CpG island from -139 to -15 and non-coding DNA sequence 3 (CNS3) CpG island from 3748 to 3971 was analyzed by bisulfite sequencing. We found decitabine-induced γδTregs displayed efficient CpG demethylation of the upstream enhancer from −5031 to −4792, and of CNS3 from 3748 to 3971, but no differences were detected in the other CpG islands investigated in contrast to common γδTregs (Fig. 2A). We subsequently investigated if DNA demethylation of CpG islands could influence upstream enhancer or CNS3 activity to promote Foxp3 transcription. The upstream enhancer from −5031 to −4792 and CNS3 from 3748 to 3971 were methylated using SssI (CpG) methylase, and methylated or unmethylated sequences were inserted into demethylated pFoxP3Pro, respectively. Vectors were added to γδT cells and electroporated using the T-023 program of the Nucleofector. Dual fluorescence-based transient reporter assays showed an obvious reduction in luciferase activity after methylation of both CpG islands, but not with the demethylated CpG islands (Fig. 2B), indicating that demethylation of the upstream enhancer and CNS3 can promote Foxp3 expression via increased enhancer activity.Transcription factors (TF) play important roles in gene expression. To test whether decitabine enhanced specific TFs expression to influence γδTreg induction, we performed TF CHIP assays in FACS-sorted common γδTregs versus decitabine-induced γδTregs. The expression levels of 245 TFs were evaluated and the result showed that NF-κb expression in decitabine-induced γδTregs was up-regulated 50 times in contrast to that in common γδTregs. NF-κb up-regulation was further comfirmed by western blot analysis from 6 different healthy volunteers.Finally, We evaluated the immunosuppressive function of the enriched γδTregs on Carboxyfluorescein Diacetate (CFSE)-labeled hPBMC proliferation and activation stimulated with anti-CD3/anti-CD28 monoclonal antibodies for 5 days in vitro. As shown in Fig. 3, both common γδTregs and decitabine-induced γδTregs exerted dose-dependent suppression of proliferation, but decitabine-induced γδTregs had a greater suppressive effect than common γδTregs.In conclusion, these data demonstrate for the first time that decitabine facilitates the generation of functional γδTregs via foxp3 gene demethylation and NF-κb up-regulation. Futhermore, our results lay the foundation for large-scale availability of induced γδTregs for potential clinical applications, and reveal novel targets for regulating Foxp3 expression in γδT cells. [Display omitted] [Display omitted] [Display omitted] Disclosures:No relevant conflicts of interest to declare.

Factors that influence negative summation in a spatial-search task with pigeons

A variant of the standard conditioned inhibition procedure was used to evaluate landmark-based spatial search in a touchscreen preparation. Pigeons were given compound trials with one landmark (A) positioned in a consistent spatial relationship to a hidden goal and another landmark (B) positioned randomly with respect to A and the hidden goal (AB+). On half of the non-reinforced inhibitory trials, A was paired with landmark X (AX-) and on the remaining trials B was paired with Y (BY-). All subjects were also given reinforced trials with a transfer excitor (T+). During conditioned inhibition training, subjects showed no change in overall responding during AX- trials but did show a decrease in the number of pecks to the goal location signaled by A. During non-reinforced summation tests with landmark T, X had a greater suppressive effect than did Y on overall responding but the percentage of pecks at the goal did not differ unless X was positioned near the expected goal signaled by T. These data demonstrate that the effectiveness of a stimulus trained as an inhibitor is dependent on the strength of the association between its training excitor (A) and the US, as well as, the spatial arrangement of stimuli during testing.

Differential effects of dairy snacks on appetite, but not overall energy intake

Dietary regulation of appetite may contribute to the prevention and management of excess body weight. The present study examined the effect of consumption of individual dairy products as snacks on appetite and subsequent ad libitum lunch energy intake. In a randomised cross-over trial, forty overweight men (age 32 (sd 9) years; BMI 27 (sd 2)kg/m2) attended four sessions 1 week apart and received three isoenergetic (841kJ) and isovolumetric (410ml) servings of dairy snacks or water (control) 120min after breakfast. Appetite profile was determined throughout the morning and ad libitum energy intake was assessed 90min after the intake of snacks. Concentrations of amino acids, glucose, insulin, ghrelin and peptide tyrosine tyrosine were measured at baseline (0min) and 80min after the intake of snacks. Although the results showed that yogurt had the greatest suppressive effect on appetite, this could be confounded by the poor sensory ratings of yogurt. Hunger rating was 8, 10 and 24% (P<0·001) lower after the intake of yogurt than cheese, milk and water, respectively. Energy intake was 11, 9 and 12% (P<0·02) lower after the intake of yogurt, cheese and milk, respectively, compared with water (4312 (se 226)kJ). Although there was no difference in the postprandial responses of hormones, alanine and isoleucine concentrations were higher after the intake of yogurt than cheese and milk (P<0·05). In conclusion, all dairy snacks reduced appetite and lunch intake compared with water. Yogurt had the greatest effect on suppressing subjective appetite ratings, but did not affect subsequent food intake compared with milk or cheese.

