Insulin resistance in human subjects having impaired glucose regulation

International Nuclear Information System (INIS)

Khan, S.H.; Khan, F.A.; Ijaz, A.

2007-01-01

To determine insulin resistance in human subjects having impaired glucose regulation (IGR) by Homeostasis Model Assessment for Insulin Resistance (HOMA-IR). A total of 100 subjects with impaired glucose regulation were selected for evaluation of metabolic syndrome as per the criteria of National Cholesterol Education Program, Adult Treatment Panel III (NCEP, ATP III), along with 47 healthy age and gender-matched controls. Physical examination to determine blood pressure and waist circumference was carried out and so was sampling for plasma glucose, serum triglycerides, HDL-cholesterol and insulin. Insulin resistance was calculated by the HOMA-IR. Finally, subjects with and without metabolic syndrome were compared with controls (n=47), using one-way ANOVA for studying insulin resistance between groups, with Tukey's post-hoc comparison. The frequency of finding metabolic syndrome in cases of IGR remained 47%. The insulin resistance demonstrated stepwise worsening from control population (mean=1.54, 95 % CI: 1.77 - 2.37) to subjects suffering from only IGR (mean=2.07, 95 % CI: 1.77- 2.37) to metabolic syndrome (mean=2.67, 95 %, CI: 2.34 - 3.00) (p < 0.001). Patients with impaired glucose regulation may have significant insulin resistance. It is, thus, recommended that a vigorous search be made to measure insulin resistance in all cases diagnosed to have impaired glucose regulation. (author)

Exposure to perfluorinated compounds and human semen quality in Arctic and European populations

DEFF Research Database (Denmark)

Toft, G; Jönsson, B A G; Lindh, C H

2012-01-01

Perfluorinated compounds (PFCs) have been suspected to adversely affect human reproductive health. The aim of this study was to investigate the associations between PFC exposure and male semen quality.......Perfluorinated compounds (PFCs) have been suspected to adversely affect human reproductive health. The aim of this study was to investigate the associations between PFC exposure and male semen quality....

Microencapsulated bitter compounds (from Gentiana lutea) reduce daily energy intakes in humans

NARCIS (Netherlands)

Mennella, Ilario; Fogliano, Vincenzo; Ferracane, Rosalia; Arlorio, Marco; Pattarino, Franco; Vitaglione, Paola

2016-01-01

Mounting evidence showed that bitter-tasting compounds modulate eating behaviour through bitter taste receptors in the gastrointestinal tract. This study aimed at evaluating the influence of microencapsulated bitter compounds on human appetite and energy intakes. A microencapsulated bitter

Anti-human rhinoviral activity of polybromocatechol compounds isolated from the rhodophyta, Neorhodomela aculeata.

Science.gov (United States)

Park, Soon-Hye; Song, Jae-Hyoung; Kim, Taejung; Shin, Woon-Seob; Park, Gab Man; Lee, Seokjoon; Kim, Young-Joo; Choi, Pilju; Kim, Heejin; Kim, Hui-Seong; Kwon, Dur-Han; Choi, Hwa Jung; Ham, Jungyeob

2012-10-01

An extract of the red alga, Neorhodomela aculeata, exhibited antiviral activity against human rhinoviruses. Bioassay-guided purification was performed to yield six compounds, which were subsequently identified as lanosol (1) and five polybromocatechols (2-6) by spectroscopic methods, including 1D and 2D NMR and mass spectrometric analyses. Structurally, all of these compounds, except compound 5, contain one or two 2,3-dibromo-4,5-dihydroxyphenyl moieties. In a biological activity assay, compound 1 was found to possess antiviral activity with a 50% inhibitory concentration (IC₅₀) of 2.50 μg/mL against HRV2. Compound 3 showed anti-HRV2 activity, with an IC₅₀ of 7.11 μg/mL, and anti-HRV3 activity, with an IC₅₀ of 4.69 μg/mL, without demonstrable cytotoxicity at a concentration of 20 μg/mL. Collectively, the results suggest that compounds 1 and 3 are candidates for novel therapeutics against two different groups of human rhinovirus.

Socially Impaired Robots: Human Social Disorders and Robots' Socio-Emotional Intelligence

OpenAIRE

Vitale, Jonathan; Williams, Mary-Anne; Johnston, Benjamin

2016-01-01

Social robots need intelligence in order to safely coexist and interact with humans. Robots without functional abilities in understanding others and unable to empathise might be a societal risk and they may lead to a society of socially impaired robots. In this work we provide a survey of three relevant human social disorders, namely autism, psychopathy and schizophrenia, as a means to gain a better understanding of social robots' future capability requirements. We provide evidence supporting...

Anti-Human Rhinoviral Activity of Polybromocatechol Compounds Isolated from the Rhodophyta, Neorhodomela aculeata

Directory of Open Access Journals (Sweden)

Hui-Seong Kim

2012-10-01

Full Text Available An extract of the red alga, Neorhodomela aculeata, exhibited antiviral activity against human rhinoviruses. Bioassay-guided purification was performed to yield six compounds, which were subsequently identified as lanosol (1 and five polybromocatechols (2–6 by spectroscopic methods, including 1D and 2D NMR and mass spectrometric analyses. Structurally, all of these compounds, except compound 5, contain one or two 2,3-dibromo-4,5-dihydroxyphenyl moieties. In a biological activity assay, compound 1 was found to possess antiviral activity with a 50% inhibitory concentration (IC50 of 2.50 μg/mL against HRV2. Compound 3 showed anti-HRV2 activity, with an IC50 of 7.11 μg/mL, and anti-HRV3 activity, with an IC50 of 4.69 μg/mL, without demonstrable cytotoxicity at a concentration of 20 μg/mL. Collectively, the results suggest that compounds 1 and 3 are candidates for novel therapeutics against two different groups of human rhinovirus.

Interactive effects of morphine and dopaminergic compounds on spatial working memory in rhesus monkeys

Institute of Scientific and Technical Information of China (English)

Jian-Hong Wang; Joshua Dominie Rizak; Yan-Mei Chen; Liang Li; Xin-Tian Hu; Yuan-Ye Ma

2013-01-01

Opiates and dopamine (DA) play key roles in learning and memory in humans and animals.Although interactions between these neurotransmitters have been found,their functional roles remain to be fully elucidated,and their dysfunction may contribute to human diseases and addiction.Here we investigated the interactions of morphine and dopaminergic neurotransmitter systems with respect to learning and memory in rhesus monkeys by using the Wisconsin General Test Apparatus (WGTA) delayed-response task.Morphine and DA agonists (SKF-38393,apomorphine and bromocriptine) or DA antagonists (SKF-83566,haloperidol and sulpiride) were co-administered to the monkeys 30 min prior to the task.We found that dose-patterned co-administration of morphine with D1 or D2 antagonists or agonists reversed the impaired spatial working memory induced by morphine or the compounds alone.For example,morphine at 0.01 mg/kg impaired spatial working memory,while morphine (0.01 mg/kg) and apomorphine (0.01 or 0.06 mg/kg) co-treatment ameliorated this effect.Our findings suggest that the interactions between morphine and dopaminergic compounds influence spatial working memory in rhesus monkeys.A better understanding of these interactive relationships may provide insights into human addiction.

Dihydrochalcone Compounds Isolated from Crabapple Leaves Showed Anticancer Effects on Human Cancer Cell Lines

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Xiaoxiao Qin

2015-11-01

Full Text Available Seven dihydrochalcone compounds were isolated from the leaves of Malus crabapples, cv. “Radiant”, and their chemical structures were elucidated by UV, IR, ESI-MS, 1H-NMR and 13C-NMR analyses. These compounds, which include trilobatin (A1, phloretin (A2, 3-hydroxyphloretin (A3, phloretin rutinoside (A4, phlorizin (A5, 6′′-O-coumaroyl-4′-O-glucopyranosylphloretin (A6, and 3′′′-methoxy-6′′-O-feruloy-4′-O-glucopyranosyl-phloretin (A7, all belong to the phloretin class and its derivatives. Compounds A6 and A7 are two new rare dihydrochalcone compounds. The results of a MTT cancer cell growth inhibition assay demonstrated that phloretin and these derivatives showed significant positive anticancer activities against several human cancer cell lines, including the A549 human lung cancer cell line, Bel 7402 liver cancer cell line, HepG2 human ileocecal cancer cell line, and HT-29 human colon cancer cell line. A7 had significant effects on all cancer cell lines, suggesting potential applications for phloretin and its derivatives. Adding a methoxyl group to phloretin dramatically increases phloretin’s anticancer activity.

High Uric Acid Activates the ROS-AMPK Pathway, Impairs CD68 Expression and Inhibits OxLDL-Induced Foam-Cell Formation in a Human Monocytic Cell Line, THP-1

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Chaohuan Luo

2016-11-01

Full Text Available Background/Aims: Hyperuricemia is part of the metabolic-syndrome cluster of abdominal obesity, impaired glucose tolerance, insulin resistance, dyslipidemia, and hypertension. Monocytes/macrophages are critical in the development of metabolic syndrome, including gout, obesity and atherosclerosis. However, how high uric acid (HUA exposure affects monocyte/macrophage function remains unclear. In this study, we investigated the molecular mechanism of HUA exposure in monocytes/macrophages and its impact on oxidized low-density lipoprotein (oxLDL-induced foam-cell formation in a human monocytic cell line, THP-1. Methods: We primed THP-1 cells with phorbol-12-myristate-13-acetate (PMA for differentiation, then exposed cells to HUA and detected the production of reactive oxygen species (ROS and analyzed the level of phospho-AMPKα. THP-1 cells were pre-incubated with Compound C, an AMPK inhibitor, or N-acetyl-L-cysteine (NAC, a ROS scavenger, or HUA before PMA, to assess CD68 expression and phospho-AMPKα level. PMA-primed THP-1 cells were pre-treated with oxLDL before Compound C and HUA treatment. Western blot analysis was used to examine the levels of phospho-AMPKα, CD68, ABCG1, ABCA1, cyclooxygenase-2 (COX-2 and NF-κB (p65. Flow cytometry was used to assess ROS production and CD68 expression in live cells. Oil-red O staining was used to observe oxLDL uptake in cells. Results: HUA treatment increased ROS production in PMA-primed THP-1 cells; NAC blocked HUA-induced oxidative stress. HUA treatment time-dependently increased phospho-AMPKα level in PMA-primed THP-1 cells. The HUA-induced oxidative stress increased phospho-AMPKα levels, which was blocked by NAC. HUA treatment impaired CD68 expression during cell differentiation by activating the AMPK pathway, which was reversed by Compound C treatment. Finally, HUA treatment inhibited oxLDL uptake in the formation of foam cells in THP-1 cells, which was blocked by Compound C treatment. HUA treatment

Concentration and distribution of dioxins and related compounds in various human organs

Energy Technology Data Exchange (ETDEWEB)

Iida, T.; Hirakawa, H.; Hori, T.; Tobiishi, K.; Matsueda, T. [Fukuoka Inst. of Health and Environmental Sciences, Dazaifu, Fukuoka (Japan); Todaka, T. [Japan Food Hygiene Association, Tokyo (Japan); Watanabe, S. [Tokyo Univ. of Agriculture, Tokyo (Japan); Yamada, T. [Keio Univ. School of Medicine, Tokyo (Japan)

2004-09-15

Polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs) and non-ortho coplanar polychlorinated biphenyls (Non-Co-PCBs) and mono-ortho coplanar polychlorinated biphenyls (Mono-Co-PCBs) accumulate in the human body due to their highly lipophilic properties. In recent years, there has been some concern about the potential health effects of dioxins and related chemicals for the general population of humans. Although there exists an enormous amount of data on this subject, most of it is from breast milk and blood, due to ease of collection; information concerning concentrations and distribution in various human organs hardly exists. Therefore, new data concerning various human tissues is required to evaluate the pathophysiological significance of dioxins and related compounds in humans. The aim of this study was to investigate the concentration levels and distribution of dioxins and related compounds in various human organ tissues. We previously reported on the concentration levels in the human liver and adipose tissues from 28 donors. In this paper, we determined the concentrations of dioxin-like isomers in 8 organs, including blood, lungs, liver, bile, spleen, pancreas, kidney and mesentery fat from 20 donors.

Human neural tuning estimated from compound action potentials in normal hearing human volunteers

Science.gov (United States)

Verschooten, Eric; Desloovere, Christian; Joris, Philip X.

2015-12-01

The sharpness of cochlear frequency tuning in humans is debated. Evoked otoacoustic emissions and psychophysical measurements suggest sharper tuning in humans than in laboratory animals [15], but this is disputed based on comparisons of behavioral and electrophysiological measurements across species [14]. Here we used evoked mass potentials to electrophysiologically quantify tuning (Q10) in humans. We combined a notched noise forward masking paradigm [9] with the recording of trans tympanic compound action potentials (CAP) from masked probe tones in awake human and anesthetized monkey (Macaca mulatta). We compare our results to data obtained with the same paradigm in cat and chinchilla [16], and find that CAP-Q10values in human are ˜1.6x higher than in cat and chinchilla and ˜1.3x higher than in monkey. To estimate frequency tuning of single auditory nerve fibers (ANFs) in humans, we derive conversion functions from ANFs in cat, chinchilla, and monkey and apply these to the human CAP measurements. The data suggest that sharp cochlear tuning is a feature of old-world primates.

Hippocampal Volume Reduction in Humans Predicts Impaired Allocentric Spatial Memory in Virtual-Reality Navigation.

Science.gov (United States)

Guderian, Sebastian; Dzieciol, Anna M; Gadian, David G; Jentschke, Sebastian; Doeller, Christian F; Burgess, Neil; Mishkin, Mortimer; Vargha-Khadem, Faraneh

2015-10-21

The extent to which navigational spatial memory depends on hippocampal integrity in humans is not well documented. We investigated allocentric spatial recall using a virtual environment in a group of patients with severe hippocampal damage (SHD), a group of patients with "moderate" hippocampal damage (MHD), and a normal control group. Through four learning blocks with feedback, participants learned the target locations of four different objects in a circular arena. Distal cues were present throughout the experiment to provide orientation. A circular boundary as well as an intra-arena landmark provided spatial reference frames. During a subsequent test phase, recall of all four objects was tested with only the boundary or the landmark being present. Patients with SHD were impaired in both phases of this task. Across groups, performance on both types of spatial recall was highly correlated with memory quotient (MQ), but not with intelligence quotient (IQ), age, or sex. However, both measures of spatial recall separated experimental groups beyond what would be expected based on MQ, a widely used measure of general memory function. Boundary-based and landmark-based spatial recall were both strongly related to bilateral hippocampal volumes, but not to volumes of the thalamus, putamen, pallidum, nucleus accumbens, or caudate nucleus. The results show that boundary-based and landmark-based allocentric spatial recall are similarly impaired in patients with SHD, that both types of recall are impaired beyond that predicted by MQ, and that recall deficits are best explained by a reduction in bilateral hippocampal volumes. In humans, bilateral hippocampal atrophy can lead to profound impairments in episodic memory. Across species, perhaps the most well-established contribution of the hippocampus to memory is not to episodic memory generally but to allocentric spatial memory. However, the extent to which navigational spatial memory depends on hippocampal integrity in humans is

Potent inhibitors of human LAT1 (SLC7A5) transporter based on dithiazole and dithiazine compounds for development of anticancer drugs.

Science.gov (United States)

Napolitano, Lara; Scalise, Mariafrancesca; Koyioni, Maria; Koutentis, Panayiotis; Catto, Marco; Eberini, Ivano; Parravicini, Chiara; Palazzolo, Luca; Pisani, Leonardo; Galluccio, Michele; Console, Lara; Carotti, Angelo; Indiveri, Cesare

2017-11-01

The LAT1 transporter is acknowledged as a pharmacological target of tumours since it is strongly overexpressed in many human cancers. The purpose of this work was to find novel compounds exhibiting potent and prolonged inhibition of the transporter. To this aim, compounds based on dithiazole and dithiazine scaffold have been screened in the proteoliposome experimental model. Inhibition was tested on the antiport catalysed by hLAT1 as transport of extraliposomal [ 3 H]histidine in exchange with intraliposomal histidine. Out of 59 compounds tested, 8 compounds, showing an inhibition higher than 90% at 100µM concentration, were subjected to dose-response analysis. Two of them exhibited IC 50 lower than 1µM. Inhibition kinetics, performed on the two best inhibitors, indicated a mixed type of inhibition with respect to the substrate. Furthermore, inhibition of the transporter was still present after removal of the compounds from the reaction mixture, but was reversed on addition of dithioerythritol, a S-S reducing agent, indicating the formation of disulfide(s) between the compounds and the protein. Molecular docking of the two best inhibitors on the hLAT1 homology structural model, highlighted interaction with the substrate binding site and formation of a covalent bond with the residue C407. Indeed, the inhibition was impaired in the hLAT1 mutant C407A confirming the involvement of that Cys residue. Treatment of SiHa cells expressing hLAT1 at relatively high level, with the two most potent inhibitors led to cell death which was not observed after treatment with a compound exhibiting very poor inhibitory effect. Copyright © 2017 Elsevier Inc. All rights reserved.

Recycling energy to restore impaired ankle function during human walking.

Directory of Open Access Journals (Sweden)

Steven H Collins

Full Text Available BACKGROUND: Humans normally dissipate significant energy during walking, largely at the transitions between steps. The ankle then acts to restore energy during push-off, which may be the reason that ankle impairment nearly always leads to poorer walking economy. The replacement of lost energy is necessary for steady gait, in which mechanical energy is constant on average, external dissipation is negligible, and no net work is performed over a stride. However, dissipation and replacement by muscles might not be necessary if energy were instead captured and reused by an assistive device. METHODOLOGY/PRINCIPAL FINDINGS: We developed a microprocessor-controlled artificial foot that captures some of the energy that is normally dissipated by the leg and "recycles" it as positive ankle work. In tests on subjects walking with an artificially-impaired ankle, a conventional prosthesis reduced ankle push-off work and increased net metabolic energy expenditure by 23% compared to normal walking. Energy recycling restored ankle push-off to normal and reduced the net metabolic energy penalty to 14%. CONCLUSIONS/SIGNIFICANCE: These results suggest that reduced ankle push-off contributes to the increased metabolic energy expenditure accompanying ankle impairments, and demonstrate that energy recycling can be used to reduce such cost.

Organobromine compound profiling in human adipose: Assessment of sources of bromophenol

International Nuclear Information System (INIS)

Gao, Shixiong; Wan, Yi; Zheng, Guomao; Luo, Kai; Kannan, Kurunthachalam; Giesy, John P.; Lam, Michael H.W.; Hu, Jianying

2015-01-01

Bromophenols (BRPs) have been widely detected in human tissues, however, relative proportions from natural products and/or anthropogenic flame retardants are not clear. 21 polybrominated diphenyl ethers (PBDEs), 15 MeO/OH-PBDEs, and 10 BRPs were simultaneously quantified in adipose collected from people from New York City, USA. An in vitro assay utilizing human liver microsomes was performed for detected predominant organobromine. High concentrations of 2,4,6-triBRP and PBDEs were observed, and extremely low concentrations of naturally occurring MeO/OH-PBDEs were detected. Similar biotransformatioin rates of BRPs and MeO/OH-PBDEs indicated that the relative high concentration of 2,4,6-triBRP in humans was not of natural origin. Significant correlation observed between concentrations of 2,4,6-triBRP and BDE-209 suggested that the two chemicals may share a common source. Both 2,4,6-triBRP and BDE-209 were detected in commercial ABS resins, suggesting that plastic products made from ABS resins could be potential sources of co-exposure of the two compounds for humans. - Highlights: • 2,4,6-triBRP detected with high concentrations in human was not of natural origin. • Co-exposure of 2,4,6-triBRP and BDE-209 was observed in human samples. • Products made from ABS resins were potential exposure sources of 2,4,6-triBRP. - The profile of organobromine compounds in human together with biotransformation behaviors indicate that anthropogenic sources mainly contribute to high levels of bromophenols in humans

Evaluation of a Silicone Membrane as an Alternative to Human Skin for Determining Skin Permeation Parameters of Chemical Compounds.

Science.gov (United States)

Uchida, Takashi; Yakumaru, Masafumi; Nishioka, Keisuke; Higashi, Yoshihiro; Sano, Tomohiko; Todo, Hiroaki; Sugibayashi, Kenji

2016-01-01

We evaluated the effectiveness of a silicone membrane as an alternative to human skin using the skin permeation parameters of chemical compounds. An in vitro permeation study using 15 model compounds was conducted, and permeation parameters comprising permeability coefficient (P), diffusion parameter (DL(-2)), and partition parameter (KL) were calculated from each permeation profile. Significant correlations were obtained in log P, log DL(-2), and log KL values between the silicone membrane and human skin. DL(-2) values of model compounds, except flurbiprofen, in the silicone membrane were independent of the lipophilicity of the model compounds and were 100-fold higher than those in human skin. For antipyrine and caffeine, which are hydrophilic, KL values in the silicone membrane were 100-fold lower than those in human skin, and P values, calculated as the product of a DL(-2) and KL, were similar. For lipophilic compounds, such as n-butyl paraben and flurbiprofen, KL values for silicone were similar to or 10-fold higher than those in human skin, and P values for silicone were 100-fold higher than those in human skin. Furthermore, for amphiphilic compounds with log Ko/w values from 0.5 to 3.5, KL values in the silicone membrane were 10-fold lower than those in human skin, and P values for silicone were 10-fold higher than those in human skin. The silicone membrane was useful as a human skin alternative in an in vitro skin permeation study. However, depending on the lipophilicity of the model compounds, some parameters may be over- or underestimated.

Peripheral inflammation acutely impairs human spatial memory via actions on medial temporal lobe glucose metabolism.

Science.gov (United States)

Harrison, Neil A; Doeller, Christian F; Voon, Valerie; Burgess, Neil; Critchley, Hugo D

2014-10-01

Inflammation impairs cognitive performance and is implicated in the progression of neurodegenerative disorders. Rodent studies demonstrated key roles for inflammatory mediators in many processes critical to memory, including long-term potentiation, synaptic plasticity, and neurogenesis. They also demonstrated functional impairment of medial temporal lobe (MTL) structures by systemic inflammation. However, human data to support this position are limited. Sequential fluorodeoxyglucose positron emission tomography together with experimentally induced inflammation was used to investigate effects of a systemic inflammatory challenge on human MTL function. Fluorodeoxyglucose positron emission tomography scanning was performed in 20 healthy participants before and after typhoid vaccination and saline control injection. After each scanning session, participants performed a virtual reality spatial memory task analogous to the Morris water maze and a mirror-tracing procedural memory control task. Fluorodeoxyglucose positron emission tomography data demonstrated an acute reduction in human MTL glucose metabolism after inflammation. The inflammatory challenge also selectively compromised human spatial, but not procedural, memory; this effect that was independent of actions on motivation or psychomotor response. Effects of inflammation on parahippocampal and rhinal glucose metabolism directly mediated actions of inflammation on spatial memory. These data demonstrate acute sensitivity of human MTL to mild peripheral inflammation, giving rise to associated functional impairment in the form of reduced spatial memory performance. Our findings suggest a mechanism for the observed epidemiologic link between inflammation and risk of age-related cognitive decline and progression of neurodegenerative disorders including Alzheimer's disease. Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Organotin compounds cause structure-dependent induction of progesterone in human choriocarcinoma Jar cells.

Science.gov (United States)

Hiromori, Youhei; Yui, Hiroki; Nishikawa, Jun-ichi; Nagase, Hisamitsu; Nakanishi, Tsuyoshi

2016-01-01

Organotin compounds, such as tributyltin (TBT) and triphenyltin (TPT), are typical environmental contaminants and suspected endocrine-disrupting chemicals because they cause masculinization in female mollusks. In addition, previous studies have suggested that the endocrine disruption by organotin compounds leads to activation of peroxisome proliferator-activated receptor (PPAR)γ and retinoid X receptor (RXR). However, whether organotin compounds cause crucial toxicities in human development and reproduction is unclear. We here investigated the structure-dependent effect of 12 tin compounds on mRNA transcription of 3β-hydroxysteroid dehydrogenase type I (3β-HSD I) and progesterone production in human choriocarcinoma Jar cells. TBT, TPT, dibutyltin, monophenyltin, tripropyltin, and tricyclohexyltin enhanced progesterone production in a dose-dependent fashion. Although tetraalkyltin compounds such as tetrabutyltin increased progesterone production, the concentrations necessary for activation were 30-100 times greater than those for trialkyltins. All tested active organotins increased 3β-HSD I mRNA transcription. We further investigated the correlation between the agonistic activity of organotin compounds on PPARγ and their ability to promote progesterone production. Except for DBTCl2, the active organotins significantly induced the transactivation function of PPARγ. In addition, PPARγ knockdown significantly suppressed the induction of mRNA transcription of 3β-HSD I by all active organotins except DBTCl2. These results suggest that some organotin compounds promote progesterone biosynthesis in vitro by inducing 3β-HSD I mRNA transcription via the PPARγ signaling pathway. The placenta represents a potential target organ for these compounds, whose endocrine-disrupting effects might cause local changes in progesterone concentration in pregnant women. Copyright © 2014 Elsevier Ltd. All rights reserved.

Neurodegeneration caused by expression of human truncated tau leads to progressive neurobehavioural impairment in transgenic rats.

Science.gov (United States)

Hrnkova, Miroslava; Zilka, Norbert; Minichova, Zuzana; Koson, Peter; Novak, Michal

2007-01-26

Human truncated tau protein is an active constituent of the neurofibrillary degeneration in sporadic Alzheimer's disease. We have shown that modified tau protein, when expressed as a transgene in rats, induced AD characteristic tau cascade consisting of tau hyperphosphorylation, formation of argyrophilic tangles and sarcosyl-insoluble tau complexes. These pathological changes led to the functional impairment characterized by a variety of neurobehavioural symptoms. In the present study we have focused on the behavioural alterations induced by transgenic expression of human truncated tau. Transgenic rats underwent a battery of behavioural tests involving cognitive- and sensorimotor-dependent tasks accompanied with neurological assessment at the age of 4.5, 6 and 9 months. Behavioural examination of these rats showed altered spatial navigation in Morris water maze resulting in less time spent in target quadrant (popen field was not influenced by transgene expression. However beam walking test revealed that transgenic rats developed progressive sensorimotor disturbances related to the age of tested animals. The disturbances were most pronounced at the age of 9 months (p<0.01). Neurological alterations indicating impaired reflex responses were other added features of behavioural phenotype of this novel transgenic rat. These results allow us to suggest that neurodegeneration, caused by the non-mutated human truncated tau derived from sporadic human AD, result in the neuronal dysfunction consequently leading to the progressive neurobehavioural impairment.

Improvement of a synthetic lure for Anopheles gambiae using compounds produced by human skin microbiota.

Science.gov (United States)

Verhulst, Niels O; Mbadi, Phoebe A; Kiss, Gabriella Bukovinszkiné; Mukabana, Wolfgang R; van Loon, Joop J A; Takken, Willem; Smallegange, Renate C

2011-02-08

Anopheles gambiae sensu stricto is considered to be highly anthropophilic and volatiles of human origin provide essential cues during its host-seeking behaviour. A synthetic blend of three human-derived volatiles, ammonia, lactic acid and tetradecanoic acid, attracts A. gambiae. In addition, volatiles produced by human skin bacteria are attractive to this mosquito species. The purpose of the current study was to test the effect of ten compounds present in the headspace of human bacteria on the host-seeking process of A. gambiae. The effect of each of the ten compounds on the attractiveness of a basic blend of ammonia, lactic and tetradecanoic acid to A. gambiae was examined. The host-seeking response of A. gambiae was evaluated in a laboratory set-up using a dual-port olfactometer and in a semi-field facility in Kenya using MM-X traps. Odorants were released from LDPE sachets and placed inside the olfactometer as well as in the MM-X traps. Carbon dioxide was added in the semi-field experiments, provided from pressurized cylinders or fermenting yeast. The olfactometer and semi-field set-up allowed for high-throughput testing of the compounds in blends and in multiple concentrations. Compounds with an attractive or inhibitory effect were identified in both bioassays. 3-Methyl-1-butanol was the best attractant in both set-ups and increased the attractiveness of the basic blend up to three times. 2-Phenylethanol reduced the attractiveness of the basic blend in both bioassays by more than 50%. Identification of volatiles released by human skin bacteria led to the discovery of compounds that have an impact on the host-seeking behaviour of A. gambiae. 3-Methyl-1-butanol may be used to increase mosquito trap catches, whereas 2-phenylethanol has potential as a spatial repellent. These two compounds could be applied in push-pull strategies to reduce mosquito numbers in malaria endemic areas.

Human immunodeficiency virus impairs reverse cholesterol transport from macrophages.

Directory of Open Access Journals (Sweden)

Zahedi Mujawar

2006-10-01

Full Text Available Several steps of HIV-1 replication critically depend on cholesterol. HIV infection is associated with profound changes in lipid and lipoprotein metabolism and an increased risk of coronary artery disease. Whereas numerous studies have investigated the role of anti-HIV drugs in lipodystrophy and dyslipidemia, the effects of HIV infection on cellular cholesterol metabolism remain uncharacterized. Here, we demonstrate that HIV-1 impairs ATP-binding cassette transporter A1 (ABCA1-dependent cholesterol efflux from human macrophages, a condition previously shown to be highly atherogenic. In HIV-1-infected cells, this effect was mediated by Nef. Transfection of murine macrophages with Nef impaired cholesterol efflux from these cells. At least two mechanisms were found to be responsible for this phenomenon: first, HIV infection and transfection with Nef induced post-transcriptional down-regulation of ABCA1; and second, Nef caused redistribution of ABCA1 to the plasma membrane and inhibited internalization of apolipoprotein A-I. Binding of Nef to ABCA1 was required for down-regulation and redistribution of ABCA1. HIV-infected and Nef-transfected macrophages accumulated substantial amounts of lipids, thus resembling foam cells. The contribution of HIV-infected macrophages to the pathogenesis of atherosclerosis was supported by the presence of HIV-positive foam cells in atherosclerotic plaques of HIV-infected patients. Stimulation of cholesterol efflux from macrophages significantly reduced infectivity of the virions produced by these cells, and this effect correlated with a decreased amount of virion-associated cholesterol, suggesting that impairment of cholesterol efflux is essential to ensure proper cholesterol content in nascent HIV particles. These results reveal a previously unrecognized dysregulation of intracellular lipid metabolism in HIV-infected macrophages and identify Nef and ABCA1 as the key players responsible for this effect. Our findings

Inorganic arsenic impairs differentiation and functions of human dendritic cells

International Nuclear Information System (INIS)

Macoch, Mélinda; Morzadec, Claudie; Fardel, Olivier; Vernhet, Laurent

2013-01-01

Experimental studies have demonstrated that the antileukemic trivalent inorganic arsenic prevents the development of severe pro-inflammatory diseases mediated by excessive Th1 and Th17 cell responses. Differentiation of Th1 and Th17 subsets is mainly regulated by interleukins (ILs) secreted from dendritic cells (DCs) and the ability of inorganic arsenic to impair interferon-γ and IL-17 secretion by interfering with the physiology of DCs is unknown. In the present study, we demonstrate that high concentrations of sodium arsenite (As(III), 1–2 μM) clinically achievable in plasma of arsenic-treated patients, block differentiation of human peripheral blood monocytes into immature DCs (iDCs) by inducing their necrosis. Differentiation of monocytes in the presence of non-cytotoxic concentrations of As(III) (0.1 to 0.5 μM) only slightly impacts endocytotic activity of iDCs or expression of co-stimulatory molecules in cells activated with lipopolysaccharide. However, this differentiation in the presence of As(III) strongly represses secretion of IL-12p70 and IL-23, two major regulators of Th1 and Th17 activities, from iDCs stimulated with different toll-like receptor (TLR) agonists in metalloid-free medium. Such As(III)-exposed DCs also exhibit reduced mRNA levels of IL12A and/or IL12B genes when activated with TLR agonists. Finally, differentiation of monocytes with non-cytotoxic concentrations of As(III) subsequently reduces the ability of activated DCs to stimulate the release of interferon-γ and IL-17 from Th cells. In conclusion, our results demonstrate that clinically relevant concentrations of inorganic arsenic markedly impair in vitro differentiation and functions of DCs, which may contribute to the putative beneficial effects of the metalloid towards inflammatory autoimmune diseases. Highlights: ► Inorganic arsenic impairs differentiation and functions of human dendritic cells (DCs) ► Arsenite (> 1 μM) blocks differentiation of dendritic cells by

Inorganic arsenic impairs differentiation and functions of human dendritic cells

Energy Technology Data Exchange (ETDEWEB)

Macoch, Mélinda; Morzadec, Claudie [UMR INSERM U1085, Institut de Recherche sur la Santé, l' Environnement et le Travail (IRSET), Université de Rennes 1, 2 avenue du Professeur Léon Bernard, 35043 Rennes (France); Fardel, Olivier [UMR INSERM U1085, Institut de Recherche sur la Santé, l' Environnement et le Travail (IRSET), Université de Rennes 1, 2 avenue du Professeur Léon Bernard, 35043 Rennes (France); Pôle Biologie, Centre Hospitalier Universitaire (CHU) Rennes, 2 rue Henri Le Guilloux, 35033 Rennes (France); Vernhet, Laurent, E-mail: laurent.vernhet@univ-rennes1.fr [UMR INSERM U1085, Institut de Recherche sur la Santé, l' Environnement et le Travail (IRSET), Université de Rennes 1, 2 avenue du Professeur Léon Bernard, 35043 Rennes (France)

2013-01-15

Experimental studies have demonstrated that the antileukemic trivalent inorganic arsenic prevents the development of severe pro-inflammatory diseases mediated by excessive Th1 and Th17 cell responses. Differentiation of Th1 and Th17 subsets is mainly regulated by interleukins (ILs) secreted from dendritic cells (DCs) and the ability of inorganic arsenic to impair interferon-γ and IL-17 secretion by interfering with the physiology of DCs is unknown. In the present study, we demonstrate that high concentrations of sodium arsenite (As(III), 1–2 μM) clinically achievable in plasma of arsenic-treated patients, block differentiation of human peripheral blood monocytes into immature DCs (iDCs) by inducing their necrosis. Differentiation of monocytes in the presence of non-cytotoxic concentrations of As(III) (0.1 to 0.5 μM) only slightly impacts endocytotic activity of iDCs or expression of co-stimulatory molecules in cells activated with lipopolysaccharide. However, this differentiation in the presence of As(III) strongly represses secretion of IL-12p70 and IL-23, two major regulators of Th1 and Th17 activities, from iDCs stimulated with different toll-like receptor (TLR) agonists in metalloid-free medium. Such As(III)-exposed DCs also exhibit reduced mRNA levels of IL12A and/or IL12B genes when activated with TLR agonists. Finally, differentiation of monocytes with non-cytotoxic concentrations of As(III) subsequently reduces the ability of activated DCs to stimulate the release of interferon-γ and IL-17 from Th cells. In conclusion, our results demonstrate that clinically relevant concentrations of inorganic arsenic markedly impair in vitro differentiation and functions of DCs, which may contribute to the putative beneficial effects of the metalloid towards inflammatory autoimmune diseases. Highlights: ► Inorganic arsenic impairs differentiation and functions of human dendritic cells (DCs) ► Arsenite (> 1 μM) blocks differentiation of dendritic cells by

Activation of PPAR{gamma} by Human Cytomegalovirus for de novo Replication Impairs Migration and Invasiveness of Cytotrophoblast from Early Placenta

DEFF Research Database (Denmark)

Rauwel, Benjamin; Mariamé, Bernard; Martin, Hélène

2010-01-01

, as assessed by using well-established in vitro models of invasive trophoblast i.e. primary cultures of EVCT isolated from first trimester placentas and the EVCT-derived cell line HIPEC. Our data provide new clues to explain how early infection during pregnancy could impair implantation, placentation...... and chromatin immunoprecipitation assays. Due to the key role of PPARgamma in placentation and its specific trophoblast expression within the human placenta, we then provided evidence that by activating PPARgamma human cytomegalovirus dramatically impaired early human trophoblast migration and invasiveness...

A Synthetic Thiourea-Based Tripodal Receptor that Impairs the Function of Human First Trimester Cytotrophoblast Cells

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Darijana Horvat

2014-07-01

Full Text Available A synthetic tripodal-based thiourea receptor (PNTTU was used to explore the receptor/ligand binding affinity using CTB cells. The human extravillous CTB cells (Sw.71 used in this study were derived from first trimester chorionic villus tissue. The cell proliferation, migration and angiogenic factors were evaluated in PNTTU-treated CTB cells. The PNTTU inhibited the CTBs proliferation and migration. The soluble fms-like tyrosine kinase-1 (sFlt-1 secretion was increased while vascular endothelial growth factor (VEGF was decreased in the culture media of CTB cells treated with ≥1 nM PNTTU. The angiotensin II receptor type 2 (AT2 expression was significantly upregulated in ≥1 nM PNTTU-treated CTB cells in compared to basal; however, the angiotensin II receptor, type 1 (AT1 and vascular endothelial growth factor receptor 1 (VEGFR-1 expression was downregulated. The anti-proliferative and anti-angiogenic effect of this compound on CTB cells are similar to the effect of CTSs. The receptor/ligand affinity of PNTTU on CTBs provides us the clue to design a potent inhibitor to prevent the CTS-induced impairment of CTB cells.

Prediction of Human Intestinal Absorption of Compounds Using Artificial Intelligence Techniques.

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Kumar, Rajnish; Sharma, Anju; Siddiqui, Mohammed Haris; Tiwari, Rajesh Kumar

2017-01-01

Information about Pharmacokinetics of compounds is an essential component of drug design and development. Modeling the pharmacokinetic properties require identification of the factors effecting absorption, distribution, metabolism and excretion of compounds. There have been continuous attempts in the prediction of intestinal absorption of compounds using various Artificial intelligence methods in the effort to reduce the attrition rate of drug candidates entering to preclinical and clinical trials. Currently, there are large numbers of individual predictive models available for absorption using machine learning approaches. Six Artificial intelligence methods namely, Support vector machine, k- nearest neighbor, Probabilistic neural network, Artificial neural network, Partial least square and Linear discriminant analysis were used for prediction of absorption of compounds. Prediction accuracy of Support vector machine, k- nearest neighbor, Probabilistic neural network, Artificial neural network, Partial least square and Linear discriminant analysis for prediction of intestinal absorption of compounds was found to be 91.54%, 88.33%, 84.30%, 86.51%, 79.07% and 80.08% respectively. Comparative analysis of all the six prediction models suggested that Support vector machine with Radial basis function based kernel is comparatively better for binary classification of compounds using human intestinal absorption and may be useful at preliminary stages of drug design and development. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Accumulation of 19 environmental phenolic and xenobiotic heterocyclic aromatic compounds in human adipose tissue.

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Wang, Lei; Asimakopoulos, Alexandros G; Kannan, Kurunthachalam

2015-05-01

The extensive use of environmental phenols (e.g., bisphenol A) and heterocyclic aromatic compounds (e.g., benzothiazole) in consumer products as well as widespread exposure of humans to these compounds have been well documented. Biomonitoring studies have used urinary measurements to assess exposures, based on the assumption that these chemicals are metabolized and eliminated in urine. Despite the fact that some of these chemicals are moderately lipophilic, the extent of their accumulation in adipose fat tissues has not been convincingly demonstrated. In this study, human adipose fat samples (N=20) collected from New York City, USA, were analyzed for the presence of environmental phenols, including bisphenol A (BPA), benzophenone-3 (BP-3), triclosan (TCS), and parabens, as well as heterocyclic aromatic compounds, including benzotriazole (BTR), benzothiazole (BTH), and their derivatives. BPA and TCS were frequently detected in adipose tissues at concentrations (geometric mean [GM]: 3.95ng/g wet wt for BPA and 7.21ng/g wet wt for TCS) similar to or below the values reported for human urine. High concentrations of BP-3 were found in human adipose tissues (GM: 43.4; maximum: 4940ng/g wet wt) and a positive correlation between BP-3 concentrations and donor's age was observed. The metabolite of parabens, p-hydroxybenzoic acid (p-HB), also was found at elevated levels (GM: 4160; max.: 17,400ng/g wet wt) and a positive correlation between donor's age and sum concentration of parabens and p-HB were found. The GM concentrations of BTR and BTH in human adipose tissues were below 1ng/g, although the methylated forms of BTR (i.e., TTR and XTR) and the hydrated form of BTH (i.e., 2-OH-BTH) were frequently detected in adipose samples, indicating widespread exposure to these compounds. Our results suggest that adipose tissue is an important repository for BP-3 and parabens, including p-HB, in the human body. Copyright © 2015 Elsevier Ltd. All rights reserved.

Various MRS application tools for Alzheimer disease and mild cognitive impairment.

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Gao, F; Barker, P B

2014-06-01

MR spectroscopy is a noninvasive technique that allows the detection of several naturally occurring compounds (metabolites) from well-defined regions of interest within the human brain. Alzheimer disease, a progressive neurodegenerative disorder, is the most common cause of dementia in the elderly. During the past 20 years, multiple studies have been performed on MR spectroscopy in patients with both mild cognitive impairment and Alzheimer disease. Generally, MR spectroscopy studies have found decreased N-acetylaspartate and increased myo-inositol in both patients with mild cognitive impairment and Alzheimer disease, with greater changes in Alzheimer disease than in mild cognitive impairment. This review summarizes the information content of proton brain MR spectroscopy and its related technical aspects, as well as applications of MR spectroscopy to mild cognitive impairment and Alzheimer disease. While MR spectroscopy may have some value in the differential diagnosis of dementias and assessing prognosis, more likely its role in the near future will be predominantly as a tool for monitoring disease response or progression in treatment trials. More work is needed to evaluate the role of MR spectroscopy as a biomarker in Alzheimer disease and its relationship to other imaging modalities. © 2014 by American Journal of Neuroradiology.

Protective effects of compound FLZ on β-amyloid peptide-(25-35)-induced mouse hippocampal injury and learning and memory impairment

Institute of Scientific and Technical Information of China (English)

Fang FANG; Geng-tao LIU

2006-01-01

Aim: To study the protective effects of compound FLZ, a novel synthetic analogue of natural squamosamide, on learning and memory impairment and lesions of the hippocampus caused by icv injection of β-amyloid25-35 (Aβ25-35) in mice. Methods: Mice were icv injected with the Aβ25-35 (15 nmol/mouse), and then treated with oral administration of 75 mg/kg or 150 mg/kg of FLZ once daily for 16 consecutive days. The impairment of learning and memory in mice were tested using step-down test and Morris water maze test. The content of malondialdehyde (MDA) and the expressions of acetylcholinesterase (AChE), Bax, and Bcl-2 in the CA1 region of the mouse hippocampus were measured by biochemical and immu-nohistochemical analysis, respectively. The pathological damages of hippocampus were observed using a microscope. Results: FLZ (75 mg/kg, 150 mg/kg) significantly attenuated Aβ25-35-induced impairment of learning and memory in the step-down test and Morris water maze test. FLZ also reduced pathological damages to the hippocampus induced by Aβ25-35 Furthermore, FLZ prevented the increase of AChE and Bax, and the decrease of Bcl-2 immunoreactive cells in the CA1 region of the hippocampus, and reduced the increase of MDA content in the hippocampus in mice injected with Aβ25-35. Conclusion: FLZ has protective action against the impairment of learning and memory and pathological damage to the hippocampus induced by icv injection of Aβ25-35 in mice.

A biotechnological approach for the development of new antifungal compounds to protect the environment and the human health

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Claudia Zani

2015-11-01

Full Text Available Background. In the Po Valley aflatoxins play a relevant role: the local food economy is heavily based on cereal cultivations for animal feed and human nutrition. Aims of this project are the identification of new compounds that inhibit Aspergillus proliferation, the development of new inhibitors of aflatoxins production, and the set-up a practical screening procedure to identify the most effective and safe compounds. Design and Methods. New compounds will be synthetized with natural origin molecules as ligands and endogenous metal ions to increase their bioavailability for the fungi as metal complexes. A biotechnological high-throughput screening will be set up to identify efficiently the most powerful substances. The newly synthesized compounds with effective antifungal activities, will be evaluated with battery of tests with different end-points to assess the toxic potential risk for environmental and human health. Expected impact of the study for public health. The fundamental step in the project will be the synthesis of new compounds and the study of their capability to inhibit aflatoxin biosynthesis. A new, simple, inexpensive and high-throughput method to screen the anti-fungine and anti-mycotoxin activity of the new synthesised compounds will be applied. The evaluation of possible risks for humans due to toxic and genotoxic activities of the molecules will be made with a new approach using different types of cells (bacteria, plants and human cells.

Extending breath analysis to the cellular level: current thoughts on the human microbiome and the expression of organic compounds in the human exposome

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Human biomarkers are comprised of compounds from cellular metabolism, oxidative stress, and the microbiome of bacteria in the gut, genitourinary, and pulmonary tracts. When we examine patterns in human biomarkers to discern human health state or diagnose specific diseases, it is...

Morphological modulation of human fibrosarcoma HT-1080 cells by hydroxybenzoate compounds during apoptosis

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Jassem G Mahdi

2015-10-01

Full Text Available Hydroxybenzoate (HB compounds have shown to modulate the morphology in human fibrosarcoma HT-1080 cells. The changes in HT-1080 cells showed marker signs of apoptosis, which included the condensation of nucleus, cell round, blebbing and the formation of apoptotic bodies. The different stages of apoptosis were assessed microscopically using different staining and immunohistochemical techniques, as well as scanning electron microscopy. In addition, HB compounds increased the expression of caspase-3, which is closely associated with the development of the modulation in HT-1080 cells that are undergoing the programmed cell death. Both acetyl salicylic acid (ASA and HBZn compounds were dose and treatment duration dependent.

The effects of compound danshen dripping pills and human umbilical cord blood mononuclear cell transplant after acute myocardial infarction.

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Jun, Yi; Chunju, Yuan; Qi, Ai; Liuxia, Deng; Guolong, Yu

2014-04-01

The low frequency of survival of stem cells implanted in the myocardium after acute myocardial infarction may be caused by inflammation and oxidative stress in the myocardial microenvironment. We evaluated the effects of a traditional Chinese medicine, Compound Danshen Dripping Pills, on the cardiac microenvironment and cardiac function when used alone or in combination with human umbilical cord blood mononuclear cell transplant after acute myocardial infarction. After surgically induced acute myocardial infarction, rabbits were treated with Compound Danshen Dripping Pills alone or in combination with human umbilical cord blood mononuclear cell transplant. Evaluation included histology, measurement of left ventricular ejection fraction and fractional shortening, leukocyte count, count of green fluorescent protein positive cells, superoxide dismutase activity, and malondialdehyde content. Combination treatment with Compound Danshen Dripping Pills and human umbilical cord blood mononuclear cell transplant significantly increased the survival of implanted cells, inhibited cardiac cell apoptosis, decreased oxidative stress, decreased the inflammatory response, and improved cardiac function. Rabbits treated with either Compound Danshen Dripping Pills or human umbilical cord blood mononuclear cells alone had improvement in these effects compared with untreated control rabbits. Combination therapy with Compound Danshen Dripping Pills and human umbilical cord blood mononuclear cells may improve cardiac function and morphology after acute myocardial infarction.

The psychoactive compound of Cannabis sativa, Δ(9)-tetrahydrocannabinol (THC) inhibits the human trophoblast cell turnover.

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Costa, M A; Fonseca, B M; Marques, F; Teixeira, N A; Correia-da-Silva, G

2015-08-06

The noxious effects of cannabis consumption for fertility and pregnancy outcome are recognized for years. Its consumption during gestation is associated with alterations in foetal growth, low birth weight and preterm labor. The main psychoactive molecule of cannabis, Δ(9)-tetrahydrocannabinol (THC) impairs the production of reproductive hormones and is also able to cross the placenta barrier. However, its effect on the main placental cells, the trophoblasts, are unknown. Actually, the role of THC in cell survival/death of primary human cytotrophoblasts (CTs) and syncytiotrophoblasts (STs) and in the syncytialization process remains to be explored. Here, we show that THC has a dual effect, enhancing MTT metabolism at low concentrations, whereas higher doses decreased cell viability, on both trophoblast phenotypes, though the effects on STs were more evident. THC also diminished the generation of oxidative and nitrative stress and the oxidized form of glutathione, whereas the reduced form of this tripeptide was increased, suggesting that THC prevents ST cell death due to an antioxidant effect. Moreover, this compound enhanced the mitochondrial function of STs, as observed by the increased MTT metabolism and intracellular ATP levels. These effects were independent of cannabinoid receptors activation. Besides, THC impaired CT differentiation into STs, since it decreased the expression of biochemical and morphological biomarkers of syncytialization, through a cannabinoid receptor-dependent mechanism. Together, these results suggest that THC interferes with trophoblast turnover, preventing trophoblast cell death and differentiation, and contribute to disclose the cellular mechanisms that lead to pregnancy complications in women that consume cannabis-derived drugs during gestation. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Strawberry Achenes Are an Important Source of Bioactive Compounds for Human Health

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María Teresa Ariza

2016-07-01

Full Text Available Strawberries are highly appreciated for their taste, nutritional value and antioxidant compounds, mainly phenolics. Fruit antioxidants derive from achenes and flesh, but achene contribution to the total fruit antioxidant capacity and to the bioaccessibility after intake is still unknown. In this work, the content of total phenolic compounds, flavonoids, anthocyanins and antioxidant capacity (TEAC, FRAP and DPPH of achenes and flesh were compared in non-digested as well as in gastric and intestinal extracts after in vitro digestion. Results showed that, despite strawberry achenes represent a small fraction of the fruit, their contribution to total fruit antioxidant content was more than 41% and accounted for 81% of antioxidant capacity (TEAC. Achenes have higher quantity and different quality of antioxidants in non-digested and digested extracts. Antioxidant release was higher in the in vitro gastric digested extracts, but digestion conditions did not only affect quantity but quality, resulting in differences in antioxidant capacity and highlighting the importance of simulating physiological-like extraction conditions for assessing fruit antioxidant properties on human health. These results give new insights into the use of strawberry achenes as a source of bioactive compounds to be considered in strawberry breeding programs for improving human health.

Strawberry Achenes Are an Important Source of Bioactive Compounds for Human Health

Science.gov (United States)

Ariza, María Teresa; Reboredo-Rodríguez, Patricia; Mazzoni, Luca; Forbes-Hernández, Tamara Yuliett; Giampieri, Francesca; Afrin, Sadia; Gasparrini, Massimiliano; Soria, Carmen; Martínez-Ferri, Elsa; Battino, Maurizio; Mezzetti, Bruno

2016-01-01

Strawberries are highly appreciated for their taste, nutritional value and antioxidant compounds, mainly phenolics. Fruit antioxidants derive from achenes and flesh, but achene contribution to the total fruit antioxidant capacity and to the bioaccessibility after intake is still unknown. In this work, the content of total phenolic compounds, flavonoids, anthocyanins and antioxidant capacity (TEAC, FRAP and DPPH) of achenes and flesh were compared in non-digested as well as in gastric and intestinal extracts after in vitro digestion. Results showed that, despite strawberry achenes represent a small fraction of the fruit, their contribution to total fruit antioxidant content was more than 41% and accounted for 81% of antioxidant capacity (TEAC). Achenes have higher quantity and different quality of antioxidants in non-digested and digested extracts. Antioxidant release was higher in the in vitro gastric digested extracts, but digestion conditions did not only affect quantity but quality, resulting in differences in antioxidant capacity and highlighting the importance of simulating physiological-like extraction conditions for assessing fruit antioxidant properties on human health. These results give new insights into the use of strawberry achenes as a source of bioactive compounds to be considered in strawberry breeding programs for improving human health. PMID:27409612

Compound K induced apoptosis via endoplasmic reticulum Ca2+ release through ryanodine receptor in human lung cancer cells

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Dong-Hyun Shin

2018-04-01

Full Text Available Background: Extended endoplasmic reticulum (ER stress may initiate apoptotic pathways in cancer cells, and ER stress has been reported to possibly increase tumor death in cancer therapy. We previously reported that caspase-8 played an important role in compound K-induced apoptosis via activation of caspase-3 directly or indirectly through Bid cleavage, cytochrome c release, and caspase-9 activation in HL-60 human leukemia cells. The mechanisms leading to apoptosis in A549 and SK-MES-1 human lung cancer cells and the role of ER stress have not yet been understood. Methods: The apoptotic effects of compound K were analyzed using flow cytometry, and the changes in protein levels were determined using Western blot analysis. The intracellular calcium levels were monitored by staining with Fura-2/AM and Fluo-3/AM. Results: Compound K-induced ER stress was confirmed through increased phosphorylation of eIF2α and protein levels of GRP78/BiP, XBP-1S, and IRE1α in human lung cancer cells. Moreover, compound-K led to the accumulation of intracellular calcium and an increase in m-calpain activities that were both significantly inhibited by pretreatment either with BAPTA-AM (an intracellular Ca2+ chelator or dantrolene (an RyR channel antagonist. These results were correlated with the outcome that compound K induced ER stress-related apoptosis through caspase-12, as z-ATAD-fmk (a specific inhibitor of caspase-12 partially ameliorated this effect. Interestingly, 4-PBA (ER stress inhibitor dramatically improved the compound K-induced apoptosis. Conclusion: Cell survival and intracellular Ca2+ homeostasis during ER stress in human lung cancer cells are important factors in the induction of the compound K-induced apoptotic pathway. Keywords: apoptosis, calcium, compound K, ER stress, lung cancer cells

Perfluorinated compounds in human serum and seminal plasma from an urban and rural population in Sri Lanka

Energy Technology Data Exchange (ETDEWEB)

Guruge, Keerthi; Miyazaki, Shigeru; Yamanaka, Noriko [National Institute of Animal Health, Tsukuba (Japan); Taniyasu, Sacgu; Yamashita, Nobuyoshi [National Institute of Advance Industrial and Technology, Tsukuba (Japan); Wijeratna, S.; Seneviratne, H. [Colombo Univ. (Sri Lanka)

2004-09-15

Fluorinated organic compounds (FOCs) have been used for variety of industrial applications such as surfactants, adhesives, insecticides, and their global production increase since 1970s. These compounds repel both water and oil. The high-energy carbon-fluorine covalent bonds in FOCs are strong enough to have high persistency in the environment. These compounds emerged as priory environmental pollutants since they are found in various biota throughout the world. Human contamination of some FOCs was reported mostly in developed countries such as USA, Japan and from Europe. In the present study, we report 10 FOCs in human serum including seminal plasma for the first time, collected from volunteers from Sri Lanka.

Early impairment of gut function and gut flora supporting a role for alteration of gastrointestinal mucosa in human immunodeficiency virus pathogenesis

NARCIS (Netherlands)

Gori, Andrea; Tincati, Camilla; Rizzardini, Giuliano; Torti, Carlo; Quirino, Tiziana; Haarman, Monique; Ben Amor, Kaouther; van Schaik, Jacqueline; Vriesema, Aldwin; Knol, Jan; Marchetti, Giulia; Welling, Gjalt; Clerici, Mario

Our results show that impairment of the gastrointestinal tracts in human immunodeficiency virus (HIV)-positive patients is present in the early phases of HIV disease. This impairment is associated with alterations in gut microbiota and intestinal inflammatory parameters. These findings support the

SEURAT-1 liver gold reference compounds: a mechanism-based review.

Science.gov (United States)

Jennings, Paul; Schwarz, Michael; Landesmann, Brigitte; Maggioni, Silvia; Goumenou, Marina; Bower, David; Leonard, Martin O; Wiseman, Jeffrey S

2014-12-01

There is an urgent need for the development of alternative methods to replace animal testing for the prediction of repeat dose chemical toxicity. To address this need, the European Commission and Cosmetics Europe have jointly funded a research program for 'Safety Evaluation Ultimately Replacing Animal Testing.' The goal of this program was the development of in vitro cellular systems and associated computational capabilities for the prediction of hepatic, cardiac, renal, neuronal, muscle, and skin toxicities. An essential component of this effort is the choice of appropriate reference compounds that can be used in the development and validation of assays. In this review, we focus on the selection of reference compounds for liver pathologies in the broad categories of cytotoxicity and lipid disorders. Mitochondrial impairment, oxidative stress, and apoptosis are considered under the category of cytotoxicity, while steatosis, cholestasis, and phospholipidosis are considered under the category of lipid dysregulation. We focused on four compound classes capable of initiating such events, i.e., chemically reactive compounds, compounds with specific cellular targets, compounds that modulate lipid regulatory networks, and compounds that disrupt the plasma membrane. We describe the molecular mechanisms of these compounds and the cellular response networks which they elicit. This information will be helpful to both improve our understanding of mode of action and help in the selection of appropriate mechanistic biomarkers, allowing us to progress the development of animal-free models with improved predictivity to the human situation.

Inhibition of ultraviolet irradiation response of human skin by topical phlogostatic compounds

International Nuclear Information System (INIS)

Weirich, E.G.; Lutz, U.C.

1977-01-01

By adaption of the model of UV dermatitis in human skin a test procedure has been developed which facilitates realistic assessment of topical contra-inflammatory activity of steroidal as well as non-steroidal compounds. Sixt typical skin drug agents were tested according to their reaction inhibition effect. (orig./MG) [de

Anti-proliferative, Cytotoxic and NF-ĸB Inhibitory Properties of Spiro(Lactone-Cyclohexanone) Compounds in Human Leukemia.

Science.gov (United States)

Bouhenna, Mustapha M; Orlikova, Barbora; Talhi, Oualid; Schram, Ben; Pinto, Diana C G A; Taibi, Nadia; Bachari, Khaldoun; Diederich, Marc; Silva, Artur M S; Mameri, Nabil

2017-09-01

NF-ĸB affects most aspects of cellular physiology. Deregulation of NF-ĸB signaling is associated with inflammatory diseases and cancer. In this study, we evaluated the cytotoxic and NF-ĸB inhibition potential of new spiro(lactone-cyclohexanone) compounds in two different human leukemia cell lines (U937 and K562). The anti-proliferative effects of the spiro(lactone-cyclohexanone) compounds on human K562 and U937 cell lines was evaluated by trypan blue staining, as well as their involvement in NF-kB regulation were analyzed by luciferase reporter gene assay, Caspase-3/7 activities were evaluated to analyze apoptosis induction. Both spiro(coumarin-cyclohexanone) 4 and spiro(6- methyllactone-cyclohexanone) 9 down-regulated cancer cell viability and proliferation. Compound 4 inhibited TNF-α-induced NF-ĸB activation in a dose-dependent manner and induced caspase-dependent apoptosis in both leukemia cell lines. Results show that compound 4 and compound 9 have potential as anti-cancer agents. In addition, compound 4 exerted NF-kB inhibition activity in leukemia cancer cells. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Cognitive impairments, HCI and daily living

DEFF Research Database (Denmark)

Keates, Simeon; Kozloski, James; Varker, Philip

2009-01-01

As computer systems become increasingly more pervasive in everyday life, it is simultaneously becoming ever more important that the concept of universal access is accepted as a design mantra. While many physical impairments and their implications for human-computer interaction are well understood......, cognitive impairments have received comparatively little attention. One of the reasons for this is the general lack of sufficiently detailed cognitive models. This paper examines how cognitive impairments can affect human-computer interaction in everyday life and the issues involved in trying to make...

Simultaneous quantitative analysis of nine vitamin D compounds in human blood using LC-MS/MS.

Science.gov (United States)

Abu Kassim, Nur Sofiah; Gomes, Fabio P; Shaw, Paul Nicholas; Hewavitharana, Amitha K

2016-01-01

It has been suggested that each member of the family of vitamin D compounds may have different function(s). Therefore, selective quantification of each compound is important in clinical research. Development and validation attempts of a simultaneous determination method of 12 vitamin D compounds in human blood using precolumn derivatization followed by LC-MS/MS is described. Internal standard calibration with 12 stable isotope labeled analogs was used to correct for matrix effects in MS detector. Nine vitamin D compounds were quantifiable in blood samples with detection limits within femtomole levels. Serum (compared with plasma) was found to be a more suitable sample type, and protein precipitation (compared with saponification) a more effective extraction method for vitamin D assay.

Direct Electrical Stimulation of the Human Entorhinal Region and Hippocampus Impairs Memory.

Science.gov (United States)

Jacobs, Joshua; Miller, Jonathan; Lee, Sang Ah; Coffey, Tom; Watrous, Andrew J; Sperling, Michael R; Sharan, Ashwini; Worrell, Gregory; Berry, Brent; Lega, Bradley; Jobst, Barbara C; Davis, Kathryn; Gross, Robert E; Sheth, Sameer A; Ezzyat, Youssef; Das, Sandhitsu R; Stein, Joel; Gorniak, Richard; Kahana, Michael J; Rizzuto, Daniel S

2016-12-07

Deep brain stimulation (DBS) has shown promise for treating a range of brain disorders and neurological conditions. One recent study showed that DBS in the entorhinal region improved the accuracy of human spatial memory. Based on this line of work, we performed a series of experiments to more fully characterize the effects of DBS in the medial temporal lobe on human memory. Neurosurgical patients with implanted electrodes performed spatial and verbal-episodic memory tasks. During the encoding periods of both tasks, subjects received electrical stimulation at 50 Hz. In contrast to earlier work, electrical stimulation impaired memory performance significantly in both spatial and verbal tasks. Stimulation in both the entorhinal region and hippocampus caused decreased memory performance. These findings indicate that the entorhinal region and hippocampus are causally involved in human memory and suggest that refined methods are needed to use DBS in these regions to improve memory. Copyright © 2016 Elsevier Inc. All rights reserved.

Dioxin-like activity of environmental compounds in human blood and environmental samples

DEFF Research Database (Denmark)

Long, Manhai; Bonefeld-Jørgensen, Eva Cecilie

2012-01-01

and humans. We found that some pesticides, plasticizers and phytoestrogens can activate the AhR, and the combined effect of compounds with no or weak AhR potency cannot be ignored. The significant DL-activity in the wastewater effluent indicates the treatment is not sufficient to prevent contamination...... of surface waters with dioxins. Our results from human studies suggest that the serum DL-activity reflect the complex mixture of persistent organic pollutants (POPs). Greenlandic Inuit had lower serum DL-activity level compared to Europeans, probably due to long distance from the dioxin sources and UV...

Designing Second Generation Anti-Alzheimer Compounds as Inhibitors of Human Acetylcholinesterase: Computational Screening of Synthetic Molecules and Dietary Phytochemicals.

Directory of Open Access Journals (Sweden)

Hafsa Amat-Ur-Rasool

Full Text Available Alzheimer's disease (AD, a big cause of memory loss, is a progressive neurodegenerative disorder. The disease leads to irreversible loss of neurons that result in reduced level of acetylcholine neurotransmitter (ACh. The reduction of ACh level impairs brain functioning. One aspect of AD therapy is to maintain ACh level up to a safe limit, by blocking acetylcholinesterase (AChE, an enzyme that is naturally responsible for its degradation. This research presents an in-silico screening and designing of hAChE inhibitors as potential anti-Alzheimer drugs. Molecular docking results of the database retrieved (synthetic chemicals and dietary phytochemicals and self-drawn ligands were compared with Food and Drug Administration (FDA approved drugs against AD as controls. Furthermore, computational ADME studies were performed on the hits to assess their safety. Human AChE was found to be most approptiate target site as compared to commonly used Torpedo AChE. Among the tested dietry phytochemicals, berberastine, berberine, yohimbine, sanguinarine, elemol and naringenin are the worth mentioning phytochemicals as potential anti-Alzheimer drugs The synthetic leads were mostly dual binding site inhibitors with two binding subunits linked by a carbon chain i.e. second generation AD drugs. Fifteen new heterodimers were designed that were computationally more efficient inhibitors than previously reported compounds. Using computational methods, compounds present in online chemical databases can be screened to design more efficient and safer drugs against cognitive symptoms of AD.

Designing Second Generation Anti-Alzheimer Compounds as Inhibitors of Human Acetylcholinesterase: Computational Screening of Synthetic Molecules and Dietary Phytochemicals.

Science.gov (United States)

Amat-Ur-Rasool, Hafsa; Ahmed, Mehboob

2015-01-01

Alzheimer's disease (AD), a big cause of memory loss, is a progressive neurodegenerative disorder. The disease leads to irreversible loss of neurons that result in reduced level of acetylcholine neurotransmitter (ACh). The reduction of ACh level impairs brain functioning. One aspect of AD therapy is to maintain ACh level up to a safe limit, by blocking acetylcholinesterase (AChE), an enzyme that is naturally responsible for its degradation. This research presents an in-silico screening and designing of hAChE inhibitors as potential anti-Alzheimer drugs. Molecular docking results of the database retrieved (synthetic chemicals and dietary phytochemicals) and self-drawn ligands were compared with Food and Drug Administration (FDA) approved drugs against AD as controls. Furthermore, computational ADME studies were performed on the hits to assess their safety. Human AChE was found to be most approptiate target site as compared to commonly used Torpedo AChE. Among the tested dietry phytochemicals, berberastine, berberine, yohimbine, sanguinarine, elemol and naringenin are the worth mentioning phytochemicals as potential anti-Alzheimer drugs The synthetic leads were mostly dual binding site inhibitors with two binding subunits linked by a carbon chain i.e. second generation AD drugs. Fifteen new heterodimers were designed that were computationally more efficient inhibitors than previously reported compounds. Using computational methods, compounds present in online chemical databases can be screened to design more efficient and safer drugs against cognitive symptoms of AD.

Human Intestinal Fluid Layer Separation: The Effect On Colloidal Structures & Solubility Of Lipophilic Compounds.

Science.gov (United States)

Danny, Riethorst; Amitava, Mitra; Filippos, Kesisoglou; Wei, Xu; Jan, Tack; Joachim, Brouwers; Patrick, Augustijns

2018-05-23

In addition to individual intestinal fluid components, colloidal structures are responsible for enhancing the solubility of lipophilic compounds. The present study investigated the link between as well as the variability in the ultrastructure of fed state human intestinal fluids (FeHIF) and their solubilizing capacity for lipophilic compounds. For this purpose, FeHIF samples from 10 healthy volunteers with known composition and ultrastructure were used to determine the solubility of four lipophilic compounds. In light of the focus on solubility and ultrastructure, the study carefully considered the methodology of solubility determination in relation to colloid composition and solubilizing capacity of FeHIF. To determine the solubilizing capacity of human and simulated intestinal fluids, the samples were saturated with the compound of interest, shaken for 24 h, and centrifuged. When using FeHIF, solubilities were determined in the micellar layer of FeHIF, i.e. after removing the upper (lipid) layer (standard procedure), as well as in 'full' FeHIF (without removal of the upper layer). Compound concentrations were determined using HPLC-UV/fluorescence. To link the solubilizing capacity with the ultrastructure, all human and simulated fluids were imaged using transmission electron microscopy (TEM) before and after centrifugation and top layer (lipid) removal. Comparing the ultrastructure and solubilizing capacity of individual FeHIF samples demonstrated a high intersubject variability in postprandial intestinal conditions. Imaging of FeHIF after removal of the upper layer clearly showed that only micellar structures remain in the lower layer. This observation suggests that larger colloids such as vesicles and lipid droplets are contained in the upper, lipid layer. The solubilizing capacity of most FeHIF samples substantially increased with inclusion of this lipid layer. The relative increase in solubilizing capacity upon inclusion of the lipid layer was most pronounced

Impact of androgenic/antiandrogenic compounds (AAC) on human sex steroid metabolizing key enzymes

International Nuclear Information System (INIS)

Allera, A.; Lo, S.; King, I.; Steglich, F.; Klingmueller, D.

2004-01-01

Various pesticides, industrial pollutants and synthetic compounds, to which human populations are exposed, are known or suspected to interfere with endogenous sex hormone functions. Such interference potentially affect the development and expression of the male and female reproductive system or both. Chemicals in this class are thus referred to as endocrine disruptors (ED). This emphazises on the relevance of screening ED for a wide range of sex hormone-mimicking effects. These compounds are believed to exert influence on hormonal actions predominantly by (i) interfering with endogenous steroids in that they functionally interact with plasma membrane-located receptors as well as with nuclear receptors both for estrogens and androgens or (ii) affecting the levels of sex hormones as a result of their impact on steroid metabolizing key enzymes. Essential sex hormone-related enzymes within the endocrine system of humans are aromatase, 5α-reductase 2 as well as specific sulfotransferases and sulfatases (so-called phase I and phase II enzymes, respectively). Using suitable human tissues and human cancer cell lines (placenta, prostate, liver and JEG-3, lymph node carcinoma of prostate (LnCaP) cells) we investigated the impact of 10 widely used chemicals suspected of acting as ED with androgenic or antiandrogenic activity (so-called AAC) on the activity of these sex hormone metabolizing key enzymes in humans. In addition, the respective effects of six substances were also studied as positive controls due to their well-known specific hormonal agonistic/antagonistic activities. The aim of this report and subsequent investigations is to improve human health risk assessment for AAC and other ED

Exposure to perfluorinated compounds and human semen quality in arctic and European populations

NARCIS (Netherlands)

Toft, G.; Jönsson, B.A.G.; Lindh, C.H.; Giwercman, A.; Spano, M.; Heederik, D.J.J.; Lenters, V.C.; Vermeulen, R.C.H.; Rylander, L.; Pedersen, H.S.; Ludwicki, J.K.; Zviezdai, V.; Bonde, J.P.

2012-01-01

BACKGROUND Perfluorinated compounds (PFCs) have been suspected to adversely affect human reproductive health. The aim of this study was to investigate the associations between PFC exposure and male semen quality. METHODS PFCs were measured in serum from 588 partners of pregnant women from Greenland,

Aryl hydrocarbon receptor activation by 2,3,7,8-tetrachlorodibenzo-p-dioxin impairs human B lymphopoiesis

International Nuclear Information System (INIS)

Li, Jinpeng; Phadnis-Moghe, Ashwini S.; Crawford, Robert B.; Kaminski, Norbert E.

