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Sample records for acid stimulation treatment

  1. Hydraulic Fracture Stimulation and Acid Treatment of Well Baca 20; Geothermal Reservoir Well Stimulation Program

    SciTech Connect

    1983-07-01

    The U.S. Department of Energy-sponsored Geothermal Reservoir Well Stimulation Program was initiated in February 1979 to pursue industry interest in geothermal well stimulation work and to develop technical expertise in areas directly related to geothermal well stimulation activities. This report provides an overview of the two experiments conducted in the high-temperature reservoir in Baca, New Mexico. The report discusses resource and reservoir properties, and provides a description of the stimulation experiment, a description of the treatment evaluation, and a summary of the experiment costs. (DJE-2005)

  2. Geochemical modelling of EGS fracture stimulation applying weak and strong acid treatments

    NASA Astrophysics Data System (ADS)

    Sigfusson, Bergur; Sif Pind Aradottir, Edda

    2015-04-01

    Engineered Geothermal systems (EGS) provide geothermal power by tapping into the Earth's deep geothermal resources that are otherwise not exploitable due to lack of water and fractures, location or rock type. EGS technologies have the potential to cost effectively produce large amounts of electricity almost anywhere in the world. The EGS technology creates permeability in the rock by hydro-fracturing the reservoir with cold water pumped into the first well (the injection well) at a high pressure. The second well (the production well) intersects the stimulated fracture system and returns the hot water to the surface where electricity can be generated. A significant technological hurdle is ensuring effective connection between the wells and the fracture system and to control the deep-rooted fractures (can exceed 5 000 m depth). A large area for heat transfer and sufficient mass flow needs to be ensured between wells without creating fast flowing paths in the fracture network. Maintaining flow through the fracture system can cause considerable energy penalty to the overall process. Therefore, chemical methods to maintain fractures and prevent scaling can be necessary to prevent excessive pressure build up in the re-injection wells of EGS systems. The effect of different acid treatments on the porosity development of selected rock types was simulated with the aid of the Petrasim interface to the Toughreact simulation code. The thermodynamic and kinetic database of Aradottir et al. (2014) was expanded to include new minerals and the most important fluoride bearing species involved in mineral reactions during acid stimulation of geothermal systems. A series of simulations with injection waters containing fluoric acid, hydrochloric acid and CO2 or mixtures thereof were then carried out and porosity development in the fracture system monitored. The periodic injection of weak acid mixtures into EGS systems may be cost effective in some isolated cases to prevent pressure

  3. New Acid Stimulation Treatment to Sustain Production - Los Angeles Downtown Oil Field

    SciTech Connect

    Russell, Richard C.

    2003-03-10

    Hydrochloric acid stimulation was successfully used on several wells in the Los Angeles Downtown Field, in the past. The decline rates after stimulation were relatively high and generally within six months to a year, production rates have returned to their prestimulation rates. The wells in Los Angeles Downtown Field have strong scale producing tendencies and many wells are treated for scale control. Four wells were carefully selected that are representative of wells that had a tendency to form calcium carbonate scale and had shown substantial decline over the last few years.

  4. Ketamine: stimulating antidepressant treatment?

    PubMed Central

    Byrow, Yulisha; Cassidy, Frederick; Cipriani, Andrea; Demyttenaere, Koen; Frye, Mark A.; Gitlin, Michael; Kennedy, Sidney H.; Ketter, Terence A.; Lam, Raymond W.; McShane, Rupert; Mitchell, Alex J.; Ostacher, Michael J.; Rizvi, Sakina J.; Thase, Michael E.; Tohen, Mauricio

    2016-01-01

    Speaker’s Bureau payments): GlaxoSmithKline, and Sunovion Pharmaceuticals; royalties from American Psychiatric Publishing, Inc. Also, AstraZeneca Pharmaceuticals LP provided publication support to Parexel for preparation of a manuscript. Spouse employee and stockholder of Janssen Pharmaceuticals. R.W.L. Honoraria for speaking/advising/consulting, and/or received research funds: AstraZeneca, Brain Canada, Bristol Myers Squibb, Canadian Institutes of Health Research, Canadian Depression Research and Intervention Network, Canadian Network for Mood and Anxiety Treatments, Canadian Psychiatric Association, Coast Capital Savings, Johnson and Johnson, Lundbeck, Lundbeck Institute, Pfizer, Servier, St. Jude Medical, Takeda University, Health Network Foundation, and Vancouver Coastal Health Research Institute. R.M. Investigator Janssen trials of esketamine; ‘paid-for’ ketamine clinic operated by Oxford Health NHS Foundation Trust - fees used to support the Trust. M.J.O. Consultant: Sunovion and Acadia Pharmaceuticals. Full-time employee of U.S. Department of Veterans Affairs. M.E.T. Advisory/Consultant: Alkermes, Allergan, AstraZeneca, Bristol-Myers Squibb Company, Cerecor inc., Eli Lilly & Co., Forest Laboratories, Gerson Lehrman Group, Fabre-Kramer Pharmaceuticals, Inc., GlaxoSmithKline, Guidepoint Global, H. Lundbeck A/S, MedAvante Inc., Merck and Co. Inc. (formerly Schering Plough and Organon), Moksha8, Naurex Inc., Neuronetics Inc., Novartis, Ortho-McNeil Pharmaceuticals (Johnson & Johnson; Janssen), Otsuka, Pamlab, L.L.C. (Nestle), Pfizer (formerly Wyeth Ayerst Pharmaceuticals), Shire US Inc., Sunovion Pharmaceuticals Inc., Trius Therapeutical Inc. and Takeda. Grant support: Agency for Healthcare Research and Quality, Alkermes, AssureRx, Avanir, Forest Pharmaceuticals, Janssen, National Institute of Mental Health, and Otsuka Pharmaceuticals. Speakers Bureau: None since June, 2010. Equity Holdings: MedAvante, Inc. Royalties: American Psychiatric Foundation, Guilford

  5. Retinoic Acid Stimulates Regeneration of Mammalian Auditory Hair Cells

    NASA Astrophysics Data System (ADS)

    Lefebvre, Philippe P.; Malgrange, Brigitte; Staecker, Hinrich; Moonen, Gustave; van de Water, Thomas R.

    1993-04-01

    Sensorineural hearing loss resulting from the loss of auditory hair cells is thought to be irreversible in mammals. This study provides evidence that retinoic acid can stimulate the regeneration in vitro of mammalian auditory hair cells in ototoxic-poisoned organ of Corti explants in the rat. In contrast, treatment with retinoic acid does not stimulate the formation of extra hair cells in control cultures of Corti's organ. Retinoic acid-stimulated hair cell regeneration can be blocked by cytosine arabinoside, which suggests that a period of mitosis is required for the regeneration of auditory hair cells in this system. These results provide hope for a recovery of hearing function in mammals after auditory hair cell damage.

  6. Cytokinin producing bacteria stimulate amino acid deposition by wheat roots.

    PubMed

    Kudoyarova, Guzel R; Melentiev, Alexander I; Martynenko, Elena V; Timergalina, Leila N; Arkhipova, Tatiana N; Shendel, Galina V; Kuz'mina, Ludmila Yu; Dodd, Ian C; Veselov, Stanislav Yu

    2014-10-01

    Phytohormone production is one mechanism by which rhizobacteria can stimulate plant growth, but it is not clear whether the bacteria gain from this mechanism. The hypothesis that microbial-derived cytokinin phytohormones stimulate root exudation of amino acids was tested. The rhizosphere of wheat plants was drenched with the synthetic cytokinin trans-zeatin or inoculated with Bacillus subtilis IB-22 (which produces zeatin type cytokinins) or B. subtilis IB-21 (which failed to accumulate cytokinins). Growing plants in a split root system allowed spatial separation of zeatin application or rhizobacterial inoculation to one compartment and analyses of amino acid release from roots (rhizodeposition) into the other compartment (without either microbial inoculation or treatment with exogenous hormone). Supplying B. subtilis IB-22 or zeatin to either the whole root system or half of the roots increased concentrations of amino acids in the soil solution although the magnitude of the increase was greater when whole roots were treated. There was some similarity in amino acid concentrations induced by either bacterial or zeatin treatment. Thus B. subtilis IB-22 increased amino acid rhizodeposition, likely due to its ability to produce cytokinins. Furthermore, B. subtilis strain IB-21, which failed to accumulate cytokinins in culture media, did not significantly affect amino acid concentrations in the wheat rhizosphere. The ability of rhizobacteria to produce cytokinins and thereby stimulate rhizodeposition may be important in enhancing rhizobacterial colonization of the rhizoplane.

  7. Chemical stimulation treatment, The Geysers: Ottoboni State 22. Geothermal-reservoir well-stimulation program

    SciTech Connect

    Not Available

    1981-02-01

    Experiment No. 6 of the Geothermal Reservoir Well Stimulation Program (GRWSP) was performed at The Geysers Field in Sonoma County, California. This well had low productivity (46,000 lb/hr), probably because it did not intersect the primary natural fracture system of the reservoir. Surrounding production wells are considered to be good wells with an average flow rate of about 100,000 lb/hr. The stimulation technique selected was an acid etching treatment (Halliburton Services' MY-T-ACID). A small water prepad was used to provide tubular cooling and fluid loss control. Following the water prepad were 500 to 750 bbl of high viscosity crosslinked gel fluid and 400 to 500 bbl of a hydrofluoric-hydrochloric (HF-HCl) acid solution. The frac fluids were expected to enter only a single or limited fracture zone within the open interval. Frac rates of 20 to 40 BPM and surface pressures of 3000 psig were estimated for this treatment. During the job, however, no significant surface pressure was recorded, and all fluids flowed easily into the interval. Subsequent evaluation of the well performance showed that no noticeable stimulation had been achieved even though the frac fluids were properly injected. Temperature and gamma ray surveys along with tracer studies indicated that the frac fluids entered natural fracture channels over a 650-foot zone of the open interval, which probably prevented the staged acid etching treatment from functioning as designed.

  8. Stimulation of monokine production by lipoteichoic acids.

    PubMed Central

    Bhakdi, S; Klonisch, T; Nuber, P; Fischer, W

    1991-01-01

    Lipoteichoic acids (LTAs) isolated from bacterial species, including Staphylococcus aureus, Streptococcus pyogenes A, Enterococcus faecalis, Streptococcus pneumoniae, and Listeria monocytogenes, were tested for their ability to stimulate the production of interleukin-1 beta (IL-1 beta), IL-6, and tumor necrosis factor alpha in cultured human monocytes. LTAs from S. aureus and S. pneumoniae failed to induce monokine production when applied in the concentration range of 0.05 to 5.0 micrograms/ml. However, LTAs from several enterococcal species (0.5 to 5 micrograms/ml) induced the release of all three monokines at levels similar to those observed after lipopolysaccharide stimulation. The kinetics of IL-1 beta and tumor necrosis factor alpha release elicited by LTAs closely resembled those observed following lipopolysaccharide application. Cytokine production occurred in the presence of both fetal calf serum and autologous human serum. Hence, it was not dependent on complement activation and could not be suppressed by naturally occurring human antibodies. Deacylation caused the total loss of monocyte stimulatory capacity. Deacylated LTAs were unable to prevent monocyte activation by intact LTAs, so primary binding of these molecules probably does not involve a simple interaction of a membrane receptor with the hydrophilic portion of the molecule. The results identify some species of LTAs as inducers of monokine production in human monocytes. PMID:1937822

  9. Retinoic acid stimulation of human dermal fibroblast proliferation is dependent on suboptimal extracellular Ca2+ concentration

    SciTech Connect

    Varani, J.; Shayevitz, J.; Perry, D.; Mitra, R.S.; Nickoloff, B.J.; Voorhees, J.J. )

    1990-06-01

    Human dermal fibroblasts failed to proliferate when cultured in medium containing 0.15 mmol/l (millimolar) Ca2+ (keratinocyte growth medium (KGM)) but did when the external Ca2+ concentration was raised to 1.4 mmol/l. All-trans retinoic acid (retinoic acid) stimulated proliferation in KGM but did not further stimulate growth in Ca2(+)-supplemented KGM. The ability of retinoic acid to stimulate proliferation was inhibited in KGM prepared without Ca2+ or prepared with 0.03 mmol/l Ca2+ and in KGM treated with 1 mmol/l ethylene-glycol-bis-(beta-aminoethyl ether)N,N'-tetra acetic acid. Using 45Ca2+ to measure Ca2+ influx and efflux, it was found that retinoic acid minimally increased Ca2+ uptake into fibroblasts. In contrast, retinoic acid treatment of fibroblasts that had been pre-equilibrated for 1 day with 45Ca2+ inhibited release of intracellular Ca2+ into the extracellular fluid. Retinoic acid also stimulated 35S-methionine incorporation into trichloroacetic acid-precipitable material but in contrast to its effect on proliferation, stimulation of 35S-methionine incorporation occurred in both high-Ca2+ and low-Ca2+ medium. These data indicate that retinoic acid stimulation of proliferation, but not protein synthesis, is dependent on the concentration of Ca2+ in the extracellular environment.

  10. Dietary Sugars Stimulate Fatty Acid Synthesis in Adults123

    PubMed Central

    Parks, Elizabeth J.; Skokan, Lauren E.; Timlin, Maureen T.; Dingfelder, Carlus S.

    2008-01-01

    The goal of this study was to determine the magnitude by which acute consumption of fructose in a morning bolus would stimulate lipogenesis (measured by infusion of 13C1-acetate and analysis by GC-MS) immediately and after a subsequent meal. Six healthy subjects [4 men and 2 women; aged (mean ± SD) 28 ± 8 y; BMI, 24.3 ± 2.8 kg/m2; and serum triacylglycerols (TG), 1.03 ± 0.32 mmol/L] consumed carbohydrate boluses of sugars (85 g each) in a random and blinded order, followed by a standardized lunch 4 h later. Subjects completed a control test of glucose (100:0) and a mixture of 50:50 glucose:fructose and one of 25:75 (wt:wt). Following the morning boluses, serum glucose and insulin after 100:0 were greater than both other treatments (P < 0.05) and this pattern occurred again after lunch. In the morning, fractional lipogenesis was stimulated when subjects ingested fructose and peaked at 15.9 ± 5.4% after the 50:50 treatment and at 16.9 ± 5.2% after the 25:75 treatment, values that were greater than after the 100:0 treatment (7.8 ± 5.7%; P < 0.02). When fructose was consumed, absolute lipogenesis was 2-fold greater than when it was absent (100:0). Postlunch, serum TG were 11–29% greater than 100:0 and TG-rich lipoprotein-TG concentrations were 76–200% greater after 50:50 and 25:75 were consumed (P < 0.05). The data demonstrate that an early stimulation of lipogenesis after fructose, consumed in a mixture of sugars, augments subsequent postprandial lipemia. The postlunch blood TG elevation was only partially due to carry-over from the morning. Acute intake of fructose stimulates lipogenesis and may create a metabolic milieu that enhances subsequent esterification of fatty acids flowing to the liver to elevate TG synthesis postprandially. PMID:18492831

  11. Motilin Stimulates Gastric Acid Secretion in Coordination with Ghrelin in Suncus murinus.

    PubMed

    Goswami, Chayon; Shimada, Yoshiaki; Yoshimura, Makoto; Mondal, Anupom; Oda, Sen-ichi; Tanaka, Toru; Sakai, Takafumi; Sakata, Ichiro

    2015-01-01

    Motilin and ghrelin constitute a peptide family, and these hormones are important for the regulation of gastrointestinal motility. In this study, we examined the effect of motilin and ghrelin on gastric acid secretion in anesthetized suncus (house musk shrew, Suncus murinus), a ghrelin- and motilin-producing mammal. We first established a gastric lumen-perfusion system in the suncus and confirmed that intravenous (i.v.) administration of histamine (1 mg/kg body weight) stimulated acid secretion. Motilin (0.1, 1.0, and 10 μg/kg BW) stimulated the acid output in a dose-dependent manner in suncus, whereas ghrelin (0.1, 1.0, and 10 μg/kg BW) alone did not induce acid output. Furthermore, in comparison with the vehicle administration, the co-administration of low-dose (1 μg/kg BW) motilin and ghrelin significantly stimulated gastric acid secretion, whereas either motilin (1 μg/kg BW) or ghrelin (1 μg/kg BW) alone did not significantly induce gastric acid secretion. This indicates an additive role of ghrelin in motilin-induced gastric acid secretion. We then investigated the pathways of motilin/motilin and ghrelin-stimulated acid secretion using receptor antagonists. Treatment with YM 022 (a CCK-B receptor antagonist) and atropine (a muscarinic acetylcholine receptor antagonist) had no effect on motilin or motilin-ghrelin co-administration-induced acid output. In contrast, famotidine (a histamine H2 receptor antagonist) completely inhibited motilin-stimulated acid secretion and co-administration of motilin and ghrelin induced gastric acid output. This is the first report demonstrating that motilin stimulates gastric secretion in mammals. Our results also suggest that motilin and co-administration of motilin and ghrelin stimulate gastric acid secretion via the histamine-mediated pathway in suncus. PMID:26115342

  12. Motilin Stimulates Gastric Acid Secretion in Coordination with Ghrelin in Suncus murinus

    PubMed Central

    Goswami, Chayon; Shimada, Yoshiaki; Yoshimura, Makoto; Mondal, Anupom; Oda, Sen-ichi; Tanaka, Toru; Sakai, Takafumi; Sakata, Ichiro

    2015-01-01

    Motilin and ghrelin constitute a peptide family, and these hormones are important for the regulation of gastrointestinal motility. In this study, we examined the effect of motilin and ghrelin on gastric acid secretion in anesthetized suncus (house musk shrew, Suncus murinus), a ghrelin- and motilin-producing mammal. We first established a gastric lumen-perfusion system in the suncus and confirmed that intravenous (i.v.) administration of histamine (1 mg/kg body weight) stimulated acid secretion. Motilin (0.1, 1.0, and 10 μg/kg BW) stimulated the acid output in a dose-dependent manner in suncus, whereas ghrelin (0.1, 1.0, and 10 μg/kg BW) alone did not induce acid output. Furthermore, in comparison with the vehicle administration, the co-administration of low-dose (1 μg/kg BW) motilin and ghrelin significantly stimulated gastric acid secretion, whereas either motilin (1 μg/kg BW) or ghrelin (1 μg/kg BW) alone did not significantly induce gastric acid secretion. This indicates an additive role of ghrelin in motilin-induced gastric acid secretion. We then investigated the pathways of motilin/motilin and ghrelin-stimulated acid secretion using receptor antagonists. Treatment with YM 022 (a CCK-B receptor antagonist) and atropine (a muscarinic acetylcholine receptor antagonist) had no effect on motilin or motilin-ghrelin co-administration-induced acid output. In contrast, famotidine (a histamine H2 receptor antagonist) completely inhibited motilin-stimulated acid secretion and co-administration of motilin and ghrelin induced gastric acid output. This is the first report demonstrating that motilin stimulates gastric secretion in mammals. Our results also suggest that motilin and co-administration of motilin and ghrelin stimulate gastric acid secretion via the histamine-mediated pathway in suncus. PMID:26115342

  13. Acid rain stimulation of Lake Michigan phytoplankton growth

    USGS Publications Warehouse

    Manny, Bruce A.; Fahnenstiel, G.L.; Gardner, W.S.

    1987-01-01

    Three laboratory experiments demonstrated that additions of rainwater to epilimnetic lake water collected in southeastern Lake Michigan stimulated chlorophyll a production more than did additions of reagent-grade water during incubations of 12 to 20 d. Chlorophyll a production did not begin until 3–5 d after the rain and lake water were mixed. The stimulation caused by additions of rain acidified to pH 3.0 was greater than that caused by additions of untreated rain (pH 4.0–4.5). Our results support the following hypotheses: (1) Acid rain stimulates the growth of phytoplankton in lake water; (2) phosphorus in rain appears to be the factor causing this stimulation. We conclude that acid rain may accelerate the growth of epilimnetic phytoplankton in Lake Michigan (and other similar lakes) during stratification when other sources of bioavailable phosphorus to the epilimnion are limited

  14. Stimulation of phosphatidic acid of calcium influx and cyclic GMP synthesis in neuroblastoma cells.

    PubMed

    Ohsako, S; Deguchi, T

    1981-11-10

    Phosphatidic acid added to the medium markedly elevated intracellular cyclic GMP content in cultured neuroblastoma N1E 115 cells. There was a significant elevation of cyclic GMP with 1 micrograms/ml and a maximum (70-fold) elevation with 100 micrograms/ml of phosphatidic acid. Other natural phospholipids did not increase, or increased only slightly, the cyclic GMP content in the cells. The elevation of cyclic GMP content by phosphatidic acid was absolutely dependent on extracellular calcium. Phosphatidic acid stimulated the influx of calcium into neuroblastoma cells 2- to 5-fold. The pattern of the calcium influx induced by phosphatidic acid was comparable to that of cyclic GMP elevation. The stimulation of calcium influx by phosphatidic acid was also observed in cultured heart cells, indicating that phosphatidic acid acts as a calcium ionophore or opens a specific calcium-gate in a variety of cell membranes. Treatment of neuroblastoma cells with phospholipase C increased 32Pi labeling of phosphatidic acid, stimulated the influx of calcium, and elevated the cyclic GMP content in the cells. Thus exogenous as well as endogenous phosphatidic acid stimulates the translocation of calcium across cell membranes and, as a consequence, induces the synthesis of cyclic GMP in the neuroblastoma cells.

  15. [Others physical methods in psychiatric treatment based on electromagnetic stimulation].

    PubMed

    Zyss, Tomasz; Rachel, Wojciech; Datka, Wojciech; Hese, Robert T; Gorczyca, Piotr; Zięba, Andrzej; Piekoszewski, Wojciech

    2016-01-01

    In the last decades a few new physical methods based on the electromagnetic head stimulation were subjected to the clinical research. To them belong:--vagus nerve stimulation (VNS),--magnetic seizure therapy/magnetoconvulsive therapy (MST/MCT),--deep stimulation of the brain (DBS) and--transcranial direct current stimulation (tDCS). The paper presents a description of mentioned techniques (nature, advantages, defects, restrictions), which were compared to the applied electroconvulsive treatment ECT, earlier described transcranial magnetic stimulation TMS and the pharmacotherapy (the basis of the psychiatric treatment). PMID:27197431

  16. [Others physical methods in psychiatric treatment based on electromagnetic stimulation].

    PubMed

    Zyss, Tomasz; Rachel, Wojciech; Datka, Wojciech; Hese, Robert T; Gorczyca, Piotr; Zięba, Andrzej; Piekoszewski, Wojciech

    2016-01-01

    In the last decades a few new physical methods based on the electromagnetic head stimulation were subjected to the clinical research. To them belong:--vagus nerve stimulation (VNS),--magnetic seizure therapy/magnetoconvulsive therapy (MST/MCT),--deep stimulation of the brain (DBS) and--transcranial direct current stimulation (tDCS). The paper presents a description of mentioned techniques (nature, advantages, defects, restrictions), which were compared to the applied electroconvulsive treatment ECT, earlier described transcranial magnetic stimulation TMS and the pharmacotherapy (the basis of the psychiatric treatment).

  17. Developing Treatments for Stimulant Abuse: A Brief Overview.

    PubMed

    Davidson, C

    2016-06-01

    The abuse of stimulants such as cocaine, amphetamine, and methamphetamine is a huge problem in many parts of the world. Abuse of these drugs does not ruin just the user's life, but also adversely affects those around them. Despite many years of research, there are no approved medications for stimulant dependence, and treatment is focused on psychotherapy and abstinence. Over the last 10 to 20 years, there have been some major changes in approach to medication development for stimulant dependence. These include assessing ligands for non-dopaminergic sites, atypical dopamine transporter ligands, blocking long-term potentiation and / or memory reconsolidation, vaccines against the stimulant, and molecular approaches including pharmacogenomics and gene silencing. Also included in this overview are non-drug treatments such as deep brain stimulation and psychosurgery. This overview highlights recent preclinical and clinical studies of treatment development for stimulant dependence. PMID:27377486

  18. Stimulating effect of phosphatidic acid on autophosphorylation of phosphorylase kinase.

    PubMed

    Negami, A I; Sasaki, H; Yamamura, H

    1985-09-16

    Autophosphorylation of phosphorylase kinase from rabbit skeletal muscle was stimulated by acidic phospholipids such as phosphatidic acid (PA), phosphatidylinositol, and phosphatidyl-serine. PA stimulated an initial velocity of autophosphorylation 3.8-fold. When fully autophosphorylated, about 11 mol of phosphate per tetramer (alpha beta gamma delta) were incorporated in the presence of PA and about 6.5 mol in the absence of PA. In the presence of PA (100 micrograms/ml), there was a concomitant enhancement of its kinase activity about 25-fold at pH 6.8. PA (100 micrograms/ml) sharply decreased an apparent Ka for Ca2+ on autophosphorylation from 4.0 X 10(-5) M to 1.0 X 10(-6) M. Available evidence indicates that the Ca2+-activated, PA-dependent autophosphorylation of phosphorylase kinase shows an ability to stimulate glycogen breakdown.

  19. Stimulation of prostacyclin synthesis in rats by phenobarbital treatment

    SciTech Connect

    Pynadath, T.I.; Haghighi, A.Z.

    1986-05-01

    Prostacyclin (PGI/sub 2/), synthesized in the endothelial cells of arteries, is known to inhibit the aggregation of platelets and hence thrombosis in blood. Low levels of PGI/sub 2/ have been observed in coronary heart disease which is associated with low levels of HDL in blood. Recently, it has been shown that synthesis of PGI/sub 2/ in vitro, is stimulated by HDL. Hence it seems likely that higher level of HDL in blood would increase the level of PGI/sub 2/ in blood. Since phenobarbital treatment is known to increase blood HDL levels in humans and animals, this study was undertaken to determine the effect of phenobarbital treatment on the synthesis of PGI/sub 2/. Coronary vascular microsomes were prepared from Sprague Dawley rats treated with phenobarbital for two days. The PGI/sub 2/ synthesizing activity was assayed by incubating these microsomes with 1-/sup 14/C-arachidonic acid and by determining the /sup 14/C-activity recovered in 6-ketoprostaglandin F/sub 1..cap alpha../, the stable decomposition product of PGI/sub 2/. Phenobarbital treatment increased the synthesis of PGI/sub 2/ nearly 2-fold. Addition of phenobarbital did not increase PGI/sub 2/ synthesis in control microsomes; however, the synthesis was increased by HDL. Thus, it appears that the observed increase in PGI/sub 2/ synthesis resulting from phenobarbital treatment was partly, if not totally, due to the increase in blood HDL level.

  20. Gibberellic acid stimulates acid invertase secretion in pea ovary protoplasts.

    PubMed

    Estruch, J J; Beltrán, J P

    1991-02-25

    Protoplasts purified from mesocarp of nonpollinated pea (Pisum sativum L.) ovaries released acid invertase to the incubation medium. The association of the acid invertase with microsomal fractions, and the sensitivity to energy-metabolism inhibitors and to tunicamycin, indicated the secretory nature of the release process. In the presence of GA3 (10 microM), the protoplasts increased their invertase secretion at about 60 min, this effect being counteracted by tunicamycin but not by cycloheximide. Subcellular fractionation of GA3-treated protoplasts showed that higher invertase secretion was the result of a promotion of invertase transfer from endoplasmic reticulum (ER) to Golgi apparatus. PMID:2001743

  1. Natural Product Anacardic Acid from Cashew Nut Shells Stimulates Neutrophil Extracellular Trap Production and Bactericidal Activity.

    PubMed

    Hollands, Andrew; Corriden, Ross; Gysler, Gabriela; Dahesh, Samira; Olson, Joshua; Raza Ali, Syed; Kunkel, Maya T; Lin, Ann E; Forli, Stefano; Newton, Alexandra C; Kumar, Geetha B; Nair, Bipin G; Perry, J Jefferson P; Nizet, Victor

    2016-07-01

    Emerging antibiotic resistance among pathogenic bacteria is an issue of great clinical importance, and new approaches to therapy are urgently needed. Anacardic acid, the primary active component of cashew nut shell extract, is a natural product used in the treatment of a variety of medical conditions, including infectious abscesses. Here, we investigate the effects of this natural product on the function of human neutrophils. We find that anacardic acid stimulates the production of reactive oxygen species and neutrophil extracellular traps, two mechanisms utilized by neutrophils to kill invading bacteria. Molecular modeling and pharmacological inhibitor studies suggest anacardic acid stimulation of neutrophils occurs in a PI3K-dependent manner through activation of surface-expressed G protein-coupled sphingosine-1-phosphate receptors. Neutrophil extracellular traps produced in response to anacardic acid are bactericidal and complement select direct antimicrobial activities of the compound. PMID:27226531

  2. Natural Product Anacardic Acid from Cashew Nut Shells Stimulates Neutrophil Extracellular Trap Production and Bactericidal Activity.

    PubMed

    Hollands, Andrew; Corriden, Ross; Gysler, Gabriela; Dahesh, Samira; Olson, Joshua; Raza Ali, Syed; Kunkel, Maya T; Lin, Ann E; Forli, Stefano; Newton, Alexandra C; Kumar, Geetha B; Nair, Bipin G; Perry, J Jefferson P; Nizet, Victor

    2016-07-01

    Emerging antibiotic resistance among pathogenic bacteria is an issue of great clinical importance, and new approaches to therapy are urgently needed. Anacardic acid, the primary active component of cashew nut shell extract, is a natural product used in the treatment of a variety of medical conditions, including infectious abscesses. Here, we investigate the effects of this natural product on the function of human neutrophils. We find that anacardic acid stimulates the production of reactive oxygen species and neutrophil extracellular traps, two mechanisms utilized by neutrophils to kill invading bacteria. Molecular modeling and pharmacological inhibitor studies suggest anacardic acid stimulation of neutrophils occurs in a PI3K-dependent manner through activation of surface-expressed G protein-coupled sphingosine-1-phosphate receptors. Neutrophil extracellular traps produced in response to anacardic acid are bactericidal and complement select direct antimicrobial activities of the compound.

  3. Stimulation of protein synthesis by phosphatidic acid in rat cardiomyocytes.

    PubMed

    Xu, Y J; Yau, L; Yu, L P; Elimban, V; Zahradka, P; Dhalla, N S

    1996-12-13

    Phosphatidic acid (PA) was observed to stimulate protein synthesis in adult cardiomyocytes in a time- and concentration-dependent manner. The maximal stimulation in protein synthesis (142 +/- 12% vs 100% as the control) was achieved at 10 microM PA within 60 min and was inhibited by actinomycin D (107 +/- 4% of the control) or cycloheximide (105 +/- 6% of the control). The increase in protein synthesis due to PA was attenuated or abolished by preincubation of cardiomyocytes with a tyrosine kinase inhibitor, genistein (94 +/- 9% of the control), phospholipase C inhibitors 2-nitro-4-carboxyphenyl N,N-diphenyl carbamate or carbon-odithioic acid O-(octahydro-4,7-methanol-1H-inden-5-yl (101 +/- 6 and 95 +/- 5% of the control, respectively), protein kinase C inhibitors staurosporine or polymyxin B (109 +/- 3 and 93 +/- 3% of the control), and chelators of extracellular and intracellular free Ca2+ EGTA or BAPTA/AM (103 +/- 6 and 95 +/- 6% of the control, respectively). PA at different concentrations (0.1 to 100 microM) also caused phosphorylation of a cell surface protein of approximately 24 kDa. In addition, mitogen-activated protein kinase was stimulated by PA in a concentration-dependent manner; maximal stimulation (217 +/- 6% of the control) was seen at 10 microM PA. These data suggest that PA increases protein synthesis in adult rat cardiomyocytes and thus may play an important role in the development of cardiac hypertrophy.

  4. Mechanism of deoxycholic acid stimulation of the rabbit colon.

    PubMed Central

    Shiff, S J; Soloway, R D; Snape, W J

    1982-01-01

    Previous studies showed that deoxycholic acid (DCA) stimulated migrating action potential complexes (MAPC) in the colon. The aim of this study was to clarify the mechanism of DCA-stimulated colonic motility. Myoelectrical and contractile activity were measured in New Zealand White rabbits from a loop constructed in the proximal colon. During the control period, slow waves were present at a frequency of 10.8 +/- 0.5 cycle/min and there were 1.5 +/- 0.5 MAPC/ h. After adding DCA (16 mM) to the loop the slow wave activity was unchanged. However, MAPC increased to 15.1 +/- 2.4 MAPC/h (P less than 0.001). MAPC activity was not stimulated in the colonic smooth muscle outside the loop. The intraluminal addition of procaine or tetrodotoxin to the colonic loop inhibited the DCA-stimulated increase in MAPC activity (0.2 +/- 0.2 MAPC/h) (P less than 0.005). Intravenous administration of atropine or phentolamine also inhibited MAPC activity that had been stimulated by DCA (P less than 0.005). Pretreatment with 6-hydroxydopamine also inhibited an increase in MAPC activity. Propranolol, trimethaphan camsylate, or hexamethonium had no effect on DCA stimulation of MAPC activity. Although the concentration of bile salt increased in the mesenteric venous outflow from the colonic loop, the intravenous administration of bile salt did not stimulate colonic MAPC activity. These studies suggest: (a) the action of DCA on smooth muscle activity is a local phenomenon, (b) the increase in MAPC activity is dependent on intact cholinergic and alpha adrenergic neurons, and (c) an increase in the concentration of bile salts in the serum is not associated with an increase in colonic MAPC activity. PMID:7076855

  5. Cranial electrotherapy stimulation for treatment of anxiety, depression, and insomnia.

    PubMed

    Kirsch, Daniel L; Nichols, Francine

    2013-03-01

    Cranial electrotherapy stimulation is a prescriptive medical device that delivers a mild form of electrical stimulation to the brain for the treatment of anxiety, depression, and insomnia. It is supported by more than 40 years of research demonstrating its effectiveness in several mechanistic studies and greater than 100 clinical studies. Adverse effects are rare (<1%), mild, and self-limiting, consisting mainly of skin irritation under the electrodes and headaches. Often used as a stand-alone therapy, because results are usually seen from the first treatment, cranial electrotherapy stimulation may also be used as an adjunctive therapy.

  6. Modulation of norepinephrine-stimulated cyclic AMP accumulation in rat pinealocytes by n-3 fatty acids.

    PubMed

    Delton-Vandenbroucke, I; Sarda, N; Molière, P; Lagarde, M; Gharib, A

    1996-10-01

    This work showed that docosahexaenoic (22:6n-3) and eicosapentaenoic (20:5n-3) acid supplementation for 48 h have opposite effects on the norepinephrine-stimulated cyclic AMP accumulation in rat pinealocytes. We found that 22:6n-3 supplementation of pineal cells, done by increasing specifically 22:6n-3 in phospholipid and triacylglycerol pools, led to inhibition of norepinephrine-stimulated cyclic AMP production whereas 20:5n-3 supplementation, by increasing 20:5n-3, and 22:5n-3 and 22:6n-3 in the same pools, stimulated it. In contrast, direct treatment of pinealocytes with each fatty acid (50 microM) did not affect cyclic AMP production in the presence of (0.1-10 microM) norepinephrine. The results indicate that, using pharmacological agents such as forskolin or prazosin: (a) neither basal nor forskolin-stimulated cyclic AMP levels were modified in fatty acid-supplemented cells compared to control cells; (b) in the presence of 1 microM prazosin, the activation by 20:5n-3 was still effective whereas no additional inhibition of norepinephrine stimulation was observed in 22:6n-3-supplemented cells. Taken together our results suggest that 22:6n-3 or 20:5n-3 supplementation modulates specifically the alpha 1- or beta-adrenoceptors in the rat pineal gland.

  7. Stimulation and binding of myocardial phospholipase C by phosphatidic acid.

    PubMed

    Henry, R A; Boyce, S Y; Kurz, T; Wolf, R A

    1995-08-01

    Exposure of adult ventricular myocytes to exogenous natural phosphatidic acid results in the production of inositol phosphates by unknown mechanism(s). We characterized stimulation of myocytic phosphoinositide-specific phospholipase C (PLC) by synthetic dioleoyl phosphatidic acid (PA) as a potential mechanism for modulation of inositol phosphate production. Our data demonstrate that exogenous PA, at 10(-8)-10(-5) M, caused a concentration-dependent increase in inositol 1,4,5-trisphosphate in adult rabbit ventricular myocytes. PA also caused a concentration-dependent increase in in vitro activity of myocytic PLC in the presence or absence of ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA). PLC-delta 1, the predominant isozyme of PLC expressed in adult rabbit ventricular myocytes, bound to liposomes of PA with high affinity in the presence of EGTA. The phosphomonoester group of PA was critical to in vitro stimulation of myocytic PLC activity and high-affinity binding of PLC-delta 1. We propose that binding of PLC-delta 1 to phosphatidic acid may be a novel mechanism for dynamic membrane association and modulation of PLC in adult ventricular myocytes.

  8. Treatment of Amino Acid Metabolism Disorders

    MedlinePlus

    ... Treatment of amino acid metabolism disorders Treatment of amino acid metabolism disorders E-mail to a friend Please ... this page It's been added to your dashboard . Amino acid metabolism disorders are rare health conditions that affect ...

  9. Cadmium inhibits acid secretion in stimulated frog gastric mucosa

    SciTech Connect

    Gerbino, Andrea; Debellis, Lucantonio; Caroppo, Rosa; Curci, Silvana; Colella, Matilde

    2010-06-01

    Cadmium, a toxic environmental pollutant, affects the function of different organs such as lungs, liver and kidney. Less is known about its toxic effects on the gastric mucosa. The aim of this study was to investigate the mechanisms by which cadmium impacts on the physiology of gastric mucosa. To this end, intact amphibian mucosae were mounted in Ussing chambers and the rate of acid secretion, short circuit current (I{sub sc}), transepithelial potential (V{sub t}) and resistance (R{sub t}) were recorded in the continuous presence of cadmium. Addition of cadmium (20 {mu}M to 1 mM) on the serosal but not luminal side of the mucosae resulted in inhibition of acid secretion and increase in NPPB-sensitive, chloride-dependent short circuit current. Remarkably, cadmium exerted its effects only on histamine-stimulated tissues. Experiments with TPEN, a cell-permeant chelator for heavy metals, showed that cadmium acts from the intracellular side of the acid secreting cells. Furthermore, cadmium-induced inhibition of acid secretion and increase in I{sub sc} cannot be explained by an action on: 1) H{sub 2} histamine receptor, 2) Ca{sup 2+} signalling 3) adenylyl cyclase or 4) carbonic anhydrase. Conversely, cadmium was ineffective in the presence of the H{sup +}/K{sup +}-ATPase blocker omeprazole suggesting that the two compounds likely act on the same target. Our findings suggest that cadmium affects the functionality of histamine-stimulated gastric mucosa by inhibiting the H{sup +}/K{sup +}-ATPase from the intracellular side. These data shed new light on the toxic effect of this dangerous environmental pollutant and may result in new avenues for therapeutic intervention in acute and chronic intoxication.

  10. Deep brain stimulation for the treatment of uncommon tremor syndromes

    PubMed Central

    Ramirez-Zamora, Adolfo; Okun, Michael S.

    2016-01-01

    ABSTRACT Introduction: Deep brain stimulation (DBS) has become a standard therapy for the treatment of select cases of medication refractory essential tremor and Parkinson’s disease however the effectiveness and long-term outcomes of DBS in other uncommon and complex tremor syndromes has not been well established. Traditionally, the ventralis intermedius nucleus (VIM) of the thalamus has been considered the main target for medically intractable tremors; however alternative brain regions and improvements in stereotactic techniques and hardware may soon change the horizon for treatment of complex tremors. Areas covered: In this article, we conducted a PubMed search using different combinations between the terms ‘Uncommon tremors’, ‘Dystonic tremor’, ‘Holmes tremor’ ‘Midbrain tremor’, ‘Rubral tremor’, ‘Cerebellar tremor’, ‘outflow tremor’, ‘Multiple Sclerosis tremor’, ‘Post-traumatic tremor’, ‘Neuropathic tremor’, and ‘Deep Brain Stimulation/DBS’. Additionally, we examined and summarized the current state of evolving interventions for treatment of complex tremor syndromes. Expert c ommentary: Recently reported interventions for rare tremors include stimulation of the posterior subthalamic area, globus pallidus internus, ventralis oralis anterior/posterior thalamic subnuclei, and the use of dual lead stimulation in one or more of these targets. Treatment should be individualized and dictated by tremor phenomenology and associated clinical features. PMID:27228280

  11. Treatment of Fatty Acid Oxidation Disorders

    MedlinePlus

    ... of fatty acid oxidation disorders Treatment of fatty acid oxidation disorders E-mail to a friend Please ... page It's been added to your dashboard . Fatty acid oxidation disorders are rare health conditions that affect ...

  12. Folic Acid Supplementation Stimulates Notch Signaling and Cell Proliferation in Embryonic Neural Stem Cells

    PubMed Central

    Liu, Huan; Huang, Guo-wei; Zhang, Xu-mei; Ren, Da-lin; X. Wilson, John

    2010-01-01

    The present study investigated the effect of folic acid supplementation on the Notch signaling pathway and cell proliferation in rat embryonic neural stem cells (NSCs). The NSCs were isolated from E14–16 rat brain and grown as neurospheres in serum-free suspension culture. Individual cultures were assigned to one of 3 treatment groups that differed according to the concentration of folic acid in the medium: Control (baseline folic acid concentration of 4 mg/l), low folic acid supplementation (4 mg/l above baseline, Folate-L) and high folic acid supplementation (40 mg/l above baseline, Folate-H). NSCs were identified by their expression of immunoreactive nestin and proliferating cells by incorporation of 5'bromo-2'deoxyuridine. Cell proliferation was also assessed by methyl thiazolyl tetrazolium assay. Notch signaling was analyzed by real-time PCR and western blot analyses of the expression of Notch1 and hairy and enhancer of split 5 (Hes5). Supplementation of NSCs with folic acid increased the mRNA and protein expression levels of Notch1 and Hes5. Folic acid supplementation also stimulated NSC proliferation dose-dependently. Embryonic NSCs respond to folic acid supplementation with increased Notch signaling and cell proliferation. This mechanism may mediate the effects of folic acid supplementation on neurogenesis in the embryonic nervous system. PMID:20838574

  13. Lauric Acid Stimulates Ketone Body Production in the KT-5 Astrocyte Cell Line.

    PubMed

    Nonaka, Yudai; Takagi, Tetsuo; Inai, Makoto; Nishimura, Shuhei; Urashima, Shogo; Honda, Kazumitsu; Aoyama, Toshiaki; Terada, Shin

    2016-08-01

    Coconut oil has recently attracted considerable attention as a potential Alzheimer's disease therapy because it contains large amounts of medium-chain fatty acids (MCFAs) and its consumption is thought to stimulate hepatic ketogenesis, supplying an alternative energy source for brains with impaired glucose metabolism. In this study, we first reevaluated the responses of plasma ketone bodies to oral administration of coconut oil to rats. We found that the coconut oil-induced increase in plasma ketone body concentration was negligible and did not significantly differ from that observed after high-oleic sunflower oil administration. In contrast, the administration of coconut oil substantially increased the plasma free fatty acid concentration and lauric acid content, which is the major MCFA in coconut oil. Next, to elucidate whether lauric acid can activate ketogenesis in astrocytes with the capacity to generate ketone bodies from fatty acids, we treated the KT-5 astrocyte cell line with 50 and 100 μM lauric acid for 4 h. The lauric acid treatments increased the total ketone body concentration in the cell culture supernatant to a greater extent than oleic acid, suggesting that lauric acid can directly and potently activate ketogenesis in KT-5 astrocytes. These results suggest that coconut oil intake may improve brain health by directly activating ketogenesis in astrocytes and thereby by providing fuel to neighboring neurons.

  14. Lauric Acid Stimulates Ketone Body Production in the KT-5 Astrocyte Cell Line.

    PubMed

    Nonaka, Yudai; Takagi, Tetsuo; Inai, Makoto; Nishimura, Shuhei; Urashima, Shogo; Honda, Kazumitsu; Aoyama, Toshiaki; Terada, Shin

    2016-08-01

    Coconut oil has recently attracted considerable attention as a potential Alzheimer's disease therapy because it contains large amounts of medium-chain fatty acids (MCFAs) and its consumption is thought to stimulate hepatic ketogenesis, supplying an alternative energy source for brains with impaired glucose metabolism. In this study, we first reevaluated the responses of plasma ketone bodies to oral administration of coconut oil to rats. We found that the coconut oil-induced increase in plasma ketone body concentration was negligible and did not significantly differ from that observed after high-oleic sunflower oil administration. In contrast, the administration of coconut oil substantially increased the plasma free fatty acid concentration and lauric acid content, which is the major MCFA in coconut oil. Next, to elucidate whether lauric acid can activate ketogenesis in astrocytes with the capacity to generate ketone bodies from fatty acids, we treated the KT-5 astrocyte cell line with 50 and 100 μM lauric acid for 4 h. The lauric acid treatments increased the total ketone body concentration in the cell culture supernatant to a greater extent than oleic acid, suggesting that lauric acid can directly and potently activate ketogenesis in KT-5 astrocytes. These results suggest that coconut oil intake may improve brain health by directly activating ketogenesis in astrocytes and thereby by providing fuel to neighboring neurons. PMID:27430387

  15. Transcranial magnetic stimulation (TMS) in the treatment of substance addiction

    PubMed Central

    Gorelick, David A.; Zangen, Abraham; George, Mark S.

    2014-01-01

    Transcranial magnetic stimulation (TMS) is a non-invasive method of brain stimulation used to treat a variety of neuropsychiatric disorders, but is still in the early stages of study as addiction treatment. We identified 19 human studies using repetitive TMS (rTMS) to manipulate drug craving or use, which exposed a total of 316 adults to active rTMS. Nine studies involved tobacco, six alcohol, three cocaine, and one methamphetamine. The majority of studies targeted high-frequency (5–20 Hz; expected to stimulate neuronal activity) rTMS pulses to the dorsolateral prefrontal cortex. Only five studies were controlled clinical trials: two of four nicotine trials found decreased cigarette smoking; the cocaine trial found decreased cocaine use. Many aspects of optimal treatment remain unknown, including rTMS parameters, duration of treatment, relationship to cue-induced craving, and concomitant treatment. The mechanisms of rTMS potential therapeutic action in treating addictions are poorly understood, but may involve increased dopamine and glutamate function in corticomesolimbic brain circuits and modulation of neural activity in brain circuits that mediate cognitive processes relevant to addiction, such as response inhibition, selective attention, and reactivity to drug-associated cues. rTMS treatment of addiction must be considered experimental at this time, but appears to have a promising future. PMID:25069523

  16. Transcranial Magnetic Stimulation and Deep Brain Stimulation in the treatment of alcohol dependence

    PubMed Central

    Alba-Ferrara, L.; Fernandez, F.; Salas, R.; de Erausquin, G. A.

    2013-01-01

    Alcohol dependence is a major social, economic, and public health problem. Alcoholism can lead to damage of the gastrointestinal, nervous, cardiovascular, and respiratory systems and it can be lethal, costing hundreds of billions to the health care system. Despite the existence of cognitive-behavioral therapy, psychosocial interventions, and spiritually integrated treatment to treat it, alcohol dependence has a high relapse rate and poor prognosis, albeit with high interindividual variability. In this review, we discuss the use of two neuromodulation techniques, namely repetitive transcranial magnetic stimulation (rTMS) and deep brain stimulation (DBS), and their advantages and disadvantages compared to first-line pharmacological treatment for alcohol dependence. We also discuss rTMS and DBS targets for alcohol dependence treatment, considering experimental animal and human evidence, with careful consideration of methodological issues preventing the identification of feasible targets for neuromodulation treatments, as well as inter-individual variability factors influencing alcoholism prognosis. Lastly, we anticipate future research aiming to tailor the treatment to each individual patient by combining neurofunctional, neuroanatomical and neurodisruptive techniques optimizing the outcome. PMID:25598743

  17. Transcranial magnetic stimulation for the treatment of major depression

    PubMed Central

    Janicak, Philip G; Dokucu, Mehmet E

    2015-01-01

    Major depression is often difficult to diagnose accurately. Even when the diagnosis is properly made, standard treatment approaches (eg, psychotherapy, medications, or their combination) are often inadequate to control acute symptoms or maintain initial benefit. Additional obstacles involve safety and tolerability problems, which frequently preclude an adequate course of treatment. This leaves an important gap in our ability to properly manage major depression in a substantial proportion of patients, leaving them vulnerable to ensuing complications (eg, employment-related disability, increased risk of suicide, comorbid medical disorders, and substance abuse). Thus, there is a need for more effective and better tolerated approaches. Transcranial magnetic stimulation is a neuromodulation technique increasingly used to partly fill this therapeutic void. In the context of treating depression, we critically review the development of transcranial magnetic stimulation, focusing on the results of controlled and pragmatic trials for depression, which consider its efficacy, safety, and tolerability. PMID:26170668

  18. Stimulants

    MedlinePlus

    Stimulants are drugs that increase your heart rate, breathing rate, and brain function. Some stimulants affect only a specific organ, such as the heart, lungs, brain, or nervous system. Epinephrine is a stimulant. It ...

  19. Chemical Stimulation Treatment of the Rossi 21-19 Well Beowawe Geothermal Field

    SciTech Connect

    1984-01-01

    The tests reported were part of the DOE Geothermal Reservoir Well Stimulation Program. This was an attempt to ameliorate near-wellbore restricted permeability in a well at a field where other wells flowed at high rates. The two stage treatment first injected HCl followed by a large volume of HCl-HF acid solution. This was a relatively inexpensive treatment, with costs shown. Injectivity tests showed a 2.2 fold increase in injectivity attributable to the second treatment, but mechanical complications with the well precluded an adequate production test. Flow of the fluid out into the formation was measured by Sandia using surface electrical potential. LANL detected microseismic events during the stimulation, which might be especially significant.

  20. Chlorogenic Acids Biosynthesis in Centella asiatica Cells Is not Stimulated by Salicylic Acid Manipulation.

    PubMed

    Ncube, E N; Steenkamp, P A; Madala, N E; Dubery, I A

    2016-07-01

    Exogenous application of synthetic and natural elicitors of plant defence has been shown to result in mass production of secondary metabolites with nutraceuticals properties in cultured cells. In particular, salicylic acid (SA) treatment has been reported to induce the production of phenylpropanoids, including cinnamic acid derivatives bound to quinic acid (chlorogenic acids). Centella asiatica is an important medicinal plant with several therapeutic properties owing to its wide spectrum of secondary metabolites. We investigated the effect of SA on C. asiatica cells by monitoring perturbation of chlorogenic acids in particular. Different concentrations of SA were used to treat C. asiatica cells, and extracts from both treated and untreated cells were analysed using an optimised UHPLC-QTOF-MS/MS method. Semi-targeted multivariate data analyses with the aid of principal component analysis (PCA) and orthogonal projection to latent structures-discriminant analysis (OPLS-DA) revealed a concentration-dependent metabolic response. Surprisingly, a range of chlorogenic acid derivatives were found to be downregulated as a consequence of SA treatment. Moreover, irbic acid (3,5-O-dicaffeoyl-4-O-malonilquinic acid) was found to be a dominant CGA in C. asiatica cells, although the SA treatment also had a negative effect on its concentration. Overall SA treatment was found to be an ineffective elicitor of CGA production in cultured C. asiatica cells.

  1. Effects of stimulation treatments on coalbeds and surrounding strata. Evidence from underground observations

    SciTech Connect

    Diamond, W.P.; Oyler, D.C.

    1987-01-01

    This Bureau of Mines report examines the coal mine roof damage potential of stimulation treatments. Vertical fractures in the coalbed were discernible for most treatments, and horizontal fractures were present for about half of the stimulations. Evidence of stimulation fluid movement could generally be traced beyond the maximum extent of sand-filled fractures when fluorescent paint was added to the treatment fluids.

  2. Optimization of epilepsy treatment with vagus nerve stimulation

    NASA Astrophysics Data System (ADS)

    Uthman, Basim; Bewernitz, Michael; Liu, Chang-Chia; Ghacibeh, Georges

    2007-11-01

    Epilepsy is one of the most common chronic neurological disorders that affects close to 50 million people worldwide. Antiepilepsy drugs (AEDs), the main stay of epilepsy treatment, control seizures in two thirds of patients only. Other therapies include the ketogenic diet, ablative surgery, hormonal treatments and neurostimulation. While other approaches to stimulation of the brain are currently in the experimental phase vagus nerve stimulation (VNS) has been approved by the FDA since July 1997 for the adjunctive treatment of intractable partial onset epilepsy with and without secondary generalization in patients twelve years of age or older. The safety and efficacy of VNS have been proven and duplicated in two subsequent double-blinded controlled studies after two pilot studies demonstrated the feasibility of VNS in man. Long term observational studies confirmed the safety of VNS and that its effectiveness is sustained over time. While AEDs influence seizure thresholds via blockade or modulation of ionic channels, inhibit excitatory neurotransmitters or enhance inhibitory neurotransmitters the exact mechanism of action of VNS is not known. Neuroimaging studies revealed that VNS increases blood flow in certain regions of the brain such as the thalamus. Chemical lesions in the rat brains showed that norepinephrine is an important link in the anticonvulsant effect of VNS. Analysis of cerebrospinal fluid obtained from patients before and after treatment with VNS showed modest decreases in excitatory neurotransmitters. Although Hammond et al. reported no effect of VNS on scalp EEG by visual analysis and Salinsky et al. found no effect of VNS on scalp EEG by spectral analysis, Kuba et al. suggested that VNS reduces interictal epileptiform activity. Further, nonlinear dynamical analysis of the electroencephalogram in the rat and man have reportedly shown predictable changes (decrease in the short term Lyapunov exponent STLmax and T-index) more than an hour prior to the

  3. Rab GTPase mediated procollagen trafficking in ascorbic acid stimulated osteoblasts.

    PubMed

    Nabavi, Noushin; Pustylnik, Sofia; Harrison, Rene E

    2012-01-01

    Despite advances in investigating functional aspects of osteoblast (OB) differentiation, especially studies on how bone proteins are deposited and mineralized, there has been little research on the intracellular trafficking of bone proteins during OB differentiation. Collagen synthesis and secretion is the major function of OBs and is markedly up-regulated upon ascorbic acid (AA) stimulation, significantly more so than in fibroblast cells. Understanding the mechanism by which collagen is mobilized in specialized OB cells is important for both basic cell biology and diseases involving defects in bone protein secretion and deposition. Protein trafficking along the exocytic and endocytic pathways is aided by many molecules, with Rab GTPases being master regulators of vesicle targeting. In this study, we used microarray analysis to identify the Rab GTPases that are up-regulated during a 5-day AA differentiation of OBs, namely Rab1, Rab3d, and Rab27b. Further, we investigated the role of identified Rabs in regulating the trafficking of collagen from the site of synthesis in the ER to the Golgi and ultimately to the plasma membrane utilizing Rab dominant negative (DN) expression. We also observed that experimental halting of biosynthetic trafficking by these mutant Rabs initiated proteasome-mediated degradation of procollagen and ceased global protein translation. Acute expression of Rab1 and Rab3d DN constructs partially alleviated this negative feedback mechanism and resulted in impaired ER to Golgi trafficking of procollagen. Similar expression of Rab27b DN constructs resulted in dispersed collagen vesicles which may represent failed secretory vesicles sequestered in the cytosol. A significant and strong reduction in extracellular collagen levels was also observed implicating the functional importance of Rab1, Rab3d and Rab27b in these major collagen-producing cells.

  4. Treatment for Stimulant Use Disorders. Treatment Improvement Protocol (TIP) Series 33.

    ERIC Educational Resources Information Center

    Substance Abuse and Mental Health Services Administration (DHHS/PHS), Rockville, MD. Center for Substance Abuse Treatment.

    This TIP on the best practice guidelines for treatment of substance abuse provides basic knowledge for practitioners, educators, and paraprofessionals about the nature and treatment of stimulant use disorders. More specifically, it reviews what is currently known about treating the medical, psychiatric, and substance abuse/dependence problems…

  5. Electrical self-stimulation in the central amygdaloid nucleus after ibotenic acid lesion of the lateral hypothalamus.

    PubMed

    Touzani, K; Velley, L

    1998-02-01

    This experiment was carried out in order to investigate the involvement of lateral hypothalamus (LH) in electrical self-stimulation of the central amygdaloid nucleus (CeA). Adult male Sprague-Dawley rats were bilaterally implanted with a guide cannula situated above each LH and with two electrodes in the CeA. Self-stimulation was subsequently obtained separately from both right and left electrodes. The LH was then lesioned unilaterally by ibotenic acid (IBO) injection. Eight days later, the effect of this unilateral lesion on self-stimulation of the ipsilateral and contralateral CeA was tested. Then the neurons of the remaining non-lesioned LH side were lesioned with IBO and self-stimulation was tested 15 days after the second lesion. Both unilateral as well as bilateral lesions of LH produced a significant decrease in CeA self-stimulation rates but had no significant effect on the reward effectiveness. The unilateral lesions did not produce any modification of the rate-intensity function in the contralateral CeA. This lesion-induced depression in performance was reversed by treatment with phenobarbital. These results provide clear evidence that the rewarding effects of CeA electrical stimulation do not result from the activation of the LH outputs and that the apparent decrease in CeA self-stimulation may result from the LH lesion-induced increase in the frequency of epileptiform manifestations that occur following amygdaloid stimulation.

  6. Treatment of Bile Acid Amidation Defects with Glycocholic Acid

    PubMed Central

    Heubi, James E.; Setchell, Kenneth D.R.; Jha, Pinky; Buckley, Donna; Zhang, Wujuan; Rosenthal, Philip; Potter, Carol; Horslen, Simon; Suskind, David

    2014-01-01

    Bile acid amidation defects were predicted to present with fat/fat soluble vitamin malabsorption with minimal cholestasis. We identified and treated 5 patients (1 male/4 females) from 4 families with defective bile acid amidation due to a genetically confirmed deficiency in bile acid CoA:amino acid N-acyl transferase (BAAT) with the conjugated bile acid, glycocholic acid (GCA). Fast atom bombardment-mass spectrometry analysis of urine and bile at baseline revealed predominantly unconjugated cholic acid and absence of the usual glycine and taurine conjugated primary bile acids. Treatment with 15 mg/kg GCA resulted in total duodenal bile acid concentrations of 23.3 ± 19.1 mmol/L (mean ± SD) and 63.5 ± 4.0% of the bile acids were secreted in bile in the conjugated form of which GCA represented 59.6 ± 9.3% of the total biliary bile acids. Unconjugated cholic acid continued to be present in high concentrations in bile because of partial intestinal deconjugation of orally administered GCA. Serum total bile acid concentrations did not significantly differ between pretreatment and post-treatment samples and serum contained predominantly unconjugated cholic acid. These findings confirmed efficient intestinal absorption, hepatic extraction and biliary secretion of the administered GCA. Oral tolerance tests for vitamin D2 (1000 IU vitamin D2/kg) and tocopherol (100 IU/kg tocopherol acetate) demonstrated improvement in fat-soluble vitamin absorption after GCA treatment. Growth improved in 3/3 growth-delayed prepubertal patients. Conclusions: Oral glycocholic acid therapy is safe and effective in improving growth and fat-soluble vitamin absorption in children and adolescents with inborn errors of bile acid metabolism due to amidation defects. PMID:25163551

  7. Thrombin stimulates albumin transcytosis in lung microvascular endothelial cells via activation of acid sphingomyelinase.

    PubMed

    Kuebler, Wolfgang M; Wittenberg, Claudia; Lee, Warren L; Reppien, Eike; Goldenberg, Neil M; Lindner, Karsten; Gao, Yizhuo; Winoto-Morbach, Supandi; Drab, Marek; Mühlfeld, Christian; Dombrowsky, Heike; Ochs, Matthias; Schütze, Stefan; Uhlig, Stefan

    2016-04-15

    Transcellular albumin transport occurs via caveolae that are abundant in lung microvascular endothelial cells. Stimulation of albumin transcytosis by proinflammatory mediators may contribute to alveolar protein leak in lung injury, yet the regulation of albumin transport and its underlying molecular mechanisms are so far incompletely understood. Here we tested the hypothesis that thrombin may stimulate transcellular albumin transport across lung microvascular endothelial cells in an acid-sphingomyelinase dependent manner. Thrombin increased the transport of fluorescently labeled albumin across confluent human lung microvascular endothelial cell (HMVEC-L) monolayers to an extent that markedly exceeds the rate of passive diffusion. Thrombin activated acid sphingomyelinase (ASM) and increased ceramide production in HMVEC-L, but not in bovine pulmonary artery cells, which showed little albumin transport in response to thrombin. Thrombin increased total caveolin-1 (cav-1) content in both whole cell lysates and lipid rafts from HMVEC-L, and this effect was blocked by inhibition of ASM or de novo protein biosynthesis. Thrombin-induced uptake of albumin into lung microvascular endothelial cells was confirmed in isolated-perfused lungs by real-time fluorescence imaging and electron microscopy of gold-labeled albumin. Inhibition of ASM attenuated thrombin-induced albumin transport both in confluent HMVEC-L and in intact lungs, whereas HMVEC-L treatment with exogenous ASM increased albumin transport and enriched lipid rafts in cav-1. Our findings indicate that thrombin stimulates transcellular albumin transport in an acid sphingomyelinase-dependent manner by inducing de novo synthesis of cav-1 and its recruitment to membrane lipid rafts. PMID:26851257

  8. Sphenopalatine ganglion stimulation for the treatment of cluster headache

    PubMed Central

    Puche, Miguel; Garcia, Ana; Gascón, Francisco

    2014-01-01

    Cluster headache is a severe, debilitating disorder with pain that ranks among the most severe known to humans. Patients with cluster headaches have few therapeutic options and further, 10–20% develop drug-resistant attacks. The often brief duration of cluster attacks makes abortive therapy a challenge, and preventive medications are almost always provided to patients, but the side effects of these preventive medications can be significant. The sphenopalatine ganglion (SPG) is believed to play a role in headache pain and cranial autonomic symptoms associated with cluster headache, which is a result of activation of the trigeminal-autonomic reflex. For over 100 years, the SPG has been a clinical target to treat primary headache disorders using pharmacologic and nonpharmacologic methods. Radiofrequency lesioning and nerve-resection therapies, while initially beneficial, are irreversible procedures, and the use of neurostimulation provides one method of interfacing with the neural pathways without causing permanent damage to neural tissue. SPG neurostimulation is both reversible and adjustable, and has recently been tested in both proof-of-concept work and in a randomized, sham-controlled trial for the treatment of cluster headache. A randomized, sham-controlled study of 32 patients was performed to evaluate further the use of SPG stimulation for the acute treatment of chronic cluster headache. Of the 32 patients, 28 completed the randomized experimental period. Overall, 68% of patients experienced an acute response, a frequency response, or both. In this study the majority of adverse events were related to the implantation procedure, which typically resolved or remained mild in nature at 3 months following the implant procedure. This and other studies highlight the promise of using SPG stimulation to treat the pain-associated cluster headache. SPG stimulation could be a safe and effective option for chronic cluster headache. PMID:24790646

  9. Deep brain stimulation in the treatment of depression.

    PubMed

    Delaloye, Sibylle; Holtzheimer, Paul E

    2014-03-01

    Major depressive disorder is a worldwide disease with debilitating effects on a patient's life. Common treatments include pharmacotherapy, psychotherapy, and electroconvulsive therapy. Many patients do not respond to these treatments; this has led to the investigation of alternative therapeutic modalities. Deep brain stimulation (DBS) is one of these modalities. It was first used with success for treating movement disorders and has since been extended to the treatment of psychiatric disorders. Although DBS is still an emerging treatment, promising efficacy and safety have been demonstrated in preliminary trials in patients with treatment-resistant depression (TRD). Further, neuroimaging has played a pivotal role in identifying some DBS targets and remains an important tool for evaluating the mechanism of action of this novel intervention. Preclinical animal studies have broadened knowledge about the possible mechanisms of action of DBS for TRD, Given that DBS involves neurosurgery in patients with severe psychiatric impairment, ethical questions concerning capacity to consent arise; these issues must continue to be carefully considered.

  10. Arachidonic acid stimulates /sup 45/calcium efflux and HPL release in isolated trophoblast cells

    SciTech Connect

    Zeitler, P.; Murphy, E.; Handwerger, S.

    1986-01-13

    Previous investigations from this laboratory have indicated that arachidonic acid stimulates a rapid, dose-dependent and reversible increase in hPL release which is not dependent on cyclooxygenase or lipoxygenase metabolism. To investigate further the mechanism by which arachidonic acid stimulates the release of hPL, the effect of arachidonic acid on the release of /sup 45/Ca from perifused cells prelabelled with /sup 45/Ca was examined in an enriched cell culture population of term human syncytiotrophoblast. Arachidonic acid (10-100 ..mu..M) stimulated a dose-dependent, rapid, and reversible increase in the release of both /sup 45/Ca and hPL from the perifused placental cells. On the other hand, palmitic acid had little effect on either hPL release or /sup 45/Ca release even at concentrations as high as 100 ..mu..M. Ionophore A23187 (1-10..mu..M) also stimulated a dose-dependent and reversible increase in hPL release. Since arachidonic acid increases the mobilization of cellular calcium, as reflected by the increased /sup 45/calcium efflux, and since an increase in the intracellular calcium concentration appears to stimulate an increase in hPL release, these results suggest that the stimulation of hPL release by arachidonic acid may be due, at least in part, to the effects of the fatty acid on cellular calcium mobilization. 26 references, 5 figures.

  11. Stimulation of indoleacetic acid production in a Rhizobium isolate of Vigna mungo by root nodule phenolic acids.

    PubMed

    Mandal, Santi M; Mandal, Santi; Mandal, Mahitosh; Das, Amit K; Das, Amit; Pati, Bikas R; Pati, Bikas; Ghosh, Ananta K; Ghosh, Ananta

    2009-04-01

    The influence of endogenous root nodules phenolic acids on indoleacetic acid (IAA) production by its symbiont (Rhizobium) was examined. The root nodules contain higher amount of IAA and phenolic acids than non-nodulated roots. Presence of IAA metabolizing enzymes, IAA oxidase, peroxidase, and polyphenol oxidase indicate the metabolism of IAA in the nodules and roots. Three most abundant endogenous root nodule phenolic acids (protocatechuic acid, 4-hydroxybenzaldehyde and p-coumaric acid) have been identified and their effects on IAA production by the symbiont have been studied in L-tryptophan supplemented yeast extract basal medium. Protocatechuic acid (1.5 microg ml(-1)) showed maximum stimulation (2.15-fold over control) of IAA production in rhizobial culture. These results indicate that the phenolic acids present in the nodule might serve as a stimulator for IAA production by the symbiont (Rhizobium).

  12. Rationale for Using Exercise in the Treatment of Stimulant Use Disorders

    PubMed Central

    Greer, Tracy L.; Ring, Kolette M.; Warden, Diane; Grannemann, Bruce D.; Church, Timothy S.; Somoza, Eugene; Blair, Steven N.; Szapocznik, Jose; Stoutenberg, Mark; Rethorst, Chad; Walker, Robrina; Morris, David W.; Kosinski, Andrzej S.; Kyle, Tiffany; Marcus, Bess; Crowell, Becca; Oden, Neal; Nunes, Edward; Trivedi, Madhukar H.