Suppressive effect of docosahexaenoyl‐lysophosphatidylcholine and 17‐hydroxydocosahexaenoyl‐lysophosphatidylcholine on levels of cytokines in spleen of mice treated with lipopolysaccharide

Lysophosphatidylcholine (lysoPC) with polyunsaturated fatty acyl chains has been known to be anti-inflammatory in vivo. In the present study, we examined the effect of docosahexaenoyl-lysophosphatidylcholine (DHE-lysoPC) and 17-hydroxydocosahexaenoyl-lysophosphatidylcholine (17-HDHE-lysoPC) on spleen weight and cytokine level in spleen of mice treated with lipopolysaccharide (LPS). For this purpose, mice were administrated i.p. with DHE-lysoPC or 17-HDHE-lysoPC 1 h before i.p. injection of LPS. First, DHE-lysoPC (50–400 µg/kg) was found to suppress the LPS-induced increase of spleen weight dose-dependently, and such a suppressive effect was greater for 17-HDHE-lysoPC, compared to DHE-lysoPC. Next, in an attempt to see the effect of DHE-lysoPC on cytokine levels in spleen of mice treated with LPS, DHE-lysoPC was found to suppress LPS-induced increase in the levels of cytokines such as TNF-α, IL-1β, or IL-6 in a dose dependent manner (50–400 µg/kg), in contrast to DHA showing a significant action at a high dose (400 µg/kg) only. The greater suppressive effect of 17-HDHE-lysoPC (15–150 µg/kg) than DHE-lysoPC suggested that action of DHE-lysoPC may be enhanced through lipoxygenation process. Presumably in support of this, when the interval time between 17-HDHE-lysoPC administration and LPS challenge was varied, the cytokine-suppressing effect was found to be augmented in a time-dependent manner. Taken all together, it is suggested that DHE-lysoPC and 17-HDHE-lysoPC may be beneficial in suppressing the inflammation in spleen tissue.

Prefrontal cortex transcranial direct current stimulation associated with aerobic exercise change aspects of appetite sensation in overweight adults

This study investigated whether transcranial direct current stimulation (tDCS) on dorsolateral prefrontal cortex (DLPFC) isolated or combined with aerobic exercise influenced the desire to eat, hunger, and satiety in overweight subjects. Nine volunteers underwent anodal or sham tDCS (2 mA; 20 min) over DLPFC and isocaloric exercise bouts (70%VO 2R; ∼200 kcal). The appetite sensations were evaluated by visual analogue scales at four moments: I – Baseline; II – After tDCS; III – Post-Exercise and IV – 30-min Post-Exercise. The tDCS on left DLPFC decreased the desire to eat at baseline (tDCS −26% vs. −14% Sham). The tDCS associated with exercise had greater suppressing effect in desire to eat compared to either tDCS or exercise alone (tDCS −39% vs. −27% Sham). Moreover, the tDCS associated with exercise decreased hunger (tDCS −48% vs. 36% Sham) and increased satiety (tDCS 28% vs. 7% Sham) immediately after exercise. The post-exercise 30-min recovery elicited an overall increase in appetite. However the increase in desire to eat and hunger after recovery was lower after tDCS (29% and 13%, respectively) compared to sham stimulation (77% and 113%, respectively). These findings in overweight subjects indicate that the combination of tDCS over DLPFC and aerobic exercise induced greater decrease in appetite sensations compared to anodal tDCS or exercise alone.

The effects of morphine and nicotine co-administration on body weight, food intake and appetite-regulating peptides in rats.