2017-01-01

The homeostasis of peripheral B cell compartment requires lifelong B lymphopoiesis from hematopoietic stem cells (HSC). As a result, the B cell repertoire is susceptible to disruptions of hematopoiesis. Increasing evidence, primarily from rodent models, shows that the aryl hydrocarbon receptor (AHR) regulates hematopoiesis. To study the effects of persistent AHR activation on human B cell development, a potent AHR agonist and known environmental contaminant, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was utilized. An in vitro B cell development model system was established by co-culturing human cord blood-derived HSCs with irradiated human primary bone marrow stromal cells. Using this in vitro model, we found that TCDD significantly suppressed the total number of hematopoietic stem and progenitor cells (HSPC) in a concentration-dependent manner. Cell death analysis demonstrated that the decrease in cell number was not due to cytotoxicity by TCDD. In addition, TCDD markedly decreased CD34 expression on HSPCs. Structure-activity relationship studies using dioxin congeners demonstrated a correlation between the relative AHR binding affinity and the magnitude of decrease in the number of HSPCs and CD34 expression, suggesting that AHR mediates the observed TCDD-elicited changes in HSPCs. Moreover, a significant reduction in lineage committed B cell-derived from HSCs was observed in the presence of TCDD, indicating impairment of human B cell development. Similar effects of TCDD were observed regardless of the use of stromal cells in cultures indicating a direct effect of TCDD on HSCs. Collectively, we demonstrate that AHR activation by TCDD on human HSCs impairs early stages of human B lymphopoiesis.

Analytical method for biomonitoring of endocrine-disrupting compounds (bisphenol A, parabens, perfluoroalkyl compounds and a brominated flame retardant) in human hair by liquid chromatography-tandem mass spectrometry

Energy Technology Data Exchange (ETDEWEB)

Martín, Julia; Santos, Juan Luis; Aparicio, Irene, E-mail: iaparicio@us.es; Alonso, Esteban

2016-11-16

In this paper, a method for the determination of four groups of endocrine-disrupting compounds in human hair is proposed. Target compounds were a plastic monomer (bisphenol A), three parabens commonly used as preservatives (methylparaben, ethylparaben and propylparaben), six perfluoroalkyl compounds commonly used as water, oil and dirt repellents (perfluorooctane sulfonic acid and five perfluoroalkyl carboxylic acids, with alkyl chains from four to eight carbon atoms) and a brominated flame retardant (hexabromocyclododecane). All of them are of especial concern to human health because they are utilized in many everyday products. The method is based on hair incubation with methanol/acetic acid solution (85:15, v/v), extraction with acetone for 15 min in an ultrasonic bath and analysis by liquid chromatography-electrospray-tandem mass spectrometry in negative ionization mode. Limits of quantification in hair samples ranged from 0.6 ng g{sup −1} to 6.1 ng g{sup −1}, except for hexabromocyclododecane (36 ng g{sup −1}). Recoveries were higher than 69%. Intra-day and inter-day precision, expressed as relative standard deviation, were lower than 15% and 10%, respectively. The applicability of the method was proven by analyzing the target compounds in hair samples from six volunteers. High frequencies of detection and concentrations were obtained for bisphenol A (83% of samples; concentrations up to 158 ng g{sup −1}) and parabens (100% of samples; concentrations up to 624 ng g{sup −1}). Lower concentrations were detected for the perfluoroalkyl compounds (up to 13 ng g{sup −1}). Hexabromocyclododecane was not detected. - Highlights: • Method for biomonitoring of endocrine-disrupting compounds in human hair. • Target compounds are commonly present in everyday products. • Method based on hair digestion and liquid chromatography-tandem mass spectrometry. • Good sensitivity, recoveries and precision and low matrix effect were obtained. �

Analytical method for biomonitoring of endocrine-disrupting compounds (bisphenol A, parabens, perfluoroalkyl compounds and a brominated flame retardant) in human hair by liquid chromatography-tandem mass spectrometry

International Nuclear Information System (INIS)

Martín, Julia; Santos, Juan Luis; Aparicio, Irene; Alonso, Esteban

2016-01-01

In this paper, a method for the determination of four groups of endocrine-disrupting compounds in human hair is proposed. Target compounds were a plastic monomer (bisphenol A), three parabens commonly used as preservatives (methylparaben, ethylparaben and propylparaben), six perfluoroalkyl compounds commonly used as water, oil and dirt repellents (perfluorooctane sulfonic acid and five perfluoroalkyl carboxylic acids, with alkyl chains from four to eight carbon atoms) and a brominated flame retardant (hexabromocyclododecane). All of them are of especial concern to human health because they are utilized in many everyday products. The method is based on hair incubation with methanol/acetic acid solution (85:15, v/v), extraction with acetone for 15 min in an ultrasonic bath and analysis by liquid chromatography-electrospray-tandem mass spectrometry in negative ionization mode. Limits of quantification in hair samples ranged from 0.6 ng g"−"1 to 6.1 ng g"−"1, except for hexabromocyclododecane (36 ng g"−"1). Recoveries were higher than 69%. Intra-day and inter-day precision, expressed as relative standard deviation, were lower than 15% and 10%, respectively. The applicability of the method was proven by analyzing the target compounds in hair samples from six volunteers. High frequencies of detection and concentrations were obtained for bisphenol A (83% of samples; concentrations up to 158 ng g"−"1) and parabens (100% of samples; concentrations up to 624 ng g"−"1). Lower concentrations were detected for the perfluoroalkyl compounds (up to 13 ng g"−"1). Hexabromocyclododecane was not detected. - Highlights: • Method for biomonitoring of endocrine-disrupting compounds in human hair. • Target compounds are commonly present in everyday products. • Method based on hair digestion and liquid chromatography-tandem mass spectrometry. • Good sensitivity, recoveries and precision and low matrix effect were obtained. • Method was successfully

Proactive Interference in Human Predictive Learning

OpenAIRE

Castro, Leyre; Ortega, Nuria; Matute, Helena

2002-01-01

The impairment in responding to a secondly trained association because of the prior training of another (i.e., proactive interference) is a well-established effect in human and animal research, and it has been demonstrated in many paradigms. However, learning theories have been concerned with proactive interference only when the competing stimuli have been presented in compound at some moment of the training phase. In this experiment we investigated the possibility of proactive interference b...

Human peripheral blood mononuclear cell in vitro system to test the efficacy of food bioactive compounds: Effects of polyunsaturated fatty acids and their relation with BMI

KAUST Repository

Cifre, Margalida

2016-11-22

Scope: To analyse the usefulness of isolated human peripheral blood mononuclear cells (PBMC) to rapidly/easily reflect n-3 long-chain polyunsaturated fatty acid (LCPUFA) effects on lipid metabolism/inflammation gene profile, and evaluate if these effects are body mass index (BMI) dependent. Methods and results: PBMC from normoweight (NW) and overweight/obese (OW/OB) subjects were incubated with physiological doses of docosahexaenoic (DHA), eicosapentaenoic acid (EPA), or their combination. PBMC reflected increased beta-oxidation-like capacity (CPT1A expression) in OW/OB but only after DHA treatment. However, insensitivity to n-3 LCPUFA was evident in OW/OB for lipogenic genes: both PUFA diminished FASN and SREBP1C expression in NW, but no effect was observed for DHA in PBMC from high-BMI subjects. This insensitivity was also evident for inflammation gene profile: all treatments inhibited key inflammatory genes in NW; nevertheless, no effect was observed in OW/OB after DHA treatment, and EPA effect was impaired. SLC27A2, IL6 and TNFα PBMC expression analysis resulted especially interesting to determine obesity-related n-3 LCPUFA insensitivity. Conclusion: A PBMC-based human in vitro system reflects n-3 LCPUFA effects on lipid metabolism/inflammation which is impaired in OW/OB. These results confirm the utility of PBMC ex vivo systems for bioactive-compound screening to promote functional food development and to establish appropriate dietary strategies for obese population.

Human peripheral blood mononuclear cell in vitro system to test the efficacy of food bioactive compounds: Effects of polyunsaturated fatty acids and their relation with BMI.

Science.gov (United States)

Cifre, Margalida; Díaz-Rúa, Rubén; Varela-Calviño, Rubén; Reynés, Bàrbara; Pericás-Beltrán, Jordi; Palou, Andreu; Oliver, Paula

2017-04-01

To analyse the usefulness of isolated human peripheral blood mononuclear cells (PBMC) to rapidly/easily reflect n-3 long-chain polyunsaturated fatty acid (LCPUFA) effects on lipid metabolism/inflammation gene profile, and evaluate if these effects are body mass index (BMI) dependent. PBMC from normoweight (NW) and overweight/obese (OW/OB) subjects were incubated with physiological doses of docosahexaenoic (DHA), eicosapentaenoic acid (EPA), or their combination. PBMC reflected increased beta-oxidation-like capacity (CPT1A expression) in OW/OB but only after DHA treatment. However, insensitivity to n-3 LCPUFA was evident in OW/OB for lipogenic genes: both PUFA diminished FASN and SREBP1C expression in NW, but no effect was observed for DHA in PBMC from high-BMI subjects. This insensitivity was also evident for inflammation gene profile: all treatments inhibited key inflammatory genes in NW; nevertheless, no effect was observed in OW/OB after DHA treatment, and EPA effect was impaired. SLC27A2, IL6 and TNFα PBMC expression analysis resulted especially interesting to determine obesity-related n-3 LCPUFA insensitivity. A PBMC-based human in vitro system reflects n-3 LCPUFA effects on lipid metabolism/inflammation which is impaired in OW/OB. These results confirm the utility of PBMC ex vivo systems for bioactive-compound screening to promote functional food development and to establish appropriate dietary strategies for obese population. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Impaired representation of geometric relationships in humans with damage to the hippocampal formation.

Science.gov (United States)

Finke, Carsten; Ostendorf, Florian; Braun, Mischa; Ploner, Christoph J

2011-01-01

The pivotal role of the hippocampus for spatial memory is well-established. However, while neurophysiological and imaging studies suggest a specialization of the hippocampus for viewpoint-independent or allocentric memory, results from human lesion studies have been less conclusive. It is currently unclear whether disproportionate impairment in allocentric memory tasks reflects impairment of cognitive functions that are not sufficiently supported by regions outside the medial temporal lobe or whether the deficits observed in some studies are due to experimental factors. Here, we have investigated whether hippocampal contributions to spatial memory depend on the spatial references that are available in a certain behavioral context. Patients with medial temporal lobe lesions affecting systematically the right hippocampal formation performed a series of three oculomotor tasks that required memory of a spatial cue either in retinal coordinates or relative to a single environmental reference across a delay of 5000 ms. Stimulus displays varied the availability of spatial references and contained no complex visuo-spatial associations. Patients showed a selective impairment in a condition that critically depended on memory of the geometric relationship between spatial cue and environmental reference. We infer that regions of the medial temporal lobe, most likely the hippocampal formation, contribute to behavior in conditions that exceed the potential of viewpoint-dependent or egocentric representations. Apparently, this already applies to short-term memory of simple geometric relationships and does not necessarily depend on task difficulty or integration of landmarks into more complex representations. Deficient memory of basic geometric relationships may represent a core deficit that contributes to impaired performance in allocentric spatial memory tasks.

45 CFR 1308.11 - Eligibility criteria: Hearing impairment including deafness.

Science.gov (United States)

2010-10-01

... OF HUMAN DEVELOPMENT SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION FOR... impairment including deafness. (a) A child is classified as deaf if a hearing impairment exists which is so... hearing loss can include impaired listening skills, delayed language development, and articulation...

Human peripheral blood mononuclear cell in vitro system to test the efficacy of food bioactive compounds: Effects of polyunsaturated fatty acids and their relation with BMI

KAUST Repository

Cifre, Margalida; Diaz Rua, Ruben; Varela-Calviñ o, Rubé n; Reyné s, Bà rbara; Pericá s-Beltrá n, Jordi; Palou, Andreu; Oliver, Paula

2016-01-01

is impaired in OW/OB. These results confirm the utility of PBMC ex vivo systems for bioactive-compound screening to promote functional food development and to establish appropriate dietary strategies for obese population.

MOLECULAR DOCKING OF COMPOUNDS FROM Chaetomium Sp. AGAINST HUMAN ESTROGEN RECEPTOR ALPHA IN SEARCHING ANTI BREAST CANCER

Directory of Open Access Journals (Sweden)

Maywan Hariono

2016-05-01

Full Text Available A study on molecular docking-based virtual screening has been conducted to select virtual hit of compounds, reported its existence in fungal endophytes of Chaetomium sp. as cytotoxic agent of breast cancer. The ligands were docked into Human Estrogen Receptor alpha (HERa as the protein which regulates the breast cancer growth via estradiol-estrogen receptor binding intervention. The results showed that two compounds bearing xanthone and two compounds bearing benzonaphtyridinedione scaffolds were selected as virtual hit ligands for HERa leading to the conclusion that these compounds were good to be developed as anti breast cancer.

Non-occlusive topical exposure of human skin in vitro as model for cytotoxicity testing of irritant compounds.

Science.gov (United States)

Lönnqvist, Susanna; Briheim, Kristina; Kratz, Gunnar

2016-02-01

Testing of irritant compounds has traditionally been performed on animals and human volunteers. Animal testing should always be restricted and for skin irritancy mice and rabbits hold poor predictive value for irritant potential in humans. Irritant testing on human volunteers is restricted by the duration subjects can be exposed, and by the subjectivity of interpreting the visual signs of skin irritation. We propose an irritant testing system using viable human full thickness skin with the loss of cell viability in the exposed skin area as end point measurement. Skin was exposed to sodium dodecyl sulfate (SDS) at 20% concentration by non-occluded topical exposure to establish a positive control response and subsequent test compounds were statistically compared with the 20% SDS response. Cell viability and metabolism were measured with 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. The model presents correlation between increased concentration of SDS and decreased viability of cells in the exposed skin area (R(2) = 0.76). We propose the model to be used for cytotoxicity testing of irritant compounds. With fully intact barrier function, the model comprises all cells present in the skin with quantifiable end point measurement.

Microencapsulated bitter compounds (from Gentiana lutea) reduce daily energy intakes in humans.

Science.gov (United States)

Mennella, Ilario; Fogliano, Vincenzo; Ferracane, Rosalia; Arlorio, Marco; Pattarino, Franco; Vitaglione, Paola

2016-11-10

Mounting evidence showed that bitter-tasting compounds modulate eating behaviour through bitter taste receptors in the gastrointestinal tract. This study aimed at evaluating the influence of microencapsulated bitter compounds on human appetite and energy intakes. A microencapsulated bitter ingredient (EBI) with a core of bitter Gentiana lutea root extract and a coating of ethylcellulose-stearate was developed and included in a vanilla microencapsulated bitter ingredient-enriched pudding (EBIP). The coating masked bitterness in the mouth, allowing the release of bitter secoiridoids in the gastrointestinal tract. A cross-over randomised study was performed: twenty healthy subjects consumed at breakfast EBIP (providing 100 mg of secoiridoids) or the control pudding (CP) on two different occasions. Blood samples, glycaemia and appetite ratings were collected at baseline and 30, 60, 120 and 180 min after breakfast. Gastrointestinal peptides, endocannabinoids (EC) and N-acylethanolamines (NAE) were measured in plasma samples. Energy intakes were measured at an ad libitum lunch 3 h after breakfast and over the rest of the day (post lunch) through food diaries. No significant difference in postprandial plasma responses of gastrointestinal hormones, glucose, EC and NAE and of appetite between EBIP and CP was found. However, a trend for a higher response of glucagon-like peptide-1 after EBIP than after CP was observed. EBIP determined a significant 30 % lower energy intake over the post-lunch period compared with CP. These findings were consistent with the tailored release of bitter-tasting compounds from EBIP along the gastrointestinal tract. This study demonstrated that microencapsulated bitter secoiridoids were effective in reducing daily energy intake in humans.

Determination of the levels of dioxin and dioxin-like compounds in the Australian population by analysis of pooled human breast milk

Energy Technology Data Exchange (ETDEWEB)

Harden, F.; Mueller, J.F.; Toms, L.M.L.; Moore, M. [National Research Centre for Environmental Toxicology, The Univ. of Queensland, Brisbane (Australia); Burniston, D.; Symons, R. [AGAL, Sydney (Australia); Ahokas, J. [RMIT, Melbourne (Australia); Fuerst, P. [State Lab. of NRW, Muenster (Germany); Paepke, O. [ERGO Forschungsgesellschaft, Hamburg (Germany)

2004-09-15

Dioxin-like compounds are ubiquitously distributed and humans are exposed to them via various sources but primarily through food. They can be detected in air, water, soil, sediment and biota. These compounds are lipid soluble, poorly eliminated and thus can accumulate in human adipose tissue. They can cross the placenta and are also transferred to breast milk during the lactation process. Therefore infants are exposed ante and postnatally. Since PCDD/PCDF concentration in blood and human milk are very similar when concentrations are expressed on a lipid basis, human milk provides a good monitoring tool of exposure for a given population in a given area. Previously the WHO has co-ordinated international studies on dioxin-like compounds in breast milk. These were conducted in 1987/88, 1992/93 and 2001. In summary, these studies demonstrated that levels of dioxins in breast milk are relatively high in industrialised countries when compared to non-industrialised countries that PCDD/PCDFs were higher in human milk from mothers with their first child and that the levels decrease over a given lactation period. The present study aims to examine the levels of these compounds in primiparae women throughout Australia.

Immortalized human myotonic dystrophy muscle cell lines to assess therapeutic compounds

OpenAIRE

Arandel, Ludovic; Polay Espinoza, Micaela; Matloka, Magdalena; Bazinet, Audrey; De Dea Diniz, Damily; Naouar, Na?ra; Rau, Fr?d?rique; Jollet, Arnaud; Edom-Vovard, Fr?d?rique; Mamchaoui, Kamel; Tarnopolsky, Mark; Puymirat, Jack; Battail, Christophe; Boland, Anne; Deleuze, Jean-Francois

2017-01-01

International audience; Myotonic dystrophy type 1 (DM1) and type 2 (DM2) are autosomal dominant neuromuscular diseases caused by microsatellite expansions and belong to the family of RNA-dominant disorders. Availability of cellular models in which the DM mutation is expressed within its natural context is essential to facilitate efforts to identify new therapeutic compounds. Here, we generated immortalized DM1 and DM2 human muscle cell lines that display nuclear RNA aggregates of expanded rep...

Impaired representation of geometric relationships in humans with damage to the hippocampal formation.

Directory of Open Access Journals (Sweden)

Carsten Finke

Full Text Available The pivotal role of the hippocampus for spatial memory is well-established. However, while neurophysiological and imaging studies suggest a specialization of the hippocampus for viewpoint-independent or allocentric memory, results from human lesion studies have been less conclusive. It is currently unclear whether disproportionate impairment in allocentric memory tasks reflects impairment of cognitive functions that are not sufficiently supported by regions outside the medial temporal lobe or whether the deficits observed in some studies are due to experimental factors. Here, we have investigated whether hippocampal contributions to spatial memory depend on the spatial references that are available in a certain behavioral context. Patients with medial temporal lobe lesions affecting systematically the right hippocampal formation performed a series of three oculomotor tasks that required memory of a spatial cue either in retinal coordinates or relative to a single environmental reference across a delay of 5000 ms. Stimulus displays varied the availability of spatial references and contained no complex visuo-spatial associations. Patients showed a selective impairment in a condition that critically depended on memory of the geometric relationship between spatial cue and environmental reference. We infer that regions of the medial temporal lobe, most likely the hippocampal formation, contribute to behavior in conditions that exceed the potential of viewpoint-dependent or egocentric representations. Apparently, this already applies to short-term memory of simple geometric relationships and does not necessarily depend on task difficulty or integration of landmarks into more complex representations. Deficient memory of basic geometric relationships may represent a core deficit that contributes to impaired performance in allocentric spatial memory tasks.

Human computer interaction and communication aids for hearing-impaired, deaf and deaf-blind people: Introduction to the special thematic session

DEFF Research Database (Denmark)

Bothe, Hans-Heinrich

2008-01-01

This paper gives ail overview and extends the Special Thematic Session (STS) oil research and development of technologies for hearing-impaired, deaf, and deaf-blind people. The topics of the session focus oil special equipment or services to improve communication and human computer interaction....... The papers are related to visual communication using captions, sign language, speech-reading, to vibro-tactile stimulation, or to general services for hearing-impaired persons....

Sleep deprivation impairs spatial retrieval but not spatial learning in the non-human primate grey mouse lemur.

Directory of Open Access Journals (Sweden)

Anisur Rahman

Full Text Available A bulk of studies in rodents and humans suggest that sleep facilitates different phases of learning and memory process, while sleep deprivation (SD impairs these processes. Here we tested the hypothesis that SD could alter spatial learning and memory processing in a non-human primate, the grey mouse lemur (Microcebus murinus, which is an interesting model of aging and Alzheimer's disease (AD. Two sets of experiments were performed. In a first set of experiments, we investigated the effects of SD on spatial learning and memory retrieval after one day of training in a circular platform task. Eleven male mouse lemurs aged between 2 to 3 years were tested in three different conditions: without SD as a baseline reference, 8 h of SD before the training and 8 h of SD before the testing. The SD was confirmed by electroencephalographic recordings. Results showed no effect of SD on learning when SD was applied before the training. When the SD was applied before the testing, it induced an increase of the amount of errors and of the latency prior to reach the target. In a second set of experiments, we tested the effect of 8 h of SD on spatial memory retrieval after 3 days of training. Twenty male mouse lemurs aged between 2 to 3 years were tested in this set of experiments. In this condition, the SD did not affect memory retrieval. This is the first study that documents the disruptive effects of the SD on spatial memory retrieval in this primate which may serve as a new validated challenge to investigate the effects of new compounds along physiological and pathological aging.

Polyphenol Compound as a Transcription Factor Inhibitor

Directory of Open Access Journals (Sweden)

Seyeon Park

2015-10-01

Full Text Available A target-based approach has been used to develop novel drugs in many therapeutic fields. In the final stage of intracellular signaling, transcription factor–DNA interactions are central to most biological processes and therefore represent a large and important class of targets for human therapeutics. Thus, we focused on the idea that the disruption of protein dimers and cognate DNA complexes could impair the transcriptional activation and cell transformation regulated by these proteins. Historically, natural products have been regarded as providing the primary leading compounds capable of modulating protein–protein or protein-DNA interactions. Although their mechanism of action is not fully defined, polyphenols including flavonoids were found to act mostly as site-directed small molecule inhibitors on signaling. There are many reports in the literature of screening initiatives suggesting improved drugs that can modulate the transcription factor interactions responsible for disease. In this review, we focus on polyphenol compound inhibitors against dimeric forms of transcription factor components of intracellular signaling pathways (for instance, c-jun/c-fos (Activator Protein-1; AP-1, c-myc/max, Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB and β-catenin/T cell factor (Tcf.

Polyphenol Compound as a Transcription Factor Inhibitor.

Science.gov (United States)

Park, Seyeon

2015-10-30

A target-based approach has been used to develop novel drugs in many therapeutic fields. In the final stage of intracellular signaling, transcription factor-DNA interactions are central to most biological processes and therefore represent a large and important class of targets for human therapeutics. Thus, we focused on the idea that the disruption of protein dimers and cognate DNA complexes could impair the transcriptional activation and cell transformation regulated by these proteins. Historically, natural products have been regarded as providing the primary leading compounds capable of modulating protein-protein or protein-DNA interactions. Although their mechanism of action is not fully defined, polyphenols including flavonoids were found to act mostly as site-directed small molecule inhibitors on signaling. There are many reports in the literature of screening initiatives suggesting improved drugs that can modulate the transcription factor interactions responsible for disease. In this review, we focus on polyphenol compound inhibitors against dimeric forms of transcription factor components of intracellular signaling pathways (for instance, c-jun/c-fos (Activator Protein-1; AP-1), c-myc/max, Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and β-catenin/T cell factor (Tcf)).

Human Elimination of Phthalate Compounds: Blood, Urine, and Sweat (BUS) Study

Science.gov (United States)

Genuis, Stephen J.; Beesoon, Sanjay; Lobo, Rebecca A.; Birkholz, Detlef

2012-01-01

Background. Individual members of the phthalate family of chemical compounds are components of innumerable everyday consumer products, resulting in a high exposure scenario for some individuals and population groups. Multiple epidemiological studies have demonstrated statistically significant exposure-disease relationships involving phthalates and toxicological studies have shown estrogenic effects in vitro. Data is lacking in the medical literature, however, on effective means to facilitate phthalate excretion. Methods. Blood, urine, and sweat were collected from 20 individuals (10 healthy participants and 10 participants with assorted health problems) and analyzed for parent phthalate compounds as well as phthalate metabolites using high performance liquid chromatography-tandem mass spectrometry. Results. Some parent phthalates as well as their metabolites were excreted into sweat. All patients had MEHP (mono(2-ethylhexyl) phthalate) in their blood, sweat, and urine samples, suggesting widespread phthalate exposure. In several individuals, DEHP (di (2-ethylhexl) phthalate) was found in sweat but not in serum, suggesting the possibility of phthalate retention and bioaccumulation. On average, MEHP concentration in sweat was more than twice as high as urine levels. Conclusions. Induced perspiration may be useful to facilitate elimination of some potentially toxic phthalate compounds including DEHP and MEHP. Sweat analysis may be helpful in establishing the existence of accrued DEHP in the human body. PMID:23213291

Effect of compounds with antibacterial activities in human milk on respiratory syncytial virus and cytomegalovirus in vitro.

Science.gov (United States)

Portelli, J; Gordon, A; May, J T

1998-11-01

The effect of some antibacterial compounds present in human milk were tested for antiviral activity against respiratory syncytial virus, Semliki Forest virus and cytomegalovirus. These included the gangliosides GM1, GM2 and GM3, sialyl-lactose, lactoferrin and chondroitin sulphate A, B and C, which were all tested for their ability to inhibit the viruses in cell culture. Of the compounds tested, only the ganglioside GM2, chondroitin sulphate B and lactoferrin inhibited the absorption and growth of respiratory syncytial virus in cell culture, and none inhibited the growth of Semliki Forest virus, indicating that lipid antiviral activity was not associated with any of the gangliosides. While the concentrations of these two compounds required to inhibit respiratory syncytial virus were in excess of those present in human milk, sialyl-lactose concentrations similar to those present in human milk increased the growth of cytomegalovirus. Lactoferrin was confirmed as inhibiting both respiratory syncytial virus and cytomegalovirus growth in culture even when used at lower concentrations than those present in human milk. The antiviral activities of GM2, chondroitin sulphate B and lactoferrin were tested when added to an infant formula. Lactoferrin continued to have antiviral activity against cytomegalovirus, but a lower activity against respiratory syncytial virus; ganglioside GM2 and chondroitin sulphate B still maintained antiviral activity against respiratory syncytial virus.

Development of an Intracellular Screen for New Compounds Able To Inhibit Mycobacterium tuberculosis Growth in Human Macrophages.

Science.gov (United States)

Sorrentino, Flavia; Gonzalez del Rio, Ruben; Zheng, Xingji; Presa Matilla, Jesus; Torres Gomez, Pedro; Martinez Hoyos, Maria; Perez Herran, Maria Esther; Mendoza Losana, Alfonso; Av-Gay, Yossef

2016-01-01

Here we describe the development and validation of an intracellular high-throughput screening assay for finding new antituberculosis compounds active in human macrophages. The assay consists of a luciferase-based primary identification assay, followed by a green fluorescent protein-based secondary profiling assay. Standard tuberculosis drugs and 158 previously recognized active antimycobacterial compounds were used to evaluate assay robustness. Data show that the assay developed is a short and valuable tool for the discovery of new antimycobacterial compounds. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Danshen-Chuanxiong-Honghua Ameliorates Cerebral Impairment and Improves Spatial Cognitive Deficits after Transient Focal Ischemia and Identification of Active Compounds

Directory of Open Access Journals (Sweden)

Xianhua Zhang

2017-07-01

Full Text Available Previously, we only apply a traditional Chinese medicine (TCM Danshen-Chuanxiong-Honghua (DCH for cardioprotection via anti-inflammation in rats of acute myocardial infarction by occluding coronary artery. Presently, we select not only DCH but also its main absorbed compound ferulic acid (FA for cerebra protection via similar action of mechanism above in animals of the transient middle cerebral artery occlusion (tMCAO. We investigated whether oral administration of DCH and FA could ameliorate MCAO-induced brain lesions in animals. By using liquid chromatography-tandem mass spectrometry (LC-MS/MS, we analyzed four compounds, including tanshinol, salvianolic acid B, hydroxysafflor yellow A and especially FA as the putative active components of DCH extract in the plasma, cerebrospinal fluid and injured hippocampus of rats with MCAO. In our study, it was assumed that FA played a similar neuroprotective role to DCH. We found that oral pretreatment with DCH (10 or 20 g/kg and FA (100 mg/kg improved neurological function and alleviated the infarct volume as well as brain edema in a dose-dependent manner. These changes were accompanied by improved ischemia-induced apoptosis and decreased the inflammatory response. Additionally, chronic treatment with DCH reversed MCAO-induced spatial cognitive deficits in a manner associated with enhanced neurogenesis and increased the expression of brain-derived neurotrophic factor in lesions of the hippocampus. These findings suggest that DCH has the ability to recover cognitive impairment and offer neuroprotection against cerebral ischemic injury via inhibiting microenvironmental inflammation and triggering of neurogenesis in the hippocampus. FA could be one of the potential active compounds.

78 FR 72899 - Draft Guidance for Industry on Registration for Human Drug Compounding Outsourcing Facilities...

Science.gov (United States)

2013-12-04

... information technology. Under the draft guidance, outsourcing facilities that elect to register should submit... guidance provides information on how an outsourcing facility should submit facility registration...] Draft Guidance for Industry on Registration for Human Drug Compounding Outsourcing Facilities Under...

Organohalogen compounds in human breast milk from Republic of Buryatia, Russia

International Nuclear Information System (INIS)

Tsydenova, Oyuna V.; Sudaryanto, Agus; Kajiwara, Natsuko; Kunisue, Tatsuya; Batoev, Valeriy B.; Tanabe, Shinsuke

2007-01-01

Human breast milk samples collected during 2003/04 in Buryatia, a Russian autonomous republic, were analyzed in order to assess human exposure to organohalogen compounds including organochlorine pesticides, polychlorinated biphenyls (PCBs), and polybrominated diphenyl ethers (PBDEs). When compared with available worldwide data, levels of HCB (23-880 ng/g lipid wt.), PCBs (69-680 ng/g lipid wt.), and HCHs (100-3700 ng/g lipid wt.) were relatively high, indicating elevated human exposure to these organochlorines (OCs) in Buryatia. In contrast to OCs, PBDE concentrations were low (0.46-1.7 ng/g lipid wt.). Out of 14 BDE congeners analyzed, BDE-28, BDE-47, BDE-100, BDE-153, BDE-197, and BDE-207 were detected. Estimated daily intakes (EDIs) of HCHs, HCB, CHLs, and PCBs by infants solely from human milk for 100%, 43%, 34%, and 17% of the samples, respectively, exceeded guideline thresholds. Although high EDIs raise concern for possible toxic effects of OCs, women in Buryatia are recommended to breastfeed due to numerous advantages of breastfeeding for mother and child. - People in the Republic of Buryatia, Russia are exposed to relatively high levels of HCHs, HCB and PCBs

Organohalogen compounds in human breast milk from Republic of Buryatia, Russia

Energy Technology Data Exchange (ETDEWEB)

Tsydenova, Oyuna V. [Center for Marine Environmental Studies (CMES), Ehime University, Bunkyo-cho 2-5, Matsuyama 790-8577 (Japan); Sudaryanto, Agus [Center for Marine Environmental Studies (CMES), Ehime University, Bunkyo-cho 2-5, Matsuyama 790-8577 (Japan); Kajiwara, Natsuko [Center for Marine Environmental Studies (CMES), Ehime University, Bunkyo-cho 2-5, Matsuyama 790-8577 (Japan); Kunisue, Tatsuya [Center for Marine Environmental Studies (CMES), Ehime University, Bunkyo-cho 2-5, Matsuyama 790-8577 (Japan); Batoev, Valeriy B. [Baikal Institute of Nature Management, Siberian Branch of Russian Academy of Sciences, Sakhyanova st. 6, Ulan-Ude 670047 (Russian Federation); Tanabe, Shinsuke [Center for Marine Environmental Studies (CMES), Ehime University, Bunkyo-cho 2-5, Matsuyama 790-8577 (Japan)]. E-mail: shinsuke@agr.ehime-u.ac.jp

2007-03-15

Human breast milk samples collected during 2003/04 in Buryatia, a Russian autonomous republic, were analyzed in order to assess human exposure to organohalogen compounds including organochlorine pesticides, polychlorinated biphenyls (PCBs), and polybrominated diphenyl ethers (PBDEs). When compared with available worldwide data, levels of HCB (23-880 ng/g lipid wt.), PCBs (69-680 ng/g lipid wt.), and HCHs (100-3700 ng/g lipid wt.) were relatively high, indicating elevated human exposure to these organochlorines (OCs) in Buryatia. In contrast to OCs, PBDE concentrations were low (0.46-1.7 ng/g lipid wt.). Out of 14 BDE congeners analyzed, BDE-28, BDE-47, BDE-100, BDE-153, BDE-197, and BDE-207 were detected. Estimated daily intakes (EDIs) of HCHs, HCB, CHLs, and PCBs by infants solely from human milk for 100%, 43%, 34%, and 17% of the samples, respectively, exceeded guideline thresholds. Although high EDIs raise concern for possible toxic effects of OCs, women in Buryatia are recommended to breastfeed due to numerous advantages of breastfeeding for mother and child. - People in the Republic of Buryatia, Russia are exposed to relatively high levels of HCHs, HCB and PCBs.

Nutraceuticals in cognitive impairment and Alzheimer's disease.

Science.gov (United States)

Mecocci, P; Tinarelli, C; Schulz, R J; Polidori, M C

2014-01-01

Several chemical substances belonging to classes of natural dietary origin display protective properties against some age-related diseases including neurodegenerative ones, particularly Alzheimer's disease (AD). These compounds, known as nutraceuticals, differ structurally, act therefore at different biochemical and metabolic levels and have shown different types of neuroprotective properties. The aim of this review is to summarize data from observational studies, clinical trials, and randomized clinical trials (RCTs) in humans on the effects of selected nutraceuticals against age-related cognitive impairment and dementia. We report results from studies on flavonoids, some vitamins and other natural substances that have been studied in AD and that might be beneficial for the maintenance of a good cognitive performance. Due to the substantial lack of high-level evidence studies there is no possibility for recommendation of nutraceuticals in dementia-related therapeutic guidelines. Nevertheless, the strong potential for their neuroprotective action warrants further studies in the field.

Quantification of volatile organic compounds in exhaled human breath. Acetonitrile as biomarker for passive smoking. Model for isoprene in human breath

International Nuclear Information System (INIS)

Prazeller, P.

2000-03-01

The topic of this thesis is the quantification of volatile organic compounds in human breath under various circumstances. The composition of exhaled breath reflects metabolic processes in the human body. Breath analysis is a non invasive technique which makes it most interesting especially for medical or toxicological applications. Measurements were done with Proton-Transfer-Reaction Mass-Spectrometry (PTR-MS). This technique combines the advantage of small fragmentation of chemical ionization with highly time resolved mass spectrometry. A big part of this work is about investigations of exposition due to tobacco smoke. After smoking cigarettes the initial increase and time dependence of some compounds in the human breath are monitored . The calculated decrease resulting only from breathing out the compounds is presented and compared to the measured decline in the breath. This allows the distinction whether breathing is the dominant loss of a compound or a different metabolic process remover it more efficiently. Acetonitrile measured in human breath is presented as a biomarker for exposition to tobacco smoke. Especially its use for quantification of passive smoking, the exposition to environmental tobacco smoke (ETS) is shown. The reached accuracy and the fast way of measuring of acetonitrile in human breath using PTR-MS offer a good alternative to common used biomarkers. Numerous publications have described measurements of breath isoprene in humans, and there has been a hope that breath isoprene analyses could be a non-invasive diagnostic tool to assess serum cholesterol levels or cholesterol synthesis rate. However, significant analytical problems in breath isoprene analysis and variability in isoprene levels with age, exercise, diet, etc. have limited the usefulness of these measurements. Here, we have applied proton-transfer-reaction mass spectrometry (PTR-MS) to this problem, allowing on-line detection of breath isoprene. We show that breath isoprene

Compound danshen tablet ameliorated aβ25-35-induced spatial memory impairment in mice via rescuing imbalance between cytokines and neurotrophins.

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Teng, Yan; Zhang, Meng-Qi; Wang, Wen; Liu, Li-Tao; Zhou, Li-Ming; Miao, Shi-Kun; Wan, Li-Hong

2014-01-14

Compound Danshen Tablet (CDT), a Traditional Chinese Medicine, has recently been reported to improve spatial cognition in a rat model of Alzheimer's disease. However, in vivo neuroprotective mechanism of the CDT in models of spatial memory impairment is not yet evaluated. The present study is aimed to elucidate the cellular mechanism of CDT on Aβ25-35-induced cognitive impairment in mice. Mice were randomly divided into 5 groups: the control group (sham operated), the Aβ25-35 treated group, the positive drug group, and large and small dosage of the CDT groups, respectively. CDT was administered at a dose of 0.81 g/kg and 0.405 g/kg for 3 weeks. The mice in the positive drug group were treated with 0.4 mg/kg of Huperzine A, whereas the mice of the control and Aβ25-35 treated groups were administrated orally with equivalent saline. After 7 days of preventive treatment, mice were subjected to lateral ventricle injection of Aβ25-35 to establish the mice model of Alzheimer's disease. Spatial memory impairment was evaluated by Morris water maze test. Choline acetyltransferase (ChAT) contents in hippocampus and cortex were quantified by ELISA. The levels of cytokines, receptor of activated protein kinase C1 (RACK1) and brain-derived neurotrophic factor (BDNF) in hippocampus were measured by RT-PCR and ELISA. The results showed that Aβ25-35 caused spatial memory impairment as demonstrated by performance in the Morris water maze test. CDT was able to confer a significant improvement in spatial memory, and protect mice from Aβ25-35-induced neurotoxicity. Additionally, CDT also inhibited the increase of TNF-α and IL-6 level, and increased the expression of choline acetyltransferase (ChAT), receptor of activated protein kinase C1 (RACK1) and brain-derived neurotrophic factor (BDNF) in brain as compared to model mice. These findings strongly implicate that CDT may be a useful treatment against learning and memory deficits in mice by rescuing imbalance between cytokines

Assessment of chimeric mice with humanized livers in new drug development: generation of pharmacokinetics, metabolism and toxicity data for selecting the final candidate compound.

Science.gov (United States)

Kamimura, Hidetaka; Ito, Satoshi

2016-01-01

1. Chimeric mice with humanized livers are expected to be a novel tool for new drug development. This review discusses four applications where these animals can be used efficiently to collect supportive data for selecting the best compound in the final stage of drug discovery. 2. The first application is selection of the final compound based on estimated pharmacokinetic parameters in humans. Since chimeric mouse livers are highly repopulated with human hepatocytes, hepatic clearance values in vivo could be used preferentially to estimate pharmacokinetic profiles for humans. 3. The second is prediction of human-specific or disproportionate metabolites. Chimeric mice reproduce human-specific metabolites of drugs under development to conform to ICH guidance M3(R2), except for compounds that were extensively eliminated by co-existing mouse hepatocytes. 4. The third is identifying metabolites with distinct pharmacokinetic profiles in humans. Slow metabolite elimination specifically in humans increases its exposure level, but if its elimination is faster in laboratory animals, the animal exposure level might not satisfy ICH guidance M3(R2). 5. Finally, two examples of reproducing acute liver toxicity in chimeric mice are introduced. Integrated pharmacokinetics, metabolism and toxicity information are expected to assist pharmaceutical scientists in selecting the best candidate compound in new drug development.

Affective Education for Visually Impaired Children.

Science.gov (United States)

Locke, Don C.; Gerler, Edwin R., Jr.

1981-01-01

Evaluated the effectiveness of the Human Development Program (HDP) and the Developing Understanding of Self and Others (DUSO) program used with visually impaired children. Although HDP and DUSO affected the behavior of visually impaired children, they did not have any effect on children's attitudes toward school. (RC)

Acute stress impairs the retrieval of extinction memory in humans

Science.gov (United States)

Raio, Candace M.; Brignoni-Perez, Edith; Goldman, Rachel; Phelps, Elizabeth A.

2014-01-01

Extinction training is a form of inhibitory learning that allows an organism to associate a previously aversive cue with a new, safe outcome. Extinction does not erase a fear association, but instead creates a competing association that may or may not be retrieved when a cue is subsequently encountered. Characterizing the conditions under which extinction learning is expressed is important to enhancing the treatment of anxiety disorders that rely on extinction-based exposure therapy as a primary treatment technique. The ventromedial prefrontal cortex, which plays an important role in the expression of extinction memory, has been shown to be functionally impaired after stress exposure. Further, recent research in rodents found that exposure to stress led to deficits in extinction retrieval, although this has yet to be tested in humans. To explore how stress might influence extinction retrieval in humans, participants underwent a differential aversive learning paradigm, in which one image was probabilistically paired with an aversive shock while the other image denoted safety. Extinction training directly followed, at which point reinforcement was omitted. A day later, participants returned to the lab and either completed an acute stress manipulation (i.e., cold pressor), or a control task, before undergoing an extinction retrieval test. Skin conductance responses and salivary cortisol concentrations were measured throughout each session as indices of fear arousal and neuroendocrine stress responses, respectively. The efficacy of our stress induction was established by observing significant increases in cortisol for the stress condition only. We examined extinction retrieval by comparing conditioned responses during the last trial of extinction (day 1) with that of the first trial of re-extinction (day 2). Groups did not differ on initial fear acquisition or extinction, however, one day later participants in the stress group (n = 27) demonstrated significantly less

Phenolic compounds apigenin, hesperidin and kaempferol reduce in vitro lipid accumulation in human adipocytes.

Science.gov (United States)

Gómez-Zorita, Saioa; Lasa, Arrate; Abendaño, Naiara; Fernández-Quintela, Alfredo; Mosqueda-Solís, Andrea; Garcia-Sobreviela, Maria Pilar; Arbonés-Mainar, Jose M; Portillo, Maria P

2017-11-21

Adipocytes derived from human mesenchymal stem cells (MSCs) are widely used to investigate adipogenesis. Taking into account both the novelty of these MSCs and the scarcity of studies focused on the effects of phenolic compounds, the aim of the present study was to analyze the effect of apigenin, hesperidin and kaempferol on pre-adipocyte and mature adipocytes derived from this type of cells. In addition, the expression of genes involved in TG accumulation was also measured. Pre-adipocytes were cultured from day 0 to day 8 and mature adipocytes for 48 h with the polyphenols at doses of 1, 10 and 25 µM. Apigenin did not show an anti-adipogenic action. Pre-adipocytes treated with hesperidin and kaempferol showed reduced TG content at the three experimental doses. Apigenin did not modify the expression of the main adipogenic genes (c/ebpβ, c/ebpα, pparγ and srebp1c), hesperidin inhibited genes involved in the three phases of adipogenesis (c/ebpβ, srebp1c and perilipin) and kaempferol reduced c/ebpβ. In mature adipocytes, the three polyphenols reduced TG accumulation at the dose of 25 µM, but not at lower doses. All compounds increased mRNA levels of atgl. Apigenin and hesperidin decreased fasn expression. The present study shows the anti-adipogenic effect and delipidating effects of apigenin, hesperidin and kaempferol in human adipocytes derived from hMSCs. While hesperidin blocks all the stages of adipogenesis, kaempferol only inhibits the early stage. Regarding mature adipocytes, the three compounds reduce TG accumulation by activating, at least in part, lipolysis, and in the case of hesperidin and apigenin, also by reducing lipogenesis. The present study shows for the first time the anti-adipogenic effect and delipidating effect of apigenin, hesperidin and kaempferol in human adipocytes derived from MSCs for the first time.

p53-independent structure-activity relationships of 3-ring mesogenic compounds' activity as cytotoxic effects against human non-small cell lung cancer lines.

Science.gov (United States)

Fukushi, Saori; Yoshino, Hironori; Yoshizawa, Atsushi; Kashiwakura, Ikuo

2016-07-25

We recently demonstrated the cytotoxicity of liquid crystal precursors (hereafter referred to as "mesogenic compounds") in the human non-small cell lung cancer (NSCLC) cell line A549 which carry wild-type p53. p53 mutations are observed in 50 % of NSCLC and contribute to their resistance to chemotherapy. To develop more effective and cancer-specific agents, in this study, we investigated the structure-activity relationships of mesogenic compounds with cytotoxic effects against multiple NSCLC cells. The pharmacological effects of mesogenic compounds were examined in human NSCLC cells (A549, LU99, EBC-1, and H1299) and normal WI-38 human fibroblast. Analyses of the cell cycle, cell-death induction, and capsases expression were performed. The 3-ring compounds possessing terminal alkyl and hydroxyl groups (compounds C1-C5) showed cytotoxicity in NSCLC cells regardless of the p53 status. The compounds C1 and C3, which possess a pyrimidine at the center of the core, induced G2/M arrest, while the compounds without a pyrimidine (C2, C4, and C5) caused G1 arrest; all compounds produced caspase-mediated cell death. These events occurred in a p53-independent manner. Furthermore, it was suggested that compounds induced cell death through p53-independent DNA damage-signaling pathway. Compounds C2, C4, and C5 did not show strong cytotoxicity in WI-38 cells, whereas C1 and C3 did. However, the cytotoxicity of compound C1 against WI-38 cells was improved by modulating the terminal alkyl chain lengths of the compound. We showed the p53-indepdent structure-activity relationships of mesogenic compounds related to the cytotoxic effects. These structure-activity relationships will be helpful in the development of more effective and cancer-specific agents.

Progress in the pharmacological treatment of human cystic and alveolar echinococcosis: Compounds and therapeutic targets

Science.gov (United States)

Siles-Lucas, Mar; Casulli, Adriano; Cirilli, Roberto

2018-01-01

Human cystic and alveolar echinococcosis are helmintic zoonotic diseases caused by infections with the larval stages of the cestode parasites Echinococcus granulosus and E. multilocularis, respectively. Both diseases are progressive and chronic, and often fatal if left unattended for E. multilocularis. As a treatment approach, chemotherapy against these orphan and neglected diseases has been available for more than 40 years. However, drug options were limited to the benzimidazoles albendazole and mebendazole, the only chemical compounds currently licensed for treatment in humans. To compensate this therapeutic shortfall, new treatment alternatives are urgently needed, including the identification, development, and assessment of novel compound classes and drug targets. Here is presented a thorough overview of the range of compounds that have been tested against E. granulosus and E. multilocularis in recent years, including in vitro and in vivo data on their mode of action, dosage, administration regimen, therapeutic outcomes, and associated clinical symptoms. Drugs covered included albendazole, mebendazole, and other members of the benzimidazole family and their derivatives, including improved formulations and combined therapies with other biocidal agents. Chemically synthetized molecules previously known to be effective against other infectious and non-infectious conditions such as anti-virals, antibiotics, anti-parasites, anti-mycotics, and anti-neoplastics are addressed. In view of their increasing relevance, natural occurring compounds derived from plant and fungal extracts are also discussed. Special attention has been paid to the recent application of genomic science on drug discovery and clinical medicine, particularly through the identification of small inhibitor molecules tackling key metabolic enzymes or signalling pathways. PMID:29677189

Progress in the pharmacological treatment of human cystic and alveolar echinococcosis: Compounds and therapeutic targets.

Directory of Open Access Journals (Sweden)

Mar Siles-Lucas

2018-04-01

Full Text Available Human cystic and alveolar echinococcosis are helmintic zoonotic diseases caused by infections with the larval stages of the cestode parasites Echinococcus granulosus and E. multilocularis, respectively. Both diseases are progressive and chronic, and often fatal if left unattended for E. multilocularis. As a treatment approach, chemotherapy against these orphan and neglected diseases has been available for more than 40 years. However, drug options were limited to the benzimidazoles albendazole and mebendazole, the only chemical compounds currently licensed for treatment in humans. To compensate this therapeutic shortfall, new treatment alternatives are urgently needed, including the identification, development, and assessment of novel compound classes and drug targets. Here is presented a thorough overview of the range of compounds that have been tested against E. granulosus and E. multilocularis in recent years, including in vitro and in vivo data on their mode of action, dosage, administration regimen, therapeutic outcomes, and associated clinical symptoms. Drugs covered included albendazole, mebendazole, and other members of the benzimidazole family and their derivatives, including improved formulations and combined therapies with other biocidal agents. Chemically synthetized molecules previously known to be effective against other infectious and non-infectious conditions such as anti-virals, antibiotics, anti-parasites, anti-mycotics, and anti-neoplastics are addressed. In view of their increasing relevance, natural occurring compounds derived from plant and fungal extracts are also discussed. Special attention has been paid to the recent application of genomic science on drug discovery and clinical medicine, particularly through the identification of small inhibitor molecules tackling key metabolic enzymes or signalling pathways.

Biologically Active Compounds of Plant Foods: Prospective Impact ...

African Journals Online (AJOL)

On the other hand, other biologically active compounds impair health by ... of essential elements through different mechanisms and giving astringent taste, odor, ... The health benefits of selected substances from Ethiopian food crops need to ...

Blocking mineralocorticoid receptors impairs, blocking glucocorticoid receptors enhances memory retrieval in humans.

Science.gov (United States)

Rimmele, Ulrike; Besedovsky, Luciana; Lange, Tanja; Born, Jan

2013-04-01

Memory retrieval is impaired at very low as well as very high cortisol levels, but not at intermediate levels. This inverted-U-shaped relationship between cortisol levels and memory retrieval may originate from different roles of the mineralocorticoid (MR) and glucocorticoid receptor (GR) that bind cortisol with distinctly different affinity. Here, we examined the role of MRs and GRs in human memory retrieval using specific receptor antagonists. In two double-blind within-subject, cross-over designed studies, young healthy men were asked to retrieve emotional and neutral texts and pictures (learnt 3 days earlier) between 0745 and 0915 hours in the morning, either after administration of 400 mg of the MR blocker spironolactone vs placebo (200 mg at 2300 hours and 200 mg at 0400 hours, Study I) or after administration of the GR blocker mifepristone vs placebo (200 mg at 2300 hours, Study II). Blockade of MRs impaired free recall of both texts and pictures particularly for emotional material. In contrast, blockade of GRs resulted in better memory retrieval for pictures, with the effect being more pronounced for neutral than emotional materials. These findings indicate indeed opposing roles of MRs and GRs in memory retrieval, with optimal retrieval at intermediate cortisol levels likely mediated by high MR but concurrently low GR activation.

45 CFR 1308.9 - Eligibility criteria: Speech or language impairments.

Science.gov (United States)

2010-10-01

... HUMAN DEVELOPMENT SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION FOR CHILDREN... language impairments. (a) A speech or language impairment means a communication disorder such as stuttering... language disorder may be characterized by difficulty in understanding and producing language, including...

The human volatilome: volatile organic compounds (VOCs) in exhaled breath, skin emanations, urine, feces and saliva.

Science.gov (United States)

Amann, Anton; Costello, Ben de Lacy; Miekisch, Wolfram; Schubert, Jochen; Buszewski, Bogusław; Pleil, Joachim; Ratcliffe, Norman; Risby, Terence

2014-09-01

Breath analysis is a young field of research with its roots in antiquity. Antoine Lavoisier discovered carbon dioxide in exhaled breath during the period 1777-1783, Wilhelm (Vilém) Petters discovered acetone in breath in 1857 and Johannes Müller reported the first quantitative measurements of acetone in 1898. A recent review reported 1765 volatile compounds appearing in exhaled breath, skin emanations, urine, saliva, human breast milk, blood and feces. For a large number of compounds, real-time analysis of exhaled breath or skin emanations has been performed, e.g., during exertion of effort on a stationary bicycle or during sleep. Volatile compounds in exhaled breath, which record historical exposure, are called the 'exposome'. Changes in biogenic volatile organic compound concentrations can be used to mirror metabolic or (patho)physiological processes in the whole body or blood concentrations of drugs (e.g. propofol) in clinical settings-even during artificial ventilation or during surgery. Also compounds released by bacterial strains like Pseudomonas aeruginosa or Streptococcus pneumonia could be very interesting. Methyl methacrylate (CAS 80-62-6), for example, was observed in the headspace of Streptococcus pneumonia in concentrations up to 1420 ppb. Fecal volatiles have been implicated in differentiating certain infectious bowel diseases such as Clostridium difficile, Campylobacter, Salmonella and Cholera. They have also been used to differentiate other non-infectious conditions such as irritable bowel syndrome and inflammatory bowel disease. In addition, alterations in urine volatiles have been used to detect urinary tract infections, bladder, prostate and other cancers. Peroxidation of lipids and other biomolecules by reactive oxygen species produce volatile compounds like ethane and 1-pentane. Noninvasive detection and therapeutic monitoring of oxidative stress would be highly desirable in autoimmunological, neurological, inflammatory diseases and cancer

Impaired Odor Recognition Memory in Patients with Hippocampal Lesions

Science.gov (United States)

Levy, Daniel A.; Squire, Larry R.; Hopkins, Ramona O.

2004-01-01

In humans, impaired recognition memory following lesions thought to be limited to the hippocampal region has been demonstrated for a wide variety of tasks. However, the importance of the human hippocampus for olfactory recognition memory has scarcely been explored. We evaluated the ability of memory-impaired patients with damage thought to be…

Documents for Recommended Toxicity Equivalency Factors for Human Health Risk Assessments of Dioxin and Dioxin-Like Compounds

Science.gov (United States)

This document describes the U.S. Environmental Protection Agency’s (U.S. EPA’s) updated approach for evaluating the human health risks from exposures to environmental media containing dioxin-like compounds (DLCs).

Comparison of the neurotoxicities between volatile organic compounds and fragrant organic compounds on human neuroblastoma SK-N-SH cells and primary cultured rat neurons

Directory of Open Access Journals (Sweden)

Yasue Yamada

2015-01-01

Full Text Available These are many volatile organic compounds (VOCs that are synthesized, produced from petroleum or derived from natural compounds, mostly plants. Fragrant and volatile organic compounds from plants have been used as food additives, medicines and aromatherapy. Several clinical and pathological studies have shown that chronic abuse of VOCs, mainly toluene, causes several neuropsychiatric disorders. Little is known about the mechanisms of neurotoxicity of the solvents. n-Octanal, nonanal, and 2-ethyl-1-hexanol, which are used catalyzers or intermediates of chemical reactions, are released into the environment. Essential oils have the functions of self-defense, sterilization, and antibiosis in plants. When volatile organic compounds enter the body, there is the possibility that they will pass through the blood–brain barrier (BBB and affect the central nervous system (CNS. However, the direct effects of volatile organic compounds on neural function and their toxicities are still unclear. We compared the toxicities of n-octanal, nonanal and 2-ethyl-1-hexanol with those of five naturally derived fragrant organic compounds (FOCs, linalool, cis-3-hexen-1-ol, isoamyl alcohol, n-propyl alcohol and n-phenethyl alcohol. MTT assay of human neuroblastoma SK-N-SH cells showed that the IC50 values of linalool, cis-3-hexen-1-ol, isoamyl alcohol, n-propyl alcohol and phenethyl alcohol were 1.33, 2.3, >5, >5, and 2.39 mM, respectively, and the IC50 values of toluene, n-octanal, nonanal and 2-ethyl-1-hexanol were 850, 37.2, 8.31 and 15.1 μM, respectively. FOCs showed lower toxicities than those of VOCs. These results indicate that FOCs are safer than other compounds.

Acacetin and Chrysin, Two Polyphenolic Compounds, Alleviate Telomeric Position Effect in Human Cells

Directory of Open Access Journals (Sweden)

Amina Boussouar

2013-01-01

Full Text Available We took advantage of the ability of human telomeres to silence neighboring genes (telomere position effect or TPE to design a high-throughput screening assay for drugs altering telomeres. We identified, for the first time, that two dietary flavones, acacetin and chrysin, are able to specifically alleviate TPE in human cells. We further investigated their influence on telomere integrity and showed that both drugs drastically deprotect telomeres against DNA damage response. However, telomere deprotection triggered by shelterin dysfunction does not affect TPE, indicating that acacetin and chrysin target several functions of telomeres. These results show that TPE-based screening assays represent valuable methods to discover new compounds targeting telomeres.

Endocrine disrupting compounds in drinking water supply system and human health risk implication.

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Wee, Sze Yee; Aris, Ahmad Zaharin

2017-09-01

To date, experimental and epidemiological evidence of endocrine disrupting compounds (EDCs) adversely affecting human and animal populations has been widely debated. Notably, human health risk assessment is required for risk mitigation. The lack of human health risk assessment and management may thus unreliably regulate the quality of water resources and efficiency of treatment processes. Therefore, drinking water supply systems (DWSSs) may be still unwarranted in assuring safe access to potable drinking water. Drinking water supply, such as tap water, is an additional and crucial route of human exposure to the health risks associated with EDCs. A holistic system, incorporating continuous research in DWSS monitoring and management using multi-barrier approach, is proposed as a preventive measure to reduce human exposure to the risks associated with EDCs through drinking water consumption. The occurrence of EDCs in DWSSs and corresponding human health risk implications are analyzed using the Needs, Approaches, Benefits, and Challenges (NABC) method. Therefore, this review may act as a supportive tool in protecting human health and environmental quality from EDCs, which is essential for decision-making regarding environmental monitoring and management purposes. Subsequently, the public could have sustainable access to safer and more reliable drinking water. Copyright © 2017 Elsevier Ltd. All rights reserved.

High-content screening of small compounds on human embryonic stem cells.

Science.gov (United States)

Barbaric, Ivana; Gokhale, Paul J; Andrews, Peter W

2010-08-01

Human ES (embryonic stem) cells and iPS (induced pluripotent stem) cells have been heralded as a source of differentiated cells that could be used in the treatment of degenerative diseases, such as Parkinson's disease or diabetes. Despite the great potential for their use in regenerative therapy, the challenge remains to understand the basic biology of these remarkable cells, in order to differentiate them into any functional cell type. Given the scale of the task, high-throughput screening of agents and culture conditions offers one way to accelerate these studies. The screening of small-compound libraries is particularly amenable to such high-throughput methods. Coupled with high-content screening technology that enables simultaneous assessment of multiple cellular features in an automated and quantitative way, this approach is proving powerful in identifying both small molecules as tools for manipulating stem cell fates and novel mechanisms of differentiation not previously associated with stem cell biology. Such screens performed on human ES cells also demonstrate the usefulness of human ES/iPS cells as cellular models for pharmacological testing of drug efficacy and toxicity, possibly a more imminent use of these cells than in regenerative medicine.

Identification of early target genes of aflatoxin B1 in human hepatocytes, inter-individual variability and comparison with other genotoxic compounds

International Nuclear Information System (INIS)

Josse, Rozenn; Dumont, Julie; Fautrel, Alain; Robin, Marie-Anne; Guillouzo, André

2012-01-01

Gene expression profiling has recently emerged as a promising approach to identify early target genes and discriminate genotoxic carcinogens from non-genotoxic carcinogens and non-carcinogens. However, early gene changes induced by genotoxic compounds in human liver remain largely unknown. Primary human hepatocytes and differentiated HepaRG cells were exposed to aflatoxin B1 (AFB1) that induces DNA damage following enzyme-mediated bioactivation. Gene expression profile changes induced by a 24 h exposure of these hepatocyte models to 0.05 and 0.25 μM AFB1 were analyzed by using oligonucleotide pangenomic microarrays. The main altered signaling pathway was the p53 pathway and related functions such as cell cycle, apoptosis and DNA repair. Direct involvement of the p53 protein in response to AFB1 was verified by using siRNA directed against p53. Among the 83 well-annotated genes commonly modulated in two pools of three human hepatocyte populations and HepaRG cells, several genes were identified as altered by AFB1 for the first time. In addition, a subset of 10 AFB1-altered genes, selected upon basis of their function or tumor suppressor role, was tested in four human hepatocyte populations and in response to other chemicals. Although they exhibited large variable inter-donor fold-changes, several of these genes, particularly FHIT, BCAS3 and SMYD3, were found to be altered by various direct and other indirect genotoxic compounds and unaffected by non-genotoxic compounds. Overall, this comprehensive analysis of early gene expression changes induced by AFB1 in human hepatocytes identified a gene subset that included several genes representing potential biomarkers of genotoxic compounds. -- Highlights: ► Gene expression profile changes induced by aflatoxin B1 in human hepatocytes. ► AFB1 modulates various genes including tumor suppressor genes and proto-oncogenes. ► Important inter-individual variations in the response to AFB1. ► Some genes also altered by other

Aging impairs transcriptional regulation of vascular endothelial growth factor in human microvascular endothelial cells: implications for angiogenesis and cell survival.

Science.gov (United States)

Ahluwalia, A; Jones, M K; Szabo, S; Tarnawski, A S

2014-04-01

In some tissues, aging impairs angiogenesis and reduces expression of vascular endothelial growth factor A (VEGF), a fundamental regulator of angiogenesis. We previously examined angiogenesis in aging and young gastric mucosa in vivo and in vitro and showed that an imbalance between expressions of VEGF (pro-angiogenic factor) and endostatin (anti-angiogenic protein) results in an aging-related impairment of angiogenesis in rats. However, the human relevance of these findings, and whether these mechanisms apply to endothelial cells derived from other tissues, is not clear. Since P-STAT3 and P-CREB are transcription factors that, in association with HIF-1α, can activate VEGF gene expression in some cells (e.g., liver cancer cells, vascular smooth muscle cells), we examined the expression of these two proteins in human dermal microvascular endothelial cells (HMVECs) derived from aging and neonatal individuals. We examined and quantified in vitro angiogenesis, expression of VEGF, P-STAT3, P-CREB and importin-α in HMVECs isolated from neonates (neonatal) and a 66 year old subject (aging). We also examined the effects of treatment with exogenous VEGF and endostatin on in vitro angiogenesis in these cells. Endothelial cells isolated from aging individuals had impaired angiogenesis (vs. neonatal endothelial cells) and reduced expression of VEGF mRNA and protein. Aged HMVECs also had reduced importin-α expression, and reduced expression and nuclear translocation of P-STAT3 and P-CREB. Reduced VEGF gene expression in aged HMVECs strongly correlated with the decreased levels of P-STAT3, P-CREB and importin-α in these cells. Our study clearly demonstrates that endothelial cells from aging individuals have impaired angiogenesis and reduced expression of VEGF likely due to impaired nuclear transport of P-STAT3 and P-CREB transcription factors in these cells.

Novel 5-HT5A receptor antagonists ameliorate scopolamine-induced working memory deficit in mice and reference memory impairment in aged rats.

Science.gov (United States)

Yamazaki, Mayako; Okabe, Mayuko; Yamamoto, Noriyuki; Yarimizu, Junko; Harada, Katsuya

2015-03-01

Despite the human 5-HT5A receptor being cloned in 1994, the biological function of this receptor has not been extensively characterized due to a lack of specific ligands. We recently reported that the selective 5-HT5A receptor antagonist ASP5736 ameliorated cognitive impairment in several animal models of schizophrenia. Given that areas of the brain with high levels of 5-HT5A receptor expression, such as the hippocampus and cerebral cortex, have important functions in cognition and memory, we evaluated the chemically diverse, potent and brain-penetrating 5-HT5A receptor antagonists ASP5736, AS2030680, and AS2674723 in rodent models of cognitive dysfunction associated with dementia. Each of these compounds exhibited a high affinity for recombinant 5-HT5A receptors that was comparable to that of the non-selective ligand of this receptor, lysergic acid diethylamide (LSD). Although each compound had a low affinity for other receptors, 5-HT5A was the only receptor for which all three compounds had a high affinity. Each of the three compounds ameliorated scopolamine-induced working memory deficit in mice and improved reference memory impairment in aged rats at similar doses. Further, ASP5736 decreased the binding of LSD to 5-HT5A receptors in the olfactory bulb of rats in a dose-dependent manner and occupied 15%-50% of brain 5-HT5A receptors at behaviorally effective doses. These results indicate that the 5-HT5A receptor is involved in learning and memory and that treatment with 5-HT5A receptor antagonists might be broadly effective for cognitive impairment associated with not only schizophrenia but also dementia. Copyright © 2015 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Chloric organic compound

International Nuclear Information System (INIS)

Moalem, F.

2000-01-01

Since many years ago, hazardous and toxic refuses which are results of human activities has been carelessly without any Biological and Engineering facts and knowledge discharged into our land and water. The effects of discharging those materials in environment are different. Some of refuse materials shows short and other has long-time adverse effects in our environment, Among hazardous organic chemical materials, chlorine, consider, to be the main element. Organic materials with chlorine is called chlorine hydrocarbon as a hazardous compound. This paper discuss the hazardous materials especially chloric organic compound and their misuse effects in environment and human being

An Overview of Plant Phenolic Compounds and Their Importance in Human Nutrition and Management of Type 2 Diabetes

Directory of Open Access Journals (Sweden)

Derong Lin

2016-10-01

Full Text Available In this paper, the biosynthesis process of phenolic compounds in plants is summarized, which includes the shikimate, pentose phosphate and phenylpropanoid pathways. Plant phenolic compounds can act as antioxidants, structural polymers (lignin, attractants (flavonoids and carotenoids, UV screens (flavonoids, signal compounds (salicylic acid and flavonoids and defense response chemicals (tannins and phytoalexins. From a human physiological standpoint, phenolic compounds are vital in defense responses, such as anti-aging, anti-inflammatory, antioxidant and anti-proliferative activities. Therefore, it is beneficial to eat such plant foods that have a high antioxidant compound content, which will cut down the incidence of certain chronic diseases, for instance diabetes, cancers and cardiovascular diseases, through the management of oxidative stress. Furthermore, berries and other fruits with low-amylase and high-glucosidase inhibitory activities could be regarded as candidate food items in the control of the early stages of hyperglycemia associated with type 2 diabetes.

Hyperglycaemia and diabetes impair gap junctional communication among astrocytes.

Science.gov (United States)

Gandhi, Gautam K; Ball, Kelly K; Cruz, Nancy F; Dienel, Gerald A

2010-03-15

Sensory and cognitive impairments have been documented in diabetic humans and animals, but the pathophysiology of diabetes in the central nervous system is poorly understood. Because a high glucose level disrupts gap junctional communication in various cell types and astrocytes are extensively coupled by gap junctions to form large syncytia, the influence of experimental diabetes on gap junction channel-mediated dye transfer was assessed in astrocytes in tissue culture and in brain slices from diabetic rats. Astrocytes grown in 15-25 mmol/l glucose had a slow-onset, poorly reversible decrement in gap junctional communication compared with those grown in 5.5 mmol/l glucose. Astrocytes in brain slices from adult STZ (streptozotocin)-treated rats at 20-24 weeks after the onset of diabetes also exhibited reduced dye transfer. In cultured astrocytes grown in high glucose, increased oxidative stress preceded the decrement in dye transfer by several days, and gap junctional impairment was prevented, but not rescued, after its manifestation by compounds that can block or reduce oxidative stress. In sharp contrast with these findings, chaperone molecules known to facilitate protein folding could prevent and rescue gap junctional impairment, even in the presence of elevated glucose level and oxidative stress. Immunostaining of Cx (connexin) 43 and 30, but not Cx26, was altered by growth in high glucose. Disruption of astrocytic trafficking of metabolites and signalling molecules may alter interactions among astrocytes, neurons and endothelial cells and contribute to changes in brain function in diabetes. Involvement of the microvasculature may contribute to diabetic complications in the brain, the cardiovascular system and other organs.

Gut Microbiota Profiling: Metabolomics Based Approach to Unravel Compounds Affecting Human Health.

Science.gov (United States)

Vernocchi, Pamela; Del Chierico, Federica; Putignani, Lorenza

2016-01-01

The gut microbiota is composed of a huge number of different bacteria, that produce a large amount of compounds playing a key role in microbe selection and in the construction of a metabolic signaling network. The microbial activities are affected by environmental stimuli leading to the generation of a wide number of compounds, that influence the host metabolome and human health. Indeed, metabolite profiles related to the gut microbiota can offer deep insights on the impact of lifestyle and dietary factors on chronic and acute diseases. Metagenomics, metaproteomics and metabolomics are some of the meta-omics approaches to study the modulation of the gut microbiota. Metabolomic research applied to biofluids allows to: define the metabolic profile; identify and quantify classes and compounds of interest; characterize small molecules produced by intestinal microbes; and define the biochemical pathways of metabolites. Mass spectrometry and nuclear magnetic resonance spectroscopy are the principal technologies applied to metabolomics in terms of coverage, sensitivity and quantification. Moreover, the use of biostatistics and mathematical approaches coupled with metabolomics play a key role in the extraction of biologically meaningful information from wide datasets. Metabolomic studies in gut microbiota-related research have increased, focusing on the generation of novel biomarkers, which could lead to the development of mechanistic hypotheses potentially applicable to the development of nutritional and personalized therapies.

Β-amyloid 1-42 oligomers impair function of human embryonic stem cell-derived forebrain cholinergic neurons.

Directory of Open Access Journals (Sweden)

Linn Wicklund

Full Text Available Cognitive impairment in Alzheimer's disease (AD patients is associated with a decline in the levels of growth factors, impairment of axonal transport and marked degeneration of basal forebrain cholinergic neurons (BFCNs. Neurogenesis persists in the adult human brain, and the stimulation of regenerative processes in the CNS is an attractive prospect for neuroreplacement therapy in neurodegenerative diseases such as AD. Currently, it is still not clear how the pathophysiological environment in the AD brain affects stem cell biology. Previous studies investigating the effects of the β-amyloid (Aβ peptide on neurogenesis have been inconclusive, since both neurogenic and neurotoxic effects on progenitor cell populations have been reported. In this study, we treated pluripotent human embryonic stem (hES cells with nerve growth factor (NGF as well as with fibrillar and oligomeric Aβ1-40 and Aβ1-42 (nM-µM concentrations and thereafter studied the differentiation in vitro during 28-35 days. The process applied real time quantitative PCR, immunocytochemistry as well as functional studies of intracellular calcium signaling. Treatment with NGF promoted the differentiation into functionally mature BFCNs. In comparison to untreated cells, oligomeric Aβ1-40 increased the number of functional neurons, whereas oligomeric Aβ1-42 suppressed the number of functional neurons. Interestingly, oligomeric Aβ exposure did not influence the number of hES cell-derived neurons compared with untreated cells, while in contrast fibrillar Aβ1-40 and Aβ1-42 induced gliogenesis. These findings indicate that Aβ1-42 oligomers may impair the function of stem cell-derived neurons. We propose that it may be possible for future AD therapies to promote the maturation of functional stem cell-derived neurons by altering the brain microenvironment with trophic support and by targeting different aggregation forms of Aβ.