    2013-01-01

    Novel approaches to the treatment of stimulant abuse and dependence are needed. Clinical data examining the use of exercise as a treatment for the abuse of nicotine, alcohol, and other substances suggest that exercise may be a beneficial treatment for stimulant abuse. In addition, exercise has been associated with improvements in many other health-related areas that may be adversely affected by stimulant use or its treatment, such as sleep disturbance, cognitive function, mood, weight, quality of life, and anhedonia. Neurobiological evidence provides plausible mechanisms by which exercise could positively affect treatment outcomes in stimulant abuse. The National Institute on Drug Abuse (NIDA) Clinical Trials Network (CTN) CTN-0037 Stimulant Reduction Intervention using Dosed Exercise (STRIDE) study is a multisite randomized clinical trial that compares exercise to health education as potential treatments for stimulant abuse or dependence. If effective, exercise may provide an additional approach to the treatment of stimulant use disorders. PMID:25364477

  13. Is deep brain stimulation a treatment option for anorexia nervosa?

    PubMed Central

    2013-01-01

    Anorexia nervosa (AN) is a severe psychiatric disorder with high rates of morbidity, comorbidity and mortality, which in a subset of patients (21%) takes on a chronic course. Since an evidence based treatment for AN is scarce, it is crucial to investigate new treatment options, preferably focused on influencing the underlying neurobiological mechanisms of AN. The objective of the present paper was to review the evidence for possible neurobiological correlates of AN, and to hypothesize about potential targets for Deep brain stimulation (DBS) as a treatment for chronic, therapy-refractory AN. One avenue for exploring new treatment options based on the neurobiological correlates of AN, is the search for symptomatologic and neurobiologic parallels between AN and other compulsivity- or reward-related disorders. As in other compulsive disorders, the fronto-striatal circuitry, in particular the insula, the ventral striatum (VS) and the prefrontal, orbitofrontal, temporal, parietal and anterior cingulate cortices, are likely to be implicated in the neuropathogenesis of AN. In this paper we will review the few available cases in which DBS has been performed in patients with AN (either as primary diagnosis or as comorbid condition). Given the overlap in symptomatology and neurocircuitry between reward-related disorders such as obsessive compulsive disorder (OCD) and AN, and the established efficacy of accumbal DBS in OCD, we hypothesize that DBS of the nucleus accumbens (NAc) and other areas associated with reward, e.g. the anterior cingulated cortex (ACC), might be an effective treatment for patients with chronic, treatment refractory AN, providing not only weight restoration, but also significant and sustained improvement in AN core symptoms and associated comorbidities and complications. Possible targets for DBS in AN are the ACC, the ventral anterior limb of the capsula interna (vALIC) and the VS. We suggest conducting larger efficacy studies that also explore the

  14. Deep brain stimulation in the treatment of obesity.

    PubMed

    Halpern, Casey H; Wolf, John A; Bale, Tracy L; Stunkard, Albert J; Danish, Shabbar F; Grossman, Murray; Jaggi, Jurg L; Grady, M Sean; Baltuch, Gordon H

    2008-10-01

    Obesity is a growing global health problem frequently intractable to current treatment options. Recent evidence suggests that deep brain stimulation (DBS) may be effective and safe in the management of various, refractory neuropsychiatric disorders, including obesity. The authors review the literature implicating various neural regions in the pathophysiology of obesity, as well as the evidence supporting these regions as targets for DBS, in order to explore the therapeutic promise of DBS in obesity. The lateral hypothalamus and ventromedial hypothalamus are the appetite and satiety centers in the brain, respectively. Substantial data support targeting these regions with DBS for the purpose of appetite suppression and weight loss. However, reward sensation associated with highly caloric food has been implicated in overconsumption as well as obesity, and may in part explain the failure rates of conservative management and bariatric surgery. Thus, regions of the brain's reward circuitry, such as the nucleus accumbens, are promising alternatives for DBS in obesity control. The authors conclude that deep brain stimulation should be strongly considered as a promising therapeutic option for patients suffering from refractory obesity. PMID:18826348

  15. High-Voltage Pulsed Current Electrical Stimulation in Wound Treatment

    PubMed Central

    Polak, Anna; Franek, Andrzej; Taradaj, Jakub

    2014-01-01

    Significance: A range of studies point to the efficacy of electrical stimulation (ES) in wound treatment, but the methodology of its application has not been determined to date. This article provides a critical review of the results of clinical trials published by researchers using high-voltage pulsed current (HVPC) to treat chronic wounds. In describing the methodology of the trials, the article gives special attention to electric stimulus parameters, the frequency of procedures and total treatment duration. Recent Advances: HVPC is a monophasic pulsed electric current that consists of double-peaked impulses (5–200 μs), at very high peak-current amplitude (2–2.5 A), and high voltage (up to 500 V), at a frequency of 1–125 pulses per second. HVPC can activate “skin battery” and cellular galvanotaxis, and improves blood flow and capillary density. Critical Issues: HVPC efficacy was evaluated in conservatively treated patients with diabetic foot, venous leg and pressure ulcers (PUs), and in some patients with surgically treated venous insufficiency. Future Directions: The efficacy of HVPC as one of several biophysical energies promoting venous leg ulcer (VLU) and PU healing has been confirmed. Additional studies are needed to investigate its effect on the healing of other types of soft tissue defects. Other areas that require more research include the identification of the therapeutic effect of HVPC on infected wounds, the determination of the efficacy of cathodal versus anodal stimulation, and the minimal daily/weekly duration of HVPC required to ensure optimal promotion of wound healing. PMID:24761351

  16. Acid peptic diseases: pharmacological approach to treatment

    PubMed Central

    Mejia, Alex; Kraft, Walter K

    2011-01-01

    Acid peptic disorders are the result of distinctive, but overlapping pathogenic mechanisms leading to either excessive acid secretion or diminished mucosal defense. They are common entities present in daily clinical practice that, owing to their chronicity, represent a significant cost to healthcare. Key elements in the success of controlling these entities have been the development of potent and safe drugs based on physiological targets. The histamine-2 receptor antagonists revolutionized the treatment of acid peptic disorders owing to their safety and efficacy profile. The proton-pump inhibitors (PPIs) represent a further therapeutic advance due to more potent inhibition of acid secretion. Ample data from clinical trials and observational experience have confirmed the utility of these agents in the treatment of acid peptic diseases, with differential efficacy and safety characteristics between and within drug classes. Paradigms in their speed and duration of action have underscored the need for new chemical entities that, from a single dose, would provide reliable duration of acid control, particularly at night. Moreover, PPIs reduce, but do not eliminate, the risk of ulcers in patients taking NSAIDs, reflecting untargeted physiopathologic pathways and a breach in the ability to sustain an intragastric pH of more than 4. This review provides an assessment of the current understanding of the physiology of acid production, a discussion of medications targeting gastric acid production and a review of efficacy in specific acid peptic diseases, as well as current challenges and future directions in the treatment of acid-mediated diseases. PMID:21822447

  17. In Vitro Influence of Mycophenolic Acid on Selected Parameters of Stimulated Peripheral Canine Lymphocytes

    PubMed Central

    Guzera, Maciej; Szulc-Dąbrowska, Lidia; Cywińska, Anna; Archer, Joy; Winnicka, Anna

    2016-01-01

    Mycophenolic acid (MPA) is an active metabolite of mycophenolate mofetil, a new immunosuppressive drug effective in the treatment of canine autoimmune diseases. The impact of MPA on immunity is ambiguous and its influence on the canine immune system is unknown. The aim of the study was to determine markers of changes in stimulated peripheral canine lymphocytes after treatment with MPA in vitro. Twenty nine healthy dogs were studied. Phenotypic and functional analysis of lymphocytes was performed on peripheral blood mononuclear cells cultured with mitogens and different MPA concentrations– 1 μM (10−3 mol/m3), 10 μM or 100 μM. Apoptotic cells were detected by Annexin V and 7-aminoactinomycin D (7-AAD). The expression of antigens (CD3, CD4, CD8, CD21, CD25, forkhead box P3 [FoxP3] and proliferating cell nuclear antigen [PCNA]) was assessed with monoclonal antibodies. The proliferation indices were analyzed in carboxyfluorescein diacetate succinimidyl ester (CFSE)-labeled cells. All analyses were performed using flow cytometry. The influence of MPA on apoptosis was dependent on the mechanism of cell activation and MPA concentration. MPA caused a decrease in the expression of lymphocyte surface antigens, CD3, CD8 and CD25. Its impact on the expression of CD4 and CD21 was negligible. Its negative influence on the expression of FoxP3 was dependent on cell stimulation. MPA inhibited lymphocyte proliferation. In conclusion, MPA inhibited the activity of stimulated canine lymphocytes by blocking lymphocyte activation and proliferation. The influence of MPA on the development of immune tolerance–expansion of Treg cells and lymphocyte apoptosis–was ambiguous and was dependent on the mechanism of cellular activation. The concentration that MPA reaches in the blood may lead to inhibition of the functions of the canine immune system. The applied panel of markers can be used for evaluation of the effects of immunosuppressive compounds in the dog. PMID:27138877

  18. Stimulant Treatment of Elementary School Children: Implications for School Counselors.

    ERIC Educational Resources Information Center

    Bramlett, Ronald K.; Nelson, Patricia; Reeves, Betty

    1997-01-01

    Determines the percentage of elementary children in the United States who are currently receiving stimulant medication at school. Forty-six states and 246,707 children were represented in the survey. Approximately 3% of children were receiving stimulant medication at school with Ritalin the stimulant most widely used. Explores assessment issues…

  19. Free amino acids in stimulated and unstimulated whole saliva: advantages or disadvantages.

    PubMed

    Masoudi Rad, H; Rabiei, M; Sobhani, A; Sadegh Khanjani, M; Rahbar Taramsar, M; Kazemnezhad Leili, E

    2014-10-01

    This study determines the mean concentrations of free amino acids in stimulated and unstimulated whole saliva in healthy young adults. Standardised salivary amino acids as a substitute for their counterpart in blood, searched for the source of free amino acids in saliva, the probable correlation between particular amino acids with caries experience. Stimulated and unstimulated whole saliva were collected by the draining method in 31 dental students. Saliva was purified, and amino acids were separated by high-performance liquid chromatography. DMFT scores were recorded, and the relation of amino acids to caries experience was explored by generalised linear model. Almost all amino acids had higher concentration in unstimulated whole saliva than in stimulated saliva. The normal range of amino acids (95% CI) and their natural logarithm were defined. There was a significant relationship between caries experience and threonine (P < 0·008), citrulline (P < 0·023) and ornithine (P < 0·001) as a detrimental factor, whereas serin (P < 0·026), glutamine (P < 0·015) and phenylalanine (P < 0·014) had an inhibiting effect on caries. However, in comparison, salivary flow rate (P < 0·013) was a more preventive factor than amino acids. Amino acids in saliva contribute as a marker, instead of their counterpart in blood. Unstimulated saliva had higher concentration of amino acids. Amino acids have different impact on caries and may be one of underlying risk factors for caries experience.

  20. Activation of AMP-Activated Protein Kinase and Stimulation of Energy Metabolism by Acetic Acid in L6 Myotube Cells.

    PubMed

    Maruta, Hitomi; Yoshimura, Yukihiro; Araki, Aya; Kimoto, Masumi; Takahashi, Yoshitaka; Yamashita, Hiromi

    2016-01-01

    Previously, we found that orally administered acetic acid decreased lipogenesis in the liver and suppressed lipid accumulation in adipose tissue of Otsuka Long-Evans Tokushima Fatty rats, which exhibit hyperglycemic obesity with hyperinsulinemia and insulin resistance. Administered acetic acid led to increased phosphorylation of AMP-activated protein kinase (AMPK) in both liver and skeletal muscle cells, and increased transcripts of myoglobin and glucose transporter 4 (GLUT4) genes in skeletal muscle of the rats. It was suggested that acetic acid improved the lipid metabolism in skeletal muscles. In this study, we examined the activation of AMPK and the stimulation of GLUT4 and myoglobin expression by acetic acid in skeletal muscle cells to clarify the physiological function of acetic acid in skeletal muscle cells. Acetic acid added to culture medium was taken up rapidly by L6 cells, and AMPK was phosphorylated upon treatment with acetic acid. We observed increased gene and protein expression of GLUT4 and myoglobin. Uptake of glucose and fatty acids by L6 cells were increased, while triglyceride accumulation was lower in treated cells compared to untreated cells. Furthermore, treated cells also showed increased gene and protein expression of myocyte enhancer factor 2A (MEF2A), which is a well-known transcription factor involved in the expression of myoglobin and GLUT4 genes. These results indicate that acetic acid enhances glucose uptake and fatty acid metabolism through the activation of AMPK, and increases expression of GLUT4 and myoglobin.

  1. Activation of AMP-Activated Protein Kinase and Stimulation of Energy Metabolism by Acetic Acid in L6 Myotube Cells.

    PubMed

    Maruta, Hitomi; Yoshimura, Yukihiro; Araki, Aya; Kimoto, Masumi; Takahashi, Yoshitaka; Yamashita, Hiromi

    2016-01-01

    Previously, we found that orally administered acetic acid decreased lipogenesis in the liver and suppressed lipid accumulation in adipose tissue of Otsuka Long-Evans Tokushima Fatty rats, which exhibit hyperglycemic obesity with hyperinsulinemia and insulin resistance. Administered acetic acid led to increased phosphorylation of AMP-activated protein kinase (AMPK) in both liver and skeletal muscle cells, and increased transcripts of myoglobin and glucose transporter 4 (GLUT4) genes in skeletal muscle of the rats. It was suggested that acetic acid improved the lipid metabolism in skeletal muscles. In this study, we examined the activation of AMPK and the stimulation of GLUT4 and myoglobin expression by acetic acid in skeletal muscle cells to clarify the physiological function of acetic acid in skeletal muscle cells. Acetic acid added to culture medium was taken up rapidly by L6 cells, and AMPK was phosphorylated upon treatment with acetic acid. We observed increased gene and protein expression of GLUT4 and myoglobin. Uptake of glucose and fatty acids by L6 cells were increased, while triglyceride accumulation was lower in treated cells compared to untreated cells. Furthermore, treated cells also showed increased gene and protein expression of myocyte enhancer factor 2A (MEF2A), which is a well-known transcription factor involved in the expression of myoglobin and GLUT4 genes. These results indicate that acetic acid enhances glucose uptake and fatty acid metabolism through the activation of AMPK, and increases expression of GLUT4 and myoglobin. PMID:27348124

  2. Activation of AMP-Activated Protein Kinase and Stimulation of Energy Metabolism by Acetic Acid in L6 Myotube Cells

    PubMed Central

    Maruta, Hitomi; Yoshimura, Yukihiro; Araki, Aya; Kimoto, Masumi; Takahashi, Yoshitaka; Yamashita, Hiromi

    2016-01-01

    Previously, we found that orally administered acetic acid decreased lipogenesis in the liver and suppressed lipid accumulation in adipose tissue of Otsuka Long-Evans Tokushima Fatty rats, which exhibit hyperglycemic obesity with hyperinsulinemia and insulin resistance. Administered acetic acid led to increased phosphorylation of AMP-activated protein kinase (AMPK) in both liver and skeletal muscle cells, and increased transcripts of myoglobin and glucose transporter 4 (GLUT4) genes in skeletal muscle of the rats. It was suggested that acetic acid improved the lipid metabolism in skeletal muscles. In this study, we examined the activation of AMPK and the stimulation of GLUT4 and myoglobin expression by acetic acid in skeletal muscle cells to clarify the physiological function of acetic acid in skeletal muscle cells. Acetic acid added to culture medium was taken up rapidly by L6 cells, and AMPK was phosphorylated upon treatment with acetic acid. We observed increased gene and protein expression of GLUT4 and myoglobin. Uptake of glucose and fatty acids by L6 cells were increased, while triglyceride accumulation was lower in treated cells compared to untreated cells. Furthermore, treated cells also showed increased gene and protein expression of myocyte enhancer factor 2A (MEF2A), which is a well-known transcription factor involved in the expression of myoglobin and GLUT4 genes. These results indicate that acetic acid enhances glucose uptake and fatty acid metabolism through the activation of AMPK, and increases expression of GLUT4 and myoglobin. PMID:27348124

  3. Low and High Frequency Repetitive Transcranial Magnetic Stimulation for the Treatment of Spasticity

    ERIC Educational Resources Information Center

    Valle, Angela C.; Dionisio, Karen; Pitskel, Naomi Bass; Pascual-Leone, Alvaro; Orsati, Fernanda; Ferreira, Merari J. L.; Boggio, Paulo S.; Lima, Moises C.; Rigonatti, Sergio P.; Fregni, Felipe

    2007-01-01

    The development of non-invasive techniques of cortical stimulation, such as transcranial magnetic stimulation (TMS), has opened new potential avenues for the treatment of neuropsychiatric diseases. We hypothesized that an increase in the activity in the motor cortex by cortical stimulation would increase its inhibitory influence on spinal…

  4. Advanced stimulation technology program helps zero in the optimum frac treatment

    SciTech Connect

    Saunders, B.

    1995-08-01

    The Gas Research Institute (GRI) has initiated the Advanced Stimulation Technology (AST) program to ensure that successful stimulation technologies developed in previous GRI programs are available to the petroleum industry and are used regularly. The AST program focuses on benefits analysis, real-time fracture treatment evaluation, and understanding critical concepts in fracture stimulation.

  5. Treatment of broiler litter with organic acids.

    PubMed

    Ivanov, I E

    2001-04-01

    Experiments for treatment of contaminated broiler litter with citric, tartaric and salicylic acids were performed. At days 2 and 6 after the treatment, pH values (using a pH-meter), the ammonia concentrations (titration with 0.1 N HCl) and the microbial cells counts were determined in both experimental and control specimens of litter. The cost of acidification of litter was also determined. Our studies showed that the treatment of the contaminated litter with 5 per cent citric acid, 4 per cent tartaric acid and 1.5 per cent salicylic acid created an acid medium with pH under 5.0 and thus reduced the microbial counts to 2.2 x 10(3)colony forming units per gram manure litter. The treatment reduced the content of ammonia in the litter and in the air under the hygienic limits, i.e. 25-50 ppm. The cost of acidification of litter with these organic acids amounted to 0.1 $ per bird and 1.5 $ per 15 birds on one square metre in a growth period of 50 days. PMID:11356097

  6. Stimulation of cysteinyl leukotriene production in mast cells by heat shock and acetylsalicylic acid.

    PubMed

    Mortaz, Esmaeil; Redegeld, Frank A; Dunsmore, Kathy; Odoms, Kelli; Wong, Hector R; Nijkamp, Frans P; Engels, Ferdi

    2007-04-30

    Immunoglobulin (Ig) E-dependent activation of mast cells is central to the allergic response. The engagement of IgE-occupied receptors initiates a series of molecular events that causes the release of preformed, and de novo synthesis of, allergic mediators. Cysteinyl leukotrienes are able to contract airway smooth muscle and increase mucus secretion and vascular permeability and recruit eosinophils. Mast cells have also recently been recognized as active participants in innate immune responses. Heat stress can modulate innate immunity by inducing stress proteins such as heat-shock proteins (HSPs). We previously demonstrated that treatment of mast cells with heat shock or acetylsalicylic acid results in an increase of TNF-alpha and IL-6 release. This effect was paralleled by expression of HSP70. In the current study, we further investigated the effects of heat shock and acetylsalicylic acid on the activation of mast cells and the release of cysteinyl leukotrienes. In mouse mast cells, derived from a culture of bone marrow cells, responsiveness to heat shock, acetylsalicylic acid and exogenous or endogenous HSP70 was monitored by measuring leukotriene C4 release. We show that after heat shock treatment and exposure to acetylsalicylic acid leukotriene production was increased. Moreover, exogenous rHSP70 also induced leukotriene production. Because it has been reported that leukotriene production in mast cells may be mediated by Toll like receptor (TLR) activation, and HSP70 also activates TLRs signaling, we further explored these issues by using mast cells that are not able to produce HSP70, i.e. heat shock factor-1 (HSF-1) knockout cells. We found that in HSF-1 knockout bone marrow derived mast cells, heat shock and acetylsalicylic acid failed to induce release of leukotrienes. Moreover, in wild type cells the surface expression of TLR4 was attenuated, whereas the intracellular expression was up-regulated. We conclude that heat shock and acetylsalicylic acid induce

  7. RAS is required for epidermal growth factor-stimulated arachidonic acid release in rat-1 fibroblasts.

    PubMed

    Warner, L C; Hack, N; Egan, S E; Goldberg, H J; Weinberg, R A; Skorecki, K L

    1993-12-01

    Previous studies have provided suggestive evidence for an interaction between ras activation and signalling pathways involved in agonist-stimulated arachidonic acid release in a variety of cell systems. In order to clarify this interaction, we have measured epidermal growth factor (EGF)-stimulated arachidonic acid release in rat-1 fibroblasts transfected with the N-17 dominant negative mutation of ras. Cells transfected with the N-17 ras mutant, display a markedly attenuated arachidonic acid-release response to EGF, compared to sham-transfected and non-transfected cells. In contrast, the response to phorbol myristate acetate (PMA) was not attenuated in the N-17-mutant expressing cells. No differences were detected between sham-transfected and N-17 mutant expressing cells in levels of immunodetectable EGF receptor, cytosolic phospholipase A2 or mitogen-activated protein (MAP) kinase. Attenuation of EGF-stimulated arachidonic acid release in the N-17 mutant expressing cells, was accompanied by a marked diminution in EGF-stimulated tyrosine phosphorylation of MAP kinase. We conclude that the signalling pathway involved in epidermal growth factor-stimulated arachidonic acid release is similar to the signalling pathway for mitogenic responses to epidermal growth factor and requires ras activation, likely followed by a downstream cascade of kinases eventuating in MAP kinase activation.

  8. Potassium channel KCNJ15 is required for histamine-stimulated gastric acid secretion.

    PubMed

    Yuan, Jianye; Liu, Wensheng; Karvar, Serhan; Baker, Susan S; He, Wenjun; Baker, Robert D; Ji, Guang; Xie, Jianqun; Zhu, Lixin

    2015-08-15

    Gastric acid secretion is mediated by the K(+)-dependent proton pump (H(+),K(+)-ATPase), which requires a continuous supply of K(+) at the luminal side of the apical membrane. Several K(+) channels are implicated in gastric acid secretion. However, the identity of the K(+) channel(s) responsible for apical K(+) supply is still elusive. Our previous studies have shown the translocation of KCNJ15 from cytoplasmic vesicles to the apical membrane on stimulation, indicating its involvement in gastric acid secretion. In this study, the stimulation associated trafficking of KCNJ15 was observed in a more native context with a live cell imaging system. KCNJ15 molecules in resting live cells were scattered in cytoplasm but exhibited apical localization after stimulation. Furthermore, knocking down KCNJ15 expression with a short hairpin RNA adenoviral construct abolished histamine-stimulated acid secretion in rabbit primary parietal cells. Moreover, KCNJ15, like H(+),K(+)-ATPase, was detected in all of the parietal cells by immunofluorescence staining, whereas only about half of the parietal cells were positive for KCNQ1 under the same condition. Consistently, the endogenous protein levels of KCNJ15, analyzed by Western blotting, were higher than those of KCNQ1 in the gastric mucosa of human, mouse, and rabbit. These results provide evidence for a major role of KCNJ15 in apical K(+) supply during stimulated acid secretion. PMID:26108660

  9. Lovastatin increases arachidonic acid levels and stimulates thromboxane synthesis in human liver and monocytic cell lines.

    PubMed Central

    Hrboticky, N; Tang, L; Zimmer, B; Lux, I; Weber, P C

    1994-01-01

    The effect of lovastatin (LOV), the inhibitor of 3-hydroxy-3-methyl-glutaryl coenzyme A reductase, on linoleic acid (LA, 18:2n-6) metabolism was examined in human monocytic Mono Mac 6 (MM6) and hepatoma Hep G2 cells. The desaturation of LA was examined after LOV (72 h, 10 microM) or dimethylsulfoxide (LOV carrier, < 0.1%) and [14C]LA (last 18 h, 0.3 microCi, 5 microM). In both cell lines, LOV reduced the percentage of 14C label associated with LA and increased the percentage of label in the 20:4n-6 and the 22:5n-6 fractions. In Hep G2 but not MM6 cells, this effect was fully reversible by means of coincubation with mevalonic acid (500 microM), but not with cholesterol or lipoproteins. In both cell lines, the LOV-mediated increase in LA desaturation resulted in dose-dependent reductions of LA and elevations of AA in cellular phospholipids. The lipids secreted by LOV-treated Hep G2 cells were also enriched in arachidonic acid (AA). In the MM6 cells, LOV increased release of thromboxane upon stimulation with the calcium ionophore A23187. In summary, our findings of higher LA desaturation and AA enrichment of lipids secreted by the Hep G2 cells suggest that LOV treatment may increase the delivery of AA from the liver to extrahepatic tissues. The changes in membrane fatty acid composition can influence a variety of cellular functions, such as eicosanoid synthesis in monocytic cells. The mechanism appears to be related to the reduced availability of intermediates of cholesterogenesis. PMID:8282787

  10. Identification of Catechin, Syringic Acid, and Procyanidin B2 in Wine as Stimulants of Gastric Acid Secretion.

    PubMed

    Liszt, Kathrin Ingrid; Eder, Reinhard; Wendelin, Sylvia; Somoza, Veronika

    2015-09-01

    Organic acids of wine, in addition to ethanol, have been identified as stimulants of gastric acid secretion. This study characterized the influence of other wine compounds, particularly phenolic compounds, on proton secretion. Forty wine parameters were determined in four red wines and six white wines, including the contents of organic acids and phenolic compounds. The secretory activity of the wines was determined in a gastric cell culture model (HGT-1 cells) by means of a pH-sensitive fluorescent dye. Red wines stimulated proton secretion more than white wines. Lactic acid and the phenolic compounds syringic acid, catechin, and procyanidin B2 stimulated proton secretion and correlated with the pro-secretory effect of the wines. Addition of the phenolic compounds to the least active white wine sample enhanced its proton secretory effect by 65 ± 21% (p < 0.05). These results indicate that not only malic and lactic acid but also bitter and astringent tasting phenolic compounds in wine contribute to its stimulatory effect on gastric acid secretion.

  11. A role for guanylate cyclase C in acid-stimulated duodenal mucosal bicarbonate secretion.

    PubMed

    Rao, S P; Sellers, Z; Crombie, D L; Hogan, D L; Mann, E A; Childs, D; Keely, S; Sheil-Puopolo, M; Giannella, R A; Barrett, K E; Isenberg, J I; Pratha, V S

    2004-01-01

    Luminal acidification provides the strongest physiological stimulus for duodenal HCO3- secretion. Various neurohumoral mechanisms are believed to play a role in acid-stimulated HCO3- secretion. Previous studies in the rat and human duodenum have shown that guanylin and Escherichia coli heat-stable toxin, both ligands of the transmembrane guanylyl cyclase receptor [guanylate cyclase C (GC-C)], are potent stimulators for duodenal HCO3- secretion. We postulated that the GC-C receptor plays an important role in acid-stimulated HCO3- secretion. In vivo perfusion studies performed in wild-type (WT) and GC-C knockout (KO) mice indicated that acid-stimulated duodenal HCO3- secretion was significantly decreased in the GC-C KO animals compared with the WT counterparts. Pretreatment with PD-98059, an MEK inhibitor, resulted in attenuation of duodenal HCO3- secretion in response to acid stimulation in the WT mice with no further effect in the KO mice. In vitro cGMP generation studies demonstrated a significant and comparable increase in cGMP levels on acid exposure in the duodenum of both WT and KO mice. In addition, a rapid, time-dependent phosphorylation of ERK was observed with acid exposure in the duodenum of WT mice, whereas a marked attenuation in ERK phosphorylation was observed in the KO animals despite equivalent levels of ERK in both groups of animals. On the basis of these studies, we conclude that transmembrane GC-C is a key mediator of acid-stimulated duodenal HCO3- secretion. Furthermore, ERK phosphorylation may be an important intracellular mediator of duodenal HCO3- secretion. PMID:12881226

  12. Investigation of mechanism of fade of gastrin-stimulated gastric acid secretion in the cat.

    PubMed

    Hirst, B H

    1988-01-01

    1. In conscious cats prepared with gastric fistulae gastric acid secretion in response to pentagastrin was found to reach a maximum after 45 min of stimulation, and to fade thereafter. Over the period 45-150 min of stimulation the fade was 5.4-7.8% of the maximum response per 15 min. 2. Once the response to pentagastrin had declined, acid secretion could not be restored by doubling the dose of pentagastrin, although an equisecretory dose of histamine could restore it. 3. Low doses of histamine were additive to the pentagastrin acid secretory response; they tended to prolong the peak response, but did not alter the subsequent fade of acid secretion. The histamine H1-receptor antagonist mepyramine did not affect maximal acid secretion or the fade of the pentagastrin response. 4. The beta-adrenoreceptor antagonist propranolol increased the secretory response to pentagastrin, whilst the alpha-adrenoreceptor antagonist phentolamine was without effect. Neither agent altered the fade of the pentagastrin response. Isoprenaline tended to inhibit pentagastrin-stimulated acid secretion and increase the rate of fade of the response. 5. The 5-hydroxytryptamine (5-HT) receptor antagonist methylsergide slightly enhanced the acid secretory response to pentagastrin, but did not alter the fade of the response. A low dose of 5-HT did not alter pentagastrin-stimulated acid secretion, whilst a higher dose of 5-HT inhibited it. 6. Tetra-, penta- and pentadecagastrin demonstrated tachyphylaxis, i.e. progressively reduced responses upon repeated stimulation, whilst histamine did not. A low dose of histamine did not prevent tachyphylaxis of the pentagastrin response. 7. It is concluded that fade of pentagastrin-stimulated acid secretion in the conscious cat cannot be satisfactorily explained by the failure of the acid secretory mechanism, depletion of histamine, release of 5-HT, or activation of histamine H1-, alpha- or beta-adreno-, or 5-HT-receptors. The similar characteristics of fade

  13. Phenylacetic acid stimulation of cellulose digestion by Ruminococcus albus 8

    SciTech Connect

    Stack, R.J.; Hungate, R.E.; Opsahl, W.P.

    1983-09-01

    The rate of cellulose digestion by Ruminococcus albus 8 grown on a defined medium could be increased by adding a minimum of 6.6% (vol/vol) rumen fluid. Strain 8 was grown on half this concentration, and the culture medium before and after growth was analyzed by gas chromatography-mass spectrometry to determine which components of the rumen fluid were used. Phenylacetic acid was identified as the component needed to make the defined medium nutritionally equivalent to one supplemented with rumen fluid. (/sup 14/C)phenylacetic acid fed to cultures of strain 8 was primarily incorporated into protein. Hydrolysis of protein samples and separation of the resulting amino acids showed that only phenylalanine was labeled. The results indicate that cellulose digestion by strain 8 was probably limited by phenylalanine biosynthesis in our previously reported medium. The data obtained on the utilization of other rumen fluid components, as well as on the production of metabolites, illustrate the potential usefulness of this method in formulating defined media to simulate those in nature. 14 references.

  14. Activation of transmembrane bile acid receptor TGR5 stimulates insulin secretion in pancreatic {beta} cells

    SciTech Connect

    Kumar, Divya P.; Rajagopal, Senthilkumar; Mahavadi, Sunila; Mirshahi, Faridoddin; Grider, John R.; Murthy, Karnam S.; Sanyal, Arun J.

    2012-10-26

    Highlights: Black-Right-Pointing-Pointer G protein coupled receptor TGR5 is expressed in mouse and human islets. Black-Right-Pointing-Pointer TGR5 is coupled to activation of Gs and Ca{sup 2+} release via cAMP/Epac/PLC-{epsilon} pathway. Black-Right-Pointing-Pointer Activation of TGR5 by bile salts and selective ligands causes insulin secretion. Black-Right-Pointing-Pointer TGR5 could be a potential therapeutic target to treat diabetes. -- Abstract: Bile acids act as signaling molecules and stimulate the G protein coupled receptor, TGR5, in addition to nuclear farnesoid X receptor to regulate lipid, glucose and energy metabolism. Bile acid induced activation of TGR5 in the enteroendocrine cells promotes glucagon like peptide-1 (GLP-1) release, which has insulinotropic effect in the pancreatic {beta} cells. In the present study, we have identified the expression of TGR5 in pancreatic {beta} cell line MIN6 and also in mouse and human pancreatic islets. TGR5 selective ligands, oleanolic acid (OA) and INT-777 selectively activated G{alpha}{sub s} and caused an increase in intracellular cAMP and Ca{sup 2+}. OA and INT-777 also increased phosphoinositide (PI) hydrolysis and the increase was blocked by NF449 (a selective G{alpha}{sub s} inhibitor) or (U73122) (PI hydrolysis inhibitor). OA, INT-777 and lithocholic acid increased insulin release in MIN6 and human islets and the increase was inhibited by treatment with NF449, (U73122) or BAPTA-AM (chelator of calcium), but not with myristoylated PKI (PKA inhibitor), suggesting that the release is dependent on G{sub s}/cAMP/Ca{sup 2+} pathway. 8-pCPT-2 Prime -O-Me-cAMP, a cAMP analog, which activates Epac, but not PKA also stimulated PI hydrolysis. In conclusion, our study demonstrates that the TGR5 expressed in the pancreatic {beta} cells regulates insulin secretion and highlights the importance of ongoing therapeutic strategies targeting TGR5 in the control of glucose homeostasis.

  15. Acupuncture inhibits vagal gastric acid secretion stimulated by sham feeding in healthy subjects.

    PubMed Central

    Lux, G; Hagel, J; Bäcker, P; Bäcker, G; Vogl, R; Ruppin, H; Domschke, S; Domschke, W

    1994-01-01

    In a prospective randomised study, the effect of acupuncture on sham feeding stimulated gastric acid secretion was investigated. In eight healthy volunteers (five men, three women, mean (SEM) age 26.3 (4.7) years) various methods of acupuncture were performed. Apart from the sham procedure, the acupuncture was performed at the classic acupuncture points. Electroacupuncture reduced gastric acid secretion expressed as median (range) significantly during the first 30 minute period to 1.6 (0-5.2) mmol compared with 3.8 (2.3-14.5) mmol (p < 0.05) during control period (sham feeding without acupuncture). Inhibition of gastric acid secretion by electroacupuncture was also significant during the second 30 minute period (0.2 (0-5.6) v 3.6 (0.3-9.1) mmol; p < 0.05) and for peak acid output (0.8 (0.2-5.1) v 7.6 (3.4-12.1) mmol; p < 0.05). Transcutaneous electrical nerve stimulation also resulted in significant reduction of gastric acid secretion during the first 30 minute period (1.0 (0-3.6) mmol v 3.8 (2.3-14.5) mmol; p < 0.05), and peak acid output (3.6 (1.2-12.0) v 7.6 (3.4-12.1) mmol; p < 0.05). The classic needle acupuncture, laser acupuncture, and sham acupuncture had no significant effect on gastric acid secretion. This study shows firstly that in healthy volunteers, only the versions of acupuncture using more pronounced stimulation (electroacupuncture, transcutaneous electrical nerve stimulation), but not those with only mild stimulation of the nerves (classic needle acupuncture, laser acupuncture), and secondly only acupuncture performed at defined points lead to significant reduction in gastric acid secretion. PMID:7926899

  16. Acupuncture inhibits vagal gastric acid secretion stimulated by sham feeding in healthy subjects.

    PubMed

    Lux, G; Hagel, J; Bäcker, P; Bäcker, G; Vogl, R; Ruppin, H; Domschke, S; Domschke, W

    1994-08-01

    In a prospective randomised study, the effect of acupuncture on sham feeding stimulated gastric acid secretion was investigated. In eight healthy volunteers (five men, three women, mean (SEM) age 26.3 (4.7) years) various methods of acupuncture were performed. Apart from the sham procedure, the acupuncture was performed at the classic acupuncture points. Electroacupuncture reduced gastric acid secretion expressed as median (range) significantly during the first 30 minute period to 1.6 (0-5.2) mmol compared with 3.8 (2.3-14.5) mmol (p < 0.05) during control period (sham feeding without acupuncture). Inhibition of gastric acid secretion by electroacupuncture was also significant during the second 30 minute period (0.2 (0-5.6) v 3.6 (0.3-9.1) mmol; p < 0.05) and for peak acid output (0.8 (0.2-5.1) v 7.6 (3.4-12.1) mmol; p < 0.05). Transcutaneous electrical nerve stimulation also resulted in significant reduction of gastric acid secretion during the first 30 minute period (1.0 (0-3.6) mmol v 3.8 (2.3-14.5) mmol; p < 0.05), and peak acid output (3.6 (1.2-12.0) v 7.6 (3.4-12.1) mmol; p < 0.05). The classic needle acupuncture, laser acupuncture, and sham acupuncture had no significant effect on gastric acid secretion. This study shows firstly that in healthy volunteers, only the versions of acupuncture using more pronounced stimulation (electroacupuncture, transcutaneous electrical nerve stimulation), but not those with only mild stimulation of the nerves (classic needle acupuncture, laser acupuncture), and secondly only acupuncture performed at defined points lead to significant reduction in gastric acid secretion.

  17. Interleukin-1β inhibits insulin signaling and prevents insulin-stimulated system A amino acid transport in primary human trophoblasts.

    PubMed

    Aye, Irving L M H; Jansson, Thomas; Powell, Theresa L

    2013-12-01

    Interleukin-1β (IL-1β) promotes insulin resistance in tissues such as liver and skeletal muscle; however the influence of IL-1β on placental insulin signaling is unknown. We recently reported increased IL-1β protein expression in placentas of obese mothers, which could contribute to insulin resistance. In this study, we tested the hypothesis that IL-1β inhibits insulin signaling and prevents insulin-stimulated amino acid transport in cultured primary human trophoblast (PHT) cells. Cultured trophoblasts isolated from term placentas were treated with physiological concentrations of IL-1β (10pg/ml) for 24h. IL-1β increased the phosphorylation of insulin receptor substrate-1 (IRS-1) at Ser307 (inhibitory) and decreased total IRS-1 protein abundance but did not affect insulin receptor β expression. Furthermore, IL-1β inhibited insulin-stimulated phosphorylation of IRS-1 (Tyr612, activation site) and Akt (Thr308) and prevented insulin-stimulated increase in PI3K/p85 and Grb2 protein expression. IL-1β alone stimulated cRaf (Ser338), MEK (Ser221) and Erk1/2 (Thr202/Tyr204) phosphorylation. The inflammatory pathways nuclear factor kappa B and c-Jun N-terminal kinase, which are involved in insulin resistance, were also activated by IL-1β treatment. Moreover, IL-1β inhibited insulin-stimulated System A, but not System L amino acid uptake, indicating functional impairment of insulin signaling. In conclusion, IL-1β inhibited the insulin signaling pathway by inhibiting IRS-1 signaling and prevented insulin-stimulated System A transport, thereby promoting insulin resistance in cultured PHT cells. These findings indicate that conditions which lead to increased systemic maternal or placental IL-1β levels may attenuate the effects of maternal insulin on placental function and consequently fetal growth.

  18. Planning and execution of Raft River stimulation treatments

    SciTech Connect

    Verity, R.V.; Crichlow, H.B.

    1980-02-07

    The following topics are discussed for two Raft River Valley wells: well characteristics and treatment objectives, treatment selection and design, treatment history, mechanical arrangements and job costs. (MHR)

  19. Acetaldehyde stimulation of net gluconeogenic carbon movement from applied malic acid in tomato fruit pericarp tissue

    SciTech Connect

    Halinska, A.; Frenkel, C. )

    1991-03-01

    Applied acetaldehyde is known to lead to sugar accumulation in fruit including tomatoes (Lycopersicon esculentum) presumably due to stimulation of gluconeogenesis. This conjecture was examined using tomato fruit pericarp discs as a test system and applied l-(U-{sup 14}C)malic acid as the source for gluconeogenic carbon mobilization. Results indicate that malic and perhaps other organic acids are carbon sources for gluconeogenesis occurring normally in ripening tomatoes. The process is stimulated by acetaldehyde apparently by attenuating the fructose-2,6-biphosphate levels. The mode of the acetaldehyde regulation of fructose-2,6-biphosphate metabolism awaits clarification.

  20. Pyroglutamic acid stimulates DNA synthesis in rat primary hepatocytes through the mitogen-activated protein kinase pathway.

    PubMed

    Inoue, Shinjiro; Okita, Yoichi; de Toledo, Andreia; Miyazaki, Hiroyuki; Hirano, Eiichi; Morinaga, Tetsuo

    2015-01-01

    We purified pyroglutamic acid from human placental extract and identified it as a potent stimulator of rat primary hepatocyte DNA synthesis. Pyroglutamic acid dose-dependently stimulated DNA synthesis, and this effect was inhibited by PD98059, a dual specificity mitogen-activated protein kinase kinase 1 (MAP2K1) inhibitor. Therefore, pyroglutamic acid stimulated DNA synthesis in rat primary hepatocytes via MAPK signaling.

  1. Ursolic acid isolated from guava leaves inhibits inflammatory mediators and reactive oxygen species in LPS-stimulated macrophages.

    PubMed

    Kim, Min-Hye; Kim, Jin Nam; Han, Sung Nim; Kim, Hye-Kyeong

    2015-06-01

    Psidium guajava (guava) leaves have been frequently used for the treatment of rheumatism, fever, arthritis and other inflammatory conditions. The purpose of this study was to identify major anti-inflammatory compounds from guava leaf extract. The methanol extract and its hexane-, dichloromethane-, ethylacetate-, n-butanol- and water-soluble phases derived from guava leaves were evaluated to determine their inhibitory activity on nitric oxide (NO) production by RAW 264.7 cells stimulated with lipopolysaccharide (LPS). The methanol extract decreased NO production in a dose-dependent manner without cytotoxicity at a concentration range of 0-100 μg/mL. The n-butanol soluble phase was the most potent among the five soluble phases. Four compounds were isolated by reversed-phase HPLC from the n-butanol soluble phase and identified to be avicularin, guaijaverin, leucocyanidin and ursolic acid by their NMR spectra. Among these compounds, ursolic acid inhibited LPS-induced NO production in a dose-dependent manner without cytotoxity at a concentration range of 1-10 µM, but the other three compounds had no effect. Ursolic acid also inhibited LPS-induced prostaglandin E2 production. A western blot analysis showed that ursolic acid decreased the LPS-stimulated inducible nitric oxide synthase and cyclooxygenase protein levels. In addition, ursolic acid suppressed the production of intracellular reactive oxygen species in LPS-stimulated RAW 264.7 cells, as measured by flow cytometry. Taken together, these results identified ursolic acid as a major anti-inflammatory compound in guava leaves. PMID:25753845

  2. Ursolic acid isolated from guava leaves inhibits inflammatory mediators and reactive oxygen species in LPS-stimulated macrophages.

    PubMed

    Kim, Min-Hye; Kim, Jin Nam; Han, Sung Nim; Kim, Hye-Kyeong

    2015-06-01

    Psidium guajava (guava) leaves have been frequently used for the treatment of rheumatism, fever, arthritis and other inflammatory conditions. The purpose of this study was to identify major anti-inflammatory compounds from guava leaf extract. The methanol extract and its hexane-, dichloromethane-, ethylacetate-, n-butanol- and water-soluble phases derived from guava leaves were evaluated to determine their inhibitory activity on nitric oxide (NO) production by RAW 264.7 cells stimulated with lipopolysaccharide (LPS). The methanol extract decreased NO production in a dose-dependent manner without cytotoxicity at a concentration range of 0-100 μg/mL. The n-butanol soluble phase was the most potent among the five soluble phases. Four compounds were isolated by reversed-phase HPLC from the n-butanol soluble phase and identified to be avicularin, guaijaverin, leucocyanidin and ursolic acid by their NMR spectra. Among these compounds, ursolic acid inhibited LPS-induced NO production in a dose-dependent manner without cytotoxity at a concentration range of 1-10 µM, but the other three compounds had no effect. Ursolic acid also inhibited LPS-induced prostaglandin E2 production. A western blot analysis showed that ursolic acid decreased the LPS-stimulated inducible nitric oxide synthase and cyclooxygenase protein levels. In addition, ursolic acid suppressed the production of intracellular reactive oxygen species in LPS-stimulated RAW 264.7 cells, as measured by flow cytometry. Taken together, these results identified ursolic acid as a major anti-inflammatory compound in guava leaves.

  3. Acute central stimulation of luteinizing hormone by parenterally administered N-methyl-D,L-aspartic acid in the male rat.

    PubMed

    Schainker, B A; Cicero, T J

    1980-02-24

    N-methyl-D,L-aspartic acid (NMA), a potent neuroexcitatory and neurotoxic glutamic acid analogue, acutely elevated serum luteinizing hormone (LH) in male rats when given subcutaneously in doses below those that cause morphologically detectable hypothalamic neurotoxicity. NMA treatment in doses known to be subtoxic by morphological criteria fails to induce any permanent neuroendocrine dysfunction as assessed by several physiological parameters, including NMA responsiveness after multiple consecutive dosees spaced at 24 h intervals, subsequent basal LH levels and subsequent postcastration LH elevations. Like naloxone, NMA elevates serum LH by reversibly stimulating a central labile pool. Neither has a direct stimulatory effect on the pituitary in vitro. Treatment with either attenuates naloxone-induced LH stimulation 2 h, but not 14 days, later while pituitary responsiveness to LHRH in vivo remains unaltered. Neither NMA nor naloxone is dependent upon testosterone for its LH stimulatory action and both increase serum LH through physiological mechanisms responsive to testosterone inhibition. It is concluded that subtoxic LH stimulating doses of NMA provide a useful tool in discerning neurotransmitter systems involved in central control of the hypothalamic-pituitary-gonadal axis.

  4. Bacterial Cyanuric Acid Hydrolase for Water Treatment

    PubMed Central

    Yeom, Sujin; Mutlu, Baris R.; Aksan, Alptekin

    2015-01-01

    Di- and trichloroisocyanuric acids are widely used as water disinfection agents, but cyanuric acid accumulates with repeated additions and must be removed to maintain free hypochlorite for disinfection. This study describes the development of methods for using a cyanuric acid-degrading enzyme contained within nonliving cells that were encapsulated within a porous silica matrix. Initially, three different bacterial cyanuric acid hydrolases were compared: TrzD from Acidovorax citrulli strain 12227, AtzD from Pseudomonas sp. strain ADP, and CAH from Moorella thermoacetica ATCC 39073. Each enzyme was expressed recombinantly in Escherichia coli and tested for cyanuric acid hydrolase activity using freely suspended or encapsulated cell formats. Cyanuric acid hydrolase activities differed by only a 2-fold range when comparing across the different enzymes with a given format. A practical water filtration system is most likely to be used with nonviable cells, and all cells were rendered nonviable by heat treatment at 70°C for 1 h. Only the CAH enzyme from the thermophile M. thermoacetica retained significant activity under those conditions, and so it was tested in a flowthrough system simulating a bioreactive pool filter. Starting with a cyanuric acid concentration of 10,000 μM, more than 70% of the cyanuric acid was degraded in 24 h, it was completely removed in 72 h, and a respike of 10,000 μM cyanuric acid a week later showed identical biodegradation kinetics. An experiment conducted with water obtained from municipal swimming pools showed the efficacy of the process, although cyanuric acid degradation rates decreased by 50% in the presence of 4.5 ppm hypochlorite. In total, these experiments demonstrated significant robustness of cyanuric acid hydrolase and the silica bead materials in remediation. PMID:26187963

  5. Bacterial Cyanuric Acid Hydrolase for Water Treatment.

    PubMed

    Yeom, Sujin; Mutlu, Baris R; Aksan, Alptekin; Wackett, Lawrence P

    2015-10-01

    Di- and trichloroisocyanuric acids are widely used as water disinfection agents, but cyanuric acid accumulates with repeated additions and must be removed to maintain free hypochlorite for disinfection. This study describes the development of methods for using a cyanuric acid-degrading enzyme contained within nonliving cells that were encapsulated within a porous silica matrix. Initially, three different bacterial cyanuric acid hydrolases were compared: TrzD from Acidovorax citrulli strain 12227, AtzD from Pseudomonas sp. strain ADP, and CAH from Moorella thermoacetica ATCC 39073. Each enzyme was expressed recombinantly in Escherichia coli and tested for cyanuric acid hydrolase activity using freely suspended or encapsulated cell formats. Cyanuric acid hydrolase activities differed by only a 2-fold range when comparing across the different enzymes with a given format. A practical water filtration system is most likely to be used with nonviable cells, and all cells were rendered nonviable by heat treatment at 70°C for 1 h. Only the CAH enzyme from the thermophile M. thermoacetica retained significant activity under those conditions, and so it was tested in a flowthrough system simulating a bioreactive pool filter. Starting with a cyanuric acid concentration of 10,000 μM, more than 70% of the cyanuric acid was degraded in 24 h, it was completely removed in 72 h, and a respike of 10,000 μM cyanuric acid a week later showed identical biodegradation kinetics. An experiment conducted with water obtained from municipal swimming pools showed the efficacy of the process, although cyanuric acid degradation rates decreased by 50% in the presence of 4.5 ppm hypochlorite. In total, these experiments demonstrated significant robustness of cyanuric acid hydrolase and the silica bead materials in remediation. PMID:26187963

  6. Bacterial Cyanuric Acid Hydrolase for Water Treatment.

    PubMed

    Yeom, Sujin; Mutlu, Baris R; Aksan, Alptekin; Wackett, Lawrence P

    2015-10-01

    Di- and trichloroisocyanuric acids are widely used as water disinfection agents, but cyanuric acid accumulates with repeated additions and must be removed to maintain free hypochlorite for disinfection. This study describes the development of methods for using a cyanuric acid-degrading enzyme contained within nonliving cells that were encapsulated within a porous silica matrix. Initially, three different bacterial cyanuric acid hydrolases were compared: TrzD from Acidovorax citrulli strain 12227, AtzD from Pseudomonas sp. strain ADP, and CAH from Moorella thermoacetica ATCC 39073. Each enzyme was expressed recombinantly in Escherichia coli and tested for cyanuric acid hydrolase activity using freely suspended or encapsulated cell formats. Cyanuric acid hydrolase activities differed by only a 2-fold range when comparing across the different enzymes with a given format. A practical water filtration system is most likely to be used with nonviable cells, and all cells were rendered nonviable by heat treatment at 70°C for 1 h. Only the CAH enzyme from the thermophile M. thermoacetica retained significant activity under those conditions, and so it was tested in a flowthrough system simulating a bioreactive pool filter. Starting with a cyanuric acid concentration of 10,000 μM, more than 70% of the cyanuric acid was degraded in 24 h, it was completely removed in 72 h, and a respike of 10,000 μM cyanuric acid a week later showed identical biodegradation kinetics. An experiment conducted with water obtained from municipal swimming pools showed the efficacy of the process, although cyanuric acid degradation rates decreased by 50% in the presence of 4.5 ppm hypochlorite. In total, these experiments demonstrated significant robustness of cyanuric acid hydrolase and the silica bead materials in remediation.

  7. Stimulation of polyunsaturated fatty acid oxidation in myocytes by regulating its cellular uptake

    SciTech Connect

    Abdel-aleem, S.; Frangakis, C. ); Badr, M. )

    1991-01-01

    In order to investigate the regulation of polyunsaturated fatty acid oxidation in the heart, the effect of the phosphodiesterase inhibitor enoximone on the oxidation of (1-{sup 14}C) arachidonic acid, and (1-{sup 14}C) arachidonyl-CoA, were studied in adult rat myocytes, and isolated rat heart mitochondria. Enoximone stimulated arachidonate oxidation by 94%, at a concentration of 0.25 mM. The apparent Vmax value of archidonate oxidation in the presence of enoximone was approximately 75% higher than the value observed with the control in isolated myocytes. Also, enoximone stimulated arachidonate uptake by 27% at a concentration of 0.25 mM. On the other hand, enoximone had no effect on the oxidation of (1-{sup 14}C) arachidonyl-CoA in isolated rat heart mitochondria. These results suggest that the oxidation of polyunsaturated fatty acids in myocytes is regulated by the rate of uptake of these acids across sarcolemmal membranes.

  8. Monoamine Transporter Inhibitors and Substrates as Treatments for Stimulant Abuse

    PubMed Central

    Howell, Leonard L.; Negus, S. Stevens

    2015-01-01

    The acute and chronic effects of abused psychostimulants on monoamine transporters and associated neurobiology have encouraged development of candidate medications that target these transporters. Monoamine transporters in general, and dopamine transporters in particular, are critical molecular targets that mediate abuse-related effects of psychostimulants such as cocaine and amphetamine. Moreover, chronic administration of psychostimulants can cause enduring changes in neurobiology reflected in dysregulation of monoamine neurochemistry and behavior. The current review will evaluate evidence for the efficacy of monoamine transporter inhibitors and substrates to reduce abuse-related effects of stimulants in preclinical assays of stimulant self-administration, drug discrimination and reinstatement. In considering deployment of monoamine transport inhibitors and substrates as agonist-type medications to treat stimulant abuse, the safety and abuse liability of the medications are an obvious concern, and this will also be addressed. Future directions in drug discovery should identify novel medications that retain efficacy to decrease stimulant use but possess lower abuse liability, and evaluate the degree to which efficacious medications can attenuate or reverse neurobiological effects of chronic stimulant use. PMID:24484977

  9. Monoamine transporter inhibitors and substrates as treatments for stimulant abuse.

    PubMed

    Howell, Leonard L; Negus, S Stevens

    2014-01-01

    The acute and chronic effects of abused psychostimulants on monoamine transporters and associated neurobiology have encouraged development of candidate medications that target these transporters. Monoamine transporters, in general, and dopamine transporters, in particular, are critical molecular targets that mediate abuse-related effects of psychostimulants such as cocaine and amphetamine. Moreover, chronic administration of psychostimulants can cause enduring changes in neurobiology reflected in dysregulation of monoamine neurochemistry and behavior. The current review will evaluate evidence for the efficacy of monoamine transporter inhibitors and substrates to reduce abuse-related effects of stimulants in preclinical assays of stimulant self-administration, drug discrimination, and reinstatement. In considering deployment of monoamine transport inhibitors and substrates as agonist-type medications to treat stimulant abuse, the safety and abuse liability of the medications are an obvious concern, and this will also be addressed. Future directions in drug discovery should identify novel medications that retain efficacy to decrease stimulant use but possess lower abuse liability and evaluate the degree to which efficacious medications can attenuate or reverse neurobiological effects of chronic stimulant use. PMID:24484977

  10. Not robots: children's perspectives on authenticity, moral agency and stimulant drug treatments.

    PubMed

    Singh, Ilina

    2013-06-01

    In this article, I examine children's reported experiences with stimulant drug treatments for attention deficit hyperactivity disorder in light of bioethical arguments about the potential threats of psychotropic drugs to authenticity and moral agency. Drawing on a study that involved over 150 families in the USA and the UK, I show that children are able to report threats to authenticity, but that the majority of children are not concerned with such threats. On balance, children report that stimulants improve their capacity for moral agency, and they associate this capacity with an ability to meet normative expectations. I argue that although under certain conditions stimulant drug treatment may increase the risk of a threat to authenticity, there are ways to minimise this risk and to maximise the benefits of stimulant drug treatment. Medical professionals in particular should help children to flourish with stimulant drug treatments, in good and in bad conditions.

  11. Phosphatidic acid stimulates inositol 1,4,5-trisphosphate production in adult cardiac myocytes.

    PubMed

    Kurz, T; Wolf, R A; Corr, P B

    1993-03-01

    The cellular content of phosphatidic acid can increase in response to several agonists either by phosphorylation of diacylglycerol after phospholipase C-catalyzed hydrolysis of phospholipids or directly through activation of phospholipase D. Although previous findings indicated that the generation of phosphatidic acid was exclusively a means of regulation of the cellular concentration of diacylglycerol, more recent studies have indicated that phosphatidic acid may also directly regulate several cellular functions. Accordingly, the present study was performed to assess whether phosphatidic acid could stimulate cardiac phospholipase C in intact adult rabbit ventricular myocytes. The mass of inositol 1,4,5-trisphosphate [Ins (1,4,5)P3] was determined by a specific and sensitive binding protein assay and by direct mass measurement using anion exchange chromatography for separation of selected inositol phosphates and gas chromatography and mass spectrometry for quantification of inositol monophosphate (IP1), inositol bisphosphate (IP2), inositol trisphosphate (IP3), and inositol tetrakisphosphate (IP4). Phosphatidic acid (10(-9)-10(-6) M) elicited a rapid concentration-dependent increase in Ins (1,4,5)P3 accumulation, with the peak fourfold to fivefold increase at 30 seconds of stimulation; the concentration required for 50% of maximal stimulation was 4.4 x 10(-8) M. The time course of individual inositol phosphates indicated a successive increase in the mass of IP3, IP4, IP2, and IP1 in response to stimulation with phosphatidic acid. The production of Ins (1,4,5)P3 in response to phosphatidic acid was not altered in the absence of extracellular calcium or in the presence of extracellular EGTA (10(-3) M). Thus, these findings indicate that phosphatidic acid is a potent activator of inositol phosphate production in adult ventricular myocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

  12. Vascular smooth muscle cells preloaded with eicosapentaenoic acid and docosahexaenoic acid fail to respond to serotonin stimulation.

    PubMed

    Pakala, R; Pakala, R; Sheng, W L; Benedict, C R

    2000-11-01

    Epidemiological, animal and clinical studies indicate that n-3 fatty acids may benefit individuals with known history of cardiovascular disease or at risk of developing it. Though there is indirect evidence to suggest that the beneficial effects of n-3 fatty acids may be because of their ability to inhibit smooth muscle cell (SMC) proliferation, there are no studies that have examined this hypothesis. In this study, the mitogenic effect of serotonin (5HT) and platelet derived growth factor (PDGF), known mitogens for vascular SMC, on aortic SMCs preloaded with eicosapentaenoic acid (EPA) and/or docosahexaenoic acid (DHA) is examined. 5HT and PDGF could only partially stimulate proliferation of SMC that were preloaded with EPA or DHA as compared to the control cells. gamma-Linolenic acid (LA) and oleic acid (OA) did not block the 5HT or PDGF induced 3[H]thymidine incorporation suggesting that the anti-proliferative effect was specific to n-3 fatty acids only. Further, when EPA and DHA were combined in the ratio they are present in fishoils, there was a synergistic interaction in inhibiting the proliferation of SMC. Further, SMC grown in the presence of EPA or DHA, when stimulated with 5HT, failed to show an increase in 5HT(2) receptor mRNA. One of the potential mechanism by which fish oils may prevent the development of atherosclerosis or restenosis could be inhibition of the mitogen induced SMC proliferation. Combination of EPA with DHA is likely to be more beneficial.

  13. Bile acids stimulate chloride secretion through CFTR and calcium-activated Cl- channels in Calu-3 airway epithelial cells.

    PubMed

    Hendrick, Siobhán M; Mroz, Magdalena S; Greene, Catherine M; Keely, Stephen J; Harvey, Brian J

    2014-09-01

    Bile acids resulting from the aspiration of gastroesophageal refluxate are often present in the lower airways of people with cystic fibrosis and other respiratory distress diseases. Surprisingly, there is little or no information on the modulation of airway epithelial ion transport by bile acids. The secretory effect of a variety of conjugated and unconjugated secondary bile acids was investigated in Calu-3 airway epithelial cells grown under an air-liquid interface and mounted in Ussing chambers. Electrogenic transepithelial ion transport was measured as short-circuit current (Isc). The taurine-conjugated secondary bile acid, taurodeoxycholic acid (TDCA), was found to be the most potent modulator of basal ion transport. Acute treatment (5 min) of Calu-3 cells with TDCA (25 μM) on the basolateral side caused a stimulation of Isc, and removal of extracellular Cl(-) abolished this response. TDCA produced an increase in the cystic fibrosis transmembrane conductance regulator (CFTR)-dependent current that was abolished by pretreatment with the CFTR inhibitor CFTRinh172. TDCA treatment also increased Cl(-) secretion through calcium-activated chloride (CaCC) channels and increased the Na(+)/K(+) pump current. Acute treatment with TDCA resulted in a rapid cellular influx of Ca(2+) and increased cAMP levels in Calu-3 cells. Bile acid receptor-selective activation with INT-777 revealed TGR5 localized at the basolateral membrane as the receptor involved in TDCA-induced Cl(-) secretion. In summary, we demonstrate for the first time that low concentrations of bile acids can modulate Cl(-) secretion in airway epithelial cells, and this effect is dependent on both the duration and sidedness of exposure to the bile acid.

  14. Complete inhibition of food-stimulated gastric acid secretion by combined application of pirenzepine and ranitidine.

    PubMed Central

    Londong, W; Londong, V; Ruthe, C; Weizert, P

    1981-01-01

    In a double-blind, placebo controlled and randomised secretory study the effectiveness of pirenzepine, ranitidine, and their combination was compared intraindividually in eight healthy subjects receiving intravenous bolus injections. Pirenzepine (0.15 mg/kg) plus ranitidine (0.6 mg/kg) suppressed peptone-stimulated gastric acid secretion from 69 +/- 11 to 2 +/- 0.4 mmol H+/3 h; the mean percentage inhibition was 97%. Postprandial gastrin was unaffected. There were only minor side-effects in a few experiments (reduction of salivation, brief blurring of vision), but no prolactin stimulation after ranitidine or ranitidine plus pirenzepine. The combined application of ranitidine and pirenzepine inhibited meal-stimulated acid secretion more effectively and produced fewer side-effects than the combination of cimetidine plus pirenzepine studied previously. PMID:6114900

  15. Insulin and amino acids stimulate whole body protein synthesis in neonates

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Insulin and amino acids (AA) stimulate muscle protein synthesis in neonatal pigs. To determine the effects of insulin and AA on whole body protein turnover, hyperinsulinemic (0 and 100 ng/(kg[0.66]/min))-euglycemic-AA clamps were performed during euaminoacidemia or hyperaminoacidemia in fasted 7-d-...

  16. TNF-α stimulates System A amino acid transport in primary human trophoblast cells mediated by p38 MAPK signaling.

    PubMed

    Aye, Irving L M H; Jansson, Thomas; Powell, Theresa L

    2015-10-01

    Maternal obesity and gestational diabetes mellitus (GDM) increase the risk of delivering infants that are large for gestational age with greater adiposity, who are prone to the development of metabolic disease in childhood and beyond. These maternal conditions are also associated with increased levels of the proinflammatory cytokine TNF-α in maternal tissues and the placenta. Recent evidence suggests that changes in placental amino acid transport contribute to altered fetal growth. TNF-α was previously shown to stimulate System A amino acid transport in primary human trophoblasts (PHTs), however the molecular mechanisms remain unknown. In this study, we tested the hypothesis that TNF-α regulates amino acid uptake in cultured PHTs by a mitogen-activated protein kinase (MAPK)-dependent mechanism. Treatment of PHTs with TNF-α significantly increased System A amino acid transport, as well as Erk and p38 MAPK signaling. Pharmacological antagonism of p38, but not Erk MAPK activity, inhibited TNF-α stimulated System A activity. Silencing of p38 MAPK using siRNA transfections prevented TNF-α stimulated System A transport in PHTs. TNF-α significantly increased the protein expression of System A transporters SNAT1 and SNAT2, but did not affect their mRNA expression. The effects of TNF-α on SNAT1 and SNAT2 protein expression were reversed by p38 MAPK siRNA silencing. In conclusion, TNF-α regulates System A activity through increased SNAT1 and SNAT2 transporter protein expression in PHTs. These findings suggest that p38 MAPK may represent a critical mechanistic link between elevated proinflammatory cytokines and increased placental amino acid transport in obese and GDM pregnancies associated with fetal overgrowth.

  17. TNF-α stimulates System A amino acid transport in primary human trophoblast cells mediated by p38 MAPK signaling.

    PubMed

    Aye, Irving L M H; Jansson, Thomas; Powell, Theresa L

    2015-10-01

    Maternal obesity and gestational diabetes mellitus (GDM) increase the risk of delivering infants that are large for gestational age with greater adiposity, who are prone to the development of metabolic disease in childhood and beyond. These maternal conditions are also associated with increased levels of the proinflammatory cytokine TNF-α in maternal tissues and the placenta. Recent evidence suggests that changes in placental amino acid transport contribute to altered fetal growth. TNF-α was previously shown to stimulate System A amino acid transport in primary human trophoblasts (PHTs), however the molecular mechanisms remain unknown. In this study, we tested the hypothesis that TNF-α regulates amino acid uptake in cultured PHTs by a mitogen-activated protein kinase (MAPK)-dependent mechanism. Treatment of PHTs with TNF-α significantly increased System A amino acid transport, as well as Erk and p38 MAPK signaling. Pharmacological antagonism of p38, but not Erk MAPK activity, inhibited TNF-α stimulated System A activity. Silencing of p38 MAPK using siRNA transfections prevented TNF-α stimulated System A transport in PHTs. TNF-α significantly increased the protein expression of System A transporters SNAT1 and SNAT2, but did not affect their mRNA expression. The effects of TNF-α on SNAT1 and SNAT2 protein expression were reversed by p38 MAPK siRNA silencing. In conclusion, TNF-α regulates System A activity through increased SNAT1 and SNAT2 transporter protein expression in PHTs. These findings suggest that p38 MAPK may represent a critical mechanistic link between elevated proinflammatory cytokines and increased placental amino acid transport in obese and GDM pregnancies associated with fetal overgrowth. PMID:26508738

  18. Noninvasive brain stimulation for the treatment of auditory verbal hallucinations in schizophrenia: methods, effects and challenges

    PubMed Central

    Kubera, Katharina M.; Barth, Anja; Hirjak, Dusan; Thomann, Philipp A.; Wolf, Robert C.

    2015-01-01

    This mini-review focuses on noninvasive brain stimulation techniques as an augmentation method for the treatment of persistent auditory verbal hallucinations (AVH) in patients with schizophrenia. Paradigmatically, we place emphasis on transcranial magnetic stimulation (TMS). We specifically discuss rationales of stimulation and consider methodological questions together with issues of phenotypic diversity in individuals with drug-refractory and persistent AVH. Eventually, we provide a brief outlook for future investigations and treatment directions. Taken together, current evidence suggests TMS as a promising method in the treatment of AVH. Low-frequency stimulation of the superior temporal cortex (STC) may reduce symptom severity and frequency. Yet clinical effects are of relatively short duration and effect sizes appear to decrease over time along with publication of larger trials. Apart from considering other innovative stimulation techniques, such as transcranial Direct Current Stimulation (tDCS), and optimizing stimulation protocols, treatment of AVH using noninvasive brain stimulation will essentially rely on accurate identification of potential responders and non-responders for these treatment modalities. In this regard, future studies will need to consider distinct phenotypic presentations of AVH in patients with schizophrenia, together with the putative functional neurocircuitry underlying these phenotypes. PMID:26528145

  19. Tactile stimulation improves neuroanatomical pathology but not behavior in rats prenatally exposed to valproic acid.

    PubMed

    Raza, S; Harker, A; Richards, S; Kolb, B; Gibb, R

    2015-04-01

    Autism is a severe neurodevelopmental disorder with a population prevalence of 1 in 68, and dramatically increasing. While no single pharmacologic intervention has successfully targeted the core symptoms of autism, emerging evidence suggests that postnatal environmental manipulations may offer greater therapeutic efficacy. Massage therapy, or tactile stimulation (TS), early in life has repeatedly been shown to be an effective, low-cost, therapeutic approach in ameliorating the cognitive, social, and emotional symptoms of autism. While early TS treatment attenuates many of the behavioral aberrations among children with autism, the neuroanatomical correlates driving such changes are unknown. The present study assessed the therapeutic effects of early TS treatment on behavior and neuroanatomy using the valproic acid (VPA) rodent model of autism. Rats were prenatally exposed to VPA on gestational day 12.5 and received TS shortly following birth. Whereas TS reversed almost all the VPA-induced alterations in neuroanatomy, it failed to do so behaviorally. The TS VPA animals, when compared to VPA animals, did not exhibit altered or improved behavior in the delayed non-match-to-sample T-maze, Whishaw tray reaching, activity box, or elevated plus maze tasks. Anatomically, however, there were significant increases in dendritic branching and spine density in the medial prefrontal cortex, orbital frontal cortex, and amygdala in VPA animals following early TS treatment, suggesting a complete reversal or remediation of the VPA-induced effects in these regions. The results suggest that postnatal TS, during a critical period in development, acts as a powerful reorganization tool that can ameliorate the neuroanatomical consequences of prenatal VPA exposure.