Summary Previous studies in humans and animals have reported that nicotine administration decreases body weight and caloric intake. Opiate and cigarette have been used concomitantly as drug abuse. The aim of the present study was, therefore, to analyze the effect of chronic co-administration of nicotine and morphine on food intake, body weight and on some feeding-associated peptides. All experiments were carried out on male Wistar rats. Animals were randomly assigned to the free-fed and pair-fed control groups, nicotine- and morphine-treated and nicotine plus morphine groups. Morphine sulfate (20 mg/kg for 14 days s.c.) and nicotine (4 mg/kg for 14 days i.p.) were injected to the rats. The serum levels of leptin and neuropeptide Y (NPY) were measured by enzyme immunosorbant assay and radioimmunoassay, respectively. The results showed that nicotine had a greater suppressing effect on total food intake than morphine alone or nicotine plus morphine. Furthermore, chronic injection of nicotine significantly decreased body weight as compared with before injection, while body weight changes were not observed in morphine-treated rats. The mean body weight in the morphine-treated rats was lower than that in the free-fed control animals. The serum level of NPY was decreased just in the nicotine-injected group. A significant decrease in leptin levels was observed in the drug treated and pair-fed groups. In conclusion, morphine modulates the decreasing effect of nicotine on food intake, and it seems that the mechanism underlying the attenuating effects of morphine on the nicotine effects involves mediation, at least in part, by preventing the effect of nicotine on NPY levels.

Effects of sevoflurane,isoflurane and desflurane on transcranial electrical motor evoked potentials in patients undergoing neurosurgery

Objective To compare the effects of sevoflurane,isoflurane and desflurane on transcranial electrical motor evoked potentials(MEPs)in patients undergoing neurosurgery.Methods Sixty ASA Ⅰ or Ⅱ patients aged 18-64 yr undergoing neurosurgery were randomly divided into 3 groups(n = 20 each): sevoflurane group,isoflurane group and desflurane group.BIS value and MEPs were monitored.The end-tidal concentrations of sevoflurane,isoflurane and desflurane were adjusted and maintained at 0.50,0.75,1.00 and 1.30 MAC respectively for at least 15 min during 6 stimuli delivered at 1000 Hz and 300 V lasting for 75 μs.The amplitudes and latency of MEPs and BIS value were recorded before administration(baseline)and the each stable state (T1-4).The failure rate of MEPs was also recorded.Results The amplitude of MEPs and BIS value were significantly decreased at T1.2 and the latency of MEPs was prolonged at T1-4 in desflurane group compared with sevoflurane and isoflurane groups(P＜0.05).There was no significant difference in the amplitudes and latency of MEPs and BIS value between group sevoflurane and isoflurane(P＞0.05).The failure rates of MEPs were 0 at baseline,T1 and T2,0,5% and 20% at T3 ,and 5%,20% and 45% at T4 in sevoflurane,isoflurane and desflurane groups respectively.The failure rate of MEPs was significantly higher in desflurane group than in sevoflurane and isoflurane groups(P＜0.05).Conclusion Desflurane has greater suppressive effect on MEPs than sevoflurane and isoflurane.1.00 MAC of sevoflurane and isoflurane,while 0.75-1.00 MAC of desflurane may be the suitable end-tidal concentration for MEP monitoring. Key words: Anesthetics,inhalation; Isoflurane; Evoked potentials,motor; Electric stimulation

Management intervention affects river-bound spatial dynamics of elephants

The potential consequences of growing elephant populations are a cause of debate and concern in many African conservation areas. Even though space use of elephants is central to understanding their biodiversity consequences, few studies explicitly consider how different management strategies influence elephants’ spatial utilization of landscapes. Here we study elephant’s spatial dispersion patterns in relation to different sized rivers under different management regimes by analyzing aerial census data collected annually during the mid dry-season between 1985 and 2007 across the 19,485 km 2 Kruger National Park. We found that different sized rivers can be used as a simple proxy for elephant density gradients in the dry-season. This has implications for stratifying and designing elephant impact monitoring programmes in semi-arid savannas. Furthermore, we found that dry-season elephant densities increased around rivers in a period after culling was stopped and large-scale artificial water provision reduced. Most importantly, these localized density increases were not spatially homogeneous, with culling and water provision having a greater suppressing effect on the localized densities around larger rivers than around smaller rivers and areas far removed from rivers. Assuming a positive correlation between elephant density and elephant impact, the impact of elephants around larger rivers has increased disproportionably compared to areas around smaller rivers and areas far removed from rivers since management stopped culling and reduced large-scale water provision. Since areas around the larger rivers have unique functional, structural and compositional characteristics, they should receive specific attention in impact monitoring programmes and elephant management policies. Furthermore, we recommend that if artificial waterholes are provided in semi-arid systems, it should not be located close to rivers that are mostly dry nor in areas far from rivers as this may compromise the spatio-temporal refugia that these areas afford aspects of biodiversity that are sensitive to continuous elephant impact.