Nutraceuticals in cognitive impairment and Alzheimer’s disease

Directory of Open Access Journals (Sweden)

Patrizia eMecocci

2014-06-01

Full Text Available Several chemical substances belonging to classes of natural dietary origin display protective properties against some age-related diseases including neurodegenerative ones, particularly Alzheimer’s disease (AD. These compounds, known as nutraceuticals, differ structurally, act therefore at different biochemical and metabolic levels and have shown different types of neuroprotective properties. The aim of this review is to summarize data from observational studies, clinical trials and randomized clinical trials (RCTs in humans on the effects of selected nutraceuticals against age-related cognitive impairment and dementia. We report results from studies on flavonoids, some vitamins and other natural substances that have been studied in AD and that might be beneficial for the maintenance of a good cognitive performance. Due to the substantial lack of high-level evidence studies there is no possibility for recommendation of nutraceuticals in dementia-related therapeutic guidelines. Nevertheless, the strong potential for their neuroprotective action warrants further studies in the field.

Pittsburgh compound B imaging and cerebrospinal fluid amyloid-β in a multicentre European memory clinic study

DEFF Research Database (Denmark)

Leuzy, Antoine; Chiotis, Konstantinos; Hasselbalch, Steen G

2016-01-01

subjects with normal cognition and patients with mild cognitive impairment, Alzheimer's disease dementia, frontotemporal dementia, and vascular dementia. All had Pittsburgh compound B positron emission tomography data, cerebrospinal fluid INNOTEST amyloid-β42 values, and cerebrospinal fluid samples...... uptake value ratio results were scaled using the Centiloid method. Concordance between Meso Scale Discovery/mass spectrometry reference measurement procedure findings and Pittsburgh compound B was high in subjects with mild cognitive impairment and Alzheimer's disease, while more variable results were...

Exposure to perfluorononanoic acid combined with a low-dose mixture of 14 human-relevant compounds disturbs energy/lipid homeostasis in rats

DEFF Research Database (Denmark)

Skov, Kasper; Kongsbak, Kristine Grønning; Hadrup, Niels

2015-01-01

, whereas effects on lipid metabolism in the liver were mainly driven by PFNA. This study verifies that a chemical mixture given at high-end human exposure levels can affect lipid homeostasis and that the combined use of metabolomics and transcriptomics can provide complimentary information allowing......Humans are constantly exposed to a significant number of compounds and many are readily detected in human body fluids. Worryingly, several of these compounds are either suspected to be, or have already been shown to be harmful to humans either individually or in combination. However, the potential...... consequences of low-dose exposure to complex mixtures remain poorly understood. We have profiled the effects on rat blood plasma and liver homeostasis using metabolomics and transcriptomics following 2-week exposure to either a mixture of 14 common chemicals (Mix), perfluorononanoic acid (PFNA) at low (0...

Bisphenol A impairs the memory function and glutamatergic homeostasis in a sex-dependent manner in mice: Beneficial effects of diphenyl diselenide.

Science.gov (United States)

Jardim, Natália S; Sartori, Glaúbia; Sari, Marcel H M; Müller, Sabrina G; Nogueira, Cristina W

2017-08-15

Bisphenol A (BPA) is a compound integrated in commodities, which consequently increases the human exposure to this toxicant. The deleterious effects of BPA exposure during periods of brain development have been documented mainly concerning the impairment in memory functions. Diphenyl diselenide (PhSe) 2 , an organoselenium compound, shows protective/restorative effects against memory deficits in experimental models. Thus, this study investigated the effects of (PhSe) 2 on the memory impairments induced by BPA exposure to male and female mice and the possible involvement of glutamatergic system in these effects. Three-week-old male and female Swiss mice received BPA (5mg/kg), intragastrically, from 21st to 60th postnatal day. After, the animals were intragastrically treated with (PhSe) 2 (1mg/kg) during seven days. The mice performed the behavioral memory tests and the [ 3 H] glutamate uptake and NMDA receptor subunits (2A and 2B) analyses were carried out in the hippocampus and cerebral cortex of mice. The results demonstrated that the BPA exposure induced impairment of object recognition memory in both sexes. However, it caused impairments in spatial memory in female and in the passive avoidance memory in male mice. Besides, BPA caused a decrease in the [ 3 H] glutamate uptake and NMDA receptor subunit levels in the cortical and hippocampal regions depending on the sex. Treatment with (PhSe) 2 reversed in a sex-independent manner the behavioral impairments and molecular alterations. In conclusion, BPA had a negative effect in different memory types as well as in the glutamatergic parameters in a sex-dependent manner and (PhSe) 2 treatment was effective against these alterations. Copyright © 2017 Elsevier Inc. All rights reserved.

Impaired production of proinflammatory cytokines in response to lipopolysaccharide (LPS) stimulation in elderly humans

DEFF Research Database (Denmark)

Bruunsgaard, H.; Pedersen, Agnes Nadelmann; Schroll, M.

1999-01-01

following LPS stimulation, representing an ex vivo model of sepsis. Levels of tumour necrosis factor-alpha (TNF-alpha), IL-1 beta and IL-6 in whole blood supernatants were measured after in vitro LPS stimulation for 24 h in 168 elderly humans aged 81 years from the 1914 cohort in Glostrup, Denmark and in 91...... of proinflammatory cytokines compared with young men, but this difference was blurred by ageing. No relation was found between circulating plasma levels of TNF-alpha and levels after in vitro LPS stimulation. In conclusion, decreased production of TNF-alpha and IL-1 beta after exposure to LPS may reflect impaired...

Human-Health Pharmaceutical Compounds in Lake Mead, Nevada and Arizona, and Las Vegas Wash, Nevada, October 2000-August 2001

National Research Council Canada - National Science Library

Boyd, Robert A; Furlong, Edward T

2002-01-01

The U.S. Geological Survey and the National Park Service conducted a reconnaissance study to investigate the occurrence of selected human-health pharmaceutical compounds in water samples collected from Lake...

The Natural Antiangiogenic Compound AD0157 Induces Caspase-Dependent Apoptosis in Human Myeloid Leukemia Cells

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Melissa García-Caballero

2017-11-01

Full Text Available Evasion of apoptosis is a hallmark of cancer especially relevant in the development and the appearance of leukemia drug resistance mechanisms. The development of new drugs that could trigger apoptosis in aggressive hematological malignancies, such as AML and CML, may be considered a promising antileukemic strategy. AD0157, a natural marine pyrrolidinedione, has already been described as a compound that inhibits angiogenesis by induction of apoptosis in endothelial cells. The crucial role played by defects in the apoptosis pathways in the pathogenesis, progression and response to conventional therapies of several forms of leukemia, moved us to analyze the effect of this compound on the growth and death of leukemia cells. In this work, human myeloid leukemia cells (HL60, U937 and KU812F were treated with AD0157 ranging from 1 to 10 μM and an experimental battery was applied to evaluate its apoptogenic potential. We report here that AD0157 was highly effective to inhibit cell growth by promotion of apoptosis in human myeloid leukemia cells, and provide evidence of its mechanisms of action. The apoptogenic activity of AD0157 on leukemia cells was verified by an increased chromatin condensation and DNA fragmentation, and confirmed by an augmentation in the apoptotic subG1 population, translocation of the membrane phosphatidylserine from the inner face of the plasma membrane to the cell surface and by cleavage of the apoptosis substrates PARP and lamin-A. In addition, AD0157 in the low micromolar range significantly enhanced the activities of the initiator caspases-8 and -9, and the effector caspases-3/-7 in a dose-dependent manner. Results presented here throw light on the apoptogenic mechanism of action of AD0157, mediated through caspase-dependent cascades, with an especially relevant role played by mitochondria. Altogether, these results suggest the therapeutic potential of this compound for the treatment of human myeloid leukemia.

Sleep deprivation impairs object recognition in mice

NARCIS (Netherlands)

Palchykova, S; Winsky-Sommerer, R; Meerlo, P; Durr, R; Tobler, Irene

2006-01-01

Many studies in animals and humans suggest that sleep facilitates learning, memory consolidation, and retrieval. Moreover, sleep deprivation (SD) incurred after learning, impaired memory in humans, mice, rats, and hamsters. We investigated the importance of sleep and its timing in in object

Peroxides and radiation impairment of oxidative phosphorylation

Energy Technology Data Exchange (ETDEWEB)

Dovgii, I E; Akoev, I G

1975-09-01

An increase in the peroxidase activity of the mitochondria and a simultaneous rise in the amount of peroxide compounds, which are half lipid-like substances, are detected within the first 10 minutes after irradiation (1000 r). A mechanism of radiation impairment of oxidative phosphorylation is connected with the penetration of its inhibitors to the mitochondria due to the disturbed permeability of membranes affected by peroxides.

Immortalized human myotonic dystrophy muscle cell lines to assess therapeutic compounds

Science.gov (United States)

Arandel, Ludovic; Polay Espinoza, Micaela; Matloka, Magdalena; Bazinet, Audrey; De Dea Diniz, Damily; Naouar, Naïra; Rau, Frédérique; Jollet, Arnaud; Edom-Vovard, Frédérique; Mamchaoui, Kamel; Tarnopolsky, Mark; Puymirat, Jack; Battail, Christophe; Boland, Anne; Deleuze, Jean-Francois; Mouly, Vincent; Klein, Arnaud F.

2017-01-01

ABSTRACT Myotonic dystrophy type 1 (DM1) and type 2 (DM2) are autosomal dominant neuromuscular diseases caused by microsatellite expansions and belong to the family of RNA-dominant disorders. Availability of cellular models in which the DM mutation is expressed within its natural context is essential to facilitate efforts to identify new therapeutic compounds. Here, we generated immortalized DM1 and DM2 human muscle cell lines that display nuclear RNA aggregates of expanded repeats, a hallmark of myotonic dystrophy. Selected clones of DM1 and DM2 immortalized myoblasts behave as parental primary myoblasts with a reduced fusion capacity of immortalized DM1 myoblasts when compared with control and DM2 cells. Alternative splicing defects were observed in differentiated DM1 muscle cell lines, but not in DM2 lines. Splicing alterations did not result from differentiation delay because similar changes were found in immortalized DM1 transdifferentiated fibroblasts in which myogenic differentiation has been forced by overexpression of MYOD1. As a proof-of-concept, we show that antisense approaches alleviate disease-associated defects, and an RNA-seq analysis confirmed that the vast majority of mis-spliced events in immortalized DM1 muscle cells were affected by antisense treatment, with half of them significantly rescued in treated DM1 cells. Immortalized DM1 muscle cell lines displaying characteristic disease-associated molecular features such as nuclear RNA aggregates and splicing defects can be used as robust readouts for the screening of therapeutic compounds. Therefore, immortalized DM1 and DM2 muscle cell lines represent new models and tools to investigate molecular pathophysiological mechanisms and evaluate the in vitro effects of compounds on RNA toxicity associated with myotonic dystrophy mutations. PMID:28188264

Immortalized human myotonic dystrophy muscle cell lines to assess therapeutic compounds

Directory of Open Access Journals (Sweden)

Ludovic Arandel

2017-04-01

Full Text Available Myotonic dystrophy type 1 (DM1 and type 2 (DM2 are autosomal dominant neuromuscular diseases caused by microsatellite expansions and belong to the family of RNA-dominant disorders. Availability of cellular models in which the DM mutation is expressed within its natural context is essential to facilitate efforts to identify new therapeutic compounds. Here, we generated immortalized DM1 and DM2 human muscle cell lines that display nuclear RNA aggregates of expanded repeats, a hallmark of myotonic dystrophy. Selected clones of DM1 and DM2 immortalized myoblasts behave as parental primary myoblasts with a reduced fusion capacity of immortalized DM1 myoblasts when compared with control and DM2 cells. Alternative splicing defects were observed in differentiated DM1 muscle cell lines, but not in DM2 lines. Splicing alterations did not result from differentiation delay because similar changes were found in immortalized DM1 transdifferentiated fibroblasts in which myogenic differentiation has been forced by overexpression of MYOD1. As a proof-of-concept, we show that antisense approaches alleviate disease-associated defects, and an RNA-seq analysis confirmed that the vast majority of mis-spliced events in immortalized DM1 muscle cells were affected by antisense treatment, with half of them significantly rescued in treated DM1 cells. Immortalized DM1 muscle cell lines displaying characteristic disease-associated molecular features such as nuclear RNA aggregates and splicing defects can be used as robust readouts for the screening of therapeutic compounds. Therefore, immortalized DM1 and DM2 muscle cell lines represent new models and tools to investigate molecular pathophysiological mechanisms and evaluate the in vitro effects of compounds on RNA toxicity associated with myotonic dystrophy mutations.

Immortalized human myotonic dystrophy muscle cell lines to assess therapeutic compounds.

Science.gov (United States)

Arandel, Ludovic; Polay Espinoza, Micaela; Matloka, Magdalena; Bazinet, Audrey; De Dea Diniz, Damily; Naouar, Naïra; Rau, Frédérique; Jollet, Arnaud; Edom-Vovard, Frédérique; Mamchaoui, Kamel; Tarnopolsky, Mark; Puymirat, Jack; Battail, Christophe; Boland, Anne; Deleuze, Jean-Francois; Mouly, Vincent; Klein, Arnaud F; Furling, Denis

2017-04-01

Myotonic dystrophy type 1 (DM1) and type 2 (DM2) are autosomal dominant neuromuscular diseases caused by microsatellite expansions and belong to the family of RNA-dominant disorders. Availability of cellular models in which the DM mutation is expressed within its natural context is essential to facilitate efforts to identify new therapeutic compounds. Here, we generated immortalized DM1 and DM2 human muscle cell lines that display nuclear RNA aggregates of expanded repeats, a hallmark of myotonic dystrophy. Selected clones of DM1 and DM2 immortalized myoblasts behave as parental primary myoblasts with a reduced fusion capacity of immortalized DM1 myoblasts when compared with control and DM2 cells. Alternative splicing defects were observed in differentiated DM1 muscle cell lines, but not in DM2 lines. Splicing alterations did not result from differentiation delay because similar changes were found in immortalized DM1 transdifferentiated fibroblasts in which myogenic differentiation has been forced by overexpression of MYOD1. As a proof-of-concept, we show that antisense approaches alleviate disease-associated defects, and an RNA-seq analysis confirmed that the vast majority of mis-spliced events in immortalized DM1 muscle cells were affected by antisense treatment, with half of them significantly rescued in treated DM1 cells. Immortalized DM1 muscle cell lines displaying characteristic disease-associated molecular features such as nuclear RNA aggregates and splicing defects can be used as robust readouts for the screening of therapeutic compounds. Therefore, immortalized DM1 and DM2 muscle cell lines represent new models and tools to investigate molecular pathophysiological mechanisms and evaluate the in vitro effects of compounds on RNA toxicity associated with myotonic dystrophy mutations. © 2017. Published by The Company of Biologists Ltd.

Fast track, dynein-dependent nuclear targeting of human immunodeficiency virus Vpr protein; impaired trafficking in a clinical isolate

Energy Technology Data Exchange (ETDEWEB)

Caly, Leon [Department of Biochemistry and Molecular Biology, Monash University, Clayton, Vic. 3800 (Australia); Kassouf, Vicki T. [Centre for Virus Research, The Westmead Institute for Medical Research, The University of Sydney, Westmead, NSW 2145 (Australia); Moseley, Gregory W. [Department of Biochemistry and Molecular Biology, Monash University, Clayton, Vic. 3800 (Australia); Diefenbach, Russell J.; Cunningham, Anthony L. [Centre for Virus Research, The Westmead Institute for Medical Research, The University of Sydney, Westmead, NSW 2145 (Australia); Jans, David A., E-mail: david.jans@monash.edu [Department of Biochemistry and Molecular Biology, Monash University, Clayton, Vic. 3800 (Australia)

2016-02-12

Nuclear import of the accessory protein Vpr is central to infection by human immunodeficiency virus (HIV). We previously identified the Vpr F72L mutation in a HIV-infected, long-term non-progressor, showing that it resulted in reduced Vpr nuclear accumulation and altered cytoplasmic localisation. Here we demonstrate for the first time that the effects of nuclear accumulation of the F72L mutation are due to impairment of microtubule-dependent-enhancement of Vpr nuclear import. We use high resolution imaging approaches including fluorescence recovery after photobleaching and other approaches to document interaction between Vpr and the dynein light chain protein, DYNLT1, and impaired interaction of the F72L mutant with DYNLT1. The results implicate MTs/DYNLT1 as drivers of Vpr nuclear import and HIV infection, with important therapeutic implications. - Highlights: • HIV-1 Vpr utilizes the microtubule network to traffic towards the nucleus. • Mechanism relies on interaction between Vpr and dynein light chain protein DYNLT1. • Long-term non-progressor derived mutation (F72L) impairs this interaction. • Key residues in the vicinity of F72 contribute to interaction with DYNLT1.

Fast track, dynein-dependent nuclear targeting of human immunodeficiency virus Vpr protein; impaired trafficking in a clinical isolate

International Nuclear Information System (INIS)

Caly, Leon; Kassouf, Vicki T.; Moseley, Gregory W.; Diefenbach, Russell J.; Cunningham, Anthony L.; Jans, David A.

2016-01-01

Nuclear import of the accessory protein Vpr is central to infection by human immunodeficiency virus (HIV). We previously identified the Vpr F72L mutation in a HIV-infected, long-term non-progressor, showing that it resulted in reduced Vpr nuclear accumulation and altered cytoplasmic localisation. Here we demonstrate for the first time that the effects of nuclear accumulation of the F72L mutation are due to impairment of microtubule-dependent-enhancement of Vpr nuclear import. We use high resolution imaging approaches including fluorescence recovery after photobleaching and other approaches to document interaction between Vpr and the dynein light chain protein, DYNLT1, and impaired interaction of the F72L mutant with DYNLT1. The results implicate MTs/DYNLT1 as drivers of Vpr nuclear import and HIV infection, with important therapeutic implications. - Highlights: • HIV-1 Vpr utilizes the microtubule network to traffic towards the nucleus. • Mechanism relies on interaction between Vpr and dynein light chain protein DYNLT1. • Long-term non-progressor derived mutation (F72L) impairs this interaction. • Key residues in the vicinity of F72 contribute to interaction with DYNLT1.

Chlorinated volatile organic compounds (Cl-VOCs) in environment - sources, potential human health impacts, and current remediation technologies.

Science.gov (United States)

Huang, Binbin; Lei, Chao; Wei, Chaohai; Zeng, Guangming

2014-10-01

Chlorinated volatile organic compounds (Cl-VOCs), including polychloromethanes, polychloroethanes and polychloroethylenes, are widely used as solvents, degreasing agents and a variety of commercial products. These compounds belong to a group of ubiquitous contaminants that can be found in contaminated soil, air and any kind of fluvial mediums such as groundwater, rivers and lakes. This review presents a summary of the research concerning the production levels and sources of Cl-VOCs, their potential impacts on human health as well as state-of-the-art remediation technologies. Important sources of Cl-VOCs principally include the emissions from industrial processes, the consumption of Cl-VOC-containing products, the disinfection process, as well as improper storage and disposal methods. Human exposure to Cl-VOCs can occur through different routes, including ingestion, inhalation and dermal contact. The toxicological impacts of these compounds have been carefully assessed, and the results demonstrate the potential associations of cancer incidence with exposure to Cl-VOCs. Most Cl-VOCs thus have been listed as priority pollutants by the Ministry of Environmental Protection (MEP) of China, Environmental Protection Agency of the U.S. (U.S. EPA) and European Commission (EC), and are under close monitor and strict control. Yet, more efforts will be put into the epidemiological studies for the risk of human exposure to Cl-VOCs and the exposure level measurements in contaminated sites in the future. State-of-the-art remediation technologies for Cl-VOCs employ non-destructive methods and destructive methods (e.g. thermal incineration, phytoremediation, biodegradation, advanced oxidation processes (AOPs) and reductive dechlorination), whose advantages, drawbacks and future developments are thoroughly discussed in the later sections. Copyright © 2014 Elsevier Ltd. All rights reserved.

Multipurpose Compound

Science.gov (United States)

1983-01-01

Specially formulated derivatives of an unusual basic compound known as Alcide may be the answer to effective treatment and prevention of the disease bovine mastitis, a bacterial inflammation of a cow's mammary gland that results in loss of milk production and in extreme cases, death. Manufactured by Alcide Corporation the Alcide compound has killed all tested bacteria, virus and fungi, shortly after contact, with minimal toxic effects on humans or animals. Alcide Corporation credits the existence of the mastitis treatment/prevention products to assistance provided the company by NERAC, Inc.

Cognitive-Enhancing Effect of Dianthus superbus var. Longicalycinus on Scopolamine-Induced Memory Impairment in Mice.

Science.gov (United States)

Weon, Jin Bae; Jung, Youn Sik; Ma, Choong Je

2016-05-01

Dianthus superbus (D. superbus) is a traditional crude drug used for the treatment of urethritis, carbuncles and carcinomas. The objective of this study was to confirm the cognitive enhancing effect of D. superbus in memory impairment induced mice and to elucidate the possible potential mechanism. Effect of D. superbus on scopolamine induced memory impairment on mice was evaluated using the Morris water maze and passive avoidance tests. We also investigated acetylcholinesterase (AChE) activity and brain-derived neurotropic factor (BDNF) expression in scopolamine-induced mice. HPLC-DAD analysis was performed to identify active compounds in D. superbus. The results revealed that D. superbus attenuated the learning and memory impairment induced by scopolamine. D. superbus also inhibited AChE levels in the hippocampi of the scopolamine-injected mice. Moreover, D. superbus increased BDNF expression in the hippocampus. Eight compounds were identified using HPLC-DAD analysis. The content of 4-hydroxyphenyl acetic acid was higher than contents of other compounds. These results indicated that D. superbus improved memory functioning accompanied by inhibition of AChE and upregulation of BDNF, suggesting that D. superbus may be a useful therapeutic agent for the prevention or treatment of Alzheimer's disease.

Polygalasaponin XXXII, a triterpenoid saponin from Polygalae Radix, attenuates scopolamine-induced cognitive impairments in mice.

Science.gov (United States)

Zhou, Heng; Xue, Wei; Chu, Shi-Feng; Wang, Zhen-Zhen; Li, Chuang-Jun; Jiang, Yi-Na; Luo, Lin-Ming; Luo, Piao; Li, Gang; Zhang, Dong-Ming; Chen, Nai-Hong

2016-08-01

Recent studies show that the extract of a Chinese herb Polygalae Radix exerts cognition-enhancing actions in rats and humans. The aim of this study was to characterize the pharmacological profiles of active compounds extracted from Polygalae Radix. Two fractions P3 and P6 and two compounds PTM-15 and polygalasaponin XXXII (PGS32) were prepared. Neuroprotective effects were evaluated in primary cortical neurons exposed to high concentration glutamate, serum deficiency or H2O2. Anti-dementia actions were assessed in scopolamine-induced amnesia in mice using step-through avoidance tests and channel water maze tests. After conducting the channel water maze tests, TrkB phosphorylation in mouse hippocampus was detected using Western blotting. Long-term potentiation (LTP) was induced in the dentate gyrus in adult rats; PGS32 (5 μL 400 μmol/L) was injected into the lateral cerebral ventricle 20 min after high frequency stimulation (HFS). Compared to the fraction P6, the fraction P3 showed more prominent neuroprotective effects in vitro and cognition-enhancing effects in scopolamine-induced amnesia in mice. One active compound PGS32 in the fraction P3 exerted potent cognition-enhancing action: oral administration of PGS32 (0.125 mg·kg(-1)·d(-1)) for 19 days abolished scopolamine-induced memory impairment in mice. Furthermore, PGS32 (0.5 and 2 mg·kg(-1)·d(-1)) significantly stimulated the phosphorylation of TrkB in the hippocampus. Intracerebroventricular injection of PGS32 significantly enhanced HFS-induced LTP in the dentate gyrus of rats. PGS32 attenuates scopolamine-induced cognitive impairments in mice, suggesting that it has a potential for the treatment of cognitive dysfunction and dementia.

Decision making under explicit risk is impaired in individuals with human immunodeficiency virus (HIV).

Science.gov (United States)

Fujiwara, Esther; Tomlinson, Sara E; Purdon, Scot E; Gill, M John; Power, Christopher

2015-01-01

Human immunodeficiency virus (HIV) can affect the frontal-striatal brain regions, which are known to subserve decision-making functions. Previous studies have reported impaired decision making among HIV+ individuals using the Iowa Gambling Task, a task that assesses decision making under ambiguity. Previous study populations often had significant comorbidities such as past or present substance use disorders and/or hepatitis C virus coinfection, complicating conclusions about the unique contributions of HIV-infection to decision making. Decision making under explicit risk has very rarely been examined in HIV+ individuals and was tested here using the Game of Dice Task (GDT). We examined decision making under explicit risk in the GDT in 20 HIV+ individuals without substance use disorder or HCV coinfection, including a demographically matched healthy control group (n = 20). Groups were characterized on a standard neuropsychological test battery. For the HIV+ group, several disease-related parameters (viral load, current and nadir CD4 T-cell count) were included. Analyses focused on the GDT and spanned between-group (t-tests; analysis of covariance, ANCOVA) as well as within-group comparisons (Pearson/Spearman correlations). HIV+ individuals were impaired in the GDT, compared to healthy controls (p = .02). Their decision-making impairments were characterized by less advantageous choices and more random choice strategies, especially towards the end of the task. Deficits in the GDT in the HIV+ group were related to executive dysfunctions, slowed processing/motor speed, and current immune system status (CD4+ T-cell levels, ps Decision making under explicit risk in the GDT can occur in HIV-infected individuals without comorbidities. The correlational patterns may point to underlying fronto-subcortical dysfunctions in HIV+ individuals. The GDT provides a useful measure to assess risky decision making in this population and should be tested in larger studies.

Oxidative stress and mitochondrial impairment can be separated from lipofuscin accumulation in aged human skeletal muscle

DEFF Research Database (Denmark)

Hütter, Eveline; Skovbro, Mette; Lener, Barbara

2007-01-01

According to the free radical theory of aging, reactive oxygen species (ROS) act as a driving force of the aging process, and it is generally believed that mitochondrial dysfunction is a major source of increased oxidative stress in tissues with high content of mitochondria, such as muscle or brain....... However, recent experiments in mouse models of premature aging have questioned the role of mitochondrial ROS production in premature aging. To address the role of mitochondrial impairment and ROS production for aging in human muscles, we have analyzed mitochondrial properties in muscle fibres isolated...... from the vastus lateralis of young and elderly donors. Mitochondrial respiratory functions were addressed by high-resolution respirometry, and ROS production was analyzed by in situ staining with the redox-sensitive dye dihydroethidium. We found that aged human skeletal muscles contain fully functional...

Transformations of Phenolic Compounds in an in vitro Model Simulating the Human Alimentary Tract

Directory of Open Access Journals (Sweden)

Aleksandra Duda-Chodak

2009-01-01

Full Text Available The aim of this work is to establish the antioxidant properties of polyphenolic compounds of selected fruits before and after their transformations during digestion. The experiment was conducted in in vitro conditions on a set of dialysis membranes which simulated the human digestive tract. Apples of the Šampion, Malinowka and Golden Delicious cultivars, black chokeberry, banana, Wegierka zwykla blue plum, melon and Lukasowka pear were chosen for examination. It was found that compounds obtained after simulated digestion of chokeberries, pears and bananas showed lower antioxidant potential than fresh fruits, while the opposite results were obtained for apples and plums. All dialysates obtained after digestion were characterized by lower content of total polyphenols in comparison with raw material (fresh fruits. It was found that the polyphenols were hydrolyzed, especially glycosides of quercetin and cyanidin. Phenolic acids and cyanidin were characterized by low availability for absorption, whereas catechin and quercetin had a very high level of accessibility in the model small intestine.

Screening of Compounds Toxicity against Human Monocytic cell line-THP-1 by Flow Cytometry

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Pick Neora

2004-01-01

Full Text Available The worldwide rapid increase in bacterial resistance to numerous antibiotics requires on-going development of new drugs to enter the market. As the development of new antibiotics is lengthy and costly, early monitoring of compound's toxicity is essential in the development of novel agents. Our interest is in a rapid, simple, high throughput screening method to assess cytotoxicity induced by potential agents. Some intracellular pathogens, such as Mycobacterium tuberculosis primary site of infection is human alveolar macrophages. Thus, evaluation of candidate drugs for macrophage toxicity is crucial. Protocols for high throughput drug toxicity screening of macrophages using flow cytometry are lacking in the literature. For this application we modified a preexisting technique, propidium iodide (PI exclusion staining and utilized it for rapid toxicity tests. Samples were prepared in 96 well plates and analyzed by flow cytometry, which allowed for rapid, inexpensive and precise assessment of compound's toxicity associated with cell death.

Brain inflammation accompanies amyloid in the majority of mild cognitive impairment cases due to Alzheimer's disease.

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Parbo, Peter; Ismail, Rola; Hansen, Kim V; Amidi, Ali; Mårup, Frederik H; Gottrup, Hanne; Brændgaard, Hans; Eriksson, Bengt O; Eskildsen, Simon F; Lund, Torben E; Tietze, Anna; Edison, Paul; Pavese, Nicola; Stokholm, Morten G; Borghammer, Per; Hinz, Rainer; Aanerud, Joel; Brooks, David J

2017-07-01

See Kreisl (doi:10.1093/awx151) for a scientific commentary on this article.Subjects with mild cognitive impairment associated with cortical amyloid-β have a greatly increased risk of progressing to Alzheimer's disease. We hypothesized that neuroinflammation occurs early in Alzheimer's disease and would be present in most amyloid-positive mild cognitive impairment cases. 11C-Pittsburgh compound B and 11C-(R)-PK11195 positron emission tomography was used to determine the amyloid load and detect the extent of neuroinflammation (microglial activation) in 42 mild cognitive impairment cases. Twelve age-matched healthy control subjects had 11C-Pittsburgh compound B and 10 healthy control subjects had 11C-(R)-PK11195 positron emission tomography for comparison. Amyloid-positivity was defined as 11C-Pittsburgh compound B target-to-cerebellar ratio above 1.5 within a composite cortical volume of interest. Supervised cluster analysis was used to generate parametric maps of 11C-(R)-PK11195 binding potential. Levels of 11C-(R)-PK11195 binding potential were measured in a selection of cortical volumes of interest and at a voxel level. Twenty-six (62%) of 42 mild cognitive impairment cases showed a raised cortical amyloid load compared to healthy controls. Twenty-two (85%) of the 26 amyloid-positive mild cognitive impairment cases showed clusters of increased cortical microglial activation accompanying the amyloid. There was a positive correlation between levels of amyloid load and 11C-(R)-PK11195 binding potentials at a voxel level within subregions of frontal, parietal and temporal cortices. 11C-(R)-PK11195 positron emission tomography reveals increased inflammation in a majority of amyloid positive mild cognitive impairment cases, its cortical distribution overlapping that of amyloid deposition. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Developmental impairment of compound action potential in the optic nerve of myelin mutant taiep rats.

Science.gov (United States)

Roncagliolo, Manuel; Schlageter, Carol; León, Claudia; Couve, Eduardo; Bonansco, Christian; Eguibar, José R

2006-01-05

The taiep rat is a myelin mutant with an initial hypomyelination, followed by a progressive demyelination of the CNS. The neurological correlates start with tremor, followed by ataxia, immobility episodes, epilepsy and paralysis. The optic nerve, an easily-isolable central tract fully myelinated by oligodendrocytes, is a suitable preparation to evaluate the developmental impairment of central myelin. We examined the ontogenic development of optic nerve compound action potentials (CAP) throughout the first 6 months of life of control and taiep rats. Control optic nerves (ON) develop CAPs characterized by three waves. Along the first month, the CAPs of taiep rats showed a delayed maturation, with lower amplitudes and longer latencies than controls; at P30, the conduction velocity has only a third of the normal value. Later, as demyelination proceeds, the conduction velocity of taiep ONs begins to decrease and CAPs undergo a gradual temporal dispersion. CAPs of control and taiep showed differences in their pharmacological sensitivity to TEA and 4-AP, two voltage dependent K+ channel-blockers. As compared with TEA, 4-AP induced a significant increase of the amplitudes and a remarkable broadening of CAPs. After P20, unlike controls, the greater sensitivity to 4-AP exhibited by taiep ONs correlates with the detachment and retraction of paranodal loops suggesting that potassium conductances could regulate the excitability as demyelination of CNS axons progresses. It is concluded that the taiep rat, a long-lived mutant, provides a useful model to study the consequences of partial demyelination and the mechanisms by which glial cells regulate the molecular organization and excitability of axonal membranes during development and disease.

Identification and quantification of major maillard cross-links in human serum albumin and lens protein. Evidence for glucosepane as the dominant compound.

Science.gov (United States)

Biemel, Klaus M; Friedl, D Alexander; Lederer, Markus O

2002-07-12

Glycation reactions leading to protein modifications (advanced glycation end products) contribute to various pathologies associated with the general aging process and long term complications of diabetes. However, only few relevant compounds have so far been detected in vivo. We now report on the first unequivocal identification of the lysine-arginine cross-links glucosepane 5, DOGDIC 6, MODIC 7, and GODIC 8 in human material. For their accurate quantification by coupled liquid chromatography-electrospray ionization mass spectrometry, (13)C-labeled reference compounds were synthesized independently. Compounds 5-8 are formed via the alpha-dicarbonyl compounds N(6)-(2,3-dihydroxy-5,6-dioxohexyl)-l-lysinate (1a,b), 3-deoxyglucosone (), methylglyoxal (), and glyoxal (), respectively. The protein-bound dideoxyosone 1a,b seems to be of prime significance for cross-linking because it presumably is not detoxified by mammalian enzymes as readily as 2-4. Hence, the follow-up product glucosepane 5 was found to be the dominant compound. Up to 42.3 pmol of 5/mg of protein was identified in human serum albumin of diabetics; the level of 5 correlates markedly with the glycated hemoglobin HbA(1c). In the water-insoluble fraction of lens proteins from normoglycemics, concentration of 5 ranges between 132.3 and 241.7 pmol/mg. The advanced glycoxidation end product GODIC 8 is elevated significantly in brunescent lenses, indicating enhanced oxidative stress in this material. Compounds 5-8 thus appear predestined as markers for pathophysiological processes.

Synaptic contacts impaired by styrene-7,8-oxide toxicity

International Nuclear Information System (INIS)

Corsi, P.; D'Aprile, A.; Nico, B.; Costa, G.L.; Assennato, G.

2007-01-01

Styrene-7,8-oxide (SO), a chemical compound widely used in industrial applications, is a potential hazard for humans, particularly in occupational settings. Neurobehavioral changes are consistently observed in occupationally exposed individuals and alterations of neurotransmitters associated with neuronal loss have been reported in animal models. Although the toxic effects of styrene have been extensively documented, the molecular mechanisms responsible for SO-induced neurotoxicity are still unclear. A possible dopamine-mediated effect of styrene neurotoxicity has been previously demonstrated, since styrene oxide alters dopamine neurotransmission in the brain. Thus, the present study hypothesizes that styrene neurotoxicity may involve synaptic contacts. Primary striatal neurons were exposed to styrene oxide at different concentrations (0.1-1 mM) for different time periods (8, 16, and 24 h) to evaluate the dose able to induce synaptic impairments. The expression of proteins crucial for synaptic transmission such as Synapsin, Synaptophysin, and RAC-1 were considered. The levels of Synaptophysin and RAC-1 decreased in a dose-dependent manner. Accordingly, morphological alterations, observed at the ultrastructural level, primarily involved the pre-synaptic compartment. In SO-exposed cultures, the biochemical cascade of caspases was activated affecting the cytoskeleton components as their target. Thus the impairments in synaptic contacts observed in SO-exposed cultures might reflect a primarily morphological alteration of neuronal cytoskeleton. In addition, our data support the hypothesis developed by previous authors of reactive oxygen species (ROS) initiating events of SO cytotoxicity

Bace1 activity impairs neuronal glucose metabolism: rescue by beta-hydroxybutyrate and lipoic acid

Directory of Open Access Journals (Sweden)

John A Findlay

2015-10-01

Full Text Available Glucose hypometabolism and impaired mitochondrial function in neurons have been suggested to play early and perhaps causative roles in Alzheimer’s disease (AD pathogenesis. Activity of the aspartic acid protease, beta-site amyloid precursor protein (APP cleaving enzyme 1 (BACE1, responsible for beta amyloid peptide generation, has recently been demonstrated to modify glucose metabolism. We therefore examined, using a human neuroblastoma (SH-SY5Y cell line, whether increased BACE1 activity is responsible for a reduction in cellular glucose metabolism. Overexpression of active BACE1, but not a protease-dead mutant BACE1, protein in SH-SY5Y cells reduced glucose oxidation and the basal oxygen consumption rate, which was associated with a compensatory increase in glycolysis. Increased BACE1 activity had no effect on the mitochondrial electron transfer process but was found to diminish substrate delivery to the mitochondria by inhibition of key mitochondrial decarboxylation reaction enzymes. This BACE1 activity-dependent deficit in glucose oxidation was alleviated by the presence of beta hydroxybutyrate or α-lipoic acid. Consequently our data indicate that raised cellular BACE1 activity drives reduced glucose oxidation in a human neuronal cell line through impairments in the activity of specific tricarboxylic acid cycle enzymes. Because this bioenergetic deficit is recoverable by neutraceutical compounds we suggest that such agents, perhaps in conjunction with BACE1 inhibitors, may be an effective therapeutic strategy in the early-stage management or treatment of AD.

Two new acetylenic compounds from Asparagus officinalis.

Science.gov (United States)

Li, Xue-Mei; Cai, Jin-Long; Wang, Wen-Xiang; Ai, Hong-Lian; Mao, Zi-Chao

2016-01-01

Two new acetylenic compounds, asparoffins A (1) and B (2), together with two known compounds, nyasol (3) and 3″-methoxynyasol (4), were isolated from stems of Asparagus officinalis. The structures of two new compounds were elucidated on the basis of detailed spectroscopic analyses (UV, IR, MS, 1D, and 2D NMR). All compounds were evaluated for their cytotoxicities against three human cancer cell lines.

Mobile phone use for 5 minutes can cause significant memory impairment in humans.

Science.gov (United States)

Kalafatakis, F; Bekiaridis-Moschou, D; Gkioka, Eirini; Tsolaki, Magda

2017-01-01

Concerns about the possible adverse health effects of mobile phones (MP) have increased along with the expansion of their use. A number of research papers have tried to address this issue. Although many investigations concluded that MP use does have negative consequences, in terms of cognitive function of the human brain, the results so far have been divisive. A number of studies reported impairment of cognitive function after exposure to mobile phone electromagnetic field (MP EMF), while others observed no effect or improved performance. The variance in the results may be attributed to methodological issues. The present article focuses on possible effects of MP use on cognitive function and more specifically on working memory processes. An emphasis is placed in the lack of a validated tool, a cognitive task, that can produce MP EMF effects on human cognition in a repeatable fashion. Sixty four (64) healthy participants as well as 20 with Mild Cognitive Impairment (MCI) were the experimental group, while 36 healthy individuals were the control group. A computerized list of 10 words was presented and the participants were asked to reproduce it. The words were presented very briefly in order to increase the difficulty and hence the sensitivity of the task. Three measurements were taken for the experimental group: a) before using the MP, b) immediately after using the MP for a duration of 5 minutes, c) 5 minutes after the second measurement with no usage of the MP in between. Three measurements of the memory task were also taken for the control group in the same time intervals with no usage of a MP. The effect of age and gender in the performance of the task was taken into account. Healthy participants of the experimental group performed worst in the memory task after using the MP. While the third measurement (5 minutes after the 2nd measurement) was better than the second (after using the MP), but worse than the first (before using the MP). In contrast for the

Interaction of Human Enteric Viruses with Microbial Compounds: Implication for Virus Persistence and Disinfection Treatments.

Science.gov (United States)

Waldman, Prunelle; Meseguer, Alba; Lucas, Françoise; Moulin, Laurent; Wurtzer, Sébastien

2017-12-05

Although the interaction between phages and bacteria has already been well described, it only recently emerged that human viruses also interact with bacteria in the mammalian gut. We studied whether this interaction could occur in tap water and thus confer enteric viruses protection against temperature and the classical disinfection treatments used in drinking water production. We demonstrated that the addition of lipopolysaccharide or peptidoglycan of bacterial origin to enterovirus provides thermal protection through stabilization of the viral capsid. This interaction plays a role when viruses are exposed to disinfection that targets the capsid, but less so when the virus genome is directly targeted. The interaction seems to be serotype-specific, suggesting that the capsid protein sequence could be important. The protection is linked to a direct association between viral particles and bacterial compounds as observed by microscopy. These results show that bacterial compounds present in the environment can affect virus inactivation.

Antibacterial Compounds from Red Seaweeds (Rhodophyta)

OpenAIRE

Noer Kasanah; Triyanto Triyanto; Drajad Sarwo Seto; Windi Amelia; Alim Isnansetyo

2015-01-01

Seaweeds produce great variety of metabolites benefit for human. Red seaweeds (Rhodophyta) are well known as producer of phycocolloids such agar, agarose, carragenan and great variety of secondary metabolites. This review discusses the red algal secondary metabolites with antibacterial activity. The chemical constituents of red algae are steroid, terpenoid, acetogenin and dominated by halogenated compounds mainly brominated compounds. Novel compounds with intriguing skeleton are also reported...

Thrombin impairs human endometrial endothelial angiogenesis; implications for progestin-only contraceptive-induced abnormal uterine bleeding.

Science.gov (United States)

Shapiro, John P; Guzeloglu-Kayisli, Ozlem; Kayisli, Umit A; Semerci, Nihan; Huang, S Joseph; Arlier, Sefa; Larsen, Kellie; Fadda, Paolo; Schatz, Frederick; Lockwood, Charles J

2017-06-01

Progestin-only contraceptives induce abnormal uterine bleeding, accompanied by prothrombin leakage from dilated endometrial microvessels and increased thrombin generation by human endometrial stromal cell (HESC)-expressed tissue factor. Initial studies of the thrombin-treated HESC secretome identified elevated levels of cleaved chondroitin sulfate proteoglycan 4 (CSPG4), impairing pericyte-endothelial interactions. Thus, we investigated direct and CSPG4-mediated effects of thrombin in eliciting abnormal uterine bleeding by disrupting endometrial angiogenesis. Liquid chromatography/tandem mass spectrometry, enzyme-linked immunosorbent assay (ELISA) and quantitative real-time-polymerase chain reaction (PCR) evaluated conditioned medium supernatant and cell lysates from control versus thrombin-treated HESCs. Pre- and post-Depo medroxyprogesterone acetate (DMPA)-administered endometria were immunostained for CSPG4. Proliferation, apoptosis and tube formation were assessed in human endometrial endothelial cells (HEECs) incubated with recombinant human (rh)-CSPG4 or thrombin or both. Thrombin induced CSPG4 protein expression in cultured HESCs as detected by mass spectrometry and ELISA (pabnormal uterine bleeding in DMPA users. Mass spectrometry analysis identified several HESC-secreted proteins regulated by thrombin. Therapeutic agents blocking angiogenic effects of thrombin in HESCs can prevent or minimize progestin-only contraceptive-induced abnormal uterine bleeding. Copyright © 2017. Published by Elsevier Inc.

The seleno-organic compound ebselen impairs mitochondrial physiology and induces cell death in AR42J cells.

Science.gov (United States)

Santofimia-Castaño, Patricia; Garcia-Sanchez, Lourdes; Ruy, Deborah Clea; Fernandez-Bermejo, Miguel; Salido, Gines M; Gonzalez, Antonio

2014-09-17

Ebselen is a seleno-organic compound that causes cell death in several cancer cell types. The mechanisms underlying its deleterious effects have not been fully elucidated. In this study, the effects of ebselen (1 μM-40 μM) on AR42J tumor cells have been examined. Cell viability was studied using AlamarBlue(®) test. Cell cycle phase determination was carried out by flow cytometry. Changes in intracellular free Ca(2+) concentration were followed by fluorimetry analysis of fura-2-loaded cells. Distribution of mitochondria, mitochondrial Ca(2+) concentration and mitochondrial membrane potential were monitored by confocal microscopy of cells loaded with Mitotracker Green™ FM, rhod-2 or TMRM respectively. Caspase-3 activity was calculated following the luorogenic substrate ACDEVD-AMC signal with a spectrofluorimeter. Results show that cell viability decreased in the presence of ebselen. An increase in the number of cells in the S-phase of the cell cycle was observed. Ebselen induced a concentration-dependent mobilization of Ca(2+) from agonist- and thapsigargin-sensitive Ca(2+) pools. Ebselen induced also a transient increase in mitochondrial Ca(2+) concentration, a progressive decrease of the mitochondrial membrane potential and a disruption of the mitochondrial network. Finally, a concentration-dependent increase in caspase-3 activity was detected. We conclude that ebselen exerts deleterious actions on the cells that involve the impairment of mitochondrial physiology and the activation of caspase-3-mediated apoptotic pathway. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Toxicology of perfluorinated compounds

Energy Technology Data Exchange (ETDEWEB)

Stahl, Thorsten [Hessian State Laboratory, Wiesbaden (Germany); Mattern, Daniela; Brunn, Hubertus [Hessian State Laboratory, Giessen (Germany)

2011-12-15

Perfluorinated compounds [PFCs] have found a wide use in industrial products and processes and in a vast array of consumer products. PFCs are molecules made up of carbon chains to which fluorine atoms are bound. Due to the strength of the carbon/fluorine bond, the molecules are chemically very stable and are highly resistant to biological degradation; therefore, they belong to a class of compounds that tend to persist in the environment. These compounds can bioaccumulate and also undergo biomagnification. Within the class of PFC chemicals, perfluorooctanoic acid and perfluorosulphonic acid are generally considered reference substances. Meanwhile, PFCs can be detected almost ubiquitously, e.g., in water, plants, different kinds of foodstuffs, in animals such as fish, birds, in mammals, as well as in human breast milk and blood. PFCs are proposed as a new class of 'persistent organic pollutants'. Numerous publications allude to the negative effects of PFCs on human health. The following review describes both external and internal exposures to PFCs, the toxicokinetics (uptake, distribution, metabolism, excretion), and the toxicodynamics (acute toxicity, subacute and subchronic toxicities, chronic toxicity including carcinogenesis, genotoxicity and epigenetic effects, reproductive and developmental toxicities, neurotoxicity, effects on the endocrine system, immunotoxicity and potential modes of action, combinational effects, and epidemiological studies on perfluorinated compounds). (orig.)

Effect of tritiated compounds on sister-chromatid exchanges (SCE) in human lymphocytes in vitro

International Nuclear Information System (INIS)

Gong Manli; Rao Yongqing; Chen Guanying; Wu Weiwei; Zhao Zilan; Shen Lei

1990-01-01

Human lymphocytes treated in vitro with various activities of 3 H-TdR and 3 H-UdR were cultured to understand the effects of tritium on the cell cycle and the frequency of SCE. The results of these experiments indicated that both tritiated compounds make the frequency of SCE increase and the cell cycle delay. The frequency of SCE increased markedly with activity of 3 H. With respect to delaying cell cycle, 3 H-UdR was more effective than 3 H-TdR. The average frequencies of SCE for 3 H-UdR were higher than those for 3 H-TdR. With the exception of 3.7 x 10 3 Bq/mL group and differences between other 3 H-UdR groups and corresponding 3 H-TdR group were significant (t test, p < 0.01). These results suggest that tritiated compounds may have the effect on the cell proliferating rate. The cell proliferating rate index (PRI) seems to be related with the frequency of SCE: the higher the frequency of SCE, the lower the PRI is

Psychological Education for Visually Impaired Children.

Science.gov (United States)

Locke, Don C.; Gerler, Edwin R., Jr.

1979-01-01

The study investigated the effects of two psychological education programs (Developing Understanding of Self and Others--DUSO, and Human Development Program--HDP or Magic Circle) on the affective growth of 42 visually impaired children in grades kindergarten through 3. (Author/SBH)

Sensory and Physiological Effects on Humans of Combined Exposures to Air Temperatures and Volatile Organic Compounds

DEFF Research Database (Denmark)

Mølhave, Lars; Liu, Zunyong; Jørgensen, Anne Hempel

1993-01-01

Ten healthy humans were exposed to combinations of volatile organic compounds (VOCs) and air temperature (0 mg/m3 and 10 mg/m3 of a mixture of 22 volatile organic compounds and 18, 22 and 26° C). Previously demonstrated effects of VOCs and thermal exposures were replicated. For the first time nasal...... cross-sectional areas and nasal volumes, as measured by acoustic rhinometry, were shown to decrease with decreasing temperature and increasing VOC exposure. Temperature and pollutant exposures affected air quality, the need for more ventilation, skin humidity on the forehead, sweating, acute sensory...... irritation and possibly watering eyes in an additive way. Interactions were found for odor intensity (p = 0.1), perceived facial skin temperature and dryness, general well-being, tear film stability, and nasal cavity dimension. The presence of interactions implies that in the future guidelines for acceptable...

Progress and Prospects in Human Genetic Research into Age-Related Hearing Impairment

Directory of Open Access Journals (Sweden)

Yasue Uchida

2014-01-01

Full Text Available Age-related hearing impairment (ARHI is a complex, multifactorial disorder that is attributable to confounding intrinsic and extrinsic factors. The degree of impairment shows substantial variation between individuals, as is also observed in the senescence of other functions. This individual variation would seem to refute the stereotypical view that hearing deterioration with age is inevitable and may indicate that there is ample scope for preventive intervention. Genetic predisposition could account for a sizable proportion of interindividual variation. Over the past decade or so, tremendous progress has been made through research into the genetics of various forms of hearing impairment, including ARHI and our knowledge of the complex mechanisms of auditory function has increased substantially. Here, we give an overview of recent investigations aimed at identifying the genetic risk factors involved in ARHI and of what we currently know about its pathophysiology. This review is divided into the following sections: (i genes causing monogenic hearing impairment with phenotypic similarities to ARHI; (ii genes involved in oxidative stress, biologic stress responses, and mitochondrial dysfunction; and (iii candidate genes for senescence, other geriatric diseases, and neurodegeneration. Progress and prospects in genetic research are discussed.

Sleep Deprivation Impairs the Human Central and Peripheral Nervous System Discrimination of Social Threat.

Science.gov (United States)

Goldstein-Piekarski, Andrea N; Greer, Stephanie M; Saletin, Jared M; Walker, Matthew P

2015-07-15

Facial expressions represent one of the most salient cues in our environment. They communicate the affective state and intent of an individual and, if interpreted correctly, adaptively influence the behavior of others in return. Processing of such affective stimuli is known to require reciprocal signaling between central viscerosensory brain regions and peripheral-autonomic body systems, culminating in accurate emotion discrimination. Despite emerging links between sleep and affective regulation, the impact of sleep loss on the discrimination of complex social emotions within and between the CNS and PNS remains unknown. Here, we demonstrate in humans that sleep deprivation impairs both viscerosensory brain (anterior insula, anterior cingulate cortex, amygdala) and autonomic-cardiac discrimination of threatening from affiliative facial cues. Moreover, sleep deprivation significantly degrades the normally reciprocal associations between these central and peripheral emotion-signaling systems, most prominent at the level of cardiac-amygdala coupling. In addition, REM sleep physiology across the sleep-rested night significantly predicts the next-day success of emotional discrimination within this viscerosensory network across individuals, suggesting a role for REM sleep in affective brain recalibration. Together, these findings establish that sleep deprivation compromises the faithful signaling of, and the "embodied" reciprocity between, viscerosensory brain and peripheral autonomic body processing of complex social signals. Such impairments hold ecological relevance in professional contexts in which the need for accurate interpretation of social cues is paramount yet insufficient sleep is pervasive. Copyright © 2015 the authors 0270-6474/15/3510135-11$15.00/0.

Distributions of polyhalogenated compounds in Hudson River (New York, USA) fish in relation to human uses along the river

International Nuclear Information System (INIS)

Skinner, Lawrence C.

2011-01-01

PCBs (as Aroclor concentrations) have been extensively examined in fish along the Hudson River, but other xenobiotic chemicals in fish have had limited assessment. This study determined concentrations and congener distributions of polybrominated diphenyl ethers (PBDEs), polybrominated and polychlorinated dibenzo-p-dioxins and dibenzofurans (PBDD/Fs and PCDD/Fs), and polychlorinated biphenyls (PCBs) in smallmouth bass and striped bass taken from a 385 km reach of the Hudson River. Concentrations of PBDEs and PCBs in smallmouth bass, and PCBs in striped bass, were positively related to human uses of the compounds in the basin. Generally low levels of PCDD/Fs were found. One striped bass, however, contained elevated 2,3,7,8-TCDD, indicating exposure to a known source in the adjacent Newark Bay-Passaic River basin. PBDDs were generally below detection. PBDFs were present in four of 18 smallmouth bass, but were not detected in striped bass. Dioxin-like PCBs contribute most to 2,3,7,8-TCDD toxic equivalents in 29 of 30 samples. - Highlights: → In the Hudson River, → PBDEs in smallmouth bass follow human population patterns, but do not for striped bass. → Proximity to known PCB sources govern PCB levels and patterns in fish. → PBDFs were in smallmouth bass but not striped bass. PBDDs were present in one fish. → PCDD/Fs were low in 29 of 30 fish. A 2,3,7,8-TCDD source affected one striped bass. → PCBs contribute most to 2,3,7,8-TCDD toxic equivalents in 29 of 30 samples. - Residues of polyhalogenated compounds in resident and migratory fish from the Hudson River are compared with human uses of the compounds in the river basin.

Distributions of polyhalogenated compounds in Hudson River (New York, USA) fish in relation to human uses along the river

Energy Technology Data Exchange (ETDEWEB)

Skinner, Lawrence C., E-mail: lxskinne@gw.dec.state.ny.us [New York State Department of Environmental Conservation, 625 Broadway, Albany, NY 12233 (United States)

2011-10-15

PCBs (as Aroclor concentrations) have been extensively examined in fish along the Hudson River, but other xenobiotic chemicals in fish have had limited assessment. This study determined concentrations and congener distributions of polybrominated diphenyl ethers (PBDEs), polybrominated and polychlorinated dibenzo-p-dioxins and dibenzofurans (PBDD/Fs and PCDD/Fs), and polychlorinated biphenyls (PCBs) in smallmouth bass and striped bass taken from a 385 km reach of the Hudson River. Concentrations of PBDEs and PCBs in smallmouth bass, and PCBs in striped bass, were positively related to human uses of the compounds in the basin. Generally low levels of PCDD/Fs were found. One striped bass, however, contained elevated 2,3,7,8-TCDD, indicating exposure to a known source in the adjacent Newark Bay-Passaic River basin. PBDDs were generally below detection. PBDFs were present in four of 18 smallmouth bass, but were not detected in striped bass. Dioxin-like PCBs contribute most to 2,3,7,8-TCDD toxic equivalents in 29 of 30 samples. - Highlights: > In the Hudson River, > PBDEs in smallmouth bass follow human population patterns, but do not for striped bass. > Proximity to known PCB sources govern PCB levels and patterns in fish. > PBDFs were in smallmouth bass but not striped bass. PBDDs were present in one fish. > PCDD/Fs were low in 29 of 30 fish. A 2,3,7,8-TCDD source affected one striped bass. > PCBs contribute most to 2,3,7,8-TCDD toxic equivalents in 29 of 30 samples. - Residues of polyhalogenated compounds in resident and migratory fish from the Hudson River are compared with human uses of the compounds in the river basin.

The action of sennosides and related compounds on human colon and rectum 1

Science.gov (United States)

Hardcastle, J. D.; Wilkins, J. L.

1970-01-01

The direct action of intraluminal senna and related compounds on the human colon and rectum has been investigated. Motility was recorded by balloon kymography with recording units inserted into well established transverse colostomies or into the rectum. The motility of the colon was not changed by intraluminal senna glycosides but the introduction of senna previously incubated with faeces or Esch. coli stimulated the colon to peristalt. The peristalsis was similar to that stimulated by rheinanthrone, an oxanthrone produced by chemical hydrolysis and reduction of senna. Both activated senna and rheinanthrone appeared to act in the colon by contact stimulation. No peristaltic response was stimulated in the rectum, either with activated senna or with rheinanthrone. PMID:4929273

Perfluorinated Compounds: Emerging POPs with Potential Immunotoxicity

Science.gov (United States)

Perfluorinated compounds (PFCs) have been recognized as an important class of environmental contaminants commonly detected in blood samples of both wildlife and humans. These compounds have been in use for more than 60 years as surface treatment chemicals, polymerization aids, an...

Speciation analysis of organotin compounds in human urine by headspace solid-phase micro-extraction and gas chromatography with pulsed flame photometric detection.

Science.gov (United States)

Valenzuela, Aníbal; Lespes, Gaëtane; Quiroz, Waldo; Aguilar, Luis F; Bravo, Manuel A

2014-07-01

A new headspace solid-phase micro-extraction (HS-SPME) method followed by gas chromatography with pulsed flame photometric detection (GC-PFPD) analysis has been developed for the simultaneous determination of 11 organotin compounds, including methyl-, butyl-, phenyl- and octyltin derivates, in human urine. The methodology has been validated by the analysis of urine samples fortified with all analytes at different concentration levels, and recovery rates above 87% and relative precisions between 2% and 7% were obtained. Additionally, an experimental-design approach has been used to model the storage stability of organotin compounds in human urine, demonstrating that organotins are highly degraded in this medium, although their stability is satisfactory during the first 4 days of storage at 4 °C and pH=4. Finally, this methodology was applied to urine samples collected from harbor workers exposed to antifouling paints; methyl- and butyltins were detected, confirming human exposure in this type of work environment. Copyright © 2014 Elsevier B.V. All rights reserved.

IRIS Toxicological Review of Thallium and Compounds ...

Science.gov (United States)

Thallium compounds are used in the semiconductor industry, the manufacture of optic lenses and low-melting glass, low-temperature thermometers, alloys, electronic devices, mercury lamps, fireworks, and imitation germs, and clinically as an imaging agent in the diagnosis of certain tumors. EPA's assessment of noncancer health effects and carcinogenic potential of thallium compounds was last prepared and added to the IRIS database between 1988 and 1990. The IRIS program is preparing an assessment that will incorporate current health effects information available for thallium and compounds, and current risk assessment methods. The IRIS assessment for thallium compounds will consist of a Toxicological Review and IRIS Summary. The Toxicological Review is a critical review of the physiochemical and toxicokinetic properties of a chemical, and its toxicity in humans and experimental systems. The assessment will present reference values for the noncancer effects of thallium compounds (RfD and Rfc), and a cancer assessment. The Toxicological Review and IRIS Summary have been subject to Agency review, Interagency review, and external scientific peer review. The final product will reflect the Agency opinion on the overall toxicity of thallium and compounds. EPA is undertaking an Integrated Risk Information System (IRIS) health assessment for thallium and compounds. IRIS is an EPA database containing Agency scientific positions on potential adverse human health effec

Apoptosis induction in human lymphocytes after in vitro exposure to cobalt/hard metal compounds

International Nuclear Information System (INIS)

Boeck, M. de; Decordier, I.; Lombaert, N.; Cundari, E.; Kirsch-Volders, M.; Lison, D.

2001-01-01

Full text: An increased risk of lung cancer is associated with occupational exposure to mixtures of cobalt metal (Co) and tungsten carbide (WC) particles, but apparently not when exposure is to cobalt alone. The mechanism for this increased cancer risk is not fully understood. The evaluation of the in vitro genotoxic effects in lymphocytes exposed to varying cobalt species demonstrated that the WC-Co hard metal mixture is more genotoxic (DNA damage, chromosome/genome mutations) than metallic Co alone. WC alone was not genotoxic. Thus, WC-Co represents a specific (geno)toxic entity. In order to assess the survival of human lymphocytes after in vitro exposure to metallic Co, CoCl 2 , WC and the WC-Co mixture, two apoptosis/necrosis detection methods were applied (annexin V staining and flow cytometry). Annexin-V staining of early apoptotic cells demonstrated a dose- and time dependent induction of apoptosis by metallic Co, CoCl 2 , WC and the WC-Co mixture. The time course of the process varied according to the metal species tested. Metallic Co and CoCl 2 caused a gradually increasing frequency of apoptotic cells with time (up to 24 h). WC-induced apoptosis displayed a typical 6 hour peak, which was not the case for the WC-Co mixture or for Co. Apoptosis induction by the WC-Co mixture was intermediate between that induced by Co and WC separately. Analysis of propidium iodide stained cells by flow cytometry was performed as a later marker for apoptosis induction. Preliminary data indicate similar tendencies of apoptosis induction as those detected by annexin-V. Identification of the apoptotic pathway triggered by the metal compounds was studied by inhibition of the ceramide-apoptosis pathway by fumonisin causing reduction of apoptosis induction for all compounds, but strongest after 6 hour exposure to WC. The use of specific caspase inhibitors will allow to further elucidate the different pathways involved. The current data demonstrating in vitro the apoptosis

Apoptosis induction in human lymphocytes after in vitro exposure to cobalt/hard metal compounds

Energy Technology Data Exchange (ETDEWEB)

Boeck, M de; Decordier, I; Lombaert, N; Cundari, E; Kirsch-Volders, M [Vrije Universiteit Brussel, Laboratorium voor Cellulaire Genetica, Brussel (Belgium); Lison, D [Universite catholique de Louvain, Unite de Toxicologie industrielle et Medecine du Travail, Bruxelles (Belgium)

2001-07-01

Full text: An increased risk of lung cancer is associated with occupational exposure to mixtures of cobalt metal (Co) and tungsten carbide (WC) particles, but apparently not when exposure is to cobalt alone. The mechanism for this increased cancer risk is not fully understood. The evaluation of the in vitro genotoxic effects in lymphocytes exposed to varying cobalt species demonstrated that the WC-Co hard metal mixture is more genotoxic (DNA damage, chromosome/genome mutations) than metallic Co alone. WC alone was not genotoxic. Thus, WC-Co represents a specific (geno)toxic entity. In order to assess the survival of human lymphocytes after in vitro exposure to metallic Co, CoCl{sub 2}, WC and the WC-Co mixture, two apoptosis/necrosis detection methods were applied (annexin V staining and flow cytometry). Annexin-V staining of early apoptotic cells demonstrated a dose- and time dependent induction of apoptosis by metallic Co, CoCl{sub 2}, WC and the WC-Co mixture. The time course of the process varied according to the metal species tested. Metallic Co and CoCl{sub 2} caused a gradually increasing frequency of apoptotic cells with time (up to 24 h). WC-induced apoptosis displayed a typical 6 hour peak, which was not the case for the WC-Co mixture or for Co. Apoptosis induction by the WC-Co mixture was intermediate between that induced by Co and WC separately. Analysis of propidium iodide stained cells by flow cytometry was performed as a later marker for apoptosis induction. Preliminary data indicate similar tendencies of apoptosis induction as those detected by annexin-V. Identification of the apoptotic pathway triggered by the metal compounds was studied by inhibition of the ceramide-apoptosis pathway by fumonisin causing reduction of apoptosis induction for all compounds, but strongest after 6 hour exposure to WC. The use of specific caspase inhibitors will allow to further elucidate the different pathways involved. The current data demonstrating in vitro the

Developmental dyscalculia is related to visuo-spatial memory and inhibition impairment ☆

OpenAIRE

Szucs, Denes; Devine, Amy; Soltesz, Fruzsina; Nobes, Alison; Gabriel, Florence

2013-01-01

Developmental dyscalculia is thought to be a specific impairment of mathematics ability. Currently dominant cognitive neuroscience theories of developmental dyscalculia suggest that it originates from the impairment of the magnitude representation of the human brain, residing in the intraparietal sulcus, or from impaired connections between number symbols and the magnitude representation. However, behavioral research offers several alternative theories for developmental dyscalculia and neuro-...

Blindness and visual impairment in opera.

Science.gov (United States)

Aydin, Pinar; Ritch, Robert; O'Dwyer, John

2018-01-01

The performing arts mirror the human condition. This study sought to analyze the reasons for inclusion of visually impaired characters in opera, the cause of the blindness or near blindness, and the dramatic purpose of the blindness in the storyline. We reviewed operas from the 18 th century to 2010 and included all characters with ocular problems. We classified the cause of each character's ocular problem (organic, nonorganic, and other) in relation to the thematic setting of the opera: biblical and mythical, blind beggars or blind musicians, historical (real or fictional characters), and contemporary or futuristic. Cases of blindness in 55 characters (2 as a choir) from 38 operas were detected over 3 centuries of repertoire: 11 had trauma-related visual impairment, 5 had congenital blindness, 18 had visual impairment of unknown cause, 9 had psychogenic or malingering blindness, and 12 were symbolic or miracle-related. One opera featured an ophthalmologist curing a patient. The research illustrates that visual impairment was frequently used as an artistic device to enhance the intent and situate an opera in its time.

Juvenile exposure to vinclozolin shifts sex ratios and impairs reproductive capacity of zebrafish.

Science.gov (United States)

Lor, Yer; Revak, Andrew; Weigand, Jenna; Hicks, Elisabeth; Howard, David R; King-Heiden, Tisha C

2015-12-01

Exposure to endocrine disruptors during critical periods of development can impact the sustainability of wild fish populations. Anti-androgenic compounds have received less attention, but are capable of modulating gonad differentiation and maturation, and impairing reproduction in fish. The fungicide vinclozolin (VZ) has been shown to impair reproduction in adult fish, but less is known about its effects following exposure earlier in development. Here we show that waterborne exposure to 400μg VZ/L during critical periods of sex differentiation (21-35 days post fertilization) permanently shifts sex ratios towards females, and alters the maturation of the gonad. Both fecundity and fertility were reduced, even when oogenesis and spermatogenesis recover and sperm motility is not altered. These results demonstrate the need to better understand the impacts of early exposure to anti-androgenic compounds on fish. Copyright © 2015 Elsevier Inc. All rights reserved.

Possible additional exposure to dioxin and dioxin-like compounds from waste incineration. Biomonitoring using human milk and animal samples

Energy Technology Data Exchange (ETDEWEB)

Sampaio, C.; M. Fatima Reis; J. Pereira Miguel [Inst. of Preventive Medicine, Univ. of Lisbon (Portugal); Murk, A. [Wageningen Univ., Dept. of Toxicology (Netherlands)

2004-09-15

In the ambit of an Environmental Health Survey Program relative to a MSW facility, which has been operating near to Lisbon since 1999 a biomonitoring study using human breast milk has been performed. Specific aims of this study were: (1) determine whether living in the vicinity of the incinerator increases dioxin maternal body burden and accordingly perinatal (intra-uterus and lactacional) exposure; (2) to investigate the possibility of increased human exposure to dioxins and dioxin-like compounds via locally produced food items from animal origin. Therefore, levels of dioxins and dioxin-like compounds have been determined in human milk samples collected in the vicinity of the incinerator and in a control area, for comparison. From the same areas, cow and sheep milk and eggs from free-range chickens have also been collected to get an indication of possible local additional exposure to air-borne dioxins via the food chain. Analyses of TCDD-equivalents (TEQs) were mainly performed with a reporter gene assay for dioxin-like activity, the DR-CALUX bioassay (Dioxin Responsive Chemical Activated LUciferase gene eXpression).To determine congeners profile, some human milk samples have also been analysed for PCDD/Fs and relevant dioxin-like PCBs, by using high-resolution gas chromatography and high-resolution mass spectrometry (HRGC/HRMS). Both the Ethics Committees of the Faculty of Medicine, University of Lisbon, and of the Maternity Dr. Alfredo da Costa have approved the study protocol.

Impairment of the transition from proliferative stage to prehypertrophic stage in chondrogenic differentiation of human induced pluripotent stem cells harboring the causative mutation of achondroplasia in fibroblast growth factor receptor 3

Directory of Open Access Journals (Sweden)

Naohiro Horie

2017-06-01

Conclusions: These results suggested that chondrocyte maturation was impaired between the proliferative stage and prehypertrophic stage in the chondrocytes of ACH. The development of chemical compounds which affect the specific maturation stage of chondrocytes is expected to contribute to the ACH treatment, and FGFR3 genome-edited hiPSCs will be a valuable tool in such research studies.

Impaired IFNγ-Signaling and Mycobacterial Clearance in IFNγR1-Deficient Human iPSC-Derived Macrophages

Directory of Open Access Journals (Sweden)

Anna-Lena Neehus

2018-01-01

Full Text Available Mendelian susceptibility to mycobacterial disease (MSMD is caused by inborn errors of interferon gamma (IFNγ immunity and is characterized by severe infections by weakly virulent mycobacteria. Although IFNγ is the macrophage-activating factor, macrophages from these patients have never been studied. We demonstrate the generation of heterozygous and compound heterozygous (iMSMD-cohet induced pluripotent stem cells (iPSCs from a single chimeric patient, who suffered from complete autosomal recessive IFNγR1 deficiency and received bone-marrow transplantation. Loss of IFNγR1 expression had no influence on the macrophage differentiation potential of patient-specific iPSCs. In contrast, lack of IFNγR1 in iMSMD-cohet macrophages abolished IFNγ-dependent phosphorylation of STAT1 and induction of IFNγ-downstream targets such as IRF-1, SOCS-3, and IDO. As a consequence, iMSMD-cohet macrophages show impaired upregulation of HLA-DR and reduced intracellular killing of Bacillus Calmette-Guérin. We provide a disease-modeling platform that might be suited to investigate novel treatment options for MSMD and to gain insights into IFNγ signaling in macrophages.

Thallium toxicity in humans.

Science.gov (United States)

Cvjetko, Petra; Cvjetko, Ivan; Pavlica, Mirjana

2010-03-01

Thallium is a naturally occurring trace element, widely distributed in the earth's crust, but at very low concentrations. It does not have a known biological use and does not appear to be an essential element for life. It has been considered one of the most toxic heavy metals.Occasionally, there are reports on thallium poisoning as results of suicide or murder attempt or accident. The main threat to humans is through occupational exposure, environmental contamination, and accumulation in food, mainly in vegetables grown on contaminated soil. Increasing use in emerging new technologies and demanding high-tech industry constantly raise concern about exposure risk to all living organisms. Thallium is considered a cumulative poison that can cause adverse health effects and degenerative changes in many organs. The effects are the most severe in the nervous system. The exact mechanism of thallium toxicity still remains unknown, although impaired glutathione metabolism, oxidative stress, and disruption of potassium-regulated homeostasis may play a role. The lack of data about mutagenic, carcinogenic, or teratogenic effects of thallium compounds in humans calls for further research.