  20. Relative turnover of (/sup 3/H)arachidonic acid and (/sup 14/C)eicosapentaenoic acid in stimulated human platelets

    SciTech Connect

    Weaver, B.J.; Holub, B.J.

    1986-03-05

    The relative release of arachidonic acid (AA) versus eicosapentaenoic acid (EPA) from platelet phospholipids may be important in accounting for the potential of dietary fish oil containing EPA to alter platelet reactivity. Human platelets enriched in EPA and prelabelled with (/sup 3/H)AA and (/sup 14/C)EPA were used to examine the relative losses of these fatty acids from platelet phospholipids upon stimulation. Washed dual-labelled platelets were incubated with and without thrombin in the presence of BW755C and in the presence and absence of trifluoperazine. The platelet lipids were extracted and the individual phospholipids as well as diacylglycerol (DG), phosphatidic acid (PA), etc. were separated by thin-layer chromatography and the radioactivity in each fraction determined. The (/sup 3/H)AA/(/sup 14/C)EPA dpm ratio for the loss in radioactivity from PC upon thrombin stimulation was similar to that for the PC in resting platelets. This suggests no marked selectivity in the degradation of AA versus EPA species of PC during platelet activation. The (/sup 3/H)/(/sup 14/C) ratios for the increased radioactivity in DG and PA upon thrombin stimulation were slightly higher than the ratio in PI from resting platelets suggesting only a minor preference for 1-acyl 2-arachidonoyl PI over 1-acyl 2-eicosapentaenoyl PI in the pathway from PI to DG to PA.

  1. Anti-inflammatory potential of ursolic acid in Mycobacterium tuberculosis-sensitized and concanavalin A-stimulated cells.

    PubMed

    Zerin, Tamanna; Lee, Minjung; Jang, Woong Sik; Nam, Kung-Woo; Song, Ho-Yeon

    2016-03-01

    Ursolic acid (3-β-3-hydroxy-urs-12-ene-28-oic-acid; UA) is a triterpenoid carboxylic acid with various pharmaceutical properties. It is commonly found in apples, basil, berries, rosemary, peppermint, lavender, oregano, thyme, hawthorn and prunes. In the present study, the activities of UA against the Mycobacterium tuberculosis H37Rv‑induced release of a panel of inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-6 from RAW 264.7 murine macrophages, A549 alveolar epithelial cells and in concanavalin A (Con A)-stimulated rat splenocytes were investigated. In addition, the present study examined the ability of UA to reduce the expression levels of the inflammatory mediators, cyclooxygenase‑2 (COX‑2) and inducible nitric oxide synthase (iNOS) in the stimulated cells. The reduction of nitric oxide (NO) release by UA was also examined in the stimulated cells. UA significantly inhibited the mRNA expression levels of TNF‑α, IL‑1β and IL‑6 in the stimulated cells. The expression levels of COX‑2 and iNOS were also suppressed by UA, as was the release of NO at a significant level. The data indicated the potency of UA on different cell types, which may assist in the development of anti‑inflammatory drugs. In the case of adjunct host‑directed immune therapy for tuberculosis, UA may be used, in addition to established antibiotic therapies, to improve treatment efficacy and outcome due to their anti‑inflammatory potential. Further detailed investigations are required to establish its use as an anti-inflammatory. PMID:26847129

  2. Insulin-induced phospho-oligosaccharide stimulates amino acid transport in isolated rat hepatocytes.

    PubMed Central

    Varela, I; Avila, M; Mato, J M; Hue, L

    1990-01-01

    The ability of the insulin-induced phospho-oligosaccharide to stimulate amino acid transport was studied in isolated rat hepatocytes. At low alpha-aminoisobutyric acid concentrations (0.1 mM), both 100 nM-insulin and 10 microM-phospho-oligosaccharide doubled amino acid uptake after 2 h of incubation. This stimulation was prevented by 0.1 mM-cycloheximide or 5 micrograms of actinomycin D/ml, indicating that the phospho-oligosaccharide, like insulin, was acting via the synthesis of a high-affinity transport component. The effects of the phospho-oligosaccharide and of insulin were blocked by Ins2P (2.5 mM), but not by myo-inositol, inositol hexaphosphoric acid or several monosaccharides such as mannose, glucosamine and galactose. Both the temporal effect on amino acid entry and the extent of stimulation of this process by the phospho-oligosaccharide indicate that this molecule mimics, and may mediate, some of the long-term actions of insulin. However, the effects of phospho-oligosaccharide and insulin were not exactly the same, since the effect of insulin, but not of the phospho-oligosaccharide, was additive with that of glucagon. PMID:2185744

  3. Stimulated microbial reductive dechlorination following surfactant treatment at the Bachman Road site.

    PubMed

    Ramsburg, C Andrew; Abriola, Linda M; Pennell, Kurt D; Löffler, Frank E; Gamache, Matthew; Amos, Benjamin K; Petrovskis, Erik A

    2004-11-15

    A pilot-scale demonstration of surfactant-enhanced aquifer remediation (SEAR) was conducted in July 2000 at the Bachman Road site located in Oscoda, MI. The Bachman aquifer is a shallow, relatively homogeneous, unconfined aquifer formation composed primarily of sandy glacial outwash with relatively low organic carbon content (0.02 wt %). A 6 wt % aqueous solution of Tween 80 (a nonionic, food-grade surfactant) was flushed through a localized dense nonaqueous phase liquid (DNAPL) source zone to recover approximately 19 L of tetrachloroethene (PCE). Post-treatment monitoring revealed PCE concentrations were reduced by up to 2 orders of magnitude within the source zone, and there was no evidence of concentration rebound after more than 450 d. Concentrations of PCE dechlorination products (trichloroethene, cis-1,2-dichloroethene) 450 d after SEAR operations ceased were more than 2 orders of magnitude greater than pretreatment values, suggesting stimulation of native dechlorination activity. Post-treatment monitoring detected increased concentrations of volatile fatty acids generated from the fermentation of residual-level Tween 80 surfactant. These field data suggest that Tween 80 not only induced and maintained anaerobiosis but also provided reducing equivalents to reductively dechlorinating populations present in the oligotrophic Bachman aquifer. Experience from this site supports application of staged treatment strategies that couple SEAR and microbial reductive dechlorination to enhance mass removal and reduce contaminant mass flux emanating from treated source zones.

  4. [Deep brain stimulation in the treatment of torticollis and Meige syndrome].

    PubMed

    Sobstyl, Michał; Ząbek, Mirosław

    2011-01-01

    Deep brain stimulation (DBS) is an established and accepted treatment modality of generalized dystonia. The stereotactic target to be approached with DBS leads is the internal segment of the globus pallidus (GPi). Bilateral GPi stimulation in patients suffering from primary generalized dystonia reduced dystonic movement not only in the trunk and limbs but also in the neck and face. These observations have led to the use of GPi stimulation in patients with severe torticollis and Meige syndrome refractory to pharmacological agents as well to botulinum toxin injections. An increasing number of reports indicate the effectiveness of GPi stimulation in the treatment of intractable focal and segmental dystonia. Moreover, DBS can be performed simultaneously on both sides during one operative session. This treatment modality is reversible and safer when compared to stereotactic ablative techniques. In future, DBS can become an alternative treatment for intractable focal and segmental dystonia.

  5. Oleic acid stimulates system A amino acid transport in primary human trophoblast cells mediated by toll-like receptor 4.

    PubMed

    Lager, Susanne; Gaccioli, Francesca; Ramirez, Vanessa I; Jones, Helen N; Jansson, Thomas; Powell, Theresa L

    2013-03-01

    Obese women have an increased risk to deliver large babies. However, the mechanisms underlying fetal overgrowth in these pregnancies are not well understood. Obese pregnant women typically have elevated circulating lipid levels. We tested the hypothesis that fatty acids stimulate placental amino acid transport, mediated via toll-like receptor 4 (TLR4) and mammalian target of rapamycin (mTOR) signaling pathways. Circulating NEFA levels and placental TLR4 expression were assessed in women with varying prepregnancy body mass index (BMI). The effects of oleic acid on system A and system L amino acid transport, and on the activation of the mTOR (4EBP1, S6K1, rpS6), TLR4 (IĸB, JNK, p38 MAPK), and STAT3 signaling pathways were determined in cultured primary human trophoblast cells. Maternal circulating NEFAs (n = 33), but not placental TLR4 mRNA expression (n = 16), correlated positively with BMI (P < 0.05). Oleic acid increased trophoblast JNK and STAT3 phosphorylation (P < 0.05), whereas mTOR activity was unaffected. Furthermore, oleic acid doubled trophoblast system A activity (P < 0.05), without affecting system L activity. siRNA-mediated silencing of TLR4 expression prevented the stimulatory effect of oleic acid on system A activity. Our data suggest that maternal fatty acids can increase placental nutrient transport via TLR4, thereby potentially affecting fetal growth.

  6. Acetic Acid Acts as a Volatile Signal To Stimulate Bacterial Biofilm Formation

    PubMed Central

    Chen, Yun; Gozzi, Kevin; Yan, Fang

    2015-01-01

    ABSTRACT Volatiles are small air-transmittable chemicals with diverse biological activities. In this study, we showed that volatiles produced by the bacterium Bacillus subtilis had a profound effect on biofilm formation of neighboring B. subtilis cells that grew in proximity but were physically separated. We further demonstrated that one such volatile, acetic acid, is particularly potent in stimulating biofilm formation. Multiple lines of genetic evidence based on B. subtilis mutants that are defective in either acetic acid production or transportation suggest that B. subtilis uses acetic acid as a metabolic signal to coordinate the timing of biofilm formation. Lastly, we investigated how B. subtilis cells sense and respond to acetic acid in regulating biofilm formation. We showed the possible involvement of three sets of genes (ywbHG, ysbAB, and yxaKC), all encoding putative holin-antiholin-like proteins, in cells responding to acetic acid and stimulating biofilm formation. All three sets of genes were induced by acetate. A mutant with a triple mutation of those genes showed a severe delay in biofilm formation, whereas a strain overexpressing ywbHG showed early and robust biofilm formation. Results of our studies suggest that B. subtilis and possibly other bacteria use acetic acid as a metabolic signal to regulate biofilm formation as well as a quorum-sensing-like airborne signal to coordinate the timing of biofilm formation by physically separated cells in the community. PMID:26060272

  7. Methyl jasmonate stimulates biosynthesis of 2-phenylethylamine, phenylacetic acid and 2-phenylethanol in seedlings of common buckwheat.

    PubMed

    Horbowicz, Marcin; Wiczkowski, Wiesław; Sawicki, Tomasz; Szawara-Nowak, Dorota; Sytykiewicz, Hubert; Mitrus, Joanna

    2015-01-01

    Methyl jasmonate has a strong effect on secondary metabolizm in plants, by stimulating the biosynthesis a number of phenolic compounds and alkaloids. Common buckwheat (Fagopyrum esculentum Moench) is an important source of biologically active compounds. This research focuses on the detection and quantification of 2-phenylethylamine and its possible metabolites in the cotyledons, hypocotyl and roots of common buckwheat seedlings treated with methyl jasmonate. In cotyledons of buckwheat sprouts, only traces of 2-phenylethylamine were found, while in the hypocotyl and roots its concentration was about 150 and 1000-times higher, respectively. Treatment with methyl jasmonate resulted in a 4-fold increase of the 2-phenylethylamine level in the cotyledons of 7-day buckwheat seedlings, and an 11-fold and 5-fold increase in hypocotyl and roots, respectively. Methyl jasmonate treatment led also to about 4-fold increase of phenylacetic acid content in all examined seedling organs, but did not affect the 2-phenylethanol level in cotyledons, and slightly enhanced in hypocotyl and roots. It has been suggested that 2-phenylethylamine is a substrate for the biosynthesis of phenylacetic acid and 2-phenylethanol, as well as cinnamoyl 2-phenethylamide. In organs of buckwheat seedling treated with methyl jasmonate, higher amounts of aromatic amino acid transaminase mRNA were found. The enzyme can be involved in the synthesis of phenylpyruvic acid, but the presence of this compound could not be confirmed in any of the examined organs of common buckwheat seedling.

  8. 10-oxo-12(Z)-octadecenoic acid, a linoleic acid metabolite produced by gut lactic acid bacteria, potently activates PPARγ and stimulates adipogenesis

    SciTech Connect

    Goto, Tsuyoshi; Kim, Young-Il; Furuzono, Tomoya; Takahashi, Nobuyuki; Yamakuni, Kanae; Yang, Ha-Eun; Li, Yongjia; Ohue, Ryuji; Nomura, Wataru; Sugawara, Tatsuya; Yu, Rina; Kitamura, Nahoko; and others

    2015-04-17

    Our previous study has shown that gut lactic acid bacteria generate various kinds of fatty acids from polyunsaturated fatty acids such as linoleic acid (LA). In this study, we investigated the effects of LA and LA-derived fatty acids on the activation of peroxisome proliferator-activated receptors (PPARs) which regulate whole-body energy metabolism. None of the fatty acids activated PPARδ, whereas almost all activated PPARα in luciferase assays. Two fatty acids potently activated PPARγ, a master regulator of adipocyte differentiation, with 10-oxo-12(Z)-octadecenoic acid (KetoA) having the most potency. In 3T3-L1 cells, KetoA induced adipocyte differentiation via the activation of PPARγ, and increased adiponectin production and insulin-stimulated glucose uptake. These findings suggest that fatty acids, including KetoA, generated in gut by lactic acid bacteria may be involved in the regulation of host energy metabolism. - Highlights: • Most LA-derived fatty acids from gut lactic acid bacteria potently activated PPARα. • Among tested fatty acids, KetoA and KetoC significantly activated PPARγ. • KetoA induced adipocyte differentiation via the activation of PPARγ. • KetoA enhanced adiponectin production and glucose uptake during adipogenesis.

  9. Stimulation of acid secretion and phosphoinositol production by rat parietal cell muscarinic M sub 2 receptors

    SciTech Connect

    Pfeiffer, A.; Rochlitz, H.; Herz, A.; Paumgartner, G. )

    1988-04-01

    The muscarinic receptor system involved in hydrogen production by enriched rat gastric parietal cells was investigated. Muscarinic receptor density determined by (N-methyl-{sup 3}H)scopolamine binding was 8,100/cell. The receptor appeared to be of the M{sub 2} muscarinic receptor subtype, since it had a low affinity (K{sub d} 189 nM) for the M{sub 1} receptor antagonist pirenzepine compared with atropine. Receptor activation by carbachol rapidly augmented levels of polyphosphoinositides, indicating an activation of phospholipase C. The dose-response relations for the increase in inositol phosphates closely paralleled the binding of carbachol to muscarinic receptors. The inositol phosphate response was antagonized by pirenzepine with a K{sub i} of 177 nM. the stimulation of inositol phosphate levels by carbachol correlated well with the stimulation of ({sup 14}C)aminopyrine uptake, determine as an index of acid secretion. The muscarinic agonists oxotremorine, pilocarpine, and bethanechol elicited partial increases in inositol phosphates at maximal drug concentrations, and these partial increases correlated with their ability to stimulate ({sup 14}C)aminopyrine uptake. These data indicate that inositolpolyphosphates may be a second messenger of M{sub 2} receptors stimulating acid secretion.

  10. Regulation by retinoic acid of acylation-stimulating protein and complement C3 in human adipocytes.

    PubMed Central

    Scantlebury, T; Sniderman, A D; Cianflone, K

    2001-01-01

    Acylation-stimulating protein (ASP), a product of complement C3, stimulates triacylglycerol synthesis in adipocytes. Previous studies have identified transthyretin, associated with chylomicrons, as a stimulator of C3 and ASP production. Since both transthyretin and chylomicrons transport retinyl ester/retinol, our goal was to investigate whether retinoic acid (RA) could be a potential hormonal mediator of the effect. Inhibitors of protein synthesis and protein secretion eliminated the stimulatory effects of chylomicrons on both C3 and ASP production in human differentiated adipocytes, suggesting that de novo protein synthesis and secretion are both required. Incubation with chylomicrons increased C3 mRNA levels (37+/-1.5%). RA alone or with chylomicrons had a stimulatory effect on C3 production (29-fold at 16.6 nM RA) and ASP production. An RA receptor antagonist blocked stimulation of C3 mRNA and C3 secretion by both RA and chylomicrons. Finally, RA and chylomicrons activated a 1.8 kb C3-promoter-luciferase construct transfected into 3T3-F442 and 3T3-L1 cells (by 41+/-0.2% and 69+/-0.3% respectively), possibly via RA receptor half-sites identified by sequence analysis. This is the first evidence documenting stimulation by RA of the C3 gene. Thus we propose RA as a novel cellular trigger in chylomicrons that subsequently results in increased ASP production by adipocytes after a meal. PMID:11368771

  11. Electrical stimulation for the treatment of lower urinary tract dysfunction after spinal cord injury

    PubMed Central

    McGee, Meredith J.; Amundsen, Cindy L.; Grill, Warren M.

    2015-01-01

    Electrical stimulation for bladder control is an alternative to traditional methods of treating neurogenic lower urinary tract dysfunction (NLUTD) resulting from spinal cord injury (SCI). In this review, we systematically discuss the neurophysiology of bladder dysfunction following SCI and the applications of electrical stimulation for bladder control following SCI, spanning from historic clinical approaches to recent pre-clinical studies that offer promising new strategies that may improve the feasibility and success of electrical stimulation therapy in patients with SCI. Electrical stimulation provides a unique opportunity to control bladder function by exploiting neural control mechanisms. Our understanding of the applications and limitations of electrical stimulation for bladder control has improved due to many pre-clinical studies performed in animals and translational clinical studies. Techniques that have emerged as possible opportunities to control bladder function include pudendal nerve stimulation and novel methods of stimulation, such as high frequency nerve block. Further development of novel applications of electrical stimulation will drive progress towards effective therapy for SCI. The optimal solution for restoration of bladder control may encompass a combination of efficient, targeted electrical stimulation, possibly at multiple locations, and pharmacological treatment to enhance symptom control. PMID:25582564

  12. Nitrogenous compounds stimulate glucose-derived acid production by oral Streptococcus and Actinomyces.

    PubMed

    Norimatsu, Yuka; Kawashima, Junko; Takano-Yamamoto, Teruko; Takahashi, Nobuhiro

    2015-09-01

    Both Streptococcus and Actinomyces can produce acids from dietary sugars and are frequently found in caries lesions. In the oral cavity, nitrogenous compounds, such as peptides and amino acids, are provided continuously by saliva and crevicular gingival fluid. Given that these bacteria can also utilize nitrogen compounds for their growth, it was hypothesized that nitrogenous compounds may influence their acid production; however, no previous studies have examined this topic. Therefore, the present study aimed to assess the effects of nitrogenous compounds (tryptone and glutamate) on glucose-derived acid production by Streptococcus and Actinomyces. Acid production was evaluated using a pH-stat method under anaerobic conditions, whereas the amounts of metabolic end-products were quantified using high performance liquid chromatography. Tryptone enhanced glucose-derived acid production by up to 2.68-fold, whereas glutamate enhanced Streptococcus species only. However, neither tryptone nor glutamate altered the end-product profiles, indicating that the nitrogenous compounds stimulate the whole metabolic pathways involving in acid production from glucose, but are not actively metabolized, nor do they alter metabolic pathways. These results suggest that nitrogenous compounds in the oral cavity promote acid production by Streptococcus and Actinomyces in vivo.

  13. Inhibition of bladder overactivity by duloxetine in combination with foot stimulation or WAY-100635 treatment in cats.

    PubMed

    Schwen, Zeyad; Matsuta, Yosuke; Shen, Bing; Wang, Jicheng; Roppolo, James R; de Groat, William C; Tai, Changfeng

    2013-12-15

    The purpose of this study was to determine whether duloxetine [a serotonin (5-HT)-norepinephrine reuptake inhibitor] combined with transcutaneous foot stimulation or WAY-100635 (a 5-HT1A antagonist) can enhance inhibition of bladder overactivity in cats. Cystometrograms were performed on eight cats under α-chloralose anesthesia by infusing saline and then 0.25% acetic acid (AA) to induce bladder overactivity. To inhibit bladder overactivity, foot stimulation (5 Hz) was applied via transcutaneous pad electrodes to the right hindfoot at two and four times the threshold intensity for inducing a toe twitch. Duloxetine (0.003-3 mg/kg) was administered intravenously to determine the effect of combination treatment. After the 3 mg/kg dose of duloxetine, WAY-100635 (0.5 mg/kg) was given intravenously. AA irritation significantly (P < 0.0001) reduced bladder capacity to 42.7 ± 7.4% of the saline control capacity. Foot stimulation alone at both two and four times the threshold intensity significantly (P < 0.0001) inhibited bladder overactivity and increased bladder capacity to 66.7 ± 6.3% and 85.7 ± 6.5% of the saline control, respectively. Duloxetine alone dose dependently inhibited bladder overactivity and completely restored bladder capacity to the saline control (109 ± 15.5%) at 3 mg/kg. Although duloxetine combined with foot stimulation did not further enhance inhibition, WAY-100635 (0.5 mg/kg) given after 3 mg/kg duloxetine further increased (P = 0.008) bladder capacity to 162.2 ± 22.5% of the saline control. Although duloxetine and foot stimulation independently inhibited bladder overactivity, combined treatment did not enhance inhibition. Duloxetine combined with WAY-100635, however, synergistically enhanced bladder inhibition, indicating a potential novel treatment for overactive bladder if duloxetine is combined with a 5-HT1A receptor antagonist drug. PMID:24154699

  14. α-Tocopheryloxyacetic acid: a novel chemotherapeutic that stimulates the antitumor immune response

    PubMed Central

    2011-01-01

    Introduction α-Tocopheryloxyacetic acid (α-TEA) is a novel ether derivative of α-tocopherol that has generated interest as a chemotherapeutic agent because of its selective toxicity toward tumor cells and its ability to suppress tumor growth in various rodent and human xenograft models. We previously reported that oral α-TEA inhibited the growth of both a transplanted (4T1) and a spontaneous MMTV-PyMT mouse model of breast cancer. Methods Because little is known about the possible immunological mechanisms underlying the in vivo α-TEA effects, we evaluated the impact of α-TEA therapy on the immune response by characterizing immune cell populations infiltrating the tumor site. Results α-TEA treatment resulted in higher frequencies of activated T cells in the tumor microenvironment and twofold and sixfold higher ratios of CD4+ and CD8+ T cells to regulatory T cells, respectively. This finding was correlated with an increased ability of tumor-draining lymph node cells and splenocytes from α-TEA-treated mice to secrete interferon (IFN)-γ in response to CD3 or to mediate a cytolytic response in a tumor-specific fashion, respectively. That the α-TEA-mediated antitumor effect had a T cell-dependent component was demonstrated by the partial abrogation of tumor suppression when CD4+ and CD8+ T cells were depleted. We also determined the intratumoral cytokine and chemokine profile and found that α-TEA treatment increased intratumoral IFN-γ levels but decreased interleukin (IL)-4 levels, suggesting a shift toward a TH1 response. In addition, α-TEA induced higher levels of the inflammatory cytokine IL-6 and the chemokine CCL5. Conclusions Taken together, these data suggest that α-TEA treatment, in addition to its direct cytotoxic effects, enhanced the anti-tumor immune response. This study provides a better understanding of the mechanisms of action of α-TEA and its effect on the immune system and may prove useful in designing immune-stimulating strategies to

  15. Receptor-mediated uptake of low density lipoprotein stimulates bile acid synthesis by cultured rat hepatocytes

    SciTech Connect

    Junker, L.H.; Davis, R.A. )

    1989-12-01

    The cellular mechanisms responsible for the lipoprotein-mediated stimulation of bile acid synthesis in cultured rat hepatocytes were investigated. Adding 280 micrograms/ml of cholesterol in the form of human or rat low density lipoprotein (LDL) to the culture medium increased bile acid synthesis by 1.8- and 1.6-fold, respectively. As a result of the uptake of LDL, the synthesis of (14C)cholesterol from (2-14C)acetate was decreased and cellular cholesteryl ester mass was increased. Further studies demonstrated that rat apoE-free LDL and apoE-rich high density lipoprotein (HDL) both stimulated bile acid synthesis 1.5-fold, as well as inhibited the formation of (14C)cholesterol from (2-14C)acetate. Reductive methylation of LDL blocked the inhibition of cholesterol synthesis, as well as the stimulation of bile acid synthesis, suggesting that these processes require receptor-mediated uptake. To identify the receptors responsible, competitive binding studies using 125I-labeled apoE-free LDL and 125I-labeled apoE-rich HDL were performed. Both apoE-free LDL and apoE-rich HDL displayed an equal ability to compete for binding of the other, suggesting that a receptor or a group of receptors that recognizes both apolipoproteins is involved. Additional studies show that hepatocytes from cholestyramine-treated rats displayed 2.2- and 3.4-fold increases in the binding of apoE-free LDL and apoE-rich HDL, respectively. These data show for the first time that receptor-mediated uptake of LDL by the liver is intimately linked to processes activating bile acid synthesis.

  16. Propionic acid and butyric acid inhibit lipolysis and de novo lipogenesis and increase insulin-stimulated glucose uptake in primary rat adipocytes.

    PubMed

    Heimann, Emilia; Nyman, Margareta; Degerman, Eva

    2015-01-01

    Fermentation of dietary fibers by colonic microbiota generates short-chain fatty acids (SCFAs), e.g., propionic acid and butyric acid, which have been described to have "anti-obesity properties" by ameliorating fasting glycaemia, body weight and insulin tolerance in animal models. In the present study, we therefore investigate if propionic acid and butyric acid have effects on lipolysis, de novo lipogenesis and glucose uptake in primary rat adipocytes. We show that both propionic acid and butyric acid inhibit isoproterenol- and adenosine deaminase-stimulated lipolysis as well as isoproterenol-stimulated lipolysis in the presence of a phosphodiesterase (PDE3) inhibitor. In addition, we show that propionic acid and butyric acid inhibit basal and insulin-stimulated de novo lipogenesis, which is associated with increased phosphorylation and thus inhibition of acetyl CoA carboxylase, a rate-limiting enzyme in fatty acid synthesis. Furthermore, we show that propionic acid and butyric acid increase insulin-stimulated glucose uptake. To conclude, our study shows that SCFAs have effects on fat storage and mobilization as well as glucose uptake in rat primary adipocytes. Thus, the SCFAs might contribute to healthier adipocytes and subsequently also to improved energy metabolism with for example less circulating free fatty acids, which is beneficial in the context of obesity and type 2 diabetes. PMID:26167409

  17. The effects of somatostatin and metiamide on tachyphylaxis of pentagastrin stimulated gastric acid and pepsin secretion in the conscious cat.

    PubMed Central

    Albinus, M; Blair, E L; Hirst, B H; Reed, J D; Schally, A V; Shaw, B

    1977-01-01

    1. Pentagastrin stimulated gastric acid and pepsin secretions show parallel rates of tachyphylaxis in the conscious cat. The responses to histamine show only slight tachyphylaxis. 2. Somatostatin 10 microng.kg(-1).hr(-1) inhibits pentagastrin but not histamine stimulated acid secretion and inhibits pentagastrin stimulated pepsin secretion. 3. The inhibition of pentagastrin stimulated acid and pepsin secretion by Somatostatin delays the tachyphylaxis of these responses, but the rates of tachyphylaxis when they do subsequently occur are identical. 4. Metiamide 10 mg-kg(-1)-hr(-1) equally inhibits histamine and pentagastrin stimulated acid secretion but does not inhibit pentagastrin stimulated pepsin secretion. 5. Inhibiton of acid secretion during metiamide infusion neither prevents nor delays acid nor pepsin tachyphylaxis. 6. It is suggested that tachyphylaxis of acid and pepsin secretion is a gastrin receptor phenomenon and that Somatostatin occupies or modifies the behaviour of these receptors, preventing tachyphylaxis. Metiamide, however, exerts its action only on the histmine H2-receptor and not the gastrin receptor mechanism, and this apparently does not prevent or delay acid tachyphylaxis. PMID:325196

  18. The effects of somatostatin and metiamide on tachyphylaxis of pentagastrin stimulated gastric acid and pepsin secretion in the conscious cat.

    PubMed

    Albinus, M; Blair, E L; Hirst, B H; Reed, J D; Schally, A V; Shaw, B

    1977-04-01

    1. Pentagastrin stimulated gastric acid and pepsin secretions show parallel rates of tachyphylaxis in the conscious cat. The responses to histamine show only slight tachyphylaxis. 2. Somatostatin 10 microng.kg(-1).hr(-1) inhibits pentagastrin but not histamine stimulated acid secretion and inhibits pentagastrin stimulated pepsin secretion. 3. The inhibition of pentagastrin stimulated acid and pepsin secretion by Somatostatin delays the tachyphylaxis of these responses, but the rates of tachyphylaxis when they do subsequently occur are identical. 4. Metiamide 10 mg-kg(-1)-hr(-1) equally inhibits histamine and pentagastrin stimulated acid secretion but does not inhibit pentagastrin stimulated pepsin secretion. 5. Inhibiton of acid secretion during metiamide infusion neither prevents nor delays acid nor pepsin tachyphylaxis. 6. It is suggested that tachyphylaxis of acid and pepsin secretion is a gastrin receptor phenomenon and that Somatostatin occupies or modifies the behaviour of these receptors, preventing tachyphylaxis. Metiamide, however, exerts its action only on the histmine H2-receptor and not the gastrin receptor mechanism, and this apparently does not prevent or delay acid tachyphylaxis.

  19. Electrical carotid sinus stimulation: chances and challenges in the management of treatment resistant arterial hypertension.

    PubMed

    Chobanyan-Jürgens, Kristine; Jordan, Jens

    2015-09-01

    Treatment resistant arterial hypertension is associated with excess cardiovascular morbidity and mortality. Electrical carotid sinus stimulators engaging baroreflex afferent activity have been developed for such patients. Indeed, baroreflex mechanisms contribute to long-term blood pressure control by governing efferent sympathetic and parasympathetic activity. The first-generation carotid sinus stimulator applying bilateral bipolar stimulation reduced blood pressure in a controlled clinical trial but nevertheless failed to meet the primary efficacy endpoint. The second-generation device utilizes smaller unilateral unipolar electrodes, thus decreasing invasiveness of the implantation while saving battery. An uncontrolled clinical study suggested improvement in blood pressure with the second-generation device. We hope that these findings as well as preliminary observations suggesting cardiovascular and renal organ protection with electrical carotid sinus stimulation will be confirmed in properly controlled clinical trials. Meanwhile, we should find ways to better identify patients who are most likely to benefit from electrical carotid sinus stimulation.

  20. Electrical stimulation of the hypoglossal nerve in the treatment of obstructive sleep apnea.

    PubMed

    Kezirian, Eric J; Boudewyns, An; Eisele, David W; Schwartz, Alan R; Smith, Philip L; Van de Heyning, Paul H; De Backer, Wilfried A

    2010-10-01

    Upper airway occlusion in obstructive sleep apnea has been attributed to a decline in pharyngeal neuromuscular activity occurring in a structurally narrowed airway. Surgical treatment focuses on the correction of anatomic abnormalities, but there is a potential role for activation of the upper airway musculature, especially with stimulation of the hypoglossal nerve and genioglossus muscle. We present evidence from research on upper airway neuromuscular electrical stimulation in animals and humans. We also present results from eight obstructive sleep apnea patients with a fully implanted system for hypoglossal nerve stimulation, demonstrating an improvement in upper airway collapsibility and obstructive sleep apnea severity. Future research, including optimization of device features and stimulation parameters as well as patient selection, is necessary to make hypoglossal nerve stimulation a viable alternative to positive airway pressure therapy and upper airway surgical procedures.

  1. Acid mine treatment with open limestone channels

    SciTech Connect

    Ziemkiewicz, P.F.; Brant, D.L.; Skousen, J.G.

    1996-12-31

    Acid mine drainage (AMD) is often associated with mining of pyritic coal and metal deposits. Typical AMD associated with coal mines in the eastern US can have acidity and iron concentrations ranging from the teens to the thousands of mg/l. Aluminum and manganese can be present in concentrations ranging from zero to the low hundreds of mg/l. Much attention has been devoted to developing inexpensive, limestone (LS)-based systems for treating AMID with little or no maintenance. However, LS tends to coat with metal hydroxides when exposed to AMID in an oxidized state, a process known as {open_quotes}armoring{close_quotes}. It is generally assumed that once armored, LS ceases to neutralize acid. Another problem is that the hydroxides tend to settle into plug the pore spaces in LS beds forcing water to move around rather than through the LS. While both are caused by the precipitation of metal hydroxides, armoring and plugging are two different problems. Plugging of LS pores can be avoided by maintaining a high flushing rate through the LS bed. Armoring, however, occurs regardless of water velocity. This study investigated the influence of armoring on LS solubility and the implications of armoring and plugging on the construction of open (oxidizing) LS channels for treating AMD. We evaluated the AMID treatment performance of armored and unarmored LS in oxidizing environments both in laboratory and field studies.

  2. Attenuated acute salivary α-amylase responses to gustatory stimulation with citric acid in thin children.

    PubMed

    Chen, Long Hui; Yang, Ze Min; Chen, Wei Wen; Lin, Jing; Zhang, Min; Yang, Xiao Rong; Zhao, Ling Bo

    2015-04-14

    Salivary α-amylase (sAA) is responsible for the 'pre-digestion' of starch in the oral cavity and accounts for up to 50 % of salivary protein in human saliva. An accumulating body of literature suggests that sAA is of nutritional importance; however, it is still not clear how sAA is related to individual's nutritional status. Although copy number variations (CNV) of the salivary amylase gene (AMY1) are associated with variation in sAA levels, a significant amount of sAA variation is not explained by AMY1 CNV. To measure sAA responses to gustatory stimulation with citric acid, we used sAA ratio (the ratio of stimulated sAA levels to those of resting sAA) and investigated acute sAA responses to citric acid in children with normal (Normal-BMI, n 22) and low (Low-BMI, n 21) BMI. The AMY1 gene copy number was determined by quantitative PCR. We, for the first time, demonstrated attenuated acute sAA responses (decreased sAA ratio) to gustatory stimulation in Low-BMI (thinness grade 3) children compared with the Normal-BMI children, which suggest that sAA responses to gustatory stimulation may be of nutritional importance. However, child's nutritional status was not directly related to their resting or stimulated sAA levels, and it was not associated with AMY1 gene copy number. Finally, AMY1 CNV might influence, but did not eventually determine, sAA levels in children. PMID:25784372

  3. Retinoic acid and 1,25-dihydroxyvitamin D3 stimulate osteoclast formation by different mechanisms

    SciTech Connect

    Scheven, B.A.; Hamilton, N.J. )

    1990-01-01

    The effects of retinoic acid (RA) and 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) on osteoclast formation were examined in intact fetal long bones of different ages/developmental stages maintained in organ culture using a chemically defined medium with or without the presence of serum. Besides stimulating bone resorption, RA and 1,25-(OH)2D3 increased the number of osteoclasts in 19-day-old fetal rat tibiae. Likewise, these bone-resorbing agents induced and stimulated osteoclast formation in 19- and 18-day-old metatarsal bones which were osteoclast-free at the beginning of the culture. The response to 1,25-(OH)2D3 was greatly enhanced by 10% fetal bovine serum (FBS) irrespective of the developmental stage of the long bone. The response to RA was not. Light microscopic autoradiography after labeling of the cultures with tritiated thymidine showed that both RA and 1,25-(OH)2D3 induced osteoclast differentiation from proliferating and postmitotic precursors. However, neither agent was able to stimulate proliferation of osteoclast progenitor cells in the older bones (19 days). Studies on the formation of osteoclast-like (tartrate-resistant acid phosphatase positive) cells in bone marrow cultures indicated that FBS was a potent inducer of osteoclast-like cell formation. In the presence of FBS, 1,25-(OH)2D3 significantly stimulated this response, but RA did not. The results demonstrate that although both RA and 1,25-(OH)2D3 stimulate osteoclast formation from proliferating and postmitotic precursors in long bones in vitro, they do so by different mechanisms.

  4. Attenuated acute salivary α-amylase responses to gustatory stimulation with citric acid in thin children.

    PubMed

    Chen, Long Hui; Yang, Ze Min; Chen, Wei Wen; Lin, Jing; Zhang, Min; Yang, Xiao Rong; Zhao, Ling Bo

    2015-04-14

    Salivary α-amylase (sAA) is responsible for the 'pre-digestion' of starch in the oral cavity and accounts for up to 50 % of salivary protein in human saliva. An accumulating body of literature suggests that sAA is of nutritional importance; however, it is still not clear how sAA is related to individual's nutritional status. Although copy number variations (CNV) of the salivary amylase gene (AMY1) are associated with variation in sAA levels, a significant amount of sAA variation is not explained by AMY1 CNV. To measure sAA responses to gustatory stimulation with citric acid, we used sAA ratio (the ratio of stimulated sAA levels to those of resting sAA) and investigated acute sAA responses to citric acid in children with normal (Normal-BMI, n 22) and low (Low-BMI, n 21) BMI. The AMY1 gene copy number was determined by quantitative PCR. We, for the first time, demonstrated attenuated acute sAA responses (decreased sAA ratio) to gustatory stimulation in Low-BMI (thinness grade 3) children compared with the Normal-BMI children, which suggest that sAA responses to gustatory stimulation may be of nutritional importance. However, child's nutritional status was not directly related to their resting or stimulated sAA levels, and it was not associated with AMY1 gene copy number. Finally, AMY1 CNV might influence, but did not eventually determine, sAA levels in children.

  5. Scale-up laccase production from Trametes versicolor stimulated by vanillic acid.

    PubMed

    Wang, Ke-Feng; Hu, Jian-Hua; Guo, Chen; Liu, Chun-Zhao

    2016-07-01

    An efficient strategy for laccase production in Trametes versicolor cultures was developed using vanillic acid as the inducer. The optimized vanillic acid treatment strategy consisted of exposing 2-day-old mycelia cultures to 80 mg/L vanillic acid. After 4 days, laccase activity of 588.84 U/L was achieved in flasks which represented a 1.79-fold increase compared to the control. In 200-L airlift bioreactor, the maximal laccase activity reached up to 785.12 U/L using the optimized vanillic acid treatment strategy. The zymograms of culture supernatants revealed three bands with laccase activity, among which Lac1 and Lac2 were abundant laccase isoforms constitutively expressed, and Lac3 was an inducible isozyme by vanillic acid. The results of real-time quantitative PCR showed that the transcription level of lcc in T. versicolor cultures grown with vanillic acid for 7 days was about 5.64-fold greater than that without vanillic acid in flasks. In 200-L airlift bioreactor cultures of T. versicolor with addition of vanillic acid, the transcript level of lcc at day 7 was 2.62-fold higher than that in flasks with vanillic acid due to the good mass transfer and oxygen supply in the bioreactor system. This study provides a basis for understanding the induction mechanism of vanillic acid for laccase production and has good potential for industrial applications. PMID:26971792

  6. Successful Treatment of Dercum's Disease by Transcutaneous Electrical Stimulation

    PubMed Central

    Martinenghi, Sabina; Caretto, Amelia; Losio, Claudio; Scavini, Marina; Bosi, Emanuele

    2015-01-01

    Abstract Dercum's disease is a rare condition of painful subcutaneous growth of adipose tissue. Etiology is unknown and pain is difficult to control. We report the case of a 57-year-old man with generalized diffuse Dercum's disease, who improved after the treatment with transcutaneous frequency rhythmic electrical modulation system (FREMS). Treatment consisted in 4 cycles of 30 minutes FREMS sessions over a 6-month period. Measures of efficacy included pain assessment (visual analogue scale, VAS), adipose tissue thickness by magnetic resonance imaging, total body composition and regional fat mass by dual-energy X-ray absorptiometry, physical disability (Barthel index), and health status (Short Form-36 questionnaire). After FREMS treatment the patient's clinical conditions significantly improved, with reduction of pain on the VAS scale from 64 to 17 points, improvement of daily life abilities (the Barthel index increased from 12 to 18) and amelioration of health status (higher scores than baseline in all Short Form-36 domains). Furthermore, we documented a 12 mm reduction in subcutaneous adipose tissue thickness at the abdominal wall and a 7040 g decrease in total body fat mass. FREMS therapy proved to be effective and safe in the treatment of this rare and disabling condition.

  7. Successful Treatment of Dercum's Disease by Transcutaneous Electrical Stimulation

    PubMed Central

    Martinenghi, Sabina; Caretto, Amelia; Losio, Claudio; Scavini, Marina; Bosi, Emanuele

    2015-01-01

    Abstract Dercum's disease is a rare condition of painful subcutaneous growth of adipose tissue. Etiology is unknown and pain is difficult to control. We report the case of a 57-year-old man with generalized diffuse Dercum's disease, who improved after the treatment with transcutaneous frequency rhythmic electrical modulation system (FREMS). Treatment consisted in 4 cycles of 30 minutes FREMS sessions over a 6-month period. Measures of efficacy included pain assessment (visual analogue scale, VAS), adipose tissue thickness by magnetic resonance imaging, total body composition and regional fat mass by dual-energy X-ray absorptiometry, physical disability (Barthel index), and health status (Short Form-36 questionnaire). After FREMS treatment the patient's clinical conditions significantly improved, with reduction of pain on the VAS scale from 64 to 17 points, improvement of daily life abilities (the Barthel index increased from 12 to 18) and amelioration of health status (higher scores than baseline in all Short Form-36 domains). Furthermore, we documented a 12 mm reduction in subcutaneous adipose tissue thickness at the abdominal wall and a 7040 g decrease in total body fat mass. FREMS therapy proved to be effective and safe in the treatment of this rare and disabling condition. PMID:26091459

  8. Luminal Nalpha-methyl histamine stimulates gastric acid secretion in duodenal ulcer patients via releasing gastrin.

    PubMed

    Konturek, P C; Konturek, S J; Sito, E; Kwiecien, N; Obtulowicz, W; Bielanski, W; Hahn, E G

    2001-01-26

    Nalpha-methyl histamine is an unusual histamine metabolite which is produced in the stomach infected by Helicobacter pylori and which was shown in animals to stimulate gastric acid secretion and to release gastrin in vitro isolated G-cells, but no information is available regarding its influence on gastric secretion and gastrin release in duodenal ulcer patients before and after H. pylori eradication. In this study, we compared the effects of intragastric administration of single or graded doses of Nalpha-methyl histamine on gastric acid secretion and plasma gastrin levels in 16 male duodenal ulcer patients (aging from 35 to 48 years and weighing 65-82 kg) before and after the eradication of H. pylori. Furthermore, the gastric luminal histamine and gastrin contents were determined before and after H. pylori eradication. In H. pylori-infected duodenal ulcer patients, the intragastric application of Nalpha-methyl histamine failed to affect gastric acid secretion or plasma gastrin levels. Following eradication of H. pylori, gastric luminal histamine and gastrin, and both basal gastric acid secretion and plasma gastrin levels, were significantly reduced. Nalpha-methyl histamine given intragastrically in graded doses to such H. pylori-eradicated duodenal ulcer patients was found to increase dose-dependently gastric acid output reaching at a dose of 5 mg, about 80% of histamine maximum induced by i.v. infusion of 25 microg/kg h of histamine dihydrochloride. We conclude that Nalpha-methyl histamine is a potent luminally active stimulant of gastrin release and gastric acid secretion in H. pylori-eradicated patients when luminal histamine is low but is not effective in H. pylori infected patients when luminal histamine is enhanced, possibly due to desensitization of gastrin (G-cells) and acid-producing (parietal) cells by Nalpha-methyl histamine produced excessively in H. pylori-infected stomach.

  9. CAR and PXR agonists stimulate hepatic bile acid and bilirubin detoxification and elimination pathways in mice.

    PubMed

    Wagner, Martin; Halilbasic, Emina; Marschall, Hanns-Ulrich; Zollner, Gernot; Fickert, Peter; Langner, Cord; Zatloukal, Kurt; Denk, Helmut; Trauner, Michael

    2005-08-01

    Induction of hepatic phase I/II detoxification enzymes and alternative excretory pumps may limit hepatocellular accumulation of toxic biliary compounds in cholestasis. Because the nuclear xenobiotic receptors constitutive androstane receptor (CAR) and pregnane X receptor (PXR) regulate involved enzymes and transporters, we aimed to induce adaptive alternative pathways with different CAR and PXR agonists in vivo. Mice were treated with the CAR agonists phenobarbital and 1,4-bis-[2-(3,5-dichlorpyridyloxy)]benzene, as well as the PXR agonists atorvastatin and pregnenolone-16alpha-carbonitrile. Hepatic bile acid and bilirubin-metabolizing/detoxifying enzymes (Cyp2b10, Cyp3a11, Ugt1a1, Sult2a1), their regulatory nuclear receptors (CAR, PXR, farnesoid X receptor), and bile acid/organic anion and lipid transporters (Ntcp, Oatp1,2,4, Bsep, Mrp2-4, Mdr2, Abcg5/8, Asbt) in the liver and kidney were analyzed via reverse-transcriptase polymerase chain reaction and Western blotting. Potential functional relevance was tested in common bile duct ligation (CBDL). CAR agonists induced Mrp2-4 and Oatp2; PXR agonists induced only Mrp3 and Oatp2. Both PXR and CAR agonists profoundly stimulated bile acid-hydroxylating/detoxifying enzymes Cyp3a11 and Cyp2b10. In addition, CAR agonists upregulated bile acid-sulfating Sult2a1 and bilirubin-glucuronidating Ugt1a1. These changes were accompanied by reduced serum levels of bilirubin and bile acids in healthy and CBDL mice and by increased levels of polyhydroxylated bile acids in serum and urine of cholestatic mice. Atorvastatin significantly increased Oatp2, Mdr2, and Asbt, while other transporters and enzymes were moderately affected. In conclusion, administration of specific CAR or PXR ligands results in coordinated stimulation of major hepatic bile acid/bilirubin metabolizing and detoxifying enzymes and hepatic key alternative efflux systems, effects that are predicted to counteract cholestasis. PMID:15986414

  10. Some Organic Acids Acting as Stimulants of Recruitment and Feeding for the Formosan Subterranean Termite (Isoptera: Rhinotermitidae)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The feeding stimulating properties of 3 organic acids (salicylic, oxalic, and glucuronic acids) and 2 nitrogen containing compounds (uric acid, and glucosamine) for the Formosan subterranean termite were tested. A two choice test between cellulosic matrices with the compounds and blanks showed that...

  11. Percutaneous tibial nerve stimulation for treatment of overactive bladder and urinary retention in an elderly population.

    PubMed

    Zinkgraf, Kristine; Quinn, Annette O'Leary; Ketterhagen, Debra; Kreuziger, Betty; Stevenson, Katherine

    2009-01-01

    Percutaneous tibial nerve stimulation (PTNS) is a treatment option for patients who present with urinary urgency, frequency, urge incontinence, or urinary retention. When behavior modification and/or pharmacotherapy did not adequately relieve symptoms, this treatment was found to decrease incidence of overactive bladder or retention symptoms in the authors' patient population.

  12. Dopamine D2High receptors stimulated by phencyclidines, lysergic acid diethylamide, salvinorin A, and modafinil.

    PubMed

    Seeman, Philip; Guan, Hong-Chang; Hirbec, Hélène

    2009-08-01

    Although it is commonly stated that phencyclidine is an antagonist at ionotropic glutamate receptors, there has been little measure of its potency on other receptors in brain tissue. Although we previously reported that phencyclidine stimulated cloned-dopamine D2Long and D2Short receptors, others reported that phencyclidine did not stimulate D2 receptors in homogenates of rat brain striatum. This study, therefore, examined whether phencyclidine and other hallucinogens and psychostimulants could stimulate the incorporation of [(35)S]GTP-gamma-S into D2 receptors in homogenates of rat brain striatum, using the same conditions as previously used to study the cloned D2 receptors. Using 10 microM dopamine to define 100% stimulation, phencyclidine elicited a maximum incorporation of 46% in rat striata, with a half-maximum concentration of 70 nM for phencyclidine, when compared with 80 nM for dopamine, 89 nM for salvinorin A (48 nM for D2Long), 105 nM for lysergic acid diethylamide (LSD), 120 nM for R-modafinil, 710 nM for dizocilpine, 1030 nM for ketamine, and >10,000 nM for S-modafinil. These compounds also inhibited the binding of the D2-selective ligand [(3)H]domperidone. The incorporation was inhibited by the presence of 200 microM guanylylimidodiphosphate and also by D2 blockade, using 10 microM S-sulpiride, but not by D1 blockade with 10 microM SCH23390. Hypertonic buffer containing 150 mM NaCl inhibited the stimulation by phencyclidine, which may explain negative results by others. It is concluded that phencyclidine and other psychostimulants and hallucinogens can stimulate dopamine D2 receptors at concentrations related to their behavioral actions.

  13. Treatment of spasticity with repetitive magnetic stimulation; a double-blind placebo-controlled study.

    PubMed

    Nielsen, J F; Sinkjaer, T; Jakobsen, J

    1996-12-01

    The effect of repetitive magnetic stimulation on spasticity was evaluated in 38 patients with multiple sclerosis in a double-blind placebo-controlled study. One group was treated with repetitive magnetic stimulation (n = 21) and the other group with sham stimulation (n = 17). Both groups were treated twice daily for 7 consecutive days. Primary end-points of the study were changes in the patients self-score, in clinical spasticity score, and in the stretch reflex threshold. The self-score of ease of daily day activities improved by 22% (P = 0.007) after treatment and by 29% (P = 0.004) after sham stimulation. The clinical spasticity score improved -3.3 +/- 4.7 arbitrary unit (AU) in treated patients and 0.7 +/- 2.5 AU in sham stimulation (P = 0.003). The stretch reflex threshold increased 4.3 +/- 7.5 deg/s in treated patients and -3.8 +/- 9.7 deg/s in sham stimulation (P = 0.001). The data presented in this study supports the idea that repetitive magnetic stimulation has an antispastic effect in multiple sclerosis. Future studies should clarify the optimal treatment regimen.

  14. Electrical Stimulation as an Adjunctive Treatment of Painful and Sensory Diabetic Neuropathy

    PubMed Central

    Thakral, Gaurav; Kim, Paul J.; LaFontaine, Javier; Menzies, Robert; Najafi, Bijan; Lavery, Lawrence A.

    2013-01-01

    Background The objective of this review is to evaluate the use of electrical stimulation to treat diabetic neuropathy. Application of electrical stimulation may provide a novel treatment option for large and small fiber neuropathy in persons with diabetes. Large and small nerve neuropathy alters pain, proprioception, touch perception, and motor function, which cause burning foot pain and serve as protective mechanisms from ulcerations. Methods A content search for clinical trials involving electrical stimulation, neuropathy, and diabetes was conducted through PubMed. Randomized clinical trials and prospective studies with outcome measures affecting the lower extremity function were selected for review. Results We identified eight studies in which electrical stimulation was used to treat diabetic neuropathy. Six studies evaluated small fiber neuropathy. Two studies evaluated patients with both small and large fiber neuropathy and reported significant improvement in vibration and monofilament testing and reduction in symptoms in the electrical stimulation treatment group. Six of the eight painful neuropathy studies identified significant improvement in symptoms. There were no studies that evaluated electrical stimulation to treated diabetic motor neuropathy, fall prevention or postural instability. Conclusions Electrical stimulation may be an effective alternative and adjunctive therapy to current interventions for diabetic peripheral neuropathy. PMID:24124947

  15. Base cation stimulation of mycorrhization and photosynthesis of sugar maple on acid soils are coupled by foliar nutrient dynamics.

    PubMed

    St Clair, Samuel B; Lynch, Jonathan P

    2005-02-01

    The nutritional benefits that mycorrhizal associations provide to plants may be constrained by acidic soil conditions resulting in decreased photosynthetic function. Sugar maple (Acer saccharum) and red maple (Acer rubrum) seedlings were grown on a native acidic (pH 4.1) soil both unamended and amended with base cations (pH 6.2). In a second study a fungicide treatment was included. Foliar nutrition, mycorrhizal colonization, photosynthesis and their relationships were assessed. On the native soil, red maple maintained higher levels of mycorrhizal colonization and photosynthesis than sugar maple but showed little response to base cation amendments. Mycorrhizal colonization and photosynthesis of sugar maple increased significantly in response to base cation amendments. Correlations were observed among mycorrhizal colonization, foliar nutrition and photosynthesis. The fungicide treatment indicated that 50% of the base cation-induced increase in sugar maple photosynthesis was mycorrhiza related. The results suggest that base cation stimulation of mycorrhization and photosynthesis of sugar maple on acid soils are coupled by foliar nutrient dynamics. Red maple exhibits much less sensitivity to these same edaphic conditions.

  16. Stimulation of wound healing by helium atmospheric pressure plasma treatment

    NASA Astrophysics Data System (ADS)

    Vasile Nastuta, Andrei; Topala, Ionut; Grigoras, Constantin; Pohoata, Valentin; Popa, Gheorghe

    2011-03-01

    New experiments using atmospheric pressure plasma have found large application in treatment of living cells or tissues, wound healing, cancerous cell apoptosis, blood coagulation on wounds, bone tissue modification, sterilization and decontamination. In this study an atmospheric pressure plasma jet generated using a cylindrical dielectric-barrier discharge was applied for treatment of burned wounds on Wistar rats' skin. The low temperature plasma jet works in helium and is driven by high voltage pulses. Oxygen and nitrogen based impurities are identified in the jet by emission spectroscopy. This paper analyses the natural epithelization of the rats' skin wounds and two methods of assisted epithelization, a classical one using polyurethane wound dressing and a new one using daily atmospheric pressure plasma treatment of wounds. Systemic and local medical data, such as haematological, biochemical and histological parameters, were monitored during entire period of study. Increased oxidative stress was observed for plasma treated wound. This result can be related to the presence in the plasma volume of active species, such as O and OH radicals. Both methods, wound dressing and plasma-assisted epithelization, provided positive medical results related to the recovery process of burned wounds. The dynamics of the skin regeneration process was modified: the epidermis re-epitelization was accelerated, while the recovery of superficial dermis was slowed down.

  17. Ursodeoxycholic Acid Is Conjugated with Taurine to Promote Secretin-Stimulated Biliary Hydrocholeresis in the Normal Rat

    PubMed Central

    Úriz, Miriam; Sáez, Elena; Prieto, Jesús

    2011-01-01

    Background & Aims Secretin induces bicarbonate-rich hydrocholeresis in healthy individuals, but not in untreated patients with primary biliary cirrhosis (PBC). Ursodeoxycholic acid (UDCA) – the first choice treatment for PBC – restores the secretin response. Compared with humans, secretin has poor effect in experimental normal-rat models with biliary drainage, although it may elicit hydrocholeresis when the bile-acid pool is maintained. In view of the benefits of UDCA in PBC, we used normal-rat models to unravel the acute contribution of UDCA (and/or taurine-conjugated TUDCA) for eliciting the biliary secretin response. Methods Intravascular and/or intrabiliary administration of agonists and inhibitors was performed in normal rats with biliary monitoring. Secretin/bile-acid interplay was analyzed in 3D cultured rat cholangiocytes that formed expansive cystic structures with intralumenal hydroionic secretion. Results In vivo, secretin stimulates hydrocholeresis upon UDCA/TUDCA infusion, but does not modify the intrinsic hypercholeretic effect of dehydrocholic acid (DHCA). The former effect is dependent on microtubule polymerization, and involves PKCα, PI3K and MEK pathways, as shown by colchicine (i.p.) and retrograde biliary inhibitors. In vitro, while secretin alone accelerates the spontaneous expansion of 3D-cystic structures, this effect is enhanced in the presence of TUDCA, but not UDCA or DHCA. Experiments with inhibitors and Ca2+-chelator confirmed that the synergistic effect of secretin plus TUDCA involves microtubules, intracellular Ca2+, PKCα, PI3K, PKA and MEK pathways. Gene silencing also demonstrated the involvement of the bicarbonate extruder Ae2. Conclusions UDCA is conjugated in order to promote secretin-stimulated hydrocholeresis in rats through Ae2, microtubules, intracellular Ca2+, PKCα, PI3K, PKA, and MEK. PMID:22194894

  18. Tauroursodeoxycholic acid stimulates hepatocellular exocytosis and mobilizes extracellular Ca++ mechanisms defective in cholestasis.

    PubMed Central

    Beuers, U; Nathanson, M H; Isales, C M; Boyer, J L

    1993-01-01

    To assess the effects of tauroursodeoxycholic acid (TUDCA) on bile excretory function, we examined whether TUDCA modulates vesicular exocytosis in the isolated perfused liver of normal rats in the presence of high (1.9 mM) or low (0.19 mM) extracellular Ca++ and in cholestatic rats 24 h after bile duct ligation. In addition, the effects of TUDCA on Ca++ homeostasis were compared in normal and in cholestatic hepatocytes. In the isolated perfused rat liver, TUDCA (25 microM) stimulated a sustained increase in the biliary excretion of horseradish peroxidase, a marker of the vesicular pathway, in the presence of high, but not low extracellular Ca++ or in the cholestatic liver. In contrast, TUDCA stimulated bile flow to the same extent regardless of the concentration of extracellular Ca++ or the presence of cholestasis. In indo-1-loaded hepatocytes, basal cytosolic free Ca++ ([Ca++]i) levels were not different between normal and cholestatic cells. However, in cholestatic cells [Ca++]i increases induced by TUDCA (10 microM) and its 7 alpha-OH epimer taurochenodeoxycholic acid (50 microM) were reduced to 22% and 26%, respectively, compared to normal cells. The impairment of TUDCA-induced [Ca++]i increase in cholestatic cells could be mimicked by exposing normal cells to low extracellular Ca++ (21%) or to the Ca++ channel blocker NiCl2 (23%). These data indicate that (a) dihydroxy bile acid-induced Ca++ entry may be of functional importance in the regulation of hepatocellular vesicular exocytosis, and (b) this Ca++ entry mechanism across the plasma membrane is impaired in cholestatic hepatocytes. We speculate that the beneficial effect of ursodeoxycholic acid in cholestatic liver diseases may be related to the Ca+(+)-dependent stimulation of vesicular exocytosis by its conjugate. PMID:8254052

  19. Stimulation of the Salicylic Acid Pathway Aboveground Recruits Entomopathogenic Nematodes Belowground.

    PubMed

    Filgueiras, Camila Cramer; Willett, Denis S; Junior, Alcides Moino; Pareja, Martin; Borai, Fahiem El; Dickson, Donald W; Stelinski, Lukasz L; Duncan, Larry W

    2016-01-01

    Plant defense pathways play a critical role in mediating tritrophic interactions between plants, herbivores, and natural enemies. While the impact of plant defense pathway stimulation on natural enemies has been extensively explored aboveground, belowground ramifications of plant defense pathway stimulation are equally important in regulating subterranean pests and still require more attention. Here we investigate the effect of aboveground stimulation of the salicylic acid pathway through foliar application of the elicitor methyl salicylate on belowground recruitment of the entomopathogenic nematode, Steinernema diaprepesi. Also, we implicate a specific root-derived volatile that attracts S. diaprepesi belowground following aboveground plant stimulation by an elicitor. In four-choice olfactometer assays, citrus plants treated with foliar applications of methyl salicylate recruited S. diaprepesi in the absence of weevil feeding as compared with negative controls. Additionally, analysis of root volatile profiles of citrus plants receiving foliar application of methyl salicylate revealed production of d-limonene, which was absent in negative controls. The entomopathogenic nematode S. diaprepesi was recruited to d-limonene in two-choice olfactometer trials. These results reinforce the critical role of plant defense pathways in mediating tritrophic interactions, suggest a broad role for plant defense pathway signaling belowground, and hint at sophisticated plant responses to pest complexes. PMID:27136916

  20. Stimulation of the Salicylic Acid Pathway Aboveground Recruits Entomopathogenic Nematodes Belowground

    PubMed Central

    Filgueiras, Camila Cramer; Willett, Denis S.; Junior, Alcides Moino; Pareja, Martin; Borai, Fahiem El; Dickson, Donald W.; Stelinski, Lukasz L.; Duncan, Larry W.

    2016-01-01

    Plant defense pathways play a critical role in mediating tritrophic interactions between plants, herbivores, and natural enemies. While the impact of plant defense pathway stimulation on natural enemies has been extensively explored aboveground, belowground ramifications of plant defense pathway stimulation are equally important in regulating subterranean pests and still require more attention. Here we investigate the effect of aboveground stimulation of the salicylic acid pathway through foliar application of the elicitor methyl salicylate on belowground recruitment of the entomopathogenic nematode, Steinernema diaprepesi. Also, we implicate a specific root-derived volatile that attracts S. diaprepesi belowground following aboveground plant stimulation by an elicitor. In four-choice olfactometer assays, citrus plants treated with foliar applications of methyl salicylate recruited S. diaprepesi in the absence of weevil feeding as compared with negative controls. Additionally, analysis of root volatile profiles of citrus plants receiving foliar application of methyl salicylate revealed production of d-limonene, which was absent in negative controls. The entomopathogenic nematode S. diaprepesi was recruited to d-limonene in two-choice olfactometer trials. These results reinforce the critical role of plant defense pathways in mediating tritrophic interactions, suggest a broad role for plant defense pathway signaling belowground, and hint at sophisticated plant responses to pest complexes. PMID:27136916

  1. Wine and five percent ethanol are potent stimulants of gastric acid secretion in humans.

    PubMed

    Lenz, H J; Ferrari-Taylor, J; Isenberg, J I

    1983-11-01

    Previous studies reported that intragastric ethanol was not a stimulus of gastric acid secretion in humans. The effect of 240 ml of 5%, 10%, and 20% ethanol (vol/vol), equicaloric-equiosmolar control solutions, white wine (12% ethanol), bourbon whiskey (1:4 dilution with water, 10% ethanol), and water on gastric acid secretion and serum gastrin concentrations were evaluated in 8 healthy subjects. Also, to stimulate the before-meal cocktail, white wine, whiskey, or water was administered 30 min before a 50-g liquid protein meal. Five percent ethanol and white wine significantly (p less than 0.01) increased basal secretion to 58% and 82%, respectively, of the peak pentagastrin response (24.2 +/- 1.6 mmol/h). After each of the 5%, 10%, and 20% ethanol solutions, 3-h acid outputs were significantly greater than their respective equicaloric-equiosmolar controls, but only the responses to 5% and 10% ethanol were significantly greater than water alone. Total 3-h responses to white wine, 5% ethanol, and 10% whiskey, respectively, were 5, 4.5, and 2 times greater than water (p less than 0.05). Although serum gastrin was not altered by any of the ethanol solutions or bourbon whiskey, white wine significantly increases serum gastrin concentration, similar to the 50-g protein meal. These results indicate that 5% ethanol and 10% bourbon whiskey increase gastric acid secretion by a mechanism other than gastrin release. White wine markedly stimulates both an increase in acid secretion and serum gastrin concentration. The constituent(s) in wine responsible for the marked acid secretory and gastrin response is unknown.

  2. Microwave treatment of naphthenic acids in water.

    PubMed

    Mishra, Sabyasachi; Meda, Venkatesh; Dalai, Ajay K; Headley, John V; Peru, Kerry M; McMartin, Dena W

    2010-08-01

    Naphthenic acids (NAs) are natural constituents of bitumen and crude oil. These compounds are concentrated as part of the oil sands process water (OSPW) during petroleum refining and separation from oil sands. NAs are considered among the major water contaminants in OSPW due to their toxicity and environmental recalcitrance. A laboratory scale microwave system was developed and experiments were conducted to determine the efficiency of NA degradation during microwave treatment. The effects of water source and quality (deionized lab water and river water) and of TiO(2) catalyst in the degradation process were also investigated. Degradation kinetic parameters for both total NAs and individual z-family were calculated. The microwave system degraded OSPW NAs and commercial Fluka NAs in river water in the presence of TiO(2) rapidly, producing half-life values of 3.32 and 3.61 hours, respectively. Toxicity assessments of the NA samples pre-and post-treatment indicated that the microwave system reduced overall toxicity of water containing Fluka NAs from high (5 min. IC(50) v/v = 15.85%) to moderate (5 min. IC(50) v/v = 36.45%) toxicity levels. However, a slight increase in toxicity was noted post-treatment in OSPW NAs.

  3. Lactogenic hormone stimulation and epigenetic control of L-amino acid oxidase expression in lactating mammary glands.

    PubMed

    Fujii, Kazuki; Zhang, Haolin; Usuda, Kento; Watanabe, Gen; Nagaoka, Kentaro

    2015-11-01

    L-amino acid oxidase (LAO), a classic flavoprotein, shows antibacterial activity by producing hydrogen peroxide. LAO exists in many tissues such as salivary gland, thymus, spleen, small intestine and testis. In particular, LAO was highly expressed in mice milk and plays an important factor in innate immunity of mammary glands. However, the mechanism which LAO expression is regulated spatially and temporally in lactating mammary glands has been unclear. In this study, we showed the contribution of lactogenic hormone and epigenetic control on LAO gene expression. In monolayer of mammary epithelial cells, treatment of lactogenic hormone mixture, dexamethasone, insulin and prolactin, did not induce LAO mRNA expression and its promoter activity, even though one of milk protein β-casein expression was stimulated. However, increase of LAO expression was observed when the cells were treated with lactogenic hormones in a 3-dimensional culture. The results of chromatin immunoprecipitation analysis revealed that histone H3K18 acetylation increased and histone H3K27 tri-methylation decreased with lactation, which is associated with a period of high LAO expression. Moreover, the treatment of histone methylation inhibitor (DZNep) as well as histone deacetylation inhibitor (Trichostatine A) induced LAO expression in monolayer of mammary cells. Taken together, this is the first demonstration showing that LAO expression is induced in cell culture, and stimulation of lactogenic hormone and change of histone modification are promising signals to show highly expression of LAO in lactating mammary glands.

  4. [Successful treatment of agranulocytosis caused by carbimazole using recombinant granulocyte-macrophage colony stimulating factor].

    PubMed

    Kreze, A; Kuviková, A; Laca, L; Kompis, S; Dobáková, M; Babusík, P; Matecek, L; Pekárová, E

    1995-07-01

    The authors describe a patient with hyperthyroidism who developed after three weeks' treatment with carbimazole agranulocytosis and the condition was complicated by septic shock. The authors used for treatment in addition to antibiotics and corticoids, for the first time in their practice, human recombinant granulocyte macrophage colonies stimulating factor (rHuGM-CSF) which produced a very favourable effect. In the meantime the patient was prepared for goitrectomy, operated and discharged in a satisfactory condition to have ambulatory treatment.

  5. Lipoapoptosis induced by saturated free fatty acids stimulates monocyte migration: a novel role for Pannexin1 in liver cells.

    PubMed

    Xiao, Feng; Waldrop, Shar L; Bronk, Steve F; Gores, Gregory J; Davis, Laurie S; Kilic, Gordan

    2015-09-01

    Recruitment of monocytes in the liver is a key pathogenic feature of hepatic inflammation in nonalcoholic steatohepatitis (NASH), but the mechanisms involved are poorly understood. Here, we studied migration of human monocytes in response to supernatants obtained from liver cells after inducing lipoapoptosis with saturated free fatty acids (FFA). Lipoapoptotic supernatants stimulated monocyte migration with the magnitude similar to a monocyte chemoattractant protein, CCL2 (MCP-1). Inhibition of c-Jun NH2-terminal kinase (JNK) in liver cells with SP600125 blocked migration of monocytes in a dose-dependent manner, indicating that JNK stimulates release of chemoattractants in lipoapoptosis. Notably, treatment of supernatants with Apyrase to remove ATP potently inhibited migration of THP-1 monocytes and partially blocked migration of primary human monocytes. Inhibition of the CCL2 receptor (CCR2) on THP-1 monocytes with RS102895, a specific CCR2 inhibitor, did not block migration induced by lipoapoptotic supernatants. Consistent with these findings, lipoapoptosis stimulated pathophysiological extracellular ATP (eATP) release that increased supernatant eATP concentration from 5 to ~60 nM. Importantly, inhibition of Panx1 expression in liver cells with short hairpin RNA (shRNA) decreased supernatant eATP concentration and inhibited monocyte migration, indicating that monocyte migration is mediated in part by Panx1-dependent eATP release. Moreover, JNK inhibition decreased supernatant eATP concentration and inhibited Pannexin1 activation, as determined by YoPro-1 uptake in liver cells in a dose-dependent manner. These results suggest that JNK regulates activation of Panx1 channels, and provide evidence that Pannexin1-dependent pathophysiological eATP release in lipoapoptosis is capable of stimulating migration of human monocytes, and may participate in the recruitment of monocytes in chronic liver injury induced by saturated FFA.