Isolation and identification of compounds from Kalanchoe pinnata having human alphaherpesvirus and vaccinia virus antiviral activity.

Science.gov (United States)

Cryer, Matthew; Lane, Kyle; Greer, Mary; Cates, Rex; Burt, Scott; Andrus, Merritt; Zou, Jiping; Rogers, Paul; Hansen, Marc D H; Burgado, Jillybeth; Panayampalli, Subbian Satheshkumar; Day, Craig W; Smee, Donald F; Johnson, Brent F

2017-12-01

Kalanchoe pinnata (Lam.) Pers. (Crassulaceae) is a succulent plant that is known for its traditional antivirus and antibacterial usage. This work examines two compounds identified from the K. pinnata plant for their antivirus activity against human alphaherpesvirus (HHV) 1 and 2 and vaccinia virus (VACV). Compounds KPB-100 and KPB-200 were isolated using HPLC and were identified using NMR and MS. Both compounds were tested in plaque reduction assay of HHV-2 wild type (WT) and VACV. Both compounds were then tested in virus spread inhibition and virus yield reduction (VYR) assays of VACV. KPB-100 was further tested in viral cytopathic effect (CPE) inhibition assay of HHV-2 TK-mutant and VYR assay of HHV-1 WT. KPB-100 and KPB-200 inhibited HHV-2 at IC 50 values of 2.5 and 2.9 μg/mL, respectively, and VACV at IC 50 values of 3.1 and 7.4 μg/mL, respectively, in plaque reduction assays. In virus spread inhibition assay of VACV KPB-100 and KPB-200 yielded IC 50 values of 1.63 and 13.2 μg/mL, respectively, and KPB-100 showed a nearly 2-log reduction in virus in VYR assay of VACV at 20 μg/mL. Finally, KPB-100 inhibited HHV-2 TK- at an IC 50 value of 4.5 μg/mL in CPE inhibition assay and HHV-1 at an IC 90 of 3.0 μg/mL in VYR assay. Both compounds are promising targets for synthetic optimization and in vivo study. KPB-100 in particular showed strong inhibition of all viruses tested.

Assembled microneedle arrays enhance the transport of compounds varying over a large range of molecular weight across human dermatomed skin

NARCIS (Netherlands)

Verbaan, F.J.; Bal, S.M.; van den Berg, D.J.; Groenink, W.H.H.; Verpoorten, H.; Lüttge, Regina; Bouwstra, J.A.

2007-01-01

In this study, we demonstrate the feasibility to use microneedle arrays manufactured from commercially available 30G hypodermal needles to enhance the transport of compounds up to a molecular weight of 72 kDa. Piercing of human dermatomed skin with microneedle arrays was studied by Trypan Blue

Fast and simple screening for the simultaneous analysis of seven metabolites derived from five volatile organic compounds in human urine using on-line solid-phase extraction coupled with liquid chromatography-tandem mass spectrometry.

Science.gov (United States)

Chiang, Wen-Chieh; Chen, Chao-Yu; Lee, Ting-Chen; Lee, Hui-Ling; Lin, Yu-Wen

2015-01-01

Recently, the International Agency for Research on cancer classified outdoor air pollution and particulate matter from outdoor air pollution as carcinogenic to humans (IARC Group 1), based on sufficient evidence of carcinogenicity in humans and experimental animals and strong mechanistic evidence. In particular, a wide variety of volatile organic compounds (VOCs) are volatized or released into the atmosphere and can become ubiquitous, as they originate from many different natural and anthropogenic sources, such as paints, pesticides, vehicle exhausts, cooking fumes, and tobacco smoke. Humans may be exposed to VOCs through inhalation, ingestion, or dermal contact, which may increase the risk of leukemia, birth defects, neurocognitive impairment, and cancer. Therefore, the focus of this study was the development of a simple, effective and rapid sample preparation method for the simultaneous determination of seven metabolites (6 mercaptic acids+t,t-muconic acid) derived from five VOCs (acrylamide, 1,3-butadiene, acrylonitrile, benzene, and xylene) in human urine by using automated on-line solid-phase extraction (SPE) coupled with liquid chromatography-electrospray tandem mass spectrometry (LC-MS/MS). An aliquot of each diluted urinary sample was directly injected into an autosampler through a trap column to reduce contamination, and then the retained target compounds were eluted by back-flush mode into an analytical column for separation. Negative electrospray ionization tandem mass spectrometry was utilized for quantification. The coefficients of correlation (r(2)) for the calibration curves were greater than 0.995. Reproducibility was assessed by the precision and accuracy of intra-day and inter-day precision, which showed results for coefficient of variation (CV) that were low 0.9 to 6.6% and 3.7 to 8.5%, respectively, and results for recovery that ranged from 90.8 to 108.9% and 92.1 to 107.7%, respectively. The limits of detection (LOD) and limits of

Impaired immune function in seals and laboratory rats exposed to dioxin-like compounds from Baltic herring

Energy Technology Data Exchange (ETDEWEB)

Ross, P.S. [Seal Rehabilitation and Research Centre, Pieterburen (Netherlands)]|[National Inst. of Public Health and Environmental Protection, Bilthoven (Netherlands); Swart, R.L. de [Seal Rehabilitation and Research Centre, Pieterburen (Netherlands)]|[Erasmus Univ., Rotterdam (Netherlands); Timmerman, H.H.; Loveren, H. van [National Inst. of Public Health and Environmental Protection, Bilthoven (Netherlands); Osterhaus, A.D.M.E. [Seal Rehabilitation and Research Centre, Pieterburen (Netherlands)]|[National Inst. of Public Health and Environmental Protection, Bilthoven (Netherlands)]|[Erasmus Univ., Rotterdam (Netherlands)

1995-12-31

Complex mixtures of lipophilic contaminants have been shown to affect certain top predators in the aquatic food chain, including seals. A recent demonstration that harbor seals (Phoca vitulina) fed Baltic Sea herring displayed impaired natural killer cell activity and T-lymphocyte function represented the first demonstration of immunotoxicity induced by ambient levels of contaminants in the environment. While these animals had a lower ability to respond to immunizations with inactivated vaccines, specific antibody responses, and in vitro antigen-specific lymphoproliferative responses, obvious constraints limited the ability to extend these results with host resistance tests or an evaluation of thymus and other lymphoid organs. The authors therefore set up a parallel study by exposing pregnant laboratory rats to the same Baltic herring contaminant mixture as received the seals. They then examined immune function parameters and host resistance to virus infection. As in the seals, rat pups of the Baltic group had impaired T-lymphocyte function. In addition, thymus cells and/or their precursors appeared to be targeted, as their numbers and function were reduced in the rats. Following challenge with rat cytomegalovirus in a host resistance study, rat pups in the Baltic group had impaired natural killer cell responses to the virus infection, and lower specific CD8 + (cytotoxic T-lymphocyte) responses following in vitro stimulation. By extrapolation, these results suggest that the impaired immune responses observed in the Baltic group of seals may lead to a less effective defense against virus infections in marine mammals inhabiting polluted coastal waters. Toxicological profiles and results of both the captive seal and laboratory rat experiments tend to implicate the 2,3,7,8-TCDD-like PCB, dioxin and furan congeners in the immunosuppression, and point to a major role for the PCBs.

Arterial stiffness and cognitive impairment.

Science.gov (United States)

Li, Xiaoxuan; Lyu, Peiyuan; Ren, Yanyan; An, Jin; Dong, Yanhong

2017-09-15

Arterial stiffness is one of the earliest indicators of changes in vascular wall structure and function and may be assessed using various indicators, such as pulse-wave velocity (PWV), the cardio-ankle vascular index (CAVI), the ankle-brachial index (ABI), pulse pressure (PP), the augmentation index (AI), flow-mediated dilation (FMD), carotid intima media thickness (IMT) and arterial stiffness index-β. Arterial stiffness is generally considered an independent predictor of cardiovascular and cerebrovascular diseases. To date, a significant number of studies have focused on the relationship between arterial stiffness and cognitive impairment. To investigate the relationships between specific arterial stiffness parameters and cognitive impairment, elucidate the pathophysiological mechanisms underlying the relationship between arterial stiffness and cognitive impairment and determine how to interfere with arterial stiffness to prevent cognitive impairment, we searched PUBMED for studies regarding the relationship between arterial stiffness and cognitive impairment that were published from 2000 to 2017. We used the following key words in our search: "arterial stiffness and cognitive impairment" and "arterial stiffness and cognitive impairment mechanism". Studies involving human subjects older than 30years were included in the review, while irrelevant studies (i.e., studies involving subjects with comorbid kidney disease, diabetes and cardiac disease) were excluded from the review. We determined that arterial stiffness severity was positively correlated with cognitive impairment. Of the markers used to assess arterial stiffness, a higher PWV, CAVI, AI, IMT and index-β and a lower ABI and FMD were related to cognitive impairment. However, the relationship between PP and cognitive impairment remained controversial. The potential mechanisms linking arterial stiffness and cognitive impairment may be associated with arterial pulsatility, as greater arterial pulsatility

Bioactive Compound Content and Cytotoxic Effect on Human Cancer Cells of Fresh and Processed Yellow Tomatoes

Directory of Open Access Journals (Sweden)

Assunta Raiola

2015-12-01

Full Text Available Tomato, as a fresh or processed product, has a high nutritional value due to its content of bioactive components such as phenolic compounds. Few studies describe the effect of processing on antioxidant content and the cancer cell growth inhibition activity. In this study we determined the phenolic and ascorbic acid content of three yellow tomato varieties, before and after thermal processing. Moreover, we determined the antioxidative power and tested the effects of tomato extracts on three human cancer cell lines. We found that the amount of phenolic acids (chlorogenic acid and caffeic acid decreased in all the samples after processing, whereas the flavonoid content increased after the heat treatment in two samples. A cytotoxic effect of tomato extracts was observed only after processing. This result well correlates with the flavonoid content after processing and clearly indicates that processed yellow tomatoes have a high content of bioactive compounds endowed with cytotoxicity towards cancer cells, thus opening the way to obtain tomato-based functional foods.

Caffeine attenuates scopolamine-induced memory impairment in humans.

Science.gov (United States)

Riedel, W; Hogervorst, E; Leboux, R; Verhey, F; van Praag, H; Jolles, J

1995-11-01

Caffeine consumption can be beneficial for cognitive functioning. Although caffeine is widely recognized as a mild CNS stimulant drug, the most important consequence of its adenosine antagonism is cholinergic stimulation, which might lead to improvement of higher cognitive functions, particularly memory. In this study, the scopolamine model of amnesia was used to test the cholinergic effects of caffeine, administered as three cups of coffee. Subjects were 16 healthy volunteers who received 250 mg caffeine and 2 mg nicotine separately, in a placebo-controlled double-blind cross-over design. Compared to placebo, nicotine attenuated the scopolamine-induced impairment of storage in short-term memory and attenuated the scopolamine-induced slowing of speed of short-term memory scanning. Nicotine also attenuated the scopolamine-induced slowing of reaction time in a response competition task. Caffeine attenuated the scopolamine-induced impairment of free recall from short- and long-term memory, quality and speed of retrieval from long-term memory in a word learning task, and other cognitive and non-cognitive measures, such as perceptual sensitivity in visual search, reading speed, and rate of finger-tapping. On the basis of these results it was concluded that caffeine possesses cholinergic cognition enhancing properties. Caffeine could be used as a control drug in studies using the scopolamine paradigm and possibly also in other experimental studies of cognitive enhancers, as the effects of a newly developed cognition enhancing drug should at least be superior to the effects of three cups of coffee.

Diet-induced obesity impairs endometrial stromal cell decidualization: a potential role for impaired autophagy.

Science.gov (United States)

Rhee, Julie S; Saben, Jessica L; Mayer, Allyson L; Schulte, Maureen B; Asghar, Zeenat; Stephens, Claire; Chi, Maggie M-Y; Moley, Kelle H

2016-06-01

What effect does diet-induced obesity have on endometrial stromal cell (ESC) decidualization? Diet-induced obesity impairs ESC decidualization. Decidualization is important for successful implantation and subsequent health of the pregnancy. Compared with normal-weight women, obese women have lower pregnancy rates (both spontaneous and by assisted reproductive technology), higher rates of early pregnancy loss and poorer oocyte quality. Beginning at 6 weeks of age, female C57Bl/6J mice were fed either a high-fat/high-sugar diet (HF/HS; 58% Fat Energy/Sucrose) or a diet of standard mouse chow (CON; 13% Fat) for 12 weeks. At this point, metabolic parameters were measured. Some of the mice (n = 9 HF/HS and 9 CON) were mated with reproductively competent males, and implantation sites were assessed. Other mice (n = 11 HF/HS and 10 CON) were mated with vasectomized males, and artificial decidualization was induced. For in vitro human studies of primary ESCs, endometrial tissue was obtained via biopsy from normo-ovulatory patients without history of infertility (obese = BMI > 30 kg/m(2), n = 11 and lean = BMI treatment with cAMP and medroxyprogesterone. The level of expression of decidualization markers was assessed by RT-qPCR (mRNA) and western blotting (protein). ATP content of ESCs was measured, and levels of autophagy were assessed by western blotting of the autophagy regulators acetyl coa carboxylase (ACC) and ULK1 (Ser 317). Autophagic flux was measured by western blot of the marker LC3b-II. Mice exposed to an HF/HS diet became obese and metabolically impaired. HF/HS-exposed mice mated to reproductively competent males had smaller implantation sites in early pregnancy (P obese women than in those of normal-weight women (Ptreatment abrogated this increase. Many aspects of obesity and metabolic impairment could contribute to the decidualization defects observed in the HF/HS-exposed mice. Although our findings suggest that both autophagy and decidualization are impaired

The pathological consequences of impaired genome integrity in humans; disorders of the DNA replication machinery.

Science.gov (United States)

O'Driscoll, Mark

2017-01-01

Accurate and efficient replication of the human genome occurs in the context of an array of constitutional barriers, including regional topological constraints imposed by chromatin architecture and processes such as transcription, catenation of the helical polymer and spontaneously generated DNA lesions, including base modifications and strand breaks. DNA replication is fundamentally important for tissue development and homeostasis; differentiation programmes are intimately linked with stem cell division. Unsurprisingly, impairments of the DNA replication machinery can have catastrophic consequences for genome stability and cell division. Functional impacts on DNA replication and genome stability have long been known to play roles in malignant transformation through a variety of complex mechanisms, and significant further insights have been gained from studying model organisms in this context. Congenital hypomorphic defects in components of the DNA replication machinery have been and continue to be identified in humans. These disorders present with a wide range of clinical features. Indeed, in some instances, different mutations in the same gene underlie different clinical presentations. Understanding the origin and molecular basis of these features opens a window onto the range of developmental impacts of suboptimal DNA replication and genome instability in humans. Here, I will briefly overview the basic steps involved in DNA replication and the key concepts that have emerged from this area of research, before switching emphasis to the pathological consequences of defects within the DNA replication network; the human disorders. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Restoring polyamines protects from age-induced memory impairment in an autophagy-dependent manner

NARCIS (Netherlands)

Gupta, V.K.; Scheunemann, L.; Eisenberg, T.; Mertel, S.; Bhukel, A.; Koemans, T.S.; Kramer, J.M.; Liu, K.S.; Schroeder, S.; Stunnenberg, H.G.; Sinner, F.; Magnes, C.; Pieber, T.R.; Dipt, S.; Fiala, A.; Schenck, A.; Schwaerzel, M.; Madeo, F.; Sigrist, S.J.

2013-01-01

Age-dependent memory impairment is known to occur in several organisms, including Drosophila, mouse and human. However, the fundamental cellular mechanisms that underlie these impairments are still poorly understood, effectively hampering the development of pharmacological strategies to treat the

Antibacterial Compounds from Red Seaweeds (Rhodophyta

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Noer Kasanah

2015-07-01

Full Text Available Seaweeds produce great variety of metabolites benefit for human. Red seaweeds (Rhodophyta are well known as producer of phycocolloids such agar, agarose, carragenan and great variety of secondary metabolites. This review discusses the red algal secondary metabolites with antibacterial activity. The chemical constituents of red algae are steroid, terpenoid, acetogenin and dominated by halogenated compounds mainly brominated compounds. Novel compounds with intriguing skeleton are also reported such as bromophycolides and neurymenolides. In summary, red seaweeds are potential sources for antibacterial agents and can serve as lead in synthesis of new natural medicines.

Cannabidiol prevents motor and cognitive impairments induced by reserpine in rats

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Fernanda Fiel Peres

2016-09-01

Full Text Available Cannabidiol (CBD is a non-psychotomimetic compound from Cannabis sativa that presents antipsychotic, anxiolytic, anti-inflammatory and neuroprotective effects. In Parkinson’s disease patients, CBD is able to attenuate the psychotic symptoms induced by L-DOPA and to improve quality of life. Repeated administration of reserpine in rodents induces motor impairments that are accompanied by cognitive deficits, and has been applied to model both tardive dyskinesia and Parkinson’s disease. The present study investigated whether CBD administration would attenuate reserpine-induced motor and cognitive impairments in rats. Male Wistar rats received four injections of CBD (0.5 or 5 mg/kg or vehicle (days 2-5. On days 3 and 5, animals received also one injection of 1 mg/kg reserpine or vehicle. Locomotor activity, vacuous chewing movements and catalepsy were assessed from day 1 to day 7. On days 8 and 9, we evaluated animals’ performance on the plus-maze discriminative avoidance task, for learning/memory assessment. CBD (0.5 and 5 mg/kg attenuated the increase in catalepsy behavior and in oral movements – but not the decrease in locomotion – induced by reserpine. CBD (0.5 mg/kg also ameliorated the reserpine-induced memory deficit in the discriminative avoidance task. Our data show that CBD is able to attenuate motor and cognitive impairments induced by reserpine, suggesting the use of this compound in the pharmacotherapy of Parkinson’s disease and tardive dyskinesia.

KCNQ channels regulate age-related memory impairment.

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Sonia Cavaliere

Full Text Available In humans KCNQ2/3 heteromeric channels form an M-current that acts as a brake on neuronal excitability, with mutations causing a form of epilepsy. The M-current has been shown to be a key regulator of neuronal plasticity underlying associative memory and ethanol response in mammals. Previous work has shown that many of the molecules and plasticity mechanisms underlying changes in alcohol behaviour and addiction are shared with those of memory. We show that the single KCNQ channel in Drosophila (dKCNQ when mutated show decrements in associative short- and long-term memory, with KCNQ function in the mushroom body α/βneurons being required for short-term memory. Ethanol disrupts memory in wildtype flies, but not in a KCNQ null mutant background suggesting KCNQ maybe a direct target of ethanol, the blockade of which interferes with the plasticity machinery required for memory formation. We show that as in humans, Drosophila display age-related memory impairment with the KCNQ mutant memory defect mimicking the effect of age on memory. Expression of KCNQ normally decreases in aging brains and KCNQ overexpression in the mushroom body neurons of KCNQ mutants restores age-related memory impairment. Therefore KCNQ is a central plasticity molecule that regulates age dependent memory impairment.

Human Impairment from Living near Confined Animal (Hog) Feeding Operations

International Nuclear Information System (INIS)

Kilburn, K.H.; Kilburn, K.H.

2012-01-01

Problem. To determine whether neighbors around manure lagoons and massive hog confinement buildings who complained of offensive odors and symptoms had impaired brain and lung functions. Method. We compared near hog manure neighbors of lagoons to people living beyond 3 kilometers in Ohio and to unexposed people controls in a nearby state for neuro physiological, cognitive, recall and memory functions, and pulmonary performance. Results. The 25 exposed subjects averaged 4.3 neuro behavioral abnormalities, significantly different from 2.5 for local controls and 2.3 for Tennessee controls. Exposed subjects mean forced vital capacity and expiratory volume in 1 sec were reduced significantly compared to local and regional controls. Conclusions. Near neighbors of hog enclosures and manure lagoon gases had impaired neuro behavioral functions and pulmonary functions and these effects extended to nearby people thought to be controls. Hydrogen sulfide must be abated because people living near lagoons cannot avoid rotten egg gas.

Age-Related Sensory Impairments and Risk of Cognitive Impairment

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Fischer, Mary E; Cruickshanks, Karen J.; Schubert, Carla R; Pinto, Alex A; Carlsson, Cynthia M; Klein, Barbara EK; Klein, Ronald; Tweed, Ted S.

2016-01-01

Background/Objectives To evaluate the associations of sensory impairments with the 10-year risk of cognitive impairment. Previous work has primarily focused on the relationship between a single sensory system and cognition. Design The Epidemiology of Hearing Loss Study (EHLS) is a longitudinal, population-based study of aging in the Beaver Dam, WI community. Baseline examinations were conducted in 1993 and follow-up exams have been conducted every 5 years. Setting General community Participants EHLS members without cognitive impairment at EHLS-2 (1998–2000). There were 1,884 participants (mean age = 66.7 years) with complete EHLS-2 sensory data and follow-up information. Measurements Cognitive impairment was a Mini-Mental State Examination score of impairment was a pure-tone average of hearing thresholds (0.5, 1, 2 and 4 kHz) of > 25 decibel Hearing Level in either ear. Visual impairment was Pelli-Robson contrast sensitivity of impairment was a San Diego Odor Identification Test score of impairment were independently associated with cognitive impairment risk [Hearing: Hazard Ratio (HR) = 1.90, 95% Confidence Interval (C.I.) = 1.11, 3.26; Vision: HR = 2.05, 95% C.I. = 1.24, 3.38; Olfaction: HR = 3.92, 95% C.I. = 2.45, 6.26]. However, 85% with hearing impairment, 81% with visual impairment, and 76% with olfactory impairment did not develop cognitive impairment during follow-up. Conclusion The relationship between sensory impairment and cognitive impairment was not unique to one sensory system suggesting sensorineural health may be a marker of brain aging. The development of a combined sensorineurocognitive measure may be useful in uncovering mechanisms of healthy brain aging. PMID:27611845

Determination of total and methylmercury compounds in the IAEA human hair intercomparison samples - Experience of the IAEA-MEL

International Nuclear Information System (INIS)

Horvat, M.; Liang, L.; Mandic, V.

1995-01-01

The programme of this CRP is focused on the analyses of human hair samples. There are only two human hair samples certified for total mercury, and no RMs for methylmercury compounds is available. One of the main objectives of this CRP is to produce, through the IAEA AQCS Programme, a human hair intercomparison material for quality assurance requirements in population monitoring programmes for total and methylmercury exposure. Through the reporting period, MESL has introduced a new method for simultaneous determination of total and methylmercury in biological samples. As the laboratory has close collaboration with the CRP's Reference Laboratory in Ljubljana, Slovenia, it has also been actively involved in the quality assurance component of this CRP. This report represents a summary on the results for total and methylmercury in two intercomparison samples, IAEA-085 and IAEA-086 using newly developed method

Partial purification of endogenous digitalis-like compound(s) in cord blood

Energy Technology Data Exchange (ETDEWEB)

Balzan, S.; Ghione, S.; Biver, P.; Gazzetti, P.; Montali, U. (C.N.R. Institute of Clinical Physiology, Pisa (Italy))

1991-02-01

Increasing evidence indicates the presence of endogenous digitalis-like compound(s) in human body fluids. In this preliminary report, we describe a study of the partial purification by HPLC of these compounds in the plasma of neonates (who have particularly high concentrations of this substance) and adults. Plasma samples from neonates (cord blood) and adults, lyophilized and extracted with methanol, were applied on a 300 x 3.9 mm C18 Nova Pak column and eluted with a mobile phase of acetonitrile/methanol/water (17/17/66 or 14/14/72 by vol) and, after 30 min, with 100% methanol. We assayed eluted fractions for inhibitory activity of 86Rb uptake and for digoxin-like immunoreactivity. The elution profile revealed a first peak of inhibitory activity of 86Rb uptake at the beginning of the chromatography; another peak was eluted with the 100% methanol. The two peaks also cross-reacted with antidigoxin antibodies. Because the second peak could possibly reflect the nonspecific interference of various lipophilic compounds, we focused our attention on the first peak. For these fractions dose-response curves for 86Rb uptake and for displacement of digoxin were parallel, respectively, to those of ouabain and digoxin, suggesting similarities of digoxin-like immunoreactive substance to cardiac glycosides. Similar chromatographic profiles were also obtained for plasma from adults, suggesting that the endogenous glycoside-like compound(s) in the neonate may be the same as those in the adult.

Impairments of spatial working memory and attention following acute psychosocial stress.

Science.gov (United States)

Olver, James S; Pinney, Myra; Maruff, Paul; Norman, Trevor R

2015-04-01

Few studies have investigated the effect of an acute psychosocial stress paradigm on impaired attention and working memory in humans. Further, the duration of any stress-related cognitive impairment remains unclear. The aim of this study was to examine the effect of an acute psychosocial stress paradigm, the Trier Social Stress, on cognitive function in healthy volunteers. Twenty-three healthy male and female subjects were exposed to an acute psychosocial stress task. Physiological measures (salivary cortisol, heart rate and blood pressure) and subjective stress ratings were measured at baseline, in anticipation of stress, immediately post-stress and after a period of rest. A neuropsychological test battery including spatial working memory and verbal memory was administered at each time point. Acute psychosocial stress produced significant increases in cardiovascular and subjective measures in the anticipatory and post-stress period, which recovered to baseline after rest. Salivary cortisol steadily declined over the testing period. Acute psychosocial stress impaired delayed verbal recall, attention and spatial working memory. Attention remained impaired, and delayed verbal recall continued to decline after rest. Acute psychosocial stress is associated with an impairment of a broad range of cognitive functions in humans and with prolonged abnormalities in attention and memory. Copyright © 2014 John Wiley & Sons, Ltd.

Bioavailability and pharmacokinetic profile of grape pomace phenolic compounds in humans.

Science.gov (United States)

Castello, Fabio; Costabile, Giuseppina; Bresciani, Letizia; Tassotti, Michele; Naviglio, Daniele; Luongo, Delia; Ciciola, Paola; Vitale, Marilena; Vetrani, Claudia; Galaverna, Gianni; Brighenti, Furio; Giacco, Rosalba; Del Rio, Daniele; Mena, Pedro

2018-05-15

Grape pomace, the major byproduct of the wine and juice industry, is a relevant source of bioactive phenolic compounds. However, polyphenol bioavailability in humans is not well understood, and the inter-individual variability in the production of phenolic metabolites has not been comprehensively assessed to date. The pharmacokinetic and excretive profiles of phenolic metabolites after the acute administration of a drink made from red grape pomace was here investigated in ten volunteers. A total of 35 and 28 phenolic metabolites were quantified in urine and plasma, respectively. The main circulating metabolites included phenyl-γ-valerolactones, hydroxybenzoic acids, simple phenols, hydroxyphenylpropionic acids, hydroxycinnamates, and (epi)catechin phase II conjugates. A high inter-individual variability was shown both in urine and plasma samples, and different patterns of circulating metabolites were unravelled by applying unsupervised multivariate analysis. Besides the huge variability in the production of microbial metabolites of colonic origin, an important variability was observed due to phase II conjugates. These results are of interest to further understand the potential health benefits of phenolic metabolites on individual basis. Copyright © 2018 Elsevier Inc. All rights reserved.

Neurodevelopmental Impairment among Infants Born to Mothers Infected with Human Immunodeficiency Virus and Uninfected Mothers from Three Peri-Urban Primary Care Clinics in Harare, Zimbabwe

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Kandawasvika, Gwendoline Q.; Ogundipe, Enitan; Gumbo, Felicity Z.; Kurewa, Edith N.; Mapingure, Munyaradzi P.; Stray-Pedersen, Babill

2011-01-01

Aim: The aim of this article is to document the risk of neurodevelopmental impairment (NDI) among infants enrolled in a programme for the prevention of mother-to-child transmission of HIV (human immunodeficiency virus) in Zimbabwe using the Bayley Infant Neurodevelopmental Screener (BINS). Method: We prospectively followed up infants at three…

Effects of the anti-malarial compound cryptolepine and its analogues in human lymphocytes and sperm in the Comet assay.

Science.gov (United States)

Gopalan, Rajendran C; Emerce, Esra; Wright, Colin W; Karahalil, Bensu; Karakaya, Ali E; Anderson, Diana

2011-12-15

Malaria is a mosquito-borne infectious disease caused by the genus Plasmodium. It causes one million deaths per year in African children under the age of 5 years. There is an increasing development of resistance of malarial parasites to chloroquine and other currently used anti-malarial drugs. Some plant products such as the indoloquinoline alkaloid cryptolepine have been shown to have potent activity against P. falciparum in vitro. On account of its toxicity, cryptolepine is not suitable for use as an antimalarial drug but a number of analogues of cryptolepine have been synthesised in an attempt to find compounds that have reduced cytotoxicity and these have been investigated in the present study in human sperm and lymphocytes using the Comet assay. The results suggest that cryptolepine and the analogues cause DNA damage in lymphocytes, but appear to have no effect on human sperm at the assessed doses. In the context of antimalarial drug development, the data suggest that all cryptolepine compounds and in particular 2,7-dibromocryptolepine cause DNA damage and therefore may not be suitable for pre clinical development as antimalarial agents. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Environmental contamination and human exposure to dioxin-related compounds in e-waste recycling sites of developing countries.

Science.gov (United States)

Tue, Nguyen Minh; Takahashi, Shin; Subramanian, Annamalai; Sakai, Shinichi; Tanabe, Shinsuke

2013-07-01

E-waste recycling using uncontrolled processes is a major source of dioxin-related compounds (DRCs), including not only the regulated polychlorinated dibenzo-p-dioxins/dibenzofurans (PCDD/Fs) and dioxin-like polychlorinated biphenyls (DL-PCBs) but also non-regulated brominated and mixed halogenated compounds (PBDD/Fs and PXDD/Fs). Various studies at informal e-waste recycling sites (EWRSs) in Asian developing countries found the soil contamination levels of PCDD/Fs from tens to ten thousand picogram TCDD-equivalents (TEQ) per gram and those of DL-PCBs up to hundreds of picogram TEQ per gram. The air concentration of PCDD/Fs was reported as high as 50 pg TEQ per m(3) in Guiyu, the largest Chinese EWRS. Non-regulated compounds also contributed substantially to the total DL toxicity of the DRC mixtures from e-waste, as evidenced by the high TEQ levels estimated for the currently identifiable PBDD/Fs as well as the large portion of unexplained bioassay-derived TEQ levels in soils/dusts from EWRSs. Considering the high exposure levels estimated for EWRS residents, especially children, comprehensive emission inventories of DRCs from informal e-waste recycling, the identities and toxic potencies of unidentified DRCs released, and their impacts on human health need to be investigated in future studies.

Influence of Laccase and Tyrosinase on the Antioxidant Capacity of Selected Phenolic Compounds on Human Cell Lines

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Matthias Riebel

2015-09-01

Full Text Available Polyphenolic compounds affect the color, odor and taste of numerous food products of plant origin. In addition to the visual and gustatory properties, they serve as radical scavengers and have antioxidant effects. Polyphenols, especially resveratrol in red wine, have gained increasing scientific and public interest due to their presumptive beneficial impact on human health. Enzymatic oxidation of phenolic compounds takes place under the influence of polyphenol oxidases (PPO, including tyrosinase and laccase. Several studies have demonstrated the radical scavenger effect of plants, food products and individual polyphenols in vitro, but, apart from resveratrol, such impact has not been proved in physiological test systems. Furthermore, only a few data exist on the antioxidant capacities of the enzymatic oxidation products of phenolic compounds generated by PPO. We report here first results about the antioxidant effects of phenolic substances, before and after oxidation by fungal model tyrosinase and laccase. In general, the common chemical 2,2-diphenyl-1-picrylhydrazyl assay and the biological tests using two different types of cell cultures (monocytes and endothelial cells delivered similar results. The phenols tested showed significant differences with respect to their antioxidant activity in all test systems. Their antioxidant capacities after enzymatic conversion decreased or increased depending on the individual PPO used.

Impaired IFNγ-Signaling and Mycobacterial Clearance in IFNγR1-Deficient Human iPSC-Derived Macrophages.

Science.gov (United States)

Neehus, Anna-Lena; Lam, Jenny; Haake, Kathrin; Merkert, Sylvia; Schmidt, Nico; Mucci, Adele; Ackermann, Mania; Schubert, Madline; Happle, Christine; Kühnel, Mark Philipp; Blank, Patrick; Philipp, Friederike; Goethe, Ralph; Jonigk, Danny; Martin, Ulrich; Kalinke, Ulrich; Baumann, Ulrich; Schambach, Axel; Roesler, Joachim; Lachmann, Nico

2018-01-09

Mendelian susceptibility to mycobacterial disease (MSMD) is caused by inborn errors of interferon gamma (IFNγ) immunity and is characterized by severe infections by weakly virulent mycobacteria. Although IFNγ is the macrophage-activating factor, macrophages from these patients have never been studied. We demonstrate the generation of heterozygous and compound heterozygous (iMSMD-cohet) induced pluripotent stem cells (iPSCs) from a single chimeric patient, who suffered from complete autosomal recessive IFNγR1 deficiency and received bone-marrow transplantation. Loss of IFNγR1 expression had no influence on the macrophage differentiation potential of patient-specific iPSCs. In contrast, lack of IFNγR1 in iMSMD-cohet macrophages abolished IFNγ-dependent phosphorylation of STAT1 and induction of IFNγ-downstream targets such as IRF-1, SOCS-3, and IDO. As a consequence, iMSMD-cohet macrophages show impaired upregulation of HLA-DR and reduced intracellular killing of Bacillus Calmette-Guérin. We provide a disease-modeling platform that might be suited to investigate novel treatment options for MSMD and to gain insights into IFNγ signaling in macrophages. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Ethyl acetate fraction from Hibiscus sabdariffa L. attenuates diabetes-associated cognitive impairment in mice.

Science.gov (United States)

Seung, Tae Wan; Park, Seon Kyeong; Kang, Jin Yong; Kim, Jong Min; Park, Sang Hyun; Kwon, Bong Seok; Lee, Chang Jun; Kang, Jeong Eun; Kim, Dae Ok; Lee, Uk; Heo, Ho Jin

2018-03-01

The ameliorating effects of the ethyl acetate fraction from Hibiscus sabdariffa L. (EFHS) 2 against diabetes mellitus (DM) 3 and DM-induced cognitive impairment were investigated on streptozotocin (STZ) 4 -induced DM mice. The EFHS groups showed improved hyperglycemia and glucose tolerance compared to the STZ group. Furthermore, their liver and kidney function and lipid metabolic imbalance in the blood serum were effectively recovered. The EFHS groups significantly ameliorated STZ-induced cognitive impairment in Y-maze, passive avoidance, and Morris water maze (MWM) 5 tests. The EFHS groups showed significant improvement in the antioxidant and cholinergic systems of the brain tissue. In addition, EFHS had an excellent ameliorating effect on protein expression levels from the tau hyperphosphorylation pathways, such as phospho-c-Jun N-terminal kinases (p-JNK), 6 phospho-tau (p-tau), 7 and cleaved poly (ADP-ribose) polymerase (c-PARP). 8 The main compounds of EFHS were identified as various phenolic compounds, including hibiscus acid, caffeoylquinic acid (CQA) 9 isomers, and quercetin derivates. Therefore, EFHS containing various physiologically active materials can potentially be used for improving DM-induced cognitive impairment via its antioxidant activity, improvement of the cholinergic system, and hyperphosphorylation tau signaling. Copyright © 2017 Elsevier Ltd. All rights reserved.

Translating cognition from animals to humans.

Science.gov (United States)

Keeler, J F; Robbins, T W

2011-06-15

Many clinical disorders, whether neurological (e.g. Alzheimer's disease) or neuropsychiatric (e.g. schizophrenia and depression), exhibit cognitive symptoms that require pharmacological treatment. Cognition is multi-faceted and includes processes of perception, attention, working memory, long-term memory, executive function, language and social cognition. This article reviews how it is feasible to model many aspects of human cognition with the use of appropriate animal models and associated techniques, including the use of computer controlled tests (e.g. touch-screens), for optimising translation of experimental research to the clinic. When investigating clinical disorders, test batteries should aim to profile cognitive function in order to determine which aspects are impaired and which are preserved. In this review we have paid particular attention to the validation of translational methods; this may be done through the application of common theoretical principles, by comparing the effects of psychological manipulations and, wherever feasible, with the demonstration of homologous neural circuitry or equivalent pharmacological actions in the animal and human paradigms. Of particular importance is the use of 'back-translation' to ensure that the animal model has validity, for example, in predicting the effects of therapeutic drugs already found in human studies. It is made clear that the choice of appropriate behavioral tests is an important element of animal models of neuropsychiatric or neurological disorder; however, of course it is also important to select appropriate manipulations, whether genetic, neurodevelopmental, neurotoxic, or pharmacological, for simulating the neural substrates relevant to the disorders that lead to predictable behavioral and cognitive impairments, for optimising the testing of candidate compounds. 2011 Elsevier Inc. All rights reserved.

Environmental and human toxicology of nickel - a review; Umwelt- und Humantoxikologie von Nickel - eine aktuelle Uebersicht

Energy Technology Data Exchange (ETDEWEB)

Beyersmann, D. [Fachbereich Biologie und Chemie, Univ. Bremen (Germany)

2006-07-01

Nickel is a relatively rare element, and its concentrations in ambient air, soils and waters are very low. Higher burdens of nickel are found in nickel industries and their proximity. The human uptake of nickel from the ambient air is neglectably low, except in industrial exposures. The main fraction of human nickel uptake is from food, nearly 50% stems from vegetables. Only about 2% of the oral uptake of nickel are resorbed and distributed over all organs investigated. The uptake of nickel compounds through the skin generally is very low. However, chronic skin contact with nickel and nickel compounds causes a specific contact allergy. This disease was observed after occupational exposure but also frequently in the general population. The number of new cases has dropped considerably due to reinforced prevention. Epidemiological studies with workers of nickel smelting and refining plants have demonstrated increased risks of nose and lung cancer. Human data are supported by results from animal experiments which have shown that inhalation of various nickel compounds caused lung cancer. Furthermore, animal experiments have yielded evidence that oral and inhalative exposure to nickel compounds impair reproduction. National and international agencies have classified various nickel compounds as carcinogenic to humans. The unit cancer risk attributed to life-long inhalation of 1 {mu}g Ni/m{sup 3} air is estimated to be between 2 x 10{sup -4} and 7 x 10{sup -4}. Occupational exposure limits in Germany have been the Technical Guidance Values of 0.5 mg/m{sup 3} for nickel and weakly soluble nickel compounds and of 0.05 mg/m{sup 3} for inhalable droplets of soluble nickel salts. The German limit value for ambient immission is 0.015 mg Ni/m{sup 2}. d, and for emission 0,5 mg Ni/m{sup 3}. Limit values for nickel in air are to be taken not as safe thresholds but as guidance values for the delimitation of the cancer risk. (orig.)

Orally administrated cinnamon extract reduces β-amyloid oligomerization and corrects cognitive impairment in Alzheimer's disease animal models.

Directory of Open Access Journals (Sweden)

Anat Frydman-Marom

Full Text Available An increasing body of evidence indicates that accumulation of soluble oligomeric assemblies of β-amyloid polypeptide (Aβ play a key role in Alzheimer's disease (AD pathology. Specifically, 56 kDa oligomeric species were shown to be correlated with impaired cognitive function in AD model mice. Several reports have documented the inhibition of Aβ plaque formation by compounds from natural sources. Yet, evidence for the ability of common edible elements to modulate Aβ oligomerization remains an unmet challenge. Here we identify a natural substance, based on cinnamon extract (CEppt, which markedly inhibits the formation of toxic Aβ oligomers and prevents the toxicity of Aβ on neuronal PC12 cells. When administered to an AD fly model, CEppt rectified their reduced longevity, fully recovered their locomotion defects and totally abolished tetrameric species of Aβ in their brain. Furthermore, oral administration of CEppt to an aggressive AD transgenic mice model led to marked decrease in 56 kDa Aβ oligomers, reduction of plaques and improvement in cognitive behavior. Our results present a novel prophylactic approach for inhibition of toxic oligomeric Aβ species formation in AD through the utilization of a compound that is currently in use in human diet.

TGF-β signaling is an effective target to impair survival and induce apoptosis of human cholangiocarcinoma cells: A study on human primary cell cultures.

Directory of Open Access Journals (Sweden)

Anna Maria Lustri

a repair mechanism in CCAs. LY2157299 failed to influence cell proliferation or apoptosis but significantly inhibited cell migration. At a 50 μM concentration, in fact, LY2157299 significantly impaired (at 24, 48 and 120 hrs the wound-healing of primary cell cultures from both mucin-and mixed-CCA. In conclusion, we demonstrated that CX4945 and LY2157299 exert relevant but distinct anticancer effects against human CCA cells, with CX4945 acting on cell viability and apoptosis, and LY2157299 impairing cell migration. These results suggest that targeting the TGF-β signaling with a combination of CX-4945 and LY2157299 could have potential benefits in the treatment of human CCA.

The human taste receptor hTAS2R14 responds to a variety of different bitter compounds

International Nuclear Information System (INIS)

Behrens, Maik; Brockhoff, Anne; Kuhn, Christina; Bufe, Bernd; Winnig, Marcel; Meyerhof, Wolfgang

2004-01-01

The recent advances in the functional expression of TAS2Rs in heterologous systems resulted in the identification of bitter tastants that specifically activate receptors of this family. All bitter taste receptors reported to date exhibit a pronounced selectivity for single substances or structurally related bitter compounds. In the present study we demonstrate the expression of the hTAS2R14 gene by RT-PCR analyses and in situ hybridisation in human circumvallate papillae. By functional expression in HEK-293T cells we show that hTAS2R14 displays a, so far, unique broad tuning towards a variety of structurally diverse bitter compounds, including the potent neurotoxins, (-)-α-thujone, the pharmacologically active component of absinthe, and picrotoxinin, a poisonous substance of fishberries. The observed activation of heterologously expressed hTAS2R14 by low concentrations of (-)-α-thujone and picrotoxinin suggests that the receptor is sufficiently sensitive to caution us against the ingestion of toxic amounts of these substances

Worsening Cognitive Impairment and Neurodegenerative Pathology Progressively Increase Risk for Delirium

Science.gov (United States)

Davis, Daniel H.J.; Skelly, Donal T.; Murray, Carol; Hennessy, Edel; Bowen, Jordan; Norton, Samuel; Brayne, Carol; Rahkonen, Terhi; Sulkava, Raimo; Sanderson, David J.; Rawlins, J. Nicholas; Bannerman, David M.; MacLullich, Alasdair M.J.; Cunningham, Colm

2015-01-01

Background Delirium is a profound neuropsychiatric disturbance precipitated by acute illness. Although dementia is the major risk factor this has typically been considered a binary quantity (i.e., cognitively impaired versus cognitively normal) with respect to delirium risk. We used humans and mice to address the hypothesis that the severity of underlying neurodegenerative changes and/or cognitive impairment progressively alters delirium risk. Methods Humans in a population-based longitudinal study, Vantaa 85+, were followed for incident delirium. Odds for reporting delirium at follow-up (outcome) were modeled using random-effects logistic regression, where prior cognitive impairment measured by Mini-Mental State Exam (MMSE) (exposure) was considered. To address whether underlying neurodegenerative pathology increased susceptibility to acute cognitive change, mice at three stages of neurodegenerative disease progression (ME7 model of neurodegeneration: controls, 12 weeks, and 16 weeks) were assessed for acute cognitive dysfunction upon systemic inflammation induced by bacterial lipopolysaccharide (LPS; 100 μg/kg). Synaptic and axonal correlates of susceptibility to acute dysfunction were assessed using immunohistochemistry. Results In the Vantaa cohort, 465 persons (88.4 ± 2.8 years) completed MMSE at baseline. For every MMSE point lost, risk of incident delirium increased by 5% (p = 0.02). LPS precipitated severe and fluctuating cognitive deficits in 16-week ME7 mice but lower incidence or no deficits in 12-week ME7 and controls, respectively. This was associated with progressive thalamic synaptic loss and axonal pathology. Conclusion A human population-based cohort with graded severity of existing cognitive impairment and a mouse model with progressing neurodegeneration both indicate that the risk of delirium increases with greater severity of pre-existing cognitive impairment and neuropathology. PMID:25239680

Clinical breath analysis: Discriminating between human endogenous compounds and exogenous (environmental) chemical confounders

Science.gov (United States)

Volatile organic compounds (VOCs) in exhaled breath originate from current or previous environmental exposures (exogenous compounds) and internal metabolic anabolic and catabolic) production (endogenous compounds). The origins of certain VOCs in breath presumed to be endogenous ...

Neuroimaging Impaired Response Inhibition and Salience Attribution in Human Drug Addiction: A Systematic Review.

Science.gov (United States)

Zilverstand, Anna; Huang, Anna S; Alia-Klein, Nelly; Goldstein, Rita Z

2018-06-06

The impaired response inhibition and salience attribution (iRISA) model proposes that impaired response inhibition and salience attribution underlie drug seeking and taking. To update this model, we systematically reviewed 105 task-related neuroimaging studies (n > 15/group) published since 2010. Results demonstrate specific impairments within six large-scale brain networks (reward, habit, salience, executive, memory, and self-directed networks) during drug cue exposure, decision making, inhibitory control, and social-emotional processing. Addicted individuals demonstrated increased recruitment of these networks during drug-related processing but a blunted response during non-drug-related processing, with the same networks also being implicated during resting state. Associations with real-life drug use, relapse, therapeutic interventions, and the relevance to initiation of drug use during adolescence support the clinical relevance of the results. Whereas the salience and executive networks showed impairments throughout the addiction cycle, the reward network was dysregulated at later stages of abuse. Effects were similar in alcohol, cannabis, and stimulant addiction. Copyright © 2018 Elsevier Inc. All rights reserved.

Neuroprotective and Cognition-Enhancing Effects of Compound K Isolated from Red Ginseng.

Science.gov (United States)

Seo, Ji Yeon; Ju, Sung Hee; Oh, Jisun; Lee, Seung Kwon; Kim, Jong-Sang

2016-04-13

The present study was aimed at elucidating the effect of compound K derived from red ginseng on memory function in mouse model and glutamate-induced cytotoxicity in mouse hippocampal HT22 cells. Compound K induced antioxidant enzymes in nuclear factor (erythroid-derived 2)-like 2 (Nrf2)-mediated manner, and effectively attenuated cytotoxicity and mitochondrial damage induced by glutamate in HT22 cells. However, the cytoprotective effect by compound K was abolished by heme oxygenase-1 inhibitor, tin protophorphyrin IX, suggesting that neuroprotective effect of compound K was caused by its Nrf2-mediated induction of antioxidant enzymes. Further, memory deficit induced by scopolamine was restored by compound K, which did not inhibit acetylcholine esterase, in C57BL/6 mice but not in Nrf2 knockout mice as assessed by passive avoidance test, Y-maze and water maze tests, suggesting that scopolamine-induced memory impairment was overcome by the induction of Nrf2-mediated antioxidant enzymes by the compound K. Overall, our data indicate that compound K could be useful in prevention and treatment of reactive oxygen species-induced neurological disorders such as Alzheimer's disease.

Compound K, a metabolite of ginseng saponin, induces apoptosis via caspase-8-dependent pathway in HL-60 human leukemia cells

International Nuclear Information System (INIS)

Cho, Sung-Hee; Chung, Kyung-Sook; Choi, Jung-Hye; Kim, Dong-Hyun; Lee, Kyung-Tae

2009-01-01

Compound K [20-O-β-(D-glucopyranosyl)-20(S)-protopanaxadiol], a metabolite of the protopanaxadiol-type saponins of Panax ginseng C.A. Meyer, has been reported to possess anti-tumor properties to inhibit angiogenesis and to induce tumor apoptosis. In the present study, we investigated the effect of Compound K on apoptosis and explored the underlying mechanisms involved in HL-60 human leukemia cells. We examined the effect of Compound K on the viabilities of various cancer cell lines using MTT assays. DAPI assay, Annexin V and PI double staining, Western blot assay and immunoprecipitation were used to determine the effect of Compound K on the induction of apoptosis. Compound K was found to inhibit the viability of HL-60 cells in a dose- and time-dependent manner with an IC 50 of 14 μM. Moreover, this cell death had typical features of apoptosis, that is, DNA fragmentation, DNA ladder formation, and the externalization of Annexin V targeted phosphatidylserine residues in HL-60 cells. In addition, compound-K induced a series of intracellular events associated with both the mitochondrial- and death receptor-dependent apoptotic pathways, namely, (1) the activation of caspases-3, -8, and -9; (2) the loss of mitochondrial membrane potential; (3) the release of cytochrome c and Smac/DIABLO to the cytosol; (4) the translocation of Bid and Bax to mitochondria; and (5) the downregulations of Bcl-2 and Bcl-xL. Furthermore, a caspase-8 inhibitor completely abolished caspase-3 activation, Bid cleavage, and subsequent DNA fragmentation by Compound K. Interestingly, the activation of caspase-3 and -8 and DNA fragmentation were significantly prevented in the presence of cycloheximide, suggesting that Compound K-induced apoptosis is dependent on de novo protein synthesis. The results indicate that caspase-8 plays a key role in Compound K-stimulated apoptosis via the activation of caspase-3 directly or indirectly through Bid cleavage, cytochrome c release, and caspase-9 activation

Compound K, a metabolite of ginseng saponin, induces apoptosis via caspase-8-dependent pathway in HL-60 human leukemia cells

Directory of Open Access Journals (Sweden)

Choi Jung-Hye

2009-12-01

Full Text Available Abstract Background Compound K [20-O-β-(D-glucopyranosyl-20(S-protopanaxadiol], a metabolite of the protopanaxadiol-type saponins of Panax ginseng C.A. Meyer, has been reported to possess anti-tumor properties to inhibit angiogenesis and to induce tumor apoptosis. In the present study, we investigated the effect of Compound K on apoptosis and explored the underlying mechanisms involved in HL-60 human leukemia cells. Methods We examined the effect of Compound K on the viabilities of various cancer cell lines using MTT assays. DAPI assay, Annexin V and PI double staining, Western blot assay and immunoprecipitation were used to determine the effect of Compound K on the induction of apoptosis. Results Compound K was found to inhibit the viability of HL-60 cells in a dose- and time-dependent manner with an IC50 of 14 μM. Moreover, this cell death had typical features of apoptosis, that is, DNA fragmentation, DNA ladder formation, and the externalization of Annexin V targeted phosphatidylserine residues in HL-60 cells. In addition, compound-K induced a series of intracellular events associated with both the mitochondrial- and death receptor-dependent apoptotic pathways, namely, (1 the activation of caspases-3, -8, and -9; (2 the loss of mitochondrial membrane potential; (3 the release of cytochrome c and Smac/DIABLO to the cytosol; (4 the translocation of Bid and Bax to mitochondria; and (5 the downregulations of Bcl-2 and Bcl-xL. Furthermore, a caspase-8 inhibitor completely abolished caspase-3 activation, Bid cleavage, and subsequent DNA fragmentation by Compound K. Interestingly, the activation of caspase-3 and -8 and DNA fragmentation were significantly prevented in the presence of cycloheximide, suggesting that Compound K-induced apoptosis is dependent on de novo protein synthesis. Conclusions The results indicate that caspase-8 plays a key role in Compound K-stimulated apoptosis via the activation of caspase-3 directly or indirectly through

Toxin-Induced Experimental Models of Learning and Memory Impairment.

Science.gov (United States)

More, Sandeep Vasant; Kumar, Hemant; Cho, Duk-Yeon; Yun, Yo-Sep; Choi, Dong-Kug

2016-09-01

Animal models for learning and memory have significantly contributed to novel strategies for drug development and hence are an imperative part in the assessment of therapeutics. Learning and memory involve different stages including acquisition, consolidation, and retrieval and each stage can be characterized using specific toxin. Recent studies have postulated the molecular basis of these processes and have also demonstrated many signaling molecules that are involved in several stages of memory. Most insights into learning and memory impairment and to develop a novel compound stems from the investigations performed in experimental models, especially those produced by neurotoxins models. Several toxins have been utilized based on their mechanism of action for learning and memory impairment such as scopolamine, streptozotocin, quinolinic acid, and domoic acid. Further, some toxins like 6-hydroxy dopamine (6-OHDA), 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and amyloid-β are known to cause specific learning and memory impairment which imitate the disease pathology of Parkinson's disease dementia and Alzheimer's disease dementia. Apart from these toxins, several other toxins come under a miscellaneous category like an environmental pollutant, snake venoms, botulinum, and lipopolysaccharide. This review will focus on the various classes of neurotoxin models for learning and memory impairment with their specific mechanism of action that could assist the process of drug discovery and development for dementia and cognitive disorders.

Plant-associated bacterial degradation of toxic organic compounds in soil.

LENUS (Irish Health Repository)

McGuinness, Martina

2009-08-01

A number of toxic synthetic organic compounds can contaminate environmental soil through either local (e.g., industrial) or diffuse (e.g., agricultural) contamination. Increased levels of these toxic organic compounds in the environment have been associated with human health risks including cancer. Plant-associated bacteria, such as endophytic bacteria (non-pathogenic bacteria that occur naturally in plants) and rhizospheric bacteria (bacteria that live on and near the roots of plants), have been shown to contribute to biodegradation of toxic organic compounds in contaminated soil and could have potential for improving phytoremediation. Endophytic and rhizospheric bacterial degradation of toxic organic compounds (either naturally occurring or genetically enhanced) in contaminated soil in the environment could have positive implications for human health worldwide and is the subject of this review.

Impaired glucose-induced thermogenesis and arterial norepinephrine response persist after weight reduction in obese humans

DEFF Research Database (Denmark)

Astrup, A; Andersen, T; Christensen, N J

1990-01-01

A reduced thermic response and an impaired activation of the sympathetic nervous system (SNS) has been reported after oral glucose in human obesity. It is, however, not known whether the reduced SNS activity returns to normal along with weight reduction. The thermic effect of glucose was lower...... in eight obese patients than in matched control subjects (1.7% vs 9.2%, p less than 0.002). The increase in arterial norepinephrine after glucose was also blunted in the obese patients. After a 30-kg weight loss their glucose and lipid profiles were markedly improved but the thermic effect of glucose...... was still lower than that of the control subjects (4.2%, p less than 0.001). The glucose-induced arterial norepinephrine response remained diminished in the reduced obese patients whereas the changes in plasma epinephrine were similar in all three groups. The results suggest that a defective SNS may...

Phenolic Compounds in Brassica Vegetables

Directory of Open Access Journals (Sweden)

Pablo Velasco

2010-12-01

Full Text Available Phenolic compounds are a large group of phytochemicals widespread in the plant kingdom. Depending on their structure they can be classified into simple phenols, phenolic acids, hydroxycinnamic acid derivatives and flavonoids. Phenolic compounds have received considerable attention for being potentially protective factors against cancer and heart diseases, in part because of their potent antioxidative properties and their ubiquity in a wide range of commonly consumed foods of plant origin. The Brassicaceae family includes a wide range of horticultural crops, some of them with economic significance and extensively used in the diet throughout the world. The phenolic composition of Brassica vegetables has been recently investigated and, nowadays, the profile of different Brassica species is well established. Here, we review the significance of phenolic compounds as a source of beneficial compounds for human health and the influence of environmental conditions and processing mechanisms on the phenolic composition of Brassica vegetables.

Permeability Barrier and Microstructure of Skin Lipid Membrane Models of Impaired Glucosylceramide Processing

OpenAIRE

Sochorov?, Michaela; Sta?kov?, Kl?ra; Pullmannov?, Petra; Kov??ik, Andrej; Zbytovsk?, Jarmila; V?vrov?, Kate?ina

2017-01-01

Ceramide (Cer) release from glucosylceramides (GlcCer) is critical for the formation of the skin permeability barrier. Changes in ?-glucocerebrosidase (GlcCer?ase) activity lead to diminished Cer, GlcCer accumulation and structural defects in SC lipid lamellae; however, the molecular basis for this impairment is not clear. We investigated impaired GlcCer-to-Cer processing in human Cer membranes to determine the physicochemical properties responsible for the barrier defects. Minor impairment (...

Human Platelet-Rich Plasma- and Extracellular Matrix-Derived Peptides Promote Impaired Cutaneous Wound Healing In Vivo

Science.gov (United States)

Demidova-Rice, Tatiana N.; Wolf, Lindsey; Deckenback, Jeffry; Hamblin, Michael R.; Herman, Ira M.

2012-01-01

Previous work in our laboratory has described several pro-angiogenic short peptides derived from endothelial extracellular matrices degraded by bacterial collagenase. Here we tested whether these peptides could stimulate wound healing in vivo. Our experiments demonstrated that a peptide created as combination of fragments of tenascin X and fibrillin 1 (comb1) applied into cranial dermal wounds created in mice treated with cyclophosphamide to impair wound healing, can improve the rate of wound closure. Furthermore, we identify and characterize a novel peptide (UN3) created and modified from two naturally-occurring peptides, which are present in human platelet-rich plasma. In vitro testing of UN3 demonstrates that it causes a 50% increase in endothelial proliferation, 250% increase in angiogenic response and a tripling of epithelial cell migration in response to injury. Results of in vivo experiments where comb1 and UN3 peptides were added together to cranial wounds in cyclophosphamide-treated mice leads to improvement of wound vascularization as shown by an increase of the number of blood vessels present in the wound beds. Application of the peptides markedly promotes cellular responses to injury and essentially restores wound healing dynamics to those of normal, acute wounds in the absence of cyclophosphamide impairment. Our current work is aimed at understanding the mechanisms underlying the stimulatory effects of these peptides as well as identification of the cellular receptors mediating these effects. PMID:22384158

Zebrafish chemical screening reveals the impairment of dopaminergic neuronal survival by cardiac glycosides.

Directory of Open Access Journals (Sweden)

Yaping Sun

Full Text Available Parkinson's disease is a neurodegenerative disorder characterized by the prominent degeneration of dopaminergic (DA neurons among other cell types. Here we report a first chemical screen of over 5,000 compounds in zebrafish, aimed at identifying small molecule modulators of DA neuron development or survival. We find that Neriifolin, a member of the cardiac glycoside family of compounds, impairs survival but not differentiation of both zebrafish and mammalian DA neurons. Cardiac glycosides are inhibitors of Na(+/K(+ ATPase activity and widely used for treating heart disorders. Our data suggest that Neriifolin impairs DA neuronal survival by targeting the neuronal enriched Na(+/K(+ ATPase α3 subunit (ATP1A3. Modulation of ionic homeostasis, knockdown of p53, or treatment with antioxidants protects DA neurons from Neriifolin-induced death. These results reveal a previously unknown effect of cardiac glycosides on DA neuronal survival and suggest that it is mediated through ATP1A3 inhibition, oxidative stress, and p53. They also elucidate potential approaches for counteracting the neurotoxicity of this valuable class of medications.

Bioprocesses for the Removal of Volatile Sulfur Compounds from Gas Streams

NARCIS (Netherlands)

Janssen, A.J.H.; bosch, van den P.L.M.; Leerdam, van R.C.; Graaff, de C.M.

2013-01-01

This chapter describes the biological removal of sulphur compounds from gas streams. First, an overview is given of the toxicity of sulphur compounds to animals and humans whereafter biological and industrial formation routes for (organic) sulphur compounds are given. Microbial degradation routes of

Endocrine disrupting compounds

DEFF Research Database (Denmark)

Bøgh, I B; Christensen, P; Dantzer, V

2001-01-01

of alkylphenols, these are disseminated in the environment with sewage sludge, and domestic animals and humans are likely to be exposed via the food chain. Using the pig as an in vivo model, we studied the effect of intrauterine exposure to tertiary octylphenol (OP) on essential reproductive parameters over 3......With the growing concern that environmental chemicals might impair human and animal fertility, it is important to investigate the possible influence of these substances on sexual differentiation and genital development of mammals. Many of these substances are suspected to interfere with endocrine...... processes, and exposure during critical periods of prenatal development might affect reproductive performance over several generations. Alkylphenols and their metabolites are lipophilic substances exerting apparent estrogenic action in in vitro and in vivo testing systems. With the widespread industrial use...

Veterinary Compounding: Regulation, Challenges, and Resources

OpenAIRE

Davidson, Gigi

2017-01-01

The spectrum of therapeutic need in veterinary medicine is large, and the availability of approved drug products for all veterinary species and indications is relatively small. For this reason, extemporaneous preparation, or compounding, of drugs is commonly employed to provide veterinary medical therapies. The scope of veterinary compounding is broad and focused primarily on meeting the therapeutic needs of companion animals and not food-producing animals in order to avoid human exposure to ...

Combined exposure to endocrine disrupting pesticides impairs parturition, causes pup mortality and affects sexual differentiation in rats

DEFF Research Database (Denmark)

Jacobsen, Pernille Rosenskjold; Christiansen, Sofie; Boberg, Julie

2010-01-01

Risk assessment is currently based on the no observed adverse effect levels (NOAELs) for single compounds. Humans are exposed to a mixture of chemicals and recent studies in our laboratory have shown that combined exposure to endocrine disrupters can cause adverse effects on male sexual development...... were gavaged during gestation and lactation with five doses of a mixture of the fungicides procymidone, mancozeb, epoxyconazole, tebuconazole and prochloraz. The mixture ratio was chosen according to the doses of each individual pesticide that produced no observable effects on pregnancy length and pup...... survival in our laboratory and the dose levels used ranged from 25 to 100% of this mixture. All dose levels caused increased gestation length and dose levels above 25% caused impaired parturition leading to markedly decreased number of live born offspring and high pup perinatal mortality. The sexual...

Interferon-gamma improves impaired dentinogenic and immunosuppressive functions of irreversible pulpitis-derived human dental pulp stem cells

Science.gov (United States)

Sonoda, Soichiro; Yamaza, Haruyoshi; Ma, Lan; Tanaka, Yosuke; Tomoda, Erika; Aijima, Reona; Nonaka, Kazuaki; Kukita, Toshio; Shi, Songtao; Nishimura, Fusanori; Yamaza, Takayoshi

2016-01-01

Clinically, irreversible pulpitis is treated by the complete removal of pulp tissue followed by replacement with artificial materials. There is considered to be a high potential for autologous transplantation of human dental pulp stem cells (DPSCs) in endodontic treatment. The usefulness of DPSCs isolated from healthy teeth is limited. However, DPSCs isolated from diseased teeth with irreversible pulpitis (IP-DPSCs) are considered to be suitable for dentin/pulp regeneration. In this study, we examined the stem cell potency of IP-DPSCs. In comparison with healthy DPSCs, IP-DPSCs expressed lower colony-forming capacity, population-doubling rate, cell proliferation, multipotency, in vivo dentin regeneration, and immunosuppressive activity, suggesting that intact IP-DPSCs may be inadequate for dentin/pulp regeneration. Therefore, we attempted to improve the impaired in vivo dentin regeneration and in vitro immunosuppressive functions of IP-DPSCs to enable dentin/pulp regeneration. Interferon gamma (IFN-γ) treatment enhanced in vivo dentin regeneration and in vitro T cell suppression of IP-DPSCs, whereas treatment with tumor necrosis factor alpha did not. Therefore, these findings suggest that IFN-γ may be a feasible modulator to improve the functions of impaired IP-DPSCs, suggesting that autologous transplantation of IFN-γ-accelerated IP-DPSCs might be a promising new therapeutic strategy for dentin/pulp tissue engineering in future endodontic treatment. PMID:26775677

Interferon-gamma improves impaired dentinogenic and immunosuppressive functions of irreversible pulpitis-derived human dental pulp stem cells.

Science.gov (United States)

Sonoda, Soichiro; Yamaza, Haruyoshi; Ma, Lan; Tanaka, Yosuke; Tomoda, Erika; Aijima, Reona; Nonaka, Kazuaki; Kukita, Toshio; Shi, Songtao; Nishimura, Fusanori; Yamaza, Takayoshi

2016-01-18

Clinically, irreversible pulpitis is treated by the complete removal of pulp tissue followed by replacement with artificial materials. There is considered to be a high potential for autologous transplantation of human dental pulp stem cells (DPSCs) in endodontic treatment. The usefulness of DPSCs isolated from healthy teeth is limited. However, DPSCs isolated from diseased teeth with irreversible pulpitis (IP-DPSCs) are considered to be suitable for dentin/pulp regeneration. In this study, we examined the stem cell potency of IP-DPSCs. In comparison with healthy DPSCs, IP-DPSCs expressed lower colony-forming capacity, population-doubling rate, cell proliferation, multipotency, in vivo dentin regeneration, and immunosuppressive activity, suggesting that intact IP-DPSCs may be inadequate for dentin/pulp regeneration. Therefore, we attempted to improve the impaired in vivo dentin regeneration and in vitro immunosuppressive functions of IP-DPSCs to enable dentin/pulp regeneration. Interferon gamma (IFN-γ) treatment enhanced in vivo dentin regeneration and in vitro T cell suppression of IP-DPSCs, whereas treatment with tumor necrosis factor alpha did not. Therefore, these findings suggest that IFN-γ may be a feasible modulator to improve the functions of impaired IP-DPSCs, suggesting that autologous transplantation of IFN-γ-accelerated IP-DPSCs might be a promising new therapeutic strategy for dentin/pulp tissue engineering in future endodontic treatment.

Applying Quality by Design Concepts to Pharmacy Compounding.

Science.gov (United States)

Timko, Robert J

2015-01-01

Compounding of medications is an important part of the practice of the pharmacy profession. Because compounded medications do not have U.S. Food and Drug Administration approval, a pharmacist has the responsibility to ensure that compounded medications are of suitable quality, safety, and efficacy. The Federal Government and numerous states have updated their laws and regulations regarding pharmacy compounding as a result of recent quality issues. Compounding pharmacists are expected to follow good preparation prodecures in their compounding practices in much the same way pharmaceutical manufacturers are required to follow Current Good Manufacturing Procedures as detailed in the United States Code of Federal Regulations. Application of Quality by Design concepts to the preparation process for a compounded medication can help in understanding the potential pitfalls and the means to mitigate their impact. The goal is to build quality into the compounding process to ensure that the resultant compounded prescription meets the human or animal patients' requirements.

Human exposure to endocrine disrupting compounds: Their role in reproductive systems, metabolic syndrome and breast cancer. A review.

Science.gov (United States)

Giulivo, Monica; Lopez de Alda, Miren; Capri, Ettore; Barceló, Damià

2016-11-01

Endocrine disrupting chemicals (EDCs) are released into the environment from different sources. They are mainly used in packaging industries, pesticides and food constituents. Clinical evidence, experimental models, and epidemiological studies suggest that EDCs have major risks for humans by targeting different organs and systems in the body (e.g. reproductive system, breast tissue, adipose tissue, pancreas, etc.). Due to the ubiquity of human exposure to these compounds the aim of this review is to describe the most recent data on the effects induced by phthalates, bisphenol A and parabens in a critical window of exposure: in utero, during pregnancy, infants, and children. The interactions and mechanisms of toxicity of EDCs in relation to human general health problems, especially those broadening the term of endocrine disruption to 'metabolic disruption', should be deeply investigated. These include endocrine disturbances, with particular reference to reproductive problems and breast, testicular and ovarian cancers, and metabolic diseases such as obesity or diabetes. Copyright © 2016 Elsevier Inc. All rights reserved.

Perceptions of Schooling, Pedagogy and Notation in the Lives of Visually-Impaired Musicians

Science.gov (United States)

Baker, David; Green, Lucy

2016-01-01

This article discusses findings on schooling, pedagogy and notation in the life-experiences of amateur and professional visually-impaired musicians/music teachers, and the professional experiences of sighted music teachers who work with visually-impaired learners. The study formed part of a broader UK Arts and Humanities Research Council funded…

PD-L1 Expression Induced by the 2009 Pandemic Influenza A(H1N1 Virus Impairs the Human T Cell Response

Directory of Open Access Journals (Sweden)

Nuriban Valero-Pacheco

2013-01-01

Full Text Available PD-L1 expression plays a critical role in the impairment of T cell responses during chronic infections; however, the expression of PD-L1 on T cells during acute viral infections, particularly during the pandemic influenza virus (A(H1N1pdm09, and its effects on the T cell response have not been widely explored. We found that A(H1N1pdm09 virus induced PD-L1 expression on human dendritic cells (DCs and T cells, as well as PD-1 expression on T cells. PD-L1 expression impaired the T cell response against A(H1N1pdm09 by promoting CD8+ T cell death and reducing cytokine production. Furthermore, we found increased PD-L1 expression on DCs and T cells from influenza-infected patients from the first and second 2009 pandemic waves in Mexico City. PD-L1 expression on CD8+ T cells correlated inversely with T cell proportions in patients infected with A(H1N1pdm09. Therefore, PD-L1 expression on DCs and T cells could be associated with an impaired T cell response during acute infection with A(H1N1pdm09 virus.

45 CFR 1308.12 - Eligibility criteria: Orthopedic impairment.

Science.gov (United States)

2010-10-01

... characterized by impaired ability to maneuver in educational or non-educational settings, to perform fine or gross motor activities, or to perform self-help skills and by adversely affected educational performance... DEVELOPMENT SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION FOR CHILDREN, YOUTH AND...

Cognitive impairment in patients with type 2 diabetes mellitus ...

African Journals Online (AJOL)

Cognitive impairment in patients with type 2 diabetes mellitus: Perspectives and ... may have a deteriorating effect on mental health including a decline in cognitive ... of Diabetes; Functional Foods and Human Diet; Quality of Life and Wellness ...

IMPAIRED MOBILITY OF VOCAL FOLDS - etiology and symptoms

Directory of Open Access Journals (Sweden)

Karlo Pintarić

2015-06-01

Full Text Available Paresis or paralysis of one or both vocal cords affects some significant aspects of a human life: breathing, swallowing and speech. The major causes for reduced mobility or even immobility are innervation damage, less often fixation of vocal cord or impaired mobility of crycoarytenoid joint. An injury of the superior or/and inferior laryngeal nerve can be a consequence of different medical procedures, tumor growth, trauma, infection, neurological disorders, radiation exposure, toxic damage, impaired circulation of the area or it is idiopathic. The symptoms are different in the case of unilateral and bilateral paresis of the vocal folds. They also depend on the cause for the impaired mobility. In the patients with unilateral vocal fold paresis, hoarseness and aspiration during swallowing are the leading symptoms. In the bilateral vocal fold paralysis, dyspnea prevails. 

A zinc-resistant human epithelial cell line is impaired in cadmium and manganese import

International Nuclear Information System (INIS)

Rousselet, Estelle; Richaud, Pierre; Douki, Thierry; Chantegrel, Jocelyne Garcia; Favier, Alain; Bouron, Alexandre; Moulis, Jean-Marc

2008-01-01

A human epithelial cell line (HZR) growing with high zinc concentrations has been analyzed for its ability to sustain high cadmium concentrations. Exposure to up to 200 μM of cadmium acetate for 24 h hardly impacted viability, whereas most of parental HeLa cells were killed by less than 10 μM of cadmium. Upon challenge by 35 fold higher cadmium concentrations than HeLa cells, HZR cells did not display increased DNA damage, increased protein oxidation, or changed intracellular cadmium localization. Rather, the main cause of resistance against cadmium was by avoiding cadmium entry into cells, which differs from that against zinc as the latter accumulates inside cells. The zinc-resistant phenotype of these cells was shown to also impair extracellular manganese uptake. Manganese and cadmium competed for entry into HeLa cells. Probing formerly identified cadmium or manganese transport systems in different animal cells did not evidence any significant change between HeLa and HZR cells. These results reveal zinc adaptation influences manganese and cadmium cellular traffic and they highlight previously unknown connections among homeostasis of divalent metals

Monitoring of selected skin- and breath-borne volatile organic compounds emitted from the human body using gas chromatography ion mobility spectrometry (GC-IMS).

Science.gov (United States)

Mochalski, Paweł; Wiesenhofer, Helmut; Allers, Maria; Zimmermann, Stefan; Güntner, Andreas T; Pineau, Nicolay J; Lederer, Wolfgang; Agapiou, Agapios; Mayhew, Christopher A; Ruzsanyi, Veronika

2018-02-15

Human smuggling and associated cross-border crimes have evolved as a major challenge for the European Union in recent years. Of particular concern is the increasing trend of smuggling migrants hidden inside shipping containers or trucks. Therefore, there is a growing demand for portable security devices for the non-intrusive and rapid monitoring of containers to detect people hiding inside. In this context, chemical analysis of volatiles organic compounds (VOCs) emitted from the human body is proposed as a locating tool. In the present study, an in-house made ion mobility spectrometer coupled with gas chromatography (GC-IMS) was used to monitor the volatile moieties released from the human body under conditions that mimic entrapment. A total of 17 omnipresent volatile compounds were identified and quantified from 35 ion mobility peaks corresponding to human presence. These are 7 aldehydes (acrolein, 2-methylpropanal, 3-methylbutanal, 2-ethacrolein, n-hexanal, n-heptanal, benzaldehyde), 3 ketones (acetone, 2-pentanone, 4-methyl-2-pentanone), 5 esters (ethyl formate, ethyl propionate, vinyl butyrate, butyl acetate, ethyl isovalerate), one alcohol (2-methyl-1-propanol) and one organic acid (acetic acid). The limits of detection (0.05-7.2 ppb) and relative standard deviations (0.6-11%) should be sufficient for detecting these markers of human presence in field conditions. This study shows that GC-IMS can be used as a portable field detector of hidden or entrapped people. Copyright © 2018 Elsevier B.V. All rights reserved.

Task-specific impairments and enhancements induced by magnetic stimulation of human visual area V5.

Science.gov (United States)

Walsh, V; Ellison, A; Battelli, L; Cowey, A

1998-03-22

Transcranial magnetic stimulation (TMS) can be used to simulate the effects of highly circumscribed brain damage permanently present in some neuropsychological patients, by reversibly disrupting the normal functioning of the cortical area to which it is applied. By using TMS we attempted to recreate deficits similar to those reported in a motion-blind patient and to assess the specificity of deficits when TMS is applied over human area V5. We used six visual search tasks and showed that subjects were impaired in a motion but not a form 'pop-out' task when TMS was applied over V5. When motion was present, but irrelevant, or when attention to colour and form were required, TMS applied to V5 enhanced performance. When attention to motion was required in a motion-form conjunction search task, irrespective of whether the target was moving or stationary, TMS disrupted performance. These data suggest that attention to different visual attributes involves mutual inhibition between different extrastriate visual areas.

Impaired STING Pathway in Human Osteosarcoma U2OS Cells Contributes to the Growth of ICP0-Null Mutant Herpes Simplex Virus.

Science.gov (United States)

Deschamps, Thibaut; Kalamvoki, Maria

2017-05-01

Human herpes simplex virus 1 (HSV-1) is a widespread pathogen, with 80% of the population being latently infected. To successfully evade the host, the virus has evolved strategies to counteract antiviral responses, including the gene-silencing and innate immunity machineries. The immediately early protein of the virus, infected cell protein 0 (ICP0), plays a central role in these processes. ICP0 blocks innate immunity, and one mechanism is by degrading hostile factors with its intrinsic E3 ligase activity. ICP0 also functions as a promiscuous transactivator, and it blocks repressor complexes to enable viral gene transcription. For these reasons, the growth of a ΔICP0 virus is impaired in most cells, except cells of the human osteosarcoma cell line U2OS, and it is only partially impaired in cells of the human osteosarcoma cell line Saos-2. We found that the two human osteosarcoma cell lines that supported the growth of the ΔICP0 virus failed to activate innate immune responses upon treatment with 2'3'-cyclic GAMP (2'3'-cGAMP), the natural agonist of STING (i.e., stimulator of interferon genes) or after infection with the ΔICP0 mutant virus. Innate immune responses were restored in these cells by transient expression of the STING protein but not after overexpression of interferon-inducible protein 16 (IFI16). Restoration of STING expression resulted in suppression of ΔICP0 virus gene expression and a decrease in viral yields. Overexpression of IFI16 also suppressed ΔICP0 virus gene expression, albeit to a lesser extent than STING. These data suggest that the susceptibility of U2OS and Saos-2 cells to the ΔICP0 HSV-1 is in part due to an impaired STING pathway. IMPORTANCE The DNA sensor STING plays pivotal role in controlling HSV-1 infection both in cell culture and in mice. The HSV-1 genome encodes numerous proteins that are dedicated to combat host antiviral responses. The immediate early protein of the virus ICP0 plays major role in this process as it targets

Effect of the Botanical Compound LCS101 on Chemotherapy-Induced Symptoms in Patients with Breast Cancer: A Case Series Report.

Science.gov (United States)

Samuels, Noah; Maimon, Yair; Zisk-Rony, Rachel Y

2013-01-01

The treatment of breast cancer invariably results in severe and often debilitating symptoms that can cause significant distress and severely impair daily function and quality-of-life (QOL). We treated a series of 20 female breast cancer patients with the botanical compound LCS101 as adjuvant to conventional chemotherapy. At the end of the treatment regimen, patients rated their symptoms. 70% reported that they had either no or mildly severe levels of fatigue; 60% none to mildly severe weakness; 85% none to mildly severe pain; 70% none to mildly severe nausea; and 80% none to mildly severe vomiting. Only 20% reported severe impairment of overall function, and only 40% severely impaired QOL. No toxic effects were attributed by patients to the LCS101 treatment, and 85% reported that they believed the botanical compound had helped reduce symptoms. The effects of LCS101 on clinical outcomes in breast cancer should be tested further using randomized controlled trials.

Esters of Bendamustine Are by Far More Potent Cytotoxic Agents than the Parent Compound against Human Sarcoma and Carcinoma Cells.

Directory of Open Access Journals (Sweden)

Stefan Huber

Full Text Available The alkylating agent bendamustine is approved for the treatment of hematopoietic malignancies such as non-Hodgkin lymphoma, chronic lymphocytic leukemia and multiple myeloma. As preliminary data on recently disclosed bendamustine esters suggested increased cytotoxicity, we investigated representative derivatives in more detail. Especially basic esters, which are positively charged under physiological conditions, were in the crystal violet and the MTT assay up to approximately 100 times more effective than bendamustine, paralleled by a higher fraction of early apoptotic cancer cells and increased expression of p53. Analytical studies performed with bendamustine and representative esters revealed pronounced cellular accumulation of the derivatives compared to the parent compound. In particular, the pyrrolidinoethyl ester showed a high enrichment in tumor cells and inhibition of OCT1- and OCT3-mediated transport processes, suggesting organic cation transporters to be involved. However, this hypothesis was not supported by the differential expression of OCT1 (SLC22A1 and OCT3 (SLC22A3, comparing a panel of human cancer cells. Bendamustine esters proved to be considerably more potent cytotoxic agents than the parent compound against a broad panel of human cancer cell types, including hematologic and solid malignancies (e.g. malignant melanoma, colorectal carcinoma and lung cancer, which are resistant to bendamustine. Interestingly, spontaneously immortalized human keratinocytes, as a model of "normal" cells, were by far less sensitive than tumor cells against the most potent bendamustine esters.

Tetrahydrocannabinol (THC) impairs encoding but not retrieval of verbal information.

Science.gov (United States)

Ranganathan, Mohini; Radhakrishnan, Rajiv; Addy, Peter H; Schnakenberg-Martin, Ashley M; Williams, Ashley H; Carbuto, Michelle; Elander, Jacqueline; Pittman, Brian; Andrew Sewell, R; Skosnik, Patrick D; D'Souza, Deepak Cyril

2017-10-03

Cannabis and agonists of the brain cannabinoid receptor (CB 1 R) produce acute memory impairments in humans. However, the extent to which cannabinoids impair the component processes of encoding and retrieval has not been established in humans. The objective of this analysis was to determine whether the administration of Δ 9 -Tetrahydrocannabinol (THC), the principal psychoactive constituent of cannabis, impairs encoding and/or retrieval of verbal information. Healthy subjects were recruited from the community. Subjects were administered the Rey-Auditory Verbal Learning Test (RAVLT) either before administration of THC (experiment #1) (n=38) or while under the influence of THC (experiment #2) (n=57). Immediate and delayed recall on the RAVLT was compared. Subjects received intravenous THC, in a placebo-controlled, double-blind, randomized manner at doses known to produce behavioral and subjective effects consistent with cannabis intoxication. Total immediate recall, short delayed recall, and long delayed recall were reduced in a statistically significant manner only when the RAVLT was administered to subjects while they were under the influence of THC (experiment #2) and not when the RAVLT was administered prior. THC acutely interferes with encoding of verbal memory without interfering with retrieval. These data suggest that learning information prior to the use of cannabis or cannabinoids is not likely to disrupt recall of that information. Future studies will be necessary to determine whether THC impairs encoding of non-verbal information, to what extent THC impairs memory consolidation, and the role of other cannabinoids in the memory-impairing effects of cannabis. Cannabinoids, Neural Synchrony, and Information Processing (THC-Gamma) http://clinicaltrials.gov/ct2/show/study/NCT00708994 NCT00708994 Pharmacogenetics of Cannabinoid Response http://clinicaltrials.gov/ct2/show/NCT00678730 NCT00678730. Copyright © 2017. Published by Elsevier Inc.

Antioxidant Activity of Inulin and Its Role in the Prevention of Human Colonic Muscle Cell Impairment Induced by Lipopolysaccharide Mucosal Exposure

Science.gov (United States)

Guarino, Michele Pier Luca; Locato, Vittoria; Cocca, Silvia; Cimini, Sara; Palma, Rossella; Alloni, Rossana; De Gara, Laura; Cicala, Michele

2014-01-01

Background Fructans, such as inulin, are dietary fibers which stimulate gastro-intestinal (GI) function acting as prebiotics. Lipopolysaccharide (LPS) impairs GI motility, through production of reactive oxygen species. The antioxidant activity of various fructans was tested and the protective effect of inulin on colonic smooth muscle cell (SMC) impairment, induced by exposure of human mucosa to LPS, was assessed in an ex vivo experimental model. Methods The antioxidant capacity of fructans was measured in an in vitro system that simulates cooking and digestion processes. Human colonic mucosa and submucosa, obtained from disease-free margins of resected segments for cancer, were sealed between two chambers, with the mucosal side facing upwards with Krebs solution with or without purified LPS from a pathogenic strain of Escherichia coli (O111:B4) and inulin (Frutafit IQ), and the submucosal side facing downwards into Krebs solution. The solutions on the submucosal side were collected following mucosal exposure to Krebs in the absence (N-undernatant) or presence of LPS (LPS-undernatant) or LPS+inulin (LPS+INU-undernatant). Undernatants were tested for their antioxidant activity and the effects on SMCs contractility. Inulin protective effects on mucosa and submucosa layers were assessed measuring the protein oxidation level in the experimental conditions analyzed. Results Antioxidant activity of inulin, which was significantly higher compared to simple sugars, remained unaltered despite cooking and digestion processes. Inulin protected the mucosal and submucosal layers against protein oxidation. Following exposure to LPS-undernatant, a significant decrease in maximal acetylcholine (Ach)-induced contraction was observed when compared to the contraction induced in cells incubated with the N-undernatant (4±1% vs 25±5% respectively, PInulin (35±5%). Conclusions Inulin protects the human colon mucosa from LPS-induced damage and this effect appears to be related to the

Impaired spontaneous anthropomorphizing despite intact perception and social knowledge

Science.gov (United States)

Heberlein, Andrea S.; Adolphs, Ralph

2004-01-01

Humans spontaneously imbue the world with social meaning: we see not only emotions and intentional behaviors in humans and other animals, but also anger in the movements of thunderstorms and willful sabotage in crashing computers. Converging evidence supports a role for the amygdala, a collection of nuclei in the temporal lobe, in processing emotionally and socially relevant information. Here, we report that a patient with bilateral amygdala damage described a film of animated shapes (normally seen as full of social content) in entirely asocial, geometric terms, despite otherwise normal visual perception. Control tasks showed that the impairment did not result from a global inability to describe social stimuli or a bias in language use, nor was a similar impairment observed in eight comparison subjects with damage to orbitofrontal cortex. This finding extends the role of the amygdala to the social attributions we make even to stimuli that are not explicitly social and, in so doing, suggests that the human capacity for anthropomorphizing draws on some of the same neural systems as do basic emotional responses. PMID:15123799

Role of Oxidative Stress in Male Reproductive Dysfunctions with Reference to Phthalate Compounds.

Science.gov (United States)

Sedha, Sapna; Kumar, Sunil; Shukla, Shruti

2015-11-14

A wide variety of environmental chemicals/xenobiotics including phthalates have been shown to cause oxidative stress targeting the endocrine system and cause reproductive anomalies. The present review describes various issues by oxidative stress causing male reproductive dysfunctions. Here in this review, the importance and role of phthalate compounds in male reproductive dysfunction has been well documented. One class of environmental endocrine disruptors is phthalates. Phthalate compounds are mostly used as plasticizers, which increase the flexibility, durability, longevity, and etc. of the plastics. Large-scale use of plastic products in our daily life as well as thousands of workers engaged in the manufacture of plastic and plastic products and recycling plastic industry are potentially exposed to these chemicals. Further, general population as well as vulnerable groups i.e. children and pregnant women are also exposed to these chemicals. Phthalates are among wide variety of environmental toxicants capable of compromising male fertility by inducing a state of oxidative stress in the testes. They may also generate reactive oxygen species (ROS) that may affect various physiological and reproductive functions. The available data points out that phthalate compounds may also induce oxidative stress in the male reproductive organs mainly testis and epididymis. They impair spermatogenic process by inducing oxidative stress and apoptosis in germ cells or target sertoli cells and thereby hamper spermatogenesis. They also impair the Leydig cell function by inducing ROS, thereby decreasing the levels of steroidogenic enzymes. Thus in utero and postnatal exposure to phthalate compounds might lead to decreased sperm count and various other reproductive anomalies in the young male.

A framework for communication between visually impaired, hearing impaired and speech impaired using arduino

Science.gov (United States)

Sujatha, R.; Khandelwa, Prakhar; Gupta, Anusha; Anand, Nayan

2017-11-01

A long time ago our society accepted the notion of treating people with disabilities not as unviable and disabled but as differently-abled, recognizing their skills beyond their disabilities. The next step has to be taken by our scientific community, that is, to normalize lives of the people with disabilities and make it so as if they are no different to us. The primary step in this direction would be to normalize communication between people. People with an impaired speech or impaired vision or impaired hearing face difficulties while having a casual conversation with others. Any form of communication feels so strenuous that the impaired end up communicating just the important information and avoid a casual conversation. To normalize conversation between the impaired we need a simple and compact device which facilitates the conversation by providing the information in the desired form.

Respiratory carcinogenicity assessment of soluble nickel compounds.

Science.gov (United States)

Oller, Adriana R

2002-10-01

The many chemical forms of nickel differ in physicochemical properties and biological effects. Health assessments for each main category of nickel species are needed. The carcinogenicity assessment of water-soluble nickel compounds has proven particularly difficult. Epidemiologic evidence indicates an association between inhalation exposures to nickel refinery dust containing soluble nickel compounds and increased risk of respiratory cancers. However, the nature of this association is unclear because of limitations of the exposure data, inconsistent results across cohorts, and the presence of mixed exposures to water-insoluble nickel compounds and other confounders that are known or suspected carcinogens. Moreover, well-conducted animal inhalation studies, where exposures were solely to soluble nickel, failed to demonstrate a carcinogenic potential. Similar negative results were seen in animal oral studies. A model exists that relates respiratory carcinogenic potential to the bioavailability of nickel ion at nuclear sites within respiratory target cells. This model helps reconcile human, animal, and mechanistic data for soluble nickel compounds. For inhalation exposures, the predicted lack of bioavailability of nickel ion at target sites suggests that water-soluble nickel compounds, by themselves, will not be complete human carcinogens. However, if inhaled at concentrations high enough to induce chronic lung inflammation, these compounds may enhance carcinogenic risks associated with inhalation exposure to other substances. Overall, the weight of evidence indicates that inhalation exposure to soluble nickel alone will not cause cancer; moreover, if exposures are kept below levels that cause chronic respiratory toxicity, any possible tumor-enhancing effects (particularly in smokers) would be avoided.

20 CFR 416.998 - If you become disabled by another impairment(s).

Science.gov (United States)

2010-04-01

... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false If you become disabled by another impairment... Disability Or Blindness § 416.998 If you become disabled by another impairment(s). If a new severe impairment(s) begins in or before the month in which your last impairment(s) ends, we will find that your...

20 CFR 404.1598 - If you become disabled by another impairment(s).

Science.gov (United States)

2010-04-01

... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false If you become disabled by another impairment... Disability § 404.1598 If you become disabled by another impairment(s). If a new severe impairment(s) begins in or before the month in which your last impairment(s) ends, we will find that your disability is...

Rejoining of DNA double-strand breaks in human fibroblasts and its impairment in one ataxia telangiectasia and two Fanconi strains

International Nuclear Information System (INIS)

Coquerelle, T.M.; Weibezahn, K.F.

1981-01-01

Using the technique of neutral elution through polycarbonate filters as a measure of DNA length, and hence of the number of double-strand breaks incurred as a result of radiation damage, we found that normal human fibroblasts rejoin 50% of all breaks within only 3 min (37 degrees C). This fast rejoining was impaired in fibroblasts from one patient with Ataxia telangiectasia and in fibroblasts from two patients with Fanconi's anemia. Also the number of residual breaks after several hours of repair was higher than in control cells. Other cases with the same diseases were normal in their rejoining of double-strand breaks

L-carnitine prevents memory impairment induced by chronic REM-sleep deprivation.

Science.gov (United States)

Alzoubi, Karem H; Rababa'h, Abeer M; Owaisi, Amani; Khabour, Omar F

2017-05-01

Sleep deprivation (SD) negatively impacts memory, which was related to oxidative stress induced damage. L-carnitine is a naturally occurring compound, synthesized endogenously in mammalian species and known to possess antioxidant properties. In this study, the effect of L-carnitine on learning and memory impairment induced by rapid eye movement sleep (REM-sleep) deprivation was investigated. REM-sleep deprivation was induced using modified multiple platform model (8h/day, for 6 weeks). Simultaneously, L-carnitine was administered (300mg/kg/day) intraperitoneally for 6 weeks. Thereafter, the radial arm water maze (RAWM) was used to assess spatial learning and memory. Additionally, the hippocampus levels of antioxidant biomarkers/enzymes: reduced glutathione (GSH), oxidized glutathione (GSSG), GSH/GSSG ratio, glutathione peroxidase (GPx), catalase, and superoxide dismutase (SOD) and thiobarbituric acid reactive substance (TBARS) were assessed. The results showed that chronic REM-sleep deprivation impaired both short- and long-term memory (Psleep deprivation induced reduction in the hippocampus ratio of GSH/GSSG, activity of catalase, GPx, and SOD. No change was observed in TBARS among tested groups (P>0.05). In conclusion, chronic REM-sleep deprivation induced memory impairment, and treatment with L-carnitine prevented this impairment through normalizing antioxidant mechanisms in the hippocampus. Copyright © 2017 Elsevier Inc. All rights reserved.

Dopamine transporter SPECT imaging of the peroral addicts of compound codeine phosphate solution

International Nuclear Information System (INIS)

Sun Taotao; Hu Shu; Jia Shaowei; Chen Qing; Fan Rong

2010-01-01

Objective: To study the damage to striatum in patients perorally addicted to compound codeine phosphate solution by using the brain dopamine transporter SPECT imaging. Methods: Patients perorally addicted to compound codeine phosphate solution (n = 29) and addicted to heroin (n = 27), as well as healthy volunteers (n = 31) were included in the study. Each of them underwent dopamine transporter (DAT) SPECT imaging with 99 Tc m -2β-[N, N'-bis-( 2- mercaptoethyl ) ethylenediamino] methyl, 3β-(4-chlorophenyl)tropane ( 99 Tc m -TRODAT-1). The striatum volume (V, cm 3 ), mass (m, g) and radioactivity ratio (Ra) of striatum to whole brain were calculated using physio-mathematical modeling method. Results: Bilateral striatum of healthy volunteers showed typical 'panda eyes' pattern and the distribution of DAT was uniform and symmetrical. Bilateral striatum of patients addicted to compound codeine phosphate showed impaired tracer uptake, similar to those addicted to heroin. The V, m and Ra of bilateral striatum of patients addicted to compound codeine phosphate were (23.68±4.94) cm 3 , (24.87±5.19) g and (5.01±0.88) %, respectively, which were significantly lower than those of healthy controls: (35.39 ±4.42) cm 3 ,(37.16±4.64) g and (7.93±0.86)% (t =-9.69, -9.69, - 13.01, all P =0.000), but significantly higher than those addicted to heroin: (18.87±4.66) cm 3 , (19.81±4.90) g and (4.26±1.02) % (t =3.74, 3.74, 2.96, P = 0.000, 0.000, 0.005). Conclusion: Long-term peroral intake of compound codeine phosphate solution may damage the function of cerebral striatum, which is someway similar to though less severe than, the impairment caused by heroin. (authors)

Increasing human Th17 differentiation through activation of orphan nuclear receptor retinoid acid-related orphan receptor γ (RORγ) by a class of aryl amide compounds.

Science.gov (United States)

Zhang, Wei; Zhang, Jing; Fang, Leiping; Zhou, Ling; Wang, Shuai; Xiang, Zhijun; Li, Yuan; Wisely, Bruce; Zhang, Guifeng; An, Gang; Wang, Yonghui; Leung, Stewart; Zhong, Zhong

2012-10-01

In a screen for small-molecule inhibitors of retinoid acid-related orphan receptor γ (RORγ), we fortuitously discovered that a class of aryl amide compounds behaved as functional activators of the interleukin 17 (IL-17) reporter in Jurkat cells. Three of these compounds were selected for further analysis and found to activate the IL-17 reporter with potencies of ∼0.1 μM measured by EC₅₀. These compounds were shown to directly bind to RORγ by circular dichroism-based thermal stability experiments. Furthermore, they can enhance an in vitro Th17 differentiation process in human primary T cells. As RORγ remains an orphan nuclear receptor, discovery of these aryl amide compounds as functional agonists will now provide pharmacological tools for us to dissect functions of RORγ and facilitate drug discovery efforts for immune-modulating therapies.

The role of familiarity in associative recognition of unitized compound word pairs.

Science.gov (United States)

Ahmad, Fahad N; Hockley, William E

2014-01-01

This study examined the effect of unitization and contribution of familiarity in the recognition of word pairs. Compound words were presented as word pairs and were contrasted with noncompound word pairs in an associative recognition task. In Experiments 1 and 2, yes-no recognition hit and false-alarm rates were significantly higher for compound than for noncompound word pairs, with no difference in discrimination in both within- and between-subject comparisons. Experiment 2 also showed that item recognition was reduced for words from compound compared to noncompound word pairs, providing evidence of the unitization of the compound pairs. A two-alternative forced-choice test used in Experiments 3A and 3B provided evidence that the concordant effect for compound word pairs was largely due to familiarity. A discrimination advantage for compound word pairs was also seen in these experiments. Experiment 4A showed that a different pattern of results is seen when repeated noncompound word pairs are compared to compound word pairs. Experiment 4B showed that memory for the individual items of compound word pairs was impaired relative to items in repeated and nonrepeated noncompound word pairs, and Experiment 5 demonstrated that this effect is eliminated when the elements of compound word pairs are not unitized. The concordant pattern seen in yes-no recognition and the discrimination advantage in forced-choice recognition for compound relative to noncompound word pairs is due to greater reliance on familiarity at test when pairs are unitized.

Impaired vascular function after exposure to diesel exhaust generated at urban transient running conditions

Directory of Open Access Journals (Sweden)

Westerholm Roger

2010-07-01

Full Text Available Abstract Background Traffic emissions including diesel engine exhaust are associated with increased respiratory and cardiovascular morbidity and mortality. Controlled human exposure studies have demonstrated impaired vascular function after inhalation of exhaust generated by a diesel engine under idling conditions. Objectives To assess the vascular and fibrinolytic effects of exposure to diesel exhaust generated during urban-cycle running conditions that mimic ambient 'real-world' exposures. Methods In a randomised double-blind crossover study, eighteen healthy male volunteers were exposed to diesel exhaust (approximately 250 μg/m3 or filtered air for one hour during intermittent exercise. Diesel exhaust was generated during the urban part of the standardized European Transient Cycle. Six hours post-exposure, vascular vasomotor and fibrinolytic function was assessed during venous occlusion plethysmography with intra-arterial agonist infusions. Measurements and Main Results Forearm blood flow increased in a dose-dependent manner with both endothelial-dependent (acetylcholine and bradykinin and endothelial-independent (sodium nitroprusside and verapamil vasodilators. Diesel exhaust exposure attenuated the vasodilatation to acetylcholine (P Conclusion Exposure to diesel exhaust generated under transient running conditions, as a relevant model of urban air pollution, impairs vasomotor function and endogenous fibrinolysis in a similar way as exposure to diesel exhaust generated at idling. This indicates that adverse vascular effects of diesel exhaust inhalation occur over different running conditions with varying exhaust composition and concentrations as well as physicochemical particle properties. Importantly, exposure to diesel exhaust under ETC conditions was also associated with a novel finding of impaired of calcium channel-dependent vasomotor function. This implies that certain cardiovascular endpoints seem to be related to general diesel

Occupant and Alcohol-Impaired Driving Deaths in States, 2003-2012

Data.gov (United States)

U.S. Department of Health & Human Services — Alcohol-Impaired Driving Fatalities 2003-2012; All persons killed in crashes involving a driver with BAC >= .08 g/dL. Occupant Fatalities 2003-2012; All occupants...

SPE-HPLC purification of endocrine disrupting compounds from human serum for assessment of xenoestrogenic activity

DEFF Research Database (Denmark)

Hjelmborg, P.S.; Ghisari, Mandana; Bonefeld-Jørgensen, Eva

2006-01-01

Assessment of xenoestrogenic activity in human serum samples requires the removal of endogenous sex hormones to assure that the activity measured originates from xenobiotic compounds only. Serum samples representing high, medium and lower accumulation of persistent organic pollutants (POPs) were...... measured by ERE-CALUX was validated and considered to be a valuable tool to assess the combined ER effect of lipophilic serum POPs where additive/synergistic and agonistic/antagonistic effects are integrated giving an overall estimate of exposure and bioactivity....... for the study. MVLN cells, stably transfected with an estrogen receptor (ER) luciferase reporter vector (ERE-CALUX), were exposed to the reconstituted SPE-HPLC extracts for determination of the integrated estrogenic activity. The effects of PCBs were analyzed by direct in vitro exposure of PCBs (138, 153...

20 CFR 220.184 - If the annuitant becomes disabled by another impairment(s).

Science.gov (United States)

2010-04-01

... impairment(s). 220.184 Section 220.184 Employees' Benefits RAILROAD RETIREMENT BOARD REGULATIONS UNDER THE... Activity or Medical Improvement § 220.184 If the annuitant becomes disabled by another impairment(s). If a new severe impairment(s) begins in or before the month in which the last impairment(s) ends, the Board...

Cytotoxic Compounds from Aloe megalacantha

Directory of Open Access Journals (Sweden)

Negera Abdissa

2017-07-01

Full Text Available Phytochemical investigation of the ethyl acetate extract of the roots of Aloe megalacantha led to the isolation of four new natural products—1,8-dimethoxynepodinol (1, aloesaponarin III (2, 10-O-methylchrysalodin (3 and methyl-26-O-feruloyl-oxyhexacosanate (4—along with ten known compounds. All purified metabolites were characterized by NMR, mass spectrometric analyses and comparison with literature data. The isolates were evaluated for their cytotoxic activity against a human cervix carcinoma cell line KB-3-1 and some of them exhibited good activity, with aloesaponarin II (IC50 = 0.98 µM being the most active compound.

Fast gradient HPLC method to determine compounds binding to human serum albumin. Relationships with octanol/water and immobilized artificial membrane lipophilicity.

Science.gov (United States)

Valko, Klara; Nunhuck, Shenaz; Bevan, Chris; Abraham, Michael H; Reynolds, Derek P

2003-11-01

A fast gradient HPLC method (cycle time 15 min) has been developed to determine Human Serum Albumin (HSA) binding of discovery compounds using chemically bonded protein stationary phases. The HSA binding values were derived from the gradient retention times that were converted to the logarithm of the equilibrium constants (logK HSA) using data from a calibration set of molecules. The method has been validated using literature plasma protein binding data of 68 known drug molecules. The method is fully automated, and has been used for lead optimization in more than 20 company projects. The HSA binding data obtained for more than 4000 compounds were suitable to set up global and project specific quantitative structure binding relationships that helped compound design in early drug discovery. The obtained HSA binding of known drug molecules were compared to the Immobilized Artificial Membrane binding data (CHI IAM) obtained by our previously described HPLC-based method. The solvation equation approach has been used to characterize the normal binding ability of HSA, and this relationship shows that compound lipophilicity is a significant factor. It was found that the selectivity of the "baseline" lipophilicity governing HSA binding, membrane interaction, and octanol/water partition are very similar. However, the effect of the presence of positive or negative charges have very different effects. It was found that negatively charged compounds bind more strongly to HSA than it would be expected from the lipophilicity of the ionized species at pH 7.4. Several compounds showed stronger HSA binding than can be expected from their lipophilicity alone, and comparison between predicted and experimental binding affinity allows the identification of compounds that have good complementarities with any of the known binding sites. Copyright 2003 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 92:2236-2248, 2003

Concentration of perfluorinated compounds and cotinine in human foetal organs, placenta, and maternal plasma

DEFF Research Database (Denmark)

Mamsen, Linn Salto; Jönsson, Bo A.G.; Lindh, Christian H.

2017-01-01

levels. Foetal exposure has previously been estimated from umbilical cord plasma, but the actual concentration in foetal organs has never been measured. Objectives The concentrations of 5 PFASs and cotinine – the primary metabolite of nicotine – were measured in human foetuses, placentas, and maternal...... plasma to evaluate to what extent these compounds were transferred from mother to foetus and to determine if the PFAS concentrations were associated with maternal cigarette smoking. Methods Thirty-nine Danish women who underwent legal termination of pregnancy before gestational week 12 were included; 24...... ratio for all five PFASs and cotinine. Smokers presented 99 ng/g cotinine in plasma, 108 ng/g in placenta, and 61 ng/g in foetal organs. No correlation between the maternal cotinine concentrations and PFAS concentrations was found. Conclusions PFASs were transferred from mother to foetus, however...

A biokinetic model of inhaled Cm compounds in dogs: Application to human exposure data

International Nuclear Information System (INIS)

Guilmette, R.A.; Mewhinney, J.A.

1989-01-01

Curium isotopes are major by-products in irradiated nuclear reactor fuel and comprise a significant fraction of the alpha-emitting radionuclide inventory. Although little use is currently being made of purified Cm sources, such usage is possible if reprocessing of spent fuel becomes feasible. Because little information is available on the biokinetics and dosimetry of inhaled Cm compounds, a study was conducted in which adult beagle dogs received a single inhalation exposure to either a monodisperse aerosol of 244Cm2O3 (1.4 micron activity median aerodynamic diameter [AMAD]; sigma g = 1.16) or a polydisperse aerosol of 244Cm (NO3)3 (1.1 micron AMAD; sigma g = 1.74). At times ranging from 4 h to 2 y after exposure, animals were sacrificed and their tissues analyzed for Cm content. The data describing the uptake and retention of 244Cm in the different organs and tissues and the measured rates of excretion of these dogs formed the basis on which a biokinetic model of Cm metabolism was constructed. This Cm model was based on a previously published model of the biokinetics of 241Am that was shown to be applicable to data from human cases of inhalation exposure to 241Am aerosols. This Cm model was found to be adequate to describe the biological distribution of Cm in dogs and was also applied to the sparse data from humans. Reasonable agreement was found between the model predictions for lung retention of Cm and for urinary excretion patterns in humans

Mutagenic activities of metal compounds in bacteria

Energy Technology Data Exchange (ETDEWEB)

Nishioka, H

1975-01-01

Environmental contaminations by certain metal compounds are bringing about serious problems to human health, including genetic hazards. It has been reported that some compounds of iron, manganese and mercury induce point mutations in microorganisms. Also it has been observed that those of aluminum, antimony, arsenic, cadmium, lead and tellurium cause chromosome aberrations in plants, insects and cultured human cells. The mechanism of mutation induction by these metals remains, however, still obscure. For screening of chemical mutagens, Kada et al, recently developed a simple and efficient method named rec-assay by observing differential growth sensitivities to drugs in wild and recombination-deficient strains of Bacillus subtilis. When a chemical is more inhibitory for Rec/sup -/ than for Rec/sup +/ cells, it is reasonable to suspect mutagenicity based on its DNA-damaging capacity. In the present report, 56 metal compounds were tested by the rec-assay. Compounds showing positive results in the assay such as potassium dichromate (K/sub 2/Cr/sub 2/O/sub 7/), ammonium molybdate ((NH/sub 4/)/sub 6/Mo/sub 7/O/sub 24/) and sodium arsenite (NaAsO/sub 2/) were then examined as to their capacities to induce reversions in E. coli Trp/sup -/ strains possessing different DNA repair pathways. 11 references, 3 tables.

Research advances in indicators for early diagnosis of liver cirrhosis patients with renal impairment

Directory of Open Access Journals (Sweden)

LU Lifang

2016-09-01

Full Text Available The liver is closely associated with the kidney, and liver injury in various stages can cause various kidney diseases to varying degrees, which further lead to renal impairment. Such renal impairment in the early stage is often functional and can be reversed by drugs, otherwise it can progress to hepatorenal syndrome, cause acute renal failure, and even threaten human life. The indicators such as serum creatinine and urea nitrogen have a limited effect in the early diagnosis of renal impairment and cannot be used for early monitoring and diagnosis of liver cirrhosis patients with renal impairment. Therefore, early monitoring of liver cirrhosis patients with renal impairment has always been a hot topic in this field. This article summarizes the research advances in the indicators for early diagnosis of renal impairment.

A rapid and sensitive screening system for human type I collagen with the aim of discovering potent anti-aging or anti-fibrotic compounds.

Science.gov (United States)

Hashem, Md Abul; Jun, Kyu-Yeon; Lee, Eunyoung; Lim, Soyun; Choo, Hea-Young Park; Kwon, Youngjoo

2008-12-31

This study was undertaken with the aim of developing an easy and quick means of analyzing the effect of various compounds on the synthesis and secretion of human type I collagen at the protein level. A modification of the ELISA method was used on HFF-1 cells. For the proof of concept, we used thirteen compounds most of which are known to be antioxidants. Each compound was tested at concentrations of 0, 10 and 100 microM on HFF-1 cells for 24 h. Thirteen sets of experiments for each compound were performed in ANOVA with three replicates. Duncan multiple range test (DMRT) was used to compare the mean values obtained from the treatment groups. From the results it was concluded that Vitamin C, undecylenic acid, conjugated linoleic acid, glycolic acid, and citric acid at 100 microM concentration could be used for anti-wrinkling or protection from premature aging, which requires enhancement of collagen synthesis. Lactic acid, EGCG, resveratrol, and retinol that can inhibit collagen synthesis effectively in a dose-dependent manner may be used for anti-fibrosis treatment purposes.

Exhaled human breath measurement method for assessing exposure to halogenated volatile organic compounds.

Science.gov (United States)

Pleil, J D; Lindstrom, A B

1997-05-01

The organic constituents of exhaled human breath are representative of blood-borne concentrations through gas exchange in the blood/breath interface in the lungs. The presence of specific compounds can be an indicator of recent exposure or represent a biological response of the subject. For volatile organic compounds (VOCs), sampling and analysis of breath is preferred to direct measurement from blood samples because breath collection is noninvasive, potentially infectious waste is avoided, and the measurement of gas-phase analytes is much simpler in a gas matrix rather than in a complex biological tissue such as blood. To exploit these advantages, we have developed the "single breath canister" (SBC) technique, a simple direct collection method for individual alveolar breath samples, and adapted conventional gas chromatography-mass spectrometry analytical methods for trace-concentration VOC analysis. The focus of this paper is to describe briefly the techniques for making VOC measurements in breath, to present some specific applications for which these methods are relevant, and to demonstrate how to estimate exposure to example VOCs on the basis of breath elimination. We present data from three different exposure scenarios: (a) vinyl chloride and cis-1,2-dichloroethene from showering with contaminated water from a private well, (b) chloroform and bromodichloromethane from high-intensity swimming in chlorinated pool water, and (c) trichloroethene from a controlled exposure chamber experiment. In all cases, for all subjects, the experiment is the same: preexposure breath measurement, exposure to halogenated VOC, and a postexposure time-dependent series of breath measurements. Data are presented only to demonstrate the use of the method and how to interpret the analytical results.

Exogenous HIV-1 Nef upsets the IFN-γ-induced impairment of human intestinal epithelial integrity.

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Maria Giovanna Quaranta

Full Text Available The mucosal tissues play a central role in the transmission of HIV-1 infection as well as in the pathogenesis of AIDS. Despite several clinical studies reported intestinal dysfunction during HIV infection, the mechanisms underlying HIV-induced impairments of mucosal epithelial barrier are still unclear. It has been postulated that HIV-1 alters enterocytic function and HIV-1 proteins have been detected in several cell types of the intestinal mucosa. In the present study, we analyzed the effect of the accessory HIV-1 Nef protein on human epithelial cell line.We used unstimulated or IFN-γ-stimulated Caco-2 cells, as a model for homeostatic and inflamed gastrointestinal tracts, respectively. We investigated the effect of exogenous recombinant Nef on monolayer integrity analyzing its uptake, transepithelial electrical resistance, permeability to FITC-dextran and the expression of tight junction proteins. Moreover, we measured the induction of proinflammatory mediators. Exogenous Nef was taken up by Caco-2 cells, increased intestinal epithelial permeability and upset the IFN-γ-induced reduction of transepithelial resistance, interfering with tight junction protein expression. Moreover, Nef inhibited IFN-γ-induced apoptosis and up-regulated TNF-α, IL-6 and MIP-3α production by Caco-2 cells while down-regulated IL-10 production. The simultaneous exposure of Caco-2 cells to Nef and IFN-γ did not affect cytokine secretion respect to untreated cells. Finally, we found that Nef counteracted the IFN-γ induced arachidonic acid cascade.Our findings suggest that exogenous Nef, perturbing the IFN-γ-induced impairment of intestinal epithelial cells, could prolong cell survival, thus allowing for accumulation of viral particles. Our results may improve the understanding of AIDS pathogenesis, supporting the discovery of new therapeutic interventions.

1,25-dihydroxyvitamin D3 impairs NF-κB activation in human naive B cells

International Nuclear Information System (INIS)

Geldmeyer-Hilt, Kerstin; Heine, Guido; Hartmann, Bjoern; Baumgrass, Ria; Radbruch, Andreas; Worm, Margitta

2011-01-01

Highlights: → In naive B cells, VDR activation by calcitriol results in reduced NF-κB p105 and p50 protein expression. → Ligating the VDR with calcitriol causes reduced nuclear translocation of NF-κB p65. → Reduced nuclear amount of p65 after calcitriol incubation results in reduced binding of p65 on the p105 promoter. → Thus, vitamin D receptor signaling may reduce or prevent activation of B cells and unwanted immune responses, e.g. in IgE dependent diseases such as allergic asthma. -- Abstract: 1α,25-dihydroxyvitamin D 3 (calcitriol), the bioactive metabolite of vitamin D, modulates the activation and inhibits IgE production of anti-CD40 and IL-4 stimulated human peripheral B cells. Engagement of CD40 results in NF-κB p50 activation, which is essential for the class switch to IgE. Herein, we investigated by which mechanism calcitriol modulates NF-κB mediated activation of human naive B cells. Naive B cells were predominantly targeted by calcitriol in comparison with memory B cells as shown by pronounced induction of the VDR target gene cyp24a1. Vitamin D receptor activation resulted in a strongly reduced p105/p50 protein and mRNA expression in human naive B cells. This effect is mediated by impaired nuclear translocation of p65 and consequently reduced binding of p65 to its binding site in the p105 promoter. Our data indicate that the vitamin D receptor reduces NF-κB activation by interference with NF-κB p65 and p105. Thus, the vitamin D receptor inhibits costimulatory signal transduction in naive B cells, namely by reducing CD40 signaling.

Antiosteoporotic compounds from seeds of Cuscuta chinensis.

Science.gov (United States)

Yang, Lijuan; Chen, Qianfeng; Wang, Fei; Zhang, Guolin

2011-05-17

The seeds of Cuscuta chinensis (Tu-Si-Zi, TSZ) have long been used for the treatment of osteoporosis in China and some Asian countries. The compounds in TSZ responsible for the antiosteoporotic activity are still poorly understood. The present study was designed to investigate the osteogenic compounds in TSZ, and to evaluate their antiosteoporotic effects in osteoblastic cells. Osteoblast-like UMR-106 cells were used for bioactivity-guided isolation of the active compounds. The activity of alkaline phosphatase (ALP) in UMR-106 cells was measured by p-nitrophenyl sodium phosphate assay. The proliferation of UMR-106 cells was assayed by Alamar-Blue method. Estrogenic activity of the extracts and isolated compounds was evaluated by activation of estrogen response element (ERE) luciferase reporter expression in HeLa cells co-transfected with human estrogen receptor subtypes (ERα or ERβ) expression vectors and 5×ERE luciferase reporter plasmid. Antiestrogenic activity of the extracts and isolated compounds were evaluated by activation of activator protein-1 (AP-1) luciferase reporter expression in HeLa cells co-transfected with human estrogen receptor subtypes (ERα or ERβ) expression vectors and 6×AP-1 luciferase reporter plasmid. ALP-guided fractionation led to the isolation of five known flavonoids, quercetin, kaempferol, isorhamnetin, hyperoside and astragalin from the crude ethanolic extract of TSZ. Further study showed that kaempferol and hyperoside significantly increased the ALP activity in UMR-106 cells. Astragalin promoted the proliferation of UMR-106 cells whereas other compounds had no such effect. The isolated compounds showed estrogenic activity but quercetin, kaempferol and isorhamnetin showed more potent ERβ agonist activity. However, compared with their ER agonist activity, only quercetin and kaempferol showed potent ER antagonist activity by activating ERα/β-mediated AP-1 reporter expression. Our findings validated the clinical use of TSZ in

Aging accelerates memory extinction and impairs memory restoration in Drosophila.

Science.gov (United States)

Chen, Nannan; Guo, Aike; Li, Yan

2015-05-15

Age-related memory impairment (AMI) is a phenomenon observed from invertebrates to human. Memory extinction is proposed to be an active inhibitory modification of memory, however, whether extinction is affected in aging animals remains to be elucidated. Employing a modified paradigm for studying memory extinction in fruit flies, we found that only the stable, but not the labile memory component was suppressed by extinction, thus effectively resulting in higher memory loss in aging flies. Strikingly, young flies were able to fully restore the stable memory component 3 h post extinction, while aging flies failed to do so. In conclusion, our findings reveal that both accelerated extinction and impaired restoration contribute to memory impairment in aging animals. Copyright © 2015 Elsevier Inc. All rights reserved.

Evaluation of the suitability of chromatographic systems to predict human skin permeation of neutral compounds.

Science.gov (United States)

Hidalgo-Rodríguez, Marta; Soriano-Meseguer, Sara; Fuguet, Elisabet; Ràfols, Clara; Rosés, Martí

2013-12-18

Several chromatographic systems (three systems of high-performance liquid chromatography and two micellar electrokinetic chromatography systems) besides the reference octanol-water partition system are evaluated by a systematic procedure previously proposed in order to know their ability to model human skin permeation. The precision achieved when skin-water permeability coefficients are correlated against chromatographic retention factors is predicted within the framework of the solvation parameter model. It consists in estimating the contribution of error due to the biological and chromatographic data, as well as the error coming from the dissimilarity between the human skin permeation and the chromatographic systems. Both predictions and experimental tests show that all correlations are greatly affected by the considerable uncertainty of the skin permeability data and the error associated to the dissimilarity between the systems. Correlations with much better predictive abilities are achieved when the volume of the solute is used as additional variable, which illustrates the main roles of both lipophilicity and size of the solute to penetrate through the skin. In this way, the considered systems are able to give precise estimations of human skin permeability coefficients. In particular, the HPLC systems with common C18 columns provide the best performances in emulating the permeation of neutral compounds from aqueous solution through the human skin. As a result, a methodology based on easy, fast, and economical HPLC measurements in a common C18 column has been developed. After a validation based on training and test sets, the method has been applied with good results to the estimation of skin permeation of several hormones and pesticides. Copyright © 2013 Elsevier B.V. All rights reserved.

Skin-mimetic chromatography for prediction of human percutaneous absorption of biologically active compounds occurring in medicinal plant extracts.

Science.gov (United States)

Stepnik, Katarzyna; Malinowska, Irena

2017-04-01

The main aim of this study was to predict quantitatively human percutaneous absorption of chosen compounds commonly occurring in plants which can be used as medicinal extracts in the drug and beauty industries. The most important human percutaneous descriptors, i.e. logK p (logarithm of the water/skin partition coefficient) and logJ max (logarithm of the maximum flux of solutes penetrating the skin), of fatty acids and polyphenols were determined using both in vitro and in silico methods. For in vitro determination of human percutaneous absorption, micellar liquid chromatography based on hexadecyltrimethylammonium bromide, sodium dodecyl sulfate and polyoxyethylene (23) lauryl ether (Brij35) was used. Human percutaneous absorption was characterized by entirely new QSAR/QRAR models based on retention, lipophilic, steric and electronic data as well as on the linear free energy relationship parameters. Many different correlations between human skin absorption and different physicochemical parameters were performed, e.g. the in silico estimated logK p value was correlated with the retention parameter logk w (logarithm of the retention factor extrapolated to pure water) from the systems imitating a cutaneous environment (R 2  = 0.92). Moreover, the influence of lipophilicity on percutaneous absorption was examined. The obtained correlation was excellent (R 2  = 0.95). Copyright © 2016 John Wiley & Sons, Ltd.

Inhibitory effects of black pepper (Piper nigrum) extracts and compounds on human tumor cell proliferation, cyclooxygenase enzymes, lipid peroxidation and nuclear transcription factor-kappa-B.

Science.gov (United States)

Liu, Yunbao; Yadev, Vivek R; Aggarwal, Bharat B; Nair, Muraleedharan G

2010-08-01

Black pepper (Piper nigrum) and hot pepper (Capsicum spp.) are widely used in traditional medicines. Although hot Capsicum spp. extracts and its active principles, capsaicinoids, have been linked with anticancer and anti-inflammatory activities, whether black pepper and its active principle exhibit similar activities is not known. In this study, we have evaluated the antioxidant, anti-inflammatory and anticancer activities of extracts and compounds from black pepper by using proinflammatory transcription factor NF-kappaB, COX-1 and -2 enzymes, human tumor cell proliferation and lipid peroxidation (LPO). The capsaicinoids, the alkylamides, isolated from the hot pepper Scotch Bonnet were also used to compare the bioactivities of alkylamides and piperine from black pepper. All compounds derived from black pepper suppressed TNF-induced NF-kappaB activation, but alkyl amides, compound 4 from black pepper and 5 from hot pepper, were most effective. The human cancer cell proliferation inhibitory activities of piperine and alklyl amides in Capsicum and black pepper were dose dependant. The inhibitory concentrations 50% (IC50) of the alklylamides were in the range 13-200 microg/mL. The extracts of black pepper at 200 microg/mL and its compounds at 25 microg/mL inhibited LPO by 45-85%, COX enzymes by 31-80% and cancer cells proliferation by 3.5-86.8%. Overall, these results suggest that black pepper and its constituents like hot pepper, exhibit anti-inflammatory, antioxidant and anticancer activities.

Cortical visual impairment

OpenAIRE

Koželj, Urša

2013-01-01

In this thesis we discuss cortical visual impairment, diagnosis that is in the developed world in first place, since 20 percent of children with blindness or low vision are diagnosed with it. The objectives of the thesis are to define cortical visual impairment and the definition of characters suggestive of the cortical visual impairment as well as to search for causes that affect the growing diagnosis of cortical visual impairment. There are a lot of signs of cortical visual impairment. ...

Vanadium Compounds as PTP Inhibitors

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Elsa Irving

2017-12-01

Full Text Available Phosphotyrosine signaling is regulated by the opposing actions of protein tyrosine kinases (PTKs and protein tyrosine phosphatases (PTPs. Here we discuss the potential of vanadium derivatives as PTP enzyme inhibitors and metallotherapeutics. We describe how vanadate in the V oxidized state is thought to inhibit PTPs, thus acting as a pan-inhibitor of this enzyme superfamily. We discuss recent developments in the biological and biochemical actions of more complex vanadium derivatives, including decavanadate and in particular the growing number of oxidovanadium compounds with organic ligands. Pre-clinical studies involving these compounds are discussed in the anti-diabetic and anti-cancer contexts. Although in many cases PTP inhibition has been implicated, it is also clear that many such compounds have further biochemical effects in cells. There also remain concerns surrounding off-target toxicities and long-term use of vanadium compounds in vivo in humans, hindering their progress through clinical trials. Despite these current misgivings, interest in these chemicals continues and many believe they could still have therapeutic potential. If so, we argue that this field would benefit from greater focus on improving the delivery and tissue targeting of vanadium compounds in order to minimize off-target toxicities. This may then harness their full therapeutic potential.

[Indoor air pollution by polychlorinated biphenyl compounds in permanently elastic sealants].

Science.gov (United States)

Burkhardt, U; Bork, M; Balfanz, E; Leidel, J

1990-10-01

A common cause for indoor pollution by polycholorinated biphenyls (PCB) are defective capacitors of luminous discharge lamps. This paper describes elastic sealing compounds as another source of PCB pollution in buildings. In several rooms of a large school building indoor concentrations of 1000 ng PCB/m3 and more were registered. The total PCB concentration in sealing compounds ranged between 124,000 and 327,000 ppm. Blood specimens drawn from the school's personnel did not show elevated PCB concentrations, but additional incorporation of PCB via the respiratory tract cannot be excluded. We do not presume that any impairment of the health has been caused by this pollutant, but we think that reduction of the PCB indoor concentrations would be advisable for prophylactic purposes. Attention should be given to so-called open PCB systems such as elastic sealing compounds. Although they have been prohibited 1978, there might be a widespread use in older buildings.

Pathogenic mutations of the human mitochondrial citrate carrier SLC25A1 lead to impaired citrate export required for lipid, dolichol, ubiquinone and sterol synthesis.

Science.gov (United States)

Majd, Homa; King, Martin S; Smith, Anthony C; Kunji, Edmund R S

2018-01-01

Missense mutations of the human mitochondrial citrate carrier, encoded by the SLC25A1 gene, lead to an autosomal recessive neurometabolic disorder characterised by neonatal-onset encephalopathy with severe muscular weakness, intractable seizures, respiratory distress, and lack of psychomotor development, often resulting in early death. Here, we have measured the effect of all twelve known pathogenic mutations on the transport activity. The results show that nine mutations abolish transport of citrate completely, whereas the other three reduce the transport rate by >70%, indicating that impaired citrate transport is the most likely primary cause of the disease. Some mutations may be detrimental to the structure of the carrier, whereas others may impair key functional elements, such as the substrate binding site and the salt bridge network on the matrix side of the carrier. To understand the consequences of impaired citrate transport on metabolism, the substrate specificity was also determined, showing that the human citrate carrier predominantly transports citrate, isocitrate, cis-aconitate, phosphoenolpyruvate and malate. Although D-2- and L-2 hydroxyglutaric aciduria is a metabolic hallmark of the disease, it is unlikely that the citrate carrier plays a significant role in the removal of hydroxyglutarate from the cytosol for oxidation to oxoglutarate in the mitochondrial matrix. In contrast, computer simulations of central metabolism predict that the export of citrate from the mitochondrion cannot be fully compensated by other pathways, restricting the cytosolic production of acetyl-CoA that is required for the synthesis of lipids, sterols, dolichols and ubiquinone, which in turn explains the severe disease phenotypes. Copyright © 2017. Published by Elsevier B.V.

Toxic compounds in honey.

Science.gov (United States)

Islam, Md Nazmul; Khalil, Md Ibrahim; Islam, Md Asiful; Gan, Siew Hua

2014-07-01

There is a wealth of information about the nutritional and medicinal properties of honey. However, honey may contain compounds that may lead to toxicity. A compound not naturally present in honey, named 5-hydroxymethylfurfural (HMF), may be formed during the heating or preservation processes of honey. HMF has gained much interest, as it is commonly detected in honey samples, especially samples that have been stored for a long time. HMF is a compound that may be mutagenic, carcinogenic and cytotoxic. It has also been reported that honey can be contaminated with heavy metals such as lead, arsenic, mercury and cadmium. Honey produced from the nectar of Rhododendron ponticum contains alkaloids that can be poisonous to humans, while honey collected from Andromeda flowers contains grayanotoxins, which can cause paralysis of limbs in humans and eventually leads to death. In addition, Melicope ternata and Coriaria arborea from New Zealand produce toxic honey that can be fatal. There are reports that honey is not safe to be consumed when it is collected from Datura plants (from Mexico and Hungary), belladonna flowers and Hyoscamus niger plants (from Hungary), Serjania lethalis (from Brazil), Gelsemium sempervirens (from the American Southwest), Kalmia latifolia, Tripetalia paniculata and Ledum palustre. Although the symptoms of poisoning due to honey consumption may differ depending on the source of toxins, most common symptoms generally include dizziness, nausea, vomiting, convulsions, headache, palpitations or even death. It has been suggested that honey should not be considered a completely safe food. Copyright © 2013 John Wiley & Sons, Ltd.

Is Toxoplasma Gondii Infection Related to Brain and Behavior Impairments in Humans? Evidence from a Population-Representative Birth Cohort.

Directory of Open Access Journals (Sweden)

Karen Sugden

Full Text Available Toxoplasma gondii (T. gondii is a protozoan parasite present in around a third of the human population. Infected individuals are commonly asymptomatic, though recent reports have suggested that infection might influence aspects of the host's behavior. In particular, Toxoplasma infection has been linked to schizophrenia, suicide attempt, differences in aspects of personality and poorer neurocognitive performance. However, these studies are often conducted in clinical samples or convenience samples.In a population-representative birth-cohort of individuals tested for presence of antibodies to T. gondii (N = 837 we investigated the association between infection and four facets of human behavior: neuropsychiatric disorder (schizophrenia and major depression, poor impulse control (suicidal behavior and criminality, personality, and neurocognitive performance. Suicide attempt was marginally more frequent among individuals with T. gondii seropositivity (p = .06. Seropositive individuals also performed worse on one out of 14 measures of neuropsychological function.On the whole, there was little evidence that T. gondii was related to increased risk of psychiatric disorder, poor impulse control, personality aberrations or neurocognitive impairment.

Exposure to multiple cholinergic pesticides impairs olfactory learning and memory in honeybees.

Science.gov (United States)

Williamson, Sally M; Wright, Geraldine A

2013-05-15

Pesticides are important agricultural tools often used in combination to avoid resistance in target pest species, but there is growing concern that their widespread use contributes to the decline of pollinator populations. Pollinators perform sophisticated behaviours while foraging that require them to learn and remember floral traits associated with food, but we know relatively little about the way that combined exposure to multiple pesticides affects neural function and behaviour. The experiments reported here show that prolonged exposure to field-realistic concentrations of the neonicotinoid imidacloprid and the organophosphate acetylcholinesterase inhibitor coumaphos and their combination impairs olfactory learning and memory formation in the honeybee. Using a method for classical conditioning of proboscis extension, honeybees were trained in either a massed or spaced conditioning protocol to examine how these pesticides affected performance during learning and short- and long-term memory tasks. We found that bees exposed to imidacloprid, coumaphos, or a combination of these compounds, were less likely to express conditioned proboscis extension towards an odor associated with reward. Bees exposed to imidacloprid were less likely to form a long-term memory, whereas bees exposed to coumaphos were only less likely to respond during the short-term memory test after massed conditioning. Imidacloprid, coumaphos and a combination of the two compounds impaired the bees' ability to differentiate the conditioned odour from a novel odour during the memory test. Our results demonstrate that exposure to sublethal doses of combined cholinergic pesticides significantly impairs important behaviours involved in foraging, implying that pollinator population decline could be the result of a failure of neural function of bees exposed to pesticides in agricultural landscapes.

Antioxidant evaluation of heterocyclic compounds by cytokinesis-block micronucleus assay.

Science.gov (United States)

Godevac, Dejan; Tesević, Vele; Vajs, Vlatka; Milosavljević, Slobodan; Stanković, Miroslava

2013-03-01

This article summarizes the results of using cytokinesis-block micronucleus (CBMN) assay to evaluate the antioxidant potential of heterocyclic compounds. Most studies were carried out with naturally occurring heterocyclic compounds such as plant polyphenols: flavonoids, xanthones, coumarins, and ellagitannins, or plant derived products (juices, extracts, supplements) rich in bioactive heterocyclic compounds. There are also some studies dealing with synthetic heterocyclic antioxidants. CBMN assay is an in vitro study that has been used to evaluate antioxidant and protective effects of heterocyclic compounds on induced chromosome aberration in human lymphocytes.

[Health effects of fluorine and its compounds].

Science.gov (United States)

Kono, K

1994-12-01

Fluoride, the ionic form of fluorine, is a natural component of the biosphere and 13th most abundant element in the crust of the earth. It is, therefore, found in a wide range of concentrations in virtually all inanimate and living things. Many trace elements perform a definite function in human metabolism and the question of the value of fluoride, always found in the body, has been raised. Much evidence suggesting that the inclusion of fluoride in drinking water has beneficial as well as adverse effects on human health was obtained. Either alone or in combination with calcium and/or vitamin D, it is used in high daily doses for the treatment of osteoporosis. Although organic fluorine compounds are used in medicine and commerce, the inorganic fluorine compounds are of greater importance toxicologically because they are more readily available. The major pathway of fluoride elimination from the human body is via the kidney. When renal function deteriorates, the ability to excrete fluoride markedly decreases, possibly resulting in greater retention of fluoride in the body. At this point, more research is needed to evaluate the effects of physiological variables on the fluoride metabolism in humans.

A high-throughput approach to identify compounds that impair envelope integrity in Escherichia coli

DEFF Research Database (Denmark)

Baker, Kristin Renee; Jana, Bimal; Franzyk, Henrik

2016-01-01

- to 125-fold) the MICs of erythromycin, fusidic acid, novobiocin and rifampin and displayed synergy (fractional inhibitory concentration index, antibiotics by checkerboard assays in two genetically distinct E. coli strains, including the high-risk multidrug-resistant, CTX-M-15-producing...... the discovery of antimicrobial helper drug candidates and targets that enhance the delivery of existing antibiotics by impairing envelope integrity in Gram-negative bacteria....

p53 modulates the AMPK inhibitor compound C induced apoptosis in human skin cancer cells

Energy Technology Data Exchange (ETDEWEB)

Huang, Shi-Wei [Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan (China); Wu, Chun-Ying [Division of Gastroenterology and Hepatology, Taichung Veterans General Hospital, Taichung, Taiwan (China); Wang, Yen-Ting [Department of Medical Research and Education, Cheng Hsin General Hospital, Taipei, Taiwan (China); Kao, Jun-Kai [Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan (China); Department of Pediatrics, Children' s Hospital, Changhua Christian Hospital, Changhua, Taiwan (China); Lin, Chi-Chen; Chang, Chia-Che; Mu, Szu-Wei; Chen, Yu-Yu [Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan (China); Chiu, Husan-Wen [Institute of Biotechnology, National Cheng-Kung University, Tainan, Taiwan (China); Agricultural Biotechnology Research Center, Academia Sinica, Taipei, Taiwan (China); Chang, Chuan-Hsun [Department of Surgical Oncology, Cheng Hsin General Hospital, Taipei, Taiwan (China); Department of Nutrition Therapy, Cheng Hsin General Hospital, Taipei, Taiwan (China); School of Nutrition and Health Sciences, Taipei Medical University, Taipei, Taiwan (China); Liang, Shu-Mei [Institute of Biotechnology, National Cheng-Kung University, Tainan, Taiwan (China); Agricultural Biotechnology Research Center, Academia Sinica, Taipei, Taiwan (China); Chen, Yi-Ju [Department of Dermatology, Taichung Veterans General Hospital, Taichung, Taiwan (China); Huang, Jau-Ling [Department of Bioscience Technology, Chang Jung Christian University, Tainan, Taiwan (China); Shieh, Jeng-Jer, E-mail: shiehjj@vghtc.gov.tw [Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan (China); Department of Education and Research, Taichung Veterans General Hospital, Taichung, Taiwan (China)

2013-02-15

Compound C, a well-known inhibitor of the intracellular energy sensor AMP-activated protein kinase (AMPK), has been reported to cause apoptotic cell death in myeloma, breast cancer cells and glioma cells. In this study, we have demonstrated that compound C not only induced autophagy in all tested skin cancer cell lines but also caused more apoptosis in p53 wildtype skin cancer cells than in p53-mutant skin cancer cells. Compound C can induce upregulation, phosphorylation and nuclear translocalization of the p53 protein and upregulate expression of p53 target genes in wildtype p53-expressing skin basal cell carcinoma (BCC) cells. The changes of p53 status were dependent on DNA damage which was caused by compound C induced reactive oxygen species (ROS) generation and associated with activated ataxia-telangiectasia mutated (ATM) protein. Using the wildtype p53-expressing BCC cells versus stable p53-knockdown BCC sublines, we present evidence that p53-knockdown cancer cells were much less sensitive to compound C treatment with significant G2/M cell cycle arrest and attenuated the compound C-induced apoptosis but not autophagy. The compound C induced G2/M arrest in p53-knockdown BCC cells was associated with the sustained inactive Tyr15 phosphor-Cdc2 expression. Overall, our results established that compound C-induced apoptosis in skin cancer cells was dependent on the cell's p53 status. - Highlights: ► Compound C caused more apoptosis in p53 wildtype than p53-mutant skin cancer cells. ► Compound C can upregulate p53 expression and induce p53 activation. ► Compound C induced p53 effects were dependent on ROS induced DNA damage pathway. ► p53-knockdown attenuated compound C-induced apoptosis but not autophagy. ► Compound C-induced apoptosis in skin cancer cells was dependent on p53 status.

p53 modulates the AMPK inhibitor compound C induced apoptosis in human skin cancer cells

International Nuclear Information System (INIS)

Huang, Shi-Wei; Wu, Chun-Ying; Wang, Yen-Ting; Kao, Jun-Kai; Lin, Chi-Chen; Chang, Chia-Che; Mu, Szu-Wei; Chen, Yu-Yu; Chiu, Husan-Wen; Chang, Chuan-Hsun; Liang, Shu-Mei; Chen, Yi-Ju; Huang, Jau-Ling; Shieh, Jeng-Jer

2013-01-01

Compound C, a well-known inhibitor of the intracellular energy sensor AMP-activated protein kinase (AMPK), has been reported to cause apoptotic cell death in myeloma, breast cancer cells and glioma cells. In this study, we have demonstrated that compound C not only induced autophagy in all tested skin cancer cell lines but also caused more apoptosis in p53 wildtype skin cancer cells than in p53-mutant skin cancer cells. Compound C can induce upregulation, phosphorylation and nuclear translocalization of the p53 protein and upregulate expression of p53 target genes in wildtype p53-expressing skin basal cell carcinoma (BCC) cells. The changes of p53 status were dependent on DNA damage which was caused by compound C induced reactive oxygen species (ROS) generation and associated with activated ataxia-telangiectasia mutated (ATM) protein. Using the wildtype p53-expressing BCC cells versus stable p53-knockdown BCC sublines, we present evidence that p53-knockdown cancer cells were much less sensitive to compound C treatment with significant G2/M cell cycle arrest and attenuated the compound C-induced apoptosis but not autophagy. The compound C induced G2/M arrest in p53-knockdown BCC cells was associated with the sustained inactive Tyr15 phosphor-Cdc2 expression. Overall, our results established that compound C-induced apoptosis in skin cancer cells was dependent on the cell's p53 status. - Highlights: ► Compound C caused more apoptosis in p53 wildtype than p53-mutant skin cancer cells. ► Compound C can upregulate p53 expression and induce p53 activation. ► Compound C induced p53 effects were dependent on ROS induced DNA damage pathway. ► p53-knockdown attenuated compound C-induced apoptosis but not autophagy. ► Compound C-induced apoptosis in skin cancer cells was dependent on p53 status

Treatment with 1,25-dihydroxyvitamin D3 reduces impairment of human osteoblast functions during cellular aging in culture

DEFF Research Database (Denmark)

Kveiborg, M.; Rattan, Suresh; Eriksen, E.F.

2001-01-01

is due to impaired responsiveness to calcitriol known to be important for the regulation of biological activities of the osteoblasts. Thus, we examined changes in vitamin D receptor (VDR) system and the osteoblastic responses to calcitriol treatment during in vitro osteoblast aging. We found no change...... in the amount of VDR at either steady state mRNA level or protein level with increasing in vitro osteoblast age and examination of VDR localization, nuclear translocation and DNA binding activity revealed no in vitro age-related changes. Furthermore, calcitriol (10(-8)M) treatment of early-passage osteoblastic......Adequate responses to various hormones, such as 1,25-dihydroxyvitamin D(3) (calcitriol) are a prerequisite for optimal osteoblast functions. We have previously characterized several human diploid osteoblastic cell lines that exhibit typical in vitro aging characteristics during long...

Five new compounds from the fungus Ganoderma petchii.

Science.gov (United States)

Dai, Wei-Feng; Guo, Ping-Xia; Tu, Zheng-Chao; Li, Rong-Tao; Cheng, Yong-Xian

2015-10-01

The fungal species of the genus Ganoderma attracted great interest in the last decades. Our recent investigation on Ganoderma petchii afforded five new compounds, (-)-petchioics A and B (1 and 2), petchiates A and B (3 and 4), petchine (5), and a known compound. The structures of the new compounds were elucidated on the basis of spectroscopic data. The absolute configurations of 1 and 2 were assigned by computational methods. Biological activities of these isolates towards human cancer cells, COX-1/2, and influenza virus were evaluated. Copyright © 2015 Elsevier B.V. All rights reserved.

Lipodystrophy in human immunodeficiency virus patients impairs insulin action and induces defects in beta-cell function

DEFF Research Database (Denmark)

Andersen, Ove; Haugaard, Steen B; Andersen, Ulrik B

2003-01-01

similar between study groups. A hyperinsulinemic euglycemic clamp showed an impaired glucose disposal rate (GDR) in HALS patients (5.6 v 8.3 mg glucose/min. kg(FFM), P =.0006). As demonstrated by indirect calorimetry, HALS patients showed an impaired nonoxidative glucose metabolism (NOGM, 2.2 v 4.2, P...

Prioritizing pesticide compounds for analytical methods development

Science.gov (United States)

Norman, Julia E.; Kuivila, Kathryn; Nowell, Lisa H.