  6. Lipoxin A4 and lipoxin B4 stimulate the release but not the oxygenation of arachidonic acid in human neutrophils: dissociation between lipid remodeling and adhesion.

    PubMed

    Nigam, S; Fiore, S; Luscinskas, F W; Serhan, C N

    1990-06-01

    The profiles of actions of lipoxin A4 (LXA4) and lipoxin B4 (LXB4), two lipoxygenase-derived eicosanoids, were examined with human neutrophils. At nanomolar concentrations, LXA4 and LXB4 each stimulated the release of [1-14C]arachidonic acid from esterified sources in neutrophils. Lipoxin-induced release of [1-14C]arachidonic acid was both dose- and time-dependent and was comparable to that induced by the chemotactic peptide f-met-leu-phe. Time-course studies revealed that lipoxin A4 and lipoxin B4 each induced a biphasic release of [1-14C]arachidonic acid, which was evident within seconds (5-15 sec) in its initial phase and minutes (greater than 30 sec) in the second phase. In contrast, the all-trans isomers of LXA4 and LXB4 did not provoke [1-14C]AA release. Lipoxin-induced release of arachidonic acid was inhibited by prior treatment of the cells with pertussis toxin but not by its beta-oligomers, suggesting the involvement of guaninine nucleotide-binding regulatory proteins in this event. Dual radiolabeling of neutrophil phospholipid classes with [1-14C]arachidonic acid and [3H]palmitic acid showed that phosphatidylcholine was a major source of lipoxin-induced release of [1-14C]arachidonic acid. They also demonstrated that lipoxins rapidly stimulate both formation of phosphatidic acid as well as phospholipid remodeling. Although both LXA4 and LXB4 (10(-8)-10(-6) M) stimulated the release of [1-14C]arachidonic acid, neither compound evoked its oxygenation by either the 5- or 15-lipoxygenase pathways (including the formation of LTB4, 20-COOH-LTB4, 5-HETE, or 15-HETE). LXA4 and LXB4 (10(-7) M) each stimulated the elevation of cytosolic Ca2+ as monitored with Fura 2-loaded cells, albeit to a lesser extent than equimolar concentrations of FMLP. Neither lipoxin altered the binding of [3H]LTB4 to its receptor on neutrophils. In addition, they did not stimulate aggregation or induce adhesion of neutrophils to human endothelial cells. Results indicate that both LXA4 and

  7. Oscillating field stimulation in the treatment of spinal cord injury.

    PubMed

    Walters, Beverly C

    2010-12-01

    The application of electrical current to injured tissue is known to promote healing. The use of this modality in healing the injured spinal cord to promote neurologic recovery has been introduced as a potential treatment for patients who previously had minimal hope of recovery. In in vitro and in vivo experiments, neural regeneration has been seen to occur, especially when an oscillating field is used. With this modality, an electrical current is applied in which the polarity changes direction on a periodic basis, preventing the "die-back" phenomenon of severed neural pathways. This mechanism of recovery has been demonstrated in several species in which sacrifice has been undertaken and spinal cords examined. In a study of humans, a small number of patients participated in a single phase Ia trial in which the safety of an implantable device was demonstrated, with indications of probable benefit, consistent with laboratory and animal studies. In addition, a number of additional patients were treated, and their results were examined along with the original cohort and were compared with historical control subjects. The device used in this mode of treatment has not been approved for use in the general spinal cord-injured population, pending further study. A larger multi-institutional trial needs to be done to further demonstrate efficacy and effectiveness, and outcomes will need to be agreed upon by spinal cord injury researchers, patients, and regulators before widespread use will be permitted. Unfortunately, some subtle changes experienced and valued by patients are not recognized as important or desirable by regulators or by all researchers. PMID:21172690

  8. Acid mine water treatment using engineered wetlands

    NASA Astrophysics Data System (ADS)

    Kleinmann, Robert L. P.

    1990-03-01

    During the last two decades, the United States mining industry has greatly increased the amount it spends on pollution control. The application of biotechnology to mine water can reduce the industry's water treatment costs (estimated at over a million dollars a day) and improve water quality in streams and rivers adversely affected by acidic mine water draining from abandoned mines. Biological treatment of mine waste water is typically conducted in a series of small excavated ponds that resemble, in a superficial way, a small marsh area. The ponds are engineered to first facilitate bacterial oxidation of iron; ideally, the water then flows through a composted organic substrate that supports a population of sulfate-reducing bacteria. The latter process raises the pH. During the past four years, over 400 wetland water treatment systems have been built on mined lands as a result of research by the U.S. Bureau of Mines. In general, mine operators find that the wetlands reduce chemical treatment costs enough to repay the cost of wetland construction in less than a year. Actual rates of iron removal at field sites have been used to develop empirical sizing criteria based on iron loading and pH. If the pH is 6 or above, the wetland area (m2) required is equivalent to the iron load (grams/day) divided by 10. Theis requirement doubles at a pH of 4 to 5. At a pH below 4, the iron load (grams/day) should be divided by 2 to estimate the area required (m2).

  9. Ghrelin stimulates gastric emptying but is without effect on acid secretion and gastric endocrine cells.

    PubMed

    Dornonville de la Cour, Charlotta; Lindström, Erik; Norlén, Per; Håkanson, Rolf

    2004-08-15

    Ghrelin, a recently discovered peptide hormone, is produced by endocrine cells in the stomach, the so-called A-like cells. Ghrelin binds to the growth hormone (GH) secretagogue receptor and releases GH. It is claimed to be orexigenic and to control gastric acid secretion and gastric motility. In this study, we examined the effects of ghrelin, des-Gln14-ghrelin, des-octanoyl ghrelin, ghrelin-18, -10 and -5 (and motilin) on gastric emptying in mice and on gastric acid secretion in chronic fistula rats and pylorus-ligated rats. We also examined whether ghrelin affected the activity of the predominant gastric endocrine cell populations, G cells, ECL cells and D cells. Ghrelin and des-Gln14-ghrelin stimulated gastric emptying in a dose-dependent manner while des-octanoyl ghrelin and motilin were without effect. The C-terminally truncated ghrelin fragments were effective but much less potent than ghrelin itself. Ghrelin, des-Gln14-ghrelin and des-octanoyl ghrelin neither stimulated nor inhibited gastric acid secretion, and ghrelin, finally, did not affect secretion from either G cells, ECL cells or D cells.

  10. Amyloid protein precursor stimulates excitatory amino acid transport. Implications for roles in neuroprotection and pathogenesis.

    PubMed

    Masliah, E; Raber, J; Alford, M; Mallory, M; Mattson, M P; Yang, D; Wong, D; Mucke, L

    1998-05-15

    Excitatory neurotransmitters such as glutamate are required for the normal functioning of the central nervous system but can trigger excitotoxic neuronal injury if allowed to accumulate to abnormally high levels. Their extracellular levels are controlled primarily by transmitter uptake into astrocytes. Here, we demonstrate that the amyloid protein precursor may participate in the regulation of this important process. The amyloid protein precursor has been well conserved through evolution, and a number of studies indicate that it may function as an endogenous excitoprotectant. However, the mechanisms underlying this neuroprotective capacity remain largely unknown. At moderate levels of expression, human amyloid protein precursors increased glutamate/aspartate uptake in brains of transgenic mice, with the 751-amino acid isoform showing greater potency than the 695-amino acid isoform. Cerebral glutamate/aspartate transporter protein levels were higher in transgenic mice than in non-transgenic controls, whereas transporter mRNA levels were unchanged. Amyloid protein precursor-dependent stimulation of aspartate uptake by cultured primary astrocytes was associated with increases in protein kinase A and C activity and could be blocked by inhibitors of these kinases. The stimulation of astroglial excitatory amino acid transport by amyloid protein precursors could protect the brain against excitotoxicity and may play an important role in neurotransmission. PMID:9575214

  11. Stimulant Treatment of ADHD and Cigarette Smoking: A Meta-Analysis

    PubMed Central

    Faraone, Stephen V.; Kollins, Scott H.

    2014-01-01

    BACKGROUND AND OBJECTIVE: Individuals with attention-deficit/hyperactivity disorder (ADHD) have a significantly higher risk of cigarette smoking. The nature of the relationship between smoking and psychostimulant medications commonly used to treat ADHD is controversial. Our objective was to examine the relationship between stimulant treatment of ADHD and cigarette smoking by using meta-analysis, and to identify study and sample characteristics that moderate this relationship. METHODS: Literature searches on PubMed and PsycInfo databases identified published studies for inclusion. Included studies compared cigarette smoking outcomes for stimulant-treated and untreated ADHD individuals. Seventeen studies met inclusion criteria, and 14 (total n = 2360) contained sufficient statistical information for inclusion in the meta-analysis. Two authors extracted odds ratios or frequencies of smokers in the treatment or nontreatment groups, and coded study characteristics including sample source, percentage of male participants, follow-up length, treatment consistency, type of smoking measure, prospective study, and controlling for comorbidities. RESULTS: Meta-analysis revealed a significant association between stimulant treatment and lower smoking rates. Meta-regression indicated that effect sizes were larger for studies that used clinical samples, included more women, measured smoking in adolescence rather than adulthood, conceptualized stimulant treatment as consistent over time, and accounted for comorbid conduct disorder. CONCLUSIONS: Nearly all studies were naturalistic, precluding causal inferences. Available data were insufficient to examine additional influences of patient demographics, treatment effectiveness, or other comorbidities. Consistent stimulant treatment of ADHD may reduce smoking risk; the effect was larger in samples with more severe psychopathology. Implications for further research, treatment of ADHD, and smoking prevention are discussed. PMID:24819571

  12. Differential stimulation of luminol-enhanced chemiluminescence (CL) and arachidonic acid metabolism in rat peritoneal neutrophils

    SciTech Connect

    Sturm, R.J.; Adams, L.M.; Cullinan, C.A.; Berkenkopf, J.W.; Weichman, B.M.

    1986-03-05

    Phorbol 12-myristate, 13-acetate (PMA) induced the production of radical oxygen species (ROS) from rat peritoneal neutrophils as assessed by CL. ROS generation occurred in a time- (maximum at 13.5 min) and dose- (concentration range of 1.7-498 nM) related fashion. However, 166 nM PMA did not induce either cyclooxygenase (CO) or lipoxygenase (LPO) product formation by 20 min post-stimulation. Conversely, A23187, at concentrations between 0.1 and 10 ..mu..M, stimulated both pathways of arachidonic acid metabolism, but had little or no effect upon ROS production. When suboptimal concentrations of PMA (5.5 nM) and A23187 (0.1-1 ..mu..M) were coincubated with the neutrophils, a synergistic ROS response was elicited. However, arachidonic acid metabolism in the presence of PMA was unchanged relative to A12187 alone. Nordihydroguaiaretic acid (NDGA) inhibited both PMA-induced CL (IC/sub 50/ = 0.9 ..mu..M) and A23187-induced arachidonic acid metabolism (IC/sub 50/ = 1.7 ..mu..M and 6.0 ..mu..M for LPO and CO, respectively). The mixed LPO-CO inhibitor, BW755C, behaved in a qualitatively similar manner to NDGA, whereas the CO inhibitors, indomethacin, piroxicam and naproxen had no inhibitory effect on ROS generation at concentrations as high as 100 ..mu..M. These results suggest that NDGA and BW755C may inhibit CL and arachidonic acid metabolism by distinct mechanisms in rat neutrophils.

  13. Brain stimulation: Neuromodulation as a potential treatment for motor recovery following traumatic brain injury☆

    PubMed Central

    Clayton, E.; Kinley-Cooper, S.K.; Weber, R.A.; Adkins, D.L.

    2016-01-01

    There is growing evidence that electrical and magnetic brain stimulation can improve motor function and motor learning following brain damage. Rodent and primate studies have strongly demonstrated that combining cortical stimulation (CS) with skilled motor rehabilitative training enhances functional motor recovery following stroke. Brain stimulation following traumatic brain injury (TBI) is less well studied, but early pre-clinical and human pilot studies suggest that it is a promising treatment for TBI-induced motor impairments as well. This review will first discuss the evidence supporting brain stimulation efficacy derived from the stroke research field as proof of principle and then will review the few studies exploring neuromodulation in experimental TBI studies. PMID:26855256

  14. Quantification and enzyme targets of fatty acid amides from duckweed root exudates involved in the stimulation of denitrification.

    PubMed

    Sun, Li; Lu, Yufang; Kronzucker, Herbert J; Shi, Weiming

    2016-07-01

    Fatty acid amides from plant root exudates, such as oleamide and erucamide, have the ability to participate in strong plant-microbe interactions, stimulating nitrogen metabolism in rhizospheric bacteria. However, mechanisms of secretion of such fatty acid amides, and the nature of their stimulatory activities on microbial metabolism, have not been examined. In the present study, collection, pre-treatment, and determination methods of oleamide and erucamide in duckweed root exudates are compared. The detection limits of oleamide and erucamide by gas chromatography (GC) (10.3ngmL(-1) and 16.1ngmL(-1), respectively) are shown to be much lower than those by liquid chromatography (LC) (1.7 and 5.0μgmL(-1), respectively). Quantitative GC analysis yielded five times larger amounts of oleamide and erucamide in root exudates of Spirodela polyrrhiza when using a continuous collection method (50.20±4.32 and 76.79±13.92μgkg(-1) FW day(-1)), compared to static collection (10.88±0.66 and 15.27±0.58μgkg(-1) FW day(-1)). Furthermore, fatty acid amide secretion was significantly enhanced under elevated nitrogen conditions (>300mgL(-1)), and was negatively correlated with the relative growth rate of duckweed. Mechanistic assays were conducted to show that erucamide stimulates nitrogen removal by enhancing denitrification, targeting two key denitrifying enzymes, nitrate and nitrite reductases, in bacteria. Our findings significantly contribute to our understanding of the regulation of nitrogen dynamics by plant root exudates in natural ecosystems. PMID:27152459

  15. Quantification and enzyme targets of fatty acid amides from duckweed root exudates involved in the stimulation of denitrification.

    PubMed

    Sun, Li; Lu, Yufang; Kronzucker, Herbert J; Shi, Weiming

    2016-07-01

    Fatty acid amides from plant root exudates, such as oleamide and erucamide, have the ability to participate in strong plant-microbe interactions, stimulating nitrogen metabolism in rhizospheric bacteria. However, mechanisms of secretion of such fatty acid amides, and the nature of their stimulatory activities on microbial metabolism, have not been examined. In the present study, collection, pre-treatment, and determination methods of oleamide and erucamide in duckweed root exudates are compared. The detection limits of oleamide and erucamide by gas chromatography (GC) (10.3ngmL(-1) and 16.1ngmL(-1), respectively) are shown to be much lower than those by liquid chromatography (LC) (1.7 and 5.0μgmL(-1), respectively). Quantitative GC analysis yielded five times larger amounts of oleamide and erucamide in root exudates of Spirodela polyrrhiza when using a continuous collection method (50.20±4.32 and 76.79±13.92μgkg(-1) FW day(-1)), compared to static collection (10.88±0.66 and 15.27±0.58μgkg(-1) FW day(-1)). Furthermore, fatty acid amide secretion was significantly enhanced under elevated nitrogen conditions (>300mgL(-1)), and was negatively correlated with the relative growth rate of duckweed. Mechanistic assays were conducted to show that erucamide stimulates nitrogen removal by enhancing denitrification, targeting two key denitrifying enzymes, nitrate and nitrite reductases, in bacteria. Our findings significantly contribute to our understanding of the regulation of nitrogen dynamics by plant root exudates in natural ecosystems.

  16. Improved Sequence Learning with Subthalamic Nucleus Deep Brain Stimulation: Evidence for Treatment-Specific Network Modulation

    PubMed Central

    Mure, Hideo; Tang, Chris C.; Argyelan, Miklos; Ghilardi, Maria-Felice; Kaplitt, Michael G.; Dhawan, Vijay; Eidelberg, David

    2015-01-01

    We used a network approach to study the effects of anti-parkinsonian treatment on motor sequence learning in humans. Eight Parkinson’s disease (PD) patients with bilateral subthalamic nucleus (STN) deep brain stimulation underwent H2 15Opositron emission tomography (PET) imaging to measure regional cerebral blood flow (rCBF) while they performed kinematically matched sequence learning and movement tasks at baseline and during stimulation. Network analysis revealed a significant learning-related spatial covariance pattern characterized by consistent increases in subject expression during stimulation (p = 0.008, permutation test). The network was associated with increased activity in the lateral cerebellum, dorsal premotor cortex, and parahippocampal gyrus, with covarying reductions in the supplementary motor area (SMA) and orbitofrontal cortex. Stimulation-mediated increases in network activity correlated with concurrent improvement in learning performance (p < 0.02). To determine whether similar changes occurred during dopaminergic pharmacotherapy, we studied the subjects during an intravenous levodopa infusion titrated to achieve a motor response equivalent to stimulation. Despite consistent improvement in motor ratings during infusion, levodopa did not alter learning performance or network activity. Analysis of learning-related rCBF in network regions revealed improvement in baseline abnormalities with STN stimulation but not levodopa. These effects were most pronounced in the SMA. In this region, a consistent rCBF response to stimulation was observed across subjects and trials (p = 0.01), although the levodopa response was not significant. These findings link the cognitive treatment response in PD to changes in the activity of a specific cerebello-premotor cortical network. Selective modulation of overactive SMA–STN projection pathways may underlie the improvement in learning found with stimulation. PMID:22357863

  17. Long-term results of a clinical trial comparing isolated vaginal stimulation with combined treatment for women with stress incontinence

    PubMed Central

    Fürst, Maria Cláudia Bicudo; de Mendonça, Rafaela Rosalba; Rodrigues, Alexandre Oliveira; de Matos, Leandro Luongo; Pompeo, Antônio Carlos Lima; Bezerra, Carlos Alberto

    2014-01-01

    ABSTRACT Objective To determine the efficacy of stress urinary incontinence treatments adding pelvic floor muscle training to vaginal electrical stimulation. Methods Forty-eight women with stress urinary incontinence were randomized into 2 groups: 24 underwent isolated vaginal electrical stimulation, and 24 vaginal electrical stimulation plus pelvic floor muscle training. History, physical examination, voiding diary, perineum strength test, and urodynamic study were assessed. Comparisons were made for adherence to treatment, muscle strength improvement, urinary symptoms, and degree of satisfaction immediately, 12 and 96 months after treatment. Results Patients' degree of satisfaction on vaginal electrical stimulation, and on vaginal electrical stimulation plus pelvic floor muscle training immediately, 12 and 96 months post treatment, were, respectively: 88.2% versus 88.9% 64.7% versus 61.1% and 42.9% versus 28.6% (p>0.05). Conclusion Vaginal electrical stimulation associated to pelvic floor muscle training did not show better results than vaginal electrical stimulation alone. PMID:25003921

  18. Evaluation of a fibrate, specific stimulant of PPARα, as a therapeutic alternative to the treatment of clinical ovine pregnancy toxaemia.

    PubMed

    Da Silva, S; Cal-Pereyra, L G; Benech, A; Acosta-Dibarrat, J; Martin, M J; Abreu, M C; Perini, S; González-Montaña, J R

    2016-10-01

    Ovine pregnancy toxaemia is a metabolic disorder affecting sheep in their last 6 weeks of pregnancy as a result of their inability to maintain adequate energy homoeostasis. Different alternative treatments are available with variable results. The aim of this research was to evaluate a peroxisome proliferator-activated receptor alpha (PPARα) stimulant as an alternative to treat clinical pregnancy toxaemia. Thirty-three adult sheep, with known gestation date and carrying a single foetus, were fasted from day 130 of gestation until animals showed clinical disease. From that moment onwards, sheep were treated during 6 days with three different therapeutic alternatives: 10 mg/kg of 2-methyl-2-phenoxy-propionic acid; 10 mg/kg of 2-methyl-2-phenoxy-propionic acid + 100 mL of propylene glycol oral; or 100 mL of propylene glycol oral. Glycaemia and serum β-hydroxybutyrate (BHOB) were determined daily. Liver biopsies were taken at day 130 of gestation, at the beginning and end of treatments and at 5 days postpartum, evaluating the extent and degree of the steatosis lesion. Even though in sheep treated with 2-methyl-2-phenoxy-propionic acid, serum concentrations of glucose and BHOB recovered more slowly, we conclude that 2-methyl-2-phenoxy-propionic acid alone or combined with propylene glycol can be used as an alternative to effectively treat fatty liver, and therefore pregnancy toxaemia.

  19. Stimulation of bacteriocin production by dialyzed culture media from different lactic acid bacteria.

    PubMed

    Vázquez, J A; González, M P; Murado, M A

    2005-04-01

    The cross-effects of dialyzed postincubates (with a cut-off at 1000 Da) on the biomass and bacteriocin production of six strains of lactic acid bacteria were studied, and a predominance of stimulating responses was found, the characteristics of which suggested merely nutritional effects or the presence of precursor fragments of the bacteriocins. Additionally, cluster analysis of the detected responses provides an approach to define groups of highly compatible (potential consortia) or doubtfully compatible strains of lactic acid bacteria. Such a definition, which does not claim taxonomic value, has practical interest, however, in cases (e.g., silage production) in which it is convenient to use mixed inocula including strains able to establish positive interactions.

  20. 18{beta}-Glycyrrhetinic acid inhibits adipogenic differentiation and stimulates lipolysis

    SciTech Connect

    Moon, Myung-Hee; Jeong, Jae-Kyo; Lee, You-Jin; Seol, Jae-Won; Ahn, Dong-Choon; Kim, In-Shik; Park, Sang-Youel

    2012-04-20

    Highlights: Black-Right-Pointing-Pointer 18{beta}-GA inhibits adipogenic differentiation in 3T3-L1 preadipocytes and stimulates lipolysis in differentiated adipocytes. Black-Right-Pointing-Pointer Anti-adipogenic effect of 18{beta}-GA is caused by down-regulation of PPAR{gamma} and inactivation of Akt signalling. Black-Right-Pointing-Pointer Lipolytic effect of 18{beta}-GA is mediated by up-regulation of HSL, ATGL and perilipin and activation of HSL. -- Abstract: 18{beta}-Glycyrrhetinic acid (18{beta}-GA) obtained from the herb liquorice has various pharmacological properties including anti-inflammatory and anti-bacterial activities. However, potential biological anti-obesity activities are unclear. In this study, novel biological activities of 18{beta}-GA in the adipogenesis of 3T3-L1 preadipocytes and in lipolysis of differentiated adipocytes were identified. Mouse 3T3-L1 cells were used as an in vitro model of adipogenesis and lipolysis, using a mixture of insulin/dexamethasone/3-isobutyl-1-methylxanthine (IBMX) to induce differentiation. The amount of lipid droplet accumulation was determined by an AdipoRed assay. The expression of several adipogenic transcription factors and enzymes was investigated using real-time reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blotting. 18{beta}-GA dose-dependently (1-40 {mu}M) significantly decreased lipid accumulation in maturing preadipocytes. In 3T3-L1 preadipocytes, 10 {mu}M of 18{beta}-GA down-regulated the transcriptional levels of the peroxisome proliferator-activated receptor {gamma}, CCAAT/enhancer-binding protein {alpha} and adiponectin, which are markers of adipogenic differentiation via Akt phosphorylation. Also, in differentiated adipocytes, 18{beta}-GA increased the level of glycerol release and up-regulated the mRNA of hormone-sensitive lipase, adipose TG lipase and perilipin, as well as the phosphorylation of hormone-sensitive lipase at Serine 563. The results indicate that 18{beta

  1. Deep Brain Stimulation for the Treatment of Severe, Medically Refractory Obsessive-Compulsive Disorder

    PubMed Central

    Sedrak, Mark; Wong, William; Wilson, Paul; Bruce, Diana; Bernstein, Ivan; Khandhar, Suketu; Pappas, Conrad; Heit, Gary; Sabelman, Eric

    2013-01-01

    Deep brain stimulation is a rapidly expanding therapy initially designed for the treatment of movement disorders and pain syndromes. The therapy includes implantation of electrodes in specific targets of the brain, delivering programmable small and safe electric impulses, like a pacemaker, that modulates both local and broad neurologic networks. The effects are thought to primarily involve a focus in the brain, probably inhibitory, which then restores a network of neural circuitry. Psychiatric diseases can be refractory and severe, leading to high medical costs, significant morbidity, and even death. Whereas surgery for psychiatric disease used to include destructive procedures, deep brain stimulation allows safe, reversible, and adjustable treatment that can be tailored for each patient. Deep brain stimulation offers new hope for these unfortunate patients, and the preliminary results are promising. PMID:24361021

  2. Electrical stimulation treatment for facial palsy after revision pleomorphic adenoma surgery

    PubMed Central

    Goldie, Simon; Sandeman, Jack; Cole, Richard; Dennis, Simon; Swain, Ian

    2016-01-01

    Surgery for pleomorphic adenoma recurrence presents a significant risk of facial nerve damage that can result in facial weakness effecting patients’ ability to communicate, mental health and self-image. We report two case studies that had marked facial weakness after resection of recurrent pleomorphic adenoma and their progress with electrical stimulation. Subjects received electrical stimulation twice daily for 24 weeks during which photographs of expressions, facial measurements and Sunnybrook scores were recorded. Both subjects recovered good facial function demonstrating Sunnybrook scores of 54 and 64 that improved to 88 and 96, respectively. Neither subjects demonstrated adverse effects of treatment. We conclude that electrical stimulation is a safe treatment and may improve facial palsy in patients after resection of recurrent pleomorphic adenoma. Larger studies would be difficult to pursue due to the low incidence of cases. PMID:27106613

  3. Isolation of three diterpenoid acids from sunflowers, as oviposition stimulants for the banded sunflower moth, Cochylis hospes.

    PubMed

    Morris, Bruce D; Charlet, Laurence D; Foster, Stephen P

    2009-01-01

    The banded sunflower moth (BSFM), Cochylis hospes Walshingham (Lepidoptera: Cochylidae) is a specialist insect, the larvae of which feed on sunflowers, Helianthus spp., and a few other species of Compositae. It is one of the most important pests of sunflower in the USA. Previous work on H. annuus, the cultivated sunflower, revealed two diterpenoids that function as oviposition stimulants for female BSFM, and that other, more polar compounds also stimulated oviposition. Using a bioassay-guided approach, we isolated three additional diterpenoids, grandifloric acid (1), 15beta-hydroxy-ent-trachyloban-19-oic acid (2), and 17-hydroxy-16alpha-ent-kauran-19-oic acid (3), from polar fractions of pre-bloom sunflower head extracts. In laboratory bioassays, purified natural samples of each of these compounds stimulated oviposition by female BSFM. Structure-activity relationships of the five diterpenoids known to stimulate oviposition by female BSFM are discussed.

  4. Glucose supplementation stimulates peripheral branched-chain amino acid catabolism in lactating dairy cows during essential amino acid infusions.

    PubMed

    Nichols, K; Kim, J J M; Carson, M; Metcalf, J A; Cant, J P; Doelman, J

    2016-02-01

    To determine how glucose modulates protein synthesis when essential AA are in abundant supply, 5 early-lactation, rumen-fistulated Holstein dairy cows were fed a diet containing 6.95 MJ/kg of net energy for lactation and 12.4% crude protein and abomasally infused for 5 d with saline, 844 or 1,126 g/d of a complete essential AA mix, with and without the inclusion of 1,000 g/d of glucose, in a 5×5 Latin square design. Infusion of essential AA increased milk yield by 4.1 kg/d, milk protein by 256 g/d, milk fat by 95 g/d, and milk urea nitrogen by 70% compared with saline, with no differences between the level of essential AA infusion. The addition of glucose to essential AA infusate did not stimulate milk protein yield or concentration, but reduced milk urea nitrogen by 17% and decreased milk fat yield. Arterial concentrations of total essential AA increased 3- to 4-fold, mammary clearance decreased 61%, and mammary uptake of essential AA increased 65% in response to essential AA infusion. Arterial branched-chain AA concentrations declined 29% in response to glucose and mammary clearance increased 48%, but mammary AA uptake was unchanged. Essential AA infusion increased plasma 3-methylhistidine by 50% and reduced muscle branched-chain α-keto acid dehydrogenase kinase abundance by 14%, indicating stimulation of muscle protein turnover and branched-chain AA catabolism, respectively. Glucose had no further effect on muscle branched-chain α-keto acid dehydrogenase kinase abundance but decreased mRNA expression of branched chain aminotransferase 1. Lack of further increases in plasma 3-methylhistidine or greater stimulation of muscle branched-chain AA catabolism indicates that muscle protein degradation was unchanged with glucose but that accretion may have been stimulated. The decrease in circulating branched-chain AA concentrations and nitrogen excretion in response to glucose suggests that surplus essential AA were redirected to peripheral, extra-mammary tissues.

  5. Cognitive Function as a Transdiagnostic Treatment Target in Stimulant Use Disorders.

    PubMed

    Sofuoglu, Mehmet; DeVito, Elise E; Waters, Andrew J; Carroll, Kathleen M

    2016-01-01

    Stimulant use disorder is an important public health problem, with an estimated 2.1 million current users in the United States alone. No pharmacological treatments are approved by the U.S. Food and Drug Administration for stimulant use disorder and behavioral treatments have variable efficacy and limited availability. Most individuals with stimulant use disorder have other comorbidities, most with overlapping symptoms and cognitive impairments. The goal of this article is to present a rationale for cognition as a treatment target in stimulant use disorder and to outline potential treatment approaches. Rates of lifetime comorbid psychiatric disorders among people with stimulant use disorders are estimated at 65% to 73%, with the most common being mood disorders (13% to 64%) and anxiety disorders (21% to 50%), as well as non-substance-induced psychotic disorders (<10%). There are several models of addictive behavior, but the dual process model particularly highlights the relevance of cognitive impairments and biases to the development and maintenance of addiction. This model explains addictive behavior as a balance between automatic processes and executive control, which in turn are related to individual (genetics, comorbid disorders, psychosocial factors) and other (craving, triggers, drug use) factors. Certain cognitive impairments, such as attentional bias and approach bias, are most relevant to automatic processes, while sustained attention, response inhibition, and working memory are primarily related to executive control. These cognitive impairments and biases are also common in disorders frequently comorbid with stimulant use disorder and predict poor treatment retention and clinical outcomes. As such, they may serve as feasible transdiagnostic treatment targets. There are promising pharmacological, cognitive, and behavioral approaches that aim to enhance cognitive function. Pharmacotherapies target cognitive impairments associated with executive control and

  6. Cognitive Function as a Transdiagnostic Treatment Target in Stimulant Use Disorders.

    PubMed

    Sofuoglu, Mehmet; DeVito, Elise E; Waters, Andrew J; Carroll, Kathleen M

    2016-01-01

    Stimulant use disorder is an important public health problem, with an estimated 2.1 million current users in the United States alone. No pharmacological treatments are approved by the U.S. Food and Drug Administration for stimulant use disorder and behavioral treatments have variable efficacy and limited availability. Most individuals with stimulant use disorder have other comorbidities, most with overlapping symptoms and cognitive impairments. The goal of this article is to present a rationale for cognition as a treatment target in stimulant use disorder and to outline potential treatment approaches. Rates of lifetime comorbid psychiatric disorders among people with stimulant use disorders are estimated at 65% to 73%, with the most common being mood disorders (13% to 64%) and anxiety disorders (21% to 50%), as well as non-substance-induced psychotic disorders (<10%). There are several models of addictive behavior, but the dual process model particularly highlights the relevance of cognitive impairments and biases to the development and maintenance of addiction. This model explains addictive behavior as a balance between automatic processes and executive control, which in turn are related to individual (genetics, comorbid disorders, psychosocial factors) and other (craving, triggers, drug use) factors. Certain cognitive impairments, such as attentional bias and approach bias, are most relevant to automatic processes, while sustained attention, response inhibition, and working memory are primarily related to executive control. These cognitive impairments and biases are also common in disorders frequently comorbid with stimulant use disorder and predict poor treatment retention and clinical outcomes. As such, they may serve as feasible transdiagnostic treatment targets. There are promising pharmacological, cognitive, and behavioral approaches that aim to enhance cognitive function. Pharmacotherapies target cognitive impairments associated with executive control and

  7. Stimulation of the amino acid transporter SLC6A19 by JAK2

    SciTech Connect

    Bhavsar, Shefalee K.; Hosseinzadeh, Zohreh; Merches, Katja; Gu, Shuchen; Broeer, Stefan; Lang, Florian

    2011-10-28

    Highlights: Black-Right-Pointing-Pointer The amino acid transporter SLC6A19 is upregulated by Janus kinase-2 JAK2. Black-Right-Pointing-Pointer The {sup V617F}JAK2 mutant, causing myeloproliferative disease, is more effective. Black-Right-Pointing-Pointer JAK2 inhibitor AG490 reverses stimulation of SLC6A19 by {sup V617F}JAK2. Black-Right-Pointing-Pointer JAK2 enhances SLC6A19 protein insertion into the cell membrane. Black-Right-Pointing-Pointer SLC6A19 may contribute to amino acid uptake into {sup V617F}JAK2 expressing tumor cells. -- Abstract: JAK2 (Janus kinase-2) is expressed in a wide variety of cells including tumor cells and contributes to the proliferation and survival of those cells. The gain of function mutation {sup V617F}JAK2 mutant is found in the majority of myeloproliferative diseases. Cell proliferation depends on the availability of amino acids. Concentrative cellular amino acid uptake is in part accomplished by Na{sup +} coupled amino acid transport through SLC6A19 (B(0)AT). The present study thus explored whether JAK2 activates SLC6A19. To this end, SLC6A19 was expressed in Xenopus oocytes with or without wild type JAK2, {sup V617F}JAK2 or inactive {sup K882E}JAK2 and electrogenic amino acid transport determined by dual electrode voltage clamp. In SLC6A19-expressing oocytes but not in oocytes injected with water or JAK2 alone, the addition of leucine (2 mM) to the bath generated a current (I{sub le}), which was significantly increased following coexpression of JAK2 or {sup V617F}JAK2, but not by coexpression of {sup K882E}JAK2. Coexpression of JAK2 enhanced the maximal transport rate without significantly modifying the affinity of the carrier. Exposure of the oocytes to the JAK2 inhibitor AG490 (40 {mu}M) resulted in a gradual decline of I{sub le}. According to chemiluminescence JAK2 enhanced the carrier protein abundance in the cell membrane. The decline of I{sub le} following inhibition of carrier insertion by brefeldin A (5 {mu}M) was similar

  8. Restricted Environmental Stimulation Therapy (REST) as a Treatment for Autistic Children.

    ERIC Educational Resources Information Center

    Suedfeld, Peter; Schwartz, Geraldine

    The study evaluated the usefulness of 48 hours of Restricted Environmental Stimulation Therapy (REST) as a treatment for eight autistic children (between 5 and 11 years old). Ss were placed in a dimly lit room which contained only a mattress, told to ask for toilet facilities when needed, and then left alone except for when meals were brought in.…

  9. Leucine and alpha-Ketoisocaproic acid, but not norleucine, stimulate skeletal muscle protein synthesis in neonatal pigs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The branched-chain amino acid, leucine, acts as a nutrient signal to stimulate protein synthesis in skeletal muscle of young pigs. However, the chemical structure responsible for this effect has not been identified. We have shown that the other branched-chain amino acids, isoleucine and valine, are ...

  10. Ultrasound biomicroscopy measurement of skin thickness change induced by cosmetic treatment with ultrasound stimulation.

    PubMed

    Mak, Tak-Man; Huang, Yan-Ping; Wang, Li-Ke; Zheng, Yong-Ping

    2014-07-01

    Moisturizing creams and lotions are commonly used in daily life for beauty and treatment of different skin conditions such as dryness and wrinkling, and ultrasound stimulation has been used to enhance the delivery of ingredients into skin. However, there is a lack of convenient methods to study the effect of ultrasound stimulation on lotion absorption by skin in vivo. Ultrasound biomicroscopy was adopted as a viable tool in this study to investigate the effectiveness of ultrasound stimulation on the enhancement of lotion delivery into skin. The forearm skin of 10 male and 10 female young subjects was tested at three different sites, including two lotion treatment sites with (Ultrasound Equipment - UE ON) and without (UE OFF) ultrasound stimulation and a control site without any lotion treatment. 1 MHz ultrasound with a duty cycle of 1.7%, a spatial peak temporal peak pressure of 195 kPa and an average power of 0.43 W was used for the stimulation. The skin thickness before, immediately after (0 min), and 15 and 30 min after the treatment was measured by an ultrasound biomicroscopic system (55 MHz). It was found that the skin thickness significantly increased immediately after the lotion treatment for both UE ON (from 1.379 ± 0.187 mm to 1.466 ± 0.182 mm, p<0.001) and UE OFF (from 1.396 ± 0.193 mm to 1.430 ± 0.194 mm, p<0.001) groups. Further comparison between the two groups revealed that the skin thickness increase of UE ON group was significantly larger than that of UE OFF group (6.5 ± 2.4% vs. 2.5 ± 1.3%, p<0.001). Furthermore, it was disclosed that the enhancement of lotion delivery by ultrasound stimulation was more effective for the female subjects than the male subjects (7.6 ± 2.3% vs. 5.4 ± 2.0% immediately after treatment, p=0.017). In conclusion, this study demonstrated that ultrasound biomicroscopy was a feasible method for studying the effectiveness of lotion treatment in vivo, and ultrasound stimulation was effective to enhance the rate of

  11. Bile acid induced colonic irritation stimulates intracolonic nitric oxide release in humans.

    PubMed Central

    Casellas, F; Mourelle, M; Papo, M; Guarner, F; Antolin, M; Armengol, J R; Malagelada, J R

    1996-01-01

    AIM--To measure the intracolonic release of nitric oxide end products (nitrates plus nitrites) and eicosanoids in response to intraluminal irritation with deoxycholic acid (DCA). PATIENTS--Seven patients with irritable bowel syndrome. METHODS--The left colon was perfused with a solution with or without 3 mM deoxycholic acid. Aspirates were assayed for eicosanoids by specific radioimmuno-assay, and for nitrates plus nitrites by the Griess reaction. To confirm that stimulated colonic mucosa can produce nitric oxide (NO), ancillary studies were performed in vitro using samples of normal mucosa obtained from five surgically resected colons. Samples were incubated for 30 minutes in Kreb's solution, 3 mM DCA or DCA with 1 mM L-nitro-arginine-methyl-ester (L-NAME) to inhibit the NO synthase. Finally, NO synthase activity was measured in five samples of human colonic mucosa. RESULTS--Intracolonic release of nitrates plus nitrites was basally undetectable in six of seven patients. Bile acid considerably increased the release of prostaglandin E2 and nitrates plus nitrites (p < 0.01). By contrast, no increase in thromboxane and leukotriene was seen. In vitro mucosal incubation with DCA increased the production of NO synthase products, which was blocked by L-NAME. Activity of Ca+2 independent NO synthase was detectable in four of five samples of human colonic mucosa. CONCLUSION--The human colonic mucosa responds to bile acid induced irritation by a surge in NO generation via NO synthase. PMID:8707118

  12. Environmental Nitrate Stimulates Abscisic Acid Accumulation in Arabidopsis Root Tips by Releasing It from Inactive Stores[OPEN

    PubMed Central

    2016-01-01

    Abscisic acid (ABA) signaling plays a major role in root system development, regulating growth and root architecture. However, the precise localization of ABA remains undetermined. Here, we present a mechanism in which nitrate signaling stimulates the release of bioactive ABA from the inactive storage form, ABA-glucose ester (ABA-GE). We found that ABA accumulated in the endodermis and quiescent center of Arabidopsis thaliana root tips, mimicking the pattern of SCARECROW expression, and (to lower levels) in the vascular cylinder. Nitrate treatment increased ABA levels in root tips; this stimulation requires the activity of the endoplasmic reticulum-localized, ABA-GE-deconjugating enzyme β-GLUCOSIDASE1, but not de novo ABA biosynthesis. Immunogold labeling demonstrated that ABA is associated with cytoplasmic structures near, but not within, the endoplasmic reticulum. These findings demonstrate a mechanism for nitrate-regulated root growth via regulation of ABA accumulation in the root tip, providing insight into the environmental regulation of root growth. PMID:26887919

  13. Vagus Nerve Stimulation and Other Neuromodulation Methods for Treatment of Traumatic Brain Injury.

    PubMed

    Neren, Daniel; Johnson, Matthew D; Legon, Wynn; Bachour, Salam P; Ling, Geoffrey; Divani, Afshin A

    2016-04-01

    The objective of this paper is to review the current literature regarding the use of vagus nerve stimulation (VNS) in preclinical models of traumatic brain injury (TBI) as well as discuss the potential role of VNS along with alternative neuromodulation approaches in the treatment of human TBI. Data from previous studies have demonstrated VNS-mediated improvement following TBI in animal models. In these cases, VNS was observed to enhance motor and cognitive recovery, attenuate cerebral edema and inflammation, reduce blood brain barrier breakdown, and confer neuroprotective effects. Yet, the underlying mechanisms by which VNS enhances recovery following TBI remain to be fully elucidated. Several hypotheses have been offered including: a noradrenergic mechanism, reduction in post-TBI seizures and hyper-excitability, anti-inflammatory effects, attenuation of blood-brain barrier breakdown, and cerebral edema. We present other potential mechanisms by which VNS acts including enhancement of synaptic plasticity and recruitment of endogenous neural stem cells, stabilization of intracranial pressure, and interaction with the ghrelin system. In addition, alternative methods for the treatment of TBI including deep brain stimulation, transcranial magnetic stimulation, transcranial direct current stimulation, and focused ultrasound stimulation are discussed. Although the primary source data show that VNS improves TBI outcomes, it remains to be determined if these findings can be translated to clinical settings. PMID:26399249

  14. Clinical and objective data on spinal cord stimulation for the treatment of severe Raynaud's phenomenon.

    PubMed

    Neuhauser, B; Perkmann, R; Klingler, P J; Giacomuzzi, S; Kofler, A; Fraedrich, G

    2001-11-01

    Ischemic vascular disease of the upper extremity represents a difficult therapeutic problem wherein medical treatment often fails. Epidural spinal cord stimulation has been shown to be an effective alternative in severe peripheral arterial disease. Although this method has been used for nearly two decades only limited experience exists in Raynaud's phenomenon of the upper limbs. In addition objective parameters to prove therapeutic success are not well defined. Herein we describe a patient with severe primary Raynaud's phenomenon over several years who had significant pain relief and complete healing of ischemic digital ulcerations after spinal cord stimulation. Pain level was evaluated using a visual rating scale before and after surgery. Microcirculatory parameters were assessed before and after spinal cord stimulation by capillary microscopy and laser Doppler anemometry. Significant improvement of red blood cell velocity, capillary density, and capillary permeability was demonstrated. At follow-up 18 months after surgery the patient had no complaints and all ulcerations of her fingertips had healed. Spinal cord stimulation appears to be an effective treatment in severe cases of Raynaud's phenomenon and we recommend its use in the case of failed medical therapy. Pain rating and capillary microscopy enable one to assess and visualize the effects of spinal cord stimulation.

  15. Percutaneous biphasic electrical stimulation for treatment of obstructive sleep apnea syndrome.

    PubMed

    Hu, Lianggang; Xu, Xiaomei; Gong, Yongsheng; Fan, Xiaofang; Wang, Liangxing; Zhang, Jianhua; Zeng, Yanjun

    2008-01-01

    In this paper, we study the effect of stimulation of the genioglossus with percutaneous biphasic electrical pulses on patients with the obstructive sleep apnea syndrome (OSAS). The experiment was conducted in 22 patients clinically diagnosed with OSAS. The patients were monitored with polysomnography (PSG) in the trial. When the sleep apnea was detected, the genioglossus was stimulated with percutaneous biphasic electrical pulses that were automatically regulated by a microcontroller to achieve the optimal effect. The percutaneous biphasic electrical stimulation caused contraction of the genioglossus, forward movement of the tongue, and relieving of the glossopharyngeal airway obstruction. The SaO2, apnea time, hypoxemia time, and change of respiratory disturbance index (RDI) were compared in patients with treatment and without treatment. With percutaneous biphasic electrical stimulation of the genioglossus, the OSAS patients showed apnea time decreased (P < 0.01), RDI decreased (P < 0.01), and SaO2 increased (P < 0.01). No tissue injury or major discomfort was noticed during the trial. The stimulation of genioglossus with percutaneous biphasic electrical current pulse is an effective method for treating OSAS. PMID:18232360

  16. Percutaneous biphasic electrical stimulation for treatment of obstructive sleep apnea syndrome.

    PubMed

    Hu, Lianggang; Xu, Xiaomei; Gong, Yongsheng; Fan, Xiaofang; Wang, Liangxing; Zhang, Jianhua; Zeng, Yanjun

    2008-01-01

    In this paper, we study the effect of stimulation of the genioglossus with percutaneous biphasic electrical pulses on patients with the obstructive sleep apnea syndrome (OSAS). The experiment was conducted in 22 patients clinically diagnosed with OSAS. The patients were monitored with polysomnography (PSG) in the trial. When the sleep apnea was detected, the genioglossus was stimulated with percutaneous biphasic electrical pulses that were automatically regulated by a microcontroller to achieve the optimal effect. The percutaneous biphasic electrical stimulation caused contraction of the genioglossus, forward movement of the tongue, and relieving of the glossopharyngeal airway obstruction. The SaO2, apnea time, hypoxemia time, and change of respiratory disturbance index (RDI) were compared in patients with treatment and without treatment. With percutaneous biphasic electrical stimulation of the genioglossus, the OSAS patients showed apnea time decreased (P < 0.01), RDI decreased (P < 0.01), and SaO2 increased (P < 0.01). No tissue injury or major discomfort was noticed during the trial. The stimulation of genioglossus with percutaneous biphasic electrical current pulse is an effective method for treating OSAS.

  17. Vagus Nerve Stimulation and Other Neuromodulation Methods for Treatment of Traumatic Brain Injury.

    PubMed

    Neren, Daniel; Johnson, Matthew D; Legon, Wynn; Bachour, Salam P; Ling, Geoffrey; Divani, Afshin A

    2016-04-01

    The objective of this paper is to review the current literature regarding the use of vagus nerve stimulation (VNS) in preclinical models of traumatic brain injury (TBI) as well as discuss the potential role of VNS along with alternative neuromodulation approaches in the treatment of human TBI. Data from previous studies have demonstrated VNS-mediated improvement following TBI in animal models. In these cases, VNS was observed to enhance motor and cognitive recovery, attenuate cerebral edema and inflammation, reduce blood brain barrier breakdown, and confer neuroprotective effects. Yet, the underlying mechanisms by which VNS enhances recovery following TBI remain to be fully elucidated. Several hypotheses have been offered including: a noradrenergic mechanism, reduction in post-TBI seizures and hyper-excitability, anti-inflammatory effects, attenuation of blood-brain barrier breakdown, and cerebral edema. We present other potential mechanisms by which VNS acts including enhancement of synaptic plasticity and recruitment of endogenous neural stem cells, stabilization of intracranial pressure, and interaction with the ghrelin system. In addition, alternative methods for the treatment of TBI including deep brain stimulation, transcranial magnetic stimulation, transcranial direct current stimulation, and focused ultrasound stimulation are discussed. Although the primary source data show that VNS improves TBI outcomes, it remains to be determined if these findings can be translated to clinical settings.

  18. Yhhu981, a novel compound, stimulates fatty acid oxidation via the activation of AMPK and ameliorates lipid metabolism disorder in ob/ob mice

    PubMed Central

    Zeng, Hong-liang; Huang, Su-ling; Xie, Fu-chun; Zeng, Li-min; Hu, You-hong; Leng, Ying

    2015-01-01

    Aim: Defects in fatty acid metabolism contribute to the pathogenesis of insulin resistance and obesity. In this study, we investigated the effects of a novel compound yhhu981 on fatty acid metabolism in vitro and in vivo. Methods: The capacity to stimulate fatty acid oxidation was assessed in C2C12 myotubes. The fatty acid synthesis was studied in HepG2 cells using isotope tracing. The phosphorylation of AMPK and acetyl-CoA carboxylase (ACC) was examined with Western blot analysis. For in vivo experiments, ob/ob mice were orally treated with yhhu981 acutely (300 mg/kg) or chronically (150 or 300 mg·kg−1·d−1 for 22 d). On the last day of treatment, serum and tissue samples were collected for analysis. Results: Yhhu981 (12.5–25 μmol/L) significantly increased fatty acid oxidation and the expression of related genes (Sirt1, Pgc1α and Mcad) in C2C12 myotubes, and inhibited fatty acid synthesis in HepG2 cells. Furthermore, yhhu981 dose-dependently increased the phosphorylation of AMPK and ACC in both C2C12 myotubes and HepG2 cells. Compound C, an AMPK inhibitor, blocked fatty acid oxidation in yhhu981-treated C2C12 myotubes and fatty acid synthesis decrease in yhhu981-treated HepG2 cells. Acute administration of yhhu981 decreased the respiratory exchange ratio in ob/ob mice, whereas chronic treatment with yhhu981 ameliorated the lipid abnormalities and ectopic lipid deposition in skeletal muscle and liver of ob/ob mice. Conclusion: Yhhu981 is a potent compound that stimulates fatty acid oxidation, and exerts pleiotropic effects on lipid metabolism by activating AMPK. PMID:25732571

  19. Lignor process for acidic rock drainage treatment.

    PubMed

    Zhuang, J M; Walsh, T

    2004-09-01

    The process using lignosulfonates for acidic rock drainage (ARD) treatment is referred to as the Lignor process. Lignosulfonates are waste by-products produced in the sulfite pulping process. The present study has shown lignosulfonates are able to protect lime from developing an external surface coating, and hence to favor its dissociation. Further, the addition of lignosulfonates to ARD solutions increased the dotting and settling rate of the formed sludge. The capability of lignosulfonates to form stable metal-lignin complexes makes them very useful in retaining metal ions and thus improving the long-term stability of the sludge against leaching. The Lignor process involves metal sorption with lignosulfonates, ARD neutralization by lime to about pH 7, pH adjustment with caustic soda to 9.4 - 9.6, air oxidation to lower the pH to a desired level, and addition of a minimum amount of FeCl3 for further removal of dissolved metals. The Lignor process removes all concerned metals (especially Al and Mn) from the ARD of the Britannia Mine (located at Britannia Beach, British Columbia, Canada) to a level lower than the limits of the B.C. Regulations. Compared with the high-density sludge (HDS) process, the Lignor process has many advantages, such as considerable savings in lime consumption, greatly reduced sludge volume, and improved sludge stability. PMID:15515269

  20. Treatment of NASH with ursodeoxycholic acid: pro.

    PubMed

    Ratziu, Vlad

    2012-09-01

    Ursodeoxycholic acid (UDCA) is one of hepatologists'oldest friends, always ready to help, throughout the years, in numerous and various liver and biliary tract diseases. On paper, it has had an impeccable track record of cytoprotection in vitro and in vivo due to its pleiotropic effects on many pathways leading to cell injury. Most of its hepatoprotective effects demonstrated under experimental conditions proved able to counteract pathogenic mechanisms involved in the transition from steatosis to steatohepatitis, and early clinical studies suggested a potentially beneficial effect in non-alcoholic steatohepatitis (NASH) as well. Yet, only scant data on the efficacy of UDCA specifically in experimental models of steatosis/NASH are available, and the few available randomized controlled clinical studies have substantial methodological issues and are discussed in this review. Thus, at this point, there is not enough evidence to either confirm or reject the efficacy of UDCA in NASH, although many NASH patients clearly experience biochemical improvements with prolonged UDCA treatment. Also, a few new UDCA derivatives have shown promising activity in preclinical models and may be worth testing in clinical trials. PMID:23141893

  1. Effects of alkali or acid treatment on the isomerization of amino acids.

    PubMed

    Ohmori, Taketo; Mutaguchi, Yuta; Doi, Katsumi; Ohshima, Toshihisa

    2012-10-01

    The effect of alkali treatment on the isomerization of amino acids was investigated. The 100×D/(D+L) values of amino acids from peptide increased with increase in the number of constituent amino acid residues. Furthermore, the N-terminal amino acid of a dipeptide was isomerized to a greater extent than the C-terminal residue.

  2. Cinnamic acid exerts anti-diabetic activity by improving glucose tolerance in vivo and by stimulating insulin secretion in vitro.

    PubMed

    Hafizur, Rahman M; Hameed, Abdul; Shukrana, Mishkat; Raza, Sayed Ali; Chishti, Sidra; Kabir, Nurul; Siddiqui, Rehan A

    2015-02-15

    Although the anti-diabetic activity of cinnamic acid, a pure compound from cinnamon, has been reported but its mechanism(s) is not yet clear. The present study was designed to explore the possible mechanism(s) of anti-diabetic activity of cinnamic acid in in vitro and in vivo non-obese type 2 diabetic rats. Non-obese type 2 diabetes was developed by injecting 90 mg/kg streptozotocin in 2-day-old Wistar pups. Cinnamic acid and cinnamaldehyde were administered orally to diabetic rats for assessing acute blood glucose lowering effect and improvement of glucose tolerance. Additionally, insulin secretory activity of cinnamic acid and cinnamaldehyde was evaluated in isolated mice islets. Cinnamic acid, but not cinnamaldehyde, decreased blood glucose levels in diabetic rats in a time- and dose-dependent manner. Oral administration of cinnamic acid with 5 and 10 mg/kg doses to diabetic rats improved glucose tolerance in a dose-dependent manner. The improvement by 10 mg/kg cinnamic acid was comparable to that of standard drug glibenclamide (5 mg/kg). Further in vitro studies showed that cinnamaldehyde has little or no effect on glucose-stimulated insulin secretion; however, cinnamic acid significantly enhanced glucose-stimulated insulin secretion in isolated islets. In conclusion, it can be said that cinnamic acid exerts anti-diabetic activity by improving glucose tolerance in vivo and stimulating insulin secretion in vitro.

  3. Physiology-driven adaptive virtual reality stimulation for prevention and treatment of stress related disorders.

    PubMed

    Cosić, Kresimir; Popović, Sinisa; Kukolja, Davor; Horvat, Marko; Dropuljić, Branimir

    2010-02-01

    The significant proportion of severe psychological problems related to intensive stress in recent large peacekeeping operations underscores the importance of effective methods for strengthening the prevention and treatment of stress-related disorders. Adaptive control of virtual reality (VR) stimulation presented in this work, based on estimation of the person's emotional state from physiological signals, may enhance existing stress inoculation training (SIT). Physiology-driven adaptive VR stimulation can tailor the progress of stressful stimuli delivery to the physiological characteristics of each individual, which is indicated for improvement in stress resistance. Following an overview of physiology-driven adaptive VR stimulation, its major functional subsystems are described in more detail. A specific algorithm of stimuli delivery applicable to SIT is outlined. PMID:20528296

  4. Improved reading measures in adults with dyslexia following transcranial direct current stimulation treatment.

    PubMed

    Heth, Inbahl; Lavidor, Michal

    2015-04-01

    To better understand the contribution of the dorsal system to word reading, we explored transcranial direct current stimulation (tDCS) effects when adults with developmental dyslexia received active stimulation over the visual extrastriate area MT/V5, which is dominated by magnocellular input. Stimulation was administered in 5 sessions spread over two weeks, and reading speed and accuracy as well as reading fluency were assessed before, immediately after, and a week after the end of the treatment. A control group of adults with developmental dyslexia matched for age, gender, reading level, vocabulary and block-design WAIS-III sub-tests and reading level was exposed to the same protocol but with sham stimulation. The results revealed that active, but not sham stimulation, significantly improved reading speed and fluency. This finding suggests that the dorsal stream may play a role in efficient retrieval from the orthographic input lexicon in the lexical route. It also underscores the potential of tDCS as an intervention tool for improving reading speed, at least in adults with developmental dyslexia.

  5. Hyaluronic Acid Suppresses the Expression of Metalloproteinases in Osteoarthritic Cartilage Stimulated Simultaneously by Interleukin 1β and Mechanical Load

    PubMed Central

    Pohlig, Florian; Guell, Florian; Lenze, Ulrich; Lenze, Florian W.; Mühlhofer, Heinrich M. L.; Schauwecker, Johannes; Toepfer, Andreas; Mayer-Kuckuk, Philipp; von Eisenhart-Rothe, Rüdiger; Burgkart, Rainer; Salzmann, Gian M.

    2016-01-01

    Purpose In patients with osteoarthritis (OA), intraarticular injection of hyaluronic acid (HA) frequently results in reduced pain and improved function for prolonged periods of time, i.e. more than 6 months. However, the mechanisms underlying these effects are not fully understood. Our underlying hypothesis is that HA modifies the enzymatic breakdown of joint tissues. Methods To test this hypothesis, we examined osteochondral cylinders from 12 OA patients. In a bioreactor, these samples were stimulated by interleukin 1β (Il1ß) (2 ng/ml) plus mechanical load (2.0 Mpa at 0.5 Hz horizontal and 0.1 Hz vertical rotation), thus the experimental setup recapitulated both catabolic and anabolic clues of the OA joint. Results Upon addition of HA at either 1 or 3 mg/ml, we observed a significant suppression of expression of metalloproteinase (MMP)-13. A more detailed analysis based on the Kellgren and Lawrence (K&L) OA grade, showed a much greater degree of suppression of MMP-13 expression in grade IV as compared to grade II OA. In contrast to the observed MMP-13 suppression, treatment with HA resulted in a suppression of MMP-1 expression only at 1 mg/ml HA, while MMP-2 expression was not significantly affected by either HA concentration. Conclusion Together, these data suggest that under concurrent catabolic and anabolic stimulation, HA exhibits a pronounced suppressive effect on MMP-13. In the long-run these findings may benefit the development of treatment strategies aimed at blocking tissue degradation in OA patients. PMID:26934732

  6. Human prostatic acid phosphatase directly stimulates collagen synthesis and alkaline phosphatase content of isolated bone cells

    SciTech Connect

    Ishibe, M.; Rosier, R.N.; Puzas, J.E. )

    1991-10-01

    Human prostatic acid phosphatase (hPAP) directly enhances the differentiated characteristics of isolated bone cells in vitro. This enzyme, when added to cell cultures for 24 h in vitro stimulates collagen synthesis and the production of alkaline phosphatase. The effects are dose dependent, with statistically significant effects occurring from 0.1-100 nM hPAP. Concentrations higher than 100 nM do not evoke greater effects. The maximal effect of hPAP occurs between 12 and 24 h of exposure. The cells stimulated to the greatest degree are osteoprogenitor cells and osteoblasts. Fibroblasts isolated from the same tissue show a lesser sensitivity to hPAP. hPAP has no detectable effect on cell proliferation, as measured by radiolabeled thymidine incorporation or total DNA synthesis. None of the observations reported in this work can be attributed to contaminating proteins in the hPAP preparation. hPAP was radiolabeled with 125I and was used for affinity binding and cross-linking studies. Scatchard analysis of specific binding indicated the presence of 1.0 X 10(5) high affinity binding sites/cell, with a Kd of 6.5 nM. Cross-linking studies demonstrated the presence of one 320-kDa binding complex. The pH profile and kinetic determinations of Km and maximum velocity for hPAP were similar to those previously reported, except for the finding of positive cooperativity of the substrate with the enzyme under the conditions of our assay. We believe that the direct stimulation of bone-forming cells by hPAP may contribute to the sclerotic nature of skeletal bone around sites of neoplastic prostatic metastases and that the effect of the enzyme is probably mediated by a plasma membrane receptor.

  7. Lobaric Acid Inhibits VCAM-1 Expression in TNF-α-Stimulated Vascular Smooth Muscle Cells via Modulation of NF-κB and MAPK Signaling Pathways

    PubMed Central

    Kwon, Ii-Seul; Yim, Joung-Han; Lee, Hong-Kum; Pyo, Suhkneung

    2016-01-01

    Lichens have been known to possess multiple biological activities, including anti-proliferative and anti-inflammatory activities. Vascular cell adhesion molecule-1 (VCAM-1) may play a role in the development of atherosclerosis. Hence, VCAM-1 is a possible therapeutic target in the treatment of the inflammatory disease. However, the effect of lobaric acid on VCAM-1 has not yet been investigated and characterized. For this study, we examined the effect of lobaric acid on the inhibition of VCAM-1 in tumor necrosis factor-alpha (TNF-α)-stimulated mouse vascular smooth muscle cells. Western blot and ELISA showed that the increased expression of VCAM-1 by TNF-α was significantly suppressed by the pre-treatment of lobaric acid (0.1–10 μg/ml) for 2 h. Lobaric acid abrogated TNF-α-induced NF-κB activity through preventing the degradation of IκB and phosphorylation of extracellular signal-regulated kinases (ERK), c-Jun N-terminal kinases (JNK), and p38 mitogen activated protein (MAP) kinase. Lobaric acid also inhibited the expression of TNF-α receptor 1 (TNF-R1). Overall, our results suggest that lobaric acid inhibited VCAM-1 expression through the inhibition of p38, ERK, JNK and NF-κB signaling pathways, and downregulation of TNF-R1 expression. Therefore, it is implicated that lobaric acid may suppress inflammation by altering the physiology of the atherosclerotic lesion. PMID:26759698

  8. Stimulation of proliferation of an essential fatty acid-deficient fish cell line by C20 and C22 polyunsaturated fatty acids and effects on fatty acid composition.

    PubMed

    Tocher, D R; Dick, J R; Sargent, J R

    1996-11-01

    Recently we reported the development of a fish cell line, EPC-EFAD, derived from the carp (Cyprinus carpio) epithelial papilloma line, EPC, that could survive and proliferate in essential fatty acid-deficient (EFAD) medium. The EPC-EFAD cell line may be a useful model system in which to study the cellular biochemical effects of EFA deficiency and has advantages in studies of polyunsaturated fatty acid (PUFA) and eicosanoid metabolism in fish in that the complications introduced by culture in relatively n-6 PUFA-rich mammalian sera are removed. In the present study, the effects on cell proliferation rate of supplementing EPC-EFAD cells with various n-3 and n-6 PUFA were investigated to determine the possible role(s) of PUFA in cell growth and division. The selectivity of incorporation of specific PUFA into individual glycerophospholipid classes and the feasibility of reproducing in vivo fatty acid compositions in vitro were also investigated. Proliferation of the EPC-EFAD cell line was stimulated by arachidonic (20:4 n-6), eicosapentaenoic (20:5 n-3) and docosahexaenoic (22:6 n-3) fatty acids but not by 18:2 n-6 or 18:3 n-3. The differential effects of PUFA on cellular proliferation may be related to the lack of significant delta 5 desaturase activity in the cells at 22 degrees C and may implicate a role for eicosanoids in the mechanism of stimulation of proliferation. PUFA supplementation increased the cytotoxic effects of longer term culture, an effect that was partly alleviated by inclusion of vitamin E in the culture medium. The cells could generally be supplemented with PUFA to produce cellular fatty acid compositions in vitro that were similar to in vivo compositions. PMID:8981632

  9. [Evaluation of repetitive transcranial magnetic stimulation effectiveness in treatment of psychiatric and neurologic diseases].

    PubMed

    Pastuszak, Żanna; Stępień, Anna; Piusińska-Macoch, Renata; Brodacki, Bogdan; Tomczykiewicz, Kazimierz

    2016-06-01

    Repetitive transcranial magnetic stimulation (rTMS) is a treatment option with proved effectiveness especially in drug resist depression. It is used in functional brain mapping before neurosurgery operations and diagnostic of corticospinal tract transmission. Many studies are performed to evaluate rTMS using in treatment of obsessive - compulsive disorder, schizophrenia, autism, strokes, tinnitus, Alzheimer and Parkinson diseases, cranial traumas. Moreover rTMS was used in treatment of multiple sclerosis, migraine, dystonia. Electromagnetical field generated by rTMS penetrate skin of the scalp and infiltrate brain tissues to a depth of 2 cm, cause neurons depolarization and generating motor, cognitive and affective effects. Depending on the stimulation frequency rTMS can stimuli or inhibit brain cortex. rTMS mechanism of action remains elusive. Probably it is connected with enhancement of neurotransmitters, modulation of signals transductions pathways in Central Nervous System, gene transcription and release of neuroprotective substances. Studies with use of animals revealed that rTMS stimulation can generate brain changes similar to those seen after electric shock therapy without provoking seizures. The aim of presenting study was to analyze actual researches evaluating rTMS use in treatment of psychiatric and neurological diseases. PMID:27403908

  10. Effects of Duloxetine Treatment on Brain Response to Painful Stimulation in Major Depressive Disorder

    PubMed Central

    López-Solà, Marina; Pujol, Jesus; Hernández-Ribas, Rosa; Harrison, Ben J; Contreras-Rodríguez, Oren; Soriano-Mas, Carles; Deus, Joan; Ortiz, Héctor; Menchón, José M; Vallejo, Julio; Cardoner, Narcís

    2010-01-01

    Major depressive disorder (MDD) is characterized by a constellation of affective, cognitive, and somatic symptoms associated with functional abnormalities in relevant brain systems. Painful stimuli are primarily stressful and can trigger consistent responses in brain regions highly overlapping with the regions altered in MDD patients. Duloxetine has proven to be effective in treating both core emotional symptoms and somatic complaints in depression. This study aimed to assess the effects of duloxetine treatment on brain response to painful stimulation in MDD patients. A total of 13 patients and a reference group of 20 healthy subjects were assessed on three occasions (baseline, treatment week 1, and week 8) with functional magnetic resonance imaging (fMRI) during local application of painful heat stimulation. Treatment with duloxetine was associated with a significant reduction in brain responses to painful stimulation in MDD patients in regions generally showing abnormally enhanced activation at baseline. Clinical improvement was associated with pain-related activation reductions in the pregenual anterior cingulate cortex, right prefrontal cortex, and pons. Pontine changes were specifically related to clinical remission. Increased baseline activations in the right prefrontal cortex and reduced deactivations in the subgenual anterior cingulate cortex predicted treatment responders at week 8. This is the first fMRI study addressed to assess the effect of duloxetine in MDD. As a novel approach, the application of painful stimulation as a basic neural stressor proved to be effective in mapping brain response changes associated with antidepressant treatment and brain correlates of symptom improvement in regions of special relevance to MDD pathophysiology. PMID:20668437

  11. Comparison of specific activity of granulocytopoiesis stimulators after treatment with cytostatics with different mechanisms of action.

    PubMed

    Dygai, A M; Zhdanov, V V; Miroshnichenko, L A; Zyuz'kov, G N; Udut, E V; Simanina, E V; Stavrova, L A; Khrichkova, T Y; Agafonov, V I

    2013-09-01

    We compared hemostimulating effects of glyciram, pantohematogen, granulocytic CSF, and D-glucuronic acid preparation on the granulocytic lineage hemopoiesis suppressed by cyclophosphamide or 5-fluorouracil. The effects hemostimulators against the background of 5-fluorouracil treatment were less pronounced that during cyclophosphamide treatment.