2012-01-01

The U.S. Geological Survey (USGS) has a periodic need to re-evaluate pesticide compounds in terms of priorities for inclusion in monitoring and studies and, thus, must also assess the current analytical capabilities for pesticide detection. To meet this need, a strategy has been developed to prioritize pesticides and degradates for analytical methods development. Screening procedures were developed to separately prioritize pesticide compounds in water and sediment. The procedures evaluate pesticide compounds in existing USGS analytical methods for water and sediment and compounds for which recent agricultural-use information was available. Measured occurrence (detection frequency and concentrations) in water and sediment, predicted concentrations in water and predicted likelihood of occurrence in sediment, potential toxicity to aquatic life or humans, and priorities of other agencies or organizations, regulatory or otherwise, were considered. Several existing strategies for prioritizing chemicals for various purposes were reviewed, including those that identify and prioritize persistent, bioaccumulative, and toxic compounds, and those that determine candidates for future regulation of drinking-water contaminants. The systematic procedures developed and used in this study rely on concepts common to many previously established strategies. The evaluation of pesticide compounds resulted in the classification of compounds into three groups: Tier 1 for high priority compounds, Tier 2 for moderate priority compounds, and Tier 3 for low priority compounds. For water, a total of 247 pesticide compounds were classified as Tier 1 and, thus, are high priority for inclusion in analytical methods for monitoring and studies. Of these, about three-quarters are included in some USGS analytical method; however, many of these compounds are included on research methods that are expensive and for which there are few data on environmental samples. The remaining quarter of Tier 1

Experimental setup and analytical methods for the non-invasive determination of volatile organic compounds, formaldehyde and NOx in exhaled human breath

International Nuclear Information System (INIS)

Riess, Ulrich; Tegtbur, Uwe; Fauck, Christian; Fuhrmann, Frank; Markewitz, Doreen; Salthammer, Tunga

2010-01-01

Different analytical devices were tested and evaluated for their suitability of breath gas analysis by examining the physiological parameters and chemical substances in the exhaled breath of ten healthy probands during light cycling in dependence of methanol-rich nutrition. The probands exercised under normal breathing conditions on a bicycle ergometer. Breath air was exhaled into a glass cylinder and collected under steady-state conditions. Non-invasively measured parameters were pulse rate, breath frequency, temperature, relative humidity, NO x , total volatile organic compounds (TVOC PAS ), carbon dioxide (CO 2 ), formaldehyde, methanol, acetaldehyde, acetone, isoprene and volatile organic compounds (VOCs). Methanol rich food and beverages strongly influenced the concentration of methanol and other organic substances in human breath. On the other hand, nutrition and smoking had no clear effect on the physical conditions of the probands. The proton transfer reaction mass spectrometry (PTR-MS) method was found to be very suitable for the analysis of breath gas but the m/z 31, if assigned to formaldehyde, is sensitive to interferences. The time vs. concentration curves of nitric oxide showed sudden peaks up to 120 ppb in most of the measurements. In one case a strong interference of the NO x signal was observed. The time resolved analysis of exhaled breath gas is of high capability and significance for different applications if reliable analytical techniques are used. Some compounds like nitric oxide (NO), methanol, different VOCs as well as sum parameters like TVOC PAS are especially suitable as markers. Formaldehyde, which is rapidly metabolized in the human body, could be measured reliably as a trace component by the acetylacetone (acac) method but not by PTR-MS.

Sleep, Torpor and Memory Impairment

Science.gov (United States)

Palchykova, S.; Tobler, I.

It is now well known that daily torpor induces a sleep deficit. Djungarian hamsters emerging from this hypometabolic state spend most of the time in sleep. This sleep is characterized by high initial values of EEG slow-wave activity (SWA) that monotonically decline during recovery sleep. These features resemble the changes seen in numerous species during recovery after prolonged wakefulness or sleep deprivation (SD). When hamsters are totally or partially sleep deprived immediately after emerging from torpor, an additional increase in SWA can be induced. It has been therefore postulated, that these slow- waves are homeostatically regulated, as predicted by the two-process model of sleep regulation, and that during daily torpor a sleep deficit is accumulated as it is during prolonged waking. The predominance of SWA in the frontal EEG observed both after SD and daily torpor provides further evidence for the similarity of these conditions. It has been shown in several animal and human studies that sleep can enhance memory consolidation, and that SD leads to memory impairment. Preliminary data obtained in the Djungarian hamster showed that both SD and daily torpor result in object recognition deficits. Thus, animals subjected to SD immediately after learning, or if they underwent an episode of daily torpor between learning and retention, displayed impaired recognition memory for complex object scenes. The investigation of daily torpor can reveal mechanisms that could have important implications for hypometabolic state induction in other mammalian species, including humans.

Impaired Phosphate Tolerance Revealed With an Acute Oral Challenge.

Science.gov (United States)

Turner, Mandy E; White, Christine A; Hopman, Wilma M; Ward, Emilie C; Jeronimo, Paul S; Adams, Michael A; Holden, Rachel M

2018-01-01

Elevated serum phosphate is consistently linked with cardiovascular disease (CVD) events and mortality in the setting of normal and impaired kidney function. However, serum phosphate does not often exceed the upper limit of normal until glomerular filtration rate (GFR) falls below 30 mL/min/m 2 . It was hypothesized that the response to an oral, bioavailable phosphate load will unmask impaired phosphate tolerance, a maladaptation not revealed by baseline serum phosphate concentrations. In this study, rats with varying kidney function as well as normo-phosphatemic human subjects, with inulin-measured GFR (13.2 to 128.3mL/min), received an oral phosphate load. Hormonal and urinary responses were evaluated over 2 hours. Results revealed that the more rapid elevation of serum phosphate was associated with subjects and rats with higher levels of kidney function, greater responsiveness to acute changes in parathyroid hormone (PTH), and significantly more urinary phosphate at 2 hours. In humans, increases in urinary phosphate to creatinine ratio did not correlate with baseline serum phosphate concentrations but did correlate strongly to early increase of serum phosphate. The blunted rise in serum phosphate in rats with CKD was not the result of altered absorption. This result suggests acute tissue deposition may be altered in the setting of kidney function impairment. Early recognition of impaired phosphate tolerance could translate to important interventions, such as dietary phosphate restriction or phosphate binders, being initiated at much higher levels of kidney function than is current practice. © 2017 American Society for Bone and Mineral Research. © 2017 American Society for Bone and Mineral Research.

Antioxidant activity of inulin and its role in the prevention of human colonic muscle cell impairment induced by lipopolysaccharide mucosal exposure.

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Valentina Pasqualetti

Full Text Available BACKGROUND: Fructans, such as inulin, are dietary fibers which stimulate gastro-intestinal (GI function acting as prebiotics. Lipopolysaccharide (LPS impairs GI motility, through production of reactive oxygen species. The antioxidant activity of various fructans was tested and the protective effect of inulin on colonic smooth muscle cell (SMC impairment, induced by exposure of human mucosa to LPS, was assessed in an ex vivo experimental model. METHODS: The antioxidant capacity of fructans was measured in an in vitro system that simulates cooking and digestion processes. Human colonic mucosa and submucosa, obtained from disease-free margins of resected segments for cancer, were sealed between two chambers, with the mucosal side facing upwards with Krebs solution with or without purified LPS from a pathogenic strain of Escherichia coli (O111:B4 and inulin (Frutafit IQ, and the submucosal side facing downwards into Krebs solution. The solutions on the submucosal side were collected following mucosal exposure to Krebs in the absence (N-undernatant or presence of LPS (LPS-undernatant or LPS+inulin (LPS+INU-undernatant. Undernatants were tested for their antioxidant activity and the effects on SMCs contractility. Inulin protective effects on mucosa and submucosa layers were assessed measuring the protein oxidation level in the experimental conditions analyzed. RESULTS: Antioxidant activity of inulin, which was significantly higher compared to simple sugars, remained unaltered despite cooking and digestion processes. Inulin protected the mucosal and submucosal layers against protein oxidation. Following exposure to LPS-undernatant, a significant decrease in maximal acetylcholine (Ach-induced contraction was observed when compared to the contraction induced in cells incubated with the N-undernatant (4±1% vs 25±5% respectively, P<0.005 and this effect was completely prevented by pre-incubation of LPS with Inulin (35±5%. CONCLUSIONS: Inulin protects

Antioxidative Effects of Phenolic Compounds of Mushroom Mycelia in Simulated Regions of the Human Colon, In Vitro Study

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Vamanu Emanuel

2018-03-01

Full Text Available Many compounds in mushrooms are biologically active; however, the in vivo actions of their metabolites are poorly understood. An in vitro system, GIS1, was used to simulate the fermentation action of microbiota in each colon region. We used MycoPo, a natural product obtained from the lyophilized mycelia of different Pleurotus ostreatus species to determine the biological effects in human-colon regions. Controls (Lentinula edodes mycelia; dried basidia of Agaricus brunnescens were chosen to confirm the biological activity of P. ostreatus mycelia in vitro. We measured total antioxidant capacity and ferric ion-reducing antioxidant power (FRAP in simulated colon regions to identify antioxidant compounds, and undertook in vitro gastrointestinal simulation and microbiological analyses. The highest FRAP was found for the ascending colon, and the antioxidant effect was higher when MycoPo was administered. A. brunnescens consumption resulted in low total antioxidant capacity. Polyphenol content was correlated with the antioxidant status and microbial composition of microbiota. Total polyphenolic content was higher after A. brunnescens consumption, and four types of polyphenols were identified by high-performance liquid chromatography. Major phenolic acids were gentisic acid, homogentisic acid, and small amounts of caffeic acid. The Enterobacteriaceae species populations varied greatly across the three parts of the colon. We noted a significant (p0.85. These data suggest a direct relationship between favorable bacterial strains and availability of bioactive compounds, with specificity for each colon region.

'Non-vocalization': a phonological error process in the speech of severely and profoundly hearing impaired adults, from the point of view of the theory of phonology as human behaviour.

Science.gov (United States)

Halpern, Orly; Tobin, Yishai

2008-01-01

'Non-vocalization' (N-V) is a newly described phonological error process in hearing impaired speakers. In N-V the hearing impaired person actually articulates the phoneme but without producing a voice. The result is an error process looking as if it is produced but sounding as if it is omitted. N-V was discovered by video recording the speech of two groups, profoundly and severely hearing impaired adults in four elicitation tasks of varying difficulty, and analysing 2065 phonological error processes (substitutions, omissions, and N-V) according to 24 criteria resulting in 49,560 data points. Results, which are discussed in view of the theory 'Phonology as Human Behaviour' (PHB), indicate that: (a) The more communicative the error process was; the more effort was made for its production and the more frequent its distribution; (b) The easier the elicitation task was, the more frequent the use of communicative error processes; c) The more difficult the elicitation task was, the more frequent the use of the relatively less communicative and easier to produce error processes; and d) The process of N-V functioned like a communicative error process for the group of profoundly hearing impaired adults.

Effect of Phenolic Compounds from Elderflowers on Glucose- and Fatty Acid Uptake in Human Myotubes and HepG2-Cells

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Giang Thanh Thi Ho

2017-01-01

Full Text Available Type 2 diabetes (T2D is manifested by progressive metabolic impairments in tissues such as skeletal muscle and liver, and these tissues become less responsive to insulin, leading to hyperglycemia. In the present study, stimulation of glucose and oleic acid uptake by elderflower extracts, constituents and metabolites were tested in vitro using the HepG2 hepatocellular liver carcinoma cell line and human skeletal muscle cells. Among the crude extracts, the 96% EtOH extract showed the highest increase in glucose and oleic acid uptake in human skeletal muscle cells and HepG2-cells. The flavonoids and phenolic acids contained therein were potent stimulators of glucose and fatty acid uptake in a dose-dependent manner. Most of the phenolic constituents and several of the metabolites showed high antioxidant activity and showed considerably higher α-amylase and α-glucosidase inhibition than acarbose. Elderflower might therefore be valuable as a functional food against diabetes.

Impaired NFAT and NFκB activation are involved in suppression of CD40 ligand expression by Δ9-tetrahydrocannabinol in human CD4+ T cells

International Nuclear Information System (INIS)

Ngaotepprutaram, Thitirat; Kaplan, Barbara L.F.; Kaminski, Norbert E.

2013-01-01

We have previously reported that Δ 9 -tetrahydrocannabinol (Δ 9 -THC), the main psychoactive cannabinoid in marijuana, suppresses CD40 ligand (CD40L) expression by activated mouse CD4 + T cells. CD40L is involved in pathogenesis of many autoimmune and inflammatory diseases. In the present study, we investigated the molecular mechanism of Δ 9 -THC-mediated suppression of CD40L expression using peripheral blood human T cells. Pretreatment with Δ 9 -THC attenuated CD40L expression in human CD4 + T cells activated by anti-CD3/CD28 at both the protein and mRNA level, as determined by flow cytometry and quantitative real-time PCR, respectively. Electrophoretic mobility shift assays revealed that Δ 9 -THC suppressed the DNA-binding activity of both NFAT and NFκB to their respective response elements within the CD40L promoter. An assessment of the effect of Δ 9 -THC on proximal T cell-receptor (TCR) signaling induced by anti-CD3/CD28 showed significant impairment in the rise of intracellular calcium, but no significant effect on the phosphorylation of ZAP70, PLCγ1/2, Akt, and GSK3β. Collectively, these findings identify perturbation of the calcium-NFAT and NFκB signaling cascade as a key mechanistic event by which Δ 9 -THC suppresses human T cell function. - Highlights: • Δ 9 -THC attenuated CD40L expression in activated human CD4+ T cells. • Δ 9 -THC suppressed DNA-binding activity of NFAT and NFκB. • Δ 9 -THC impaired elevation of intracellular Ca2+. • Δ 9 -THC did not affect phosphorylation of ZAP70, PLCγ1/2, Akt, and GSK3β

Arctigenin, a natural lignan compound, induces G0/G1 cell cycle arrest and apoptosis in human glioma cells

OpenAIRE

Maimaitili, Aisha; Shu, Zunhua; Cheng, Xiaojiang; Kaheerman, Kadeer; Sikandeer, Alifu; Li, Weimin

2016-01-01

The aim of the current study was to investigate the anticancer potential of arctigenin, a natural lignan compound, in malignant gliomas. The U87MG and T98G human glioma cell lines were treated with various concentrations of arctigenin for 48 h and the effects of arctigenin on the aggressive phenotypes of glioma cells were assessed. The results demonstrated that arctigenin dose-dependently inhibited the growth of U87MG and T98G cells, as determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphen...

Mindset Changes Lead to Drastic Impairments in Rule Finding

Science.gov (United States)

ErEl, Hadas; Meiran, Nachshon

2011-01-01

Rule finding is an important aspect of human reasoning and flexibility. Previous studies associated rule finding "failure" with past experience with the test stimuli and stable personality traits. We additionally show that rule finding performance is severely impaired by a mindset associated with applying an instructed rule. The mindset was…

Triorganotin as a compound with potential reproductive toxicity in mammals

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V.S. Delgado Filho

2011-09-01

Full Text Available Organotin compounds are typical environmental contaminants and suspected endocrine-disrupting substances, which cause irreversible sexual abnormality in female mollusks, called "imposex". However, little is known about the capability of triorganotin compounds, such as tributyltin and triphenyltin, to cause disorders in the sexual development and reproductive functions of mammals, including humans and rodents. Moreover, these compounds can act as potential competitive inhibitors of aromatase enzyme and other steroidogenic enzymes, affecting the reproductive capacity of male and female mammals. In this review, we discuss the cellular, biochemical, and molecular mechanisms by which triorganotin compounds induce adverse effects in the mammalian reproductive function.

Genetic and Chemical Correction of Cholesterol Accumulation and Impaired Autophagy in Hepatic and Neural Cells Derived from Niemann-Pick Type C Patient-Specific iPS Cells

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Dorothea Maetzel

2014-06-01

Full Text Available Niemann-Pick type C (NPC disease is a fatal inherited lipid storage disorder causing severe neurodegeneration and liver dysfunction with only limited treatment options for patients. Loss of NPC1 function causes defects in cholesterol metabolism and has recently been implicated in deregulation of autophagy. Here, we report the generation of isogenic pairs of NPC patient-specific induced pluripotent stem cells (iPSCs using transcription activator-like effector nucleases (TALENs. We observed decreased cell viability, cholesterol accumulation, and dysfunctional autophagic flux in NPC1-deficient human hepatic and neural cells. Genetic correction of a disease-causing mutation rescued these defects and directly linked NPC1 protein function to impaired cholesterol metabolism and autophagy. Screening for autophagy-inducing compounds in disease-affected human cells showed cell type specificity. Carbamazepine was found to be cytoprotective and effective in restoring the autophagy defects in both NPC1-deficient hepatic and neuronal cells and therefore may be a promising treatment option with overall benefit for NPC disease.

Novel compound heterozygous mutations of ALDH1A3 contribute to anophthalmia in a non-consanguineous Chinese family

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Yunqiang Liu

2017-06-01

Full Text Available Abstract Anophthalmia is a rare eye development anomaly resulting in absent ocular globes or tissue in the orbit since birth. Here, we investigated a newborn with bilateral anophthalmia in a Chinese family. Exome sequencing revealed that compound heterozygous mutations c.287G > A (p.(Arg96His and c.709G > A (p.(Gly237Arg of the ALDH1A3 gene were present in the affected newborn. Both mutations were absent in all of the searched databases, including 10,000 in-house Chinese exome sequences, and these mutations were confirmed as having been transmitted from the parents. Comparative amino acid sequence analysis across distantly related species revealed that the residues at positions 96 and 234 were evolutionarily highly conserved. In silico analysis predicted these changes to be damaging, and in vitro expression analysis revealed that the mutated alleles were associated with decreased protein production and impaired tetrameric protein formation. This study firstly reported that compound heterozygous mutations of the ALDH1A3 gene can result in anophthalmia in humans, thus highlighting those heterozygous mutations in ALDH1A3 should be considered for molecular screening in anophthalmia, particularly in cases from families without consanguineous relationships.

Toxicity prediction of compounds from turmeric (Curcuma longa L).

Science.gov (United States)

Balaji, S; Chempakam, B

2010-10-01

Turmeric belongs to the ginger family Zingiberaceae. Currently, cheminformatics approaches are not employed in any of the spices to study the medicinal properties traditionally attributed to them. The aim of this study is to find the most efficacious molecule which does not have any toxic effects. In the present study, toxicity of 200 chemical compounds from turmeric were predicted (includes bacterial mutagenicity, rodent carcinogenicity and human hepatotoxicity). The study shows out of 200 compounds, 184 compounds were predicted as toxigenic, 136 compounds are mutagenic, 153 compounds are carcinogenic and 64 compounds are hepatotoxic. To cross validate our results, we have chosen the popular curcumin and found that curcumin and its derivatives may cause dose dependent hepatotoxicity. The results of these studies indicate that, in contrast to curcumin, few other compounds in turmeric which are non-mutagenic, non-carcinogenic, non-hepatotoxic, and do not have any side-effects. Hence, the cost-effective approach presented in this paper could be used to filter toxic compounds from the drug discovery lifecycle. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

Neutral and emotional episodic memory: global impairment after lorazepam or scopolamine.

Science.gov (United States)

Kamboj, Sunjeev K; Curran, H Valerie

2006-11-01

Benzodiazepines and anticholinergic drugs have repeatedly been shown to impair episodic memory for emotionally neutral material in humans. However, their effect on memory for emotionally laden stimuli has been relatively neglected. We sought to investigate the effects of the benzodiazepine, lorazepam, and the anticholinergic, scopolamine, on incidental episodic memory for neutral and emotional components of a narrative memory task in humans. A double-blind, placebo-controlled independent group design was used with 48 healthy volunteers to examine the effects of these drugs on emotional and neutral episodic memory. As expected, the emotional memory advantage was retained for recall and recognition memory under placebo conditions. However, lorazepam and scopolamine produced anterograde recognition memory impairments on both the neutral and emotional components of the narrative, although floor effects were obtained for recall memory. Furthermore, compared with placebo, recognition memory for both central (gist) and peripheral (detail) aspects of neutral and emotional elements of the narrative was poorer after either drug. Benzodiazepine-induced GABAergic enhancement or scopolamine-induced cholinergic hypofunction results in a loss of the enhancing effect of emotional arousal on memory. Furthermore, lorazepam- and scopolamine-induced memory impairment for both gist (which is amygdala dependent) and detail raises the possibility that their effects on emotional memory do not depend only on the amygdala. We discuss the results with reference to potential clinical/forensic implications of processing emotional memories under conditions of globally impaired episodic memory.

Interplay of mycolic acids, antimycobacterial compounds and pulmonary surfactant membrane: a biophysical approach to disease.

Science.gov (United States)

Pinheiro, Marina; Giner-Casares, Juan J; Lúcio, Marlene; Caio, João M; Moiteiro, Cristina; Lima, José L F C; Reis, Salette; Camacho, Luis

2013-02-01

This work focuses on the interaction of mycolic acids (MAs) and two antimycobacterial compounds (Rifabutin and N'-acetyl-Rifabutin) at the pulmonary membrane level to convey a biophysical perspective of their role in disease. For this purpose, accurate biophysical techniques (Langmuir isotherms, Brewster angle microscopy, and polarization-modulation infrared reflection spectroscopy) and lipid model systems were used to mimic biomembranes: MAs mimic bacterial lipids of the Mycobacterium tuberculosis (MTb) membrane, whereas Curosurf® was used as the human pulmonary surfactant (PS) membrane model. The results obtained show that high quantities of MAs are responsible for significant changes on PS biophysical properties. At the dynamic inspiratory surface tension, high amounts of MAs decrease the order of the lipid monolayer, which appears to be a concentration dependent effect. These results suggest that the amount of MAs might play a critical role in the initial access of the bacteria to their targets. Both molecules also interact with the PS monolayer at the dynamic inspiratory surface. However, in the presence of higher amounts of MAs, both compounds improve the phospholipid packing and, therefore, the order of the lipid surfactant monolayer. In summary, this work discloses the putative protective effects of antimycobacterial compounds against the MAs induced biophysical impairment of PS lipid monolayers. These protective effects are most of the times overlooked, but can constitute an additional therapeutic value in the treatment of pulmonary tuberculosis (Tb) and may provide significant insights for the design of new and more efficient anti-Tb drugs based on their behavior as membrane ordering agents. Copyright © 2012 Elsevier B.V. All rights reserved.

1,25-dihydroxyvitamin D{sub 3} impairs NF-{kappa}B activation in human naive B cells

Energy Technology Data Exchange (ETDEWEB)

Geldmeyer-Hilt, Kerstin, E-mail: kerstin.hilt@charite.de [Allergie-Centrum-Charite, CCM, Klinik fuer Dermatologie und Allergologie, Charite - Universitaetsmedizin Berlin, Chariteplatz 1, 10117 Berlin (Germany); Heine, Guido, E-mail: guido.heine@charite.de [Allergie-Centrum-Charite, CCM, Klinik fuer Dermatologie und Allergologie, Charite - Universitaetsmedizin Berlin, Chariteplatz 1, 10117 Berlin (Germany); Deutsches Rheuma-Forschungszentrum Berlin, Chariteplatz 1, 10117 Berlin (Germany); Hartmann, Bjoern, E-mail: bjoern.hartmann@charite.de [Allergie-Centrum-Charite, CCM, Klinik fuer Dermatologie und Allergologie, Charite - Universitaetsmedizin Berlin, Chariteplatz 1, 10117 Berlin (Germany); Baumgrass, Ria, E-mail: baumgrass@drfz.de [Deutsches Rheuma-Forschungszentrum Berlin, Chariteplatz 1, 10117 Berlin (Germany); Radbruch, Andreas, E-mail: radbruch@drfz.de [Deutsches Rheuma-Forschungszentrum Berlin, Chariteplatz 1, 10117 Berlin (Germany); Worm, Margitta, E-mail: margitta.worm@charite.de [Allergie-Centrum-Charite, CCM, Klinik fuer Dermatologie und Allergologie, Charite - Universitaetsmedizin Berlin, Chariteplatz 1, 10117 Berlin (Germany)

2011-04-22

Highlights: {yields} In naive B cells, VDR activation by calcitriol results in reduced NF-{kappa}B p105 and p50 protein expression. {yields} Ligating the VDR with calcitriol causes reduced nuclear translocation of NF-{kappa}B p65. {yields} Reduced nuclear amount of p65 after calcitriol incubation results in reduced binding of p65 on the p105 promoter. {yields} Thus, vitamin D receptor signaling may reduce or prevent activation of B cells and unwanted immune responses, e.g. in IgE dependent diseases such as allergic asthma. -- Abstract: 1{alpha},25-dihydroxyvitamin D{sub 3} (calcitriol), the bioactive metabolite of vitamin D, modulates the activation and inhibits IgE production of anti-CD40 and IL-4 stimulated human peripheral B cells. Engagement of CD40 results in NF-{kappa}B p50 activation, which is essential for the class switch to IgE. Herein, we investigated by which mechanism calcitriol modulates NF-{kappa}B mediated activation of human naive B cells. Naive B cells were predominantly targeted by calcitriol in comparison with memory B cells as shown by pronounced induction of the VDR target gene cyp24a1. Vitamin D receptor activation resulted in a strongly reduced p105/p50 protein and mRNA expression in human naive B cells. This effect is mediated by impaired nuclear translocation of p65 and consequently reduced binding of p65 to its binding site in the p105 promoter. Our data indicate that the vitamin D receptor reduces NF-{kappa}B activation by interference with NF-{kappa}B p65 and p105. Thus, the vitamin D receptor inhibits costimulatory signal transduction in naive B cells, namely by reducing CD40 signaling.

Interactions between wine phenolic compounds and human saliva in astringency perception.

Science.gov (United States)

García-Estévez, Ignacio; Ramos-Pineda, Alba María; Escribano-Bailón, María Teresa

2018-03-01

Astringency is a complex perceptual phenomenon involving several sensations that are perceived simultaneously. The mechanism leading to these sensations has been thoroughly and controversially discussed in the literature and it is still not well understood since there are many contributing factors. Although we are still far from elucidating the mechanisms whereby astringency develops, the interaction between phenolic compounds and proteins (from saliva, oral mucosa or cells) seems to be most important. This review summarizes the recent trends in the protein-phenol interaction, focusing on the effect of the structure of the phenolic compound on the interaction with salivary proteins and on methodologies based on these interactions to determine astringency.

Cognitive Compensation of Speech Perception With Hearing Impairment, Cochlear Implants, and Aging : How and to What Degree Can It Be Achieved?

NARCIS (Netherlands)

Baskent, Deniz; Clarke, Jeanne; Pals, Carina; Benard, Michel R.; Bhargava, Pranesh; Saija, Jefta; Sarampalis, Anastasios; Wagner, Anita; Gaudrain, Etienne

2016-01-01

External degradations in incoming speech reduce understanding, and hearing impairment further compounds the problem. While cognitive mechanisms alleviate some of the difficulties, their effectiveness may change with age. In our research, reviewed here, we investigated cognitive compensation with

Tinnitus-provoking salicylate treatment triggers social impairments in mice.

Science.gov (United States)

Guitton, Matthieu J

2009-09-01

Tinnitus (perception of sound in silence) strongly affects the quality of life of sufferers. Tinnitus sufferers and their relatives frequently complain about major social impairments. However, it is not known whether this impairment directly results from the occurrence of tinnitus or is the indirect expression of a preexisting psychological vulnerability. Using the well-characterized animal model of salicylate-induced tinnitus, we investigate in mice whether the occurrence of tinnitus can trigger social impairments. Experiments were performed on 32 male Balb/C mice. Tinnitus was induced in mice using salicylate treatment. Social behavior was assessed in experimental and control animals using social interaction paradigm. Interaction time, number of social events, and number of nonsocial events were assessed in all animals. We demonstrate for the first time that treatment known to induce tinnitus triggers complex social impairments in mice. While salicylate-treated animals present a massive decrease in their overall social interactions compared to control untreated animals, they also display a paradoxal increase in the number of conspecific followings. Tinnitus can thus trigger a complex set of modifications of behavior, which will not only find their expression at the individual level, but also at the social level. Our results suggest that tinnitus can directly be a cause of psychosocial impairment in human and have strong implications for the clinical management of tinnitus sufferers.

Impaired glucose-induced glucagon suppression after partial pancreatectomy

DEFF Research Database (Denmark)

Schrader, Henning; Menge, Bjoern A; Breuer, Thomas G K

2009-01-01

INTRODUCTION: The glucose-induced decline in glucagon levels is often lost in patients with type 2 diabetes. It is unclear whether this is due to an independent defect in alpha-cell function or secondary to the impairment in insulin secretion. We examined whether a partial pancreatectomy in humans...... would also impair postchallenge glucagon concentrations and, if so, whether this could be attributed to the reduction in insulin levels. PATIENTS AND METHODS: Thirty-six patients with pancreatic tumours or chronic pancreatitis were studied before and after approximately 50% pancreatectomy with a 240-min...... oral glucose challenge, and the plasma concentrations of glucose, insulin, C-peptide, and glucagon were determined. RESULTS: Fasting and postchallenge insulin and C-peptide levels were significantly lower after partial pancreatectomy (P

Human neuron-astrocyte 3D co-culture-based assay for evaluation of neuroprotective compounds.

Science.gov (United States)

Terrasso, Ana Paula; Silva, Ana Carina; Filipe, Augusto; Pedroso, Pedro; Ferreira, Ana Lúcia; Alves, Paula Marques; Brito, Catarina

Central nervous system drug development has registered high attrition rates, mainly due to the lack of efficacy of drug candidates, highlighting the low reliability of the models used in early-stage drug development and the need for new in vitro human cell-based models and assays to accurately identify and validate drug candidates. 3D human cell models can include different tissue cell types and represent the spatiotemporal context of the original tissue (co-cultures), allowing the establishment of biologically-relevant cell-cell and cell-extracellular matrix interactions. Nevertheless, exploitation of these 3D models for neuroprotection assessment has been limited due to the lack of data to validate such 3D co-culture approaches. In this work we combined a 3D human neuron-astrocyte co-culture with a cell viability endpoint for the implementation of a novel in vitro neuroprotection assay, over an oxidative insult. Neuroprotection assay robustness and specificity, and the applicability of Presto Blue, MTT and CytoTox-Glo viability assays to the 3D co-culture were evaluated. Presto Blue was the adequate endpoint as it is non-destructive and is a simpler and reliable assay. Semi-automation of the cell viability endpoint was performed, indicating that the assay setup is amenable to be transferred to automated screening platforms. Finally, the neuroprotection assay setup was applied to a series of 36 test compounds and several candidates with higher neuroprotective effect than the positive control, Idebenone, were identified. The robustness and simplicity of the implemented neuroprotection assay with the cell viability endpoint enables the use of more complex and reliable 3D in vitro cell models to identify and validate drug candidates. Copyright © 2016 Elsevier Inc. All rights reserved.

Functional cardiotoxicity assessment of cosmetic compounds using human-induced pluripotent stem cell-derived cardiomyocytes.

Science.gov (United States)

Chaudhari, Umesh; Nemade, Harshal; Sureshkumar, Poornima; Vinken, Mathieu; Ates, Gamze; Rogiers, Vera; Hescheler, Jürgen; Hengstler, Jan Georg; Sachinidis, Agapios

2018-01-01

There is a large demand of a human relevant in vitro test system suitable for assessing the cardiotoxic potential of cosmetic ingredients and other chemicals. Using human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), we have already established an in vitro cardiotoxicity assay and identified genomic biomarkers of anthracycline-induced cardiotoxicity in our previous work. Here, five cosmetic ingredients were studied by the new hiPSC-CMs test; kojic acid (KJA), triclosan (TS), triclocarban (TCC), 2,7-naphthalenediol (NPT), and basic red 51 (BR51) based on cytotoxicity as well as ATP assays, beating rate, and genomic biomarkers to determine the lowest observed effect concentration (LOEC) and no observed effect concentration (NOEC). The LOEC for beating rate were 400, 10, 3, >400, and 3 µM for KJA, TS, TCC, NPT, and BR51, respectively. The corresponding concentrations for cytotoxicity or ATP depletion were similar, with the exception of TS and TCC, where the cardiomyocyte-beating assay showed positive results at non-cytotoxic concentrations. Functional analysis also showed that the individual compounds caused different effects on hiPSC-CMs. While exposure to KJA, TS, TCC, and BR51 induced significant arrhythmic beating, NPT slightly decreased cell viability, but did not influence beating. Gene expression studies showed that TS and NPT caused down-regulation of cytoskeletal and cardiac ion homeostasis genes. Moreover, TS and NPT deregulated genomic biomarkers known to be affected also by anthracyclines. The present study demonstrates that hiPSC-CMs can be used to determine LOECs and NOECs in vitro, which can be compared to human blood concentrations to determine margins of exposure. Our in vitro assay, which so far has been tested with several anthracyclines and cosmetics, still requires validation by larger numbers of positive and negative controls, before it can be recommended for routine analysis.

Autosomal recessive progressive myoclonus epilepsy due to impaired ceramide synthesis.

Science.gov (United States)

Ferlazzo, Edoardo; Striano, Pasquale; Italiano, Domenico; Calarese, Tiziana; Gasparini, Sara; Vanni, Nicola; Fruscione, Floriana; Genton, Pierre; Zara, Federico

2016-09-01

Autosomal recessive progressive myoclonus epilepsy due to impaired ceramide synthesis is an extremely rare condition, so far reported in a single family of Algerian origin presenting an unusual, severe form of progressive myoclonus epilepsy characterized by myoclonus, generalized tonic-clonic seizures and moderate to severe cognitive impairment, with probable autosomal recessive inheritance. Disease onset was between 6 and 16 years of age. Genetic study allowed to identify a homozygous nonsynonymous mutation in CERS1, the gene encoding ceramide synthase 1, a transmembrane protein of the endoplasmic reticulum (ER), catalyzes the biosynthesis of C18-ceramides. The mutation decreased C18-ceramide levels. In addition, downregulation of CerS1 in neuroblastoma cell line showed activation of ER stress response and induction of proapoptotic pathways. This observation demonstrates that impairment of ceramide biosynthesis underlies neurodegeneration in humans.

Organic compounds assessed in Neuse River water used for public supply near Smithfield, North Carolina, 2002-2005

Science.gov (United States)

Moorman, Michelle C.

2012-01-01

Organic compounds studied in a U.S. Geological Survey (USGS) assessment of water samples from the Neuse River and the public supply system for the Town of Smithfield, North Carolina, generally are manmade and include pesticides, gasoline hydrocarbons, solvents, personal-care and domestic-use products, disinfection by-products, and manufacturing additives. Of the 277 compounds assessed, a total of 113 compounds were detected in samples collected approximately monthly during 2002–2005 at the drinking-water intake for the town's water-treatment plant on the Neuse River. Fifty-two organic compounds were commonly detected (in at least 20 percent of the samples) in source water and (or) finished water. The diversity of compounds detected suggests a variety of sources and uses, including wastewater discharges, industrial, agricultural, domestic, and others. Only once during the study did an organic compound concentration exceed a human-health benchmark (benzo[a]pyrene). A human-health benchmark is a chemical concentration specific to water above which there is a risk to humans, however, benchmarks were available for only 18 of the 42 compounds with detected concentrations greater than 0.1 micrograms per liter. On the basis of this assessment, adverse effects to human health are assumed to be negligible.

Isoniazid suppresses antioxidant response element activities and impairs adipogenesis in mouse and human preadipocytes

International Nuclear Information System (INIS)

Chen, Yanyan; Xue, Peng; Hou, Yongyong; Zhang, Hao; Zheng, Hongzhi; Zhou, Tong; Qu, Weidong; Teng, Weiping; Zhang, Qiang; Andersen, Melvin E.; Pi, Jingbo

2013-01-01

Transcriptional signaling through the antioxidant response element (ARE), orchestrated by the Nuclear factor E2-related factor 2 (Nrf2), is a major cellular defense mechanism against oxidative or electrophilic stress. Here, we reported that isoniazid (INH), a widely used antitubercular drug, displays a substantial inhibitory property against ARE activities in diverse mouse and human cells. In 3T3-L1 preadipocytes, INH concentration-dependently suppressed the ARE-luciferase reporter activity and mRNA expression of various ARE-dependent antioxidant genes under basal and oxidative stressed conditions. In keeping with our previous findings that Nrf2-ARE plays a critical role in adipogenesis by regulating expression of CCAAT/enhancer-binding protein β (C/EBPβ) and peroxisome proliferator-activated receptor γ (PPARγ), suppression of ARE signaling by INH hampered adipogenic differentiation of 3T3-L1 cells and human adipose-derived stem cells (ADSCs). Following adipogenesis induced by hormonal cocktails, INH-treated 3T3-L1 cells and ADSCs displayed significantly reduced levels of lipid accumulation and attenuated expression of C/EBPα and PPARγ. Time-course studies in 3T3-L1 cells revealed that inhibition of adipogenesis by INH occurred in the early stage of terminal adipogenic differentiation, where reduced expression of C/EBPβ and C/EBPδ was observed. To our knowledge, the present study is the first to demonstrate that INH suppresses ARE signaling and interrupts with the transcriptional network of adipogenesis, leading to impaired adipogenic differentiation. The inhibition of ARE signaling may be a potential underlying mechanism by which INH attenuates cellular antioxidant response contributing to various complications. - Highlights: • Isoniazid suppresses ARE-mediated transcriptional activity. • Isoniazid inhibits adipogenesis in preadipocytes. • Isoniazid suppresses adipogenic gene expression during adipogenesis

Serum metabolome biomarkers associate low-level environmental perfluorinated compound exposure with oxidative /nitrosative stress in humans.

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Wang, Xiaofei; Liu, Liangpo; Zhang, Weibing; Zhang, Jie; Du, Xiaoyan; Huang, Qingyu; Tian, Meiping; Shen, Heqing

2017-10-01

Previous in vivo and in vitro studies have linked perfluorinated compound (PFC) exposure with metabolic interruption, but the inter-species difference and high treatment doses usually make the results difficult to be extrapolated to humans directly. The best strategy for identifying the metabolic interruption may be to establish the direct correlations between monitored PFCs data and metabolic data on human samples. In this study, serum metabolome data and PFC concentrations were acquired for a Chinese adult male cohort. The most abundant PFCs are PFOA and PFOS with concentration medians 7.56 and 12.78 nM, respectively; in together they count around 81.6% of the total PFCs. PFC concentration-related serum metabolic profile changes and the related metabolic biomarkers were explored by using partial least squares-discriminant analysis (PLS-DA). Respectively taking PFOS, PFOA and total PFC as the classifiers, serum metabolome can be differentiated between the lowest dose group (1st quartile PFCs) and the highest PFC dose group (4th quartile PFCs). Ten potential PFC biomarkers were identified, mainly involving in pollutant detoxification, antioxidation and nitric oxide (NO) signal pathways. These suggested that low-level environmental PFC exposure has significantly adverse impacts on glutathione (GSH) cycle, Krebs cycle, nitric oxide (NO) generation and purine oxidation in humans. To the best of our knowledge, this is the first report investigating the association of environmental PFC exposure with human serum metabolome alteration. Given the important biological functions of the identified biomarkers, we suggest that PFC could increase the metabolism syndromes risk including diabetes and cardiovascular diseases. Copyright © 2017 Elsevier Ltd. All rights reserved.

Quantification of the Triazole Antifungal Compounds Voriconazole and Posaconazole in Human Serum or Plasma Using Liquid Chromatography Electrospray Tandem Mass Spectrometry (HPLC-ESI-MS/MS).

Science.gov (United States)

Molinelli, Alejandro R; Rose, Charles H

2016-01-01

Voriconazole and posaconazole are triazole antifungal compounds used in the treatment of fungal infections. Therapeutic drug monitoring of both compounds is recommended in order to guide drug dosing to achieve optimal blood concentrations. In this chapter we describe an HPLC-ESI-MS/MS method for the quantification of both compounds in human plasma or serum following a simple specimen preparation procedure. Specimen preparation consists of protein precipitation using methanol and acetonitrile followed by a cleanup step that involves filtration through a cellulose acetate membrane. The specimen is then injected into an HPLC-ESI-MS/MS equipped with a C18 column and separated over an acetonitrile gradient. Quantification of the drugs in the specimen is achieved by comparing the response of the unknown specimen to that of the calibrators in the standard curve using multiple reaction monitoring.

Leg blood flow is impaired during small muscle mass exercise in patients with COPD

DEFF Research Database (Denmark)

Iepsen, Ulrik Winning; Munch, Gregers Druedal Wibe; Rugbjerg, Mette

2017-01-01

to both endothelium-independent (SNP) and endothelium-dependent (ACh) stimulation. The results suggests that leg muscle blood flow is impaired during small muscle mass exercise in patients with COPD possibly due to impaired formation of prostacyclin and increased levels of endothelin-1.......Skeletal muscle blood flow is regulated to match the oxygen demand and dysregulation could contribute to exercise intolerance in patients with COPD. We measured leg hemodynamics and metabolites from vasoactive compounds in muscle interstitial fluid and plasma at rest, during one-legged knee...... the formation of interstitial prostacyclin (vasodilator) was only increased in the controls. There was no difference between groups in the nitrite/nitrate levels (vasodilator) in plasma or interstitial fluid during exercise. Moreover, patients and controls showed similar vasodilatory capacity in response...

Caspase-2 cleavage of tau reversibly impairs memory.

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Zhao, Xiaohui; Kotilinek, Linda A; Smith, Benjamin; Hlynialuk, Chris; Zahs, Kathleen; Ramsden, Martin; Cleary, James; Ashe, Karen H

2016-11-01

In Alzheimer's disease (AD) and other tauopathies, the tau protein forms fibrils, which are believed to be neurotoxic. However, fibrillar tau has been dissociated from neuron death and network dysfunction, suggesting the involvement of nonfibrillar species. Here we describe a novel pathological process in which caspase-2 cleavage of tau at Asp314 impairs cognitive and synaptic function in animal and cellular models of tauopathies by promoting the missorting of tau to dendritic spines. The truncation product, Δtau314, resists fibrillation and is present at higher levels in brains from cognitively impaired mice and humans with AD. The expression of tau mutants that resisted caspase-2 cleavage prevented tau from infiltrating spines, dislocating glutamate receptors and impairing synaptic function in cultured neurons, and it prevented memory deficits and neurodegeneration in mice. Decreasing the levels of caspase-2 restored long-term memory in mice that had existing deficits. Our results suggest an overall treatment strategy for re-establishing synaptic function and restoring memory in patients with AD by preventing tau from accumulating in dendritic spines.

Impairments and compensation in mouth and limb use in free feeding after unilateral dopamine depletions in a rat analog of human Parkinson's disease.

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Whishaw, I Q; Coles, B L; Pellis, S M; Miklyaeva, E I

1997-03-01

Rats depleted unilaterally of dopamine (DA) with the neurotoxin 6-hydroxydopamine (6-OHDA) have contralateral sensorimotor deficits. These include pronounced impairments in using the contralateral limbs (bad limbs) for skilled movements in tests of reaching and bar pressing. There has been no systematic examination of the changes that take place in movements of spontaneous food handling. This was the purpose of the present study. Rats were filmed as they picked up and ate pieces of angel hair pasta (Capelli d'Angelo), a food item that challenges the rats to use delicate and bilaterally coordinated limb and paw movements. Control rats picked up the food with their incisors, transferred it to their paws, and manipulated it using a variety of bilaterally coordinated limb and paw movements. The DA-depleted rats were impaired in both their mouth and paw movements. They seemed unable to use their teeth to grasp the food and so used their tongue. They did not use the bad side of their mouth to chew and relied upon the good side of their mouth. The bad paw was impaired in grasping the food, grasped only with a whole paw grip, did not make manipulatory movements, and did not open to release the food or open to regain support once the food was eaten. Although the rats improved over a 30-day recovery period, much of the improvement was due to compensatory adjustments. That unilateral DA-depletion results in profound contralateral impairments of the mouth and limb with improvements due mainly to compensatory adjustments confirms a role for dopaminergic systems in motor control. Additionally, the behavioral tests described here could provide important adjuncts for assessing therapies in this animal analog of human Parkinson's disease.

Binding Energy calculation of GSK-3 protein of Human against some anti-diabetic compounds of Momordica charantia linn (Bitter melon).

Science.gov (United States)

Hazarika, Ridip; Parida, Pratap; Neog, Bijoy; Yadav, Raj Narain Singh

2012-01-01

Diabetes is one of the major life threatening diseases worldwide. It creates major health problems in urban India. Glycogen Synthase Kinase-3 (GSK-3) protein of human is known for phosphorylating and inactivating glycogen synthase which also acts as a negative regulator in the hormonal control of glucose homeostasis. In traditional medicine, Momordica charantia is used as antidiabetic plant because of its hypoglycemic effect. Hence to block the active site of the GSK-3 protein three anti-diabetic compounds namely, charantin, momordenol & momordicilin were taken from Momordica charantia for docking study and calculation of binding energy. The aim of present investigation is to find the binding energy of three major insulin-like active compounds against glycogen synthase kinase-3 (GSK-3), one of the key proteins involved in carbohydrate metabolism, with the help of molecular docking using ExomeTM Horizon suite. The study recorded minimum binding energy by momordicilin in comparison to the others.

Memory Impairment in Children with Language Impairment

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Baird, Gillian; Dworzynski, Katharina; Slonims, Vicky; Simonoff, Emily

2010-01-01

Aim: The aim of this study was to assess whether any memory impairment co-occurring with language impairment is global, affecting both verbal and visual domains, or domain specific. Method: Visual and verbal memory, learning, and processing speed were assessed in children aged 6 years to 16 years 11 months (mean 9y 9m, SD 2y 6mo) with current,…

Characterization of the apoptotic response of human leukemia cells to organosulfur compounds

International Nuclear Information System (INIS)

Wong, W Wei-Lynn; Langler, Richard F; Penn, Linda Z; Boutros, Paul C; Wasylishen, Amanda R; Guckert, Kristal D; O'Brien, Erin M; Griffiths, Rebecca; Martirosyan, Anna R; Bros, Christina; Jurisica, Igor

2010-01-01

Novel therapeutic agents that selectively induce tumor cell death are urgently needed in the clinical management of cancers. Such agents would constitute effective adjuvant approaches to traditional chemotherapy regimens. Organosulfur compounds (OSCs), such as diallyl disulfide, have demonstrated anti-proliferative effects on cancer cells. We have previously shown that synthesized relatives of dysoxysulfone, a natural OSC derived from the Fijian medicinal plant, Dysoxylum richi, possess tumor-specific antiproliferative effects and are thus promising lead candidates. Because our structure-activity analyses showed that regions flanking the disulfide bond mediated specificity, we synthesized 18 novel OSCs by structural modification of the most promising dysoxysulfone derivatives. These compounds were tested for anti-proliferative and apoptotic activity in both normal and leukemic cells. Six OSCs exhibited tumor-specific killing, having no effect on normal bone marrow, and are thus candidates for future toxicity studies. We then employed mRNA expression profiling to characterize the mechanisms by which different OSCs induce apoptosis. Using Gene Ontology analysis we show that each OSC altered a unique set of pathways, and that these differences could be partially rationalized from a transcription factor binding site analysis. For example, five compounds altered genes with a large enrichment of p53 binding sites in their promoter regions (p < 0.0001). Taken together, these data establish OSCs derivatized from dysoxysulfone as a novel group of compounds for development as anti-cancer agents

NMDA receptor antagonist ketamine impairs feature integration in visual perception.

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Meuwese, Julia D I; van Loon, Anouk M; Scholte, H Steven; Lirk, Philipp B; Vulink, Nienke C C; Hollmann, Markus W; Lamme, Victor A F

2013-01-01

Recurrent interactions between neurons in the visual cortex are crucial for the integration of image elements into coherent objects, such as in figure-ground segregation of textured images. Blocking N-methyl-D-aspartate (NMDA) receptors in monkeys can abolish neural signals related to figure-ground segregation and feature integration. However, it is unknown whether this also affects perceptual integration itself. Therefore, we tested whether ketamine, a non-competitive NMDA receptor antagonist, reduces feature integration in humans. We administered a subanesthetic dose of ketamine to healthy subjects who performed a texture discrimination task in a placebo-controlled double blind within-subject design. We found that ketamine significantly impaired performance on the texture discrimination task compared to the placebo condition, while performance on a control fixation task was much less impaired. This effect is not merely due to task difficulty or a difference in sedation levels. We are the first to show a behavioral effect on feature integration by manipulating the NMDA receptor in humans.

NMDA receptor antagonist ketamine impairs feature integration in visual perception.

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Julia D I Meuwese

Full Text Available Recurrent interactions between neurons in the visual cortex are crucial for the integration of image elements into coherent objects, such as in figure-ground segregation of textured images. Blocking N-methyl-D-aspartate (NMDA receptors in monkeys can abolish neural signals related to figure-ground segregation and feature integration. However, it is unknown whether this also affects perceptual integration itself. Therefore, we tested whether ketamine, a non-competitive NMDA receptor antagonist, reduces feature integration in humans. We administered a subanesthetic dose of ketamine to healthy subjects who performed a texture discrimination task in a placebo-controlled double blind within-subject design. We found that ketamine significantly impaired performance on the texture discrimination task compared to the placebo condition, while performance on a control fixation task was much less impaired. This effect is not merely due to task difficulty or a difference in sedation levels. We are the first to show a behavioral effect on feature integration by manipulating the NMDA receptor in humans.

Do estrogenic compounds in drinking water migrating from plastic pipe distribution system pose adverse effects to human? An analysis of scientific literature.

Science.gov (United States)

Liu, Ze-Hua; Yin, Hua; Dang, Zhi

2017-01-01

With the widespread application of plastic pipes in drinking water distribution system, the effects of various leachable organic chemicals have been investigated and their occurrence in drinking water supplies is monitored. Most studies focus on the odor problems these substances may cause. This study investigates the potential endocrine disrupting effects of the migrating compound 2,4-di-tert-butylphenol (2,4-d-t-BP). The summarized results show that the migration of 2,4-d-t-BP from plastic pipes could result in chronic exposure and the migration levels varied greatly among different plastic pipe materials and manufacturing brands. Based on estrogen equivalent (EEQ), the migrating levels of the leachable compound 2,4-d-t-BP in most plastic pipes were relative low. However, the EEQ levels in drinking water migrating from four out of 15 pipes may pose significant adverse effects. With the increasingly strict requirements on regulation of drinking water quality, these results indicate that some drinking water transported with plastic pipes may not be safe for human consumption due to the occurrence of 2,4-d-t-BP. Moreover, 2,4-d-t-BP is not the only plastic pipe-migrating estrogenic compound, other compounds such as 2-tert-butylphenol (2-t-BP), 4-tert-butylphenol (4-t-BP), and others may also be leachable from plastic pipes.

Impairments in component processes of executive function and episodic memory in alcoholism, HIV infection, and HIV infection with alcoholism comorbidity

Science.gov (United States)

Fama, Rosemary; Sullivan, Edith V.; Sassoon, Stephanie A.; Pfefferbaum, Adolf; Zahr, Natalie M.

2016-01-01

Background Executive functioning and episodic memory impairment occur in HIV infection (HIV) and chronic alcoholism (ALC). Comorbidity of these conditions (HIV+ALC) is prevalent and heightens risk for vulnerability to separate and compounded deficits. Age and disease-related variables can also serve as mediators of cognitive impairment and should be considered, given the extended longevity of HIV-infected individuals in this era of improved pharmacological therapy. Methods HIV, ALC, HIV+ALC, and normal controls (NC) were administered traditional and computerized tests of executive function and episodic memory. Test scores were expressed as age- and education-corrected Z-scores; selective tests were averaged to compute Executive Function and Episodic Memory Composite scores. Efficiency scores were calculated for tests with accuracy and response times. Results HIV, ALC, and HIV+ALC had lower scores than NC on Executive Function and Episodic Memory Composites, with HIV+ALC even lower than ALC and HIV on the Episodic Memory Composite. Impairments in planning and free recall of visuospatial material were observed in ALC, whereas impairments in psychomotor speed, sequencing, narrative free recall, and pattern recognition were observed in HIV. Lower decision-making efficiency scores than NC occurred in all three clinical groups. In ALC, age and lifetime alcohol consumption were each unique predictors of Executive Function and Episodic Memory Composite scores. In HIV+ALC, age was a unique predictor of Episodic Memory Composite score. Conclusions Disease-specific and disease-overlapping patterns of impairment in HIV,ALC, and HIV+ALC have implications regarding brain systems disrupted by each disease and clinical ramifications regarding the complexities and compounded damping of cognitive functioning associated with dual diagnosis that may be exacerbated with aging. PMID:27759882

A fluorescence-based rapid screening assay for cytotoxic compounds

International Nuclear Information System (INIS)

Montoya, Jessica; Varela-Ramirez, Armando; Estrada, Abril; Martinez, Luis E.; Garza, Kristine; Aguilera, Renato J.

2004-01-01

A simple fluorescence-based assay was developed for the rapid screening of potential cytotoxic compounds generated by combinatorial chemistry. The assay is based on detection of nuclear green fluorescent protein (GFP) staining of a human cervical cancer cell line (HeLa) carrying an integrated histone H2B-GFP fusion gene. Addition of a cytotoxic compound to the HeLa-GFP cells results in the eventual degradation of DNA and loss of the GFP nuclear fluorescence. Using this assay, we screened 11 distinct quinone derivatives and found that several of these compounds were cytotoxic. These compounds are structurally related to plumbagin an apoptosis-inducing naphthoquinone isolated from Black Walnut. In order to determine the mechanism by which cell death was induced, we performed additional experiments with the most cytotoxic quinones. These compounds were found to induce morphological changes (blebbing and nuclear condensation) consistent with induction of apoptosis. Additional tests revealed that the cytotoxic compounds induce both necrotic and apoptotic modes of death

Serum Compounds of Energy Metabolism Impairment Are Related to Disability, Disease Course and Neuroimaging in Multiple Sclerosis.

Science.gov (United States)

Lazzarino, Giacomo; Amorini, Angela M; Petzold, Axel; Gasperini, Claudio; Ruggieri, Serena; Quartuccio, Maria Esmeralda; Lazzarino, Giuseppe; Di Stasio, Enrico; Tavazzi, Barbara

2017-11-01

Multiple sclerosis (MS) is characterized by primary inflammation, demyelination, and progressive neurodegeneration. A biochemical MS feature is neuronal mitochondrial dysfunction, compensated by anaerobic metabolism increase, likely aggravating progression of neurodegeneration. Here, we characterized a pragmatic serum profile of compounds related to mitochondrial energy metabolism of potential clinical use. Blood samples of 518 well characterized (disability, disease course) MS patients and 167 healthy controls were analyzed for serum purines, pyrimidines, creatinine, and lactate. Nine of the 15 compounds assayed, hypoxanthine, xanthine, uric acid, inosine, uracil, β-pseudouridine, uridine, creatinine, and lactate, differed significantly between MS patients and controls (p < 0.0001). Using these nine compounds, a unifying Biomarker Score was calculated. Controls and MS patients had mean Biomarker Scores of 0.4 ± 0.7 and 4.4 ± 1.9, respectively (p < 0.00001). The Biomarker Score was higher in patients with progressive (6.0 ± 1.8 than with relapsing remitting disease course (3.6 ± 1.5, p < 0.00001). High association between the Biomarker Score and increase in disability (EDSS) was also observed. Additionally, in 50 patients who underwent magnetic resonance imaging (MRI), increase in the Biomarker Score correlated to neuroanatomical alterations. These results, obtained in a large cohort of MS patients evaluated for serum metabolic compounds connected to energy metabolism, demonstrated that the Biomarker Score might represent a pragmatic, resource saving, easy to obtain, laboratory tool useful to monitor MS patients and predict at an early stage who will switch from an RR to a progressive disease course. For the first time, it was also clearly shown a link between mitochondrial dysfunction and MRI lesions characteristic of MS.

Transient impairment of the axolemma following regional anaesthesia by lidocaine in humans

DEFF Research Database (Denmark)

Moldovan, Mihai; Lange, Kai Henrik Wiborg; Aachmann-Andersen, Niels Jacob

2014-01-01

The local anaesthetic lidocaine is known to block voltage-gated Na(+) channels (VGSCs), although at high concentration it was also reported to block other ion channel currents as well as to alter lipid membranes. The aim of this study was to investigate whether the clinical regional anaesthetic...... reflect, at least in part, a reversible structural impairment of the axolemma....

Training of Speechreading for Severely Hearing-Impaired Persons by Human and Computer

DEFF Research Database (Denmark)

Bothe, Hans-Heinrich

2007-01-01

This paper describes evaluation results for a software programme that is intended to be used as a training-aid for lipreading in German. Tests were carried out in schools for hearing-impaired children in Germany which indicate that the ability to lipread increases significantly already after use...... of the software during a short period of time....

A window of vulnerability: impaired fear extinction in adolescence.

Science.gov (United States)

Baker, Kathryn D; Den, Miriam L; Graham, Bronwyn M; Richardson, Rick

2014-09-01

There have been significant advances made towards understanding the processes mediating extinction of learned fear. However, despite being of clear theoretical and clinical significance, very few studies have examined fear extinction in adolescence, which is often described as a developmental window of vulnerability to psychological disorders. This paper reviews the relatively small body of research examining fear extinction in adolescence. A prominent finding of this work is that adolescents, both humans and rodents, exhibit a marked impairment in extinction relative to both younger (e.g., juvenile) and older (e.g., adult) groups. We then review some potential mechanisms that could produce the striking extinction deficit observed in adolescence. For example, one neurobiological candidate mechanism for impaired extinction in adolescence involves changes in the functional connectivity within the fear extinction circuit, particularly between prefrontal cortical regions and the amygdala. In addition, we review research on emotion regulation and attention processes that suggests that developmental changes in attention bias to threatening cues may be a cognitive mechanism that mediates age-related differences in extinction learning. We also examine how a differential reaction to chronic stress in adolescence impacts upon extinction retention during adolescence as well as in later life. Finally, we consider the findings of several studies illustrating promising approaches that overcome the typically-observed extinction impairments in adolescent rodents and that could be translated to human adolescents. Copyright © 2013 Elsevier Inc. All rights reserved.

Developmental dyscalculia is related to visuo-spatial memory and inhibition impairment.

Science.gov (United States)

Szucs, Denes; Devine, Amy; Soltesz, Fruzsina; Nobes, Alison; Gabriel, Florence

2013-01-01

Developmental dyscalculia is thought to be a specific impairment of mathematics ability. Currently dominant cognitive neuroscience theories of developmental dyscalculia suggest that it originates from the impairment of the magnitude representation of the human brain, residing in the intraparietal sulcus, or from impaired connections between number symbols and the magnitude representation. However, behavioral research offers several alternative theories for developmental dyscalculia and neuro-imaging also suggests that impairments in developmental dyscalculia may be linked to disruptions of other functions of the intraparietal sulcus than the magnitude representation. Strikingly, the magnitude representation theory has never been explicitly contrasted with a range of alternatives in a systematic fashion. Here we have filled this gap by directly contrasting five alternative theories (magnitude representation, working memory, inhibition, attention and spatial processing) of developmental dyscalculia in 9-10-year-old primary school children. Participants were selected from a pool of 1004 children and took part in 16 tests and nine experiments. The dominant features of developmental dyscalculia are visuo-spatial working memory, visuo-spatial short-term memory and inhibitory function (interference suppression) impairment. We hypothesize that inhibition impairment is related to the disruption of central executive memory function. Potential problems of visuo-spatial processing and attentional function in developmental dyscalculia probably depend on short-term memory/working memory and inhibition impairments. The magnitude representation theory of developmental dyscalculia was not supported. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

Exposure to a High-Fat Diet during Early Development Programs Behavior and Impairs the Central Serotonergic System in Juvenile Non-Human Primates

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Jacqueline R. Thompson

2017-07-01

Full Text Available Perinatal exposure to maternal obesity and high-fat diet (HFD consumption not only poses metabolic risks to offspring but also impacts brain development and mental health. Using a non-human primate model, we observed a persistent increase in anxiety in juvenile offspring exposed to a maternal HFD. Postweaning HFD consumption also increased anxiety and independently increased stereotypic behaviors. These behavioral changes were associated with modified cortisol stress response and impairments in the development of the central serotonin synthesis, with altered tryptophan hydroxylase-2 mRNA expression in the dorsal and median raphe. Postweaning HFD consumption decreased serotonergic immunoreactivity in area 10 of the prefrontal cortex. These results suggest that perinatal exposure to HFD consumption programs development of the brain and endocrine system, leading to behavioral impairments associated with mental health and neurodevelopmental disorders. Also, an early nutritional intervention (consumption of the control diet at weaning was not sufficient to ameliorate many of the behavioral changes, such as increased anxiety, that were induced by maternal HFD consumption. Given the level of dietary fat consumption and maternal obesity in developed nations these findings have important implications for the mental health of future generations.

From Valeriana officinalis to cancer therapy: the success of a bio-sourced compound

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Hamaidia, M.

2016-01-01

Full Text Available Introduction. Over the centuries, bio-sourced compounds isolated from plants, insects and microorganisms have been a potent source of drugs for the treatment of human diseases. Literature. Bio-sourced extracts offer a wide diversity of compounds with a large number of potentially beneficial effects in humans. Serendipity has frequently played a key role in the discovery of new medicines. The canonical discovery of penicillin required both chance and a prepared mind to understand and exploit its potential for the treatment of human infections. Nowadays, most anti-cancer drugs currently in clinical use were at least partly discovered by a "fortunate happenstance". Conclusions. In this review, we recapitulate the story of one of these compounds, 2-propylpentanoic acid, derived from the Valeriana officinalis flowering plant and its path to validation as a cancer treatment.

First translational 'Think Tank' on cerebrovascular disease, cognitive impairment and dementia

NARCIS (Netherlands)

Barone, F.C.; Gustafson, D.; Crystal, H.A.; Moreno, H.; Adamski, M.G.; Arai, K.; Baird, A.E.; Balucani, C.; Brickman, A.M.; Cechetto, D.; Gorelick, P.; Biessels, G.J.; Kiliaan, A.J.; Launer, L.; Schneider, J.; Sorond, F.A.; Whitmer, R.; Wright, C.; Zhang, Z.G.

2016-01-01

As the human population continues to age, an increasing number of people will exhibit significant deficits in cognitive function and dementia. It is now recognized that cerebrovascular, metabolic and neurodegenerative diseases all play major roles in the evolution of cognitive impairment and

Visual Impairment

Science.gov (United States)

... site Sitio para adolescentes Body Mind Sexual Health Food & Fitness Diseases & Conditions Infections Drugs & Alcohol School & Jobs Sports Expert Answers (Q&A) Staying Safe Videos for Educators Search English Español Visual Impairment KidsHealth / For Teens / Visual Impairment What's in ...

Prevention of vision loss protects against age-related impairment in learning and memory performance in DBA/2J mice

Directory of Open Access Journals (Sweden)

Aimee eWong

2013-09-01

Full Text Available The DBA/2J mouse is a model of pigmentary glaucoma in humans as it shows age‐related increases in intraocular pressure, retinal ganglion cell death and visual impairment. Previously, we showed that visual ability declines from 9 ‐12 months of age and visual impairment is correlated with poor learning and memory performance in visuo‐spatial tasks but not in tasks that do not depend on visual cues. To test the sensory impairment hypothesis of aging, which postulates that sensory impaired individuals are disadvantaged in their performance on psychometric tests as a direct result of difficulties in sensory perception, we treated DBA/2J mice with a conventional glaucoma medication used in humans (Timoptic‐XE, 0.00, 0.25 or 0.50% daily from 9 weeks to 12 months of age to determine whether prevention of vision loss prevented the decline in visuo-spatial learning and memory performance. At all ages tested (3, 6, 9 and 12 months of age, mice treated with Timoptic-XE (0.25 and 0.50% maintained a high level of performance, while 12 month old control mice (0.00% exhibited impaired performance in visually‐dependent, but not non‐visual tasks. These results demonstrate that when sensory function is preserved, cognitive performance is normalized. Thus, as in many aging humans, DBA/2J mice show age-related decrements in performance on visually presented cognitive tests, not because of cognitive impairment but as a direct consequence of poor visual ability. Our results demonstrate that age-related impairment in performance in visuo-spatial tasks in DBA/2J mice can be prevented by the preservation of visual ability.

Prevention of vision loss protects against age-related impairment in learning and memory performance in DBA/2J mice.

Science.gov (United States)

Wong, Aimée A; Brown, Richard E

2013-01-01

The DBA/2J mouse is a model of pigmentary glaucoma in humans as it shows age-related increases in intraocular pressure (IOP), retinal ganglion cell death and visual impairment. Previously, we showed that visual ability declines from 9 to 12 months of age and visual impairment is correlated with poor learning and memory performance in visuo-spatial tasks but not in tasks that do not depend on visual cues. To test the "sensory impairment" hypothesis of aging, which postulates that sensory impaired individuals are disadvantaged in their performance on psychometric tests as a direct result of difficulties in sensory perception, we treated DBA/2J mice with a conventional glaucoma medication used in humans (Timoptic-XE, 0.00, 0.25, or 0.50%) daily from 9 weeks to 12 months of age to determine whether prevention of vision loss prevented the decline in visuo-spatial learning and memory performance. At all ages tested (3, 6, 9, and 12 months of age), mice treated with Timoptic-XE (0.25 and 0.50%) maintained a high level of performance, while 12 month old control mice (0.00%) exhibited impaired performance in visually-dependent, but not non-visual tasks. These results demonstrate that when sensory function is preserved, cognitive performance is normalized. Thus, as in many aging humans, DBA/2J mice show age-related decrements in performance on visually presented cognitive tests, not because of cognitive impairment but as a direct consequence of poor visual ability. Our results demonstrate that age-related impairment in performance in visuo-spatial tasks in DBA/2J mice can be prevented by the preservation of visual ability.

Different Patterns of Theory of Mind Impairment in Mild Cognitive Impairment.

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Moreau, Noémie; Rauzy, Stéphane; Bonnefoi, Bernadette; Renié, Laurent; Martinez-Almoyna, Laurent; Viallet, François; Champagne-Lavau, Maud

2015-01-01

Theory of Mind refers to the ability to infer other’s mental states, their beliefs, intentions, or knowledge. To date, only two studies have reported the presence of Theory of Mind impairment in mild cognitive impairment (MCI). In the present study,we evaluated 20 MCI patients and compared them with 25 healthy control participants using two Theory of Mind tasks. The first task was a false belief paradigm as frequently used in the literature, and the second one was a referential communication task,assessing Theory of Mind in a real situation of interaction and which had never been used before in this population. The results showed that MCI patients presented difficulties inferring another person’s beliefs about reality and attributing knowledge to them in a situation of real-life interaction. Two different patterns of Theory of Mind emerged among the patients. In comparison with the control group, some MCI patients demonstrated impairment only in the interaction task and presented isolated episodicmemory impairment, while others were impaired in both Theory of Mind tasks and presented cognitive impairment impacting both episodic memory and executive functioning. Theory of Mind is thus altered in the very early stages of cognitive impairment even in real social interaction, which could impact precociously relationships in daily life.

Electrical brain responses in language-impaired children reveal grammar-specific deficits.

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Elisabeth Fonteneau

2008-03-01

Full Text Available Scientific and public fascination with human language have included intensive scrutiny of language disorders as a new window onto the biological foundations of language and its evolutionary origins. Specific language impairment (SLI, which affects over 7% of children, is one such disorder. SLI has received robust scientific attention, in part because of its recent linkage to a specific gene and loci on chromosomes and in part because of the prevailing question regarding the scope of its language impairment: Does the disorder impact the general ability to segment and process language or a specific ability to compute grammar? Here we provide novel electrophysiological data showing a domain-specific deficit within the grammar of language that has been hitherto undetectable through behavioural data alone.We presented participants with Grammatical(G-SLI, age-matched controls, and younger child and adult controls, with questions containing syntactic violations and sentences containing semantic violations. Electrophysiological brain responses revealed a selective impairment to only neural circuitry that is specific to grammatical processing in G-SLI. Furthermore, the participants with G-SLI appeared to be partially compensating for their syntactic deficit by using neural circuitry associated with semantic processing and all non-grammar-specific and low-level auditory neural responses were normal.The findings indicate that grammatical neural circuitry underlying language is a developmentally unique system in the functional architecture of the brain, and this complex higher cognitive system can be selectively impaired. The findings advance fundamental understanding about how cognitive systems develop and all human language is represented and processed in the brain.

UVA-mediated down-regulation of MMP-2 and MT1-MMP coincides with impaired angiogenic phenotype of human dermal endothelial cells

International Nuclear Information System (INIS)

Cauchard, Jean-Hubert; Robinet, Arnaud; Poitevin, Stephane; Bobichon, Helene; Maziere, Jean-Claude; Bellon, Georges; Hornebeck, William

2006-01-01

UVA irradiation, dose-dependently (5-20 J/cm 2 ), was shown to impair the morphogenic differentiation of human microvascular endothelial cells (HMECs) on Matrigel. Parallely, UVA down-regulated the expression of MMP-2 and MT1-MMP, both at the protein and the mRNA levels. On the contrary, the production of MMP-1 and TIMP-1 by HMECs increased following UVA treatment. The inhibitory effect of UVA on MMP expression and pseudotubes formation was mediated by UVA-generated singlet oxygen ( 1 O 2 ). The contribution of MT1-MMP, but not TIMP-1, to the regulation of HMECs' angiogenic phenotype following UVA irradiation was suggested using elastin-derived peptides and TIMP-1 blocking antibody, respectively

Impaired mental rotation in benign paroxysmal positional vertigo and acute vestibular neuritis.

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Matteo eCandidi

2013-11-01

Full Text Available Vestibular processing is fundamental to our sense of orientation in space which is a core aspect of the representation of the self. Vestibular information is processed in a large subcortical-cortical neural network. Tasks requiring mental rotations of human bodies in space are known to activate neural regions within this network suggesting that vestibular processing is involved in the control of mental rotation. We studied whether mental rotation is impaired in patients suffering from two different forms of unilateral vestibular disorders (Vestibular Neuritis – VN- and Benign Paroxysmal positional Vertigo – BPPV with respect to healthy matched controls (C. We used two mental rotation tasks in which participants were required to: i mentally rotate their own body in space (egocentric rotation thus using vestibular processing to a large extent and ii mentally rotate human figures (allocentric rotation thus using own body representations to a smaller degree. Reaction times and accuracy of responses showed that VN and BPPV patients were impaired in both tasks with respect to C. Significantly, the pattern of results was similar in the three groups suggesting that patients were actually performing the mental rotation without using a different strategy from the control individuals. These results show that dysfunctional vestibular inflow impairs mental rotation of both own body and human figures suggesting that unilateral acute disorders of the peripheral vestibular input massively affect the cerebral processes underlying mental rotations.

Sleep deprivation and daily torpor impair object recognition in Djungarian hamsters

NARCIS (Netherlands)

Palchykova, S; Crestani, F; Meerlo, P; Tobler, Irene

2006-01-01

Sleep has been shown to play a facilitating role in memory consolidation, whereas sleep deprivation leads to performance impairment both in humans and rodents. The effects of 4-h sleep deprivation on recognition memory were investigated in the Djungarian hamster (Phodopus sungorus). Because sleep

[Is olfactory function impaired in moderate height?].

Science.gov (United States)

Kühn, M; Welsch, H; Zahnert, T; Hummel, Thomas

2009-09-01

The human sense of smell seems to be influenced by the surrounding barometric pressure. These factors appear to be especially important during flights, for example, in order to recognize the smell of fire etc. Thus, questions are whether pilots or passengers exhibit an impaired smell sensitivity when tested at moderate heights, or, whether changes in humidity would affect the sense of smell. Using climate chambers, odor discrimination and butanol odor thresholds were tested in 77 healthy normosmic volunteers (5 female, 72 male; aged 25+/-8 years from 18 up to 53 years) under hypobaric (2 700+/-20 m, 20 degrees C+/-1 K, rh=50+/-5%) and hyperbaric, (10+/-0.5 m (2 bar)) and different humidity conditions (30 vs. 80%, 20 degrees C+/-1 K, normobaric). During all conditions cognitive performance was tested. Among other effects, olfactory sensitivity was impaired at threshold, but not suprathreshold level, in a hypobaric compared to a hyperbaric milieu, and thresholds were lower in humid, compared to relatively dry conditions. In conclusion, environmental conditions modulate the sense of smell, and may, consecutively, influence results from olfactory tests. During flight hypobaric conditions, mild hypoxia and dry air may cause impaired sensitivity of smell. Georg Thieme Verlag KG Stuttgart * New York.

Simulated Evaluation of Drug-Impaired Psychomotor Performance

OpenAIRE

Richmond R

2014-01-01

The purpose of this placebo-controlled, randomized-crossover study was to evaluate a computer-based divided-attention task as a method for measure impaired human psychomotor performance. The ability of the divided-attention task to detect and differentiate was evaluated using single oral doses of placebo, caffeine and diphenhydramine. Ten healthy men were the subjects of the study. Subject performance on divided-attention was compared with tests of short-term memory and a set of visual analog...

Anti-inflammatory compound resveratrol suppresses homocysteine formation in stimulated human peripheral blood mononuclear cells in vitro.

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Schroecksnadel, Katharina; Winkler, Christiana; Wirleitner, Barbara; Schennach, Harald; Weiss, Günter; Fuchs, Dietmar

2005-01-01

Inflammation, immune activation and oxidative stress play a major role in the pathogenesis of cardiovascular disorders. In addition to markers of inflammation, moderate hyperhomocysteinemia is an independent risk factor for cardiovascular disease, and there is a link between the activation of immunocompetent cells and the enhanced formation of homocysteine in vitro. Likewise, anti-inflammatory drugs and nutrients rich in antioxidant vitamins are able to reduce cardiovascular risk and to slow down the atherogenic process. Resveratrol, a phenolic antioxidant synthesized in grapes and vegetables and present in wine, has also been supposed to be beneficial for the prevention of cardiovascular events. Apart from its strong antioxidant properties, resveratrol has also been demonstrated to act as an anti-inflammatory agent. In this study the influence of resveratrol on the production of homocysteine by stimulated human peripheral blood mononuclear cells (PBMCs) was investigated. Results were compared to earlier described effects of the anti-inflammatory compounds aspirin and salicylic acid and of the lipid-lowering drug atorvastatin. Stimulation of PBMCs with the mitogens concanavalin A and phytohemagglutinin induced significantly higher homocysteine accumulation in supernatants compared with unstimulated cells. Treatment with 10-100 muM resveratrol suppressed homocysteine formation in a dose-dependent manner. Resveratrol did not influence the release of homocysteine from resting PBMCs. The data suggest that resveratrol may prevent homocysteine accumulation in the blood by suppressing immune activation cascades and the proliferation of mitogen-driven T-cells. The effect of resveratrol to down-regulate the release of homo-cysteine was comparable to the decline of neopterin concentrations in the same experiments. The suppressive effect of resveratrol was very similar to results obtained earlier with aspirin, salicylic acid and atorvastatin; however, it appeared that doses

Sleep deprivation specifically impairs short-term olfactory memory in Drosophila.

Science.gov (United States)

Li, Xinjian; Yu, Feng; Guo, Aike

2009-11-01

Sleep is crucial to memory consolidation in humans and other animals; however, the effect of insufficient sleep on subsequent learning and memory remains largely elusive. Learning and memory after 1-day sleep deprivation (slpD) was evaluated using Pavlovian olfactory conditioning in Drosophila, and locomotor activity was measured using the Drosophila Activity Monitoring System in a 12:12 light-dark cycle. We found that slpD specifically impaired 1-h memory in wild type Canton-S flies, and this effect could persist for at least 2 h. However, alternative stresses (heat stress, oxidative stress, starvation, and rotation stress) did not result in a similar effect and left the flies' memory intact. Mechanistic studies demonstrated that flies with either silenced transmission of the mushroom body (MB) during slpD or down-regulated cAMP levels in the MB demonstrated no slpD-induced 1-h memory impairment. We found that slpD specifically impaired 1-h memory in Drosophila, and either silencing of MB transmission during slpD or down-regulation of the cAMP level in the MB protected the flies from slpD-induced impairment.

STUDENTS’ MISCONCEPTIONS ABOUT THE NATURE OF MATTER AND HOW IT IMPAIRS BIOCHEMISTRY LEARNING

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E. Montagna

2015-08-01

Full Text Available Introduction: It is widely known that misconceptions impairs student’s learning. IUBMB proposed a concept inventory which defines biochemistry’s teaching scope. Even though it is known that many of them are subject of misconceptions by students, we collected informal data suggesting a deeper and most pervasive misconception related to the students’ perceptions about what is and is not a molecule through their classroom statements and tests. We hypothesize that students’ impairments on biochemistry learning possibly come from failure to assume that names are related to well defined molecules indicating lack of matter’s representative levels of integration. Objectives The present work aims to detect in freshmen students’ misconceptions about the chemical nature of main small and macromolecules which potentialy impairs biochemistry learning. Materials and methods: A list of assertions about real life situations involving and citing main biomolecules – ATP, DNA, protein, lipid, carbohydrate, enzyme, hormon, vitamin – were mixed with other containing vague common terms – toxin, transgenic, healthy, unwanted elements, chemical compound – not suggesting hazardous situations in order to capture students’ impressions. More than 150 students from five courses in three different higher education institutions answered true or false on 35 assertions. Results and discussion: More than 70% of students had more than 80% error in this task designed to be not tricky, misleading or with unpreviously studied concepts. Results suggests students do not understand compounds as molecules but as entities unrelated to real life situations; on the other hand vague terms triggers a negative perception not necessarily related to harm or hazardous situations. We suggest that it is originated by poor scientific literacy from previous scholarity as well as lack of criteria on media vehicles about the topics here cited. Conclusion: We conclude that many

21 CFR 500.84 - Conditions for approval of the sponsored compound.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Conditions for approval of the sponsored compound. 500.84 Section 500.84 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... Used in Food-Producing Animals § 500.84 Conditions for approval of the sponsored compound. (a) On the...

20 CFR 220.102 - Non-severe impairment(s), defined.

Science.gov (United States)

2010-04-01

... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false Non-severe impairment(s), defined. 220.102 Section 220.102 Employees' Benefits RAILROAD RETIREMENT BOARD REGULATIONS UNDER THE RAILROAD RETIREMENT... these include— (1) Physical functions such as walking, standing, sitting, lifting, pushing, pulling...

Isolation and characterization of an anticancer catechol compound from Semecarpus anacardium.

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Nair, P K Raveedran; Melnick, Steven J; Wnuk, Stanislaw F; Rapp, Magdalena; Escalon, Enrique; Ramachandran, Cheppail

2009-04-21

The fruits and seeds of Semecarpus anacardium are used widely for the treatment of human cancers and other diseases in the Ayurvedic and Sidda systems of medicine in India. The principal aim of this investigation was to isolate and characterize the anticancer compound from the kernel of Semecarpus anacardium nut. The bioactivity-tailored isolation and detailed chemical characterization were used to identify the active compound. Cytotoxicity, apoptosis, cell cycle arrest as well as synergism between the identified anticancer compound and doxorubicin in human tumor cell lines were analyzed. GC/MS, IR, proton NMR, carbon NMR and collisionally induced dissociation (CID) spectra analysis showed that the isolated active compound is 3-(8'(Z),11'(Z)-pentadecadienyl) catechol (SA-3C). SA-3C is cytotoxic to tumor cell lines with IC(50) values lower than doxorubicin and even multidrug resistant tumor cell lines were equally sensitive to SA-3C. SA-3C induced apoptosis in human leukemia cell lines in a dose-dependent manner and showed synergistic cytotoxicity with doxorubicin. The cell cycle arrest induced by SA-3C at S- and G(2)/M-phases correlated with inhibition of checkpoint kinases. SA-3C isolated from the kernel of Semecarpus anacardium can be developed as an important anticancer agent for single agent and/or multiagent cancer therapy.

Cognitive impairment and MRI-findings in patients with HIV on antiretroviral treatment

NARCIS (Netherlands)

Su, T.

2017-01-01

With combination antiretroviral therapy (cART), human immunodeficiency virus (HIV) associated morbidity and mortality has decreased remarkably. Although life expectancy has increased, the frequently reported milder forms of HIV-associated cognitive impairment remain a concern and its pathogenesis is

Medical Applications and Toxicities of Gallium Compounds

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Christopher R. Chitambar

2010-05-01

Full Text Available Over the past two to three decades, gallium compounds have gained importance in the fields of medicine and electronics. In clinical medicine, radioactive gallium and stable gallium nitrate are used as diagnostic and therapeutic agents in cancer and disorders of calcium and bone metabolism. In addition, gallium compounds have displayed anti-inflammatory and immunosuppressive activity in animal models of human disease while more recent studies have shown that gallium compounds may function as antimicrobial agents against certain pathogens. In a totally different realm, the chemical properties of gallium arsenide have led to its use in the semiconductor industry. Gallium compounds, whether used medically or in the electronics field, have toxicities. Patients receiving gallium nitrate for the treatment of various diseases may benefit from such therapy, but knowledge of the therapeutic index of this drug is necessary to avoid clinical toxicities. Animals exposed to gallium arsenide display toxicities in certain organ systems suggesting that environmental risks may exist for individuals exposed to this compound in the workplace. Although the arsenic moiety of gallium arsenide appears to be mainly responsible for its pulmonary toxicity, gallium may contribute to some of the detrimental effects in other organs. The use of older and newer gallium compounds in clinical medicine may be advanced by a better understanding of their mechanisms of action, drug resistance, pharmacology, and side-effects. This review will discuss the medical applications of gallium and its mechanisms of action, the newer gallium compounds and future directions for development, and the toxicities of gallium compounds in current use.

Are patients with schizophrenia impaired in processing non-emotional features of human faces?

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Hayley eDarke

2013-08-01

Full Text Available It is known that individuals with schizophrenia exhibit signs of impaired face processing, however, the exact perceptual and cognitive mechanisms underlying these deficits are yet to be elucidated. One possible source of confusion in the current literature is the methodological and conceptual inconsistencies that can arise from the varied treatment of different aspects of face processing relating to emotional and non-emotional aspects of face perception. This review aims to disentangle the literature by focusing on the performance of patients with schizophrenia in a range of tasks that required processing of non-emotional features of face stimuli (e.g. identity or gender. We also consider the performance of patients on non-face stimuli that share common elements such as familiarity (e.g. cars and social relevance (e.g. gait. We conclude by exploring whether observed deficits are best considered as face-specific and note that further investigation is required to properly assess the potential contribution of more generalised attentional or perceptual impairments.

Dystypia: isolated typing impairment without aphasia, apraxia or visuospatial impairment.

Science.gov (United States)

Otsuki, Mika; Soma, Yoshiaki; Arihiro, Shoji; Watanabe, Yoshimasa; Moriwaki, Hiroshi; Naritomi, Hiroaki

2002-01-01

We report a 60-year-old right-handed Japanese man who showed an isolated persistent typing impairment without aphasia, agraphia, apraxia or any other neuropsychological deficit. We coined the term 'dystypia' for this peculiar neuropsychological manifestation. The symptom was caused by an infarction in the left frontal lobe involving the foot of the second frontal convolution and the frontal operculum. The patient's typing impairment was not attributable to a disturbance of the linguistic process, since he had no aphasia or agraphia. The impairment was not attributable to the impairment of the motor execution process either, since he had no apraxia. Thus, his typing impairment was deduced to be based on a disturbance of the intermediate process where the linguistic phonological information is converted into the corresponding performance. We hypothesized that there is a specific process for typing which branches from the motor programming process presented in neurolinguistic models. The foot of the left second frontal convolution and the operculum may play an important role in the manifestation of 'dystypia'. Copyright 2002 S. Karger AG, Basel

Crispoic acid, a new compound from Laelia marginata (Orchidaceae), and biological evaluations against parasites, human cancer cell lines and Zika virus.

Science.gov (United States)

Belloto, Andrezza C; Souza, Gredson K; Perin, Paula C; Schuquel, Ivania T A; Santin, Silvana M O; Chiavelli, Lucas U R; Garcia, Francielle P; Kaplum, Vanessa; Rodrigues, Jean H S; Scariot, Débora B; Delvecchio, Rodrigo; Machado-Ferreira, Erik; Santana Aguiar, Renato; Soares, Carlos A G; Nakamura, Celso V; Pomini, Armando M

2017-11-08

The phytochemical study of Laelia marginata (Lindl.) L. O. Williams (Orchidaceae) led to the isolation of a new natural product named crispoic acid (1), together with six other known compounds (2-7). The new natural product was identified as a dimer of eucomic acid and was structurally characterised based upon 1D and 2D NMR and HRMS data. Biological assays with plant crude extract, fractions and isolated compounds were performed against two human cancer cell lines (Hela and Siha), and the tropical parasites Trypanosoma cruzi and Leishmania (Leishmania) amazonensis. The phenantrenoid 9,10-dihydro-4-methoxyphenanthren-2,7-diol 2 was active against Hela and Siha cells (CC 50 5.86 ± 0.19 and 20.78 ± 2.72 μg/mL, respectively). Sub-lethal concentrations of the flavone rhamnazin 4 were not able to rescue the viability of the Vero cells infected by Zika virus.

Impact of Salinomycin on human cholangiocarcinoma: induction of apoptosis and impairment of tumor cell proliferation in vitro

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Lieke Thorsten

2012-10-01

Full Text Available Abstract Background Cholangiocarcinoma (CC is a primary liver cancer with increasing incidence worldwide. Despite all efforts made in past years, prognosis remains to be poor. At least in part, this might be explained by a pronounced resistance of CC cells to undergo apoptosis. Thus, new therapeutic strategies are imperatively required. In this study we investigated the effect of Salinomycin, a polyether ionophore antibiotic, on CC cells as an appropriate agent to treat CC. Salinomycin was quite recently identified to induce apoptosis in cancer stem cells and to overcome apoptosis-resistance in several leukemia-cells and other cancer cell lines of different origin. Methods To delineate the effects of Salinomycin on CC, we established an in vitro cell culture model using three different human CC cell lines. After treatment apoptosis as well as migration and proliferation behavior was assessed and additional cell cycle analyses were performed by flowcytometry. Results By demonstrating Annexin V and TUNEL positivity of human CC cells, we provide evidence that Salinomycin reveals the capacity to break apoptosis-resistance in CC cells. Furthermore, we are able to demonstrate that the non-apoptotic cell fraction is characterized by sustainable impaired migration and proliferation. Cell cycle analyses revealed G2-phase accumulation of human CC cells after treatment with Salinomycin. Even though apoptosis is induced in two of three cell lines of CC cells, one cell line remained unaffected in regard of apoptosis but revealed as the other CC cells decreased proliferation and migration. Conclusion In this study, we are able to demonstrate that Salinomycin is an effective agent against previously resistant CC cells and might be a potential candidate for the treatment of CC in the future.

Impaired NFAT and NFκB activation are involved in suppression of CD40 ligand expression by Δ{sup 9}-tetrahydrocannabinol in human CD4{sup +} T cells

Energy Technology Data Exchange (ETDEWEB)

Ngaotepprutaram, Thitirat [Department of Pharmacology and Toxicology, Michigan State University (United States); Center for Integrative Toxicology, Michigan State University (United States); Kaplan, Barbara L.F. [Department of Pharmacology and Toxicology, Michigan State University (United States); Center for Integrative Toxicology, Michigan State University (United States); Neuroscience Program, Michigan State University (United States); Kaminski, Norbert E., E-mail: kamins11@msu.edu [Department of Pharmacology and Toxicology, Michigan State University (United States); Center for Integrative Toxicology, Michigan State University (United States)

2013-11-15

We have previously reported that Δ{sup 9}-tetrahydrocannabinol (Δ{sup 9}-THC), the main psychoactive cannabinoid in marijuana, suppresses CD40 ligand (CD40L) expression by activated mouse CD4{sup +} T cells. CD40L is involved in pathogenesis of many autoimmune and inflammatory diseases. In the present study, we investigated the molecular mechanism of Δ{sup 9}-THC-mediated suppression of CD40L expression using peripheral blood human T cells. Pretreatment with Δ{sup 9}-THC attenuated CD40L expression in human CD4{sup +} T cells activated by anti-CD3/CD28 at both the protein and mRNA level, as determined by flow cytometry and quantitative real-time PCR, respectively. Electrophoretic mobility shift assays revealed that Δ{sup 9}-THC suppressed the DNA-binding activity of both NFAT and NFκB to their respective response elements within the CD40L promoter. An assessment of the effect of Δ{sup 9}-THC on proximal T cell-receptor (TCR) signaling induced by anti-CD3/CD28 showed significant impairment in the rise of intracellular calcium, but no significant effect on the phosphorylation of ZAP70, PLCγ1/2, Akt, and GSK3β. Collectively, these findings identify perturbation of the calcium-NFAT and NFκB signaling cascade as a key mechanistic event by which Δ{sup 9}-THC suppresses human T cell function. - Highlights: • Δ{sup 9}-THC attenuated CD40L expression in activated human CD4+ T cells. • Δ{sup 9}-THC suppressed DNA-binding activity of NFAT and NFκB. • Δ{sup 9}-THC impaired elevation of intracellular Ca2+. • Δ{sup 9}-THC did not affect phosphorylation of ZAP70, PLCγ1/2, Akt, and GSK3β.

Quinolone Amides as Antitrypanosomal Lead Compounds with In Vivo Activity.

Science.gov (United States)

Hiltensperger, Georg; Hecht, Nina; Kaiser, Marcel; Rybak, Jens-Christoph; Hoerst, Alexander; Dannenbauer, Nicole; Müller-Buschbaum, Klaus; Bruhn, Heike; Esch, Harald; Lehmann, Leane; Meinel, Lorenz; Holzgrabe, Ulrike

2016-08-01

Human African trypanosomiasis (HAT) is a major tropical disease for which few drugs for treatment are available, driving the need for novel active compounds. Recently, morpholino-substituted benzyl amides of the fluoroquinolone-type antibiotics were identified to be compounds highly active against Trypanosoma brucei brucei Since the lead compound GHQ168 was challenged by poor water solubility in previous trials, the aim of this study was to introduce structural variations to GHQ168 as well as to formulate GHQ168 with the ultimate goal to increase its aqueous solubility while maintaining its in vitro antitrypanosomal activity. The pharmacokinetic parameters of spray-dried GHQ168 and the newly synthesized compounds GHQ242 and GHQ243 in mice were characterized by elimination half-lives ranging from 1.5 to 3.5 h after intraperitoneal administration (4 mice/compound), moderate to strong human serum albumin binding for GHQ168 (80%) and GHQ243 (45%), and very high human serum albumin binding (>99%) for GHQ242. For the lead compound, GHQ168, the apparent clearance was 112 ml/h and the apparent volume of distribution was 14 liters/kg of body weight (BW). Mice infected with T. b. rhodesiense (STIB900) were treated in a stringent study scheme (2 daily applications between days 3 and 6 postinfection). Exposure to spray-dried GHQ168 in contrast to the control treatment resulted in mean survival durations of 17 versus 9 days, respectively, a difference that was statistically significant. Results that were statistically insignificantly different were obtained between the control and the GHQ242 and GHQ243 treatments. Therefore, GHQ168 was further profiled in an early-treatment scheme (2 daily applications at days 1 to 4 postinfection), and the results were compared with those obtained with a control treatment. The result was statistically significant mean survival times exceeding 32 days (end of the observation period) versus 7 days for the GHQ168 and control treatments

Compound sensory action potential in normal and pathological human nerves

DEFF Research Database (Denmark)

Krarup, Christian

2004-01-01

The compound sensory nerve action potential (SNAP) is the result of phase summation and cancellation of single fiber potentials (SFAPs) with amplitudes that depend on fiber diameter, and the amplitude and shape of the SNAP is determined by the distribution of fiber diameters. Conduction velocitie...... effort and attention to theory and practical detail that may be time consuming....

Experimental setup and analytical methods for the non-invasive determination of volatile organic compounds, formaldehyde and NO{sub x} in exhaled human breath

Energy Technology Data Exchange (ETDEWEB)

Riess, Ulrich; Tegtbur, Uwe [Hannover Medical School, Sports Physiology and Sports Medicine, Carl-Neuberg-Str. 1, 30625 Hannover (Germany); Fauck, Christian; Fuhrmann, Frank; Markewitz, Doreen [Fraunhofer WKI, Department of Material Analysis and Indoor Chemistry, Bienroder Weg 54 E, 38108 Braunschweig (Germany); Salthammer, Tunga, E-mail: tunga.salthammer@wki.fraunhofer.de [Fraunhofer WKI, Department of Material Analysis and Indoor Chemistry, Bienroder Weg 54 E, 38108 Braunschweig (Germany)

2010-06-11

Different analytical devices were tested and evaluated for their suitability of breath gas analysis by examining the physiological parameters and chemical substances in the exhaled breath of ten healthy probands during light cycling in dependence of methanol-rich nutrition. The probands exercised under normal breathing conditions on a bicycle ergometer. Breath air was exhaled into a glass cylinder and collected under steady-state conditions. Non-invasively measured parameters were pulse rate, breath frequency, temperature, relative humidity, NO{sub x}, total volatile organic compounds (TVOC{sub PAS}), carbon dioxide (CO{sub 2}), formaldehyde, methanol, acetaldehyde, acetone, isoprene and volatile organic compounds (VOCs). Methanol rich food and beverages strongly influenced the concentration of methanol and other organic substances in human breath. On the other hand, nutrition and smoking had no clear effect on the physical conditions of the probands. The proton transfer reaction mass spectrometry (PTR-MS) method was found to be very suitable for the analysis of breath gas but the m/z 31, if assigned to formaldehyde, is sensitive to interferences. The time vs. concentration curves of nitric oxide showed sudden peaks up to 120 ppb in most of the measurements. In one case a strong interference of the NO{sub x} signal was observed. The time resolved analysis of exhaled breath gas is of high capability and significance for different applications if reliable analytical techniques are used. Some compounds like nitric oxide (NO), methanol, different VOCs as well as sum parameters like TVOC{sub PAS} are especially suitable as markers. Formaldehyde, which is rapidly metabolized in the human body, could be measured reliably as a trace component by the acetylacetone (acac) method but not by PTR-MS.

A compound methodology to assess the impact of human and organizational factors impact on the risk level of hazardous industrial plants

DEFF Research Database (Denmark)

Monferini, A.; Konstandinidou, M.; Nivolianitou, Z.

2013-01-01

This paper presents a compound methodology devised to relate Human and Organizational Factors (HOFs) to operators’ response time in critical operations within hazardous industrial plants. The methodology has been based on a sensitivity analysis of the nine “families” of the Common Performance Con...... with the variation of one CPC at a time aiming at the detection and containment operation of a gas leakage in a pressure-reduction NG terminal. The whole case study has been run within the framework of the VIRTHUALIS EU project....

Blind's Eye: Employing Google Directions API for Outdoor Navigation of Visually Impaired Pedestrians

Directory of Open Access Journals (Sweden)

SABA FEROZMEMON

2017-07-01

Full Text Available Vision plays a paramount role in our everyday life and assists human in almost every walk of life. The people lacking vision sense require assistance to move freely. The inability of unassisted navigation and orientation in outdoor environments is one of the most important constraints for people with visual impairment. Motivated by this problem, we developed a simplified and user friendly navigation system that allows visually impaired pedestrians to reach their desired outdoor location. We designed a Braille keyboard to allow the blind user to input their destination. The proposed system makes use of Google Directions API (Application Program Interface to generate the right path to a destination. The visually impaired pedestrians have to wear a vibration belt to keep them on the track. The evaluation exposes shortcomings of Google Directions API when used for navigating the visually impaired pedestrians in an outdoor environment.

Impairments in Component Processes of Executive Function and Episodic Memory in Alcoholism, HIV Infection, and HIV Infection with Alcoholism Comorbidity.

Science.gov (United States)

Fama, Rosemary; Sullivan, Edith V; Sassoon, Stephanie A; Pfefferbaum, Adolf; Zahr, Natalie M

2016-12-01

Executive functioning and episodic memory impairment occur in HIV infection (HIV) and chronic alcoholism (ALC). Comorbidity of these conditions (HIV + ALC) is prevalent and heightens risk of vulnerability to separate and compounded deficits. Age and disease-related variables can also serve as mediators of cognitive impairment and should be considered, given the extended longevity of HIV-infected individuals in this era of improved pharmacological therapy. HIV, ALC, HIV + ALC, and normal controls (NC) were administered traditional and computerized tests of executive function and episodic memory. Test scores were expressed as age- and education-corrected Z-scores; selective tests were averaged to compute Executive Function and Episodic Memory Composite scores. Efficiency scores were calculated for tests with accuracy and response times. HIV, ALC, and HIV + ALC had lower scores than NC on Executive Function and Episodic Memory Composites, with HIV + ALC even lower than ALC and HIV on the Episodic Memory Composite. Impairments in planning and free recall of visuospatial material were observed in ALC, whereas impairments in psychomotor speed, sequencing, narrative free recall, and pattern recognition were observed in HIV. Lower decision-making efficiency scores than NC occurred in all 3 clinical groups. In ALC, age and lifetime alcohol consumption were each unique predictors of Executive Function and Episodic Memory Composite scores. In HIV + ALC, age was a unique predictor of Episodic Memory Composite score. Disease-specific and disease-overlapping patterns of impairment in HIV, ALC, and HIV + ALC have implications regarding brain systems disrupted by each disease and clinical ramifications regarding the complexities and compounded damping of cognitive functioning associated with dual diagnosis that may be exacerbated with aging. Copyright © 2016 by the Research Society on Alcoholism.

Carcinogenicity assessment of water-soluble nickel compounds.

Science.gov (United States)

Goodman, Julie E; Prueitt, Robyn L; Dodge, David G; Thakali, Sagar

2009-01-01

IARC is reassessing the human carcinogenicity of nickel compounds in 2009. To address the inconsistencies among results from studies of water-soluble nickel compounds, we conducted a weight-of-evidence analysis of the relevant epidemiological, toxicological, and carcinogenic mode-of-action data. We found the epidemiological evidence to be limited, in that some, but not all, data suggest that exposure to soluble nickel compounds leads to increased cancer risk in the presence of certain forms of insoluble nickel. Although there is no evidence that soluble nickel acts as a complete carcinogen in animals, there is limited evidence that suggests it may act as a tumor promoter. The mode-of-action data suggest that soluble nickel compounds will not be able to cause genotoxic effects in vivo because they cannot deliver sufficient nickel ions to nuclear sites of target cells. Although the mode-of-action data suggest several possible non-genotoxic effects of the nickel ion, it is unclear whether soluble nickel compounds can elicit these effects in vivo or whether these effects, if elicited, would result in tumor promotion. The mode-of-action data equally support soluble nickel as a promoter or as not being a causal factor in carcinogenesis at all. The weight of evidence does not indicate that soluble nickel compounds are complete carcinogens, and there is only limited evidence that they could act as tumor promoters.

Repeatability of two-dimensional chemical shift imaging multivoxel proton magnetic resonance spectroscopy for measuring human cerebral choline-containing compounds.

Science.gov (United States)

Puri, Basant K; Egan, Mary; Wallis, Fintan; Jakeman, Philip

2018-03-22

To investigate the repeatability of proton magnetic resonance spectroscopy in the in vivo measurement of human cerebral levels of choline-containing compounds (Cho). Two consecutive scans were carried out in six healthy resting subjects at a magnetic field strength of 1.5 T. On each occasion, neurospectroscopy data were collected from 64 voxels using the same 2D chemical shift imaging (CSI) sequence. The data were analyzed in the same way, using the same software, to obtain the values for each voxel of the ratio of Cho to creatine. The Wilcoxon related-samples signed-rank test, coefficient of variation (CV), repeatability coefficient (RC), and intraclass correlation coefficient (ICC) were used to assess the repeatability. The CV ranged from 2.75% to 33.99%, while the minimum RC was 5.68%. There was excellent reproducibility, as judged by significant ICC values, in 26 voxels. Just three voxels showed significant differences according to the Wilcoxon related-samples signed-rank test. It is therefore concluded that when CSI multivoxel proton neurospectroscopy is used to measure cerebral choline-containing compounds at 1.5 T, the reproducibility is highly acceptable.

Novel strategies for microdose studies using non-radiolabeled compounds.

Science.gov (United States)

Maeda, Kazuya; Sugiyama, Yuichi

2011-06-19

Microdose studies using non-radiolabeled compounds enable assessment of the clinical pharmacokinetics of drug candidates in humans without the need to synthesize radiolabeled compounds. We have demonstrated that the quantification limits of many drugs measured by LC-MS/MS are low enough to allow estimation of their pharmacokinetic parameters following administration of a microdose. Our previous microdose studies with LC-MS/MS demonstrated the linear pharmacokinetics of fexofenadine between microdoses and therapeutic doses. We also obtained time profiles of plasma concentrations of nicardipine and its multiple metabolites following administration of a microdose. A significant advantage of using non-radiolabeled compounds is the ability to perform cassette microdose studies. By administering multiple drug candidates to the same subject, we can select compounds with appropriate pharmacokinetic properties simultaneously. We can also clarify major factors dominating the pharmacokinetics of drug candidates by cocktail microdosing of the test compounds and probe substrates with or without specific inhibitors for enzymes/transporters. Copyright © 2011 Elsevier B.V. All rights reserved.

Exploring Marine Cyanobacteria for Lead Compounds of Pharmaceutical Importance

Directory of Open Access Journals (Sweden)

Bushra Uzair

2012-01-01

Full Text Available The Ocean, which is called the “mother of origin of life,” is also the source of structurally unique natural products that are mainly accumulated in living organisms. Cyanobacteria are photosynthetic prokaryotes used as food by humans. They are excellent source of vitamins and proteins vital for life. Several of these compounds show pharmacological activities and are helpful for the invention and discovery of bioactive compounds, primarily for deadly diseases like cancer, acquired immunodeficiency syndrome (AIDS, arthritis, and so forth, while other compounds have been developed as analgesics or to treat inflammation, and so forth. They produce a large variety of bioactive compounds, including substances with anticancer and antiviral activity, UV protectants, specific inhibitors of enzymes, and potent hepatotoxins and neurotoxins. Many cyanobacteria produce compounds with potent biological activities. This paper aims to showcase the structural diversity of marine cyanobacterial secondary metabolites with a comprehensive coverage of alkaloids and other applications of cyanobacteria.

Peripheral surgical wounding may induce cognitive impairment through interlukin-6-dependent mechanisms in aged mice

OpenAIRE

Dong, Yuanlin; Xu, Zhipeng; Huang, Lining; Zhang, Yiying; Xie, Zhongcong

2016-01-01

Post-operative cognitive dysfunction (POCD) is associated with morbidity, mortality and increased cost of medical care. However, the neuropathogenesis and targeted interventions of POCD remain largely to be determined. We have found that the peripheral surgical wounding induces an age-dependent A? accumulation, neuroinflammation and cognitive impairment in aged mice. Pro-inflammatory cytokine interlukin-6 (IL-6) has been reported to be associated with cognitive impairment in rodents and human...

Navigation skill impairment: Another dimension of the driving difficulties in minimal hepatic encephalopathy.

Science.gov (United States)

Bajaj, Jasmohan S; Hafeezullah, Muhammad; Hoffmann, Raymond G; Varma, Rajiv R; Franco, Jose; Binion, David G; Hammeke, Thomas A; Saeian, Kia

2008-02-01

Patients with minimal hepatic encephalopathy (MHE) have attention, response inhibition, and working memory difficulties that are associated with driving impairment and high motor vehicle accident risk. Navigation is a complex system needed for safe driving that requires functioning working memory and other domains adversely affected by MHE. The aim of this study was to determine the effect of MHE on navigation skills and correlate them with psychometric impairment. Forty-nine nonalcoholic patients with cirrhosis (34 MHE+, 15 MHE-; divided on the basis of a battery of block design, digit symbol, and number connection test A) and 48 age/education-matched controls were included. All patients underwent the psychometric battery and inhibitory control test (ICT) (a test of response inhibition) and driving simulation. Driving simulation consisted of 4 parts: (1) training; (2) driving (outcome being accidents); (3) divided attention (outcome being missed tasks); and (4) navigation, driving along a marked path on a map in a "virtual city" (outcome being illegal turns). Illegal turns were significantly higher in MHE+ (median 1; P = 0.007) compared with MHE-/controls (median 0). Patients who were MHE+ missed more divided attention tasks compared with others (median MHE+ 1, MHE-/controls 0; P = 0.001). Similarly, accidents were higher in patients who were MHE+ (median 2.5; P = 0.004) compared with MHE- (median 1) or controls (median 2). Accidents and illegal turns were significantly correlated (P = 0.001, r = 0.51). ICT impairment was the test most correlated with illegal turns (r = 0.6) and accidents (r = 0.44), although impairment on the other tests were also correlated with illegal turns. Patients positive for MHE have impaired navigation skills on a driving simulator, which is correlated with impairment in response inhibition (ICT) and attention. This navigation difficulty may pose additional driving problems, compounding the pre-existing deleterious effect of attention

Glucocorticoids mediate stress-induced impairment of retrieval of stimulus-response memory.

Science.gov (United States)

Atsak, Piray; Guenzel, Friederike M; Kantar-Gok, Deniz; Zalachoras, Ioannis; Yargicoglu, Piraye; Meijer, Onno C; Quirarte, Gina L; Wolf, Oliver T; Schwabe, Lars; Roozendaal, Benno

2016-05-01

Acute stress and elevated glucocorticoid hormone levels are well known to impair the retrieval of hippocampus-dependent 'declarative' memory. Recent findings suggest that stress might also impair the retrieval of non-hippocampal memories. In particular, stress shortly before retention testing was shown to impair the retrieval of striatal stimulus-response associations in humans. However, the mechanism underlying this stress-induced retrieval impairment of non-hippocampal stimulus-response memory remains elusive. In the present study, we investigated whether an acute elevation in glucocorticoid levels mediates the impairing effects of stress on retrieval of stimulus-response memory. Male Sprague-Dawley rats were trained on a stimulus-response task in an eight-arm radial maze until they learned to associate a stimulus, i.e., cue, with a food reward in one of the arms. Twenty-four hours after successful acquisition, they received a systemic injection of vehicle, corticosterone (1mg/kg), the corticosterone-synthesis inhibitor metyrapone (35mg/kg) or were left untreated 1h before retention testing. We found that the corticosterone injection impaired the retrieval of stimulus-response memory. We further found that the systemic injection procedure per se was stressful as the vehicle administration also increased plasma corticosterone levels and impaired the retrieval of stimulus-response memory. However, memory retrieval was not impaired when rats were tested 2min after the systemic vehicle injection, before any stress-induced elevation in corticosterone levels had occurred. Moreover, metyrapone treatment blocked the effect of injection stress on both plasma corticosterone levels and memory retrieval impairment, indicating that the endogenous corticosterone response mediates the stress-induced memory retrieval impairment. None of the treatments affected rats' locomotor activity or motivation to search for the food reward within the maze. These findings show that stress

Screening of pharmacologically active small molecule compounds identifies antifungal agents against Candida biofilms

Directory of Open Access Journals (Sweden)

Takao eWatamoto

2015-12-01

Full Text Available Candida species have emerged as important and common opportunistic human pathogens, particularly in immunocompromised individuals. The current antifungal therapies either have toxic side effects or are insufficiently effect. The aim of this study is develop new small-molecule antifungal compounds by library screening methods using C. albicans, and to evaluate their antifungal effects on Candida biofilms and cytotoxic effects on human cells. Wild-type C. albicans strain SC5314 was used in library screening. To identify antifungal compounds, we screened a small-molecule library of 1,280 pharmacologically active compounds (LOPAC1280TM using an antifungal susceptibility test (AST. To investigate the antifungal effects of the hit compounds, ASTs were conducted using Candida strains in various growth modes, including biofilms. We tested the cytotoxicity of the hit compounds using human gingival fibroblast (hGF cells to evaluate their clinical safety. Only 35 compounds were identified by screening, which inhibited the metabolic activity of C. albicans by >50%. Of these, 26 compounds had fungistatic effects and 9 compounds had fungicidal effects on C. albicans. Five compounds, BAY11-7082, BAY11-7085, sanguinarine chloride hydrate, ellipticine and CV-3988, had strong fungicidal effects and could inhibit the metabolic activity of Candida biofilms. However, BAY11-7082, BAY11-7085, sanguinarine chloride hydrate and ellipticine were cytotoxic to hGF cells at low concentrations. CV-3988 showed no cytotoxicity at a fungicidal concentration.Four of the compounds identified, BAY11-7082, BAY11-7085, sanguinarine chloride hydrate and ellipticine, had toxic effects on Candida strains and hGF cells. In contrast, CV-3988 had fungicidal effects on Candida strains, but low cytotoxic effects on hGF cells. Therefore, this screening reveals agent, CV-3988 that was previously unknown to be antifungal agent, which could be a novel therapies for superficial mucosal

Mutations in Alström protein impair terminal differentiation of cardiomyocytes.

Science.gov (United States)

Shenje, Lincoln T; Andersen, Peter; Halushka, Marc K; Lui, Cecillia; Fernandez, Laviel; Collin, Gayle B; Amat-Alarcon, Nuria; Meschino, Wendy; Cutz, Ernest; Chang, Kenneth; Yonescu, Raluca; Batista, Denise A S; Chen, Yan; Chelko, Stephen; Crosson, Jane E; Scheel, Janet; Vricella, Luca; Craig, Brian D; Marosy, Beth A; Mohr, David W; Hetrick, Kurt N; Romm, Jane M; Scott, Alan F; Valle, David; Naggert, Jürgen K; Kwon, Chulan; Doheny, Kimberly F; Judge, Daniel P

2014-03-04

Cardiomyocyte cell division and replication in mammals proceed through embryonic development and abruptly decline soon after birth. The process governing cardiomyocyte cell cycle arrest is poorly understood. Here we carry out whole-exome sequencing in an infant with evidence of persistent postnatal cardiomyocyte replication to determine the genetic risk factors. We identify compound heterozygous ALMS1 mutations in the proband, and confirm their presence in her affected sibling, one copy inherited from each heterozygous parent. Next, we recognize homozygous or compound heterozygous truncating mutations in ALMS1 in four other children with high levels of postnatal cardiomyocyte proliferation. Alms1 mRNA knockdown increases multiple markers of proliferation in cardiomyocytes, the percentage of cardiomyocytes in G2/M phases, and the number of cardiomyocytes by 10% in cultured cells. Homozygous Alms1-mutant mice have increased cardiomyocyte proliferation at 2 weeks postnatal compared with wild-type littermates. We conclude that deficiency of Alström protein impairs postnatal cardiomyocyte cell cycle arrest.

Impairments of Motor Function While Multitasking in HIV.

Science.gov (United States)

Kronemer, Sharif I; Mandel, Jordan A; Sacktor, Ned C; Marvel, Cherie L

2017-01-01

Human immunodeficiency virus (HIV) became a treatable illness with the introduction of combination antiretroviral therapy (CART). As a result, patients with regular access to CART are expected to live decades with HIV. Long-term HIV infection presents unique challenges, including neurocognitive impairments defined by three major stages of HIV-associated neurocognitive disorders (HAND). The current investigation aimed to study cognitive and motor impairments in HIV using a novel multitasking paradigm. Unlike current standard measures of cognitive and motor performance in HIV, multitasking increases real-world validity by mimicking the dual motor and cognitive demands that are part of daily professional and personal settings (e.g., driving, typing and writing). Moreover, multitask assessments can unmask compensatory mechanisms, normally used under single task conditions, to maintain performance. This investigation revealed that HIV+ participants were impaired on the motor component of the multitask, while cognitive performance was spared. A patient-specific positive interaction between motor performance and working memory recall was driven by poor HIV+ multitaskers. Surprisingly, HAND stage did not correspond with multitask performance and a variety of commonly used assessments indicated normal motor function among HIV+ participants with poor motor performance during the experimental task. These results support the use of multitasks to reveal otherwise hidden impairment in chronic HIV by expanding the sensitivity of clinical assessments used to determine HAND stage. Future studies should examine the capability of multitasks to predict performance in personal, professional and health-related behaviors and prognosis of patients living with chronic HIV.

Antiviral lead compounds from marine sponges

KAUST Repository

Sagar, Sunil

2010-10-11

Marine sponges are currently one of the richest sources of pharmacologically active compounds found in the marine environment. These bioactive molecules are often secondary metabolites, whose main function is to enable and/or modulate cellular communication and defense. They are usually produced by functional enzyme clusters in sponges and/or their associated symbiotic microorganisms. Natural product lead compounds from sponges have often been found to be promising pharmaceutical agents. Several of them have successfully been approved as antiviral agents for clinical use or have been advanced to the late stages of clinical trials. Most of these drugs are used for the treatment of human immunodeficiency virus (HIV) and herpes simplex virus (HSV). The most important antiviral lead of marine origin reported thus far is nucleoside Ara-A (vidarabine) isolated from sponge Tethya crypta. It inhibits viral DNA polymerase and DNA synthesis of herpes, vaccinica and varicella zoster viruses. However due to the discovery of new types of viruses and emergence of drug resistant strains, it is necessary to develop new antiviral lead compounds continuously. Several sponge derived antiviral lead compounds which are hopedto be developed as future drugs are discussed in this review. Supply problems are usually the major bottleneck to the development of these compounds as drugs during clinical trials. However advances in the field of metagenomics and high throughput microbial cultivation has raised the possibility that these techniques could lead to the cost-effective large scale production of such compounds. Perspectives on biotechnological methods with respect to marine drug development are also discussed. 2010 by the authors; licensee MDPI.

The relationship between impaired driving crashes and beliefs about impaired driving: do residents in high crash rate counties have greater concerns about impaired driving?

Science.gov (United States)

Beck, Kenneth H; Yan, Alice F; Wang, Min Qi; Kerns, Timothy J; Burch, Cynthia A

2009-04-01

The purpose of this investigation was to examine the relationship between impaired driving crashes and public beliefs and concerns about impaired driving across each of Maryland's twenty-four counties (including Baltimore City). It was hypothesized that residents of counties that experience higher impaired driving crashes would express more concerns about impaired driving and perceive more risks about driving impaired than residents of counties that have lower rates of impaired driving. Data for alcohol impaired driving crashes were obtained for the years 2004-2006. These data were compared to public opinion data that was obtained annually by random-digit-dial telephone surveys from 2004 to 2007. Concerns about drunk driving as well as perceptions of the likelihood of being stopped by the police if one were to drive after having too much to drink were related to counties with higher serious impaired driving crash rates, as were perceptions that the police and the legal system were too lenient. Perceptions about the likelihood of being stopped by the police were higher in those counties with more impaired driving enforcement activity. Perceptions of concern appear to be shaped more by crash exposure than enforcement activity. Campaigns that address impaired driving prevention should substantially increase enforcement, strengthen the adjudication process of impaired drivers, and emphasize the potential seriousness of drinking-driving crashes in their promotional activities.

Organic Compounds in Clackamas River Water Used for Public Supply near Portland, Oregon, 2003-05

Science.gov (United States)

Carpenter, Kurt D.; McGhee, Gordon

2009-01-01

Organic compounds studied in this U.S. Geological Survey (USGS) assessment generally are man-made, including pesticides, gasoline hydrocarbons, solvents, personal care and domestic-use products, disinfection by-products, and manufacturing additives. In all, 56 compounds were detected in samples collected approximately monthly during 2003-05 at the intake for the Clackamas River Water plant, one of four community water systems on the lower Clackamas River. The diversity of compounds detected suggests a variety of different sources and uses (including wastewater discharges, industrial, agricultural, domestic, and others) and different pathways to drinking-water supplies (point sources, precipitation, overland runoff, ground-water discharge, and formation during water treatment). A total of 20 organic compounds were commonly detected (in at least 20 percent of the samples) in source water and (or) finished water. Fifteen compounds were commonly detected in source water, and five of these compounds (benzene, m- and p-xylene, diuron, simazine, and chloroform) also were commonly detected in finished water. With the exception of gasoline hydrocarbons, disinfection by-products, chloromethane, and the herbicide diuron, concentrations in source and finished water were less than 0.1 microgram per liter and always less than human-health benchmarks, which are available for about 60 percent of the compounds detected. On the basis of this screening-level assessment, adverse effects to human health are assumed to be negligible (subject to limitations of available human-health benchmarks).

Organic Compounds in Potomac River Water Used for Public Supply near Washington, D.C., 2003-05

Science.gov (United States)

Brayton, Michael J.; Denver, Judith M.; Delzer, Gregory C.; Hamilton, Pixie A.

2008-01-01

Organic compounds studied in this U.S. Geological Survey (USGS) assessment generally are man-made, including, in part, pesticides, solvents, gasoline hydrocarbons, personal care and domestic-use products, and refrigerants and propellants. A total of 85 of 277 compounds were detected at least once among the 25 samples collected approximately monthly during 2003-05 at the intake of the Washington Aqueduct, one of several community water systems on the Potomac River upstream from Washington, D.C. The diversity of compounds detected indicate a variety of different sources and uses (including wastewater discharge, industrial, agricultural, domestic, and others) and different pathways (including treated wastewater outfalls located upstream, overland runoff, and ground-water discharge) to drinking-water supplies. Seven compounds were detected year-round in source-water intake samples, including selected herbicide compounds commonly used in the Potomac River Basin and in other agricultural areas across the United States. Two-thirds of the 26 compounds detected most commonly in source water (in at least 20 percent of the samples) also were detected most commonly in finished water (after treatment but prior to distribution). Concentrations for all detected compounds in source and finished water generally were less than 0.1 microgram per liter and always less than human-health benchmarks, which are available for about one-half of the detected compounds. On the basis of this screening-level assessment, adverse effects to human health are expected to be negligible (subject to limitations of available human-health benchmarks).

Governing processes for reactive nitrogen compounds in the European atmosphere

DEFF Research Database (Denmark)

Hertel, Ole; Skjøth, Carsten Ambelas; Reis, S.

2012-01-01

+)), oxidized nitrogen (NOy: nitrogen monoxide (NO) + nitrogen dioxide (NO2) and their reaction products) as well as organic nitrogen compounds (organic N). Pollution abatement strategies need to take into account the differences in the governing processes of these compounds when assessing their impact...... on ecosystem services, biodiversity, human health and climate. NOx (NO+NO2) emitted from traffic affects human health in urban areas where the presence of buildings increases the residence time in streets. In urban areas this leads to enhanced exposure of the population to NOx concentrations. NOx emissions.......5 and PM10 (mass of aerosols with an aerodynamic diameter of less than 2.5 and 10 mu m, respectively) with an impact on radiation balance as well as potentially on human health. Little is known quantitatively and qualitatively about organic N in the atmosphere, other than that it contributes a significant...

Phenolic Compounds in the Potato and Its Byproducts: An Overview

Science.gov (United States)

Akyol, Hazal; Riciputi, Ylenia; Capanoglu, Esra; Caboni, Maria Fiorenza; Verardo, Vito

2016-01-01

The potato (Solanum tuberosum L.) is a tuber that is largely used for food and is a source of different bioactive compounds such as starch, dietary fiber, amino acids, minerals, vitamins, and phenolic compounds. Phenolic compounds are synthetized by the potato plant as a protection response from bacteria, fungi, viruses, and insects. Several works showed that these potato compounds exhibited health-promoting effects in humans. However, the use of the potato in the food industry submits this vegetable to different processes that can alter the phenolic content. Moreover, many of these compounds with high bioactivity are located in the potato’s skin, and so are eliminated as waste. In this review the most recent articles dealing with phenolic compounds in the potato and potato byproducts, along with the effects of harvesting, post-harvest, and technological processes, have been reviewed. Briefly, the phenolic composition, main extraction, and determination methods have been described. In addition, the “alternative” food uses and healthy properties of potato phenolic compounds have been addressed. PMID:27240356

Reduced expression of glutamate transporter EAAT2 and impaired glutamate transport in human primary astrocytes exposed to HIV-1 or gp120

International Nuclear Information System (INIS)

Wang Zhuying; Pekarskaya, Olga; Bencheikh, Meryem; Chao Wei; Gelbard, Harris A.; Ghorpade, Anuja; Rothstein, Jeffrey D.; Volsky, David J.

2003-01-01

L-Glutamate is the major excitatory neurotransmitter in the brain. Astrocytes maintain low levels of synaptic glutamate by high-affinity uptake and defects in this function may lead to neuronal cell death by excitotoxicity. We tested the effects of HIV-1 and its envelope glycoprotein gp120 upon glutamate uptake and expression of glutamate transporters EAAT1 and EAAT2 in fetal human astrocytes in vitro. Astrocytes isolated from fetal tissues between 16 and 19 weeks of gestation expressed EAAT1 and EAAT2 RNA and proteins as detected by Northern blot analysis and immunoblotting, respectively, and the cells were capable of specific glutamate uptake. Exposure of astrocytes to HIV-1 or gp120 significantly impaired glutamate uptake by the cells, with maximum inhibition within 6 h, followed by gradual decline during 3 days of observation. HIV-1-infected cells showed a 59% reduction in V max for glutamate transport, indicating a reduction in the number of active transporter sites on the cell surface. Impaired glutamate transport after HIV-1 infection or gp120 exposure correlated with a 40-70% decline in steady-state levels of EAAT2 RNA and protein. EAAT1 RNA and protein levels were less affected. Treatment of astrocytes with tumor necrosis factor-α (TNF-α) decreased the expression of both EAAT1 and EAAT2, but neither HIV-1 nor gp120 were found to induce TNF-α production by astrocytes. These findings demonstrate that HIV-1 and gp120 induce transcriptional downmodulation of the EAAT2 transporter gene in human astrocytes and coordinately attenuate glutamate transport by the cells. Reduction of the ability of HIV-1-infected astrocytes to take up glutamate may contribute to the development of neurological disease

Factors that influence the volatile organic compound content in human breath

NARCIS (Netherlands)

Blanchet, L.; Smolinska, Agnieszka; Baranska, Agnieszka; Tigchelaar-Feenstra, E.; Swertz, M.; Zhernakova, A.; Dallinga, J. W.; Wijmenga, C.; van Schooten, Frederik J.

Background. Thousands of endogenous and exogenous volatile organic compounds (VOCs) are excreted in each breath. Inflammatory and deviant metabolic processes affect the level of endogeneous VOCs, which can serve as specific biomarkers for clinical diagnosis and disease monitoring. Important issues

20 CFR 416.921 - What we mean by a not severe impairment(s) in an adult.

Science.gov (United States)

2010-04-01

... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false What we mean by a not severe impairment(s) in an adult. 416.921 Section 416.921 Employees' Benefits SOCIAL SECURITY ADMINISTRATION SUPPLEMENTAL... Disability § 416.921 What we mean by a not severe impairment(s) in an adult. (a) Non-severe impairment(s). An...

Cannabinoid-like anti-inflammatory compounds from flax fiber.

Science.gov (United States)

Styrczewska, Monika; Kulma, Anna; Ratajczak, Katarzyna; Amarowicz, Ryszard; Szopa, Jan

2012-09-01

Flax is a valuable source of fibers, linseed and oil. The compounds of the latter two products have already been widely examined and have been proven to possess many health-beneficial properties. In the course of analysis of fibers extract from previously generated transgenic plants overproducing phenylpropanoids a new terpenoid compound was discovered.The UV spectra and the retention time in UPLC analysis of this new compound reveal similarity to a cannabinoid-like compound, probably cannabidiol (CBD). This was confirmed by finding two ions at m/z 174.1 and 231.2 in mass spectra analysis. Further confirmation of the nature of the compound was based on a biological activity assay. It was found that the compound affects the expression of genes involved in inflammatory processes in mouse and human fibroblasts and likely the CBD from Cannabis sativa activates the specific peripheral cannabinoid receptor 2 (CB2) gene expression. Besides fibers, the compound was also found in all other flax tissues. It should be pointed out that the industrial process of fabric production does not affect CBD activity.The presented data suggest for the first time that flax products can be a source of biologically active cannabinoid-like compounds that are able to influence the cell immunological response. These findings might open up many new applications for medical flax products, especially for the fabric as a material for wound dressing with anti-inflammatory properties.

The combined effect of visual impairment and cognitive impairment on disability in older people.

Science.gov (United States)

Whitson, Heather E; Cousins, Scott W; Burchett, Bruce M; Hybels, Celia F; Pieper, Carl F; Cohen, Harvey J

2007-06-01

To determine the risk of disability in individuals with coexisting visual and cognitive impairment and to compare the magnitude of risk associated with visual impairment, cognitive impairment, or the multimorbidity. Prospective cohort. North Carolina. Three thousand eight hundred seventy-eight participants in the North Carolina Established Populations for the Epidemiologic Studies of the Elderly with nonmissing visual status, cognitive status, and disability status data at baseline Short Portable Mental Status Questionnaire (cognitive impairment defined as > or =4 errors), self reported visual acuity (visual impairment defined as inability to see well enough to recognize a friend across the street or to read newspaper print), demographic and health-related variables, disability status (activities of daily living (ADLs), instrumental activities of daily living (IADLs), mobility), death, and time to nursing home placement. Participants with coexisting visual and cognitive impairment were at greater risk of IADL disability (odds ratio (OR)=6.50, 95% confidence interval (CI)=4.34-9.75), mobility disability (OR=4.04, 95% CI=2.49-6.54), ADL disability (OR=2.84, 95% CI=1.87-4.32), and incident ADL disability (OR=3.66, 95%, CI=2.36-5.65). In each case, the estimated OR associated with the multimorbidity was greater than the estimated OR associated with visual or cognitive impairment alone, a pattern that was not observed for other adverse outcomes assessed. No significant interactions were observed between cognitive impairment and visual impairment as predictors of disability status. Individuals with coexisting visual impairment and cognitive impairment are at high risk of disability, with each condition contributing additively to disability risk. Further study is needed to improve functional trajectories in patients with this prevalent multimorbidity. When visual or cognitive impairment is present, efforts to maximize the other function may be beneficial.

Multiple nutritional deficiencies in cerebral palsy compounding physical and functional impairments

Directory of Open Access Journals (Sweden)

P G Hariprasad

2017-01-01

Full Text Available Introduction: Cerebral palsy (CP refers to a spectrum of disorders causing physical and intellectual morbidity. Macro and micro nutrient deficiencies often contribute to the subnormal physical and mental capabilities of them. Objectives: To assess the growth, nutritional status, physical and functional ability and quality of life in cerebral palsy children and to determine any relation with their gross motor and functional capabilities. Method: The study was conducted at a Tertiary Care Centre, with the participants in the age group 1-16 years. A pretested evaluation tool was prepared which included Anthropometric measurements, tests for hemoglobin and Vitamin D estimation, evidence of micronutrient deficiencies, Dietary patterns, Epidemiological factors, Functional assessment using GMFM (Gross Motor Function Measure and FIM (Functional Independent Measurement scales and Quality of life (QOL assessment. The data was statistically analyzed. Results: Out of the 41 children, 30 had quadriplegia, 3 had hemiplegia and 8 had spastic diplegia. 34 (82.9% were severely underweight, 35 (85.4% had severe stunting and 38 (92.7% had severe wasting. Micronutrient deficiencies were noted like vitamin B complex deficiency in 37 (90.2%, vitamin A deficiency in 31 (75.6%, low vitamin D levels in 27 (65.9% and insufficient levels in 9 (22%, severe anemia in 5 (12.2% and moderate anemia in 26 (63.4%.The gross motor and functional scores were suboptimum in the majority of patients and the care givers had significant impairment in the quality of life. Conclusion: Majority of children with cerebral palsy had multiple nutritional deficiencies, gross motor and functional disabilities. QOL of the children and their care givers were suboptimum. A comprehensive package that address dietary intake, correction of micronutrient deficiencies especially anemia and vitamin D deficiency, physical and emotional support is recommended for the wellbeing of the affected children.

Dialogue enabling speech-to-text user assistive agent system for hearing-impaired person.

Science.gov (United States)

Lee, Seongjae; Kang, Sunmee; Han, David K; Ko, Hanseok

2016-06-01

A novel approach for assisting bidirectional communication between people of normal hearing and hearing-impaired is presented. While the existing hearing-impaired assistive devices such as hearing aids and cochlear implants are vulnerable in extreme noise conditions or post-surgery side effects, the proposed concept is an alternative approach wherein spoken dialogue is achieved by means of employing a robust speech recognition technique which takes into consideration of noisy environmental factors without any attachment into human body. The proposed system is a portable device with an acoustic beamformer for directional noise reduction and capable of performing speech-to-text transcription function, which adopts a keyword spotting method. It is also equipped with an optimized user interface for hearing-impaired people, rendering intuitive and natural device usage with diverse domain contexts. The relevant experimental results confirm that the proposed interface design is feasible for realizing an effective and efficient intelligent agent for hearing-impaired.

Extent and neural basis of semantic memory impairment in mild cognitive impairment.

Science.gov (United States)

Barbeau, Emmanuel J; Didic, Mira; Joubert, Sven; Guedj, Eric; Koric, Lejla; Felician, Olivier; Ranjeva, Jean-Philippe; Cozzone, Patrick; Ceccaldi, Mathieu

2012-01-01

An increasing number of studies indicate that semantic memory is impaired in mild cognitive impairment (MCI). However, the extent and the neural basis of this impairment remain unknown. The aim of the present study was: 1) to evaluate whether all or only a subset of semantic domains are impaired in MCI patients; and 2) to assess the neural substrate of the semantic impairment in MCI patients using voxel-based analysis of MR grey matter density and SPECT perfusion. 29 predominantly amnestic MCI patients and 29 matched control subjects participated in this study. All subjects underwent a full neuropsychological assessment, along with a battery of five tests evaluating different domains of semantic memory. A semantic memory composite Z-score was established on the basis of this battery and was correlated with MRI grey matter density and SPECT perfusion measures. MCI patients were found to have significantly impaired performance across all semantic tasks, in addition to their anterograde memory deficit. Moreover, no temporal gradient was found for famous faces or famous public events and knowledge for the most remote decades was also impaired. Neuroimaging analyses revealed correlations between semantic knowledge and perirhinal/entorhinal areas as well as the anterior hippocampus. Therefore, the deficits in the realm of semantic memory in patients with MCI is more widespread than previously thought and related to dysfunction of brain areas beyond the limbic-diencephalic system involved in episodic memory. The severity of the semantic impairment may indicate a decline of semantic memory that began many years before the patients first consulted.

The Use of Plant Antimicrobial Compounds for Food Preservation

Science.gov (United States)

Hintz, Tana; Matthews, Karl K.

2015-01-01

Foodborne disease is a global issue with significant impact on human health. With the growing consumer demand for natural preservatives to replace chemical compounds, plant antimicrobial compounds must be thoroughly investigated for their potential to serve as biopreservatives. This review paper will focus on the plant-derived products as antimicrobial agents for use in food preservation and to control foodborne pathogens in foods. Structure, modes of action, stability, and resistance to these plant compounds will be discussed as well as their application in food industries and possible technologies by which they can be delivered. Benefits as well as challenges, such as the need for further research for implementation and governmental regulation, will be highlighted. PMID:26539472

Physiological Aβ Concentrations Produce a More Biomimetic Representation of the Alzheimer's Disease Phenotype in iPSC Derived Human Neurons.

Science.gov (United States)

Berry, Bonnie J; Smith, Alec S T; Long, Christopher J; Martin, Candace C; Hickman, James J

2018-05-22

Alzheimer's disease (AD) is characterized by slow, progressive neurodegeneration leading to severe neurological impairment, but current drug development efforts are limited by the lack of robust, human-based disease models. Amyloid-β (Aβ) is known to play an integral role in AD progression as it has been shown to interfere with neurological function. However, studies into AD pathology commonly apply Aβ to neurons for short durations at nonphysiological concentrations to induce an exaggerated dysfunctional phenotype. Such methods are unlikely to elucidate early stage disease dysfunction, when treatment is still possible, since damage to neurons by these high concentrations is extensive. In this study, we investigated chronic, pathologically relevant Aβ oligomer concentrations to induce an electrophysiological phenotype that is more representative of early AD progression compared to an acute high-dose application in human cortical neurons. The high, acute oligomer dose resulted in severe neuronal toxicity as well as upregulation of tau and phosphorylated tau. Chronic, low-dose treatment produced significant functional impairment without increased cell death or accumulation of tau protein. This in vitro phenotype more closely mirrors the status of early stage neural decline in AD pathology and could provide a valuable tool to further understanding of early stage AD pathophysiology and for screening potential therapeutic compounds.

Congenital hearing impairment

Energy Technology Data Exchange (ETDEWEB)

Robson, Caroline D. [Children' s Hospital and Harvard Medical School, Division of Neuroradiology, Department of Radiology, Boston, MA (United States)

2006-04-15

Establishing the etiology of congenital hearing impairment can significantly improve treatment for certain causes of hearing loss and facilitates genetic counseling. High-resolution CT and MRI have contributed to the evaluation and management of hearing impairment. In addition, with the identification of innumerable genetic loci and genetic defects involved in hearing loss, genetic testing has emerged as an invaluable tool in the assessment of hearing impairment. Some of the common forms of congenital hearing loss are reviewed and their imaging features illustrated. (orig.)

Congenital hearing impairment

International Nuclear Information System (INIS)

Robson, Caroline D.

2006-01-01

Establishing the etiology of congenital hearing impairment can significantly improve treatment for certain causes of hearing loss and facilitates genetic counseling. High-resolution CT and MRI have contributed to the evaluation and management of hearing impairment. In addition, with the identification of innumerable genetic loci and genetic defects involved in hearing loss, genetic testing has emerged as an invaluable tool in the assessment of hearing impairment. Some of the common forms of congenital hearing loss are reviewed and their imaging features illustrated. (orig.)

Physical Impairment

Science.gov (United States)

Trewin, Shari

Many health conditions can lead to physical impairments that impact computer and Web access. Musculoskeletal conditions such as arthritis and cumulative trauma disorders can make movement stiff and painful. Movement disorders such as tremor, Parkinsonism and dystonia affect the ability to control movement, or to prevent unwanted movements. Often, the same underlying health condition also has sensory or cognitive effects. People with dexterity impairments may use a standard keyboard and mouse, or any of a wide range of alternative input mechanisms. Examples are given of the diverse ways that specific dexterity impairments and input mechanisms affect the fundamental actions of Web browsing. As the Web becomes increasingly sophisticated, and physically demanding, new access features at the Web browser and page level will be necessary.

Muscle mitochondrial metabolism and calcium signaling impairment in patients treated with statins

Energy Technology Data Exchange (ETDEWEB)

Sirvent, P., E-mail: pascal.sirvent@univ-bpclermont.fr [U1046, INSERM, Université Montpellier 1 and Université Montpellier 2, 34295 Montpellier (France); CHRU Montpellier, 34295 Montpellier (France); Clermont Université, Université Blaise Pascal, EA 3533, Laboratoire des Adaptations Métaboliques à l' Exercice en conditions Physiologiques et Pathologiques (AME2P), BP 80026, F-63171 Aubière cedex (France); Fabre, O.; Bordenave, S. [U1046, INSERM, Université Montpellier 1 and Université Montpellier 2, 34295 Montpellier (France); CHRU Montpellier, 34295 Montpellier (France); Hillaire-Buys, D. [CHRU Montpellier, 34295 Montpellier (France); Raynaud De Mauverger, E.; Lacampagne, A.; Mercier, J. [U1046, INSERM, Université Montpellier 1 and Université Montpellier 2, 34295 Montpellier (France); CHRU Montpellier, 34295 Montpellier (France)

2012-03-01

The most common and problematic side effect of statins is myopathy. To date, the patho-physiological mechanisms of statin myotoxicity are still not clearly understood. In previous studies, we showed that acute application in vitro of simvastatin caused impairment of mitochondrial function and dysfunction of calcium homeostasis in human and rat healthy muscle samples. We thus evaluated in the present study, mitochondrial function and calcium signaling in muscles of patients treated with statins, who present or not muscle symptoms, by oxygraphy and recording of calcium sparks, respectively. Patients treated with statins showed impairment of mitochondrial respiration that involved mainly the complex I of the respiratory chain and altered frequency and amplitude of calcium sparks. The muscle problems observed in statin-treated patients appear thus to be related to impairment of mitochondrial function and muscle calcium homeostasis, confirming the results we previously reported in vitro. -- Highlights: ► The most common and problematic side effect of statins is myopathy. ► Patients treated with statins showed impairment of mitochondrial respiration. ► Statins-treated patients showed altered frequency and amplitude of calcium sparks.

Muscle mitochondrial metabolism and calcium signaling impairment in patients treated with statins

International Nuclear Information System (INIS)

Sirvent, P.; Fabre, O.; Bordenave, S.; Hillaire-Buys, D.; Raynaud De Mauverger, E.; Lacampagne, A.; Mercier, J.

2012-01-01

The most common and problematic side effect of statins is myopathy. To date, the patho-physiological mechanisms of statin myotoxicity are still not clearly understood. In previous studies, we showed that acute application in vitro of simvastatin caused impairment of mitochondrial function and dysfunction of calcium homeostasis in human and rat healthy muscle samples. We thus evaluated in the present study, mitochondrial function and calcium signaling in muscles of patients treated with statins, who present or not muscle symptoms, by oxygraphy and recording of calcium sparks, respectively. Patients treated with statins showed impairment of mitochondrial respiration that involved mainly the complex I of the respiratory chain and altered frequency and amplitude of calcium sparks. The muscle problems observed in statin-treated patients appear thus to be related to impairment of mitochondrial function and muscle calcium homeostasis, confirming the results we previously reported in vitro. -- Highlights: ► The most common and problematic side effect of statins is myopathy. ► Patients treated with statins showed impairment of mitochondrial respiration. ► Statins-treated patients showed altered frequency and amplitude of calcium sparks.

Organic Compounds in Truckee River Water Used for Public Supply near Reno, Nevada, 2002-05

Science.gov (United States)

Thomas, Karen A.

2009-01-01

Organic compounds studied in this U.S. Geological Survey (USGS) assessment generally are man-made, including, in part, pesticides, solvents, gasoline hydrocarbons, personal care and domestic-use products, and refrigerants and propellants. Of 258 compounds measured, 28 were detected in at least 1 source water sample collected approximately monthly during 2002-05 at the intake of the Chalk Bluff Treatment Plant, on the Truckee River upstream of Reno, Nevada. The diversity of compounds detected indicate various sources and uses (including wastewater discharge, industrial, agricultural, domestic, and others) and different pathways (including point sources from treated wastewater outfalls upstream of the sampling location, overland runoff, and groundwater discharge) to drinking-water supply intakes. Three compounds were detected in more than 20 percent of the source-water intake samples at low concentrations (less than 0.1 microgram per liter), including caffeine, p-cresol (a wood preservative), and toluene (a gasoline hydrocarbon). Sixteen of the 28 compounds detected in source water also were detected in finished water (after treatment, but prior to distribution; 2004-05). Additionally, two disinfection by-products not detected in source water, bromodichloromethane and dibromochloromethane, were detected in all finished water samples. Two detected compounds, cholesterol and 3-beta-coprostanol, are among five naturally occurring biochemicals analyzed in this study. Concentrations for all detected compounds in source and finished water generally were less than 0.1 microgram per liter and always less than human-health benchmarks, which are available for about one-half of the compounds. Seven compounds (toluene, chloroform, bromodichloromethane, dibromodichloromethane, bisphenol A, cholesterol, and 3-beta-coprostanol) were measured at concentrations greater than 0.1 microgram per liter. On the basis of this screening-level assessment, adverse effects to human health are

Natural Bioactive Compounds from Winery By-Products as Health Promoters: A Review

Directory of Open Access Journals (Sweden)

Ana Teixeira

2014-09-01

Full Text Available The relevance of food composition for human health has increased consumers’ interest in the consumption of fruits and vegetables, as well as foods enriched in bioactive compounds and nutraceuticals. This fact has led to a growing attention of suppliers on reuse of agro-industrial wastes rich in healthy plant ingredients. On this matter, grape has been pointed out as a rich source of bioactive compounds. Currently, up to 210 million tons of grapes (Vitis vinifera L. are produced annually, being the 15% of the produced grapes addressed to the wine-making industry. This socio-economic activity generates a large amount of solid waste (up to 30%, w/w of the material used. Winery wastes include biodegradable solids namely stems, skins, and seeds. Bioactive compounds from winery by-products have disclosed interesting health promoting activities both in vitro and in vivo. This is a comprehensive review on the phytochemicals present in winery by-products, extraction techniques, industrial uses, and biological activities demonstrated by their bioactive compounds concerning potential for human health.

Natural bioactive compounds from winery by-products as health promoters: a review.

Science.gov (United States)

Teixeira, Ana; Baenas, Nieves; Dominguez-Perles, Raul; Barros, Ana; Rosa, Eduardo; Moreno, Diego A; Garcia-Viguera, Cristina

2014-09-04

The relevance of food composition for human health has increased consumers' interest in the consumption of fruits and vegetables, as well as foods enriched in bioactive compounds and nutraceuticals. This fact has led to a growing attention of suppliers on reuse of agro-industrial wastes rich in healthy plant ingredients. On this matter, grape has been pointed out as a rich source of bioactive compounds. Currently, up to 210 million tons of grapes (Vitis vinifera L.) are produced annually, being the 15% of the produced grapes addressed to the wine-making industry. This socio-economic activity generates a large amount of solid waste (up to 30%, w/w of the material used). Winery wastes include biodegradable solids namely stems, skins, and seeds. Bioactive compounds from winery by-products have disclosed interesting health promoting activities both in vitro and in vivo. This is a comprehensive review on the phytochemicals present in winery by-products, extraction techniques, industrial uses, and biological activities demonstrated by their bioactive compounds concerning potential for human health.

Phenolic Compounds in Extra Virgin Olive Oil Stimulate Human Osteoblastic Cell Proliferation.