  12. Lysophosphatidic acid stimulates thrombomodulin lectin-like domain shedding in human endothelial cells

    SciTech Connect

    Wu Hualin; Lin ChiIou; Huang Yuanli; Chen, Pin-Shern; Kuo, Cheng-Hsiang; Chen, Mei-Shing; Wu, G.C.-C.; Shi, G.-Y.; Yang, H.-Y.; Lee Hsinyu

    2008-02-29

    Thrombomodulin (TM) is an anticoagulant glycoprotein highly expressed on endothelial cell surfaces. Increased levels of soluble TM in circulation have been widely accepted as an indicator of endothelial damage or dysfunction. Previous studies indicated that various proinflammatory factors stimulate TM shedding in various cell types such as smooth muscle cells and epithelial cells. Lysophosphatidic acid (LPA) is a bioactive lipid mediator present in biological fluids during endothelial damage or injury. In the present study, we first observed that LPA triggered TM shedding in human umbilical vein endothelial cells (HUVECs). By Cyflow analysis, we showed that the LPA-induced accessibility of antibodies to the endothelial growth factor (EGF)-like domain of TM is independent of matrix metalloproteinases (MMPs), while LPA-induced TM lectin-like domain shedding is MMP-dependent. Furthermore, a stable cell line expressing TM without its lectin-like domain exhibited a higher cell proliferation rate than a stable cell line expressing full-length TM. These results imply that LPA induces TM lectin-like domain shedding, which might contribute to the exposure of its EGF-like domain for EGF receptor (EGFR) binding, thereby stimulating subsequent cell proliferation. Based on our findings, we propose a novel mechanism for the exposure of TM EGF-like domain, which possibly mediates LPA-induced EGFR transactivation.

  13. Non-Invasive Vagus Nerve Stimulation as Treatment for Trigeminal Allodynia

    PubMed Central

    Oshinsky, Michael L.; Murphy, Angela L.; Hekierski, Hugh; Cooper, Marnie; Simon, Bruce J.

    2014-01-01

    Implanted vagus nerve stimulation (VNS) has been used to treat seizures and depression. In this study, we explore the mechanism of action of non-invasive vagus nerve stimulation (nVNS) for the treatment of trigeminal allodynia. Rats were repeatedly infused with inflammatory mediators directly onto the dura, which leads to chronic trigeminal allodynia. nVNS for 2min decreases periorbital sensitivity in rats with periorbital trigeminal allodynia for up to 3.5hr after stimulation. Using microdialysis, we quantified levels of extracellular neurotransmitters in the trigeminal nucleus caudalis (TNC). Allodynic rats showed a 7.7±0.9 fold increase in extracellular glutamate in the TNC following i.p. administration of the chemical headache trigger, glyceryl trinitrate (GTN; 0.1mg/kg). Allodynic rats, which received nVNS, had only a 2.3±0.4 fold increase in extracellular glutamate following GTN similar to the response in control naive rats. When nVNS was delayed until 120min after GTN treatment, the high levels of glutamate in the TNC were reversed following nVNS. The nVNS stimulation parameters used in this study did not produce significant changes in blood pressure or heart rate. These data suggest that nVNS may be used to treat trigeminal allodynia. PMID:24530613

  14. The SCFA butyrate stimulates the epithelial production of retinoic acid via inhibition of epithelial HDAC.

    PubMed

    Schilderink, Ronald; Verseijden, Caroline; Seppen, Jurgen; Muncan, Vanesa; van den Brink, Gijs R; Lambers, Tim T; van Tol, Eric A; de Jonge, Wouter J

    2016-06-01

    In the intestinal mucosa, retinoic acid (RA) is a critical signaling molecule. RA is derived from dietary vitamin A (retinol) through conversion by aldehyde dehydrogenases (aldh). Reduced levels of short-chain fatty acids (SCFAs) are associated with pathological microbial dysbiosis, inflammatory disease, and allergy. We hypothesized that SCFAs contribute to mucosal homeostasis by enhancing RA production in intestinal epithelia. With the use of human and mouse epithelial cell lines and primary enteroids, we studied the effect of SCFAs on the production of RA. Functional RA conversion was analyzed by Adlefluor activity assays. Butyrate (0-20 mM), in contrast to other SCFAs, dose dependently induced aldh1a1 or aldh1a3 transcript expression and increased RA conversion in human and mouse epithelial cells. Epithelial cell line data were replicated in intestinal organoids. In these organoids, butyrate (2-5 mM) upregulated aldh1a3 expression (36-fold over control), whereas aldh1a1 was not significantly affected. Butyrate enhanced maturation markers (Mucin-2 and villin) but did not consistently affect stemness markers or other Wnt target genes (lgr5, olfm4, ascl2, cdkn1). In enteroids, the stimulation of RA production by SCFA was mimicked by inhibitors of histone deacetylase 3 (HDAC3) but not by HDAC1/2 inhibitors nor by agonists of butyrate receptors G-protein-coupled receptor (GPR)43 or GPR109A, indicating that butyrate stimulates RA production via HDAC3 inhibition. We conclude that the SCFA butyrate inhibits HDAC3 and thereby supports epithelial RA production. PMID:27151945

  15. The use of dopaminergic and stimulant drugs for the treatment of depression.

    PubMed

    Howland, Robert H

    2012-02-01

    The brain reward system consists of extensive neural pathways that mediate reward behavior such as pleasure and motivation. These pathways may be involved in the development of symptoms such as apathy, anhedonia, and cognitive dysfunction seen in patients with major depression. These pathways are served primarily, although not exclusively, by the chemical neurotransmitter dopamine, which has suggested a therapeutic role for drugs that influence dopamine activity. A small number of clinical trials using various dopaminergic and stimulant drugs for the treatment of major depression and bipolar depression have demonstrated some benefit when combined with standard antidepressant drugs. Based on this work, several ongoing trials are investigating the use of the stimulant drug lisdexamfetamine (Vyvanse®) as an adjunctive treatment for depression.

  16. The requirement for membrane sialic acid in the stimulation of superoxide production during phagocytosis by human polymorphonuclear leukocytes

    PubMed Central

    1976-01-01

    The effect of desialylation on phagocytosis of latex particles and oxidative metabolism of human polymorphonuclear leukocytes was studied. Removal of 20% total leukocyte sialic acid by bacterial neuraminidase had no effect on phagocytosis of latex particles and phagocytosis- associated activation of hexose monophosphate shunt in human polymorphonuclear leukocytes. In contrast, desialylation prevented the stimulation of superoxide production either by phagocytosis or by concanavalin A. It is concluded that membrane sialic acid is essential for the stimulation of superoxide production by human polymorphonuclear leukocytes. PMID:178821

  17. Systematic review of stimulant and nonstimulant laxatives for the treatment of functional constipation

    PubMed Central

    Paré, Pierre; Fedorak, Richard N

    2014-01-01

    BACKGROUND: Constipation is an uncomfortable and common condition that affects many, irrespective of age. Since 1500 BC and before, health care practitioners have provided treatments and prevention strategies to patients for chronic constipation despite the significant variation in both medical and personal perceptions of the condition. OBJECTIVE: To review relevant research evidence from clinical studies investigating the efficacy and safety of commercially available pharmacological laxatives in Canada, with emphasis on studies adopting the Rome criteria for defining functional constipation. SEARCH METHODS: PubMed, Medline, Embase and Evidence-Based Medicine Reviews databases were searched for blinded or randomized clinical trials and meta-analyses assessing the efficacy of nonstimulant and stimulant laxatives for the treatment of functional constipation. RESULTS: A total of 19 clinical studies and four meta-analyses were retrieved and abstracted regarding study design, participants, interventions and outcomes. The majority of studies focused on polyethylene glycol compared with placebo. Both nonstimulant and stimulant laxatives provided better relief of constipation symptoms than placebo according to both objective and subjective measures. Only one study compared the efficacy of a nonstimulant versus a stimulant laxative, while only two reported changes in quality of life. All studies reported minor side effects due to laxative use, regardless of treatment duration, which ranged from one week to one year. Laxatives were well tolerated by both adults and children. PMID:25390617

  18. Regulation of primary metabolic pathways in oyster mushroom mycelia induced by blue light stimulation: accumulation of shikimic acid.

    PubMed

    Kojima, Masanobu; Kimura, Ninako; Miura, Ryuhei

    2015-02-27

    Shikimic acid is a key intermediate in the aromatic amino acid pathway as well as an important starting material for the synthesis of Tamiflu, a potent and selective inhibitor of the neuraminidase enzyme of influenza viruses A and B. Here we report that in oyster mushroom (Pleurotus ostreatus) mycelia cultivated in the dark, stimulation with blue light-emitting diodes induces the accumulation of shikimic acid. An integrated analysis of primary metabolites, gene expression and protein expression suggests that the accumulation of shikimic acid caused by blue light stimulation is due to an increase in 3-deoxy-D-arabinoheptulosonate 7-phosphate synthase (DAHPS, EC2.5.1.54), the rate-determining enzyme in the shikimic acid pathway, as well as phosphofructokinase (PFK, EC2.7.1.11) and glucose-6-phosphate dehydrogenase (G6PD, EC1.1.1.49), the rate-determining enzymes in the glycolysis and pentose phosphate pathways, respectively. This stimulation results in increased levels of phosphoenolpyruvic acid (PEP) and erythrose-4-phosphate (E4P), the starting materials of shikimic acid biosynthesis.

  19. Regulation of primary metabolic pathways in oyster mushroom mycelia induced by blue light stimulation: accumulation of shikimic acid.

    PubMed

    Kojima, Masanobu; Kimura, Ninako; Miura, Ryuhei

    2015-01-01

    Shikimic acid is a key intermediate in the aromatic amino acid pathway as well as an important starting material for the synthesis of Tamiflu, a potent and selective inhibitor of the neuraminidase enzyme of influenza viruses A and B. Here we report that in oyster mushroom (Pleurotus ostreatus) mycelia cultivated in the dark, stimulation with blue light-emitting diodes induces the accumulation of shikimic acid. An integrated analysis of primary metabolites, gene expression and protein expression suggests that the accumulation of shikimic acid caused by blue light stimulation is due to an increase in 3-deoxy-D-arabinoheptulosonate 7-phosphate synthase (DAHPS, EC2.5.1.54), the rate-determining enzyme in the shikimic acid pathway, as well as phosphofructokinase (PFK, EC2.7.1.11) and glucose-6-phosphate dehydrogenase (G6PD, EC1.1.1.49), the rate-determining enzymes in the glycolysis and pentose phosphate pathways, respectively. This stimulation results in increased levels of phosphoenolpyruvic acid (PEP) and erythrose-4-phosphate (E4P), the starting materials of shikimic acid biosynthesis. PMID:25721093

  20. Regulation of Primary Metabolic Pathways in Oyster Mushroom Mycelia Induced by Blue Light Stimulation: Accumulation of Shikimic Acid

    PubMed Central

    Kojima, Masanobu; Kimura, Ninako; Miura, Ryuhei

    2015-01-01

    Shikimic acid is a key intermediate in the aromatic amino acid pathway as well as an important starting material for the synthesis of Tamiflu, a potent and selective inhibitor of the neuraminidase enzyme of influenza viruses A and B. Here we report that in oyster mushroom (Pleurotus ostreatus) mycelia cultivated in the dark, stimulation with blue light-emitting diodes induces the accumulation of shikimic acid. An integrated analysis of primary metabolites, gene expression and protein expression suggests that the accumulation of shikimic acid caused by blue light stimulation is due to an increase in 3-deoxy-D-arabinoheptulosonate 7-phosphate synthase (DAHPS, EC2.5.1.54), the rate-determining enzyme in the shikimic acid pathway, as well as phosphofructokinase (PFK, EC2.7.1.11) and glucose-6-phosphate dehydrogenase (G6PD, EC1.1.1.49), the rate-determining enzymes in the glycolysis and pentose phosphate pathways, respectively. This stimulation results in increased levels of phosphoenolpyruvic acid (PEP) and erythrose-4-phosphate (E4P), the starting materials of shikimic acid biosynthesis. PMID:25721093

  1. Transforming growth factor-beta 1 stimulates vascular smooth muscle cell L-proline transport by inducing system A amino acid transporter 2 (SAT2) gene expression.

    PubMed Central

    Ensenat, D; Hassan, S; Reyna, S V; Schafer, A I; Durante, W

    2001-01-01

    Transforming growth factor-beta1 (TGF-beta 1) is a multifunctional cytokine that contributes to arterial remodelling by stimulating vascular smooth muscle cell (SMC) growth and collagen synthesis at sites of vascular injury. Since l-proline is essential for the synthesis of collagen, we examined whether TGF-beta 1 regulates the transcellular transport of l-proline by vascular SMCs. l-Proline uptake by vascular SMCs was primarily sodium-dependent, pH-sensitive, blocked by neutral amino acids and alpha-(methylamino)isobutyric acid, and exhibited trans-inhibition. Treatment of SMCs with TGF-beta 1 stimulated l-proline transport in a concentration- and time-dependent manner. The TGF-beta 1-mediated l-proline uptake was inhibited by cycloheximide or actinomycin D. Kinetic studies indicated that TGF-beta 1-induced l-proline transport was mediated by an increase in transport capacity independent of any changes in the affinity for l-proline. TGF-beta 1 stimulated the expression of system A amino acid transporter 2 (SAT2) mRNA in a time-dependent fashion that paralleled the increase in l-proline transport. Reverse transcriptase PCR failed to detect the presence of SAT1 or amino acid transporter 3 (ATA3) in either untreated or TGF-beta 1-treated SMCs. These results demonstrate that l-proline transport by vascular SMCs is mediated predominantly by the SAT and that TGF-beta 1 stimulates SMC l-proline uptake by inducing the expression of the SAT2 gene. The ability of TGF-beta 1 to induce SAT2 expression may function to provide SMCs with the necessary levels of l-proline required for collagen synthesis and cell growth. PMID:11716780

  2. Lysophosphatidic Acid Stimulates MCP-1 Secretion from C2C12 Myoblast.

    PubMed

    Tsukahara, Tamotsu; Haniu, Hisao

    2012-01-01

    Chemokines are regulatory proteins that play an important role in muscle cell migration and proliferation. In this study, C2C12 cells treated with lysophosphatidic acid (LPA) showed an increase in endogenous monocyte chemotactic protein-1 (MCP-1) expression and secretion. LPA is a naturally occurring bioactive lysophospholipid with hormone- and growth-factor-like activities. LPA is produced by activated platelets, cytokine-stimulated leukocytes, and possibly by other cell types. However, the LPA analog cyclic phosphatidic acid (cPA) had no effect on the expression and secretion of MCP-1. LPA, although similar in structure to cPA, had potent inducing effects on MCP-1 expression in C2C12 cells. In this study, we showed that LPA enhanced MCP-1 mRNA expression and protein secretion in a dose-dependent manner. Taken together, these results suggest that LPA enhances MCP-1 secretion in C2C12 cells and thus may play an important role in cell proliferation. PMID:24049655

  3. Lipoxygenase-mediated pro-radical effect of melatonin via stimulation of arachidonic acid metabolism

    SciTech Connect

    Radogna, F.; Sestili, P.; Martinelli, C.; Paolillo, M.; Paternoster, L.; Albertini, M.C.; Accorsi, A.; Gualandi, G.; Ghibelli, L.

    2009-07-15

    We have shown that melatonin immediately and transiently stimulates intracellular free radical production on a set of leukocytes, possibly as a consequence of calmodulin binding. We show here that melatonin-induced ROS are produced by lipoxygenase (LOX), since they are prevented by a set of LOX inhibitors, and are accompanied by increase of the 5-LOX product 5-HETE. LOX activation is accompanied by strong liberation of AA; inhibition of Ca{sup 2+}-independent, but not Ca{sup 2+}-dependent, phospholipase A2 (PLA2), prevents both melatonin-induced arachidonic acid and ROS production, whereas LOX inhibition only prevents ROS, indicating that PLA2 is upstream with respect to LOX, as occurs in many signaling pathways. Chlorpromazine, an inhibitor of melatonin-calmodulin interaction, inhibits both ROS and arachidonic acid production, thus possibly placing calmodulin at the origin of a melatonin-induced pro-radical pathway. Interestingly, it is known that Ca{sup 2+}-independent PLA2 binds to calmodulin: our results are compatible with PLA2 being liberated by melatonin from a steady-state calmodulin sequestration, thus initiating an arachidonate signal transduction. These results delineate a novel molecular pathway through which melatonin may participate to the inflammatory response.

  4. Segmental noxious versus innocuous electrical stimulation for chronic pain relief and the effect of fading sensation during treatment.

    PubMed

    Defrin, Ruth; Ariel, Efrat; Peretz, Chava

    2005-05-01

    It is not clear whether segmental innocuous stimulation has a stronger analgesic effect than segmental noxious stimulation for chronic pain and whether the fading of current sensation during treatment interferes with the analgesic effect, as suggested by the gate control theory. Electrical stimulation (by way of Interferential Current) applied at the pain area (segmental) was administered to 4 groups of patients with osteoarthritis (OA) knee pain. Two groups were administered with noxious stimulation (30% above pain threshold) and two with innocuous stimulation (30% below pain threshold). In each group half of the patients received a fixed current intensity while the other half raised the intensity continuously during treatment whenever fading of sensation was perceived. Group 5 and 6 received sham stimulation and no treatment, respectively. The outcome measures were: chronic pain intensity, morning stiffness, range of motion (ROM), pain threshold and % pain reduction. Both noxious and innocuous stimulation significantly decreased chronic pain (P<0.001) and morning stiffness (P<0.01) and significantly increased pain threshold (P<0.001) and ROM (P<0.001) compared with the control groups. Nevertheless, noxious stimulation decreased pain intensity (P<0.05) and increased pain threshold (P<0.001) significantly more than innocuous stimulation. No differences in treatment outcomes were found between adjusted and unadjusted stimulation. (a) Interferential current is very effective for chronic OA knee pain, (b) segmental noxious stimulation produces a stronger analgesic effect than segmental innocuous stimulation, (c) the fading of sensation during treatment, does not decrease the analgesic effect. Possible mechanisms explaining the findings are discussed.

  5. Hippo signaling disruption and Akt stimulation of ovarian follicles for infertility treatment.

    PubMed

    Kawamura, Kazuhiro; Cheng, Yuan; Suzuki, Nao; Deguchi, Masashi; Sato, Yorino; Takae, Seido; Ho, Chi-hong; Kawamura, Nanami; Tamura, Midori; Hashimoto, Shu; Sugishita, Yodo; Morimoto, Yoshiharu; Hosoi, Yoshihiko; Yoshioka, Nobuhito; Ishizuka, Bunpei; Hsueh, Aaron J

    2013-10-22

    Primary ovarian insufficiency (POI) and polycystic ovarian syndrome are ovarian diseases causing infertility. Although there is no effective treatment for POI, therapies for polycystic ovarian syndrome include ovarian wedge resection or laser drilling to induce follicle growth. Underlying mechanisms for these disruptive procedures are unclear. Here, we explored the role of the conserved Hippo signaling pathway that serves to maintain optimal size across organs and species. We found that fragmentation of murine ovaries promoted actin polymerization and disrupted ovarian Hippo signaling, leading to increased expression of downstream growth factors, promotion of follicle growth, and the generation of mature oocytes. In addition to elucidating mechanisms underlying follicle growth elicited by ovarian damage, we further demonstrated additive follicle growth when ovarian fragmentation was combined with Akt stimulator treatments. We then extended results to treatment of infertility in POI patients via disruption of Hippo signaling by fragmenting ovaries followed by Akt stimulator treatment and autografting. We successfully promoted follicle growth, retrieved mature oocytes, and performed in vitro fertilization. Following embryo transfer, a healthy baby was delivered. The ovarian fragmentation-in vitro activation approach is not only valuable for treating infertility of POI patients but could also be useful for middle-aged infertile women, cancer patients undergoing sterilizing treatments, and other conditions of diminished ovarian reserve.

  6. Treatment for Traumatic Brain Injury in Mice Using Transcranial Magnetic Stimulation: A Preliminary Study

    NASA Astrophysics Data System (ADS)

    Carr, Alexandria; Zenitsky, Gary; Crowther, Lawrence; Hadimani, Ravi; Anantharam, Vellareddy; Kanthasamy, Anumantha; Jiles, David

    2014-03-01

    Transcranial magnetic stimulation (TMS) is a non-invasive surgery-free tool used to stimulate the brain by time-varying magnetic fields. TMS is currently being investigated as a treatment for neurological disorders such as depression, Parkinson's disease and TBI. Before moving to human TMS/TBI trials, animal testing should be pursued to determine suitability and adverse effects. As an initial study, four healthy mice were treated with TMS at different power levels to determine short-term behavioral effects and set a control group baseline. The mouse's behavior was studied using the Rotorod test, which measures the animal's latency to fall off a rotating rod, and the Versamax test, which measures horizontal and vertical movement, and total distance traveled. The Rotorod test has shown for TMS power levels >=90% the mice begin to fall directly post-treatment. Similarly, the Versamax test has shown for power levels >=80% the mice are less mobile directly post-treatment. Versamax mobility was found to return to normal the day following treatment. These mice were housed in the facility for 4 months and the behavioral tests were repeated. Versamax results showed there was no significant variation in mobility indicating there are no long-term side effects of TMS treatment on the mice. This work was supported by the Barbara and James Palmer Endowment and the Carver Charitable Trust at the Department of Electrical and Computer Engineering, Iowa State University.

  7. The earthworm Aporrectodea caliginosa stimulates abundance and activity of phenoxyalkanoic acid herbicide degraders

    PubMed Central

    Liu, Ya-Jun; Zaprasis, Adrienne; Liu, Shuang-Jiang; Drake, Harold L; Horn, Marcus A

    2011-01-01

    2-Methyl-4-chlorophenoxyacetic acid (MCPA) is a widely used phenoxyalkanoic acid (PAA) herbicide. Earthworms represent the dominant macrofauna and enhance microbial activities in many soils. Thus, the effect of the model earthworm Aporrectodea caliginosa (Oligochaeta, Lumbricidae) on microbial MCPA degradation was assessed in soil columns with agricultural soil. MCPA degradation was quicker in soil with earthworms than without earthworms. Quantitative PCR was inhibition-corrected per nucleic acid extract and indicated that copy numbers of tfdA-like and cadA genes (both encoding oxygenases initiating aerobic PAA degradation) in soil with earthworms were up to three and four times higher than without earthworms, respectively. tfdA-like and 16S rRNA gene transcript copy numbers in soil with earthworms were two and six times higher than without earthworms, respectively. Most probable numbers (MPNs) of MCPA degraders approximated 4 × 105 gdw−1 in soil before incubation and in soil treated without earthworms, whereas MPNs of earthworm-treated soils were approximately 150 × higher. The aerobic capacity of soil to degrade MCPA was higher in earthworm-treated soils than in earthworm-untreated soils. Burrow walls and 0–5 cm depth bulk soil displayed higher capacities to degrade MCPA than did soil from 5–10 cm depth bulk soil, expression of tfdA-like genes in burrow walls was five times higher than in bulk soil and MCPA degraders were abundant in burrow walls (MPNs of 5 × 107 gdw−1). The collective data indicate that earthworms stimulate abundance and activity of MCPA degraders endogenous to soil by their burrowing activities and might thus be advantageous for enhancing PAA degradation in soil. PMID:20740027

  8. Physiologic hyperinsulinemia stimulates protein synthesis and enhances transport of selected amino acids in human skeletal muscle.

    PubMed Central

    Biolo, G; Declan Fleming, R Y; Wolfe, R R

    1995-01-01

    We have investigated the mechanisms of the anabolic effect of insulin on muscle protein metabolism in healthy volunteers, using stable isotopic tracers of amino acids. Calculations of muscle protein synthesis, breakdown, and amino acid transport were based on data obtained with the leg arteriovenous catheterization and muscle biopsy. Insulin was infused (0.15 mU/min per 100 ml leg) into the femoral artery to increase femoral venous insulin concentration (from 10 +/- 2 to 77 +/- 9 microU/ml) with minimal systemic perturbations. Tissue concentrations of free essential amino acids decreased (P < 0.05) after insulin. The fractional synthesis rate of muscle protein (precursor-product approach) increased (P < 0.01) after insulin from 0.0401 +/- 0.0072 to 0.0677 +/- 0.0101%/h. Consistent with this observation, rates of utilization for protein synthesis of intracellular phenylalanine and lysine (arteriovenous balance approach) also increased from 40 +/- 8 to 59 +/- 8 (P < 0.05) and from 219 +/- 21 to 298 +/- 37 (P < 0.08) nmol/min per 100 ml leg, respectively. Release from protein breakdown of phenylalanine, leucine, and lysine was not significantly modified by insulin. Local hyperinsulinemia increased (P < 0.05) the rates of inward transport of leucine, lysine, and alanine, from 164 +/- 22 to 200 +/- 25, from 126 +/- 11 to 221 +/- 30, and from 403 +/- 64 to 595 +/- 106 nmol/min per 100 ml leg, respectively. Transport of phenylalanine did not change significantly. We conclude that insulin promoted muscle anabolism, primarily by stimulating protein synthesis independently of any effect on transmembrane transport. Images PMID:7860765

  9. Treatment of neurological and psychiatric disorders with deep brain stimulation; raising hopes and future challenges.

    PubMed

    Sharifi, Mohammad Sharif

    2013-01-01

    The technology of Neural Stimulation in recent years has become the focus of the research and treatment, although it has been around for many years. The potential use of stimulating the brain and nerves ranges from the spinal cord stimulation to the implantations of cochlear and bionic eyes with a large discrepancy between the clinical readiness for these various uses. Electrical high-frequency Deep Brain Stimulation (DBS) was developed as an alternative option to treat a few neurological disorders. However, with advancing in surgical procedures, technologies and safeties, the applications of DBS are expanding not only for therapeutic purposes but also for research. Although the exact mechanisms of action/s are not fully understood, the outcome of the ongoing research and clinical trials are promising. DBS has been used to treat the essential tremor since 1997, Parkinson's disease (PD) since 2002 and dystonia since 2003. It has also been used to treat various disorders, including major depression. The therapeutic effect of DBS in PD is well established but for other diseases such as epilepsy the outcomes are unclear and ambiguous. This article is a succinct review of the literature, focusing on PD, epilepsy and Obsessive Compulsive Disorder (OCD). PMID:25337356

  10. Deep brain stimulation for treatment of the epilepsies: the centromedian thalamic target.

    PubMed

    Velasco, F; Velasco, A L; Velasco, M; Jiménez, F; Carrillo-Ruiz, J D; Castro, G

    2007-01-01

    Electrical stimulation (ES) of the thalamic centromedian nucleus (CMN) has been proposed as a minimally invasive alternative for the treatment of difficult-to-control seizures of multifocal origin and seizures that are generalized from the onset. ES intends to interfere with seizure propagation in a non-specific manner through the thalamic system. By adopting a frontal parasagittal approach and based on anterior-posterior (AC-PC) commissure intersection, deep brain stimulation (DBS) electrodes are stereotactically inserted. Electrophysiologic confirmation of electrodes position is accomplished by eliciting cortical recruiting responses and direct current (DC) shifts by low- and high-frequency stimulation through the electrodes. Cycling mode of bipolar stimulation has been used at 60-130 Hz, 0.45 msec, 2.5-3.5 V, 1 min ON in one side 4 min OFF, 1 min ON in the other side and 4 min OFF forward and back for 24h. ES of CMN significantly decreases generalized seizures of cortical origin and focal motor seizures. Best results are obtained in non-focal generalized tonic clonic seizures and atypical absences of the Lennox-Gastaut syndrome. Experience has indicated that the most effective target for seizure control is the thalamic parvocellular centromedian subnucleus. PMID:17691321

  11. Peripheral Nerve Stimulation for Treatment of Post-Amputation Pain – A Case Report

    PubMed Central

    Rauck, Richard L.; Kapural, Leonardo; Cohen, Steven P.; North, James M.; Gilmore, Christopher A.; Zang, Rosemary H.; Boggs, Joseph W.

    2012-01-01

    Many amputees suffer from post-amputation pain, which can be extremely debilitating, decrease quality of life, increase the risk of depression, and negatively affect interpersonal relationships and the ability to work. Present methods of treatment, including medications, are often unsatisfactory in reducing post-amputation pain. Electrical stimulation of the nerve innervating the painful area could reduce the pain, but peripheral nerve stimulation is rarely used to treat post-amputation pain because present methods require invasive surgical access and precise placement of the leads in close proximity (≤ 2 mm) with the nerve. The present study investigated a novel approach to peripheral nerve stimulation in which a lead was placed percutaneously a remote distance (> 1 cm) away from the femoral nerve in a patient with severe residual limb pain 33 years following a below-knee amputation. Electrical stimulation generated ≥ 75% paresthesia coverage, reduced residual limb pain by > 60%, and improved quality of life outcomes as measured by the pain interference scale of the Brief Pain Inventory-Short Form (100% reduction in pain interference), Pain Disability Index (74% reduction in disability), and the Patient Global Impression of Change (Very Much Improved) during a 2-week home trial. There were no adverse events. The ability to generate significant paresthesia coverage and pain relief with a single lead inserted percutaneously and remotely from the target nerve holds promise for providing relief of post-amputation pain. PMID:22548686

  12. Effect of early treatment with transcutaneous electrical diaphragmatic stimulation (TEDS) on pulmonary inflammation induced by bleomycin

    PubMed Central

    Santos, Laisa A.; Silva, Carlos A.; Polacow, Maria L. O.

    2013-01-01

    Background Bleomycin (B) is an antineoplastic drug that has pulmonary fibrosis as a side effect. There are few experimental studies about the effects of physical therapy treatment in this case. Objective The objective was to study rat lungs treated with B and precocious intervention by transcutaneous electrical diaphragmatic stimulation (TEDS). Method Wistar rats were divided into 4 groups (n=5): a control group (C); a stimulated group (TEDS); a group treated with a single dose of B (intratracheally, 2.5 mg/kg) (B); and a group treated with B and electric stimulation (B + TEDS). After the B instillation, the electrical stimulation was applied for 7 days, for a duration of 20 minutes. Lung fragments were histologically processed with hematoxylin and eosin (HE) and 8-isoprostane-PGF2α (8-iso-PGF2α). The density of the alveolar area was determined by planimetry, the inflammatory profile was defined by the number of cells, and the level of oxidative stress in the pulmonary tissue was evaluated by 8-iso-PGF2α. For statistical analysis of the data, the Shapiro-Wilk test was used, followed by a one-way ANOVA with the post-hoc Bonferroni test (p≤0.05). Results The B group exhibited a significant reduction in the area density, and the acute treatment with B + TEDS prevented this reduction. There were increased numbers of fibroblasts, leukocytes, and macrophages in the B group, as well as increased lipid peroxidation, which was observed only in this group. Conclusion B promoted a reduction in the alveolar density area, thereby inducing the inflammatory process and increasing the production of free radicals. These effects were minimized by the application of TEDS at the initial treatment stage. PMID:24346295

  13. Selective stimulation of excitatory amino acid receptor subtypes and the survival of cerebellar granule cells in culture: effect of kainic acid.

    PubMed

    Balázs, R; Hack, N; Jørgensen, O S

    1990-01-01

    Our previous studies showed that the survival of cerebellar granule cells in culture is promoted by treatment with N-methyl-D-aspartate. Here we report on the influence of another glutamate analogue, kainic acid, which, in contrast to N-methyl-D-aspartate, is believed to stimulate transmitter receptors mediating fast excitatory postsynaptic potentials. The kainate effect was complex: increased survival at low concentrations (the maximum, at 25-50 microM, was about 50% promotion), whereas concentrations exceeding 50 microM resulted first in a loss of the effect, and then at concentrations of 2-5 x 10(-4) M cells became vulnerable to kainate. The trophic influence of kainate is mediated through receptors other than the N-methyl-D-aspartate preferring subtype. In contrast to the effect of N-methyl-D-aspartate, that of kainate did not depend on the medium K+ level and was potently blocked by dinitroquinoxalinedione, which--at the concentration used here--did not counteract the promotion of cell survival evoked by N-methyl-D-aspartate. Quisqualate was a potent inhibitor of the rescue by kainate. Furthermore, blockade of N-methyl-D-aspartate receptors with the selective antagonists MK-801 or aminophosphonovalerate did not inhibit, but rather potentiated the trophic effect of kainate. Possible mechanisms underlying the trophic effect of chronic depolarization or treatment with excitatory amino acids are discussed, and it is proposed that they involve elevated free cytoplasmic calcium activity following increased influx through voltage-sensitive Ca2+ channels (high K+ and kainate) or receptorgated channels (N-methyl-D-aspartate).

  14. Stimulation of mitochondrial functions by glucagon treatment. Evidence that effects are not artifacts of mitochondrial isolation.

    PubMed

    Jensen, C B; Sistare, F D; Hamman, H C; Haynes, R C

    1983-03-15

    (1) Activation of rat liver mitochondrial functions following glucagon treatment was demonstrated in mitochondria that had not been isolated by the conventional technique of differential centrifugation and washing in sucrose solutions. Crude liver homogenates in 0.3 M-sucrose or 0.15 M-KCl prepared from rats treated with glucagon showed stimulation of State-3 and uncoupled respiration, carboxylation of pyruvate, and citrulline synthesis comparable with those previously reported in isolated mitochondria. (2) During the isolation procedure of mitochondria the hormonal stimulations of pyruvate carboxylation and citrulline formation were shown not to be enhanced by sequential washing. (3) Mitochondria isolated from glucagon-treated rats by differential centrifugation and washing in 0.3 M-mannitol/1 mM-EGTA, pH 7.0, exhibited a mean rate of citrulline synthesis that was greater than twice that of the control. Liver homogenates prepared in 0.3 M-sucrose or 0.3 M-mannitol showed identical rates of State-3 respiration and percentage stimulations of respiration by glucagon treatment. (4) Addition of glucagon led to a rapid accumulation of malate and aspartate and decreased the amounts of glutamate and citrate in isolated hepatocytes incubated with L-lactate. When gluconeogenesis was inhibited at the phosphoenolpyruvate carboxykinase (EC 4.1.1.32) reaction these phenomena were accentuated, lending support to the interpretation that they are the direct result of stimulation of carboxylation and oxidation reactions in the mitochondria. These results do not support the proposal [Siess, Fahimi & Wieland (1981) Hoppe-Seyler's Z. Physiol. Chem. 362. 1643-1651] that the mitochondrial effects of glucagon treatment result from a stabilization of mitochondria to detrimental effects of sucrose during their isolation. (5) The mean hormonal stimulation of pyruvate carboxylation in mitochondria isolated in 0.3 M-sucrose was shown to be approx. 2.5-fold when assayed either at 37 degrees C

  15. Acid mine water aeration and treatment system

    DOEpatents

    Ackman, Terry E.; Place, John M.

    1987-01-01

    An in-line system is provided for treating acid mine drainage which basically comprises the combination of a jet pump (or pumps) and a static mixer. The jet pump entrains air into the acid waste water using a Venturi effect so as to provide aeration of the waste water while further aeration is provided by the helical vanes of the static mixer. A neutralizing agent is injected into the suction chamber of the jet pump and the static mixer is formed by plural sections offset by 90 degrees.

  16. Novel neuromuscular electrical stimulation system for treatment of dysphagia after brain injury.

    PubMed

    Toyama, Keiichi; Matsumoto, Shuji; Kurasawa, Miho; Setoguchi, Haruka; Noma, Tomokazu; Takenaka, Keita; Soeda, Akina; Shimodozono, Megumi; Kawahira, Kazumi

    2014-01-01

    The purpose of this study was to compare the effects of a novel neuromuscular electrical stimulation (NMES) to the effects of conventional treatment in patients with dysphagia after brain injury. In total, 26 patients were non-randomly divided into an experimental group (n = 12) and a control group (n = 14). The experimental group received NMES intervention followed by conventional treatment, including thermaltactile stimulation with intensive repetition of a dry-swallow task. The control group received conventional treatment without NMES. NMES at a fixed pulse duration of 50 μs and a frequency of 50 Hz was delivered over the skin areas above the motor point of the target muscles, i.e., the bilateral geniohyoid, mylohyoid/anterior belly of the digastric, and thyrohyoid muscles, using a high-voltage pulsed-current device. The two groups received 40-min treatments once a day, 5 days per week, for 8 weeks. Outcome, assessed before and 8 weeks after treatment, was evaluated with regard to the videofluoroscopic dysphagia scale (VDS), the anterior and superior displacement of the hyoid bone and larynx, and the functional oral intake scale. Both groups exhibited improvement, but the experimental group exhibited more significant improvement in the displacement of the hyoid bone and larynx, VDS-total score, and VDS-pharyngeal score than the control group did. The results suggest that NMES combined with conventional treatment is superior to conventional treatment alone in patients with dysphagia following treatment for brain injury. Further investigations are necessary to examine the effects of NMES in patients with more varied types of diseases. PMID:24670314

  17. Enhanced type 1alpha metabotropic glutamate receptor-stimulated phosphoinositide signaling after pertussis toxin treatment.

    PubMed

    Carruthers, A M; Challiss, R A; Mistry, R; Saunders, R; Thomsen, C; Nahorski, S R

    1997-09-01

    The regulation of phosphoinositide hydrolysis by the type 1alpha metabotropic glutamate receptor (mGluR1alpha) was investigated in stably transfected baby hamster kidney (BHK) cells. Incubation of the cells with L-glutamate, quisqualate, and 1-aminocyclopentane-1S, 3R-dicarboxylic acid resulted in a marked accumulation of [3H]inositol monophosphate (InsP1) and inositol-1,4,5-trisphosphate [Ins(1,4,5)P3] mass in a time- and concentration-dependent manner. Pretreatment of BHK-mGluR1alpha cells with pertussis toxin [ 100 ng/ml, 24 hr] led to a dramatic 12-16-fold increase in the accumulation of [3H]InsP1 and a 2-fold increase in Ins(1,4,5)P3 in the absence of added agonist. Although only very low levels (treatment. Consistent with this hypothesis, in the presence of glutamic-pyruvic transaminase/pyruvate, the maximal [3H]InsP1 response to quisqualate was increased by >/=75%, and the EC50 shifted leftward by 65-fold [-log EC50 values (molar), 7.26 +/- 0.23 versus 5.45 +/- 0.07; n = 4) in PTX-treated compared with control cells. In contrast, antagonist effects on agonist-stimulated [3H]InsP1 responses were similar in control and PTX-treated BHK-mGluR1alpha cells. These changes in the concentration-effect curves for mGluR agonists are consistent with a model in which the receptor associates with PTX-sensitive inhibitory (Gi/o) and PTX-insensitive stimulatory (Gq/11) G proteins that can each influence PIC activity. The present observations are consistent with a dual regulation of mGluR1alpha-mediated PIC activity that could be fundamental in

  18. Involvement of lipoxygenase in lysophosphatidic acid-stimulated hydrogen peroxide release in human HaCaT keratinocytes.

    PubMed Central

    Sekharam, M; Cunnick, J M; Wu, J

    2000-01-01

    Although it is now recognized that low levels of reactive oxygen species (ROS) are required for the mitogenic response, mitogen-induced signalling pathways that regulate ROS generation in non-phagocytic cells remain largely uncharacterized. Using a real-time assay for measuring hydrogen peroxide (H(2)O(2)) formation, we analysed H(2)O(2) release in human HaCaT keratinocytes in response to lysophosphatidic acid (LPA), a mitogen for keratinocytes. LPA rapidly increased H(2)O(2) release in HaCaT cells. Unlike LPA-induced mitogen-activated protein (MAP) kinase activation, LPA-stimulated H(2)O(2) release was independent of the tyrosine kinase activity of the epidermal growth factor (EGF) receptor. Calcium chelators, phospholipase A(2) inhibitors, and lipoxygenase inhibitors effectively blocked LPA-stimulated H(2)O(2) release, whereas cyclooxygenase inhibitors were without effect. Addition of 5-lipoxygenase products 5-hydroperoxyeicosatetraenoic acid (5-HPETE) and leukotriene B(4), but not 5-hydroxyeicosatetraenoic acid (5-HETE) and leukotriene C(4), restored LPA-stimulated H(2)O(2) release in cells treated with the lipoxygenase inhibitors nordihydroguaiaretic acid and Zileuton. These results suggest that the lipoxygenase products 5-HPETE and leukotriene B(4) are required for LPA-stimulated H(2)O(2) release in HaCaT cells. PMID:10698703

  19. 300 Area waste acid treatment system closure plan. Revision 1

    SciTech Connect

    1996-03-01

    This section provides a description of the Hanford Site, identifies the proposed method of 300 Area Waste Acid Treatment System (WATS) closure, and briefly summarizes the contents of each chapter of this plan.

  20. 15. INTERIOR MIDDLE BAY DETAIL VIEW, FACING WEST. ACID TREATMENT, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    15. INTERIOR MIDDLE BAY DETAIL VIEW, FACING WEST. ACID TREATMENT, CUTTING EQUIPMENT, LOCKERS ABANDONED ON SITE. TRACKS FOR MOVEMENT OF MATERIALS VISIBLE HANGING FROM CEILING. - NASA Industrial Plant, Missile Research Laboratory, 12214 Lakewood Boulevard, Downey, Los Angeles County, CA

  1. [Advances in the research of treatment of hydrofluoric acid burn].

    PubMed

    Wang, Xin-gang; Zhang, Yuan-hai; Han, Chun-mao

    2013-08-01

    Hydrofluoric acid (HF) is one of the most common inorganic acids used widely in industrial circle. HF not only causes cutaneous burn, but also induces systemic toxicity by its unique injury mechanism. Accurate and timely diagnosis and treatment are critical after HF burns. To date, the strategies for treating HF burns have been developed, mainly including topical treatments and systematic support. However, there is no standard treatment strategy with wide acceptance in the world. This paper presents a comprehensive overview of the advances in the research of strategies for the treatment of HF burns.

  2. Omega-3 fatty acids in the treatment of psychiatric disorders.

    PubMed

    Peet, Malcolm; Stokes, Caroline

    2005-01-01

    The importance of omega-3 fatty acids for physical health is now well recognised and there is increasing evidence that omega-3 fatty acids may also be important to mental health. The two main omega-3 fatty acids in fish oil, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have important biological functions in the CNS. DHA is a major structural component of neuronal membranes, and changing the fatty acid composition of neuronal membranes leads to functional changes in the activity of receptors and other proteins embedded in the membrane phospholipid. EPA has important physiological functions that can affect neuronal activity. Epidemiological studies indicate an association between depression and low dietary intake of omega-3 fatty acids, and biochemical studies have shown reduced levels of omega-3 fatty acids in red blood cell membranes in both depressive and schizophrenic patients. Five of six double-blind, placebo-controlled trials in schizophrenia, and four of six such trials in depression, have reported therapeutic benefit from omega-3 fatty acids in either the primary or secondary statistical analysis, particularly when EPA is added on to existing psychotropic medication. Individual clinical trials have suggested benefits of EPA treatment in borderline personality disorder and of combined omega-3 and omega-6 fatty acid treatment for attention-deficit hyperactivity disorder. The evidence to date supports the adjunctive use of omega-3 fatty acids in the management of treatment unresponsive depression and schizophrenia. As these conditions are associated with increased risk of coronary heart disease and diabetes mellitus, omega-3 fatty acids should also benefit the physical state of these patients. However, as the clinical research evidence is preliminary, large, and definitive randomised controlled trials similar to those required for the licensing of any new pharmacological treatment are needed.

  3. Cholera toxin treatment stimulates tumorigenicity of Rous sarcoma virus-transformed cells.

    PubMed Central

    Gottesman, M M; Roth, C; Vlahakis, G; Pastan, I

    1984-01-01

    Chinese hamster ovary cells transformed by Rous sarcoma virus form tumors poorly in nude mice. Tumorigenicity was markedly stimulated by pretreatment of the cells with cholera toxin, which raises cyclic AMP levels and activates cyclic AMP-dependent protein kinase. Increased tumorigenicity was manifested by a severalfold increase in the rate of tumor formation, as well as earlier appearance and more rapid growth of tumors. In contrast, spontaneously transformed Chinese hamster ovary cells showed decreased tumorigenicity after cholera toxin treatment. The activation of tumorigenic potential in Rous sarcoma virus-transformed Chinese hamster ovary cells by cholera toxin correlated with increased phosphorylation of the viral oncogene product pp60src and stimulation of its tyrosine kinase activity. PMID:6098816

  4. Salvianolic Acid B Prevents Bone Loss in Prednisone-Treated Rats through Stimulation of Osteogenesis and Bone Marrow Angiogenesis

    PubMed Central

    Cui, Liao; Li, Ting; Liu, Yuyu; Zhou, Le; Li, Pinghua; Xu, Bilian; Huang, Lianfang; Chen, Yan; Liu, Yanzhi; Tian, Xiaoyan; Jee, Webster S. S.; Wu, Tie

    2012-01-01

    Glucocorticoid (GC) induced osteoporosis (GIO) is caused by the long-term use of GC for treatment of autoimmune and inflammatory diseases. The GC related disruption of bone marrow microcirculation and increased adipogenesis contribute to GIO development. However, neither currently available anti-osteoporosis agent is completely addressed to microcirculation and bone marrow adipogenesis. Salvianolic acid B (Sal B) is a polyphenolic compound from a Chinese herbal medicine, Salvia miltiorrhiza Bunge. The aim of this study was to determine the effects of Sal B on osteoblast bone formation, angiogenesis and adipogenesis-associated GIO by performing marrow adipogenesis and microcirculation dilation and bone histomorphometry analyses. (1) In vivo study: Bone loss in GC treated rats was confirmed by significantly decreased BMD, bone strength, cancellous bone mass and architecture, osteoblast distribution, bone formation, marrow microvessel density and diameter along with down-regulation of marrow BMPs expression and increased adipogenesis. Daily treatment with Sal B (40 mg/kg/d) for 12 weeks in GC male rats prevented GC-induced cancellous bone loss and increased adipogenesis while increasing cancellous bone formation rate with improved local microcirculation by capillary dilation. Treatment with Sal B at a higher dose (80 mg/kg/d) not only prevented GC-induced osteopenia, but also increased cancellous bone mass and thickness, associated with increase of marrow BMPs expression, inhibited adipogenesis and further increased microvessel diameters. (2) In vitro study: In concentration from 10−6 mol/L to 10−7 mol/L, Sal B stimulated bone marrow stromal cell (MSC) differentiation to osteoblast and increased osteoblast activities, decreased GC associated adipogenic differentiation by down-regulation of PPARγ mRNA expression, increased Runx2 mRNA expression without osteoblast inducement, and, furthermore, Sal B decreased Dickkopf-1 and increased β-catenin mRNA expression with

  5. Upper Airway Stimulation for Obstructive Sleep Apnea: Durability of the Treatment Effect at 18 Months

    PubMed Central

    Strollo, Patrick J.; Gillespie, M. Boyd; Soose, Ryan J.; Maurer, Joachim T.; de Vries, Nico; Cornelius, Jason; Hanson, Ronald D.; Padhya, Tapan A.; Steward, David L.; Woodson, B. Tucker; Verbraecken, Johan; Vanderveken, Olivier M.; Goetting, Mark G.; Feldman, Neil; Chabolle, Frédéric; Badr, M. Safwan; Randerath, Winfried; Strohl, Kingman P.

    2015-01-01

    Objective: To determine the stability of improvement in polysomnographic measures of sleep disordered breathing, patient reported outcomes, the durability of hypoglossal nerve recruitment and safety at 18 months in the Stimulation Treatment for Apnea Reduction (STAR) trial participants. Design: Prospective multicenter single group trial with participants serving as their own controls. Setting: Twenty-two community and academic sleep medicine and otolaryngology practices. Measurements: Primary outcome measures were the apnea-hypopnea index (AHI) and the 4% oxygen desaturation index (ODI). Secondary outcome measures were the Epworth Sleepiness Scale (ESS), the Functional Outcomes of Sleep Questionnaire (FOSQ), and oxygen saturation percent time < 90% during sleep. Stimulation level for each participant was collected at three predefined thresholds during awake testing. Procedure- and/or device-related adverse events were reviewed and coded by the Clinical Events Committee Results: The median AHI was reduced by 67.4% from the baseline of 29.3 to 9.7/h at 18 mo. The median ODI was reduced by 67.5% from 25.4 to 8.6/h at 18 mo. The FOSQ and ESS improved significantly at 18 mo compared to baseline values. The functional threshold was unchanged from baseline at 18 mo. Two participants experienced a serious device-related adverse event requiring neurostimulator repositioning and fixation. No tongue weakness reported at 18 mo. Conclusion: Upper airway stimulation via the hypoglossal nerve maintained a durable effect of improving airway stability during sleep and improved patient reported outcomes (Epworth Sleepiness Scale and Functional Outcomes of Sleep Questionnaire) without an increase of the stimulation thresholds or tongue injury at 18 mo of follow-up. Citation: Strollo PJ, Gillespie MB, Soose RJ, Maurer JT, de Vries N, Cornelius J, Hanson RD, Padhya TA, Steward DL, Woodson BT, Verbraecken J, Vanderveken OM, Goetting MG, Feldman N, Chabolle F, Badr MS, Randerath W

  6. Treatment of ADHD with Stimulant Medications: Response to Nissen Perspective in the New England Journal of Medicine

    ERIC Educational Resources Information Center

    Biederman, Joseph; Spencer, Thomas J.; Wilens, Timothy E.; Prince, Jefferson B.; Faraone, Stephen V.

    2006-01-01

    This article is a response to Dr. Steven E. Nissen's comments (Nissen, 2006) about attention deficit/hyperactivity disorder (ADHD) and its treatment with stimulant medications. In this article, the authors refute his arguments and provide accurate information. Here, they answer the questions, such as: (1) Do stimulants increase the risk for sudden…

  7. 300 Area waste acid treatment system closure plan

    SciTech Connect

    LUKE, S.N.

    1999-05-17

    The Hanford Facility Dangerous Waste Permit Application is considered to be a single application organized into a General Information Portion (document number DOERL-91-28) and a Unit-Specific Portion. The scope of the Unit-Specific Portion includes closure plan documentation submitted for individual, treatment, storage, and/or disposal units undergoing closure, such as the 300 Area Waste Acid Treatment System. Documentation contained in the General Information Portion is broader in nature and could be used by multiple treatment, storage, and/or disposal units (e.g., the glossary provided in the General Information Portion). Whenever appropriate, 300 Area Waste Acid Treatment System documentation makes cross-reference to the General Information Portion, rather than duplicating text. This 300 Area Waste Acid Treatment System Closure Plan (Revision 2) includes a Hanford Facility Dangerous Waste Permit Application, Part A, Form 3. Information provided in this closure plan is current as of April 1999.

  8. Spinal cord stimulation for treatment of pain in a patient with post thoracotomy pain syndrome.

    PubMed

    Graybill, Jordan; Conermann, Till; Kabazie, Abraham J; Chandy, Sunil

    2011-01-01

    Post Thoracotomy Pain Syndrome (PTPS) is defined as pain that occurs or persists in the area of the thoracotomy incision for at least 2 months following the initial procedure.  The true incidence of PTPS is hard to define as literature reports a wide range of occurrence from 5% to 90%.  Thoracotomy is associated with a high risk of severe chronic postoperative pain.  Presenting symptoms include both neuropathic pain in the area of the incision, as well as myofascial pain commonly in the ipsilateral scapula and shoulder.  Pain management can be challenging in these patients.  Multiple treatments have been described including conservative treatments with oral nonsteroidal anti-inflammatory drugs (NSAIDs); topically applied, peripherally acting drugs; neuromodulating agents; physical therapy; transcutaneous electrical nerve stimulation as well as more invasive treatments including intercostal nerve blocks, trigger point steroid injections, epidural steroid injections, radiofrequency nerve ablation, cryoablation, and one case report of spinal cord stimulation.  Unfortunately, a portion of these patients will have persistent pain in spite of multiple treatment modalities, and in some cases will experience worsening of pain. This case report describes the novel utility and complete resolution of symptoms with spinal cord stimulation (SCS) in treatment of a patient with persistent PTPS. In the operating room, a percutaneous octet electrode lead was placed using sterile technique under fluoroscopic guidance and loss-of-resistance technique.  The octet electrode lead was subsequently advanced with the aid of fluoroscopy to the level of the T3 superior endplate just right of midline.  The patient's pain distribution was captured optimally with stimulation at this level.  With the assistance of a neurosurgeon, the lead was anchored, tunneled, and connected to a generator, which was implanted over the right iliac crest.  The patient tolerated the procedure well with

  9. Anti-neuro-inflammatory effects of Nardostachys chinensis in lipopolysaccharide-and lipoteichoic acid-stimulated microglial cells.

    PubMed

    Park, Sun Young; Kim, Young Hun; Park, Geuntae

    2016-05-01

    Excessive microglial cell activation is related to the progression of chronic neuro-inflammatory disorders. Heme oxygenase-1 (HO-1) expression mediated by the NFE2-related factor (Nrf-2) pathway is a key regulator of neuro-inflammation. Nardostachys chinensis is used as an anti-malarial, anti-nociceptive, and neurotrophic treatment in traditional Asian medicines. In the present study, we examined the effects of an ethyl acetate extract of N. chinensis (EN) on the anti-neuro-inflammatory effects mediated by HO-1 up-regulation in Salmonella lipopolysaccharide (LPS)- or Staphylococcus aureus lipoteichoic acid (LTA)-stimulated BV2 microglial cells. Our results indicated that EN suppressed pro-inflammatory cytokine production and induced HO-1 transcription and translation through Nrf-2/antioxidant response element (ARE) signaling. EN markedly inhibited LPS- and LTA-induced activation of nuclear factor-kappa B (NF-κB) as well as phosphorylation of mitogen-activated protein kinases (MAPKs) and signal transducer and activator of transcription (STAT). Furthermore, EN protected hippocampal HT22 cells from indirect neuronal toxicity mediated by LPS- and LTA-treated microglial cells. These results suggested that EN impairs LPS- and LTA-induced neuro-inflammatory responses in microglial cells and confers protection against indirect neuronal damage to HT22 cells. In conclusion, our findings indicate that EN could be used as a natural anti-neuro-inflammatory and neuroprotective agent. PMID:27478097

  10. Regulation on RhoA in vascular smooth muscle cells under inflammatory stimulation proposes a novel mechanism mediating the multiple-beneficial action of acetylsalicylic acid.

    PubMed

    Li, Dong-Bo; Yang, Guo-Jie; Xu, Hong-Wei; Fu, Zhi-Xuan; Wang, Shan-Wei; Hu, Shen-Jiang

    2013-12-01

    Recent studies have revealed the additional beneficial effects of acetylsalicylic acid (aspirin) in the medication of cardiovascular diseases. The small GTPase RhoA as an important signaling factor is implicated in a wide range of cell functions. This study aimed to investigate the regulatory effect of acetylsalicylic acid on RhoA in vascular smooth muscle cells (VSMCs). We found that aspirin at 300 μM suppressed VSMCs proliferation stimulated by LPS, and this inhibitory effect was partially mediated by inhibiting the iNOS/NO pathway. RhoA overexpression was downregulated by aspirin (both 30 and 300 μM) because of enhanced degradation of RhoA protein. The effect of LPS on increasing active RhoA level was significantly attenuated by aspirin (300 μM), which exerted no effect on RhoA translocation. The promoted RhoA phosphorylation under LPS stimulation, coupled with RhoA protein expression, was greatly decreased by aspirin treatment. No effect of aspirin was found on the expression, activation, and phosphorylation of RhoA in VSMCs devoid of inflammatory stimulation. Our investigation indicates that the regulation of RhoA by aspirin in VSMCs under inflammatory stimulus could be a novel mechanism via which aspirin, apart from the COX-dependent action, exerted the multiple beneficial effects.

  11. Stimulation of mitochondrial functions by glucagon treatment, starvation and by treatment of isolated mitochondria with glycogen-bound enzymes.

    PubMed

    Wojtczak, A B; Davis-van Thienen, W I

    1987-01-01

    Liver mitochondria isolated from rats starved overnight, or fed rats injected with glucagon, exhibited a similar increase of the respiration rate with succinate (by 30-40%) and glutamate plus malate (by 20-30%), as compared to mitochondria from control fed animals. The content of mitochondrial adenine nucleotides was elevated by 30-45% by glucagon treatment or starvation. Mitochondrial respiration and citrulline synthesis were stimulated by 30-40% when mitochondria isolated from fed rats were briefly preincubated with the extract from liver glycogen granules, ATP and MgCl2. This effect was abolished by heating the extract at 100 degrees C. PMID:3036619

  12. HYALURONIC ACID: THE USE OF ITS PRECURSOR IN SKIN BIO-STIMULATION.

    PubMed

    Avantaggiato, A; Martinelli, M; Palmieri, A; Pascali, M; Bertuzzi, G; Carinci, F

    2015-01-01

    Bio-stimulation is an injective therapy aimed to boost the anabolic functions of dermal fibroblasts to obtain skin improvement. It can be achieved with multiple intradermal injections (0.05–0.1 ml each) of a solution of 400 mg (3 ml) of injectable glucosamine sulphate, plus 5.623 mg (3 ml) of polideoxyribonucleotide, 1 ml of lidocaine and 0.5–1 ml of sodium bicarbonate, to repeat every 7, 14, 21, and 28 days. The administration of glucosamine sulphate to skin fibroblasts is believed to lead to its incorporation in glycosaminoglycans, and thereby to the stimulation of extracellular matrix synthesis, whereas polideoxyribonucleotide possesses anti-inflammatory and regenerative capability. This study aims to elucidate the in-vitro effects of this treatment by studying what happens to several genes related to connective tissue integrity. Human dermal fibroblasts were seeded in a culture medium enriched with either two drugs alone or combined: glucosamine sulphate and/or polideoxyribonucleotide. After the end of the exposure time of 24 h, 48 h, and 72 h, the cells were trypsinized and lysed for RNA extraction. Reverse transcription to cDNA was performed directly from cultured cell lysate. Finally, the cDNA was amplified by real-time PCR and a panel of genes involved in dermal integrity was tested. Gene expression of Hyaluronan synthase 1 (HAS1), Elastine (ELN), Insulin like growth factor 1 (IGF1), Growth differentiation factor 6 (GDF6) and of a series of catabolic enzymes, such as Metalloproteases (MMP) 2, 3 and 13, the neutrophyl expressed Elastase (ELANE) and the Hyaluronidase 1 (HYAL1) were tested after 24, 48 and 72 hours of exposure to glucosamine sulphate and polideoxyribonucleotide alone or combined. All the tested genes but one were up-regulated. A negative synergism on several enzymes (particularly appreciable for Insulin-like growth factor 1 and metalloprotease 13) was observed when the two drugs were delivered together. Glucosamine sulphate acts not only as

  13. Phosphatidic acid stimulates cardiac KATP channels like phosphatidylinositols, but with novel gating kinetics.

    PubMed

    Fan, Zheng; Gao, Lizhi; Wang, Wenxia

    2003-01-01

    Membrane-bound anionic phospholipids such as phosphatidylinositols have the capacity to modulate ATP-sensitive potassium (K(ATP)) channels through a mechanism involving long-range electrostatic interaction between the lipid headgroup and channel. However, it has not yet been determined whether the multiple effects of phosphatidylinositols reported in the literature all result from this general electrostatic interaction or require a specific headgroup structure. The present study investigated whether phosphatidic acid (PA), an anionic phospholipid substantially different in structure from phosphatidylinositols, evokes effects similar to phosphatidylinositols on native K(ATP) channels of rat heart and heterogeneous Kir6.2/SUR2A channels. Channels treated with PA (0.2-1 mg/ml applied to the cytoplasmic side of the membrane) exhibited higher activity, lower sensitivity to ATP inhibition, less Mg(2+)-dependent nucleotide stimulation, and poor sulfonylurea inhibition. These effects match the spectrum of phosphatidylinositols' effects, but, in addition, PA also induced a novel pattern in gating kinetics, represented by a decreased mean open time (from 12.2 +/- 2.0 to 3.3 +/- 0.7 ms). This impact on gating kinetics clearly distinguishes PA's effects from those of phosphatidylinositols. Results indicate that multiple effects of anionic phospholipids on K(ATP) channels are related phenomena and can likely be attributed to a common mechanism, but additional specific effects due to other mechanisms may also coincide.

  14. Fumaric acid esters: an alternative systemic treatment for psoriasis.

    PubMed

    Ameen, M; Russell-Jones, R

    1999-09-01

    We report the successful clearance of severe chronic plaque psoriasis following treatment with fumaric acid esters (FAE) in two patients who had failed previous systemic therapy. FAE is gaining increasing acceptance for the treatment of psoriasis in countries such as Germany and the Netherlands, but at present remains unlicensed in Britain.

  15. The role of aromatase inhibitors in ameliorating deleterious effects of ovarian stimulation on outcome of infertility treatment

    PubMed Central

    Mitwally, Mohamed FM; Casper, Robert F; Diamond, Michael P

    2005-01-01

    Clinical utilization of ovulation stimulation to facilitate the ability of a couple to conceive has not only provided a valuable therapeutic approach, but has also yielded extensive information on the physiology of ovarian follicular recruitment, endometrial receptivity and early embryo competency. One of the consequences of the use of fertility enhancing agents for ovarian stimulation has been the creation of a hyperestrogenic state, which may influence each of these parameters. Use of aromatase inhibitors reduces hyperestrogenism inevitably attained during ovarian stimulation. In addition, the adjunct use of aromatase inhibitors during ovarian stimulation reduces amount of gonadotropins required for optimum stimulation. The unique approach of reducing hyperestrogenism, as well as lowering amount of gonadotropins without affecting the number of mature ovarian follicles is an exciting strategy that could result in improvement in the treatment outcome by ameliorating the deleterious effects of the ovarian stimulation on follicular development, endometrial receptivity, as well as oocyte and embryo quality. PMID:16202169

  16. Pallidal deep brain stimulation: an effective treatment in Chinese patients with tardive dystonia.

    PubMed

    Woo, Peter Y M; Chan, Danny T M; Zhu, X L; Yeung, Jonas H M; Chan, Anne Y Y; Au, Angie C W; Cheng, K M; Lau, K Y; Wing, Y K; Mok, Vincent C T; Poon, W S

    2014-10-01

    Tardive dystonia is an iatrogenic complication of dopamine receptor antagonist medication such as first-generation antipsychotics. It occurs in up to 2% of patients and only 10% recover after stopping medication. Deep brain stimulation for primary dystonia has proven to be effective and its application for secondary dystonias is gaining acceptance. We report our experience in treating three ethnic Chinese schizophrenia patients with severe medically refractory tardive dystonia by globus pallidus internus deep brain stimulation. Preoperatively, all required assistance with essential activities of daily living and two were bed-bound. The mean Burke-Fahn-Marsden Dystonia Rating Scale score was 61 (range, 44-80) and mean Global Dystonia Rating Scale score was 47 (range, 40-52). No procedure-related complications were encountered. By 3 months all could return to unassisted living and walk with support with a mean of 77% and 66% improvement in the Burke-Fahn-Marsden Dystonia Rating Scale and Global Dystonia Rating Scale scores, respectively. Quality-of-life assessment performed for two patients using the EuroQol-5 dimensions visual analogue scale showed a mean improvement of 86% at 3 months. On clinical follow-up, the effect was well maintained for a period of 3 to 10 years. Pallidal deep brain stimulation is a safe and highly effective form of symptomatic treatment for patients with medically refractory tardive dystonia.

  17. Motor cortex stimulation for the treatment of refractory peripheral neuropathic pain.

    PubMed

    Lefaucheur, Jean-Pascal; Drouot, Xavier; Cunin, Patrick; Bruckert, Rémy; Lepetit, Hélène; Créange, Alain; Wolkenstein, Pierre; Maison, Patrick; Keravel, Yves; Nguyen, Jean-Paul

    2009-06-01

    Epidural motor cortex stimulation (MCS) has been proposed as a treatment for chronic, drug-resistant neuropathic pain of various origins. Regarding pain syndromes due to peripheral nerve lesion, only case series have previously been reported. We present the results of the first randomized controlled trial using chronic MCS in this indication. Sixteen patients were included with pain origin as follows: trigeminal neuralgia (n = 4), brachial plexus lesion (n = 4), neurofibromatosis type-1 (n = 3), upper limb amputation (n = 2), herpes zoster ophthalmicus (n = 1), atypical orofacial pain secondary to dental extraction (n = 1) and traumatic nerve trunk transection in a lower limb (n = 1). A quadripolar lead was implanted, under radiological and electrophysiological guidance, for epidural cortical stimulation. A randomized crossover trial was performed between 1 and 3 months postoperative, during which the stimulator was alternatively switched 'on' and 'off' for 1 month, followed by an open phase during which the stimulator was switched 'on' in all patients. Clinical assessment was performed up to 1 year after implantation and was based on the following evaluations: visual analogue scale (VAS), brief pain inventory, McGill Pain questionnaire, sickness impact profile and medication quantification scale. The crossover trial included 13 patients and showed a reduction of the McGill Pain questionnaire-pain rating index (P = 0.0166, Wilcoxon test) and McGill Pain questionnaire sensory subscore (P = 0.01) when the stimulator was switched 'on' compared to the 'off-stimulation' condition. However, these differences did not persist after adjustment for multiple comparisons. In the 12 patients who completed the open study, the VAS and sickness impact profile scores varied significantly in the follow-up and were reduced at 9-12 months postoperative, compared to the preoperative baseline. At final examination, the mean rate of pain relief on VAS scores was 48% (individual results

  18. Similar increases in extracellular lactic acid in the limbic system during epileptic and/or olfactory stimulation.

    PubMed

    Fornai, F; Bassi, L; Gesi, M; Giorgi, F S; Guerrini, R; Bonaccorsi, I; Alessandrì, M G

    2000-01-01

    Previous studies have shown that physiological stimulation of brain activity increases anaerobic glucose consumption, both in humans and in experimental animals. To investigate this phenomenon further, we measured extracellular lactate levels within different rat brain regions, using microdialysis. Experiments were performed comparing the effects of natural, physiological olfactory stimulation of the limbic system with experimental limbic seizures. Olfactory stimulation was carried out by using different odors (i.e. both conventional odors: 2-isobutyl-3-methoxypyrazine, green pepper essence; thymol; and 2-sec-butylthiazoline, a sexual pheromone). Limbic seizures were either induced by systemic injection of pilocarpine (200-400 mg/kg) or focally elicited by microinfusions of chemoconvulsants (bicuculline 118 pmol and cychlothiazide 1.2 nmol) within the anterior piriform cortex. Seizures induced by systemic pilocarpine tripled lactic acid within the hippocampus, whereas limbic seizures elicited by focal microinfusion of chemoconvulsants within the piriform cortex produced a less pronounced increase in extracellular lactic acid. Increases in extracellular lactate occurring during olfactory stimulation with the sexual pheromone (three times the baseline levels) were non-significantly different from those occurring after systemic pilocarpine. Increases in lactic acid following natural olfactory stimulation were abolished both by olfactory bulbectomy and by the focal microinfusion of tetrodotoxin, while they were significantly attenuated by the local application of the N-methyl-D-aspartate antagonist AP-5. Increases in hippocampal lactate induced by short-lasting stimuli (olfactory stimulation or microinfusion of subthreshold doses of chemoconvulsants, bicuculline 30 pmol) were reproducible after a short delay (1 h) and cumulated when applied sequentially. In contrast, limbic status epilepticus led to a long-lasting refractoriness to additional lactate-raising stimuli

  19. The short chain fatty acid, butyrate, stimulates MUC2 mucin production in the human colon cancer cell line, LS174T

    SciTech Connect

    Hatayama, Hajime; Iwashita, Jun; Kuwajima, Akiko; Abe, Tatsuya . E-mail: abetats@akita-pu.ac.jp

    2007-05-11

    The short fatty acid, butyrate, which is produced by intestinal anaerobic bacteria in the colon, has inhibitory activity on histone deacetylases (HDACs). Treatment of the human colon cancer cell line, LS174T, with 1-2 mM sodium butyrate stimulated MUC2 mucin production, as determined by histological PAS staining of carbohydrate chains of mucin, and confirmed at the protein and mRNA levels by immunoblotting with anti-MUC2 antibody and real-time RT-PCR, respectively. Increases in acetylated histone H3 in the LS174T cells treated with butyrate suggest inhibition of HDACs in these cells. Butyrate-stimulated MUC2 production in the LS174T cells was inhibited by the MEK inhibitor, U0126, implicating the involvement of extracellular signal-regulated kinase (ERK) cascades in this process. Proliferation of the LS174T cells was inhibited by butyrate treatment. Although apoptotic nuclear DNA fragmentation could not be detected, cell-cycle arrest at the G0/G1 phase in the butyrate-treated cells was demonstrated by flow cytometry. Thus butyrate, an HDAC inhibitor, inhibits proliferation of LS174T cells but stimulates MUC2 production in individual cells.