Science.gov (United States)

García-Martínez, Olga; De Luna-Bertos, Elvira; Ramos-Torrecillas, Javier; Ruiz, Concepción; Milia, Egle; Lorenzo, María Luisa; Jimenez, Brigida; Sánchez-Ortiz, Araceli; Rivas, Ana

2016-01-01

In this study, we aimed to clarify the effects of phenolic compounds and extracts from different extra virgin olive oil (EVOO) varieties obtained from fruits of different ripening stages on osteoblast cells (MG-63) proliferation. Cell proliferation was increased by hydroxytyrosol, luteolin, apigenin, p-coumaric, caffeic, and ferulic acids by approximately 11-16%, as compared with controls that were treated with one vehicle alone, while (+)-pinoresinol, oleuropein, sinapic, vanillic acid and derivative (vanillin) did not affect cell proliferation. All phenolic extracts stimulated MG-63 cell growth, and they induced higher cell proliferation rates than individual compounds. The most effective EVOO phenolic extracts were those obtained from the Picual variety, as they significantly increased cell proliferation by 18-22%. Conversely, Arbequina phenolic extracts increased cell proliferation by 9-13%. A decline in osteoblast proliferation was observed in oils obtained from olive fruits collected at the end of the harvest period, as their total phenolic content decreases at this late stage. Further research on the signaling pathways of olive oil phenolic compounds involved in the processes and their metabolism should be carried out to develop new interventions and adjuvant therapies using EVOO for bone health (i.e.osteoporosis) in adulthood and the elderly.

Phenolic Compounds in Extra Virgin Olive Oil Stimulate Human Osteoblastic Cell Proliferation

Science.gov (United States)

García-Martínez, Olga; De Luna-Bertos, Elvira; Ramos-Torrecillas, Javier; Ruiz, Concepción; Milia, Egle; Lorenzo, María Luisa; Jimenez, Brigida; Sánchez-Ortiz, Araceli; Rivas, Ana

2016-01-01

In this study, we aimed to clarify the effects of phenolic compounds and extracts from different extra virgin olive oil (EVOO) varieties obtained from fruits of different ripening stages on osteoblast cells (MG-63) proliferation. Cell proliferation was increased by hydroxytyrosol, luteolin, apigenin, p-coumaric, caffeic, and ferulic acids by approximately 11–16%, as compared with controls that were treated with one vehicle alone, while (+)-pinoresinol, oleuropein, sinapic, vanillic acid and derivative (vanillin) did not affect cell proliferation. All phenolic extracts stimulated MG-63 cell growth, and they induced higher cell proliferation rates than individual compounds. The most effective EVOO phenolic extracts were those obtained from the Picual variety, as they significantly increased cell proliferation by 18–22%. Conversely, Arbequina phenolic extracts increased cell proliferation by 9–13%. A decline in osteoblast proliferation was observed in oils obtained from olive fruits collected at the end of the harvest period, as their total phenolic content decreases at this late stage. Further research on the signaling pathways of olive oil phenolic compounds involved in the processes and their metabolism should be carried out to develop new interventions and adjuvant therapies using EVOO for bone health (i.e.osteoporosis) in adulthood and the elderly. PMID:26930190

Method for Screening Compounds That Influence Virulence Gene Expression in Staphylococcus aureus

DEFF Research Database (Denmark)

Nielsen, A.; Nielsen, Kristian Fog; Frees, D.

2010-01-01

We present a simple assay to examine effects of compounds on virulence gene expression in the human pathogen Staphylococcus aureus. The assay employs transcriptional reporter strains carrying lacZ fused to central virulence genes. Compounds affecting virulence gene expression and activity...... of the agr locus are scored based on color change in the presence of a chromogenic beta-galactosidase substrate. The assay can be used to screen for novel antivirulence compounds from many different sources, such as fungi, as demonstrated here....

New cytotoxic and anti-inflammatory compounds isolated from Morus alba L.

Science.gov (United States)

Qin, Jing; Fan, Min; He, Juan; Wu, Xing-De; Peng, Li-Yan; Su, Jia; Cheng, Xiao; Li, Yan; Kong, Ling-Mei; Li, Rong-Tao; Zhao, Qin-Shi

2015-01-01

Six Diels-Alder adducts (1-6) and nine prenylated flavanones (7-15) were isolated from the root bark of Morus alba L. Among them, soroceal B (1) and sanggenol Q (7) were new compounds. Their structures were elucidated on the basis of extensive spectroscopic methods, including 1D and 2D NMR techniques. Compounds 1-3, 9, 10, 12, 13 and 15 exhibited cytotoxic activity against five human tumour lines and compound 2 inhibited significantly selective cytotoxic activities towards HL-60 and AGS cells with IC50 of 3.4 and 3.6 μM. Compounds 3, 5, 9 and 12 exhibited moderate inhibitory activity against nitric oxide production in LPS-activated RAW264.7.

Cytotoxic and Antimicrobial Compounds from the Marine-Derived Fungus, Penicillium Species

Directory of Open Access Journals (Sweden)

Diaa T. A. Youssef

2018-02-01

Full Text Available The organic extract of liquid cultures of the marine-derived Penicillium sp. was investigated. Fractionation of the extracts of the fungus led to the purification and identification of two new compounds, penicillatides A (1 and B (2, together with the previously reported cyclo(R-Pro–S-Phe (3 and cyclo(R-Pro–R-Phe (4. The structures of compounds 1–4 were assigned by extensive interpretation of their NMR and high-resolution mass spectrometry (HRMS. The antiproliferative and cytotoxic activities of the compounds against three human cancer cell lines as well as their antimicrobial activity against several pathogens were evaluated. Compounds 2–4 displayed variable cytotoxic and antimicrobial activities.

Synthesis and anti-lung cancer activity of a novel arsenomolybdate compound

Science.gov (United States)

Zhu, Tian-Tian; Wang, Juan; Chen, Song-Hu

2017-12-01

The new compound based on Wells-Dawson-type arsenomolybdate: [{Cu10(pz)11Cl4}{As2IIIAs2VMo6VMo12VIO62}]·H2O (1) has been hydrothermally synthesized and characterized by single-crystal X-ray diffraction analysis, X-ray powder diffraction (XRPD), XPS spectroscopy and thermogravimetric analysis (TG). Compound 1 is consisted of two As caps Wells-dawson-type arsenomolybdate and {Cu10(py)11} complexes by chloride bridge. In addition, the antitumor effects of the title compound 1 were studied on three human lung cancer cells (A549, SK-LU-1 and SW1573). The results showed that compared with the positive reference drug carboplatin, compound 1 displayed efficient antitumor activity.

Compound heterozygous mutations (p.Leu13Pro and p.Tyr294*) associated with factor VII deficiency cause impaired secretion through ineffective translocation and extensive intracellular degradation of factor VII.

Science.gov (United States)

Suzuki, Keijiro; Sugawara, Takeshi; Ishida, Yoji; Suwabe, Akira

2013-02-01

Congenital coagulation factor VII (FVII) deficiency is a rare coagulation disease. We investigated the molecular mechanisms of this FVII deficiency in a patient with compound heterozygous mutations. A 22-year-old Japanese female was diagnosed with asymptomatic FVII deficiency. The FVII activity and antigen were greatly reduced (activity, 13.0%; antigen, 10.8%). We analyzed the F7 gene of this patient and characterized mutant FVII proteins using in vitro expression studies. Sequence analysis revealed that the patient was compound heterozygous with a point mutation (p.Leu13Pro) in the central hydrophobic core of the signal peptides and a novel non-sense mutation (p.Tyr294*) in the catalytic domain. Expression studies revealed that mutant FVII with p.Leu13Pro (FVII13P) showed less accumulation in the cells (17.5%) and less secretion into the medium (64.8%) than wild type showed. Truncated FVII resulting from p.Tyr294* (FVII294X) was also decreased in the cells (32.0%), but was not secreted into the medium. Pulse-chase experiments revealed that both mutants were extensively degraded intracellularly compared to wild type. The majority of FVII13P cannot translocate into endoplasmic reticulum (ER). However, a small amount of FVII13P was processed normally with post-translational modifications and was secreted into the medium. The fact that FVII294X was observed only in ER suggests that it is retained in ER. Proteasome apparently plays a central role in these degradations. These findings demonstrate that both mutant FVIIs impaired secretion through ineffective translocation to and retention in ER with extensive intracellular degradation, resulting in an insufficient phenotype. Copyright © 2012 Elsevier Ltd. All rights reserved.

Bioprospecting Sponge-Associated Microbes for Antimicrobial Compounds.

Science.gov (United States)

Indraningrat, Anak Agung Gede; Smidt, Hauke; Sipkema, Detmer

2016-05-02

Sponges are the most prolific marine organisms with respect to their arsenal of bioactive compounds including antimicrobials. However, the majority of these substances are probably not produced by the sponge itself, but rather by bacteria or fungi that are associated with their host. This review for the first time provides a comprehensive overview of antimicrobial compounds that are known to be produced by sponge-associated microbes. We discuss the current state-of-the-art by grouping the bioactive compounds produced by sponge-associated microorganisms in four categories: antiviral, antibacterial, antifungal and antiprotozoal compounds. Based on in vitro activity tests, identified targets of potent antimicrobial substances derived from sponge-associated microbes include: human immunodeficiency virus 1 (HIV-1) (2-undecyl-4-quinolone, sorbicillactone A and chartarutine B); influenza A (H1N1) virus (truncateol M); nosocomial Gram positive bacteria (thiopeptide YM-266183, YM-266184, mayamycin and kocurin); Escherichia coli (sydonic acid), Chlamydia trachomatis (naphthacene glycoside SF2446A2); Plasmodium spp. (manzamine A and quinolone 1); Leishmania donovani (manzamine A and valinomycin); Trypanosoma brucei (valinomycin and staurosporine); Candida albicans and dermatophytic fungi (saadamycin, 5,7-dimethoxy-4-p-methoxylphenylcoumarin and YM-202204). Thirty-five bacterial and 12 fungal genera associated with sponges that produce antimicrobials were identified, with Streptomyces, Pseudovibrio, Bacillus, Aspergillus and Penicillium as the prominent producers of antimicrobial compounds. Furthemore culture-independent approaches to more comprehensively exploit the genetic richness of antimicrobial compound-producing pathways from sponge-associated bacteria are addressed.

Impaired Air Conditioning within the Nasal Cavity in Flat-Faced Homo.

Directory of Open Access Journals (Sweden)

Takeshi Nishimura

2016-03-01

Full Text Available We are flat-faced hominins with an external nose that protrudes from the face. This feature was derived in the genus Homo, along with facial flattening and reorientation to form a high nasal cavity. The nasal passage conditions the inhaled air in terms of temperature and humidity to match the conditions required in the lung, and its anatomical variation is believed to be evolutionarily sensitive to the ambient atmospheric conditions of a given habitat. In this study, we used computational fluid dynamics (CFD with three-dimensional topology models of the nasal passage under the same simulation conditions, to investigate air-conditioning performance in humans, chimpanzees, and macaques. The CFD simulation showed a horizontal straight flow of inhaled air in chimpanzees and macaques, contrasting with the upward and curved flow in humans. The inhaled air is conditioned poorly in humans compared with nonhuman primates. Virtual modifications to the human external nose topology, in which the nasal vestibule and valve are modified to resemble those of chimpanzees, change the airflow to be horizontal, but have little influence on the air-conditioning performance in humans. These findings suggest that morphological variation of the nasal passage topology was only weakly sensitive to the ambient atmosphere conditions; rather, the high nasal cavity in humans was formed simply by evolutionary facial reorganization in the divergence of Homo from the other hominin lineages, impairing the air-conditioning performance. Even though the inhaled air is not adjusted well within the nasal cavity in humans, it can be fully conditioned subsequently in the pharyngeal cavity, which is lengthened in the flat-faced Homo. Thus, the air-conditioning faculty in the nasal passages was probably impaired in early Homo members, although they have survived successfully under the fluctuating climate of the Plio-Pleistocene, and then they moved "Out of Africa" to explore the more

Adapting for Impaired Patrons.

Science.gov (United States)

Schuyler, Michael

1999-01-01

Describes how a library, with an MCI Corporation grant, approached the process of setting up computers for the visually impaired. Discusses preparations, which included hiring a visually-impaired user as a consultant and contacting the VIP (Visually Impaired Persons) group; equipment; problems with the graphical user interface; and training.…

Compound heterozygous TYK2 mutations underlie primary immunodeficiency with T-cell lymphopenia.

Science.gov (United States)

Nemoto, Michiko; Hattori, Hiroyoshi; Maeda, Naoko; Akita, Nobuhiro; Muramatsu, Hideki; Moritani, Suzuko; Kawasaki, Tomonori; Maejima, Masami; Ode, Hirotaka; Hachiya, Atsuko; Sugiura, Wataru; Yokomaku, Yoshiyuki; Horibe, Keizo; Iwatani, Yasumasa

2018-05-03

Complete tyrosine kinase 2 (TYK2) deficiency has been previously described in patients with primary immunodeficiency diseases. The patients were infected with various pathogens, including mycobacteria and/or viruses, and one of the patients developed hyper-IgE syndrome. A detailed immunological investigation of these patients revealed impaired responses to type I IFN, IL-10, IL-12 and IL-23, which are associated with increased susceptibility to mycobacterial and/or viral infections. Herein, we report a recessive partial TYK2 deficiency in two siblings who presented with T-cell lymphopenia characterized by low naïve CD4 + T-cell counts and who developed Epstein-Barr virus (EBV)-associated B-cell lymphoma. Targeted exome-sequencing of the siblings' genomes demonstrated that both patients carried novel compound heterozygous mutations (c.209_212delGCTT/c.691C > T, p.Cys70Serfs*21/p.Arg231Trp) in the TYK2. The TYK2 protein levels were reduced by 35% in the T cells of the patient. Unlike the response under complete TYK2 deficiency, the patient's T cells responded normally to type I IFN, IL-6, IL-10 and IL-12, whereas the cells displayed an impaired response to IL-23. Furthermore, the level of STAT1 was low in the cells of the patient. These studies reveal a new clinical entity of a primary immunodeficiency with T-cell lymphopenia that is associated with compound heterozygous TYK2 mutations in the patients.

Assessment of an in vitro model of human cells to evaluate the toxic and irritating potential of chemical compounds

Directory of Open Access Journals (Sweden)

M. Catalano

2011-01-01

Full Text Available We attempted to induce differentation in unidifferentiated NCTC2544 human keratinocyte line, by exposure to ZnSO4 and CaCl2. Analysis of specific markers, transglutaminase I, involucrin and loricrin, show that basal NCTC2544 (BL reached spinous- (SL and granular-like (GL phenotypes. BL-, SI- and GL- NCTC were exposed to SDS, as irritant stimulus and Neutral red uptake (NRU and MTT cytoxicity tests evidenced a relatively higher toxicity in SL- and GL cells on lysosomes respect to mitochondria. ILIα cytokine was monitored as early inflammation marker. The complex of data provides evidence for the suitability of our in vitro model to the analysis of cytotoxic/biological effects of topically applied exogenous compounds.

A naringenin–tamoxifen combination impairs cell proliferation and survival of MCF-7 breast cancer cells

Energy Technology Data Exchange (ETDEWEB)

Hatkevich, Talia; Ramos, Joseph; Santos-Sanchez, Idalys; Patel, Yashomati M., E-mail: ympatel@uncg.edu

2014-10-01

Since over 60% of breast cancers are estrogen receptor positive (ER+), many therapies have targeted the ER. The ER is activated by both estrogen binding and phosphorylation. While anti-estrogen therapies, such as tamoxifen (Tam) have been successful they do not target the growth factor promoting phosphorylation of the ER. Other proliferation pathways such as the phosphatidylinositol-3 kinase, (PI3K) and the mitogen-activated protein kinase (MAPK) pathways are activated in breast cancer cells and are associated with poor prognosis. Thus targeting multiple cellular proliferation and survival pathways at the onset of treatment is critical for the development of more effective therapies. The grapefruit flavanone naringenin (Nar) is an inhibitor of both the PI3K and MAPK pathways. Previous studies examining either Nar or Tam used charcoal-stripped serum which removed estrogen as well as other factors. We wanted to use serum containing medium in order to retain all the potential inducers of cell proliferation so as not to exclude any targets of Nar. Here we show that a Nar–Tam combination is more effective than either Tam alone or Nar alone in MCF-7 breast cancer cells. We demonstrate that a Nar–Tam combination impaired cellular proliferation and viability to a greater extent than either component alone in MCF-7 cells. Furthermore, the use of a Nar–Tam combination requires lower concentrations of both compounds to achieve the same effects on proliferation and viability. Nar may function by inhibiting both PI3K and MAPK pathways as well as localizing ERα to the cytoplasm in MCF-7 cells. Our results demonstrate that a Nar–Tam combination induces apoptosis and impairs proliferation signaling to a greater extent than either compound alone. These studies provide critical information for understanding the molecular mechanisms involved in cell proliferation and apoptosis in breast cancer cells. - Highlights: • Nar–Tam impairs cell viability more effectively than

A naringenin–tamoxifen combination impairs cell proliferation and survival of MCF-7 breast cancer cells

International Nuclear Information System (INIS)

Hatkevich, Talia; Ramos, Joseph; Santos-Sanchez, Idalys; Patel, Yashomati M.

2014-01-01

Since over 60% of breast cancers are estrogen receptor positive (ER+), many therapies have targeted the ER. The ER is activated by both estrogen binding and phosphorylation. While anti-estrogen therapies, such as tamoxifen (Tam) have been successful they do not target the growth factor promoting phosphorylation of the ER. Other proliferation pathways such as the phosphatidylinositol-3 kinase, (PI3K) and the mitogen-activated protein kinase (MAPK) pathways are activated in breast cancer cells and are associated with poor prognosis. Thus targeting multiple cellular proliferation and survival pathways at the onset of treatment is critical for the development of more effective therapies. The grapefruit flavanone naringenin (Nar) is an inhibitor of both the PI3K and MAPK pathways. Previous studies examining either Nar or Tam used charcoal-stripped serum which removed estrogen as well as other factors. We wanted to use serum containing medium in order to retain all the potential inducers of cell proliferation so as not to exclude any targets of Nar. Here we show that a Nar–Tam combination is more effective than either Tam alone or Nar alone in MCF-7 breast cancer cells. We demonstrate that a Nar–Tam combination impaired cellular proliferation and viability to a greater extent than either component alone in MCF-7 cells. Furthermore, the use of a Nar–Tam combination requires lower concentrations of both compounds to achieve the same effects on proliferation and viability. Nar may function by inhibiting both PI3K and MAPK pathways as well as localizing ERα to the cytoplasm in MCF-7 cells. Our results demonstrate that a Nar–Tam combination induces apoptosis and impairs proliferation signaling to a greater extent than either compound alone. These studies provide critical information for understanding the molecular mechanisms involved in cell proliferation and apoptosis in breast cancer cells. - Highlights: • Nar–Tam impairs cell viability more effectively than

Occurrence of cyanazine compounds in groundwater: Degradates more prevalent than the parent compound

Science.gov (United States)

Kolpin, D.W.; Thurman, E.M.; Linhart, S.M.

2001-01-01

A recently developed analytical method using liquid chromatography/mass spectrometry was used to investigate the occurrence of cyanazine and its degradates cyanazine acid (CAC), cyanazine amide (CAM), deethylcyanazine (DEC), and deethylcyanazine acid (DCAC) in groundwater. This research represents some of the earliest data on the occurrence of cyanazine degradates in groundwater. Although cyanazine was infrequently detected in the 64 wells across Iowa sampled in 1999, cyanazine degradates were commonly found during this study. The most frequently detected cyanazine compound was DCAC (32.8%) followed by CAC (29.7%), CAM (17.2%), DEC (3.1%), and cyanazine (3.1%). The frequency of detection for cyanazine or one or more of its degradates (CYTOT) was more than 12-fold over that of cyanazine alone (39.1% for CYTOT versus 3.1% for cyanazine). Of the total measured concentration of cyanazine, only 0.2% was derived from its parent compound - with DCAC (74.1%) and CAC (18.4%) comprising 92.5% of this total. Thus, although DCAC and CAC had similar frequencies of detection, DCAC was generally present in higher concentrations. No concentrations of cyanazine compounds for this study exceeded water-quality criteria for the protection of human health. Only cyanazine, however, has such a criteria established. Nevertheless, because these cyanazine degradates are still chlorinated, they may have similar toxicity as their parent compound - similar to what has been found with the chlorinated degradates of atrazine. Thus, the results of this study documented that data on the degradates for cyanazine are critical for understanding its fate and transport in the hydrologic system. Furthermore, the prevalence of the chlorinated degradates of cyanazine found in groundwater suggests that to accurately determine the overall effect on human health and the environment from cyanazine its degradates should also be considered. In addition, because CYTOT was found in 57.6% of the samples collected

Acute, subacute and long-term subjective effects of psilocybin in healthy humans: a pooled analysis of experimental studies.

Science.gov (United States)

Studerus, Erich; Kometer, Michael; Hasler, Felix; Vollenweider, Franz X

2011-11-01

Psilocybin and related hallucinogenic compounds are increasingly used in human research. However, due to limited information about potential subjective side effects, the controlled medical use of these compounds has remained controversial. We therefore analysed acute, short- and long-term subjective effects of psilocybin in healthy humans by pooling raw data from eight double-blind placebo-controlled experimental studies conducted between 1999 and 2008. The analysis included 110 healthy subjects who had received 1-4 oral doses of psilocybin (45-315 µg/kg body weight). Although psilocybin dose-dependently induced profound changes in mood, perception, thought and self-experience, most subjects described the experience as pleasurable, enriching and non-threatening. Acute adverse drug reactions, characterized by strong dysphoria and/or anxiety/panic, occurred only in the two highest dose conditions in a relatively small proportion of subjects. All acute adverse drug reactions were successfully managed by providing interpersonal support and did not need psychopharmacological intervention. Follow-up questionnaires indicated no subsequent drug abuse, persisting perception disorders, prolonged psychosis or other long-term impairment of functioning in any of our subjects. The results suggest that the administration of moderate doses of psilocybin to healthy, high-functioning and well-prepared subjects in the context of a carefully monitored research environment is associated with an acceptable level of risk.

Impaired glycogen synthase activity and mitochondrial dysfunction in skeletal muscle

DEFF Research Database (Denmark)

Højlund, Kurt; Beck-Nielsen, Henning

2006-01-01

Insulin resistance in skeletal muscle is a major hallmark of type 2 diabetes and an early detectable abnormality in the development of this disease. The cellular mechanisms of insulin resistance include impaired insulin-mediated muscle glycogen synthesis and increased intramyocellular lipid content......, whereas impaired insulin activation of muscle glycogen synthase represents a consistent, molecular defect found in both type 2 diabetic and high-risk individuals. Despite several studies of the insulin signaling pathway believed to mediate dephosphorylation and hence activation of glycogen synthase......, the molecular mechanisms responsible for this defect remain unknown. Recently, the use of phospho-specific antibodies in human diabetic muscle has revealed hyperphosphorylation of glycogen synthase at sites not regulated by the classical insulin signaling pathway. In addition, novel approaches such as gene...

Occurrence and potential human-health relevance of volatile organic compounds in drinking water from domestic wells in the United States

Science.gov (United States)

Rowe, B.L.; Toccalino, P.L.; Moran, M.J.; Zogorski, J.S.; Price, C.V.

2011-01-01

BACKGROUND: As the population and demand for safe drinking water from domestic wells increase, it is important to examine water quality and contaminant occurrence. A national assessment in 2006 by the U.S. Geological Survey reported findings for 55 volatile organic compounds (VOCs) based on 2,401 domestic wells sampled during 1985-2002. OBJECTIVES: We examined the occurrence of individual and multiple VOCs and assessed the potential human-health relevance of VOC concentrations. We also identified hydrogeologic and anthropogenic variables that influence the probability of VOC occurrence. METHODS: The domestic well samples were collected at the wellhead before treatment of water and analyzed for 55 VOCs. Results were used to examine VOC occurrence and identify associations of multiple explanatory variables using logistic regression analyses. We used a screening-level assessment to compare VOC concentrations to U.S. Environmental Protection Agency maximum contaminant levels (MCLs) and health-based screening levels. RESULTS: We detected VOCs in 65% of the samples; about one-half of these samples contained VOC mixtures. Frequently detected VOCs included chloroform, toluene, 1,2,4-trimethylbenzene, and perchloroethene. VOC concentrations generally were < 1 ??g/L. One or more VOC concentrations were greater than MCLs in 1.2% of samples, including dibromochloropropane, 1,2-dichloropropane, and ethylene dibromide (fumigants); perchloroethene and trichloroethene (solvents); and 1,1-dichloroethene (organic synthesis compound). CONCLUSIONS: Drinking water supplied by domestic wells is vulnerable to low-level VOC contamination. About 1% of samples had concentrations of potential human-health concern. Identifying factors associated with VOC occurrence may aid in understanding the sources, transport, and fate of VOCs in groundwater.

Impairments of Motor Function While Multitasking in HIV

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Cherie L. Marvel

2017-04-01

Full Text Available Human immunodeficiency virus (HIV became a treatable illness with the introduction of combination antiretroviral therapy (CART. As a result, patients with regular access to CART are expected to live decades with HIV. Long-term HIV infection presents unique challenges, including neurocognitive impairments defined by three major stages of HIV-associated neurocognitive disorders (HAND. The current investigation aimed to study cognitive and motor impairments in HIV using a novel multitasking paradigm. Unlike current standard measures of cognitive and motor performance in HIV, multitasking increases real-world validity by mimicking the dual motor and cognitive demands that are part of daily professional and personal settings (e.g., driving, typing and writing. Moreover, multitask assessments can unmask compensatory mechanisms, normally used under single task conditions, to maintain performance. This investigation revealed that HIV+ participants were impaired on the motor component of the multitask, while cognitive performance was spared. A patient-specific positive interaction between motor performance and working memory recall was driven by poor HIV+ multitaskers. Surprisingly, HAND stage did not correspond with multitask performance and a variety of commonly used assessments indicated normal motor function among HIV+ participants with poor motor performance during the experimental task. These results support the use of multitasks to reveal otherwise hidden impairment in chronic HIV by expanding the sensitivity of clinical assessments used to determine HAND stage. Future studies should examine the capability of multitasks to predict performance in personal, professional and health-related behaviors and prognosis of patients living with chronic HIV.

Mediodorsal thalamus hypofunction impairs flexible goal-directed behavior.

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Parnaudeau, Sébastien; Taylor, Kathleen; Bolkan, Scott S; Ward, Ryan D; Balsam, Peter D; Kellendonk, Christoph

2015-03-01

Cognitive inflexibility is a core symptom of several mental disorders including schizophrenia. Brain imaging studies in schizophrenia patients performing cognitive tasks have reported decreased activation of the mediodorsal thalamus (MD). Using a pharmacogenetic approach to model MD hypofunction, we recently showed that decreasing MD activity impairs reversal learning in mice. While this demonstrates causality between MD hypofunction and cognitive inflexibility, questions remain about the elementary cognitive processes that account for the deficit. Using the Designer Receptors Exclusively Activated by Designer Drugs system, we reversibly decreased MD activity during behavioral tasks assessing elementary cognitive processes inherent to flexible goal-directed behaviors, including extinction, contingency degradation, outcome devaluation, and Pavlovian-to-instrumental transfer (n = 134 mice). While MD hypofunction impaired reversal learning, it did not affect the ability to learn about nonrewarded cues or the ability to modulate action selection based on the outcome value. In contrast, decreasing MD activity delayed the ability to adapt to changes in the contingency between actions and their outcomes. In addition, while Pavlovian learning was not affected by MD hypofunction, decreasing MD activity during Pavlovian learning impaired the ability of conditioned stimuli to modulate instrumental behavior. Mediodorsal thalamus hypofunction causes cognitive inflexibility reflected by an impaired ability to adapt actions when their consequences change. Furthermore, it alters the encoding of environmental stimuli so that they cannot be properly utilized to guide behavior. Modulating MD activity could be a potential therapeutic strategy for promoting adaptive behavior in human subjects with cognitive inflexibility. Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

HIV-1 impairs human retinal pigment epithelial barrier function: possible association with the pathogenesis of HIV-associated retinopathy.

Science.gov (United States)

Tan, Suiyi; Duan, Heng; Xun, Tianrong; Ci, Wei; Qiu, Jiayin; Yu, Fei; Zhao, Xuyan; Wu, Linxuan; Li, Lin; Lu, Lu; Jiang, Shibo; Liu, Shuwen

2014-07-01

The breakdown of human retinal pigment epithelial (HRPE) barrier is considered as the etiology of retinopathy, which affects the quality of life of HIV/AIDS patients. Here we demonstrate that HIV-1 could directly impair HRPE barrier function, which leads to the translocation of HIV-1 and bacteria. HRPE cells (D407) were grown to form polarized, confluent monolayers and treated with different HIV-1 infectious clones. A significant increase of monolayer permeability, as measured by trans-epithelial electrical resistance (TEER) and apical-basolateral movements of sodium fluorescein, was observed. Disrupted tightness of HRPE barrier was associated with the downregulation of several tight junction proteins in D407 cells, including ZO-1, Occludin, Claudin-1, Claudin-2, Claudin-3, Claudin-4, and Claudin-5, after exposure to HIV-1, without affecting the viability of cells. HIV-1 gp120 was shown to participate in the alteration of barrier properties, as evidenced by decreased TEER and weakened expression of tight junction proteins in D407 monolayers after exposure to pseudotyped HIV-1, UV-inactivated HIV-1, and free gp120, but not to an envelope (Env)-defective mutant of HIV. Furthermore, exposure to HIV-1 particles could induce the release of pro-inflammatory cytokines in D407, including IL-6 and MCP-1, both of which downregulated the expression of ZO-1 in the HRPE barrier. Disrupted HRPE monolayer allowed translocation of HIV-1 and bacteria across the epithelium. Overall, these findings suggest that HIV-1 may exploit its Env glycoprotein to induce an inflammatory state in HRPE cells, which could result in impairment of HRPE monolayer integrity, allowing virus and bacteria existing in ocular fluids to cross the epithelium and penetrate the HRPE barrier. Our study highlights the role of HIV-1 in the pathogenesis of HIV/AIDS-related retinopathy and suggests potential therapeutic targets for this ocular complication.

Compound heterozygous MYO7A mutations segregating Usher syndrome type 2 in a Han family.

Science.gov (United States)

Zong, Ling; Chen, Kaitian; Wu, Xuan; Liu, Min; Jiang, Hongyan

2016-11-01

Identification of rare deafness genes for inherited congenital sensorineural hearing impairment remains difficult, because a large variety of genes are implicated. In this study we applied targeted capture and next-generation sequencing to uncover the underlying gene in a three-generation Han family segregating recessive inherited hearing loss and retinitis pigmentosa. After excluding mutations in common deafness genes GJB2, SLC26A4 and the mitochondrial gene, genomic DNA of the proband of a Han family was subjected to targeted next-generation sequencing. The candidate mutations were confirmed by Sanger sequencing and subsequently analyzed with in silico tools. An unreported splice site mutation c.3924+1G > C compound with c.6028G > A in the MYO7A gene were detected to cosegregate with the phenotype in this pedigree. Both mutations, located in the evolutionarily conserved FERM domain in myosin VIIA, were predicted to be pathogenic. In this family, profound sensorineural hearing impairment and retinitis pigmentosa without vestibular disorder, constituted the typical Usher syndrome type 2. Identification of novel mutation in compound heterozygosity in MYO7A gene revealed the genetic origin of Usher syndrome type 2 in this Han family. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

High glucose impairs superoxide production from isolated blood neutrophils

DEFF Research Database (Denmark)

Perner, A; Nielsen, S E; Rask-Madsen, J

2003-01-01

Superoxide (O(2)(-)), a key antimicrobial agent in phagocytes, is produced by the activity of NADPH oxidase. High glucose concentrations may, however, impair the production of O(2)(-) through inhibition of glucose-6-phosphate dehydrogenase (G6PD), which catalyzes the formation of NADPH. This study...... measured the acute effects of high glucose or the G6PD inhibitor dehydroepiandrosterone (DHEA) on the production of O(2)(-) from isolated human neutrophils....

Investigation of fruit peel extracts as sources for compounds with antioxidant and antiproliferative activities against human cell lines.

Science.gov (United States)

Khonkarn, Ruttiros; Okonogi, Siriporn; Ampasavate, Chadarat; Anuchapreeda, Songyot

2010-01-01

The aim of this study was to evaluate antioxidant activity and cytotoxicity against human cell lines of fruit peel extracts from rambutan, mangosteen and coconut. The highest antioxidant activity was found from rambutan peel crude extract where the highest radical scavenging capacity via ABTS assay was from its ethyl acetate fraction with a TEAC value of 23.0mM/mg and the highest ferric ion reduction activity via FRAP assay was from its methanol fraction with an EC value of 20.2mM/mg. Importantly, using both assays, these fractions had a higher antioxidant activity than butylated hydroxyl toluene and vitamin E. It was shown that the ethyl acetate fraction of rambutan peel had the highest polyphenolic content with a gallic acid equivalent of 2.3mg/mL. The results indicate that the polyphenolic compounds are responsible for the observed antioxidant activity of the extracts. Interestingly, the hexane fraction of coconut peel showed a potent cytotoxic effect on KB cell line by MTT assay (IC(50)=7.7 microg/mL), and no detectable cytotoxicity toward normal cells. We concluded that the ethyl acetate fraction of rambutan peel is a promising resource for potential novel antioxidant agents whereas the hexane fraction of coconut peel may contain novel anticancer compounds. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

Development of sampling method and chromatographic analysis of volatile organic compounds emitted from human skin.

Science.gov (United States)

Grabowska-Polanowska, Beata; Miarka, Przemysław; Skowron, Monika; Sułowicz, Joanna; Wojtyna, Katarzyna; Moskal, Karolina; Śliwka, Ireneusz

2017-10-01

The studies on volatile organic compounds emitted from skin are an interest for chemists, biologists and physicians due to their role in development of different scientific areas, including medical diagnostics, forensic medicine and the perfume design. This paper presents a proposal of two sampling methods applied to skin odor collection: the first one uses a bag of cellulose film, the second one, using cellulose sachets filled with active carbon. Volatile organic compounds were adsorbed on carbon sorbent, removed via thermal desorption and analyzed using gas chromatograph with mass spectrometer. The first sampling method allowed identification of more compounds (52) comparing to the second one (30). Quantitative analyses for acetone, butanal, pentanal and hexanal were done. The skin odor sampling method using a bag of cellulose film, allowed the identification of many more compounds when compared with the method using a sachet filled with active carbon.

The Impairing Role of Stress on Autobiographical Memory Reconsolidation

Directory of Open Access Journals (Sweden)

Zeinab Azimi

2012-10-01

Full Text Available Background: Despite some studies indicating improving role of stress on memory consolidation, very few animal and human studies show that stress impairs reconsolidation of memories. This study aimed to determine the effect of stress on autobiographical memory reconsolidation.Materials and Methods: The present study was done with an experimental method (Solomon Four-Group design. The statistical society of this study was all undergraduate female students in 2009-2010 academic year at Tabriz University. Forty students were selected using random cluster sampling, and we ensure about their physical and mental health by GHQ-28 and interview. Tools for this study were cueing autobiographical memory test, SECPT (for raising blood pressure and stress induction, autobiographical memory test, PANAS and general health questionnaire (GHQ-28. MANOVA was used for data analysis by SPSS-17.Results: The results show that stress after activation of memory impairs memory for neutral events (p0.05. None of stress and memory activation alone had effect on memory performance (p>0.05.Conclusion: These findings indicate that stress impairs autobiographical memory reconsolidation, which is opposite to its effects on memory consolidation, so it supports the view that consolidation and reconsolidation are separate process.

Tocopherols and tocotrienols plasma levels are associated with cognitive impairment.

Science.gov (United States)

Mangialasche, Francesca; Xu, Weili; Kivipelto, Miia; Costanzi, Emanuela; Ercolani, Sara; Pigliautile, Martina; Cecchetti, Roberta; Baglioni, Mauro; Simmons, Andrew; Soininen, Hilkka; Tsolaki, Magda; Kloszewska, Iwona; Vellas, Bruno; Lovestone, Simon; Mecocci, Patrizia

2012-10-01

Vitamin E includes 8 natural compounds (4 tocopherols, 4 tocotrienols) with potential neuroprotective activity. α-Tocopherol has mainly been investigated in relation to cognitive impairment. We examined the relation of all plasma vitamin E forms and markers of vitamin E damage (α-tocopherylquinone, 5-nitro-γ-tocopherol) to mild cognitive impairment (MCI) and Alzheimer's disease (AD). Within the AddNeuroMed-Project, plasma tocopherols, tocotrienols, α-tocopherylquinone, and 5-nitro-γ-tocopherol were assessed in 168 AD cases, 166 MCI, and 187 cognitively normal (CN) people. Compared with cognitively normal subjects, AD and MCI had lower levels of total tocopherols, total tocotrienols, and total vitamin E. In multivariable-polytomous-logistic regression analysis, both MCI and AD cases had 85% lower odds to be in the highest tertile of total tocopherols and total vitamin E, and they were, respectively, 92% and 94% less likely to be in the highest tertile of total tocotrienols than the lowest tertile. Further, both disorders were associated with increased vitamin E damage. Low plasma tocopherols and tocotrienols levels are associated with increased odds of MCI and AD. Copyright © 2012 Elsevier Inc. All rights reserved.

Some information needs for air quality modeling. [Environmental effects of sulfur compounds

Energy Technology Data Exchange (ETDEWEB)

Hill, F B

1975-09-01

The following topics were considered at the workshop: perturbation of the natural sulfur cycle by human activity; ecosystem responses to a given environmental dose of sulfur compounds; movement of sulfur compounds within the atmosphere; air quality models; contribution of biogenic sulfur compounds to atmospheric burden of sulfur; production of acid rain from sulfur dioxide; meteorological processes; and rates of oxidation of SO/sub 2/ via direct photo-oxidation, oxidation resulting from photo-induced free radical chemistry, and catalytic oxidation in cloud droplets and on dry particles. (HLW)

IRIS Toxicological Review of Thallium and Compounds (Final Report)

Science.gov (United States)

EPA has finalized the Toxicological Review of Thallium and Compounds: in support of the Integrated Risk Information System (IRIS). Now final, this assessment may be used by EPA’s program and regional offices to inform decisions to protect human health.

The comparison of stress and marital satisfaction status of parents of hearing-impaired and normal children

Directory of Open Access Journals (Sweden)

Karim Gharashi

2013-03-01

Full Text Available Background and Aim: Stress is the source of many problems in human-kind lives and threatens people's life constantly. Having hearing-impaired child, not only causes stress in parents, but also affects their marital satisfaction. The purpose of this study was comparing the stress and marital satisfaction status between the normal and hearing-impaired children's parents.Methods: This was a causal-comparative study. Eighty parents of normal children and 80 parents of hearing-impaired children were chosen from rehabilitation centers and kindergartens in city of Tabriz, Iran by available and clustering sampling method. All parents were asked to complete the Friedrich's source of stress and Enrich marital satisfaction questionnaires.Results: Parents of hearing-impaired children endure more stress than the normal hearing ones (p<0.001. The marital satisfaction of hearing-impaired children's parents was lower than the parents of normal hearing children, too (p<0.001.Conclusion: Having a hearing-impaired child causes stress and threatens the levels of marital satisfaction. This requires much more attention and a distinct planning for parents of handicap children to reduce their stress.

Utilization of Cyanoacetohydrazide and Oxadiazolyl Acetonitrile in the Synthesis of Some New Cytotoxic Heterocyclic Compounds.

Science.gov (United States)

Shaker, Soheir A; Marzouk, Magda I

2016-01-29

A (pyridazinyl)acetate derivative was reacted with thiosemicarbazide and hydrazine hydrate to yield spiropyridazinone and acetohydrazide derivatives, respectively. The acetohydrazide derivative was used as a starting material for synthesizing some new heterocyclic compounds such as oxoindolinylidene, dimethylpyrazolyl, methylpyrazolyl, oxopyrazolyl, cyanoacetylacetohydrazide and oxadiazolylacetonitrile derivatives. The behavior of the cyanoacetylacetohydrazide and oxadiazolylacetonitrile derivatives towards nitrogen and carbon nucleophiles was investigated. The assigned structures of the prepared compounds were elucidated by spectral methods (IR, ¹H-NMR (13)C-NMR and mass spectroscopy). Some of the newly prepared compounds were tested in vitro against a panel of four human tumor cell lines, namely hepatocellular carcinoma (liver) HePG-2, colon cancer HCT-116, human prostate cancer PC3, and mammary gland breast MCF-7. Also they were tested as antioxidants. Almost all of the tested compounds showed satisfactory activity.

Cognitive effects of a dietary supplement made from extract of Bacopa monnieri, astaxanthin, phosphatidylserine, and vitamin E in subjects with mild cognitive impairment: a noncomparative, exploratory clinical study

Directory of Open Access Journals (Sweden)

Zanotta D

2014-02-01

Full Text Available Danilo Zanotta, Silvana Puricelli, Guido Bonoldi Unità Operativa di Medicina 2, Ospedale di Circolo di Busto Arsizio, Varese, Italy Abstract: A prospective cohort, noncomparative, multicenter trial was conducted to explore the potential of a phytotherapeutic compound, available as a dietary supplement and containing extracts of Bacopa monnieri and Haematococcus pluvialis (astaxanthin plus phosphatidylserine and vitamin E, in improving cognition in subjects diagnosed with mild cognitive impairment. Enrolled subjects (n=104 were aged 71.2±9.9 years and had a mini-mental state examination score of 26.0±2.0 (mean ± standard deviation. They underwent the Alzheimer’s Disease Assessment Scale-cognitive subscale (ADAS-cog test and the clock drawing test at baseline and upon completion of a 60-day period of dietary supplementation with one tablet daily of the tested compound. In 102 assessable subjects, total ADAS-cog scores improved from 13.7±5.8 at baseline to 9.7±4.9 on day 60, and the clock drawing test scores improved from 8.5±2.3 to 9.1±1.9. Both changes were statistically significant (P<0.001. Memory tasks were the individual components of ADAS-cog showing the largest improvements. In a multivariate analysis, larger improvements in total ADAS-cog score were associated with less compromised baseline mini-mental state examination scores. Perceived efficacy was rated as excellent or good by 62% of study subjects. The tested compound was well tolerated; one nonserious adverse event was reported in the overall study population, and perceived tolerability was rated excellent or good by 99% of the subjects. In conclusion, dietary supplementation with the tested compound shows potential for counteracting cognitive impairment in subjects with mild cognitive impairment and warrants further investigation in adequately controlled, longer-term studies. Keywords: mild cognitive impairment, Bacopa monnieri, astaxanthin, ADAS-cog test, clock drawing

The impairment of MAGMAS function in human is responsible for a severe skeletal dysplasia.

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Cybel Mehawej

2014-05-01

Full Text Available Impairment of the tightly regulated ossification process leads to a wide range of skeletal dysplasias and deciphering their molecular bases has contributed to the understanding of this complex process. Here, we report a homozygous mutation in the mitochondria-associated granulocyte macrophage colony stimulating factor-signaling gene (MAGMAS in a novel and severe spondylodysplastic dysplasia. MAGMAS, also referred to as PAM16 (presequence translocase-associated motor 16, is a mitochondria-associated protein involved in preprotein translocation into the matrix. We show that MAGMAS is specifically expressed in trabecular bone and cartilage at early developmental stages and that the mutation leads to an instability of the protein. We further demonstrate that the mutation described here confers to yeast strains a temperature-sensitive phenotype, impairs the import of mitochondrial matrix pre-proteins and induces cell death. The finding of deleterious MAGMAS mutations in an early lethal skeletal dysplasia supports a key role for this mitochondrial protein in the ossification process.

Impaired control of body cooling during heterothermia represents the major energetic constraint in an aging non-human primate exposed to cold.

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Jeremy Terrien

2009-10-01

Full Text Available Daily heterothermia is used by small mammals for energy and water savings, and seems to be preferentially exhibited during winter rather than during summer. This feature induces a trade-off between the energy saved during daily heterothermia and the energy cost of arousal, which can impact energy balance and survival under harsh environmental conditions. Especially, aging may significantly affect such trade off during cold-induced energy stress, but direct evidences are still lacking. We hypothesized that aging could alter the energetics of daily heterothermia, and that the effects could differ according to season. In the gray mouse lemur (Microcebus murinus, a non-human primate species which exhibits daily heterothermia, we investigated the effects of exposures to 25 and 12 degrees C on body composition, energy balance, patterns of heterothermia and water turnover in adult (N = 8 and aged animals (N = 7 acclimated to winter-like or summer-like photoperiods. Acclimation to summer prevented animals from deep heterothermia, even during aging. During winter, adult animals at 12 degrees C and aged animals at 25 degrees C exhibited low levels of energy expenditure with minor modulations of heterothermia. The major effects of cold were observed during winter, and were particularly pronounced in aged mouse lemurs which exhibited deep heterothermia phases. Body composition was not significantly affected by age and could not explain the age-related differences in heterothermia patterns. However, aging was associated with increased levels of energy expenditure during cold exposure, in concomitance with impaired energy balance. Interestingly, increased energy expenditure and depth of heterothermia phases were strongly correlated. In conclusion, it appeared that the exhibition of shallow heterothermia allowed energy savings during winter in adult animals only. Aged animals exhibited deep heterothermia and increased levels of energy expenditure, impairing

Cryopreservation of human skeletal muscle impairs mitochondrial function

DEFF Research Database (Denmark)

Larsen, Steen; Wright-Paradis, C; Gnaiger, E

2012-01-01

functionality after long term cryopreservation (1 year). Skeletal muscle samples were preserved in dimethyl sulfoxide (DMSO) for later analysis. Human skeletal muscle fibres were thawed and permeabilised with saponin, and mitochondrial respiration was measured by high-resolution respirometry. The capacity...

Impaired endothelial progenitor cell mobilization and dysfunctional bone marrow stroma in diabetes mellitus.

Science.gov (United States)

Westerweel, Peter E; Teraa, Martin; Rafii, Shahin; Jaspers, Janneke E; White, Ian A; Hooper, Andrea T; Doevendans, Pieter A; Verhaar, Marianne C

2013-01-01

Circulating Endothelial Progenitor Cell (EPC) levels are reduced in diabetes mellitus. This may be a consequence of impaired mobilization of EPC from the bone marrow. We hypothesized that under diabetic conditions, mobilization of EPC from the bone marrow to the circulation is impaired -at least partly- due to dysfunction of the bone marrow stromal compartment. Diabetes was induced in mice by streptozotocin injection. Circulating Sca-1(+)Flk-1(+) EPC were characterized and quantified by flow cytometry at baseline and after mobilization with G-CSF/SCF injections. In vivo hemangiogenic recovery was tested by 5-FU challenge. Interaction within the bone marrow environment between CD34(+) hematopoietic progenitor cells (HPC) and supporting stroma was assessed by co-cultures. To study progenitor cell-endothelial cell interaction under normoglycemic and hyperglycemic conditions, a co-culture model using E4Orf1-transfected human endothelial cells was employed. In diabetic mice, bone marrow EPC levels were unaffected. However, circulating EPC levels in blood were lower at baseline and mobilization was attenuated. Diabetic mice failed to recover and repopulate from 5-FU injection. In vitro, primary cultured bone marrow stroma from diabetic mice was impaired in its capacity to support human CFU-forming HPC. Finally, hyperglycemia hampered the HPC supportive function of endothelial cells in vitro. EPC mobilization is impaired under experimental diabetic conditions and our data suggest that diabetes induces alterations in the progenitor cell supportive capacity of the bone marrow stroma, which could be partially responsible for the attenuated EPC mobilization and reduced EPC levels observed in diabetic patients.

Impaired endothelial progenitor cell mobilization and dysfunctional bone marrow stroma in diabetes mellitus.

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Peter E Westerweel

Full Text Available Circulating Endothelial Progenitor Cell (EPC levels are reduced in diabetes mellitus. This may be a consequence of impaired mobilization of EPC from the bone marrow. We hypothesized that under diabetic conditions, mobilization of EPC from the bone marrow to the circulation is impaired -at least partly- due to dysfunction of the bone marrow stromal compartment.Diabetes was induced in mice by streptozotocin injection. Circulating Sca-1(+Flk-1(+ EPC were characterized and quantified by flow cytometry at baseline and after mobilization with G-CSF/SCF injections. In vivo hemangiogenic recovery was tested by 5-FU challenge. Interaction within the bone marrow environment between CD34(+ hematopoietic progenitor cells (HPC and supporting stroma was assessed by co-cultures. To study progenitor cell-endothelial cell interaction under normoglycemic and hyperglycemic conditions, a co-culture model using E4Orf1-transfected human endothelial cells was employed.In diabetic mice, bone marrow EPC levels were unaffected. However, circulating EPC levels in blood were lower at baseline and mobilization was attenuated. Diabetic mice failed to recover and repopulate from 5-FU injection. In vitro, primary cultured bone marrow stroma from diabetic mice was impaired in its capacity to support human CFU-forming HPC. Finally, hyperglycemia hampered the HPC supportive function of endothelial cells in vitro.EPC mobilization is impaired under experimental diabetic conditions and our data suggest that diabetes induces alterations in the progenitor cell supportive capacity of the bone marrow stroma, which could be partially responsible for the attenuated EPC mobilization and reduced EPC levels observed in diabetic patients.

Memory deficits for facial identity in patients with amnestic mild cognitive impairment (MCI).

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Savaskan, Egemen; Summermatter, Daniel; Schroeder, Clemens; Schächinger, Hartmut

2018-01-01

Faces are among the most relevant social stimuli revealing an encounter's identity and actual emotional state. Deficits in facial recognition may be an early sign of cognitive decline leading to social deficits. The main objective of the present study is to investigate if individuals with amnestic mild cognitive impairment show recognition deficits in facial identity. Thirty-seven individuals with amnestic mild cognitive impairment, multiple-domain (15 female; age: 75±8 yrs.) and forty-one healthy volunteers (24 female; age 71±6 yrs.) participated. All participants completed a human portrait memory test presenting unfamiliar faces with happy and angry emotional expressions. Five and thirty minutes later, old and new neutral faces were presented, and discrimination sensitivity (d') and response bias (C) were assessed as signal detection parameters of cued facial identity recognition. Memory performance was lower in amnestic mild cognitive impairment as compared to control subjects, mainly because of an altered response bias towards an increased false alarm rate (favoring false OLD ascription of NEW items). In both groups, memory performance declined between the early and later testing session, and was always better for acquired happy than angry faces. Facial identity memory is impaired in patients with amnestic mild cognitive impairment. Liberalization of the response bias may reflect a socially motivated compensatory mechanism maintaining an almost identical recognition hit rate of OLD faces in individuals with amnestic mild cognitive impairment.

Carcinogenic compounds in alcoholic beverages: an update.

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Pflaum, Tabea; Hausler, Thomas; Baumung, Claudia; Ackermann, Svenja; Kuballa, Thomas; Rehm, Jürgen; Lachenmeier, Dirk W

2016-10-01

The consumption of alcoholic beverages has been classified as carcinogenic to humans by the International Agency for Research on Cancer (IARC) since 1988. More recently, in 2010, ethanol as the major constituent of alcoholic beverages and its metabolite acetaldehyde were also classified as carcinogenic to humans. Alcoholic beverages as multi-component mixtures may additionally contain further known or suspected human carcinogens as constituent or contaminant. This review will discuss the occurrence and toxicology of eighteen carcinogenic compounds (acetaldehyde, acrylamide, aflatoxins, arsenic, benzene, cadmium, ethanol, ethyl carbamate, formaldehyde, furan, glyphosate, lead, 3-MCPD, 4-methylimidazole, N-nitrosodimethylamine, pulegone, ochratoxin A, safrole) occurring in alcoholic beverages as identified based on monograph reviews by the IARC. For most of the compounds of alcoholic beverages, quantitative risk assessment provided evidence for only a very low risk (such as margins of exposure above 10,000). The highest risk was found for ethanol, which may reach exposures in ranges known to increase the cancer risk even at moderate drinking (margin of exposure around 1). Other constituents that could pose a risk to the drinker were inorganic lead, arsenic, acetaldehyde, cadmium and ethyl carbamate, for most of which mitigation by good manufacturing practices is possible. Nevertheless, due to the major effect of ethanol, the cancer burden due to alcohol consumption can only be reduced by reducing alcohol consumption in general or by lowering the alcoholic strength of beverages.

Enterolactone: A novel radiosensitizer for human breast cancer cell lines through impaired DNA repair and increased apoptosis

International Nuclear Information System (INIS)

Bigdeli, Bahareh; Goliaei, Bahram; Masoudi-Khoram, Nastaran; Jooyan, Najmeh; Nikoofar, Alireza; Rouhani, Maryam; Haghparast, Abbas; Mamashli, Fatemeh

2016-01-01

human breast cancer. • Enterolactone pretreatment enhances radiation induced apoptosis. • Enterolactone pretreatment impairs repair of radiation-induced DNA damages. • Chromosomal aberrations increases in cells receiving enterolactone and X-ray. • Micronuclei formation is elevated after combined treatment with enterolactone.

Enterolactone: A novel radiosensitizer for human breast cancer cell lines through impaired DNA repair and increased apoptosis

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Bigdeli, Bahareh, E-mail: bhr.bigdeli@ut.ac.ir [Department of Biophysics, Institute of Biochemistry and Biophysics, University of Tehran, 16th Azar St., Enghelab Sq., Tehran (Iran, Islamic Republic of); Goliaei, Bahram, E-mail: goliaei@ut.ac.ir [Department of Biophysics, Institute of Biochemistry and Biophysics, University of Tehran, 16th Azar St., Enghelab Sq., Tehran (Iran, Islamic Republic of); Masoudi-Khoram, Nastaran, E-mail: n.masoudi@alumni.ut.ac.ir [Department of Biophysics, Institute of Biochemistry and Biophysics, University of Tehran, 16th Azar St., Enghelab Sq., Tehran (Iran, Islamic Republic of); Jooyan, Najmeh, E-mail: n.jooyan@ut.ac.ir [Department of Biophysics, Institute of Biochemistry and Biophysics, University of Tehran, 16th Azar St., Enghelab Sq., Tehran (Iran, Islamic Republic of); Nikoofar, Alireza, E-mail: nikoofar@iums.ac.ir [Department of Radiotherapy, Iran University of Medical Sciences (IUMS), Shahid Hemmat Highway, Tehran (Iran, Islamic Republic of); Rouhani, Maryam, E-mail: rouhani@iasbs.ac.ir [Department of Biological Sciences, Institute for Advanced Studies in Basic Sciences (IASBS), Prof. Yousef Sobouti Blvd., Gava Zang, Zanjan (Iran, Islamic Republic of); Haghparast, Abbas, E-mail: Haghparast@sbmu.ac.ir [Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Daneshjo St., Evin, Tehran (Iran, Islamic Republic of); Mamashli, Fatemeh, E-mail: mamashli@ut.ac.ir [Department of Biophysics, Institute of Biochemistry and Biophysics, University of Tehran, 16th Azar St., Enghelab Sq., Tehran (Iran, Islamic Republic of)

2016-12-15

human breast cancer. • Enterolactone pretreatment enhances radiation induced apoptosis. • Enterolactone pretreatment impairs repair of radiation-induced DNA damages. • Chromosomal aberrations increases in cells receiving enterolactone and X-ray. • Micronuclei formation is elevated after combined treatment with enterolactone.

Formal Thought Disorder and language impairment in schizophrenia

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Marcia Radanovic

2013-01-01

Full Text Available Schizophrenia is a psychiatric illness in which disorders of thought content are a prominent feature. The disruption of normal flow of thought, or “Formal Thought Disorder” (FTD, has been traditionally assessed through the content and form of patients’ speech, and speech abnormalities in schizophrenia were considered as a by-product of the disruption in conceptual structures and associative processes related to psychosis. This view has been changed due to increasing evidence that language per se is impaired in schizophrenia, especially its semantic, discursive, and pragmatic aspects. Schizophrenia is currently considered by some authors as a “language related human specific disease” or “logopathy”, and the neuroanatomical and genetic correlates of the language impairment in these patients are under investigation. Such efforts may lead to a better understanding about the pathophysiology of this devastating mental disease. We present some current concepts related to FTD as opposed to primary neurolinguistic abnormalities in schizophrenia.

Servey of the oil and gas pollutant impacts on the human and environment

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Sina Dobaradaran

2014-04-01

Full Text Available Oil has vital importance in many industries and is the main source of energy internationally it supplies 32% of energy in Europe and Asia and more than 53% in Middle East. The most volume of oil industry products includes fuel oil and gasoline (diesel. Oil is used as the basic material in producing chemical products such as medicines, solvents, chemical fertilizers, pesticides and etc. Considering the importance of petroleum industry in the world we should not ignore its harms to humans and the environment and should look for solutions to reduce them. Nowaday petroleum refineries emit million pounds of air pollutants that pose a serious risk of harm to human health and the environment as well as impairs the life quality of the people that living nearby these industries. These pollutants consist of volatile organic compounds, SO2, NOx, particulate matter, CO, H2S and HAPs. These pollutants have different adverse impacts on different parts of ecosystem, environment and animals. So this paper deals with some of these problems.

Impaired mTORC2 signaling in catecholaminergic neurons exaggerates high fat diet-induced hyperphagia

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Olga I. Dadalko

2015-09-01

Conclusions: Our data support a model in which mTORC2 signaling within catecholaminergic neurons constrains consumption of a high-fat diet, while disruption causes high-fat diet-specific exaggerated hyperphagia. In parallel, impaired mTORC2 signaling leads to aberrant striatal DA neurotransmission, which has been associated with obesity in human and animal models, as well as with escalating substance abuse. These data suggest that defects localized to the catecholaminergic pathways are capable of overriding homeostatic circuits, leading to obesity, metabolic impairment, and aberrant DA-dependent behaviors.

Human figure drawing distinguishes Alzheimer's patients: a cognitive screening test study.

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Stanzani Maserati, Michelangelo; D'Onofrio, Renato; Matacena, Corrado; Sambati, Luisa; Oppi, Federico; Poda, Roberto; De Matteis, Maddalena; Naldi, Ilaria; Liguori, Rocco; Capellari, Sabina

2018-05-01

To study human figure drawing in a group of Alzheimer's disease (AD) patients and compare it with a group of patients with mild cognitive impairment (MCI) and controls. We evaluated consecutive outpatients over a one-year period. Patients were classified as affected by AD or by MCI. All patients and controls underwent a simplified version of the human-figure drawing test and MMSE. A qualitative and quantitative analysis of all human figures was obtained. 112 AD, 100 MCI patients and 104 controls were enrolled. AD patients drew human figures poor in details and globally smaller than MCI patients and controls. Human figures drawn by MCI patients are intermediate in body height between those of the AD patients and the healthy subjects. The head-to-body ratio of human figures drawn by AD patients is greater than controls and MCI patients, while the human figure size-relative-to-page space index is significantly smaller. Body height is an independent predictor of cognitive impairment correlating with its severity and with the number of the figure's details. Human figures drawn by AD patients are different from those drawn by healthy subjects and MCI patients. Human figure drawing test is a useful tool for orienting cognitive impairment's diagnosis.

Antibacterial activity of sphagnum acid and other phenolic compounds found in Sphagnum papillosum against food-borne bacteria.

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Mellegård, H; Stalheim, T; Hormazabal, V; Granum, P E; Hardy, S P

2009-07-01

To identify the phenolic compounds in the leaves of Sphagnum papillosum and examine their antibacterial activity at pH appropriate for the undissociated forms. Bacterial counts of overnight cultures showed that whilst growth of Staphylococcus aureus 50084 was impaired in the presence of milled leaves, the phenol-free fraction of holocellulose of S. papillosum had no bacteriostatic effect. Liquid chromatography-mass spectrometry analysis of an acetone-methanol extract of the leaves detected eight phenolic compounds. Antibacterial activity of the four dominating phenols specific to Sphagnum leaves, when assessed in vitro as minimal inhibitory concentrations (MICs), were generally >2.5 mg ml(-1). MIC values of the Sphagnum-specific compound 'sphagnum acid' [p-hydroxy-beta-(carboxymethyl)-cinnamic acid] were >5 mg ml(-1). No synergistic or antagonistic effects of the four dominating phenols were detected in plate assays. Sphagnum-derived phenolics exhibit antibacterial activity in vitro only at concentrations far in excess of those found in the leaves. We have both identified the phenolic compounds in S. papillosum and assessed their antibacterial activity. Our data indicate that phenolic compounds in isolation are not potent antibacterial agents and we question their potency against food-borne pathogens.

Transcriptional response to organic compounds from diverse gasoline and biogasoline fuel emissions in human lung cells.

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Libalova, Helena; Rossner, Pavel; Vrbova, Kristyna; Brzicova, Tana; Sikorova, Jitka; Vojtisek-Lom, Michal; Beranek, Vit; Klema, Jiri; Ciganek, Miroslav; Neca, Jiri; Machala, Miroslav; Topinka, Jan

2018-04-01

Modern vehicles equipped with Gasoline Direct Injection (GDI) engine have emerged as an important source of particulate emissions potentially harmful to human health. We collected and characterized gasoline exhaust particles (GEPs) produced by neat gasoline fuel (E0) and its blends with 15% ethanol (E15), 25% n-butanol (n-But25) and 25% isobutanol (i-But25). To study the toxic effects of organic compounds extracted from GEPs, we analyzed gene expression profiles in human lung BEAS-2B cells. Despite the lowest GEP mass, n-But25 extract contained the highest concentration of polycyclic aromatic hydrocarbons (PAHs), while i-But25 extract the lowest. Gene expression analysis identified activation of the DNA damage response and other subsequent events (cell cycle arrest, modulation of extracellular matrix, cell adhesion, inhibition of cholesterol biosynthesis) following 4 h exposure to all GEP extracts. The i-But25 extract induced the most distinctive gene expression pattern particularly after 24 h exposure. Whereas E0, E15 and n-But25 extract treatments resulted in persistent stress signaling including DNA damage response, MAPK signaling, oxidative stress, metabolism of PAHs or pro-inflammatory response, i-But25 induced changes related to the metabolism of the cellular nutrients required for cell recovery. Our results indicate that i-But25 extract possessed the weakest genotoxic potency possibly due to the low PAH content. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Potential anticancer properties of bioactive compounds of Gymnema sylvestre and its biofunctionalized silver nanoparticles.

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Arunachalam, Kantha Deivi; Arun, Lilly Baptista; Annamalai, Sathesh Kumar; Arunachalam, Aarrthy M

2015-01-01

Gymnema sylvestre is an ethno-pharmacologically important medicinal plant used in many polyherbal formulations for its potential health benefits. Silver nanoparticles (SNPs) were biofunctionalized using aqueous leaf extracts of G. sylvestre. The anticancer properties of the bioactive compounds and the biofunctionalized SNPs were compared using the HT29 human adenoma colon cancer cell line. The preliminary phytochemical screening for bioactive compounds from aqueous extracts revealed the presence of alkaloids, triterpenes, flavonoids, steroids, and saponins. Biofunctionalized SNPs were synthesized using silver nitrate and characterized by ultraviolet-visible spectroscopy, scanning electron microscopy, energy-dispersive X-ray analysis, Fourier transform infrared spectroscopy, and X-ray diffraction for size and shape. The characterized biofunctionalized G. sylvestre were tested for its in vitro anticancer activity against HT29 human colon adenocarcinoma cells. The biofunctionlized G. sylvestre SNPs showed the surface plasmon resonance band at 430 nm. The scanning electron microscopy images showed the presence of spherical nanoparticles of various sizes, which were further determined using the Scherrer equation. In vitro cytotoxic activity of the biofunctionalized green-synthesized SNPs (GSNPs) indicated that the sensitivity of HT29 human colon adenocarcinoma cells for cytotoxic drugs is higher than that of Vero cell line for the same cytotoxic agents and also higher than the bioactive compound of the aqueous extract. Our results show that the anticancer properties of the bioactive compounds of G. sylvestre can be enhanced through biofunctionalizing the SNPs using the bioactive compounds present in the plant extract without compromising their medicinal properties.

Selective Inducible Nitric Oxide Synthase Inhibitor Reversed Zinc Chloride-Induced Spatial Memory Impairment via Increasing Cholinergic Marker Expression.

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Tabrizian, Kaveh; Azami, Kian; Belaran, Maryam; Soodi, Maliheh; Abdi, Khosrou; Fanoudi, Sahar; Sanati, Mehdi; Mottaghi Dastjerdi, Negar; Soltany Rezaee-Rad, Mohammad; Sharifzadeh, Mohammad

2016-10-01

Zinc, an essential micronutrient and biochemical element of the human body, plays structural, catalytic, and regulatory roles in numerous physiological functions. In the current study, the effects of a pretraining oral administration of zinc chloride (10, 25, and 50 mg/kg) for 14 consecutive days and post-training bilateral intra-hippocampal infusion of 1400W as a selective inducible nitric oxide synthase (iNOS) inhibitor (10, 50, and 100 μM/side), alone and in combination, on the spatial memory retention in Morris water maze (MWM) were investigated. Animals were trained for 4 days and tested 48 h after completion of training. Also, the molecular effects of these compounds on the expression of choline acetyltransferase (ChAT), as a cholinergic marker in the CA1 region of the hippocampus and medial septal area (MSA), were evaluated. Behavioral and molecular findings of this study showed that a 2-week oral administration of zinc chloride (50 mg/kg) impaired spatial memory retention in MWM and decreased ChAT expression. Immunohistochemical analysis of post-training bilateral intra-hippocampal infusion of 1400W revealed a significant increase in ChAT immunoreactivity. Furthermore, post-training bilateral intra-hippocampal infusion of 1400W into the CA1 region of the hippocampus reversed zinc chloride-induced spatial memory impairment in MWM and significantly increased ChAT expression in comparison with zinc chloride-treated animals. Taken together, these results emphasize the role of selective iNOS inhibitors in reversing zinc chloride-induced spatial memory deficits via modulation of cholinergic marker expression.

Chronopathological aspects of sleep disorders and cognitive dysfunctions in children with visual impairments

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I. A. Kelmanson

2015-01-01

Full Text Available The most important and noticeable rhythmical phenomenon observed in the human body is a sleep-wake rhythm and related physical and mental changes. The so-called circadian rhythms that vary over a period of approximately 24 hours are most important. The suprachi-asmatic nucleus of the hypothalamus is a primary circadian pacemaker in mammals; and light pulses out of all stimuli obtained by this structure have been mostly studied. The light pulses unrelated to visual perception serve as the most important synchronizers of circadian rhythms. Children with visual impairments lack adequate photic stimulation and hence circadian rhythm disorders develop and cognitive impairments worsen with a high probability. The most important types of sleep disorders in children with visual impairments are considered; their negative impact on a child's cognitive functions is discussed; possible correction approaches are laid down.

Structure-based virtual screening and characterization of a novel IL-6 antagonistic compound from synthetic compound database

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Wang J

2016-12-01

Full Text Available Jing Wang,1,* Chunxia Qiao,1,* He Xiao,1 Zhou Lin,1 Yan Li,1 Jiyan Zhang,1 Beifen Shen,1 Tinghuan Fu,2 Jiannan Feng1 1Department of Molecular Immunology, Beijing Institute of Basic Medical Sciences, 2First Affiliated Hospital of PLA General Hospital, Beijing, People’s Republic of China *These authors contributed equally to this work Abstract: According to the three-dimensional (3D complex structure of (hIL-6·hIL-6R·gp 1302 and the binding orientation of hIL-6, three compounds with high affinity to hIL-6R and bioactivity to block hIL-6 in vitro were screened theoretically from the chemical databases, including 3D-Available Chemicals Directory (ACD and MDL Drug Data Report (MDDR, by means of the computer-guided virtual screening method. Using distance geometry, molecular modeling and molecular dynamics trajectory analysis methods, the binding mode and binding energy of the three compounds were evaluated theoretically. Enzyme-linked immunosorbent assay analysis demonstrated that all the three compounds could block IL-6 binding to IL-6R specifically. However, only compound 1 could effectively antagonize the function of hIL-6 and inhibit the proliferation of XG-7 cells in a dose-dependent manner, whereas it showed no cytotoxicity to SP2/0 or L929 cells. These data demonstrated that the compound 1 could be a promising candidate of hIL-6 antagonist. Keywords: virtual screening, structural optimization, human interlukin-6, small molecular antagonist, XG-7 cells, apoptosis

Human heart disease : lessons from human pluripotent stem cell-derived cardiomyocytes

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Giacomelli, E.; Mummery, C.L.; Bellin, M.

2017-01-01

Technical advances in generating and phenotyping cardiomyocytes from human pluripotent stem cells (hPSC-CMs) are now driving their wider acceptance as in vitro models to understand human heart disease and discover therapeutic targets that may lead to new compounds for clinical use. Current

Moving the hands and feet specifically impairs working memory for arm- and leg-related action words.

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Shebani, Zubaida; Pulvermüller, Friedemann

2013-01-01

Language and action systems of the human brain are functionally interwoven. Speaking about actions and understanding action-related speech sparks the motor system of the human brain and, conversely, motor system activation has an influence on the comprehension of action words and sentences. Although previous research has shown that motor systems become active when we understand language, a major question still remains whether these motor system activations are necessary for processing action words. We here report that rhythmic movements of either the hands or the feet lead to a differential impairment of working memory for concordant arm- and leg-related action words, with hand/arm movements predominantly impairing working memory for words used to speak about arm actions and foot/leg movements primarily impairing leg-related word memory. The resulting cross-over double dissociation demonstrates that body part specific and meaning-related processing resources in specific cortical motor systems are shared between overt movements and working memory for action-related words, thus documenting a genuine motor locus of semantic meaning. Copyright © 2011. Published by Elsevier Srl.

Isotopically modified compounds

International Nuclear Information System (INIS)

Kuruc, J.

2009-01-01

In this chapter the nomenclature of isotopically modified compounds in Slovak language is described. This chapter consists of following parts: (1) Isotopically substituted compounds; (2) Specifically isotopically labelled compounds; (3) Selectively isotopically labelled compounds; (4) Non-selectively isotopically labelled compounds; (5) Isotopically deficient compounds.

Global simulation of aromatic volatile organic compounds in the atmosphere