  20. Comparison of 2 methods of non-invasive treatment between transcutaneous electrical stimulation and pulsed electromagnetic field stimulation as replacement of invasive manual acupuncture.

    PubMed

    Kim, Soo-Byeong; Kim, Jung-Yoon; Park, Sun-Woo; Lee, Na-Ra; Lee, Seung-Wook; Kim, Young-Ho; Lee, Yong-Heum

    2012-01-01

    The aim of this study was to find the non-invasive optimal alternative method for Manual Acupuncture. Existing researches had reported that Transcutaneous Electrical Acupoint Stimulation (TEAS) was an effective treatment method instead of manual acupuncture. In place of the TEAS, we suggested the Pulsed Electromagnetic Fields (PEMFs). Thus, we designed the PEMFs system which can stimulate only an acupoint. There have been no researches which reported therapeutic effect when stimulating at an identical acupoint by TEAS and PEMFs. Hence, this study investigated the therapeutic effect on the muscle fatigue after the strenuous knee extension/flexion exercise by two stimulations. We selected the stimulation method of both TEAS and PEMFs by using 2Hz biphasic rectangular wave pulse and pulse width 0.2ms. The magnetic flux was the 30.92mT (309.2gauss) at 2 Hz. The electromyogram (EMG) and the maximal voluntary contraction (MVC) at rectus femoris were measured. The Median Frequency (MF) at TEAS group was significantly effective at 6 minutes (p=0.499). The PEMFs group was recovered to the MF rapidly after 4 minutes (p=0.166). The results of the peak torque indicated that both non-stimulation group and TEAS group did not recover to the peak torque at pre-exercise during the recovery period (p<0.05). In contrast, the significant treatment effect of PEMFs group was found after 14 minutes (p=0.135). The results of this study demonstrated that PEMFs were better than TEAS as a non-invasive method to replace the manual acupuncture.

  1. Proteomic analysis of the molecular response of Raji cells to maslinic acid treatment.

    PubMed

    Yap, W H; Khoo, K S; Lim, S H; Yeo, C C; Lim, Y M

    2012-01-15

    Maslinic acid, a natural pentacyclic triterpene has been shown to inhibit growth and induce apoptosis in some tumour cell lines. We studied the molecular response of Raji cells towards maslinic acid treatment. A proteomics approach was employed to identify the target proteins. Seventeen differentially expressed proteins including those involved in DNA replication, microtubule filament assembly, nucleo-cytoplasmic trafficking, cell signaling, energy metabolism and cytoskeletal organization were identified by MALDI TOF-TOF MS. The down-regulation of stathmin, Ran GTPase activating protein-1 (RanBP1), and microtubule associated protein RP/EB family member 1 (EB1) were confirmed by Western blotting. The study of the effect of maslinic acid on Raji cell cycle regulation showed that it induced a G1 cell cycle arrest. The differential proteomic changes in maslinic acid-treated Raji cells demonstrated that it also inhibited expression of dUTPase and stathmin which are known to induce early S and G2 cell cycle arrests. The mechanism of maslinic acid-induced cell cycle arrest may be mediated by inhibiting cyclin D1 expression and enhancing the levels of cell cycle-dependent kinase (CDK) inhibitor p21 protein. Maslinic acid suppressed nuclear factor-kappa B (NF-κB) activity which is known to stimulate expression of anti-apoptotic and cell cycle regulatory gene products. These results suggest that maslinic acid affects multiple signaling molecules and inhibits fundamental pathways regulating cell growth and survival in Raji cells. PMID:21893403

  2. High temperature stimulates acetic acid accumulation and enhances the growth inhibition and ethanol production by Saccharomyces cerevisiae under fermenting conditions.

    PubMed

    Woo, Ji-Min; Yang, Kyung-Mi; Kim, Sae-Um; Blank, Lars M; Park, Jin-Byung

    2014-07-01

    Cellular responses of Saccharomyces cerevisiae to high temperatures of up to 42 °C during ethanol fermentation at a high glucose concentration (i.e., 100 g/L) were investigated. Increased temperature correlated with stimulated glucose uptake to produce not only the thermal protectant glycerol but also ethanol and acetic acid. Carbon flux into the tricarboxylic acid (TCA) cycle correlated positively with cultivation temperature. These results indicate that the increased demand for energy (in the form of ATP), most likely caused by multiple stressors, including heat, acetic acid, and ethanol, was matched by both the fermentation and respiration pathways. Notably, acetic acid production was substantially stimulated compared to that of other metabolites during growth at increased temperature. The acetic acid produced in addition to ethanol seemed to subsequently result in adverse effects, leading to increased production of reactive oxygen species. This, in turn, appeared to cause the specific growth rate, and glucose uptake rate reduced leading to a decrease of the specific ethanol production rate far before glucose depletion. These results suggest that adverse effects from heat, acetic acid, ethanol, and oxidative stressors are synergistic, resulting in a decrease of the specific growth rate and ethanol production rate and, hence, are major determinants of cell stability and ethanol fermentation performance of S. cerevisiae at high temperatures. The results are discussed in the context of possible applications.

  3. The use of transcranial magnetic stimulation in diagnosis, prognostication and treatment evaluation in multiple sclerosis.

    PubMed

    Simpson, Marion; Macdonell, Richard

    2015-09-01

    Despite advances in brain imaging which have revolutionised the diagnosis and monitoring of patients with Multiple Sclerosis (MS), current imaging techniques have limitations, including poor correlation with clinical disability and prognosis. There is growing evidence that electrophysiological techniques may provide complementary functional information which can aid in diagnosis, prognostication and perhaps even monitoring of treatment response in patients with MS. Transcranial magnetic stimulation (TMS) is an underutilised technique with potential to assist diagnosis, predict prognosis and provide an objective surrogate marker of clinical progress and treatment response. This review explores the existing body of evidence relating to the use of TMS in patients with MS, outlines the practical aspects and scope of TMS testing and reviews the current evidence relating to the use of TMS in diagnosis, disease classification, prognostication and response to symptomatic and disease-modifying therapies.

  4. Hydrothermal acid treatment for sugar extraction from Golenkinia sp.

    PubMed

    Choi, Sun-A; Choi, Won-Il; Lee, Jin-Suk; Kim, Seung Wook; Lee, Gye-An; Yun, Jihyun; Park, Ji-Yeon

    2015-08-01

    In this study, hydrothermal acid treatment for efficient recovery of sugar from Golenkinia sp. was investigated. The initial glucose and XMG (xylose, mannose, and galactose) contents of a prepared Golenkinia sp. solution (40g/L) were 15.05 and 5.24g/L, respectively. The microalgal cell walls were hydrolyzed, for sugar recovery, by enzymatic saccharification and/or hydrothermal acid treatment. Among the various hydrothermal acid treatment conditions, the most optimal were the 2.0% H2SO4 concentration at 150°C for 15min, under which the glucose- and XMG-extraction yields were 71.7% and 64.9%, respectively. By pH 4.8, 50°C enzymatic hydrolysis after optimal hydrothermal acid treatment, the glucose- and XMG-extraction yields were additionally increased by 8.3% and 0.8%, respectively. After hydrothermal acid treatment, the combination with the enzymatic hydrolysis process improved the total sugar yield of Golenkinia sp. to 75.4%.

  5. UNANSWERED QUESTIONS IN THE TRANSCRANIAL MAGNETIC STIMULATION TREATMENT OF PATIENTS WITH DEPRESSION.

    PubMed

    Morvai, Szabolcs; Nagy, Attila; Kovács, Attila; Móre, Csaba E; Berecz, Roland; Frecska, Ede

    2016-01-30

    According to the WHO fact sheet depression is a common mental disorder affecting 350 million people of all ages worldwide. Transcranial Magnetic Stimulation (TMS) is a technique which allows the investigator to stimulate and study cortical functions in healthy subjects and patients suffering from various mental and neurological disorders. In the early 1990s, studies revealed that it is possible to evoke long term mood changes in healthy volunteers by rapid rate repetitive, TMS (rTMS) over the frontal cortex. Subsequent studies involving depressed patients found frontal cortical rTMS administered daily to be clinically effective. In the past two decades, numerous trials examined the therapeutic potential of rTMS application in the treatment of mood disorders with constantly evolving treatment protocols. The aim of this paper is to review the literature of the past two decades, focusing on trials addressing the efficacy and safety of rTMS in depressed patients. Our primary goal is to evaluate the results in order to direct future studies which may help investigators in the development of treatment protocols suitable in hospital settings. The time is not far when TMS devices will be used routinely by practitioners primarily for therapeutic purpose rather than clinical research. To our knowledge, a widely accepted "gold standard" that would offer the highest efficacy, with the best tolerability has not been established yet. In order to approach this goal, the most important factors to be addressed by further studies are: localization, frequency, intensity, concurrent medication, maintenance treatments, number of pulses, trains, unilateral, or bilateral mode of application. PMID:26987235

  6. Ultrasound-stimulated microbubble enhancement of radiation treatments: endothelial cell function and mechanism

    PubMed Central

    Al-Mahrouki, Azza A.; Wong, Emily; Czarnota, Gregory J.

    2015-01-01

    Endothelial cell death caused by novel microbubble-enhanced ultrasound cancer therapy leads to secondary tumour cell death. In order to characterize and optimize these treatments, the molecular mechanisms resulting from the interaction with endothelial cells were investigated here. Endothelial cells (HUVEC) were treated with ultrasound-stimulated microbubbles (US/MB), radiation (XRT), or a combination of US/MB+XRT. Effects on cells were evaluated at 0, 3, 6, and 24 hours after treatment. Experiments took place in the presence of modulators of sphingolipid-based signalling including ceramide, fumonisin B1, monensin, and sphingosine-1-phosphate. Experimental outcomes were evaluated using histology, TUNEL, clonogenic survival methods, immuno-fluorescence, electron microscopy, and endothelial cell blood-vessel-like tube forming assays. Fewer cells survived after treatment using US/MB+XRT compared to either the control or XRT. The functional ability to form tubes was only reduced in the US/ MB+XRT condition in the control, the ceramide, and the sphingosine-1-phosphate treated groups. The combined treatment had no effect on tube forming ability in either the fumonisin B1 or in the monensin exposed groups, since both interfere with ceramide production at different cellular sites. In summary, experimental results supported the role of ceramide signalling as a key element in cell death initiation with treatments using US/MB+XRT to target endothelial cells. PMID:26909363

  7. New chlorinated amphetamine-type-stimulants disinfection-by-products formed during drinking water treatment.

    PubMed

    Huerta-Fontela, Maria; Pineda, Oriol; Ventura, Francesc; Galceran, Maria Teresa

    2012-06-15

    Previous studies have demonstrated high removal rates of amphetamine-type-stimulants (ATSs) through conventional drinking water treatments; however the behaviour of these compounds through disinfection steps and their transformation into disinfection-by-products (DBPs) is still unknown. In this work, for the first time, the reactivity of some ATSs such as amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA) and 3,4-methylenedioxyethylamphetamine (MDEA) with chlorine has been investigated under simulated and real drinking water treatment conditions in order to evaluate their ability to give rise to transformation products. Two new DBPs from these illicit drugs have been found. A common chlorinated-by-product (3-chlorobenzo)-1,3-dioxole, was identified for both MDA and MDEA while for MDMA, 3-chlorocatechol was found. The presence of these DBPs in water samples collected through drinking water treatment was studied in order to evaluate their formation under real conditions. Both compounds were generated through treatment from raw river water samples containing ATSs at concentration levels ranging from 1 to 15 ng/L for MDA and from 2.3 to 78 ng/L for MDMA. One of them, (3-chlorobenzo)-1,3-dioxole, found after the first chlorination step, was eliminated after ozone and GAC treatment while the MDMA DBP mainly generated after the postchlorination step, showed to be recalcitrant and it was found in final treated waters at concentrations ranging from 0.5 to 5.8 ng/L.

  8. Stimulation of Insulin Secretion by Long-Chain Free Fatty Acids. A DIRECT PANCREATIC EFFECT

    PubMed Central

    Crespin, Stephen R.; Greenough, William B.; Steinberg, Daniel

    1973-01-01

    A continuous-flow centrifuge was used to infuse sodium salts of oleic, linoleic, lauric, or palmitic acid into the pancreatic artery of anesthetized dogs. In these regional perfusion studies there was no increase in FFA levels in the general circulation. Elevation of pancreatic FFA levels produced an immediate increase in pancreatic venous immunoreactive insulin (IRI). After 10 min of FFA infusion. IRI levels declined somewhat from the initial peak response but soon rose again to high levels which were then sustained until the infusion was terminated. All four long-chain FFA tested produced a similar biphasic IRI response. Clearcut increases in IRI were associated with absolute FFA levels (measured in pancreaticoduodenal venous plasma) as low as 0.6-0.8 μeq/ml and with increments over basal levels of as little as 0.4-0.5 μeq/ml. At higher levels of FFA, absolute IRI levels in the pancreatic venous effluent exceeded 1,000 μU/ml in some experiments and 5- to 10-fold increases over basal values were observed. These studies indicate that long-chain FFA, in physiological concentrations, can markedly stimulate insulin secretion by a direct effect on the pancreas. The results lend support to the concept of insulin as a hormone that is importantly involved in regulating the metabolism of all three principal classes of metabolic substrates and whose release is in turn regulated by all of them. The relative importance and precise nature of its physiologic role in the regulation of lipolysis, lipid deposition, and ketone body formation remains to be established. Images PMID:4719673

  9. Long-term stimulant medication treatment of attention-deficit/hyperactivity disorder: results from a population-based study.

    PubMed

    Barbaresi, William J; Katusic, Slavica K; Colligan, Robert C; Weaver, Amy L; Leibson, Cynthia L; Jacobsen, Steven J

    2014-09-01

    The purpose of this study was to offer detailed information about stimulant medication treatment provided throughout childhood to 379 children with research-identified attention-deficit hyperactivity disorder (ADHD) in the 1976-1982 Rochester, MN, birth cohort. Subjects were retrospectively followed from birth until a mean of 17.2 years of age. The complete medical record of each subject was reviewed. The history and results of each episode of stimulant treatment were compared by gender, DSMIV subtype of ADHD, and type of stimulant medication. Overall, 77.8% of subjects were treated with stimulants. Boys were 1.8 times more likely than girls to be treated. The median age at initiation (9.8 years), median duration of treatment (33.8 months), and likelihood of developing at least one side effect (22.3%) were not significantly different by gender. Overall, 73.1% of episodes of stimulant treatment were associated with a favorable response. The likelihood of a favorable response was comparable for boys and girls. Treatment was initiated earlier for children with either ADHD combined type or ADHD hyperactive-impulsive type than for children with ADHD predominantly inattentive type and duration of treatment was longer for ADHD combined type. There was no association between DSM-IV subtype and likelihood of a favorable response or of side effects. Dextroamphetamine and methylphenidate were equally likely to be associated with a favorable response, but dextroamphetamine was more likely to be associated with side effects. These results demonstrate that the effectiveness of stimulant medication treatment of ADHD provided throughout childhood is comparable to the efficacy of stimulant treatment demonstrated in clinical trials.

  10. Neuroprotection of lipoic acid treatment promotes angiogenesis and reduces the glial scar formation after brain injury.

    PubMed

    Rocamonde, B; Paradells, S; Barcia, J M; Barcia, C; García Verdugo, J M; Miranda, M; Romero Gómez, F J; Soria, J M

    2012-11-01

    After trauma brain injury, a large number of cells die, releasing neurotoxic chemicals into the extracellular medium, decreasing cellular glutathione levels and increasing reactive oxygen species that affect cell survival and provoke an enlargement of the initial lesion. Alpha-lipoic acid is a potent antioxidant commonly used as a treatment of many degenerative diseases such as multiple sclerosis or diabetic neuropathy. Herein, the antioxidant effects of lipoic acid treatment after brain cryo-injury in rat have been studied, as well as cell survival, proliferation in the injured area, gliogenesis and angiogenesis. Thus, it is shown that newborn cells, mostly corresponded with blood vessels and glial cells, colonized the damaged area 15 days after the lesion. However, lipoic acid was able to stimulate the synthesis of glutathione, decrease cell death, promote angiogenesis and decrease the glial scar formation. All those facts allow the formation of new neural tissue. In view of the results herein, lipoic acid might be a plausible pharmacological treatment after brain injury, acting as a neuroprotective agent of the neural tissue, promoting angiogenesis and reducing the glial scar formation. These findings open new possibilities for restorative strategies after brain injury, stroke or related disorders.

  11. Amoxycillin and clavulanic acid in the treatment of urinary infection.

    PubMed Central

    Al Roomi, L G; Sutton, A M; Cockburn, F; McAllister, T A

    1984-01-01

    The pharmacokinetics and clinical efficacy of amoxycillin combined with clavulanic acid in the treatment of 32 children with urinary tract infection were studied. Twenty one (80%) of 26 children with proved urinary tract infection showed a favourable clinical and bacteriological response. Fifteen of these children had amoxycillin resistant organisms and were treated successfully. In 20 children the serum and urine concentrations of amoxycillin and clavulanic acid were measured after the first oral dose. PMID:6712275

  12. The botanical molecule p-hydroxycinnamic acid as a new osteogenic agent: insight into the treatment of cancer bone metastases.

    PubMed

    Yamaguchi, Masayoshi

    2016-10-01

    Bone homeostasis is maintained through a balance between osteoblastic bone formation and osteoclastic bone resorption. Bone loss with aging is induced by decreasing in osteoblastic bone formation and increasing in osteoclastic bone resorption, thereby leading to osteoporosis. Osteoporosis with its accompanying decrease in bone mass is widely recognized as a major public heath problem. Pharmacologic and nutritional factors may play a role in the prevention and treatment of bone loss with aging. p-Hydroxycinnamic acid (HCA), which stimulates bone mineralization in mouse bone tissues in vitro, has been found to be present in the leafstalk of wasabi (Wasabi japonica MATSUM) among various food and plants. Other phenolic acids including cinnamic acid, ferulic acid, caffeic acid and 3,4-dimethoxycinnamic acid did not have osteogenic effects. HCA was demonstrated to stimulate osteoblastic bone formation and suppresses osteoclastic bone resorption in vitro by antagonizing activation of the nuclear factor kappa B. Oral administration of HCA was found to exhibit restorative effects on bone loss induced by ovariectomy and diabetic states, supporting a role in the treatment of osteoporosis. Moreover, HCA was demonstrated to prevent the suppressed osteoblastic mineralization and the enhanced osteoclastogenesis in mouse bone marrow cells cocultured with bone metastatic MDA-MB-231 human breast cancer cells in vitro. The botanical molecule HCA, as a new osteogenic agent, is suggested to play a role in the treatment of cancer bone metastases. This review will discuss an advanced recent finding that HCA may be a useful agent to treat bone metabolic disorder. PMID:27573001

  13. Changes of cytokine production and cell viability of peripheral blood mononuclear cells from silicosis patients: effect of in vitro treatment with acetylsalicylic acid.

    PubMed

    Dobreva, Zlatka Georgieva; Prakova, Gospodinka Radeva; Slavov, Emil Slavov; Stanilova, Spaska Angelova

    2010-02-01

    In this study, IL-6 and IL-12p40 production and cell viability of peripheral blood mononuclear cells from silicosis patients after in vitro stimulation were investigated. Furthermore, the effects of introducing acetylsalicylic acid to stimulated patients' peripheral blood mononuclear cells on cytokine production and cell viability were determined. Nine patients with moderate silicosis, 11 with severe silicosis and 14 healthy subjects were recruited for this study. The level of IL-6 produced by patients peripheral blood mononuclear cells decreased depending on the stage of the disease. The addition of acetylsalicylic acid had significantly suppressive effect on the IL-6 production by lipopolysaccharide-stimulated patients' peripheral blood mononuclear cells. Acetylsalicylic acid treatment of C3 binding glycoprotein-stimulated patients' peripheral blood mononuclear cells led to significant upregulation of IL-12p40 production. Results showed a stage-dependent decrease of cell viability of peripheral blood mononuclear cells from silicosis patients. Acetylsalicylic acid significantly decreased cell viability entirely in stimulated peripheral blood mononuclear cells from patients with severe silicosis. In conclusion, this study showed that the disease progression affects peripheral blood mononuclear cells in patients with silicosis and causes functional changes that became apparent after stimulation. Our study demonstrated that in severe silicosis the treatment with acetylsalicylic acid, as an anti-inflammatory agent, might not be beneficial for patients.

  14. Longitudinal magnetic resonance imaging reveals striatal hypertrophy in a rat model of long-term stimulant treatment

    PubMed Central

    Biezonski, D; Shah, R; Krivko, A; Cha, J; Guilfoyle, D N; Hrabe, J; Gerum, S; Xie, S; Duan, Y; Bansal, R; Leventhal, B L; Peterson, B S; Kellendonk, C; Posner, J

    2016-01-01

    Stimulant treatment is highly effective in mitigating symptoms associated with attention-deficit/hyperactivity disorder (ADHD), though the neurobiological underpinnings of this effect have not been established. Studies using anatomical magnetic resonance imaging (MRI) in children with ADHD have suggested that long-term stimulant treatment may improve symptoms of ADHD in part by stimulating striatal hypertrophy. This conclusion is limited, however, as these studies have either used cross-sectional sampling or did not assess the impact of treatment length on their dependent measures. We therefore used longitudinal anatomical MRI in a vehicle-controlled study design to confirm causality regarding stimulant effects on striatal morphology in a rodent model of clinically relevant long-term stimulant treatment. Sprague Dawley rats were orally administered either lisdexamfetamine (LDX, ‘Vyvanse') or vehicle (N=12 per group) from postnatal day 25 (PD25, young juvenile) until PD95 (young adult), and imaged one day before and one day after the 70-day course of treatment. Our LDX dosing regimen yielded blood levels of dextroamphetamine comparable to those documented in patients. Longitudinal analysis of striatal volume revealed significant hypertrophy in LDX-treated animals when compared to vehicle-treated controls, with a significant treatment by time point interaction. These findings confirm a causal link between long-term stimulant treatment and striatal hypertrophy, and support utility of longitudinal MRI in rodents as a translational approach for bridging preclinical and clinical research. Having demonstrated comparable morphological effects in both humans and rodents using the same imaging technology, future studies may now use this rodent model to identify the underlying cellular mechanisms and behavioral consequences of stimulant-induced striatal hypertrophy. PMID:27598968

  15. Longitudinal magnetic resonance imaging reveals striatal hypertrophy in a rat model of long-term stimulant treatment.

    PubMed

    Biezonski, D; Shah, R; Krivko, A; Cha, J; Guilfoyle, D N; Hrabe, J; Gerum, S; Xie, S; Duan, Y; Bansal, R; Leventhal, B L; Peterson, B S; Kellendonk, C; Posner, J

    2016-01-01

    Stimulant treatment is highly effective in mitigating symptoms associated with attention-deficit/hyperactivity disorder (ADHD), though the neurobiological underpinnings of this effect have not been established. Studies using anatomical magnetic resonance imaging (MRI) in children with ADHD have suggested that long-term stimulant treatment may improve symptoms of ADHD in part by stimulating striatal hypertrophy. This conclusion is limited, however, as these studies have either used cross-sectional sampling or did not assess the impact of treatment length on their dependent measures. We therefore used longitudinal anatomical MRI in a vehicle-controlled study design to confirm causality regarding stimulant effects on striatal morphology in a rodent model of clinically relevant long-term stimulant treatment. Sprague Dawley rats were orally administered either lisdexamfetamine (LDX, 'Vyvanse') or vehicle (N=12 per group) from postnatal day 25 (PD25, young juvenile) until PD95 (young adult), and imaged one day before and one day after the 70-day course of treatment. Our LDX dosing regimen yielded blood levels of dextroamphetamine comparable to those documented in patients. Longitudinal analysis of striatal volume revealed significant hypertrophy in LDX-treated animals when compared to vehicle-treated controls, with a significant treatment by time point interaction. These findings confirm a causal link between long-term stimulant treatment and striatal hypertrophy, and support utility of longitudinal MRI in rodents as a translational approach for bridging preclinical and clinical research. Having demonstrated comparable morphological effects in both humans and rodents using the same imaging technology, future studies may now use this rodent model to identify the underlying cellular mechanisms and behavioral consequences of stimulant-induced striatal hypertrophy. PMID:27598968

  16. Does zinc moderate essential fatty acid and amphetamine treatment of attention-deficit/hyperactivity disorder?

    PubMed

    Arnold, L E; Pinkham, S M; Votolato, N

    2000-01-01

    Zinc is an important co-factor for metabolism relevant to neurotransmitters, fatty acids, prostaglandins, and melatonin, and indirectly affects dopamine metabolism, believed intimately involved in attention-deficit/hyperactivity disorder (ADHD). To explore the relationship of zinc nutrition to essential fatty acid supplement and stimulant effects in treatment of ADHD, we re-analyzed data from an 18-subject double-blind, placebo-controlled crossover treatment comparison of d-amphetamine and Efamol (evening primrose oil, rich in gamma-linolenic acid). Subjects were categorized as zinc-adequate (n = 5), borderline zinc (n = 5), and zinc-deficient (n = 8) by hair, red cell, and urine zinc levels; for each category, placebo-active difference means were calculated on teachers' ratings. Placebo-controlled d-amphetamine response appeared linear with zinc nutrition, but the relationship of Efamol response to zinc appeared U-shaped; Efamol benefit was evident only with borderline zinc. Placebo-controlled effect size (Cohen's d) for both treatments ranged up to 1.5 for borderline zinc and dropped to 0.3-0.7 with mild zinc deficiency. If upheld by prospective research, this post-hoc exploration suggests that zinc nutrition may be important for treatment of ADHD even by pharmacotherapy, and if Efamol benefits ADHD, it likely does so by improving or compensating for borderline zinc nutrition. PMID:10933121

  17. [Safety and neuroethical consideration of deep brain stimulation as a psychiatric treatment].

    PubMed

    Takagi, Miyako

    2009-01-01

    Deep brain stimulation (DBS) is a surgical treatment involving the implantation of a medical device, which sends electrical impulses to specific parts of the brain. DBS in select brain regions has provided remarkable therapeutic benefits for treatment-resistant movement and affective disorders such as Parkinson's disease. DBS directly alters brain activity in a controlled manner, and its effects are reversible. Lately, DBS treatment has been used for the treatment of various psychiatric disorders, such as obsessive compulsive disorder, Tourette syndrome, and severe depression. However, DBS therapies for affective disorders are still at their experimental stage, and some scientists point out that there may be a risk involved, because the device implanted in a person's brain may alter his/her brain function and hence his personal identity. With support from the New Energy and Industrial Technology Development Organization (NEDO), Japanese government, we conducted international research on the effects of DBS therapies for psychiatric disorders, examined the safety of such therapies, and clarified the conditions for proper application of the DBS technique. The research items were as follows: (1) safety issues concerning the deterioration of DBS electrodes and the possibilities of developing new and better materials, (2) the role of coordinators who mediate between patients and DBS devices, (3) social concerns regarding personality changes/brain plasticity, (4) re-examination of ethical debates on prefrontal lobotomy (lessons from the past), (5) possible use of DBS for the purpose of brain enhancement, and (6) end users' expectations and fears toward DBS.

  18. Brain stimulation for treatment and enhancement in children: an ethical analysis

    PubMed Central

    Maslen, Hannah; Earp, Brian D.; Cohen Kadosh, Roi; Savulescu, Julian

    2014-01-01

    Davis (2014) called for “extreme caution” in the use of non-invasive brain stimulation (NIBS) to treat neurological disorders in children, due to gaps in scientific knowledge. We are sympathetic to his position. However, we must also address the ethical implications of applying this technology to minors. Compensatory trade-offs associated with NIBS present a challenge to its use in children, insofar as these trade-offs have the effect of limiting the child’s future options. The distinction between treatment and enhancement has some normative force here. As the intervention moves away from being a treatment toward being an enhancement—and thus toward a more uncertain weighing of the benefits, risks, and costs—considerations of the child’s best interests (as judged by the parents) diminish, and the need to protect the child’s (future) autonomy looms larger. NIBS for enhancement involving trade-offs should therefore be delayed, if possible, until the child reaches a state of maturity and can make an informed, personal decision. NIBS for treatment, by contrast, is permissible insofar as it can be shown to be at least as safe and effective as currently approved treatments, which are themselves justified on a best interests standard. PMID:25566011

  19. [Effect of ascorbic acid, epidermal growth factor and follicle stimulating hormone on in vitro culture of sheep ovarian cortical tissue].

    PubMed

    Peng, Xiayu; Wang, Liqin; Yang, Mei; Chen, Tong; Guo, Zhiqin

    2010-06-01

    In this study, we evaluated the effects of ascorbic acid (VC), epidermal growth factor (EGF) and follicle stimulating hormone (FSH) on in vitro culture of sheep ovarian cortical tissue. Using 2 x 2 x 2 factor experimental design, we cultured sheep ovarian cortex fragments in 8 media with MEM (control), MEM+VC (50 microg/mL), MEM +EGF (100 ng/mL), MEM+FSH (50 ng/mL), MEM+VC+EGF, MEM+VC+FSH, MEM+EGF+FSH, MEM+VC+EGF+FSH. After 0 (non-cultured control), 2, 6, 12 days of culture, the pieces of ovarian cortex were proceed to histological and proliferating cell nuclear antigen (PCNA) examination, or observed by transmission electron microscopy (TEM). The percentages of developing follicles were increased (P < 0.05) and the percentages of healthy follicles were reduced (P < 0.05). When compared to the MEM group, the addition of FSH with VC or EGF promoted a significant increase of follicles diameter and follicles survival rate (P < 0.05), and stimulated the proliferation of granulosa cells. After 12 days of culture, medium supplemented with MEM+VC+EGF resulted the lowest proportion of developing follicles (49.3% +/- 3.2%), follicles diameter((32.3 +/- 2.3) microm), follicles survival rate (41.6% +/- 3.1%) and the proportion of PCNA stained follicles (26.4% +/- 1.2%, P < 0.05). In contrast, MEM+VC+EGF+FSH resulted the highest follicles diameter ((42.5 +/- 5.1) microm), follicles survival rate (59.7% +/- 6.1%) and proportion of PCNA stained follicles (43.5% +/- 4.1%, P < 0.05). Ultrastructural analysis confirmed the integrity of follicles cultured in VC+EGF+FSH group, while follicles cultured in MEM+VC+EGF groups showed more degeneration characters. In conclusion, the addition of VC and EGF to culture medium inhibited follicular development, VC+EGF+FSH was the most effective treatment to maintain follicular integrity and promote sheep primordial follicular activation and growth during in vitro culture.

  20. Selective stimulation of excitatory amino acid receptor subtypes and the survival of granule cells in culture: effect of quisqualate and AMPA.

    PubMed

    Hack, N; Balázs, R

    1994-09-01

    Differentiating granule cells develop survival requirements in vitro which can be met by treatment with high K+ or excitatory amino acids. Promotion of cell survival by N-methyl-D-aspartate (NMDA) or kainate has already been established and here we report that treatment of the cells with alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate (AMPA) or quisqualate (QA) also leads to cell rescue. In comparison with the effect of NMDA, the influence of AMPA/QA is small, resulting in a 20-30% increase in cell survival, with a peak at a very narrow concentration range (0.5-2.0 microM QA and 5-10 microM AMPA). The effect is exclusive to AMPA receptor stimulation, since stimulation of metabotropic glutamate receptors with (1S3R)-1-amino-cyclopentane-1,3-dicarboxylic acid (ACPD) has no effect. Furthermore, AMPA/QA rescue of cells is blocked by ionotropic non-NMDA receptor antagonists, 6,7-dinitroquinoxaline-2,3-dione (DNQX) and 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzoquinoxaline (NBQX). In addition, both nifedipine and dizolcipline (MK-801) interfered with the cell survival promoting effect of AMPA, suggesting that the influence of AMPA is mediated via calcium influx involving both depolarization-activated voltage sensitive calcium channels and NMDA receptors stimulated as a result of AMPA-induced release of glutamate. Possible reasons for the small cell survival promoting effect of AMPA/QA compared with the influence of high K+ or NMDA are discussed.

  1. The nitric oxide-donating derivative of acetylsalicylic acid, NCX 4016, stimulates glucose transport and glucose transporters translocation in 3T3-L1 adipocytes.

    PubMed

    Kaddai, V; Gonzalez, T; Bolla, M; Le Marchand-Brustel, Y; Cormont, M

    2008-07-01

    NCX 4016 is a nitric oxide (NO)-donating derivative of acetylsalicylic acid. NO and salicylate, in vivo metabolites of NCX 4016, were shown to be potential actors in controlling glucose homeostasis. In this study, we evaluated the action of NCX 4016 on the capacity of 3T3-L1 adipocytes to transport glucose in basal and insulin-stimulated conditions. NCX 4016 induced a twofold increase in glucose uptake in parallel with the translocation of the glucose transporters GLUT1 and GLUT4 to the plasma membrane, leaving unaffected their total expression levels. Importantly, NCX 4016 further increased glucose transport induced by a physiological concentration of insulin. The stimulatory effect of NCX 4016 on glucose uptake appears to be mediated by its NO moiety. Indeed, it is inhibited by a NO scavenger and treatment with acetylsalicylic or salicylic acid had no effect. Although NO is involved in the action of NCX 4016, it did not mainly depend on the soluble cGMP cyclase/protein kinase G pathway. Furthermore, NCX 4016-stimulated glucose transport did not involve the insulin-signaling cascade required to stimulate glucose transport. NCX 4016 induces a small activation of the mitogen-activated protein kinases p38 and c-Jun NH(2)-terminal kinase and no activation of other stress-activated signaling molecules, including extracellular signal-regulated kinase, inhibitory factor kappaB, or AMP-activated kinases. Interestingly, NCX 4016 modified the content of S-nitrosylated proteins in adipocytes. Taken together, our results indicate that NCX 4016 induced glucose transport in adipocytes through a novel mechanism possibly involving S-nitrosylation. NCX 4016 thus possesses interesting characteristics to be considered as a candidate molecule for the treatment of patients suffering from metabolic syndrome and type 2 diabetes. PMID:18492771

  2. Theobromine Inhibits Uric Acid Crystallization. A Potential Application in the Treatment of Uric Acid Nephrolithiasis

    PubMed Central

    Grases, Felix; Rodriguez, Adrian; Costa-Bauza, Antonia

    2014-01-01

    Purpose To assess the capacity of methylxanthines (caffeine, theophylline, theobromine and paraxanthine) to inhibit uric acid crystallization, and to evaluate their potential application in the treatment of uric acid nephrolithiasis. Materials and Methods The ability of methylxathines to inhibit uric acid nucleation was assayed turbidimetrically. Crystal morphology and its modification due to the effect of theobromine were evaluated by scanning electron microscopy (SEM). The ability of theobromine to inhibit uric acid crystal growth on calculi fragments resulting from extracorporeal shock wave lithotripsy (ESWL) was evaluated using a flow system. Results The turbidimetric assay showed that among the studied methylxanthines, theobromine could markedly inhibit uric acid nucleation. SEM images showed that the presence of theobromine resulted in thinner uric acid crystals. Furthermore, in a flow system theobromine blocked the regrowth of post-ESWL uric acid calculi fragments. Conclusions Theobromine, a natural dimethylxanthine present in high amounts in cocoa, acts as an inhibitor of nucleation and crystal growth of uric acid. Therefore, theobromine may be clinically useful in the treatment of uric acid nephrolithiasis. PMID:25333633

  3. Stimulation of sympathetic innervation in the upper gastrointestinal tract as a treatment for obesity

    PubMed Central

    Zheng, Jolene; DiLorenzo, Daniel J.; McLaughlin, Leslie; Roberts, Andrew T.; Greenway, Frank L.

    2009-01-01

    SUMMARY Sympathetic activity and obesity have a reciprocal relationship. Firstly, hypothalamic obesity is associated with decreased sympathetic activity. Caffeine and ephedrine increase sympathetic activity and induce weight loss, of which 25% is due to increased metabolic rate and 75% is due to a reciprocally decreased food intake. Secondly, hormones and drugs that affect body weight have an inverse relationship between food intake and metabolic rate. Neuropeptide Y decreases sympathetic activity and increases food intake and body weight. Thirdly, a gastric pacemaker Transcend® and vagotomy increase the ratio of sympathetic to parasympathetic activation, decrease food intake, and block gut satiety hormones. Weight loss with the pacemaker or vagotomy is variable. Significant weight reduction is seen only in a small group of those treated. This suggests that activation of the sympathetic arm of the autonomic nervous system may be most important for weight loss. Systemic sympathetic activation causes weight loss in obese patients, but side effects limited its use. We hypothesize that selective local electrical sympathetic stimulation of the upper gastrointestinal tract may induce weight loss and offer a safer, yet effective, obesity treatment. Celiac ganglia delivers sympathetic innervation to the upper gastrointestinal tract. Voltage regulated electrical simulation of the rat celiac ganglia increased metabolic rate in a dose-dependent manner. Stimulation of 6, 3, or 1.5 V increased metabolic rate 15.6%, 6.2%, and 5%, respectively in a single rat. These responses support our hypothesis that selective sympathetic stimulation of the upper GI tract may treat obesity while avoiding side effects of systemic sympathetic activation. PMID:19246162

  4. Treatment of facial molluscum contagiosum with trichloroacetic acid.

    PubMed

    Bard, Susan; Shiman, Michael I; Bellman, Betty; Connelly, Elizabeth Alvarez

    2009-01-01

    Molluscum contagiosum (MC) virus is a common cutaneous infection in the pediatric population, most commonly affecting school-aged children. Spontaneous clearing of lesions usually occurs over time; however, treatment is often sought due to cosmetic significance, pruritus, or concerns of transmission and autoinoculation. Chemical destruction with cantharidin, which is derived from blister beetle extract, is very safe and highly effective, making it the treatment of choice in the pediatric population. However, treatment of facial lesions or those in the diaper area are not recommended with this agent. Trichloroacetic acid is a safe and effective agent frequently utilized in dermatologic practice, most commonly in the treatment of verrucae. We have successfully used topical trichloroacetic acid to treat facial molluscum contagiousum and present the following technique for proper application. PMID:19689517

  5. The assessment of a novel electrical stimulation waveform recently introduced for the treatment of overactive bladder.

    PubMed

    Slovak, M; Barker, A T; Chapple, C R

    2013-05-01

    Transdermal amplitude modulated signal (TAMS) is a novel electrical stimulus which has been recently introduced for the treatment of overactive bladder (OAB) syndrome. It has been suggested that it has advantages over conventional waveforms by providing more effective penetration of the skin to enhance the efficacy of therapy. As there is no literature which supports this, we performed this study to evaluate potential advantages of the TAMS signal for electrical stimulation of subcutaneous nerves as compared to conventional stimuli. The stimuli were applied on forearms of ten healthy volunteers and electrical parameters of stimuli and sensation measurements were recorded. None of the recorded electrical parameters showed significant differences (paired t-test p ≥ 0.250) between the TAMS and conventional waveforms. Similarly, the mean sensation recorded at motor threshold level and at 50% of maximal motor response level showed no differences (paired t-test p = 0.242 and p = 0.687 respectively). It is unlikely, based on the results of this study, that TAMS provides any enhancement of the efficacy of conventional stimuli. We would recommend that further studies are carried out to clearly demonstrate in man what, if any, advantages the TAMS waveform has over conventional stimulation before it is widely deployed into clinical practice. PMID:23571145

  6. Gastric Electrical Stimulation for the Treatment of Obesity: From Entrainment to Bezoars—A Functional Review

    PubMed Central

    Mintchev, Martin P.

    2013-01-01

    Growing worldwide obesity epidemic has prompted the development of two main treatment streams: (a) conservative approaches and (b) invasive techniques. However, only invasive surgical methods have delivered significant and sustainable benefits. Therefore, contemporary research exploration has focused on the development of minimally invasive gastric manipulation methods featuring a safe but reliable and long-term sustainable weight loss effect similar to the one delivered by bariatric surgeries. This antiobesity approach is based on placing external devices in the stomach ranging from electrodes for gastric electrical stimulation to temporary intraluminal bezoars for gastric volume displacement for a predetermined amount of time. The present paper examines the evolution of these techniques from invasively implantable units to completely noninvasive patient-controllable implements, from a functional, rather than from the traditional, parametric point of view. Comparative discussion over the available pilot and clinical studies related to gastric electrical stimulation outlines the promises and the fallacies of this concept as a reliable alternative anti-obesity strategy. PMID:23476793

  7. Caloric vestibular stimulation as a treatment for conversion disorder: a case report and medical hypothesis.

    PubMed

    Noll-Hussong, Michael; Holzapfel, Sabrina; Pokorny, Dan; Herberger, Simone

    2014-01-01

    Conversion disorder is a medical condition in which a person has paralysis, blindness, or other neurological symptoms that cannot be clearly explained physiologically. To date, there is neither specific nor conclusive treatment. In this paper, we draw together a number of disparate pieces of knowledge to propose a novel intervention to provide transient alleviation for this condition. As caloric vestibular stimulation has been demonstrated to modulate a variety of cognitive functions associated with brain activations, especially in the temporal-parietal cortex, anterior cingulate cortex, and insular cortex, there is evidence to assume an effect in specific mental disorders. Therefore, we go on to hypothesize that lateralized cold vestibular caloric stimulation will be effective in treating conversion disorder and we present provisional evidence from one patient that supports this conclusion. If our hypothesis is correct, this will be the first time in psychiatry and neurology that a clinically well-known mental disorder, long considered difficult to understand and to treat, is relieved by a simple or common, non-invasive medical procedure.

  8. Caloric Vestibular Stimulation as a Treatment for Conversion Disorder: A Case Report and Medical Hypothesis

    PubMed Central

    Noll-Hussong, Michael; Holzapfel, Sabrina; Pokorny, Dan; Herberger, Simone

    2014-01-01

    Conversion disorder is a medical condition in which a person has paralysis, blindness, or other neurological symptoms that cannot be clearly explained physiologically. To date, there is neither specific nor conclusive treatment. In this paper, we draw together a number of disparate pieces of knowledge to propose a novel intervention to provide transient alleviation for this condition. As caloric vestibular stimulation has been demonstrated to modulate a variety of cognitive functions associated with brain activations, especially in the temporal–parietal cortex, anterior cingulate cortex, and insular cortex, there is evidence to assume an effect in specific mental disorders. Therefore, we go on to hypothesize that lateralized cold vestibular caloric stimulation will be effective in treating conversion disorder and we present provisional evidence from one patient that supports this conclusion. If our hypothesis is correct, this will be the first time in psychiatry and neurology that a clinically well-known mental disorder, long considered difficult to understand and to treat, is relieved by a simple or common, non-invasive medical procedure. PMID:24917828

  9. Interventional treatment of obesity and diabetes: An interim report on gastric electrical stimulation.

    PubMed

    Lebovitz, Harold E

    2016-03-01

    Gastric electrical stimulation has been applied to treat human obesity since 1995. Dilatation of the stomach causes a series of neural reflexes which result in satiation and satiety. In non-obese individuals food ingestion is limited in part by this mechanism. In obese individuals, satiation and satiety are defective and unable to limit energy intake and prevent excessive weight gain. Several gastric electrical stimulatory (GES) devices have been developed, tested in clinical trials and even approved for the treatment of obesity. The design and clinical utility of three devices (Transend®, Maestro® and DIAMOND®) that have been extensively studied are presented as well as that of a new device (abiliti®) which is in early development. The Transcend®, a low energy GES device, showed promising results in open label studies but failed to show a difference from placebo in decreasing weight in obese subjects. The results of the clinical trials in treating obese subjects with the Maestro®, a vagal nerve stimulator, were sufficient to gain approval for marketing the device. The DIAMOND®, a multi-electrode GES device, has been used to treat type 2 diabetes and an associated benefit is to reduce body weight and lower systolic blood pressure. PMID:27106829

  10. A Novel Neuromuscular Electrical Stimulation Treatment for Recovery of Ankle Dorsiflexion in Chronic Hemiplegia

    PubMed Central

    Knutson, Jayme S.; Chae, John

    2011-01-01

    Objective To evaluate the feasibility of improving active ankle dorsiflexion with contralaterally controlled neuromuscular electrical stimulation (CCNMES). Design CCNMES dorsiflexes the paretic ankle with a stimulation intensity that is directly proportional to the degree of voluntary dorsiflexion of the unimpaired contralateral ankle, which is detected by an instrumented sock. Three subjects with chronic (>6-mo poststroke) dorsiflexor paresis participated in a 6-wk CCNMES treatment, which consisted of self-administering CCNMES-assisted ankle dorsiflexion exercises at home daily and practicing an ankle motor control task in the research laboratory twice a week. Results For subjects 1 and 2, respectively, maximum voluntary ankle dorsiflexion increased by 13 and 17 degrees, ankle movement tracking error decreased by ~57% and 57%, and lower limb Fugl-Meyer score (maximum score is 34) increased by 4 and 5 points. Subject 3 had no appreciable improvement in these measures. Both subjects 1 and 2 maintained their performance in ankle movement tracking through the 3-mo follow-up; subject 2 also maintained the gains in maximum ankle dorsiflexion and Fugl-Meyer score. Conclusions These results suggest that CCNMES may have a positive effect on ankle motor impairment in some stroke survivors. Further investigation of the effect of CCNMES on gait is warranted. PMID:20531158

  11. Can anti-Müllerian hormone concentrations be used to determine gonadotrophin dose and treatment protocol for ovarian stimulation?

    PubMed

    Fleming, R; Broekmans, F; Calhaz-Jorge, C; Dracea, L; Alexander, H; Nyboe Andersen, A; Blockeel, C; Jenkins, J; Lunenfeld, B; Platteau, P; Smitz, J; de Ziegler, D

    2013-05-01

    The ability to predict the response potential of women to ovarian stimulation may allow the development of individualized ovarian stimulation protocols. This tailored approach to ovarian stimulation could reduce the incidence of ovarian hyperstimulation syndrome in women predicted to have an excessive response to stimulation or could improve pregnancy outcomes in women classed as poor responders. Namely, variation of the type of gonadotrophin-releasing hormone (GnRH) analogue or the form and dosage of gonadotrophin used for stimulation could be adjusted according to an individual's response potential. The serum concentration of anti-Müllerian hormone (AMH) is established as a reliable marker of ovarian reserve, with decreasing concentrations correlated with reduced response potential. This review examines the current evidence evaluating individualized ovarian stimulation protocols using AMH concentration as a predictive marker of ovarian response. The rationale behind why specific treatment protocols based on individual response potential may be more suitable is also discussed. Based on current evidence, it appears that the use of AMH serum concentrations to predict ovarian response and optimize treatment strategies is a promising approach for improving pregnancy outcomes in women undergoing ovarian stimulation. However, prospective randomized controlled trials evaluating this approach are needed before any firm conclusions can be drawn.

  12. Salvianolic acid B stimulates osteogenesis in dexamethasone-treated zebrafish larvae

    PubMed Central

    Luo, Shi-ying; Chen, Jing-feng; Zhong, Zhi-guo; Lv, Xiao-hua; Yang, Ya-jun; Zhang, Jing-jing; Cui, Liao

    2016-01-01

    Aim: Our previous studies show that salvianolic acid B (Sal B) promotes osteoblast differentiation and matrix mineralization. In this study, we evaluated the protective effects of Sal B on the osteogenesis in dexamethasone (Dex)-treated larval zebrafish, and elucidated the underlying mechanisms. Methods: At 3 d post fertilization, wild-type AB zebrafish larvae or bone transgenic tg (sp7:egfp) zebrafish larvae were exposed to Sal B, Dex, or a mixture of Dex+Sal B for 6 d. Bone mineralization in AB strain larval zebrafish was assessed with alizarin red staining, and osteoblast differentiation in tg (sp7:egfp) larval zebrafish was examined with fluorescence scanning. The expression of osteoblast-specific genes in the larvae was detected using qRT-PCR assay. The levels of oxidative stress markers (ROS and MDA) in the larvae were also measured. Results: Exposure to Dex (5–20 μmol/L) dose-dependently decreased the bone mineralization area and integral optical density (IOD) in wild-type AB zebrafish larvae and the osteoblast fluorescence area and IOD in tg (sp7:egfp) zebrafish larvae. Exposure to Dex (10 μmol/L) significantly reduced the expression of osteoblast-specific genes, including runx2a, osteocalcin (OC), alkaline phosphatase (ALP) and osterix (sp7), and increased the accumulation of ROS and MDA in the larvae. Co-exposure to Sal B (0.2–2 μmol/L) dose-dependently increased the bone mineralization area and IOD in AB zebafish larvae and osteoblast fluorescence in tg (sp7:egfp) zebrafish larvae. Co-exposure to Sal B (2 μmol/L) significantly attenuated deleterious alterations in bony tissue and oxidative stress in both Dex-treated AB zebafish larvae and tg (sp7:egfp) zebrafish larvae. Conclusion: Sal B stimulates bone formation and rescues GC-caused inhibition on osteogenesis in larval zebrafish by counteracting oxidative stress and increasing the expression of osteoblast-specific genes. Thus, Sal B may have protective effects on bone loss trigged by GC. PMID

  13. H-coil repetitive transcranial magnetic stimulation for treatment of temporal lobe epilepsy: A case report.

    PubMed

    Gersner, R; Oberman, L; Sanchez, M J; Chiriboga, N; Kaye, H L; Pascual-Leone, A; Libenson, M; Roth, Y; Zangen, A; Rotenberg, A

    2016-01-01

    Low frequency repetitive TMS (rTMS) of a cortical seizure focus is emerging as an antiepileptic treatment. While conventional rTMS stimulators activate only superficial cortical areas, reaching deep epileptic foci, for example in temporal lobe epilepsy (TLE), is possible using specially designed H-coils. We report the results of rTMS in a young adult with pharmacoresistant bilateral TLE who underwent three courses (of 10, 15, and 30 daily sessions) of unilateral rTMS over the hemisphere from which seizures originated most often. Seizure frequency was assessed before and after each block of rTMS sessions, as was the tolerability of the procedure. Seizure frequency declined significantly, by 50 to 70% following each rTMS course. All sessions were well-tolerated. PMID:27114902

  14. Neridronic acid for the treatment of bone metabolic diseases.

    PubMed

    Gatti, Davide; Viapiana, Ombretta; Idolazzi, Luca; Fracassi, Elena; Adami, Silvano

    2009-10-01

    Neridronic acid (6-amino-1-idroxyesilidene-1,1-bisphosphonate) is a nitrogen-containing bisphosphonate licensed in Italy for the treatment of osteogenesis imperfecta and Paget's disease of bone. The pharmacodynamic profile is similar to that of other nitrogen-containing bisphosphonates and is characterized by its high affinity for bone tissue particularly at sites undergoing a process of remodeling. In growing children affected by osteogenesis imperfect, neridronic acid rapidly increases bone mineral density as measured by dual X-ray absortiometry and this is associated with a significant decrease in fracture cumulative number. Similar results have been obtained also in newborns (< 12 month old) and in adult patients. In Paget's disease of bone, 200 mg intravenous neridronic acid is associated with a 65% rate of full remission and a biochemical response (decrease of > 75% of bone turnover markers) in 95% of the patients. Neridronic acid treatment has been reported to be effective also in other skeletal diseases such as osteoporosis, algodystrophy, hypercalcemia of malignancy and bone metastasis. Neridronic acid has been developed only for parenteral use, and it is the only one used as intramuscular injection. This avoids all the limitations of oral bisphosphonates and may be offered for a home treatment with simple nursing assistance. PMID:19761412

  15. Culture Conditions stimulating high γ-Linolenic Acid accumulation by Spirulina platensis

    PubMed Central

    Ronda, Srinivasa Reddy; Lele, S.S.

    2008-01-01

    Gamma-linolenic acid (GLA) production by Spirulina platensis under different stress-inducing conditions was studied. Submerged culture studies showed that low temperature (25°C), strong light intensity (6 klux) and primrose oil supplement (0.8%w/v) induced 13.2 mg/g, 14.6 mg/g and 13.5 mg linolenic acid per gram dry cell weight respectively. A careful observation of fatty acid profile of the cyanobacteria shows that, oleic acid and linoleic acid, in experiments with varying growth temperature and oil supplements respectively, helped in accumulating excess γ-linolenic acid. In addition, cultures grown at increasing light regimes maintained the γ-linolenic acid to the total fatty acid ratio(GLA/TFA) constant, despite any change in γ-linolenic acid content of the cyanobacteria. PMID:24031291

  16. Stimulation of butyrate production by gluconic acid in batch culture of pig cecal digesta and identification of butyrate-producing bacteria.

    PubMed

    Tsukahara, Takamitsu; Koyama, Hironari; Okada, Masaaki; Ushida, Kazunari

    2002-08-01

    Gluconic acid reaches the large intestine to stimulate lactic acid bacteria. However, the fermentation pattern of gluconic acid has yet to be elucidated. Accordingly, we examined the fermentation properties induced by gluconic acid in the pig cecal digesta in vitro. We also tested sorbitol and glucose, substrates for which the fermentation rate and patterns are known. The gluconic acid-utilizing bacteria were further isolated from pig cecal digesta and identified to examine the effect of gluconic acid on hind gut fermentation. Gluconic acid was fermented more slowly than were the other two substrates. Gluconic acid stimulated butyrate production; the butyrate molar percentage reached 26%, which is considered a high butyrate production. The majority of gluconic acid fermenters were identified as lactic acid bacteria, such as Lactobacillus reuteri and L. mucosae, and acid-utilizing bacteria, such as Megasphaera elsdenii and Mitsuokella multiacida. The gluconic acid fermented by lactic acid bacteria, and the lactate and acetate that were produced were used to form butyrate by acid-utilizing bacteria, such as M. elsdenii. Gluconic acid may be useful as a prebiotic to stimulate butyrate production in the large intestine.

  17. Difference in physiological responses to sound stimulation in subjects with and without fear of dental treatments.

    PubMed

    Kudo, Takumu; Mishima, Riho; Yamamura, Kensuke; Mostafeezur, Rahman; Zakir, Hossain Md; Kurose, Masayuki; Yamada, Yoshiaki

    2008-07-01

    The effects of sound generated by an ultrasonic dental scaler and a dental turbine on heart rate, systolic and diastolic blood pressure, and hemodynamic changes in the frontal cortex were measured and compared with those of pure tone stimulation in 17 young volunteers. Near-infrared spectroscopy and the Finapres technique were used to measure hemodynamic and cardiovascular responses, respectively. The dental sound changed the various physiological parameters. To determine if this change was related to participants' previous experiences with dental treatment, participants were divided into two groups: those who had a previous unpleasant experience with dental treatment and those who had not. Participants with previous unpleasant dental experiences showed a significant decrease in cerebral blood flow. Participants who had not had an unpleasant dental experience did not show significant changes in cerebral blood flow. Thus, although sounds associated with dental treatment may reduce cerebral blood flow, this effect may depend on the dental experiences of the patient. It is recommended that dentists treat patients gently and with empathy to promote a friendly image of dentistry.

  18. Deep brain stimulation in childhood: an effective treatment for early onset idiopathic generalised dystonia

    PubMed Central

    Parr, Jeremy R; Green, Alex L; Joint, Carole; Andrew, Morag; Gregory, Ralph P; Scott, Richard B; McShane, Michael A; Aziz, Tipu Z

    2007-01-01

    Background Early onset idiopathic generalised dystonia is a progressive and profoundly disabling condition. Medical treatment may ameliorate symptoms. However, many children have profound, intractable disability including the loss of ambulation and speech, and difficulties with feeding. Following the failure of medical management, deep brain stimulation (DBS) of the globus pallidus internus (GPi) has emerged as an alternative treatment for the disorder. Methods We describe four children who presented with dystonia. Results Following the failure of a range of medical therapies, DBS systems were implanted in the GPi in an attempt to ameliorate the children's disabilities. All children found dystonic movements to be less disabling following surgery. Compared with preoperative Burke, Fahn and Marsden Dystonia Rating Scale scores, postoperative scores at 6 months were improved. Conclusions DBS is effective in improving symptoms and function in children with idiopathic dystonia refractory to medical treatment. Whilst surgery is complex and can be associated with intraoperative and postoperative complications, this intervention should be considered following the failure of medical therapy. PMID:17460025

  19. Clinical Efficacy in the Treatment of Overactive Bladder Refractory to Anticholinergics by Posterior Tibial Nerve Stimulation

    PubMed Central

    Palao-Yago, Francisco; Campon-Pacheco, Iluminada; Martinez-Sanchez, Maribel; Zuluaga-Gomez, Armando; Arrabal-Martin, Miguel

    2012-01-01

    Purpose Overactive bladder (OAB) is a clinical syndrome that is currently treated initially with anticholinergics, although some other therapeutic alternatives exist, such as neuromodulation, botulinum toxin, and posterior tibial nerve stimulation (PTNS). The purpose of this study was to assess the efficacy of PTNS in patients with OAB refractory to anticholinergics. Materials and Methods We present a cohort study of 14 women with OAB to whom we applied PTNS. We assessed (before and after the treatment) the diurnal micturitional frequency, the nocturnal micturitional frequency, urgency episodes, and urge incontinence episodes. Results were analyzed by using the Wilcoxon test for nonparametric samples. Results We observed statistically significant improvement in the diurnal micturitional frequency (p=0.05), in episodes of micturitional urgency (p=0.03), and in episodes of urge incontinence (p=0.004). A total of 50% of the patients felt subjective improvement from their pathology. Conclusions PTNS is a valid, minimally invasive treatment option with minimum morbidity for patients with OAB refractory to treatment with anticholinergics. PMID:22866220

  20. Two-year outcome of vagus nerve stimulation in treatment-resistant depression.

    PubMed

    Bajbouj, Malek; Merkl, Angela; Schlaepfer, Thomas E; Frick, Caroline; Zobel, Astrid; Maier, Wolfgang; O'Keane, Veronica; Corcoran, Ciaran; Adolfsson, Rolf; Trimble, Michael; Rau, Harald; Hoff, Hans-Joachim; Padberg, Frank; Müller-Siecheneder, Florian; Audenaert, Kurt; van den Abbeele, Dirk; Matthews, Keith; Christmas, David; Eljamel, Sam; Heuser, Isabella

    2010-06-01

    One of the major goals of antidepressant treatment is a sustained response and remission of depressive symptoms. Some of the previous studies of vagus nerve stimulation (VNS) have suggested antidepressant effects. Our naturalistic study assessed the efficacy and the safety of VNS in 74 European patients with therapy-resistant major depressive disorder. Psychometric measures were obtained after 3, 12, and 24 months of VNS. Mixed-model repeated-measures analysis of variance revealed a significant reduction (P < or = 0.05) at all the 3 time points in the 28-item Hamilton Rating Scale for Depression (HRSD28) score, the primary outcome measure. After 2 years, 53.1% (26/49) of the patients fulfilled the response criteria (> or =50% reduction in the HRSD28 scores from baseline) and 38.9% (19/49) fulfilled the remission criteria (HRSD28 scores < or = 10). The proportion of patients who fulfilled the remission criteria remained constant as the duration of VNS treatment increased. Voice alteration, cough, and pain were the most frequently reported adverse effects. Two patients committed suicide during the study; no other deaths were reported. No statistically significant differences were seen in the number of concomitant antidepressant medications. The results of this 2-year open-label trial suggest a clinical response and a comparatively benign adverse effect profile among patients with treatment-resistant depression.

  1. Critical appraisal of omega-3 fatty acids in attention-deficit/hyperactivity disorder treatment

    PubMed Central

    Königs, Anja; Kiliaan, Amanda J

    2016-01-01

    Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder. The classical treatment of ADHD where stimulant medication is used has revealed severe side effects and intolerance. Consequently, the demand to search for alternative treatment has increased rapidly. When comparing levels of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) in ADHD patients with those in age-matching controls, lower levels are found in ADHD patients’ blood. ω-3 PUFAs are essential nutrients and necessary for a proper brain function and development. Additionally, there are strong indications that ω-3 PUFA supplements could have beneficial effects on ADHD. However, the results of ω-3 PUFA supplementation studies show a high variability. Therefore, we reviewed recent studies published between 2000 and 2015 to identify effective treatment combinations, the quality of design, and safety and tolerability of ω-3-containing food supplements. We searched the databases MEDLINE, PubMed, and Web of Science with keywords such as “ADHD” and “ω-3/6 PUFA” and identified 25 studies that met the inclusion and exclusion criteria. The results of these ω-3 PUFA studies are contradictory but, overall, show evidence for a successful treatment of ADHD symptoms. Tolerability of the given supplements was high, and only mild side effects were reported. In conclusion, there is evidence that a ω-3 PUFA treatment has a positive effect on ADHD. It should be added that treatment could be more effective in patients with mild forms of ADHD. Moreover, the dosage of stimulant medication could be reduced when used in combination with ω-3 PUFA supplements. Further studies are necessary to investigate underlying mechanisms that can lead to a reduction of ADHD symptoms due to ω-3 PUFA treatments and also to determine the optimal concentrations of ω-3 PUFAs, whether used as single treatment or in combination with other medication. PMID:27555775

  2. Critical appraisal of omega-3 fatty acids in attention-deficit/hyperactivity disorder treatment.

    PubMed

    Königs, Anja; Kiliaan, Amanda J

    2016-01-01

    Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder. The classical treatment of ADHD where stimulant medication is used has revealed severe side effects and intolerance. Consequently, the demand to search for alternative treatment has increased rapidly. When comparing levels of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) in ADHD patients with those in age-matching controls, lower levels are found in ADHD patients' blood. ω-3 PUFAs are essential nutrients and necessary for a proper brain function and development. Additionally, there are strong indications that ω-3 PUFA supplements could have beneficial effects on ADHD. However, the results of ω-3 PUFA supplementation studies show a high variability. Therefore, we reviewed recent studies published between 2000 and 2015 to identify effective treatment combinations, the quality of design, and safety and tolerability of ω-3-containing food supplements. We searched the databases MEDLINE, PubMed, and Web of Science with keywords such as "ADHD" and "ω-3/6 PUFA" and identified 25 studies that met the inclusion and exclusion criteria. The results of these ω-3 PUFA studies are contradictory but, overall, show evidence for a successful treatment of ADHD symptoms. Tolerability of the given supplements was high, and only mild side effects were reported. In conclusion, there is evidence that a ω-3 PUFA treatment has a positive effect on ADHD. It should be added that treatment could be more effective in patients with mild forms of ADHD. Moreover, the dosage of stimulant medication could be reduced when used in combination with ω-3 PUFA supplements. Further studies are necessary to investigate underlying mechanisms that can lead to a reduction of ADHD symptoms due to ω-3 PUFA treatments and also to determine the optimal concentrations of ω-3 PUFAs, whether used as single treatment or in combination with other medication.

  3. Critical appraisal of omega-3 fatty acids in attention-deficit/hyperactivity disorder treatment.

    PubMed

    Königs, Anja; Kiliaan, Amanda J

    2016-01-01

    Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder. The classical treatment of ADHD where stimulant medication is used has revealed severe side effects and intolerance. Consequently, the demand to search for alternative treatment has increased rapidly. When comparing levels of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) in ADHD patients with those in age-matching controls, lower levels are found in ADHD patients' blood. ω-3 PUFAs are essential nutrients and necessary for a proper brain function and development. Additionally, there are strong indications that ω-3 PUFA supplements could have beneficial effects on ADHD. However, the results of ω-3 PUFA supplementation studies show a high variability. Therefore, we reviewed recent studies published between 2000 and 2015 to identify effective treatment combinations, the quality of design, and safety and tolerability of ω-3-containing food supplements. We searched the databases MEDLINE, PubMed, and Web of Science with keywords such as "ADHD" and "ω-3/6 PUFA" and identified 25 studies that met the inclusion and exclusion criteria. The results of these ω-3 PUFA studies are contradictory but, overall, show evidence for a successful treatment of ADHD symptoms. Tolerability of the given supplements was high, and only mild side effects were reported. In conclusion, there is evidence that a ω-3 PUFA treatment has a positive effect on ADHD. It should be added that treatment could be more effective in patients with mild forms of ADHD. Moreover, the dosage of stimulant medication could be reduced when used in combination with ω-3 PUFA supplements. Further studies are necessary to investigate underlying mechanisms that can lead to a reduction of ADHD symptoms due to ω-3 PUFA treatments and also to determine the optimal concentrations of ω-3 PUFAs, whether used as single treatment or in combination with other medication. PMID:27555775

  4. Hydrochloric acid-pumice treatment of fluorosis-stained enamel.

    PubMed

    Jagger, R G; al Rayes, S A

    1990-02-01

    The management of dark staining of teeth caused by dental fluorosis is discussed. The results of treatment of 20 patients with dental fluorosis by a hydrochloric acid-pumice technique are described. All patients showed considerable improvement in colour which was maintained for review periods of (up to) two years.

  5. DEVELOPMENT OF SRB TREATMENT SYSTEMS FOR ACID MINE DRAINAGE

    EPA Science Inventory

    Over the past decade, significant advances have been made in the development of sulfate- reducing bacteria (SRB) technology to treat acid mine drainage (AMD), Bench-scale testing, field demonstrations, and engineered applications of SRBs for the treatment of AMD will be presented...

  6. Penile vibratory stimulation and electroejaculation in the treatment of ejaculatory dysfunction.

    PubMed

    Sønksen, Jens; Ohl, Dana A

    2002-12-01

    The purpose of this review is to present the current understanding of penile vibratory stimulation (PVS) and electroejaculation (EEJ) procedures and its clinical use in men with ejaculatory dysfunction. Unfortunately, the record of treating such individuals has been quite poor, but within recent years development and refinement of PVS and EEJ in men with spinal cord injury (SCI) has significantly enhanced the prospects for treatment of ejaculatory dysfunction. The majority of spinal cord injured men are not able to produce antegrade ejaculation by masturbation or sexual stimulation. However, approximately 80% of all spinal cord injured men with an intact ejaculatory reflex arc (above T10) can obtain antegrade ejaculation with PVS. Electroejaculation may be successful in obtaining ejaculate from men with all types of SCI, including men who do not have major components of the ejaculatory reflex arc. Because vibratory stimulation is very simple in use, non-invasive, it does not require anaesthesia and is preferred by the patients when compared with EEJ, PVS is recommended to be the first choice of treatment in spinal cord injured men. Furthermore, EEJ has been successfully used to induce ejaculation in men with multiple sclerosis and diabetic neuropathy. Any other conditions which affect the ejaculatory mechanism of the central and/or peripheral nervous system including surgical nerve injury may be treated successfully with EEJ. Finally, for sperm retrieval and sperm cryopreservation before intensive anticancer therapy in pubertal boys, PVS and EEJ have been successfully performed in patients who failed to obtain ejaculation by masturbation. Nearly all data concerning semen characteristics in men with ejaculatory dysfuntion originate from spinal cord injured men. Semen analyses demonstrate low sperm motility rates in the majority of spinal cord injured men. The data give evidence of a decline in spermatogenesis and motility of ejaculated spermatozoa shortly after (few

  7. Comparison of clindamycin 1% and benzoyl peroxide 5% gel to a novel composition containing salicylic acid, capryloyl salicylic acid, HEPES, glycolic acid, citric acid, and dioic acid in the treatment of acne vulgaris.

    PubMed

    Baumann, Leslie S; Oresajo, Christian; Yatskayer, Margarita; Dahl, Amanda; Figueras, Kristian

    2013-03-01

    This study evaluated the tolerance and efficacy of 2 facial skin products in subjects with acne using the following acne treatments: 1) treatment A, a combination of salicylic acid, capryloyl salicylic acid, HEPES, glycolic acid, citric acid, and dioic acid, and 2) treatment B (BenzaClin®, clindamycin 1% and benzoyl peroxide 5% gel). The treatment design included the split-face application of treatment A and treatment B and the full-face application of the cleanser, moisturizer, and sunscreen. Data were collected through physician visual assessments, subject irritation questionnaires and assessments, along with clinical photography. Results showed similar tolerance and efficacy for both treatments.

  8. Caffeic acid phenethyl ester stimulates human antioxidant response element-mediated expression of the NAD(P)H:quinone oxidoreductase (NQO1) gene.

    PubMed

    Jaiswal, A K; Venugopal, R; Mucha, J; Carothers, A M; Grunberger, D

    1997-02-01

    Caffeic acid phenethyl ester (CAPE) is a phenolic antioxidant derived from the propolis of honeybee hives. CAPE was shown to inhibit the formation of intracellular hydrogen peroxide and oxidized bases in DNA of 12-O-tetradecanoylphorbol-13-acetate (TPA)-treated HeLa cells and was also found to induce a redox change that correlated with differential growth effects in transformed cells but not the nontumorigenic parental ones. Mediated via the electrophile or human antioxidant response element (hARE), induction of the expression of NAD(P)H quinone oxidoreductase (NQO1) and glutathione S-transferase Ya subunit genes by certain phenolic antioxidants has been correlated with the chemopreventive properties of these agents. Here, we determined by Northern analysis that CAPE treatment of hepatoma cells stimulates NQO1 gene expression in cultured human hepatoma cells (HepG2), and we characterized the effects of CAPE treatment on the expression of a reporter gene either containing or lacking the hARE or carrying a mutant version of this element in rodent hepatoma (Hepa-1) transfectants. A dose-dependent transactivation of human hARE-mediated chloramphenicol acetyltransferase (cat) gene expression was observed upon treatments of the Hepa-1 transfectants with TPA, a known inducer, as well as with CAPE. The combined treatments resulted in an apparent additive stimulation of the reporter expression. To learn whether this activation of cat gene expression was effected by protein kinase C in CAPE-treated cells, a comparison was made of cat gene activity after addition of calphostin, a protein kinase C inhibitor. Calphostin reduced the cat gene induction by TPA but not by CAPE, suggesting that stimulation of gene expression in this system by these agents proceeds via distinct mechanisms. Band-shift experiments to examine binding of transactivator proteins from nuclear extracts of treated and untreated cells to a hARE DNA probe showed that TPA exposure increased the binding level

  9. A Novel Lactobacillus casei LP1 Producing 1,4-Dihydroxy-2-Naphthoic Acid, a Bifidogenic Growth Stimulator.

    PubMed

    Kang, Jo-Eun; Kim, Tae-Jung; Moon, Gi-Seong

    2015-03-01

    1,4-Dihydroxy-2-naphthoic acid (DHNA) is a bifidogenic growth stimulator (BGS) and could be a functional food ingredient since bifidobacteria are beneficial for human health. For that reason, lactic acid bacteria producing DHNA have been screened. A lactic acid bacterium LP1 strain isolated from a natural cheese was confirmed to produce DHNA, analyzed by a HPLC method. The strain was identified as Lactobacillus casei by 16S rRNA gene sequence analysis. The cell-free supernatant of fermented whey produced by L. casei LP1 presented the BGS activity for three bifidobacterial strains such as Bifidobacterium longum subsp. infantis KCTC 3127, Bifidobacterium bifidum KCTC 3202, and Bifidobacterium breve KCTC 3220 which were human-originated. To the best of our knowledge, a L. casei strain which can produce DHNA was firstly identified in this study. PMID:25866754

  10. Influence of stimulant and non-stimulant drug treatment on driving performance in patients with attention deficit hyperactivity disorder: a systematic review.

    PubMed

    Gobbo, Maria Angela; Louzã, Mario R

    2014-09-01

    Adults with Attention Deficit Hyperactivity Disorder (ADHD), especially teenagers and young adults, show important car driving impairments, including risky driving, accidents, fines and suspension of driver׳s license. We systematically reviewed the efficacy of stimulant and non-stimulant drugs on driving performance of ADHD patients. We searched several databases for randomized controlled trials (RCTs) published through March, 2013. Fifteen RCTs (the majority with crossover design) evaluated methylphenidate (MPH) immediate-release (MPH-IR), MPH osmotic-controlled oral system (MPH-OROS), MPH transdermal system (MTS), extended-release mixed amphetamine salts (MAS-XR); atomoxetine (ATX) and lisdexamfetamine (LDX). Methods varied widely; including simulators and/or cars and different courses and scenarios. Various outcomes of driving performance, including a 'composite' or 'overall' driving score were considered. In general, stimulants improved driving performance in ADHD patients (either in RCTs conducted in simulators and/or cars). MPH-OROS improved driving performance compared with MAS-XR, placebo, or no-drug conditions. Although MPH-OROS and MPH-IR produced similar improvements during the day, MPH-IR lost its efficacy in the evening. MAS-XR also improved driving performance, but worsened driving performance in the evening. MTS (one study) showed a positive effect, but drug compliance varied widely across patients. LDX had positive effect on driving (two studies with the same sample). Studies with ATX report conflicting results. Improvement was more consistent in teenagers and young adults. In general, treatment with psychostimulants or ATX in therapeutic dosages had no negative impact on driving performance of ADHD patients. To conclude, treatment with stimulants in therapeutic doses improves driving performance in ADHD patients, especially teenagers and young adults.

  11. Hepatic fatty acid biosynthesis is more responsive to protein than carbohydrate in rainbow trout during acute stimulations.

    PubMed

    Dai, Weiwei; Panserat, Stéphane; Kaushik, Sadasivam; Terrier, Frédéric; Plagnes-Juan, Elisabeth; Seiliez, Iban; Skiba-Cassy, Sandrine

    2016-01-01

    The link between dietary carbohydrate/protein and de novo lipogenesis (DNL) remains debatable in carnivorous fish. We aimed to evaluate and compare the response of hepatic lipogenic gene expression to dietary carbohydrate intake/glucose and dietary protein intake/amino acids (AAs) during acute stimulations using both in vivo and in vitro approaches. For the in vivo trial, three different diets and a controlled-feeding method were employed to supply fixed amount of dietary protein or carbohydrate in a single meal; for the in vitro trial, primary hepatocytes were stimulated with a low or high level of glucose (3 mM or 20 mM) and a low or high level of AAs (one-fold or four-fold concentrated AAs). In vitro data showed that a high level of AAs upregulated the expression of enzymes involved in DNL [fatty acid synthase (FAS) and ATP citrate lyase (ACLY)], lipid bioconversion [elongation of very long chain fatty acids like-5 (Elovl5), Elovl2, Δ6 fatty acyl desaturase (D6D) and stearoyl-CoA desaturase-1 (SCD1)], NADPH production [glucose-6-phosphate dehydrogenase (G6PDH) and malic enzyme (ME)], and transcriptional factor sterol regulatory element binding protein 1-like, while a high level of glucose only elevated the expression of ME. Data in trout liver also showed that high dietary protein intake induced higher lipogenic gene expression (FAS, ACLY, and Elovl2) regardless of dietary carbohydrate intake, while high carbohydrate intake markedly suppressed the expression of acetyl-CoA carboxylase (ACC) and Elovl5. Overall, we conclude that, unlike rodents or humans, hepatic fatty acid biosynthetic gene expression in rainbow trout is more responsive to dietary protein intake/AAs than dietary carbohydrate intake/glucose during acute stimulations. This discrepancy probably represents one important physiological and metabolic difference between carnivores and omnivores. PMID:26491101

  12. Hepatic fatty acid biosynthesis is more responsive to protein than carbohydrate in rainbow trout during acute stimulations.

    PubMed

    Dai, Weiwei; Panserat, Stéphane; Kaushik, Sadasivam; Terrier, Frédéric; Plagnes-Juan, Elisabeth; Seiliez, Iban; Skiba-Cassy, Sandrine

    2016-01-01

    The link between dietary carbohydrate/protein and de novo lipogenesis (DNL) remains debatable in carnivorous fish. We aimed to evaluate and compare the response of hepatic lipogenic gene expression to dietary carbohydrate intake/glucose and dietary protein intake/amino acids (AAs) during acute stimulations using both in vivo and in vitro approaches. For the in vivo trial, three different diets and a controlled-feeding method were employed to supply fixed amount of dietary protein or carbohydrate in a single meal; for the in vitro trial, primary hepatocytes were stimulated with a low or high level of glucose (3 mM or 20 mM) and a low or high level of AAs (one-fold or four-fold concentrated AAs). In vitro data showed that a high level of AAs upregulated the expression of enzymes involved in DNL [fatty acid synthase (FAS) and ATP citrate lyase (ACLY)], lipid bioconversion [elongation of very long chain fatty acids like-5 (Elovl5), Elovl2, Δ6 fatty acyl desaturase (D6D) and stearoyl-CoA desaturase-1 (SCD1)], NADPH production [glucose-6-phosphate dehydrogenase (G6PDH) and malic enzyme (ME)], and transcriptional factor sterol regulatory element binding protein 1-like, while a high level of glucose only elevated the expression of ME. Data in trout liver also showed that high dietary protein intake induced higher lipogenic gene expression (FAS, ACLY, and Elovl2) regardless of dietary carbohydrate intake, while high carbohydrate intake markedly suppressed the expression of acetyl-CoA carboxylase (ACC) and Elovl5. Overall, we conclude that, unlike rodents or humans, hepatic fatty acid biosynthetic gene expression in rainbow trout is more responsive to dietary protein intake/AAs than dietary carbohydrate intake/glucose during acute stimulations. This discrepancy probably represents one important physiological and metabolic difference between carnivores and omnivores.

  13. Bilateral Transcranial Direct Current Stimulation Language Treatment Enhances Functional Connectivity in the Left Hemisphere: Preliminary Data from Aphasia.

    PubMed

    Marangolo, Paola; Fiori, Valentina; Sabatini, Umberto; De Pasquale, Giada; Razzano, Carmela; Caltagirone, Carlo; Gili, Tommaso

    2016-05-01

    Several studies have already shown that transcranial direct current stimulation (tDCS) is a useful tool for enhancing recovery in aphasia. However, no reports to date have investigated functional connectivity changes on cortical activity because of tDCS language treatment. Here, nine aphasic persons with articulatory disorders underwent an intensive language therapy in two different conditions: bilateral anodic stimulation over the left Broca's area and cathodic contralesional stimulation over the right homologue of Broca's area and a sham condition. The language treatment lasted 3 weeks (Monday to Friday, 15 sessions). In all patients, language measures were collected before (T0) and at the end of treatment (T15). Before and after each treatment condition (real vs. sham), each participant underwent a resting-state fMRI study. Results showed that, after real stimulation, patients exhibited the greatest recovery not only in terms of better accuracy in articulating the treated stimuli but also for untreated items on different tasks of the language test. Moreover, although after the sham condition connectivity changes were confined to the right brain hemisphere, real stimulation yielded to stronger functional connectivity increase in the left hemisphere. In conclusion, our data provide converging evidence from behavioral and functional imaging data that bilateral tDCS determines functional connectivity changes within the lesioned hemisphere, enhancing the language recovery process in stroke patients. PMID:26807842

  14. Bilateral Transcranial Direct Current Stimulation Language Treatment Enhances Functional Connectivity in the Left Hemisphere: Preliminary Data from Aphasia.

    PubMed

    Marangolo, Paola; Fiori, Valentina; Sabatini, Umberto; De Pasquale, Giada; Razzano, Carmela; Caltagirone, Carlo; Gili, Tommaso

    2016-05-01

    Several studies have already shown that transcranial direct current stimulation (tDCS) is a useful tool for enhancing recovery in aphasia. However, no reports to date have investigated functional connectivity changes on cortical activity because of tDCS language treatment. Here, nine aphasic persons with articulatory disorders underwent an intensive language therapy in two different conditions: bilateral anodic stimulation over the left Broca's area and cathodic contralesional stimulation over the right homologue of Broca's area and a sham condition. The language treatment lasted 3 weeks (Monday to Friday, 15 sessions). In all patients, language measures were collected before (T0) and at the end of treatment (T15). Before and after each treatment condition (real vs. sham), each participant underwent a resting-state fMRI study. Results showed that, after real stimulation, patients exhibited the greatest recovery not only in terms of better accuracy in articulating the treated stimuli but also for untreated items on different tasks of the language test. Moreover, although after the sham condition connectivity changes were confined to the right brain hemisphere, real stimulation yielded to stronger functional connectivity increase in the left hemisphere. In conclusion, our data provide converging evidence from behavioral and functional imaging data that bilateral tDCS determines functional connectivity changes within the lesioned hemisphere, enhancing the language recovery process in stroke patients.

  15. Repetitive Transcranial Magnetic Stimulation for Treatment-Resistant Depression: An Economic Analysis

    PubMed Central

    Tu, Hong Anh; Palimaka, Stefan; Sehatzadeh, Shayan; Blackhouse, Gord; Yap, Belinda; Tsoi, Bernice; Bowen, Jim; O'Reilly, Daria

    2016-01-01

    Background Major depressive disorder (MDD, 10% over a person's lifetime) is common and costly to the health system. Unfortunately, many MDD cases are resistant to treatment with antidepressant drugs and require other treatment to reduce or eliminate depression. Electroconvulsive therapy (ECT) has long been used to treat persons with treatment-resistant depression (TRD). Despite its effectiveness, ECT has side effects that make patients intolerant to the treatment, or they refuse to use it. Repetitive transcranial magnetic stimulation (rTMS), which has fewer side effects than ECT and might be an alternative for TRD patients who are ineligible for or unwilling to undergo ECT, has been developed to treat TRD. Objectives This analysis evaluates the cost-effectiveness of rTMS for patients with TRD compared with ECT or sham rTMS and estimates the potential budgetary impact of various levels of implementation of rTMS in Ontario. Review Methods A cost-utility analysis compared the costs and health outcomes of two treatments for persons with TRD in Ontario: rTMS alone compared with ECT alone and rTMS alone compared with sham rTMS. We calculated the six-month incremental costs and quality-adjusted life-years (QALYs) for these treatments. One-way and probabilistic sensitivity analyses were performed to test the robustness of the model's results. A 1-year budget impact analysis estimated the costs of providing funding for rTMS. The base-case analysis examined the additional costs for funding six centres, where rTMS infrastructure is in place. Sensitivity and scenario analyses explored the impact of increasing diffusion of rTMS to centres with existing ECT infrastructure. All analyses were conducted from the Ontario health care payer perspective. Results ECT was cost effective compared to rTMS when the willingness to pay is greater than $37,640.66 per QALY. In the base-case analysis, which had a six-month time horizon, the cost and effectiveness for rTMS was $5,272 and 0

  16. The Gibberellic Acid Stimulated-Like gene family in maize and its role in lateral root development.

    PubMed

    Zimmermann, Roman; Sakai, Hajime; Hochholdinger, Frank

    2010-01-01

    In an approach to study lateral root development in monocots, genome-wide searches for homologs of the Gibberellic Acid Stimulated Transcript-like (GAST-like) gene family in rice (Oryza sativa) and maize (Zea mays) were carried out. Six novel GAST-like genes in rice and 10 members of the gene family in maize, which were designated ZmGSL (for Z. mays Gibberellic Acid Stimulated-Like), were identified. The ZmGSL family encodes small proteins of 75 to 128 amino acids, which are characterized by a conserved 59 to 64 amino acid C-terminal domain. Within this domain, 17 amino acids, including 12 cysteines, are perfectly conserved. The transcript of the ZmGSL1 gene is differentially spliced into the alternative variants ZmGSL1a and ZmGSL1b, the latter of which is translated into a premature protein that lacks the C-terminal domain. The presence of an additional N-terminal cleavable signal sequence in eight of the 10 ZmGSL proteins suggests that they are secreted into the extracellular matrix. In-depth root-specific gene expression analyses carried out in the wild type and the lateral root mutants lrt1 and rum1 suggest a role for ZmGSL genes in early lateral root development, which is likely regulated by gibberellic acid. Expression patterns of ZmGSL1a and ZmGSL1b propose antagonistic functions of these splice variants during early lateral root formation.

  17. Parameters affecting the formation of perfluoroalkyl acids during wastewater treatment.

    PubMed

    Guerra, P; Kim, M; Kinsman, L; Ng, T; Alaee, M; Smyth, S A

    2014-05-15

    This study examined the fate and behaviour of perfluoroalkyl acids (PFAAs) in liquid and solid samples from five different wastewater treatment types: facultative and aerated lagoons, chemically assisted primary treatment, secondary aerobic biological treatment, and advanced biological nutrient removal treatment. To the best of our knowledge, this is the largest data set from a single study available in the literature to date for PFAAs monitoring study in wastewater treatment. Perfluorooctanoic acid (PFOA) was the predominant PFAA in wastewater with levels from 2.2 to 150ng/L (influent) and 1.9 to 140ng/L (effluent). Perfluorooctanesulfonic acid (PFOS) was the predominant compound in primary sludge, waste biological sludge, and treated biosolids with concentrations from 6.4 to 2900ng/g dry weight (dw), 9.7 to 8200ng/gdw, and 2.1 to 17,000ng/gdw, respectively. PFAAs were formed during wastewater treatment and it was dependant on both process temperature and treatment type; with higher rates of formation in biological wastewater treatment plants (WWTPs) operating at longer hydraulic retention times and higher temperatures. PFAA removal by sorption was influenced by different sorption tendencies; median log values of the solid-liquid distribution coefficient estimated from wastewater biological sludge and final effluent were: PFOS (3.73)>PFDA (3.68)>PFNA (3.25)>PFOA (2.49)>PFHxA (1.93). Mass balances confirmed the formation of PFAAs, low PFAA removal by sorption, and high PFAA levels in effluents. PMID:24691135

  18. Spinal cord stimulation for treatment of failed back surgery syndrome--two case reports.

    PubMed

    Vijayan, R; Ahmad, T S

    1999-12-01

    Severe, persistent back pain following back surgery is often referred to as Failed Back Surgery Syndrome (FBSS). Conservative measures such as physiotherapy, back strengthening exercises, transcutaneous electrical nerve stimulation and epidural steroids may be inadequate to alleviate pain. Spinal Cord Stimulators were implanted into two patients suffering from FBSS. Both patients responded successfully to spinal cord stimulation with reduction of pain and disability.

  19. Rapid acid treatment of Escherichia coli: transcriptomic response and recovery

    PubMed Central

    Kannan, Geetha; Wilks, Jessica C; Fitzgerald, Devon M; Jones, Brian D; BonDurant, Sandra S; Slonczewski, Joan L

    2008-01-01

    Background Many E. coli genes show pH-dependent expression during logarithmic growth in acid (pH 5–6) or in base (pH 8–9). The effect of rapid pH change, however, has rarely been tested. Rapid acid treatment could distinguish between genes responding to external pH, and genes responding to cytoplasmic acidification, which occurs transiently following rapid external acidification. It could reveal previously unknown acid-stress genes whose effects are transient, as well as show which acid-stress genes have a delayed response. Results Microarray hybridization was employed to observe the global gene expression of E. coli K-12 W3110 following rapid acidification of the external medium, from pH 7.6 to pH 5.5. Fluorimetric observation of pH-dependent tetR-YFP showed that rapid external acidification led to a half-unit drop in cytoplasmic pH (from pH 7.6 to pH 6.4) which began to recover within 20 s. Following acid treatment, 630 genes were up-regulated and 586 genes were down-regulated. Up-regulated genes included amino-acid decarboxylases (cadA, adiY, gadA), succinate dehydrogenase (sdhABCD), biofilm-associated genes (bdm, gatAB, and ymgABC), and the Gad, Fur and Rcs regulons. Genes with response patterns consistent with cytoplasmic acid stress were revealed by addition of benzoate, a membrane-permeant acid that permanently depresses cytoplasmic pH without affecting external pH. Several genes (yagU, ygiN, yjeI, and yneI) were up-regulated specifically by external acidification, while other genes (fimB, ygaC, yhcN, yhjX, ymgABC, yodA) presented a benzoate response consistent with cytoplasmic pH stress. Other genes (the nuo operon for NADH dehydrogenase I, and the HslUV protease) showed delayed up-regulation by acid, with expression rising by 10 min following the acid shift. Conclusion Transcriptomic profiling of E. coli K-12 distinguished three different classes of change in gene expression following rapid acid treatment: up-regulation with or without recovery, and

  20. Brain stimulation for the treatment of pain: A review of costs, clinical effects, and mechanisms of treatment for three different central neuromodulatory approaches

    PubMed Central

    Zaghi, Soroush; Heine, Nikolas; Fregni, Felipe

    2010-01-01

    Methods of cortical stimulation including epidural motor cortex stimulation (MCS), repetitive transcranial magnetic stimulation (rTMS), and transcranial direct current stimulation (tDCS) are emerging as alternatives in the management of pain in patients with chronic medically-refractory pain disorders. Here we consider the three methods of brain stimulation that have been investigated for the treatment of central pain: MCS, rTMS, and tDCS. While all three treatment modalities appear to induce significant clinical gains in patients with chronic pain, tDCS is revealed as the most cost-effective approach (compared to rTMS and MCS) when considering a single year of treatment. However, if a 5-year treatment is considered, MCS is revealed as the most cost-effective modality (as compared to rTMS and tDCS) for the neuromodulatory treatment of chronic pain. We discuss the theory behind the application of each modality as well as efficacy, cost, safety, and practical considerations. PMID:20585474

  1. p38 mitogen-activated protein kinase interacts with vinculin at focal adhesions during fatty acid-stimulated cell adhesion

    PubMed Central

    George, Margaret D.; Wine, Robert N.; Lackford, Brad; Kissling, Grace E.; Akiyama, Steven K.; Olden, Kenneth; Roberts, John D.

    2014-01-01

    Arachidonic acid stimulates cell adhesion by activating α2β1 integrins in a process that depends on protein kinases, including p38 mitogen activated protein kinase. Here, we describe the interaction of cytoskeletal components with key signaling molecules that contribute to spreading of, and morphological changes in, arachidonic acid-treated MDA-MB-435 human breast carcinoma cells. Arachidonic acid-treated cells showed increased attachment and spreading on collagen type IV as measured by electric cell-substrate impedance sensing. Fatty acid-treated cells displayed short cortical actin filaments associated with an increased number of β1 integrin-containing pseudopodia whereas untreated cells displayed elongated stress fibers and fewer clusters of β1 integrins. Confocal microscopy of arachidonic acid-treated cells showed that vinculin and phospho-p38 both appeared enriched in pseudopodia and at the tips of actin filaments, and fluorescence ratio imaging indicated the increase was specific for the phospho-(active) form of p38. Immunoprecipitates of phospho-p38 from extracts of arachidonic acid-treated cells contained vinculin, and GST-vinculin fusion proteins carrying the central region of vinculin bound phospho-p38, whereas fusion proteins expressing the terminal portions of vinculin did not. These data suggest that phospho-p38 associates with particular domains on critical focal adhesion proteins that are involved in tumor cell adhesion and spreading and that this association can be regulated by factors in the tumor microenvironment. PMID:24219282

  2. Self-stimulation and task-related responding: the role of sensory reinforcement in maintaining and extending treatment effects.

    PubMed

    Lancioni, G E; Smeets, P M; Ceccarani, P S; Goossens, A J

    1983-03-01

    The present study was aimed at (a) eliminating self-stimulation and increasing task-related responding in severely handicapped children, and (b) assessing maintenance and carry-over of treatment effects following the use of sensory reinforcement. The results showed that applying sensory or edible-liquid reinforcement, contingent on low rates of task-related responses, did not increase these responses nor decrease self-stimulation. These behavior changes were obtained with the combination of reinforcement and punishment. Sensory reinforcement was effective in maintaining and extending the treatment results, while edible-liquid contingencies were not. PMID:6863550

  3. Self-stimulation and task-related responding: the role of sensory reinforcement in maintaining and extending treatment effects.

    PubMed

    Lancioni, G E; Smeets, P M; Ceccarani, P S; Goossens, A J

    1983-03-01

    The present study was aimed at (a) eliminating self-stimulation and increasing task-related responding in severely handicapped children, and (b) assessing maintenance and carry-over of treatment effects following the use of sensory reinforcement. The results showed that applying sensory or edible-liquid reinforcement, contingent on low rates of task-related responses, did not increase these responses nor decrease self-stimulation. These behavior changes were obtained with the combination of reinforcement and punishment. Sensory reinforcement was effective in maintaining and extending the treatment results, while edible-liquid contingencies were not.

  4. Treatment of iatrogenic Cushing's syndrome in dogs with electroacupuncture stimulation of stomach 36.

    PubMed

    Lin, J H; Su, H L; Chang, S H; Shien, Y S; Wu, L S

    1991-01-01

    This study was conducted to evaluate the effectiveness of electroacupuncture (EA) on the recovery of adrenocortical function from Iatrogenic Cushings Syndrome (ICS) in dogs. Experiment I: Selection of the most effective Acupuncture point to treat ICS--Six healthy adult female dogs were treated bilaterally with EA for 15 minutes at loci BL22 + BL23 + BL24, ST36, or a non-locus control point on M. brachialis. Each dog was tested at all three sites in rotation. Blood samples were collected before and 0, 15 and 60 minutes after EA, and the serum cortisol levels were measured by radioimmunoassay. The data showed that EA at ST36 resulted in the highest response of serum cortisol levels among the three treatments. Experiment II: Evaluation of the effectiveness of EA ST36 in the treatment of ICS in dogs--Eight healthy adult female dogs were given prednisolone acetate 2mg/kg/day IM for 3 weeks. They were then randomly divided into ST36 and control groups of 4 dogs each. In the ST36 group, ST36 was treated bilaterally with EA for 30 minutes, 3 times per week, for 3 consecutive weeks. For the control, a non-locus point on M. brachialis was treated bilaterally with the same protocol. After the first week of EA, the serum cortisol levels of the ST36 and control groups were 0.9 +/- 0.1 and 0.5 +/- 0.1 micrograms/dl (P less than 0.005) baseline and 2.5 +/- 0.2 and 1.4 +/- 0.4 micrograms/dl (p less than 0.05) and after ACTH stimulation test, respectively. After the third week of EA treatment, the results were 1.0 +/- 0.1 and 0.6 +/- 0.2 micrograms/dl (p less than 0.05) baseline and 4.0 +/- 0.5 and 1.7 +/- 0.5 micrograms/dl (p less than 0.001) after ACTH stimulation respectively. These data indicated that EA at ST36 could restore the adrenocortical hypofunction resulting from ICS in dogs.

  5. Betulinic acid, a bioactive pentacyclic triterpenoid, inhibits skeletal-related events induced by breast cancer bone metastases and treatment

    SciTech Connect

    Park, Se Young; Kim, Hyun-Jeong; Kim, Ki Rim; Lee, Sun Kyoung; Lee, Chang Ki; Park, Kwang-Kyun Chung, Won-Yoon

    2014-03-01

    Many breast cancer patients experience bone metastases and suffer skeletal complications. The present study provides evidence on the protective and therapeutic potential of betulinic acid on cancer-associated bone diseases. Betulinic acid is a naturally occurring triterpenoid with the beneficial activity to limit the progression and severity of cancer, diabetes, cardiovascular diseases, atherosclerosis, and obesity. We first investigated its effect on breast cancer cells, osteoblastic cells, and osteoclasts in the vicious cycle of osteolytic bone metastasis. Betulinic acid reduced cell viability and the production of parathyroid hormone-related protein (PTHrP), a major osteolytic factor, in MDA-MB-231 human metastatic breast cancer cells stimulated with or without tumor growth factor-β. Betulinic acid blocked an increase in the receptor activator of nuclear factor-kappa B ligand (RANKL)/osteoprotegerin ratio by downregulating RANKL protein expression in PTHrP-treated human osteoblastic cells. In addition, betulinic acid inhibited RANKL-induced osteoclastogenesis in murine bone marrow macrophages and decreased the production of resorbed area in plates with a bone biomimetic synthetic surface by suppressing the secretion of matrix metalloproteinase (MMP)-2, MMP-9, and cathepsin K in RANKL-induced osteoclasts. Furthermore, oral administration of betulinic acid inhibited bone loss in mice intra-tibially inoculated with breast cancer cells and in ovariectomized mice causing estrogen deprivation, as supported by the restored bone morphometric parameters and serum bone turnover markers. Taken together, these findings suggest that betulinic acid may have the potential to prevent bone loss in patients with bone metastases and cancer treatment-induced estrogen deficiency. - Highlights: • Betulinic acid reduced PTHrP production in human metastatic breast cancer cells. • Betulinic acid blocked RANKL/OPG ratio in PTHrP-stimulated human osteoblastic cells. • Betulinic

  6. Principles of using Cold Atmospheric Plasma Stimulated Media for Cancer Treatment

    NASA Astrophysics Data System (ADS)

    Yan, Dayun; Talbot, Annie; Nourmohammadi, Niki; Cheng, Xiaoqian; Canady, Jerome; Sherman, Jonathan; Keidar, Michael

    2015-12-01

    To date, the significant anti-cancer capacity of cold atmospheric plasma (CAP) on dozens of cancer cell lines has been demonstrated in vitro and in mice models. Conventionally, CAP was directly applied to irradiate cancer cells or tumor tissue. Over past three years, the CAP irradiated media was also found to kill cancer cells as effectively as the direct CAP treatment. As a novel strategy, using the CAP stimulated (CAPs) media has become a promising anti-cancer tool. In this study, we demonstrated several principles to optimize the anti-cancer capacity of the CAPs media on glioblastoma cells and breast cancer cells. Specifically, using larger wells on a multi-well plate, smaller gaps between the plasma source and the media, and smaller media volume enabled us to obtain a stronger anti-cancer CAPs media composition without increasing the treatment time. Furthermore, cysteine was the main target of effective reactive species in the CAPs media. Glioblastoma cells were more resistant to the CAPs media than breast cancer cells. Glioblastoma cells consumed the effective reactive species faster than breast cancer cells did. In contrast to nitric oxide, hydrogen peroxide was more likely to be the effective reactive species.

  7. Principles of using Cold Atmospheric Plasma Stimulated Media for Cancer Treatment.

    PubMed

    Yan, Dayun; Talbot, Annie; Nourmohammadi, Niki; Cheng, Xiaoqian; Canady, Jerome; Sherman, Jonathan; Keidar, Michael

    2015-01-01

    To date, the significant anti-cancer capacity of cold atmospheric plasma (CAP) on dozens of cancer cell lines has been demonstrated in vitro and in mice models. Conventionally, CAP was directly applied to irradiate cancer cells or tumor tissue. Over past three years, the CAP irradiated media was also found to kill cancer cells as effectively as the direct CAP treatment. As a novel strategy, using the CAP stimulated (CAPs) media has become a promising anti-cancer tool. In this study, we demonstrated several principles to optimize the anti-cancer capacity of the CAPs media on glioblastoma cells and breast cancer cells. Specifically, using larger wells on a multi-well plate, smaller gaps between the plasma source and the media, and smaller media volume enabled us to obtain a stronger anti-cancer CAPs media composition without increasing the treatment time. Furthermore, cysteine was the main target of effective reactive species in the CAPs media. Glioblastoma cells were more resistant to the CAPs media than breast cancer cells. Glioblastoma cells consumed the effective reactive species faster than breast cancer cells did. In contrast to nitric oxide, hydrogen peroxide was more likely to be the effective reactive species.

  8. Principles of using Cold Atmospheric Plasma Stimulated Media for Cancer Treatment.

    PubMed

    Yan, Dayun; Talbot, Annie; Nourmohammadi, Niki; Cheng, Xiaoqian; Canady, Jerome; Sherman, Jonathan; Keidar, Michael

    2015-01-01

    To date, the significant anti-cancer capacity of cold atmospheric plasma (CAP) on dozens of cancer cell lines has been demonstrated in vitro and in mice models. Conventionally, CAP was directly applied to irradiate cancer cells or tumor tissue. Over past three years, the CAP irradiated media was also found to kill cancer cells as effectively as the direct CAP treatment. As a novel strategy, using the CAP stimulated (CAPs) media has become a promising anti-cancer tool. In this study, we demonstrated several principles to optimize the anti-cancer capacity of the CAPs media on glioblastoma cells and breast cancer cells. Specifically, using larger wells on a multi-well plate, smaller gaps between the plasma source and the media, and smaller media volume enabled us to obtain a stronger anti-cancer CAPs media composition without increasing the treatment time. Furthermore, cysteine was the main target of effective reactive species in the CAPs media. Glioblastoma cells were more resistant to the CAPs media than breast cancer cells. Glioblastoma cells consumed the effective reactive species faster than breast cancer cells did. In contrast to nitric oxide, hydrogen peroxide was more likely to be the effective reactive species. PMID:26677750

  9. Differential stimulation of diphenhydramine, pethidine, morphine and aniline metabolism by chronic methaqualone treatment.

    PubMed

    Ali, B; Gupta, K P; Kumar, A; Bhargava, K P

    1980-01-01

    In the present study, the effect of chronic oral methaqualone treatment (60 mg/kg/24 h for 25 days) was examined on the metabolism of diphenhydramine, pethidine, morphine and aniline in rat liver microsomes. Such chronic methaqualone treatment caused an enhancement of microsomal drug metabolizing enzymes catalyzed N-demethylations of diphenhydramine, pethidine, morphine and aromatic hydroxylation of aniline. A single oral dose of methaqualone (60 mg/kg) did not result in any significant change in the activities of drug metabolizing enzymes. Methaqualone inhibited drug metabolizing enzymes when used at final concentrations of 1 and 3 mmol/l in vitro. These observations led to suggest that the stimulation of drug metabolism noted in this study is possibly due to the induction of microsomal drug metabolizing enzymes. It was interesting to note that the induction of N-demethylases by repeated methaqualone intake was differential in nature since diphenhydramine and morphine N-demethylases were induced about twofold whereas pethidine N-demethylase was enhanced about fourfold. These results should be of extreme importance in understanding the biochemical mechanism of the specific and differential drug tolerance by continued methaqualone abuse and its possible interaction with other drugs.

  10. Principles of using Cold Atmospheric Plasma Stimulated Media for Cancer Treatment

    PubMed Central

    Yan, Dayun; Talbot, Annie; Nourmohammadi, Niki; Cheng, Xiaoqian; Canady, Jerome; Sherman, Jonathan; Keidar, Michael

    2015-01-01

    To date, the significant anti-cancer capacity of cold atmospheric plasma (CAP) on dozens of cancer cell lines has been demonstrated in vitro and in mice models. Conventionally, CAP was directly applied to irradiate cancer cells or tumor tissue. Over past three years, the CAP irradiated media was also found to kill cancer cells as effectively as the direct CAP treatment. As a novel strategy, using the CAP stimulated (CAPs) media has become a promising anti-cancer tool. In this study, we demonstrated several principles to optimize the anti-cancer capacity of the CAPs media on glioblastoma cells and breast cancer cells. Specifically, using larger wells on a multi-well plate, smaller gaps between the plasma source and the media, and smaller media volume enabled us to obtain a stronger anti-cancer CAPs media composition without increasing the treatment time. Furthermore, cysteine was the main target of effective reactive species in the CAPs media. Glioblastoma cells were more resistant to the CAPs media than breast cancer cells. Glioblastoma cells consumed the effective reactive species faster than breast cancer cells did. In contrast to nitric oxide, hydrogen peroxide was more likely to be the effective reactive species. PMID:26677750

  11. Phasic Treatment with Interferon Gamma Stimulates Release of Exosomes that Protect Against Spreading Depression.

    PubMed

    Pusic, Aya D; Kraig, Richard P

    2015-10-01

    The detrimental effects of T-cell-secreted interferon gamma (IFNγ) on oxidative stress (OS) and demyelination in multiple sclerosis (MS) are well recognized. Recently, we demonstrated that IFNγ-mediated damage to myelin also increases susceptibility to spreading depression (SD; the likely basis of migraine with aura). However, before onset of MS, induction of physiological levels of IFNγ, like that produced by environmental enrichment (EE), protects against demyelination and OS. Accordingly, we focused on the potential for physiological levels of IFNγ to protect against SD. EE, which occurs with a moderate and phasic increase in proinflammatory cytokines, reduces migraine frequency. Thus, we applied phasic or pulsed IFNγ to brain slice cultures to emulate EE. This treatment reduced OS, increased myelin basic protein, a marker for myelin, and reduced susceptibility to SD. Building on our research on exosomes in EE-based neuroprotection, we found that IFNγ stimulation of slice cultures induced release of exosomes, likely from the microglia that produce the same protective effects as IFNγ treatment when applied to naive cultures. Finally, nasal administration of IFNγ to rats recapitulated in vitro effects, reducing OS, increasing myelin, and reducing SD. These results support phasic IFNγ signaling as a therapeutic target for prevention of SD and, by extension, migraine.

  12. Effect of acid concentration and treatment time on acid-alcohol modified jackfruit seed starch properties.

    PubMed

    Dutta, Himjyoti; Paul, Sanjib Kumar; Kalita, Dipankar; Mahanta, Charu Lata

    2011-09-15

    The properties of starch extracted from jackfruit (Artocarpus heterophyllus Lam.) seeds, collected from west Assam after acid-alcohol modification by short term treatment (ST) for 15-30min with concentrated hydrochloric acid and long term treatment (LT) for 1-15days with 1M hydrochloric acid, were investigated. Granule density, freeze thaw stability, solubility and light transmittance of the treated starches increased. A maximum decrease in the degree of polymerisation occurred in ST of 30min (2607.6). Jackfruit starch had 27.1±0.04% amylose content (db), which in ST initially decreased and then increased with the severity of treatment; in LT the effect was irregular. The pasting profile and granule morphology of the treated samples were severely modified. Native starch had the A-type crystalline pattern and crystalline structure increased on treatment. FTIR spectra revealed slight changes in bond stretching and bending. Colour measurement indicated that whiteness increased on treatment. Acid modified jackfruit seed starch can have applications in the food industry.

  13. Effect of acid concentration and treatment time on acid-alcohol modified jackfruit seed starch properties.

    PubMed

    Dutta, Himjyoti; Paul, Sanjib Kumar; Kalita, Dipankar; Mahanta, Charu Lata

    2011-09-15

    The properties of starch extracted from jackfruit (Artocarpus heterophyllus Lam.) seeds, collected from west Assam after acid-alcohol modification by short term treatment (ST) for 15-30min with concentrated hydrochloric acid and long term treatment (LT) for 1-15days with 1M hydrochloric acid, were investigated. Granule density, freeze thaw stability, solubility and light transmittance of the treated starches increased. A maximum decrease in the degree of polymerisation occurred in ST of 30min (2607.6). Jackfruit starch had 27.1±0.04% amylose content (db), which in ST initially decreased and then increased with the severity of treatment; in LT the effect was irregular. The pasting profile and granule morphology of the treated samples were severely modified. Native starch had the A-type crystalline pattern and crystalline structure increased on treatment. FTIR spectra revealed slight changes in bond stretching and bending. Colour measurement indicated that whiteness increased on treatment. Acid modified jackfruit seed starch can have applications in the food industry. PMID:25212133

  14. Long-term treatment with responsive brain stimulation in adults with refractory partial seizures

    PubMed Central

    Bergey, Gregory K.; Mizrahi, Eli M.; Goldman, Alica; King-Stephens, David; Nair, Dileep; Srinivasan, Shraddha; Jobst, Barbara; Gross, Robert E.; Shields, Donald C.; Barkley, Gregory; Salanova, Vicenta; Olejniczak, Piotr; Cole, Andrew; Cash, Sydney S.; Noe, Katherine; Wharen, Robert; Worrell, Gregory; Murro, Anthony M.; Edwards, Jonathan; Duchowny, Michael; Spencer, David; Smith, Michael; Geller, Eric; Gwinn, Ryder; Skidmore, Christopher; Eisenschenk, Stephan; Berg, Michel; Heck, Christianne; Van Ness, Paul; Fountain, Nathan; Rutecki, Paul; Massey, Andrew; O'Donovan, Cormac; Labar, Douglas; Duckrow, Robert B.; Hirsch, Lawrence J.; Courtney, Tracy; Sun, Felice T.; Seale, Cairn G.

    2015-01-01

    Objective: The long-term efficacy and safety of responsive direct neurostimulation was assessed in adults with medically refractory partial onset seizures. Methods: All participants were treated with a cranially implanted responsive neurostimulator that delivers stimulation to 1 or 2 seizure foci via chronically implanted electrodes when specific electrocorticographic patterns are detected (RNS System). Participants had completed a 2-year primarily open-label safety study (n = 65) or a 2-year randomized blinded controlled safety and efficacy study (n = 191); 230 participants transitioned into an ongoing 7-year study to assess safety and efficacy. Results: The average participant was 34 (±11.4) years old with epilepsy for 19.6 (±11.4) years. The median preimplant frequency of disabling partial or generalized tonic-clonic seizures was 10.2 seizures a month. The median percent seizure reduction in the randomized blinded controlled trial was 44% at 1 year and 53% at 2 years (p < 0.0001, generalized estimating equation) and ranged from 48% to 66% over postimplant years 3 through 6 in the long-term study. Improvements in quality of life were maintained (p < 0.05). The most common serious device-related adverse events over the mean 5.4 years of follow-up were implant site infection (9.0%) involving soft tissue and neurostimulator explantation (4.7%). Conclusions: The RNS System is the first direct brain responsive neurostimulator. Acute and sustained efficacy and safety were demonstrated in adults with medically refractory partial onset seizures arising from 1 or 2 foci over a mean follow-up of 5.4 years. This experience supports the RNS System as a treatment option for refractory partial seizures. Classification of evidence: This study provides Class IV evidence that for adults with medically refractory partial onset seizures, responsive direct cortical stimulation reduces seizures and improves quality of life over a mean follow-up of 5.4 years. PMID:25616485

  15. Differences in phosphatidic acid signalling and metabolism between ABA and GA treatments of barley aleurone cells.

    PubMed

    Villasuso, Ana Laura; Di Palma, Maria A; Aveldaño, Marta; Pasquaré, Susana J; Racagni, Graciela; Giusto, Norma M; Machado, Estela E

    2013-04-01

    Phosphatidic acid (PA) is the common lipid product in abscisic acid (ABA) and gibberellic acid (GA) response. In this work we investigated the lipid metabolism in response to both hormones. We could detect an in vivo phospholipase D activity (PLD, EC 3.1.4.4). This PLD produced [(32)P]PA (phosphatidic acid) rapidly (minutes) in the presence of ABA, confirming PA involvement in signal transduction, and transiently, indicating rapid PA removal after generation. The presence of PA removal by phosphatidate phosphatase 1 and 2 isoforms (E.C. 3.1.3.4) was verified in isolated aleurone membranes in vitro, the former but not the latter being specifically responsive to the presence of GA or ABA. The in vitro DGPP phosphatase activity was not modified by short time incubation with GA or ABA while the in vitro PA kinase - that allows the production of 18:2-DGPP from 18:2-PA - is stimulated by ABA. The long term effects (24 h) of ABA or GA on lipid and fatty acid composition of aleurone layer cells were then investigated. An increase in PC and, to a lesser extent, in PE levels is the consequence of both hormone treatments. ABA, in aleurone layer cells, specifically activates a PLD whose product, PA, could be the substrate of PAP1 and/or PAK activities. Neither PLD nor PAK activation can be monitored by GA treatment. The increase in PAP1 activity monitored after ABA or GA treatment might participate in the increase in PC level observed after 24 h hormone incubation.

  16. Cooperative role of electrical stimulation on microbial metabolism and selection of thermophilic communities for p-fluoronitrobenzene treatment.

    PubMed

    Zhang, Xueqin; Shen, Dongsheng; Feng, Huajun; Wang, Yanfeng; Li, Na; Han, Jingyi; Long, Yuyang

    2015-01-01

    A novel thermophilic bioelectrochemical system (TBES) based on electrical stimulation was established for the enhanced treatment of p-fluoronitrobenzene (p-FNB) wastewater. p-FNB removal rate constant in the TBES was 78.6% higher than that of the mesophilic BES (MBES), the elevation of which owing to high-temperature overtook the rate improvement of 50.8% in the electrocatalytic system (ECS). Additionally, an overwhelming mineralization efficiency of 91.96% ± 5.70% was obtained in the TBES. The superiority of TBES was attributed to the integrated role of electrical stimulation and high-temperature. Electrical stimulation provided an alternative for the microbial growth independent energy requirements, compensating insufficient energy support from p-FNB metabolism under the high-temperature stress. Besides, electrical stimulation facilitated microbial community evolution to form specific thermophilic biocatalysis. The uniquely selected thermophilic microorganisms including Coprothermobacter sp. and other ones cooperated to enhance p-FNB mineralization.

  17. Effect of 82% Lactic Acid in Treatment of Melasma

    PubMed Central

    Singh, Rashmi; Goyal, Sapna; Ahmed, Qazi Rais; Gupta, Narendra; Singh, Sujata

    2014-01-01

    Melasma is an acquired, chronic, and symmetrical hypermelanosis, characterized by brown patches of variable darkness on sun exposed areas of body. There are numerous modalities of treatment currently in use for this disease, of which the chemical peeling is very commonly used. Therefore, the present work was done to see the effect of 82% lactic acid peel in the treatment of melasma. A total number of 20 patients of either sex attending the OPD of dermatology department with clinically evident melasma were included in the study. 82% Lactic acid peel was applied on the face for 12 weeks in each patient. Patients were evaluated clinically and photographically at various intervals and in follow-up till 24 weeks. Assessment of patient satisfaction and side effects were also noted. All the subjects completed the study. Application of this peel for 12 weeks significantly decreased the melasma area severity index score and also melasma severity scale score. Patient and physician analogue scales also showed the improvement by the treatment. Regarding the adverse effects, burning sensation was the only side effect noted in our study. In conclusion, 82% lactic acid peel is well tolerated and can be used for the treatment of melasma. PMID:27355080

  18. Prolonged treatment with ursodeoxycholic acid for primary biliary cirrhosis.

    PubMed

    Crippa, G; Cagnoni, C; Castelli, A; Concesi, C; Girometta, S; Pancotti, D; Sverzellati, E; Tacchini, G; Pierfranceschi, M G; Carrara, G C

    1995-05-01

    Eighteen patients affected with biopsy-proved primary biliary cirrhosis (PBC) (histological stage III and IV) received ursodeoxicholic acid (UDCA) 600 mg for 1 year. Signs and symptoms and biochemical tests (glutamic and oxalcetic transaminase, glutamic and pyruvic transaminase, bilirubine, gamma-glutamyl transpeptidase, alkaline phosphatase, leucine aminopeptidase, bile acids, plasma proteins electrophoresis, immunoglubulins A, G and M) and antimitochondrial antibodies were evaluated before the treatment and every four months during the treatment. The results were compared with those obtained in 8 untreated patients affected PBC. The control group of patients were comparable (as far as age, histological stage, biochemical tests are concerned) to the group who received UDCA. Bilirubine, ALP, gamma-GT and LAP decreased during the treatment with UDCA and remained lower than baseline values until the end of the observation (12 months), while no changes occurred in the untreated patients. Both in the treated and untreated group plasma protein electrophoresis, serum immunoglubulins A, G and M remained unchanged, as well as anti-mitochondrial antibody. A moderate reduction of transaminases and bile acids was observed in the group of patients receiving UDCA but it did not reach statistical significance. In 16 out of the 18 treated patients pruritus disappeared and resulted diminished in the remaining 2 patients. No significant amelioration of pruritus was observed in the patients who did not receive UDCA. In conclusion, our data show that prolonged treatment with UDCA drastically reduces pruritus and improves cholestasis biochemical tests in patients affected with symptomatic PBC.(ABSTRACT TRUNCATED AT 250 WORDS)

  19. tDCS in post-stroke aphasia: the role of stimulation parameters, behavioral treatment and patient characteristics.

    PubMed

    de Aguiar, Vânia; Paolazzi, Caterina Laura; Miceli, Gabriele

    2015-02-01

    Neurostimulation techniques have been recently adopted in aphasia rehabilitation. In several studies transcranial direct current stimulation (tDCS) was used to enhance treatment effects. The methodology adopted in different studies is characterized by a large variability, as concerns stimulation parameters (e.g., montage type, current intensity, session duration, number and frequency of treatment sessions), participant inclusion criteria (subacute vs chronic, selected vs general aphasia types) and characteristics of associated behavioral treatments (online vs offline treatment, focused on different underlying deficits). Group analyses report on positive results for most of the adopted paradigms. We review the available literature focusing on tDCS in the rehabilitation of stroke-related aphasia, with reference to the current views on tDCS's action mechanisms and on the factors that may influence the effects of stimulation. Even though our understanding of the mechanisms activated by neurostimulation techniques is still limited, available evidence already allows to propose methodological recommendations for studies intending to use tDCS as a treatment adjuvant. Where several options for a specific stimulation parameter seem suitable, we provide information to reach a knowledgeable decision.

  20. Retinoic acid stimulate differentiation of hippocampal stem cells into opsin expressing cells in vitro.

    PubMed

    Safari, M; Nobakht, M; Roshandel, N Rahbar; Ghazi, F; Joghataee, M T

    2009-09-01

    The results of several studies have demonstrated that cell differentiation influenced by derivatives of retinoic acid. To determine whether retinoic acid mediate the differentiation of neural stem cells we treated dissociated hippocampal stem cells with different concentrations of all trans or 9-cis retinoic acid and analyzed the effects on cell fate by specific monoclonal antibody for photoreceptors. Addition of exogenous retinoic acid caused a dose dependent specific in the elevation of the cell number that developed as photoreceptors in culture. Also results ofimmunohistochemical studies using monoclonal antibody demonstrated that the primary effect ofretinoic acid was to influence progenitor cells the developed as mature and immature photoreceptors. These results suggest that retinoic acid may play an important effect in the normal development of photoreceptor cells in vitro.

  1. IMAGING SIGNAL TRANSDUCTION VIA ARACHIDONIC ACID IN THE HUMAN BRAIN DURING VISUAL STIMULATION, BY MEANS OF POSITRON EMISSION TOMOGRAPHY

    PubMed Central

    Esposito, Giuseppe; Giovacchini, Giampiero; Der, Margaret; Liow, Jeih-San; Bhattacharjee, Abesh K.; Ma, Kaizong; Herscovitch, Peter; Channing, Michael; Eckelman, William C.; Hallett, Mark; Carson, Richard E.; Rapoport, Stanley I.

    2007-01-01

    Background Arachidonic acid (AA, 20:4n-6), an important second messenger, is released from membrane phospholipid following receptor mediated activation of phospholipase A2 (PLA2). This signaling process can be imaged in brain as a regional brain AA incorporation coefficient K*. Hypothesis K* will be increased in brain visual areas of subjects submitted to visual stimulation. Subjects and methods Regional values of K* were measured with positron emission tomography (PET), following the intravenous injection of [1-11C]AA, in 16 healthy volunteers subjected to visual stimulation at flash frequencies 2.9 Hz (8 subjects) or 7.8 Hz (8 subjects), compared with the dark (0 Hz) condition. Regional cerebral blood flow (rCBF) was measured with intravenous [15O]water under comparable conditions. Results During flash stimulation at 2.9 Hz or 7.8 Hz vs. 0 Hz, K* was increased significantly by 2.3–8.9% in Brodmann areas 17, 18 and 19, and in additional frontal, parietal and temporal cortical regions. rCBF was increased significantly by 3.1% – 22%, often in comparable regions. Increments at 7.8 Hz often exceeded those at 2.9 Hz for both K* and rCBF. Decrements in both parameters also were produced, particularly in frontal brain regions. Conclusions AA plays a role in signaling processes provoked by visual stimulation, since visual stimulation at flash frequencies of 2.9 and 7.8 Hz compared to 0 Hz modifies both K* for AA and rCBF in visual and related areas of the human brain. The two-stimulus condition paradigm of this study might be used with PET to image effects of other functional activations and of drugs on brain signaling via AA. PMID:17196833

  2. Outcomes of assisted reproduction treatment after dopamine agonist -cabergoline- for prevention of ovarian hyper stimulation syndrome

    PubMed Central

    Movahedi, Shohreh; Safdarian, Leili; Agahoseini, Marzieh; Aleyasin, Ashraf; Khodaverdi, Sepideh; Asadollah, Sara; Kord Valeshabad, Ali; Fallahi, Parvin; Rezaeeian, Zahra

    2016-01-01

    Background: Release of vascular endothelial growth factor (VEGF) by ovaries in response to HCG administration is one of the main mechanisms of ovarian hyper stimulation syndrome. Since Dopamine/dopamine receptor2 (Dp-r2) pathway activity -mediated by VEGF/ Vascular endothelial growth factor receptor 2 (VEGFR- 2) signaling-, is associated with angiogenic events, dopamine agonists were used for the management of severe forms of OHSS. In order to assess the effects of Cabergoline on angiogenesis in the human endometrium, and subsequently its impacts on the implantation rate this study was conducted. Methods: This historical cohort study was conducted based on existing data of 115 patients (20-40 years) whom underwent assisted reproductive treatment (ART) and with a high probability for developing OHSS between March 2007 and September 2008. Forty five cases received Cabergoline were compared to 70 control subjects. The statistical methods used were: Unpaired t-test for continuous variables and the chi-square test (or Fisher’s exact test if required) for categorical variables. Results: None of the patients (treatment or control group) developed OHSS. The etiologies of infertility and administration of GnRH agonist or antagonist protocols were similar in two groups (p>0.2). Number of transferred embryos and zygote intra-fallopian transfer (ZIFT) did not differ between the two groups (p≥0.06). Implantation rate in treatment (3.1%) and control (6.6%) subjects was similar (p=0.4). No significant difference was observed in fertilization rate, chemical, clinical and ongoing pregnancies between the two groups (p>0.5). Conclusion: Cabergoline can be safely administered in ART protocols to prevent OHSS, without compromising ART outcomes. PMID:27493915

  3. Biofeedback is superior to electrogalvanic stimulation and massage for treatment of levator ani syndrome

    PubMed Central

    Chiarioni, Giuseppe; Nardo, Adriana; Vantini, Italo; Romito, Antonella; Whitehead, William E.

    2010-01-01

    Background & Aims Levator ani syndrome (LAS) might be treated using biofeedback to teach pelvic floor relaxation, electrogalvanic stimulation (EGS), or massage of levator muscles. We performed a prospective, randomized controlled trial to compare the effectiveness of these techniques and assess physiological mechanisms for treatment. Methods Inclusion criteria were Rome II symptoms plus weekly pain. Patients were categorized as “highly likely” to have LAS if they reported tenderness with traction on the levator muscles, or as “possible” LAS if they did not. All 157 patients received 9 sessions including psychological counseling plus biofeedback, EGS, or massage. Outcomes were reassessed at 1, 3, 6, and 12 months. Results Among patients with “highly likely” LAS, adequate relief was reported by 87% for biofeedback, 45% for EGS, and 22% for massage. Pain days per month decreased from 14.7 at baseline to 3.3 after biofeedback, 8.9 after EGS, and 13.3 after massage. Pain intensity decreased from 6.8 (0–10 scale) at baseline to 1.8 after biofeedback, 4.7 after EGS, and 6.0 after massage. Improvements were maintained for 12 months. Patients with only a “possible” diagnosis of LAS did not benefit from any treatment. Biofeedback and EGS improved LAS by increasing the ability to relax pelvic floor muscles and evacuate a water-filled balloon, and by reducing the urge and pain thresholds. Conclusions Biofeedback is the most effective of these treatments, and EGS is somewhat effective. Only patients with tenderness on rectal examination benefit. The pathophysiology of LAS is similar to that of dyssynergic defecation. PMID:20044997

  4. Suppression of Aflatoxin Biosynthesis in Aspergillus flavus by 2-Phenylethanol Is Associated with Stimulated Growth and Decreased Degradation of Branched-Chain Amino Acids

    PubMed Central

    Chang, Perng-Kuang; Hua, Sui Sheng T.; Sarreal, Siov Bouy L.; Li, Robert W.

    2015-01-01

    The saprophytic soil fungus Aspergillus flavus infects crops and produces aflatoxin. Pichia anomala, which is a biocontrol yeast and produces the major volatile 2-phenylethanol (2-PE), is able to reduce growth of A. flavus and aflatoxin production when applied onto pistachio trees. High levels of 2-PE are lethal to A. flavus and other fungi. However, at low levels, the underlying mechanism of 2-PE to inhibit aflatoxin production remains unclear. In this study, we characterized the temporal transcriptome response of A. flavus to 2-PE at a subinhibitory level (1 µL/mL) using RNA-Seq technology and bioinformatics tools. The treatment during the entire 72 h experimental period resulted in 131 of the total A. flavus 13,485 genes to be significantly impacted, of which 82 genes exhibited decreased expression. They included those encoding conidiation proteins and involved in cyclopiazonic acid biosynthesis. All genes in the aflatoxin gene cluster were also significantly decreased during the first 48 h treatment. Gene Ontology (GO) analyses showed that biological processes with GO terms related to catabolism of propionate and branched-chain amino acids (valine, leucine and isoleucine) were significantly enriched in the down-regulated gene group, while those associated with ribosome biogenesis, translation, and biosynthesis of α-amino acids were over-represented among the up-regulated genes. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that metabolic pathways negatively impacted among the down-regulated genes parallel to those active at 30 °C, a condition conducive to aflatoxin biosynthesis. In contrast, metabolic pathways positively related to the up-regulated gene group resembled those at 37 °C, which favors rapid fungal growth and is inhibitory to aflatoxin biosynthesis. The results showed that 2-PE at a low level stimulated active growth of A. flavus but concomitantly rendered decreased activities in branched-chain amino acid degradation

  5. Suppression of Aflatoxin Biosynthesis in Aspergillus flavus by 2-Phenylethanol Is Associated with Stimulated Growth and Decreased Degradation of Branched-Chain Amino Acids.

    PubMed

    Chang, Perng-Kuang; Hua, Sui Sheng T; Sarreal, Siov Bouy L; Li, Robert W

    2015-10-01

    The saprophytic soil fungus Aspergillus flavus infects crops and produces aflatoxin. Pichia anomala, which is a biocontrol yeast and produces the major volatile 2-phenylethanol (2-PE), is able to reduce growth of A. flavus and aflatoxin production when applied onto pistachio trees. High levels of 2-PE are lethal to A. flavus and other fungi. However, at low levels, the underlying mechanism of 2-PE to inhibit aflatoxin production remains unclear. In this study, we characterized the temporal transcriptome response of A. flavus to 2-PE at a subinhibitory level (1 μL/mL) using RNA-Seq technology and bioinformatics tools. The treatment during the entire 72 h experimental period resulted in 131 of the total A. flavus 13,485 genes to be significantly impacted, of which 82 genes exhibited decreased expression. They included those encoding conidiation proteins and involved in cyclopiazonic acid biosynthesis. All genes in the aflatoxin gene cluster were also significantly decreased during the first 48 h treatment. Gene Ontology (GO) analyses showed that biological processes with GO terms related to catabolism of propionate and branched-chain amino acids (valine, leucine and isoleucine) were significantly enriched in the down-regulated gene group, while those associated with ribosome biogenesis, translation, and biosynthesis of α-amino acids OPEN ACCESS Toxins 2015, 7 3888 were over-represented among the up-regulated genes. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that metabolic pathways negatively impacted among the down-regulated genes parallel to those active at 30 °C, a condition conducive to aflatoxin biosynthesis. In contrast, metabolic pathways positively related to the up-regulated gene group resembled those at 37 °C, which favors rapid fungal growth and is inhibitory to aflatoxin biosynthesis. The results showed that 2-PE at a low level stimulated active growth of A. flavus but concomitantly rendered decreased activities in

  6. Inhibition of 2,4-dichlorophenoxyacetic acid-stimulated elongation of pea stem segments by a xyloglucan oligosaccharide

    SciTech Connect

    York, W.S.; Darvill, A.G.; Albersheim, P.

    1984-06-01

    Xyloglucan, isolated from the soluble extracellular polysaccharides of suspension-cultured sycamore (Acer pseudoplatanus) cells, was digested with an endo-..beta..-1,4-glucanase purified from the culture fluid of Trichoderma viride. A nonasaccharide-rich Bio-Gel P-2 fraction of this digest inhibited 2,4-dichlorophenoxyacetic-acid-stimulated elongation of etiolated pea stem segments. The inhibitory activity of this oligosaccharide fraction exhibited a well-define concentraction optimum between 10/sup -2/ and 10/sup -1/ micrograms per milliliter. Another fraction of the same xyloglucan digest, rich in a structurally related heptasaccharide, did not, at similar concentrations, significantly inhibit the elongation. 11 references, 3 figures.

  7. Acetylsalicylic acid treatment improves differentiation and immunomodulation of SHED.

    PubMed

    Liu, Y; Chen, C; Liu, S; Liu, D; Xu, X; Chen, X; Shi, S

    2015-01-01

    Stem cells from exfoliated deciduous teeth (SHED) possess multipotent differentiation and immunomodulatory properties. They have been used for orofacial bone regeneration and autoimmune disease treatment. In this study, we show that acetylsalicylic acid (ASA) treatment is able to significantly improve SHED-mediated osteogenic differentiation and immunomodulation. Mechanistically, ASA treatment upregulates the telomerase reverse transcriptase (TERT)/Wnt/β-catenin cascade, leading to improvement of SHED-mediated bone regeneration, and also upregulates TERT/FASL signaling, leading to improvement of SHED-mediated T-cell apoptosis and ameliorating disease phenotypes in dextran sodium sulfate-induced colitis mice. These data indicate that ASA treatment is a practical approach to improving SHED-based cell therapy.

  8. Microsecond-pulsed dielectric barrier discharge plasma stimulation of tissue macrophages for treatment of peripheral vascular disease

    SciTech Connect

    Miller, V. Lin, A.; Brettschneider, J.; Fridman, G.; Fridman, A.; Kako, F.; Gabunia, K.; Kelemen, S.; Autieri, M.

    2015-12-15

    Angiogenesis is the formation of new blood vessels from pre-existing vessels and normally occurs during the process of inflammatory reactions, wound healing, tissue repair, and restoration of blood flow after injury or insult. Stimulation of angiogenesis is a promising and an important step in the treatment of peripheral artery disease. Reactive oxygen species have been shown to be involved in stimulation of this process. For this reason, we have developed and validated a non-equilibrium atmospheric temperature and pressure short-pulsed dielectric barrier discharge plasma system, which can non-destructively generate reactive oxygen species and other active species at the surface of the tissue being treated. We show that this plasma treatment stimulates the production of vascular endothelial growth factor, matrix metalloproteinase-9, and CXCL 1 that in turn induces angiogenesis in mouse aortic rings in vitro. This effect may be mediated by the direct effect of plasma generated reactive oxygen species on tissue.

  9. Microsecond-pulsed dielectric barrier discharge plasma stimulation of tissue macrophages for treatment of peripheral vascular disease

    NASA Astrophysics Data System (ADS)

    Miller, V.; Lin, A.; Kako, F.; Gabunia, K.; Kelemen, S.; Brettschneider, J.; Fridman, G.; Fridman, A.; Autieri, M.

    2015-12-01

    Angiogenesis is the formation of new blood vessels from pre-existing vessels and normally occurs during the process of inflammatory reactions, wound healing, tissue repair, and restoration of blood flow after injury or insult. Stimulation of angiogenesis is a promising and an important step in the treatment of peripheral artery disease. Reactive oxygen species have been shown to be involved in stimulation of this process. For this reason, we have developed and validated a non-equilibrium atmospheric temperature and pressure short-pulsed dielectric barrier discharge plasma system, which can non-destructively generate reactive oxygen species and other active species at the surface of the tissue being treated. We show that this plasma treatment stimulates the production of vascular endothelial growth factor, matrix metalloproteinase-9, and CXCL 1 that in turn induces angiogenesis in mouse aortic rings in vitro. This effect may be mediated by the direct effect of plasma generated reactive oxygen species on tissue.

  10. Usefulness of retinoic acid in the treatment of melasma.

    PubMed

    Pathak, M A; Fitzpatrick, T B; Kraus, E W

    1986-10-01

    Melasma is a circumscribed brown macular hypermelanosis of the areas of the face and neck that are exposed to light. Clinical trials with various depigmenting formulations containing hydroquinone were conducted to determine the ideal concentration of hydroquinone, retinoic acid, and corticosteroids for the treatment of melasma. The compounds were tested with and without the concomitant use of topical sunscreen preparations. Based on the results of the trials and our earlier clinical experience, we conclude that treatment of melasma should involve the following: avoidance of sun exposure, constant use of broad-spectrum sunscreens, and topical application of a cream or lotion containing 2% hydroquinone and 0.05% to 0.1% retinoic acid (tretinoin). Patients should suspend use of oral contraceptives and other agents that promote skin pigmentation. The monobenzyl ether of hydroquinone should never be used in melasma therapy.

  11. Removal of coagulant aluminum from water treatment residuals by acid.

    PubMed

    Okuda, Tetsuji; Nishijima, Wataru; Sugimoto, Mayo; Saka, Naoyuki; Nakai, Satoshi; Tanabe, Kazuyasu; Ito, Junki; Takenaka, Kenji; Okada, Mitsumasa

    2014-09-01

    Sediment sludge during coagulation and sedimentation in drinking water treatment is called "water treatment residuals (WTR)". Polyaluminum chloride (PAC) is mainly used as a coagulant in Japan. The recycling of WTR has been desired; one method for its reuse is as plowed soil. However, WTR reuse in this way is inhibited by the aluminum from the added PAC, because of its high adsorption capacity for phosphate and other fertilizer components. The removal of such aluminum from WTR would therefore be advantageous for its reuse as plowed soil; this research clarified the effect of acid washing on aluminum removal from WTR and on plant growth in the treated soil. The percentage of aluminum removal from raw WTR by sulphuric acid solution was around 90% at pH 3, the percentage decreasing to 40% in the case of a sun-dried sample. The maximum phosphate adsorption capacity was decreased and the available phosphorus was increased by acid washing, with 90% of aluminum removal. The enhancement of Japanese mustard spinach growth and the increased in plant uptake of phosphates following acid washing were observed.

  12. Combining TMS-EEG with transcranial direct current stimulation language treatment in aphasia.

    PubMed

    Cipollari, Susanna; Veniero, Domenica; Razzano, Carmela; Caltagirone, Carlo; Koch, Giacomo; Marangolo, Paola

    2015-01-01

    Despite the fact that different studies have been performed using transcranial direct current stimulation (tDCS) in aphasia, so far, to what extent the stimulation of a cerebral region may affect the activity of anatomically connected regions remains unclear. The authors used a combination of transcranial magnetic stimulation (TMS) and electroencephalography (EEG) to explore brain areas' excitability modulation before and after active and sham tDCS. Six chronic aphasics underwent 3 weeks of language training coupled with tDCS over the right inferior frontal gyrus. To measure the changes induced by tDCS, TMS-EEG closed to the area stimulated with tDCS were calculated. A significant improvement after tDCS stimulation was found which was accompained by a modification of the EEG over the stimulated region.

  13. Combining TMS-EEG with transcranial direct current stimulation language treatment in aphasia.

    PubMed

    Cipollari, Susanna; Veniero, Domenica; Razzano, Carmela; Caltagirone, Carlo; Koch, Giacomo; Marangolo, Paola

    2015-01-01

    Despite the fact that different studies have been performed using transcranial direct current stimulation (tDCS) in aphasia, so far, to what extent the stimulation of a cerebral region may affect the activity of anatomically connected regions remains unclear. The authors used a combination of transcranial magnetic stimulation (TMS) and electroencephalography (EEG) to explore brain areas' excitability modulation before and after active and sham tDCS. Six chronic aphasics underwent 3 weeks of language training coupled with tDCS over the right inferior frontal gyrus. To measure the changes induced by tDCS, TMS-EEG closed to the area stimulated with tDCS were calculated. A significant improvement after tDCS stimulation was found which was accompained by a modification of the EEG over the stimulated region. PMID:26109229

  14. Electrical stimulation as a treatment intervention to improve function, edema or pain following acute lateral ankle sprains: A systematic review.

    PubMed

    Feger, Mark A; Goetschius, John; Love, Hailey; Saliba, Sue A; Hertel, Jay

    2015-11-01

    The purpose of this systematic review was to assess whether electrical stimulation (ES), when used in conjunction with a standard treatment, can reduce levels of functional impairment, edema, and pain compared to a standard treatment alone, in patients following a lateral ankle sprain. We searched PubMed, CINAHL, SportDiscus, and Medline (OVID) databases through June 2014 using the terms "ankle sprain or ankle sprains or ligament injury or ligamentous injury," and "electric stimulation or electric stimulation or electrotherapy." Our search identified four randomized control trials, of which, neuromuscular ES and high-voltage pulsed stimulation were the only two ES modalities utilized. Effect sizes and 95% confidence intervals (CI) were estimated using Cohen's d for comparison between treatment groups. Three of four effect sizes for function had 95% CI that crossed zero. Twenty-four of the thirty-two effect sizes for edema had 95% CI that crossed zero. All effect sizes for pain had 95% CI that crossed zero. Therefore, the use of ES is not recommended as a means to improve function, reduce edema, or decrease pain in the treatment of acute lateral ankle sprains.

  15. Transcutaneous noninvasive vagus nerve stimulation (tVNS) in the treatment of schizophrenia: a bicentric randomized controlled pilot study.

    PubMed

    Hasan, Alkomiet; Wolff-Menzler, Claus; Pfeiffer, Sebastian; Falkai, Peter; Weidinger, Elif; Jobst, Andrea; Hoell, Imke; Malchow, Berend; Yeganeh-Doost, Peyman; Strube, Wolfgang; Quast, Silke; Müller, Norbert; Wobrock, Thomas

    2015-10-01

    Despite many pharmacological and psychosocial treatment options, schizophrenia remains a debilitating disorder. Thus, new treatment strategies rooted in the pathophysiology of the disorder are needed. Recently, vagus nerve stimulation (VNS) has been proposed as a potential treatment option for various neuropsychiatric disorders including schizophrenia. The objective of this study was to investigate for the first time the feasibility, safety and efficacy of transcutaneous VNS in stable schizophrenia. A bicentric randomized, sham-controlled, double-blind trial was conducted from 2010 to 2012. Twenty schizophrenia patients were randomly assigned to one of two treatment groups. The first group (active tVNS) received daily active stimulation of the left auricle for 26 weeks. The second group (sham tVNS) received daily sham stimulation for 12 weeks followed by 14 weeks of active stimulation. Primary outcome was defined as change in the Positive and Negative Symptom Scale total score between baseline and week 12. Various other secondary measures were assessed to investigate safety and efficacy. The intervention was well tolerated with no relevant adverse effects. We could not observe a statistically significant difference in the improvement of schizophrenia psychopathology during the observation period. Neither psychopathological and neurocognitive measures nor safety measures showed significant differences between study groups. Application of tVNS was well tolerated, but did not improve schizophrenia symptoms in our 26-week trial. While unsatisfactory compliance questions the feasibility of patient-controlled neurostimulation in schizophrenia, the overall pattern of symptom change might warrant further investigations in this population.

  16. Combining Stimulants and Monoamine Oxidase Inhibitors: A Reexamination of the Literature and a Report of a New Treatment Combination

    PubMed Central

    Israel, Joshua A.

    2015-01-01

    This report reviews the medical literature on combining stimulants with monoamine oxidase inhibitors. A case is also presented documenting successful treatment of major depressive disorder and comorbid attention-deficit/hyperactivity disorder using the previously undocumented combination of transdermal selegiline and lisdexamfetamine. This combination should be used cautiously and with ongoing monitoring of heart rate and blood pressure. PMID:27057401

  17. Treatment-Resistant Depression Entering Remission Following a Seizure during the Course of Repetitive Transcranial Magnetic Stimulation.

    PubMed

    Kim, Ju-Wan; Bae, Kyung-Yeol; Kim, Sung-Wan; Kang, Hee-Ju; Shin, Il-Seon; Yoon, Jin-Sang; Kim, Jae-Min

    2016-07-01

    Major depressive disorder is often resistant to antidepressant treatment. Repetitive transcranial magnetic stimulation (rTMS) has been used in treatment-resistant depression (TRD). Known adverse events of rTMS include transient headache, local pain, syncope, seizure induction, and hypomania induction. This report outlines a patient with TRD who unexpectedly improved following a seizure during the course of rTMS, which has never been reported. PMID:27482250

  18. Treatment-Resistant Depression Entering Remission Following a Seizure during the Course of Repetitive Transcranial Magnetic Stimulation

    PubMed Central

    Kim, Ju-Wan; Bae, Kyung-Yeol; Kim, Sung-Wan; Kang, Hee-Ju; Shin, Il-Seon; Yoon, Jin-Sang

    2016-01-01

    Major depressive disorder is often resistant to antidepressant treatment. Repetitive transcranial magnetic stimulation (rTMS) has been used in treatment-resistant depression (TRD). Known adverse events of rTMS include transient headache, local pain, syncope, seizure induction, and hypomania induction. This report outlines a patient with TRD who unexpectedly improved following a seizure during the course of rTMS, which has never been reported. PMID:27482250

  19. Granulocyte colony-stimulating factor (G-CSF): A saturated fatty acid-induced myokine with insulin-desensitizing properties in humans

    PubMed Central

    Ordelheide, Anna-Maria; Gommer, Nadja; Böhm, Anja; Hermann, Carina; Thielker, Inga; Machicao, Fausto; Fritsche, Andreas; Stefan, Norbert; Häring, Hans-Ulrich; Staiger, Harald

    2016-01-01

    Objective Circulating long-chain free fatty acids (FFAs) are important metabolic signals that acutely enhance fatty acid oxidation, thermogenesis, energy expenditure, and insulin secretion. However, if chronically elevated, they provoke inflammation, insulin resistance, and β-cell failure. Moreover, FFAs act via multiple signaling pathways as very potent regulators of gene expression. In human skeletal muscle cells differentiated in vitro (myotubes), we have shown in previous studies that the expression of CSF3, the gene encoding granulocyte colony-stimulating factor (G-CSF), is markedly induced upon FFA treatment and exercise. Methods and results We now report that CSF3 is induced in human myotubes by saturated, but not unsaturated, FFAs via Toll-like receptor 4-dependent and -independent pathways including activation of Rel-A, AP-1, C/EBPα, Src, and stress kinases. Furthermore, we show that human adipocytes and myotubes treated with G-CSF become insulin-resistant. In line with this, a functional polymorphism in the CSF3 gene affects adipose tissue- and whole-body insulin sensitivity and glucose tolerance in human subjects with elevated plasma FFA concentrations. Conclusion G-CSF emerges as a new player in FFA-induced insulin resistance and thus may be of interest as a target for prevention and treatment of type 2 diabetes. PMID:27069870

  20. Repetitive Transcranial Magnetic Stimulation to Supplementary Motor Area in Refractory Obsessive-Compulsive Disorder Treatment: a Sham-Controlled Trial

    PubMed Central

    Harika-Germaneau, Ghina; Rachid, Fady; Gaudeau-Bosma, Christian; Tanguy, Marie-Laure; BenAdhira, Rene; Bouaziz, Noomane; Popa, Traian; Wassouf, Issa; Saba, Ghassen; Januel, Dominique; Jaafari, Nematollah

    2016-01-01

    Background: Repetitive transcranial magnetic stimulation has been explored in patients with obsessive-compulsive disorder, but with negative or conflicting results. This randomized double-blind study was designed to assess the efficacy of 1-Hz repetitive transcranial magnetic stimulation over the presupplementary area. Methods: Forty medication-resistant patients were assigned to 4 weeks of either active or sham repetitive transcranial magnetic stimulation targeting the presupplementary area with the help of a neuronavigation system. Results: According to the Yale-Brown obsessive-compulsive scale, the baseline-week 4 evolution showed no significant differences between groups. Responder rates at week 4 were not different between groups (repetitive transcranial magnetic stimulation 10.5% vs sham 20%; P=.63). Conclusion: Low-frequency repetitive transcranial magnetic stimulation applied to the presupplementary area seems ineffective for the treatment of obsessive-compulsive disorder patients, at least in severe and drug-refractory cases such as those included in this study. Further research is required to determine profiles of responder patients and appropriate repetitive transcranial magnetic stimulation parameters for obsessive-compulsive disorder. PMID:27207923

  1. The History and Challenges Surrounding Ovarian Stimulation in the Treatment of Infertility

    PubMed Central

    Beall, Stephanie A.; Decherney, Alan

    2014-01-01

    OBJECTIVE To examine the history of superovulation for ovulation induction, its contributions to reproductive medicine and its impact on multiple births. DESIGN A search of the relevant literature using Pubmed and other online tools. RESULT(S) Infertility has been a condition known and studied for thousands of years. However, it was not until this past century that effective treatments were developed. With the advancement of our knowledge of the hypothalamic-pituitary axis, therapies utilizing gonadotropins were developed to stimulate ovulation. Not only were we now able to treat anovulatory infertility, but also induce superovulation for in vitro fertilization. With these successes came consequences, including increased multiple pregnancies. Several countries recognized the high costs associated with multiple births and implemented regulations on the infertility industry. The rate of triplet and higher-order multiples has declined over the past decade. This is largely attributed to a decreased number of embryos transferred. Nonetheless, the twin rate has remained consistently high. CONCLUSION(S) Superovulation has become a routine medical therapy used for ovulation induction and in vitro fertilization. With the development of this technology have come effective therapies for infertility and new ethical and medical challenges. Since the advent of gonadotropin therapy we have already developed technologies to improve monitoring and decrease hyperstimulation and high order multiple pregnancies. In the future, we anticipate new tools devised to optimize one embryo for one singleton live birth. PMID:22463773

  2. Stimulation of hydrogen peroxide production by drinking water contaminants in HL-60 cells sensitized by retinoic acid.

    PubMed

    Yoshida, H; Inoue, S; Yoshida, K; Nakajima, O; Mizuno, S

    1998-07-01

    Chemical carcinogens, such as chloroform and trichloroethylene, are present in drinking water in Japan. As these contaminants are believed to have a role in carcinogenesis, we examined if chloroform and trichloroethylene, as well as methylene chloride, xylene, benzene, and ethanol, have the ability to generate hydrogen peroxide (H(2)O(2)) in human polymorphonuclear leukocytes (PMN) and human leukemia (HL-60) cells. Methylene chloride, benzene, xylene, trichloroethylene, and ethanol did not increase cellular H(2)O(2): production as measured by flow cytometry nor as observed by confocal laser microscopy. In PMN and RAuntreated HL-60 cells chloroform did not significantly affect H(2)O(2) levels. However, in HL-60 cells sensitized by pretreatment of 10 nM retinoic acid (RA) for 12 h, chloroform induced a significant increase in H(2)O(2), but the increase induced by trichloroethylene was not significant. The observed increase in fluorescence was confirmed using a confocal laser microscope. These results indicate that chloroform and trichloroethylene may stimulate H(2)O(2) production in HL60 cells sensitized by pretreatment of RA. Our method may be useful to test if weak stimulants can stimulate intracellular H(2)O(2) production.

  3. Lipopolysaccharide Stimulates Butyric Acid-Induced Apoptosis in Human Peripheral Blood Mononuclear Cells

    PubMed Central

    Kurita-Ochiai, Tomoko; Fukushima, Kazuo; Ochiai, Kuniyasu

    1999-01-01

    We previously reported that butyric acid, an extracellular metabolite from periodontopathic bacteria, induced apoptosis in murine thymocytes, splenic T cells, and human Jurkat T cells. In this study, we examined the ability of butyric acid to induce apoptosis in peripheral blood mononuclear cells (PBMC) and the effect of bacterial lipopolysaccharide (LPS) on this apoptosis. Butyric acid significantly inhibited the anti-CD3 monoclonal antibody- and concanavalin A-induced proliferative responses in a dose-dependent fashion. This inhibition of PBMC growth by butyric acid depended on apoptosis in vitro. It was characterized by internucleosomal DNA digestion and revealed by gel electrophoresis followed by a colorimetric DNA fragmentation assay to occur in a concentration-dependent fashion. Butyric acid-induced PBMC apoptosis was accompanied by caspase-3 protease activity but not by caspase-1 protease activity. LPS potentiated butyric acid-induced PBMC apoptosis in a dose-dependent manner. Flow-cytometric analysis revealed that LPS increased the proportion of sub-G1 cells and the number of late-stage apoptotic cells induced by butyric acid. Annexin V binding experiments with fractionated subpopulations of PBMC in flow cytometory revealed that LPS accelerated the butyric acid-induced CD3+-T-cell apoptosis followed by similar levels of both CD4+- and CD8+-T-cell apoptosis. The addition of LPS to PBMC cultures did not cause DNA fragmentation, suggesting that LPS was unable to induce PBMC apoptosis directly. These data suggest that LPS, in combination with butyric acid, potentiates CD3+ PBMC T-cell apoptosis and plays a role in the apoptotic depletion of CD4+ and CD8+ cells. PMID:9864191

  4. Human macrophage colony-stimulating factor induces macrophage colonies after L-phenylalanine methylester treatment of human marrow.

    PubMed

    Rosenfeld, C S; Evans, C; Shadduck, R K

    1990-11-01

    Macrophage-colony stimulating factor (M-CSF) has well-known effects on murine bone marrow, but its colony stimulating activity for human bone marrow is controversial. After treatment of human bone marrow with L-phenylalanine methylester (PME), macrophage-colonies (CFU-M) were induced by M-CSF in a dose-dependent fashion. The optimal concentration of recombinant human-macrophage colony stimulating factor (rhM-CSF) was 1,000 U/mL. Purified human urine M-CSF had colony stimulating activity similar to rhM-CSF. Further studies were performed to determine the factors responsible for the enhanced CFU-M formation from PME treated marrow. Compared with nylon wool and carbonyl iron monocyte depletion methods, PME eliminated significantly more monocytes and myeloid cells. This observation suggested that these cells may release hematopoietic inhibitory factors for CFU-M. Low concentrations (1%) but not normal (10%) concentrations of blood monocytes were inhibitory (mean inhibition, 48%) to CFU-M. High concentrations of monocytes (50%) augmented CFU-M colonies. HL-60 conditioned media was used to simulate secretory products of early myeloid cells. HL-60 conditioned media (1%) inhibited CFU-M formation but not granulocyte macrophage or granulocyte colonies. We conclude that M-CSF has colony stimulating activity for human marrow that can be recognized after removal of inhibitory cells by PME treatment. PMID:2224128

  5. Individualized treatment with transcranial direct current stimulation in patients with chronic non-fluent aphasia due to stroke

    PubMed Central

    Shah-Basak, Priyanka P.; Norise, Catherine; Garcia, Gabriella; Torres, Jose; Faseyitan, Olufunsho; Hamilton, Roy H.

    2015-01-01

    While evidence suggests that transcranial direct current stimulation (tDCS) may facilitate language recovery in chronic post-stroke aphasia, individual variability in patient response to different patterns of stimulation remains largely unexplored. We sought to characterize this variability among chronic aphasic individuals, and to explore whether repeated stimulation with an individualized optimal montage could lead to persistent reduction of aphasia severity. In a two-phase study, we first stimulated patients with four active montages (left hemispheric anode or cathode; right hemispheric anode or cathode) and one sham montage (Phase 1). We examined changes in picture naming ability to address (1) variability in response to different montages among our patients, and (2) whether individual patients responded optimally to at least one montage. During Phase 2, subjects who responded in Phase 1 were randomized to receive either real-tDCS or to receive sham stimulation (10 days); patients who were randomized to receive sham stimulation first were then crossed over to receive real-tDCS (10 days). In both phases, 2 mA tDCS was administered for 20 min per real-tDCS sessions and patients performed a picture naming task during stimulation. Patients' language ability was re-tested after 2-weeks and 2-months following real and sham tDCS in Phase 2. In Phase 1, despite considerable individual variability, the greatest average improvement was observed after left-cathodal stimulation. Seven out of 12 subjects responded optimally to at least one montage as demonstrated by transient improvement in picture-naming. In Phase 2, aphasia severity improved at 2-weeks and 2-months following real-tDCS but not sham. Despite individual variability with respect to optimal tDCS approach, certain montages result in consistent transient improvement in persons with chronic post-stroke aphasia. This preliminary study supports the notion that individualized tDCS treatment may enhance aphasia

  6. Dihydrotestosterone stimulates amino acid uptake and the expression of LAT2 in mouse skeletal muscle fibres through an ERK1/2-dependent mechanism.

    PubMed

    Hamdi, M M; Mutungi, G

    2011-07-15

    Dihydrotestosterone (DHT) has acute/non-genomic actions in adult mammalian skeletal muscles whose physiological functions are still poorly understood. Therefore, the primary aim of this study was to investigate the acute/non-genomic effects of DHT on amino acid uptake as well as the cellular signal transduction events underlying these actions in mouse fast- and slow-twitch skeletal muscle fibre bundles. 14C-Labelled amino acids were used to investigate the effects of DHT and testosterone (T) on amino acid uptake and pharmacological interventions were used to determine the cellular signal transduction events mediating these actions. While T had no effect on the uptake of isoleucine (Ile) and α-methylaminoisobutyric acid (MeAIB) in both fibre types, DHT increased their uptake in the fast-twitch fibre bundles. This effect was reversed by inhibitors of protein translation, the epidermal growth factor receptor (EGFR), system A, system L, mTOR and MEK. However, it was relatively insensitive to inhibitors of transcription, androgen receptors and PI3K/Akt. Additionally, DHT treatment increased the expression of LAT2 and the phosphorylation of the EGFR in the fast-twitch fibre bundles and that of ERK1/2, RSK1/2 and ATF2 in both fibre types. Also, it decreased the phosphorylation of eEF2 and increased the incorporation of Ile into proteins in both fibre types. Most of these effects were reversed by EGFR and MEK inhibitors. From these findings we suggest that another physiological function of the acute/non-genomic actions of DHT in isolated mammalian skeletal muscle fibres is to stimulate amino acid uptake. This effect is mediated through the EGFR and involves the activation of the MAPK pathway and an increase in LAT2 expression.

  7. Effect of Subliminal Stimulation of Symbiotic Fantasies on Behavior Modification Treatment of Obesity.

    ERIC Educational Resources Information Center

    And Others; Silverman, Lloyd H.

    1978-01-01

    Obese women were treated in behavior modification programs for overeating. Behavior programs were accompanied by subliminal stimulation and by symbiotic and control messages. The symbiotic condition gave evidence of enhancing weight loss. This finding supports the proposition that subliminal stimulation of symbiotic fantasies can enhance the…

  8. A new treatment for obstructive sleep apnea syndrome by electrical stimulation of submental region.

    PubMed

    Miki, H; Hida, W; Inoue, H; Takishima, T

    1988-01-01

    Loss of upper airway muscle tone during sleep has been thought to be responsible for obstructive apnea episodes. To examine the effect of electrical stimulation of the submental region on sleep apnea episodes, patients with obstructive sleep apnea syndrome were polysomnographically studied during all-night session with and without stimulation.

  9. Cathepsin K in treatment monitoring following intravenous zoledronic acid

    PubMed Central

    JAHN, OLIVER; WEX, THOMAS; KLOSE, SILKE; KROPF, SIEGFRIED; ADOLF, DANIELA; PIATEK, STEFAN

    2014-01-01

    Cathepsin K (CatK) is mainly expressed by osteoclasts and plays an important role in bone resorption. As CatK is expressed and secreted by osteoclasts during active bone resorption, it may be a useful and specific biochemical marker of osteoclastic activity. Therefore, CatK serum levels were studied for monitoring the treatment of females with postmenopausal osteoporosis by zoledronic acid. The serum CatK levels were determined in nine postmenopausal females before and after 3, 6 and 12 months of treatment. The levels were significantly reduced after 3 and 6 months (P<0.05), whereas they returned to baseline after 1 year. Taken together, the serum level of CatK may be suitable for monitoring anti-osteoporotic therapy in association with treatment response. PMID:25279169

  10. Atrial ganglionated plexi stimulation may be an effective therapeutic tool for the treatment of heart failure.

    PubMed

    He, Bo; Lu, Zhibing; Jiang, Hong

    2013-11-01

    An autonomic imbalance, i.e., increased sympathetic tone and/or decreased parasympathetic tone is a critical characteristic of heart failure, which is associated with progressive ventricular remodeling, ventricular arrhythmia generation and disease progression. Increasing cardiac parasympathetic tone by vagus nerve stimulation has been shown to significantly improve heart failure symptoms, hemodynamics, left ventricular function and quality of life. However, cervical surgery is needed to position vagal stimulation electrode and vagus nerve stimulation may also cause some undesired side effects. Our recent studies showed that ablation of the main atrial ganglionated plexi (GP) facilitated the occurrence of ventricular arrhythmias in acute myocardial ischemic heart while low-intensity atrial GP stimulation inhibited the occurrence of ventricular arrhythmias during acute myocardial ischemia and ischemia reperfusion. Based on these results, we hypothesize that atrial GP stimulation may ameliorate autonomic dysfunction in heart failure, inhibit heart failure progression and improve heart failure prognosis.

  11. Intravenous infusion of L-isomers of phenylalanine and tryptophan stimulate gastric acid secretion at physiologic plasma concentrations in normal subjects and after parietal cell vagotomy.

    PubMed Central

    McArthur, K E; Isenberg, J I; Hogan, D L; Dreier, S J

    1983-01-01

    To determine whether intravenous infusion of individual amino acids stimulated gastric acid secretion in man, graded doses of phenylalanine, tryptophan, glycine, alanine, histidine, and NaCl control were infused on separate days in nine healthy subjects. Intravenous infusion of phenylalanine and tryptophan significantly stimulated gastric acid secretion to 50 and 52%, respectively, of the acid secretory response to intragastric peptone. Intravenous alanine and histidine were without effect, whereas glycine produced a slight response. Serum gastrin concentrations did not significantly change during intravenous amino acid infusion, except in response to 0.1 M phenylalanine. However, the increase in serum gastrin occurred 2 h after acid secretion had significantly increased in response to the 0.025 M phenylalanine infusion. Plasma amino acid concentrations were measured during intravenous amino acid infusion and in response to a steak meal in five of the subjects. At a time when acid secretion was significantly increased during intravenous infusion of phenylalanine and tryptophan, plasma amino acids were similar to, or less than, that observed after the steak meal, suggesting that circulating levels of these three amino acids have a physiologic effect on gastric secretion in man. Intravenous infusion of a combination of graded doses of phenylalanine plus a continuous infusion of 0.01 M tryptophan shifted the dose-response curve to the left and resulted in a significantly greater response than to either amino acid alone. In five subjects with parietal cell vagotomy, intravenous phenylalanine and tryptophan stimulated acid secretion, whereas histidine was without effect, similar to normal subjects. These studies indicate that intravenous infusion of small amounts of phenylalanine (0.025 M, 3.1 mmol/h) and tryptophan (0.01 M, 1.25 mmol/h) stimulated gastric acid secretion at plasma concentrations similar to those observed after a steak meal, suggesting a physiologic role

  12. Osteogenesis differentiation of human periodontal ligament cells by CO2 laser-treatment stimulating macrophages via BMP2 signalling pathway

    NASA Astrophysics Data System (ADS)

    Hsieh, Wen-Hui; Chen, Yi-Jyun; Hung, Chi-Jr; Huang, Tsui-Hsien; Kao, Chia-Tze; Shie, Ming-You

    2014-11-01

    Immune reactions play an important role in determining the biostimulation of bone formation, either in new bone formation or inflammatory fibrous tissue encapsulation. Macrophage cell, the important effector cells in the immune reaction, which are indispensable for osteogenesis and their heterogeneity and plasticity, render macrophages a primer target for immune system modulation. However, there are very few studies about the effects of macrophage cells on laser treatment-regulated osteogenesis. In this study, we used CO2 laser as a model biostimulation to investigate the role of macrophage cells on the CO2 laser stimulated osteogenesis. Bone morphogenetic protein 2 (BMP2) was also significantly up regulated by the CO2 laser stimulation, indicating that macrophage may participate in the CO2 laser stimulated osteogenesis. Interestingly, when laser treatment macrophage-conditioned medium were applied to human periodontal ligament cells (hPDLs), the osteogenesis differentiation of hPDLs was significantly enhanced, indicating the important role of macrophages in CO2 laser-induced osteogenesis. These findings provided valuable insights into the mechanism of CO2 laser-stimulated osteogenic differentiation, and a strategy to optimize the evaluation system for the in vitro osteogenesis capacity of laser treatment.

  13. Mineral phosphate solubilization by Streptomyces sp. CTM396 involves the excretion of gluconic acid and is stimulated by humic acids.

    PubMed

    Farhat, Mounira Ben; Boukhris, Ines; Chouayekh, Hichem

    2015-03-01

    The actinomycetes isolates (128) which were taken from agricultural soil samples and collected near a rock phosphate processing unit were screened for mineral phosphate-solubilizing (MPS) ability. A significant MPS activity was observed for 30 isolates on various phosphate sources when grown in the National Botanical Research Institute's phosphate broth. CTM396 and CTM397 strains which showed the highest MPS abilities were identified by 16S rDNA sequencing as members of the genus Streptomyces. Their MPS activity was proved to be concomitant with a drop in pH due to the secretion of gluconic acid (GA). This was correlated with the simultaneous detection by PCR of genes gdh [encoding the glucose dehydrogenase (GDH) responsible for GA production from glucose] and pqq (involved in biosynthesis of the pyrroloquinoline quinone cofactor of GDH), as well as the highlighting of GHD enzyme activity, for the first time in a Streptomyces sp. strain producing GA. Furthermore, the 0.05% of humic acids proved to have a stimulatory effect on the growth and the ability of CTM396 to solubilize Gafsa rock phosphate. According to this study, it is possible to use humic acids and Gafsa rock phosphate in association with spores of ad hoc Streptomyces strains as natural and efficient amendments to improve plant growth with no need of costly and pollutant transformation of Gafsa rock phosphate.

  14. Mineral phosphate solubilization by Streptomyces sp. CTM396 involves the excretion of gluconic acid and is stimulated by humic acids.

    PubMed

    Farhat, Mounira Ben; Boukhris, Ines; Chouayekh, Hichem

    2015-03-01

    The actinomycetes isolates (128) which were taken from agricultural soil samples and collected near a rock phosphate processing unit were screened for mineral phosphate-solubilizing (MPS) ability. A significant MPS activity was observed for 30 isolates on various phosphate sources when grown in the National Botanical Research Institute's phosphate broth. CTM396 and CTM397 strains which showed the highest MPS abilities were identified by 16S rDNA sequencing as members of the genus Streptomyces. Their MPS activity was proved to be concomitant with a drop in pH due to the secretion of gluconic acid (GA). This was correlated with the simultaneous detection by PCR of genes gdh [encoding the glucose dehydrogenase (GDH) responsible for GA production from glucose] and pqq (involved in biosynthesis of the pyrroloquinoline quinone cofactor of GDH), as well as the highlighting of GHD enzyme activity, for the first time in a Streptomyces sp. strain producing GA. Furthermore, the 0.05% of humic acids proved to have a stimulatory effect on the growth and the ability of CTM396 to solubilize Gafsa rock phosphate. According to this study, it is possible to use humic acids and Gafsa rock phosphate in association with spores of ad hoc Streptomyces strains as natural and efficient amendments to improve plant growth with no need of costly and pollutant transformation of Gafsa rock phosphate. PMID:25743071

  15. A randomized trial of concurrent smoking-cessation and substance use disorder treatment in stimulant-dependent smokers

    PubMed Central

    Winhusen, Theresa M.; Brigham, Gregory S.; Kropp, Frankie; Lindblad, Robert; Gardin, John G.; Penn, Pat; Hodgkins, Candace; Kelly, Thomas M.; Douaihy, Antoine; McCann, Michael; Love, Lee D.; DeGravelles, Eliot; Bachrach, Ken; Sonne, Susan C.; Hiott, Bob; Haynes, Louise; Sharma, Gaurav; Lewis, Daniel F.; VanVeldhuisen, Paul; Theobald, Jeff; Ghitza, Udi

    2014-01-01

    Objective To evaluate the impact of concurrent substance use disorder (SUD) and nicotine-dependence treatment for stimulant-dependent patients. Method A randomized, 10-week trial with follow-up at 3 and 6 months post-smoking quit date conducted at 12 SUD treatment programs between February 2010 and July 2012. Adults, meeting DSM-IV-TR criteria for cocaine and/or methamphetamine-dependence and interested in quitting smoking were randomized to treatment as usual (TAU; n=271) or TAU with smoking-cessation treatment (TAU+SCT, n=267). All participants received SUD TAU. TAU+SCT participants received weekly individual smoking cessation counseling and extended-release (XL) bupropion (300 mg/day) during weeks 1–10. During post-quit treatment (weeks 4–10), TAU+SCT participants received a nicotine inhaler and contingency management for smoking abstinence. Weekly proportion of stimulant-abstinent participants during the treatment phase, as assessed by urine drug screens and self-report, was the primary outcome. Secondary measures included other substance/nicotine use outcomes and treatment attendance. Results There were no significant treatment effects on stimulant-use outcomes, as measured by the primary outcome and stimulant-free days, on drug-abstinence, or on attendance. TAU+SCT, relative to TAU, participants had significantly better outcomes for drug-free days at 6-month follow-up (X2(1)=4.09, p<.05), with a decrease in drug-free days from baseline of −1.3% in TAU+SCT and of −7.6% in TAU. TAU+SCT, relative to TAU, participants had significantly better outcomes on smoking point-prevalence abstinence (25.5% vs. 2.2%; X2(1)=44.69, p<.001; OR=18.2). Conclusions These results suggest that providing smoking-cessation treatment to illicit stimulant-dependent patients in outpatient SUD treatment will not worsen, and may enhance, abstinence from non-nicotine substance use. PMID:24345356

  16. Synergy of interleukin 1 and granulocyte colony-stimulating factor: in vivo stimulation of stem-cell recovery and hematopoietic regeneration following 5-fluorouracil treatment of mice

    SciTech Connect

    Moore, M.A.S.; Warren, D.J.

    1987-10-01

    The human bladder carcinoma cell line 5637 produces hematopoietic growth factors (granulocyte and granulocyte/macrophage colony-stimulating factors (G-CSF and GM-CSF)) and hemopoietin 1, which synergizes with CSFs to stimulate colony formation by primitive hematopoietic stem cells in 5-fluorouracil-treated mouse bone marrow. Molecular and functional properties of hemopoietin 1 identified it as identical to interleukin 1..cap alpha.. (IL-1..cap alpha..). When bone marrow cells from 5-fluorouracil-treated mice were cultured in suspension for 7 days with recombinant human IL-1..cap alpha.. and/or G-CSF, it was found that the two factors synergized to enhance recovery of myelopoietic cells and colony-forming cells of both high and low proliferative potential. G-CSF alone did not sustain these populations, but the combination had greater-than-additive stimulating capacity. In vivo, 5-fluorouracil (150 mg/kg) produced profound myelosuppression and delayed neutrophil regeneration for up to 2 weeks in C3H/HeJ mice. Daily administration of recombinant human G-CSF or human IL-1..cap alpha.. accelerated recovery of stem cells, progenitor cells, and blood neutrophils by up to 4 days in 5-fluorouracil-treated C3H/HeJ and B6D2F/sub 1/ mice. The combination of IL-1..cap alpha.. and G-CSF acted synergistically, reducing neutropenia and accelerating recovery of normal neutrophil numbers by up to 7 days. These results indicate the possible therapeutic potential of combination therapy with IL-1 and hematopoietic growth factors such as G-CSF in the treatment of chemotherapy- or radiation-induced myelosuppression.

  17. Examining Longitudinal Stimulant Use and Treatment Attendance as Parallel Outcomes in Two Contingency Management Randomized Clinical Trials.

    PubMed

    McPherson, Sterling; Brooks, Olivia; Barbosa-Leiker, Celestina; Lederhos, Crystal; Lamp, Amanda; Murphy, Sean; Layton, Matthew; Roll, John

    2016-02-01

    The primary aim of this study was to examine stimulant use and longitudinal treatment attendance in one 'parallel outcomes' model in order to determine how these two outcomes are related to one another during treatment, and to quantify how the intervention impacts these two on- and off-target outcomes differently. Data came from two multi-site randomized clinical trials (RCTs) of contingency management (CM) that targeted stimulant use. We used parallel multilevel modeling to examine the impact of multiple pre-specified covariates, including selected Addiction Severity Index (ASI) scores, age and sex, in addition to CM on concurrent attendance and stimulant use in two separate analyses, i.e., one per trial. In one trial, CM was positively associated with attending treatment throughout the trial (β=0.060, p<0.05). In the second trial, CM predicted negative urinalysis ((-)UA) over the 12-week treatment period (β=0.069, p<0.05). In both trials, there was a significant, positive relationship between attendance and (-)UA submission, but in the first trial a (-)UA at both baseline and over time was related to attendance over time (r=0.117; r=0.013, respectively) and in the second trial, a (-)UA submission at baseline was associated with increased attendance over time (r=0.055). These findings indicate that stimulant use and treatment attendance over time are related but distinct outcomes that, when analyzed simultaneously, portray a more informative picture of their predictors and the separate trajectories of each. This 'indirect reinforcement' between two clinically meaningful on-target (directly reinforced behavior) and off-target (indirectly reinforced behavior) outcomes is in need of further examination in order to fully exploit the potential clinical benefits that could be realized in substance use disorder treatment trials.

  18. Examining Longitudinal Stimulant Use and Treatment Attendance as Parallel Outcomes in Two Contingency Management Randomized Clinical Trials.

    PubMed

    McPherson, Sterling; Brooks, Olivia; Barbosa-Leiker, Celestina; Lederhos, Crystal; Lamp, Amanda; Murphy, Sean; Layton, Matthew; Roll, John

    2016-02-01

    The primary aim of this study was to examine stimulant use and longitudinal treatment attendance in one 'parallel outcomes' model in order to determine how these two outcomes are related to one another during treatment, and to quantify how the intervention impacts these two on- and off-target outcomes differently. Data came from two multi-site randomized clinical trials (RCTs) of contingency management (CM) that targeted stimulant use. We used parallel multilevel modeling to examine the impact of multiple pre-specified covariates, including selected Addiction Severity Index (ASI) scores, age and sex, in addition to CM on concurrent attendance and stimulant use in two separate analyses, i.e., one per trial. In one trial, CM was positively associated with attending treatment throughout the trial (β=0.060, p<0.05). In the second trial, CM predicted negative urinalysis ((-)UA) over the 12-week treatment period (β=0.069, p<0.05). In both trials, there was a significant, positive relationship between attendance and (-)UA submission, but in the first trial a (-)UA at both baseline and over time was related to attendance over time (r=0.117; r=0.013, respectively) and in the second trial, a (-)UA submission at baseline was associated with increased attendance over time (r=0.055). These findings indicate that stimulant use and treatment attendance over time are related but distinct outcomes that, when analyzed simultaneously, portray a more informative picture of their predictors and the separate trajectories of each. This 'indirect reinforcement' between two clinically meaningful on-target (directly reinforced behavior) and off-target (indirectly reinforced behavior) outcomes is in need of further examination in order to fully exploit the potential clinical benefits that could be realized in substance use disorder treatment trials. PMID:26456717

  19. Physiotherapeutic stimulation: Early prevention of lymphedema following axillary lymph node dissection for breast cancer treatment

    PubMed Central

    SARRI, ALMIR JOSÉ; MORIGUCHI, SONIA MARTA; DIAS, ROGÉRIO; PERES, STELA VERZINHASSE; DA SILVA, EDUARDO TINÓIS; KOGA, KÁTIA HIROMOTO; ZUCCA MATTHES, ÂNGELO GUSTAVO; DOS SANTOS, MARCELO JOSÉ; DA ROCHA, EUCLIDES TIMÓTEO; HAIKEL, RAPHAEL LUIZ

    2010-01-01

    The aim of this study was to confirm the effectiveness of early physiotherapeutic stimulation for lymphatic flow progression in patients with breast cancer undergoing axillary dissection. This was a randomized experimental study on 22 patients who underwent lymphoscintigraphy in their arms on two different occasions, firstly without stimulation and secondly after randomization into two groups: without physiotherapeutic stimulation (WOPS; n=10) and with physiotherapeutic stimulation (WPS; n=12). The lymphoscintigraphy scan was performed with 99mTc-phytate administered into the second interdigital space of the hand, ipsilaterally to the dissected axilla, in three phases: dynamic, static, and delayed whole body imaging. Physiotherapeutic stimulation was carried out using Földi's technique. In both groups, images from the two examinations of each patient were compared. Flow progression was considered positive when, on the second examination, the radiopharmaceutical reached areas more distant from the injection site. Statistical analysis was used to evaluate frequencies, percentages and central trend measurements, and non-parametric tests were conducted. Descriptive analysis showed that the WPS and WOPS groups were similar in terms of mean age, weight, height, body mass index and number of lymph nodes removed. There were statistically significant associations between physiotherapeutic stimulation and radiopharmaceutical progression at all three phases of the study (p<0.0001). Early physiotherapeutic stimulation in breast cancer patients undergoing radical axillary dissection is effective, and can therefore be indicated as a preventive measure against lymphedema. PMID:23136607

  20. Modulation of the endocannabinoid system: vulnerability factor and new treatment target for stimulant addiction.

    PubMed

    Olière, Stéphanie; Joliette-Riopel, Antoine; Potvin, Stéphane; Jutras-Aswad, Didier

    2013-01-01

    Cannabis is one of the most widely used illicit substance among users of stimulants such as cocaine and amphetamines. Interestingly, increasing recent evidence points toward the involvement of the endocannabinoid system (ECBS) in the neurobiological processes related to stimulant addiction. This article presents an up-to-date review with deep insights into the pivotal role of the ECBS in the neurobiology of stimulant addiction and the effects of its modulation on addictive behaviors. This article aims to: (1) review the role of cannabis use and ECBS modulation in the neurobiological substrates of psychostimulant addiction and (2) evaluate the potential of cannabinoid-based pharmacological strategies to treat stimulant addiction. A growing number of studies support a critical role of the ECBS and its modulation by synthetic or natural cannabinoids in various neurobiological and behavioral aspects of stimulants addiction. Thus, cannabinoids modulate brain reward systems closely involved in stimulants addiction, and provide further evidence that the cannabinoid system could be explored as a potential drug discovery target for treating addiction across different classes of stimulants. PMID:24069004

  1. Foam for fracturing and acid stimulation. Part 2. Job control of a foam operation and a case history

    SciTech Connect

    Holcomb, D.L.

    1982-02-01

    This 3-part series of works is a comprehensive guide to the background, design and implementation of foamed stimulation for the treatment of oil and gas wells. It is adapted from the foam stimulation training manual developed and in use by Smith Energy Services. The manual is the product of 7 yr research and includes edited material already published, as well as information made available for the first time. This work should allow an interested party to acquire a basic understanding of the principles of foam and how it is utilized successfully as a stimulation medium. The following conclusions are made. Charts can be used onsite to maintain designed parameters during fracturing, if treating conditions are not as anticipated. Equations are used to determine wellhead treating pressures and changes in foam rate and quality. Increasing or decreasing the nitrogen rate maintains foam rate and quality. Increasing or decreasing the water rate maintains foam quality, but changes the frac rate correspondingly. Pumping rates can be changed and foam quality maintained, if there is a partial loss in nitrogen or water rate.

  2. Non-Invasive Brain Stimulation for Treatment of Focal Hand Dystonia: Update and Future Direction

    PubMed Central

    Cho, Hyun Joo; Hallett, Mark

    2016-01-01

    Focal hand dystonia (FHD) is characterized by excessive and unwanted muscle activation in both the hand and arm resulting in impaired performance in particular tasks. Understanding the pathophysiology of FHD has progressed significantly for several decades and this has led to consideration of other potential therapies such as non-invasive brain stimulation (NIBS). A number of studies have been conducted to develop new therapy for FHD using transcranial magnetic stimulation and transcranial direct current stimulation. In this paper, we review previous studies and describe the potential therapeutic use of NIBS for FHD. We also discuss the future direction of NIBS to treat FHD. PMID:27240806

  3. A review of sacral nerve stimulation parameters used in the treatment of faecal incontinence.

    PubMed

    Devane, Liam A; Evers, Judith; Jones, James F X; Ronan O'Connell, P

    2015-06-01

    Sacral nerve stimulation (SNS) was originally developed in the field of urinary incontinence. Without adaptation, it was subsequently applied to treat faecal incontinence. SNS has now become a first line therapy for this socially disabling condition, however the mechanism of action is unknown. This review examines the evidence for stimulation parameters currently used for SNS in humans and considers the potential electrophysiological effects of changing these parameters. However, without a proper understanding of the physiology of SNS, changing stimulation parameters remains empirical. PMID:25623489

  4. Spinal cord stimulation for treatment of the pain associated with hereditary multiple osteochondromas

    PubMed Central

    Mirpuri, Ravi G; Brammeier, Jereme; Chen, Hamilton; Hsu, Frank PK; Chiu, Vi K; Chang, Eric Y

    2015-01-01

    Objective Hereditary multiple osteochondromas (HMO) usually presents with neoplastic lesions throughout the skeletal system. These lesions frequently cause chronic pain and are conventionally treated with surgical resection and medication. In cases where conventional treatments have failed, spinal cord stimulation (SCS) could be considered as a potential option for pain relief. The objective of this case was to determine if SCS may have a role in treating pain secondary to neoplastic lesions from HMO. Case presentation We report a 65-year-old female who previously received both surgical and pharmacological interventions for treating HMO neoplastic pain in the lumbar, pelvis, femur, and tibial regions. These interventions either failed to offer significant pain relief or caused excessive lethargy. A SCS trial was then offered with a dual 16-contact lead trial leading to 70%–80% improvement in pain from baseline and 85% reduction in oxycodone IR intake. This was followed by permanent implantation of two 2×8 contact paddle leads (T7–T8 and T9–T10 interspaces). After 8-week follow-up, settings were further optimized resulting in an additional 30% improvement in pain compared to last visit. At 6-month follow-up, the patient reported continued pain relief. Conclusion This case demonstrates the first successful use of SCS to treat both HMO and nonmalignant neoplastic-related pain. The patient reported pain improvement from baseline, reduced pain medication requirements, and subjective improvement in quality of life. Additionally, this case demonstrates the potential advantage of trialing multiple painful areas with a 16-contact lead in order to avoid multiple trials and placement. PMID:26316806

  5. Combined treatment with dabrafenib and trametinib with immune-stimulating antibodies for BRAF mutant melanoma.

    PubMed

    Homet Moreno, Blanca; Mok, Stephen; Comin-Anduix, Begonya; Hu-Lieskovan, Siwen; Ribas, Antoni

    2016-07-01

    The combination of targeted therapy with BRAF and MEK inhibitors has become the standard of care in patients with BRAF (V600E) mutant melanoma, but responses are not durable. In addition, the impressive clinical benefits with anti-PD-1 and anti-PD-L1 antibodies (Ab) in patients with heavily pretreated metastatic melanoma and the synergistic effect of dabrafenib, trametinib and anti-PD-1 compared with single therapy alone groups support the idea that combining dabrafenib, trametinib and immunotherapy based on PD-1 blockade could be an interesting approach in the treatment of metastatic melanoma. With our mouse model of syngeneic BRAF (V600E) driven melanoma (SM1), we tested whether the addition of an immunostimulatory Ab targeting CD137 (4-1BB) and/or CD134 (OX40) would enhance the antitumor effect of dabrafenib, trametinib and anti-PD-1 or anti-PD-L1 therapy. In vitro studies showed that the combination group of dabrafenib, trametinib and anti-PD-1 increases CD8(+) tumor infiltrating lymphocytes (TILs), as well as CD4(+) T cells and tumor-associated macrophages (TAMs). An upregulation of PD-L1 was observed in the combination of dabrafenib, trametinib and anti-PD-1 therapy. Combination of dabrafenib, trametinib and anti-PD-1, with either anti-CD137 or anti-CD134, showed a superior antitumor effect, but the five-agent combination was not superior to the four-agent combinations. In conclusion, the combination of dabrafenib, trametinib, anti-PD1 or anti-PD-L1 therapy results in robust antitumor activity, which is further improved by adding the immune-stimulating Ab anti-CD137 or anti-CD134. Our findings support the testing of these combinations in patients with BRAF (V600E) mutant metastatic melanoma.

  6. Combined treatment with dabrafenib and trametinib with immune-stimulating antibodies for BRAF mutant melanoma.

    PubMed

    Homet Moreno, Blanca; Mok, Stephen; Comin-Anduix, Begonya; Hu-Lieskovan, Siwen; Ribas, Antoni

    2016-07-01

    The combination of targeted therapy with BRAF and MEK inhibitors has become the standard of care in patients with BRAF (V600E) mutant melanoma, but responses are not durable. In addition, the impressive clinical benefits with anti-PD-1 and anti-PD-L1 antibodies (Ab) in patients with heavily pretreated metastatic melanoma and the synergistic effect of dabrafenib, trametinib and anti-PD-1 compared with single therapy alone groups support the idea that combining dabrafenib, trametinib and immunotherapy based on PD-1 blockade could be an interesting approach in the treatment of metastatic melanoma. With our mouse model of syngeneic BRAF (V600E) driven melanoma (SM1), we tested whether the addition of an immunostimulatory Ab targeting CD137 (4-1BB) and/or CD134 (OX40) would enhance the antitumor effect of dabrafenib, trametinib and anti-PD-1 or anti-PD-L1 therapy. In vitro studies showed that the combination group of dabrafenib, trametinib and anti-PD-1 increases CD8(+) tumor infiltrating lymphocytes (TILs), as well as CD4(+) T cells and tumor-associated macrophages (TAMs). An upregulation of PD-L1 was observed in the combination of dabrafenib, trametinib and anti-PD-1 therapy. Combination of dabrafenib, trametinib and anti-PD-1, with either anti-CD137 or anti-CD134, showed a superior antitumor effect, but the five-agent combination was not superior to the four-agent combinations. In conclusion, the combination of dabrafenib, trametinib, anti-PD1 or anti-PD-L1 therapy results in robust antitumor activity, which is further improved by adding the immune-stimulating Ab anti-CD137 or anti-CD134. Our findings support the testing of these combinations in patients with BRAF (V600E) mutant metastatic melanoma. PMID:27622011

  7. Evaluation and Treatment of Gastric Stimulator Failure in Patients With Gastroparesis

    PubMed Central

    Harrison, Nancy Salloum; Williams, Patrick A.; Walker, Micah R.; Nikitini, Yana; Helling, Thomas S.; Abell, Thomas L.; Lahr, Christopher J.

    2016-01-01

    Objective This study evaluates treatment of gastroparesis patients refractory to gastric electrical stimulation (GES) therapy with surgical replacement of the entire GES system. Summary Background Data Some patients who have symptomatic improvement with GES later develop recurrent symptoms. Some patients improve by simply altering pulse parameter settings. Others continue to have symptoms with maximized pulse parameters. For these patients, we have shown that surgical implantation of a new device and leads at a different gastric location will improve symptoms of gastroparesis. Methods This study evaluates 15 patients with recurrent symptoms after initial GES therapy who subsequently received a second GES system. Positive response to GES replacement therapy is evaluated by symptoms scores for vomiting, nausea, epigastric pain, early satiety, and bloating using a modified Likert score system, 0 to 4. Results Total symptom scores improved for 12 of 15 patients with GES replacement surgery. Total score for the replacement group decreased from 17.3 ± 1.6 to 13.6 ± 3.7 with a difference of 3.6 (P value = .017). This score is compared with that of the control group with a preoperative symptom score of 15.8 ± 3.6 and postoperative score of 12.3 ± 3.5 with a difference of 3.5 (P value = .011). The control group showed a 20.3% decrease in mean total symptoms score, whereas the study group showed a 22.5% decrease in mean with an absolute reduction of 2.2. Conclusion Reimplantation of a GES at a new gastric location should be considered a viable option for patients who have initially failed GES therapy for gastroparesis. PMID:24056201

  8. Combined treatment with dabrafenib and trametinib with immune-stimulating antibodies for BRAF mutant melanoma

    PubMed Central

    Homet Moreno, Blanca; Mok, Stephen; Comin-Anduix, Begonya; Hu-Lieskovan, Siwen; Ribas, Antoni

    2016-01-01

    The combination of targeted therapy with BRAF and MEK inhibitors has become the standard of care in patients with BRAFV600E mutant melanoma, but responses are not durable. In addition, the impressive clinical benefits with anti-PD-1 and anti-PD-L1 antibodies (Ab) in patients with heavily pretreated metastatic melanoma and the synergistic effect of dabrafenib, trametinib and anti-PD-1 compared with single therapy alone groups support the idea that combining dabrafenib, trametinib and immunotherapy based on PD-1 blockade could be an interesting approach in the treatment of metastatic melanoma. With our mouse model of syngeneic BRAFV600E driven melanoma (SM1), we tested whether the addition of an immunostimulatory Ab targeting CD137 (4-1BB) and/or CD134 (OX40) would enhance the antitumor effect of dabrafenib, trametinib and anti-PD-1 or anti-PD-L1 therapy. In vitro studies showed that the combination group of dabrafenib, trametinib and anti-PD-1 increases CD8+ tumor infiltrating lymphocytes (TILs), as well as CD4+ T cells and tumor-associated macrophages (TAMs). An upregulation of PD-L1 was observed in the combination of dabrafenib, trametinib and anti-PD-1 therapy. Combination of dabrafenib, trametinib and anti-PD-1, with either anti-CD137 or anti-CD134, showed a superior antitumor effect, but the five-agent combination was not superior to the four-agent combinations. In conclusion, the combination of dabrafenib, trametinib, anti-PD1 or anti-PD-L1 therapy results in robust antitumor activity, which is further improved by adding the immune-stimulating Ab anti-CD137 or anti-CD134. Our findings support the testing of these combinations in patients with BRAFV600E mutant metastatic melanoma. PMID:27622011

  9. Treatment results of high dose cabergoline as an adjuvant therapy in six patients with established severe ovarian hyper stimulation syndrome

    PubMed Central

    Saharkhiz, Nasrin; Akbari Sene, Azadeh; Salehpour, Saghar; Tamimi, Maryam; Vasheghani Farahani, Masoumeh; Sheibani, Kourosh

    2014-01-01

    Background: The beneficial role of cabergoline as a prophylactic agent to prevent ovarian hyper stimulation syndrome (OHSS) among high-risk patients has been demonstrated in previous studies. But data for its role as a treatment for established severe OHSS is still limited. We represent the treatment results of high dose oral cabergoline in management of six patients after the syndrome is established. Case: High-dose oral cabergoline (1 mg daily for eight days) was prescribed as an adjuvant to symptomatic treatment for six hospitalized patients with established severe OHSS following infertility treatment cycles. In two cases OHSS resolved rapidly despite the occurrence of ongoing pregnancy. Conclusion: Considering the treatment outcomes of our patients, high dose cabergoline did not eliminate the need for traditional treatments, but it was a relatively effective and safe therapy in management of established severe OHSS, and prevented the increase in its severity following the occurrence of pregnancy. PMID:25469130

  10. Ricinoleic acid stimulation of active anion secretion in colonic mucosa of the rat.

    PubMed Central

    Racusen, L C; Binder, H J

    1979-01-01

    Perfusion of the colon with ricinoleic acid produces fluid and electrolyte accumulation. The mechanism of these changes in water and electrolyte movement is uknown. These studies were designed to determine whether ricinoleic acid effects active ion transport across isolated rat colonic mucosa. 0.5 mM Na ricinoleate produced significant increases in potential difference (3.8 +/- 0.5 mV) and short-circuit current (Isc) (99.2 +/- 10.1 muA/cm2). The increases in Isc produced by Na ricinoleate were inhibited by both removal of bicarbonate and chloride and by the presence of theophylline. The hydroxy fatty acid also resulted in a significant decrease in net Na absorption from 4.7 +/- 0.8 to 0.1 +/- 0.7 mueq/h cm2 and reversed net Cl transport from absorption (+ 4.5 +/- 0.9) to secretion (-2.2 +/- mueq/h cm2). In parallel studies 0.5 mM Na ricinoleate increased mucosal cyclic AMP content by 58%. The concentrations of Na ricinoleate required to produce detectable and maximal increases in both Isc and cyclic AMP were the same. These results provide evidence in support of the concept that hydroxy fatty acid-induced fluid and electrolyte accumulation is driven by an active ion secretory process. PMID:220281

  11. Glucocorticoid-dependent induction of interleukin-6 receptor expression in human hepatocytes facilitates interleukin-6 stimulation of amino acid transport.

    PubMed Central

    Fischer, C P; Bode, B P; Takahashi, K; Tanabe, K K; Souba, W W

    1996-01-01

    OBJECTIVE: The authors studied the effects of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) on glutamine and alanine transport in isolated human hepatocytes. They also evaluated the role of dexamethasone in modulating this response and its effects on the expression of the plasma membrane high-affinity IL-6 receptor. SUMMARY BACKGROUND DATA: Animal studies indicate that cytokines are important mediators of the increased hepatic amino acid uptake that occurs during cancer and sepsis, but studies in human tissues are lacking. The control of transport by cytokines and cytokine receptor expression in the liver may provide a mechanism by which hepatocytes can modulate amino acid availability during catabolic disease states. METHODS: Human hepatocytes were isolated from wedge biopsy specimens and plated in 24-well trays. Interleukin-6 and TNF-alpha, in combination with the synthetic glucocorticoid dexamethasone, were added to hepatocytes in culture, and the transport of radiolabeled glutamine and alanine was measured. Fluorescent-activated cell sorter (FACS) analysis was used to study the effects of dexamethasone on IL-6 receptor number in the well-differentiated human hepatoma HepG2. RESULTS: Both IL-6 and TNF-alpha exerted a small stimulatory effect on alanine and glutamine transport. Dexamethasone alone did not alter transport rates, but pretreatment of cells augmented the effects of both cytokines on carrier-mediated amino acid uptake. Dexamethasone pretreatment and a combination of IL-6 and TNF-alpha resulted in a greater than twofold increase in transport activity. Fluorescent-activated cell sorter analysis demonstrated that dexamethasone induced a threefold increase in the expression of high-affinity IL-6 receptors. CONCLUSIONS: Interleukin-6 and TNF-alpha work coordinately with glucocorticoids to stimulate amino acid uptake in human hepatocytes. Dexamethasone exerts a permissive effect on cytokine-mediated increases in transport by increasing IL

  12. [PREPARATIONS OF PAMIDRONOVIC ACID IN COMPLEX TREATMENT ON OSTEOGENESIS IMPERFECTA].

    PubMed

    Zyma, A M; Guk, Yu M; Magomedov, O M; Gayko, O G; Kincha-Polishchuk, T A

    2015-07-01

    Modern view of drug therapy in the complex treatment of orthopedic manifestations of osteogenesis imperfecta (OI) was submitted. Developed and tested system of drug correction of structural and functional state of bone tissue (BT) using drugs pamidronovic acid, depending on osteoporosis severity and type of disease. Such therapy is appropriate to apply both independently and in conjunction with surgery to correct deformations of long bones of the lower extremities. Effectiveness and feasibility of the proposed methods of drug therapy was proved, most patients resume features walking and support. PMID:26591224

  13. Nitric-phosphoric acid treatment of TRU wastes

    SciTech Connect

    Smith, J.R.; Pierce, R.A.; Sturcken, E.F.

    1993-09-30

    A general process is being developed for the treatment of solid TRU and hazardous organic waste. Experimental data indicates that 100 lb/hr of aliphatic organic (plastics) and 1,000 lb/hr of non-aliphatic organic compounds can be quantitatively oxidized in a 1,000 gallon reaction vessel. The process uses dilute nitric acid in a concentrated phosphoric acid media as the main oxidant for the organic compounds. Phosphoric acid allows oxidation at temperatures up to 200{degrees}C and is relatively non-corrosive on 304-L stainless steel, especially at room temperature. Many organic materials have been completely oxidized to CO{sub 2}, CO, and inorganic acids in a 0.1M HNO{sub 3}/14.8M H{sub 3}PO{sub 4} solution. Addition of 0.001M Pd{sup 2+} reduces the CO to near 1% of the released carbon gases. To accomplish complete oxidation the solution temperature must be maintained above 130--150{degrees}C. Organic materials quantitatively destroyed include neoprene, cellulose, EDTA, TBP, tartaric acid, and nitromethane. The oxidation is usually complete in a few hours for soluble organic materials. The oxidation rate for non-aliphatic organic solids is moderately fast and surface area dependent. Polyethylene is quantitatively oxidized in 1.0M HNO{sub 3}/13.8M H{sub 3}PO{sub 4} solution while contained in pressure vessels heated with microwave energy. This is probably due to the high concentrations of NO{sub 2}{center_dot} obtained in the reaction environment.

  14. Evoked potentials and contingent negative variation during treatment of multiple sclerosis with spinal cord stimulation.

    PubMed Central

    Sedgwick, E M; Illis, L S; Tallis, R C; Thornton, A R; Abraham, P; El-Negamy, E; Docherty, T B; Soar, J S; Spencer, S C; Taylor, F M

    1980-01-01

    Cervical somatosensory evoked potentials, brainstem evoked potentials, visual evoked potentials, and the cerebral contingent negative variation were recorded in patients with definite multiple sclerosis before, during, and after spinal cord stimulation. Improvements were seen in the cervical somatosensory and brainstem evoked potentials but neither the visual evoked potential nor the contingent negative variation changed in association with spinal cord stimulation. The results indicate that spinal cord stimulation acts at spinal and brainstem levels and that the clinical improvements seen in patients are caused by an action at these levels rather than by any cerebral arousal or motivational effect. The evoked potentials were not useful in predicting which patients were likely to respond to stimulation. PMID:7354352

  15. Unilateral and bilateral MRI-targeted repetitive transcranial magnetic stimulation for treatment-resistant depression: a randomized controlled study

    PubMed Central

    Blumberger, Daniel M.; Maller, Jerome J.; Thomson, Lauren; Mulsant, Benoit H.; Rajji, Tarek K.; Maher, Missy; Brown, Patrick E.; Downar, Jonathan; Vila-Rodriguez, Fidel; Fitzgerald, Paul B.; Daskalakis, Zafiris J.

    2016-01-01

    Background Several factors may mitigate the efficacy of repetitive transcranial magnetic stimulation (rTMS) over sham rTMS in patients with treatment-resistant depression (TRD). These factors include unilateral stimulation (i.e., treatment of only the left dorsolateral prefrontal cortex [DLPFC]), suboptimal methods of targeting the DLPFC and insufficient stimulation intensity (based on coil-to-cortex distance). Methods We recruited patients with TRD between the ages of 18 and 85 years from a university hospital, and participants were randomized to receive sequential bilateral rTMS (600 pulses at 1 Hz followed by 1500 pulses at 10 Hz), unilateral high-frequency left (HFL)-rTMS (2100 pulses at 10 Hz) or sham rTMS for 3 or 6 weeks depending on treatment response. Stimulation was targeted with MRI localization over the junction of the middle and anterior thirds of the middle frontal gyrus, using 120% of the coil-to-cortex adjusted motor threshold. Our primary outcome of interest was the remission rate. Results A total of 121 patients participated in this study. The remission rate was significantly higher in the bilateral group than the sham group. The remission rate in the HFL-rTMS group was intermediate and did not differ statistically from the rate in the 2 other groups. There were no significant differences in reduction of depression scores among the 3 groups. Limitations The number of pulses used per session in the unilateral group was somewhat lower in our trial than in more recent trials, and the sham condition did not involve active stimulation. Conclusion Our findings suggest that sequential bilateral rTMS is superior to sham rTMS; however, adjusting for coil-to-cortex distance did not yield enhanced efficacy rates. PMID:27269205

  16. Device-based brain stimulation to augment fear extinction: implications for PTSD treatment and beyond.

    PubMed

    Marin, Marie-France; Camprodon, Joan A; Dougherty, Darin D; Milad, Mohammed R

    2014-04-01

    Conditioned fear acquisition and extinction paradigms have been widely used both in animals and humans to examine the neurobiology of emotional memory. Studies have also shown that patients suffering from posttraumatic stress disorder (PTSD) exhibit deficient extinction recall along with dysfunctional activation of the fear extinction network, including the ventromedial prefrontal cortex, amygdala, and hippocampus. A great deal of overlap exists between this fear extinction network and brain regions associated with symptom severity in PTSD. This suggests that the neural nodes of fear extinction could be targeted to reduce behavioral deficits that may subsequently translate into symptom improvement. In this article, we discuss potential applications of brain stimulation and neuromodulation methods, which, combined with a mechanistic understanding of the neurobiology of fear extinction, could be used to further our understanding of the pathophysiology of anxiety disorders and develop novel therapeutic tools. To this end, we discuss the following stimulation approaches: deep-brain stimulation, vagus nerve stimulation, transcranial direct current stimulation, and transcranial magnetic stimulation. We propose new translational research avenues that, from a systems neuroscience perspective, aim to expand our understanding of circuit dynamics and fear processing toward the practical development of clinical tools, to be used alone or in combination with behavioral therapies.

  17. Device-based brain stimulation to augment fear extinction: implications for PTSD treatment and beyond.

    PubMed

    Marin, Marie-France; Camprodon, Joan A; Dougherty, Darin D; Milad, Mohammed R

    2014-04-01

    Conditioned fear acquisition and extinction paradigms have been widely used both in animals and humans to examine the neurobiology of emotional memory. Studies have also shown that patients suffering from posttraumatic stress disorder (PTSD) exhibit deficient extinction recall along with dysfunctional activation of the fear extinction network, including the ventromedial prefrontal cortex, amygdala, and hippocampus. A great deal of overlap exists between this fear extinction network and brain regions associated with symptom severity in PTSD. This suggests that the neural nodes of fear extinction could be targeted to reduce behavioral deficits that may subsequently translate into symptom improvement. In this article, we discuss potential applications of brain stimulation and neuromodulation methods, which, combined with a mechanistic understanding of the neurobiology of fear extinction, could be used to further our understanding of the pathophysiology of anxiety disorders and develop novel therapeutic tools. To this end, we discuss the following stimulation approaches: deep-brain stimulation, vagus nerve stimulation, transcranial direct current stimulation, and transcranial magnetic stimulation. We propose new translational research avenues that, from a systems neuroscience perspective, aim to expand our understanding of circuit dynamics and fear processing toward the practical development of clinical tools, to be used alone or in combination with behavioral therapies. PMID:24634247

  18. Hypothalamic deep brain stimulation in the treatment of chronic cluster headache

    PubMed Central

    Leone, Massimo; Franzini, Angelo; Cecchini, Alberto Proietti; Broggi, Giovanni; Bussone, Gennaro

    2010-01-01

    Cluster headache (CH) is a short-lasting unilateral headache associated with ipsilateral craniofacial autonomic manifestations. A positron emission tomography (PET) study has shown that the posterior hypothalamus is activated during CH attacks, suggesting that hypothalamic hyperactivity plays a key role in CH pathophysiology. On this basis, stimulation of the ipsilateral posterior hypothalamus was hypothesized to counteract such hyperactivity to prevent intractable CH. Ten years after its introduction, hypothalamic stimulation has been proved to successfully prevent attacks in more than 60% of 58 hypothalamic implanted drug-resistant chronic CH patients. The implantation procedure has generally been proved to be safe, although it carries a small risk of brain haemorrhage. Long-term stimulation is safe, and nonsymptomatic impairment of orthostatic adaptation is the only noteworthy change. Microrecording studies will make it possible to better identify the target site. Neuroimaging investigations have shown that hypothalamic stimulation activates ipsilateral trigeminal complex, but with no immediate perceived sensation within the trigeminal distribution. Other studies on the pain threshold in chronically stimulated patients showed increased threshold for cold pain in the distribution of the first trigeminal branch ipsilateral to stimulation. These studies suggest that activation of the hypothalamus and of the trigeminal system are both necessary, but not sufficient to generate CH attacks. In addition to the hypothalamus, other unknown brain areas are likely to play a role in the pathophysiology of this illness. Hypothalamus implantation is associated with a small risk of intracerebral haemorrhage and must be performed by an expert neurosurgical team, in selected patients. PMID:21179610

  19. Treatment of vinasse from tequila production using polyglutamic acid.

    PubMed

    Carvajal-Zarrabal, Octavio; Nolasco-Hipólito, Cirilo; Barradas-Dermitz, Dulce Ma; Hayward-Jones, Patricia M; Aguilar-Uscanga, Ma Guadalupe; Bujang, Kopli

    2012-03-01

    Vinasse, the wastewater from ethanol distillation, is characterised by high levels of organic and inorganic matter, high exit process temperature (ca. 90°C) and low pH (3.0-4.5). In this study, the treatment of tequila vinasse was achieved by a flocculation-coagulation process using poly-γ-glutamic acid (PGA). Results showed that the use of PGA (250-300 ppm) combined with sodium hypochlorite and sand filtration managed to remove about 70% of the turbidity and reduced chemical oxygen demand (COD) by 79.5% with the extra benefit of colour removal. PGA showed its best flocculating activity at pH 2.5-3.5 and a temperature of 30-55°C. Such a treatment may be a solution for small tequila companies for which other solutions to deal with their vinasse may not be economically affordable.

  20. Treatment of vinasse from tequila production using polyglutamic acid.

    PubMed

    Carvajal-Zarrabal, Octavio; Nolasco-Hipólito, Cirilo; Barradas-Dermitz, Dulce Ma; Hayward-Jones, Patricia M; Aguilar-Uscanga, Ma Guadalupe; Bujang, Kopli

    2012-03-01

    Vinasse, the wastewater from ethanol distillation, is characterised by high levels of organic and inorganic matter, high exit process temperature (ca. 90°C) and low pH (3.0-4.5). In this study, the treatment of tequila vinasse was achieved by a flocculation-coagulation process using poly-γ-glutamic acid (PGA). Results showed that the use of PGA (250-300 ppm) combined with sodium hypochlorite and sand filtration managed to remove about 70% of the turbidity and reduced chemical oxygen demand (COD) by 79.5% with the extra benefit of colour removal. PGA showed its best flocculating activity at pH 2.5-3.5 and a temperature of 30-55°C. Such a treatment may be a solution for small tequila companies for which other solutions to deal with their vinasse may not be economically affordable. PMID:21600690

  1. Effect of folic acid plus glycine supplement on uterine prostaglandin and endometrial granulocyte-macrophage colony-stimulating factor expression during early pregnancy in pigs.

    PubMed

    Guay, Frédéric; Matte, J Jacques; Girard, Christiane L; Palin, Marie-France; Giguère, Alain; Laforest, Jean-Paul

    2004-01-15

    The objective was to determine the effects of folic acid+glycine supplement on uterine metabolism of prostaglandin and mRNA expression of endometrial granulocyte-macrophage colony-stimulating factor (GM-CSF) in nulliparous (NYL) and multiparous Yorkshire-Landrace (YL) sows, and in multiparous Meishan-Landrace sows (ML). In each of these three groups, sows were randomly assigned to two treatments: 15 ppm folic acid+0.6% glycine or no supplement. The dietary supplement was given from the estrus before mating to slaughter on Day 25 of pregnancy. At slaughter, endometrial tissue was collected to determine endometrial expression levels of GM-CSF mRNA, cyclooxygenase-1 (COX1) and -2 (COX2) and to evaluate in vitro endometrial secretion of prostaglandin E2 (PGE2) secretion. Allantoic fluid samples were also collected to determine the concentration of PGE2, prostaglandin F2alpha (PGF2alpha), estradiol-17beta (E2), progesterone (P4), and transforming-growth factor-beta2 (TGF-beta2). The allantoic contents of PGF2alpha, E2 and P4, and endometrial in vitro secretion of PGE2 were not significantly influenced by the folic acid+glycine supplement. The folic acid+glycine supplement tended (P<0.07) to increase allantoic content of PGE2 and TGF-beta2 in all sows and increased (P<0.05) endometrial expression of COX2, especially in NYL sows. The endometrial expression of COX1 was decreased (P<0.05) by folic acid+glycine supplement, especially in multiparous YL sows. The allantoic contents of PGE2 and PGF2alpha were not significantly affected by sow type. However, NYL sows had higher (P<0.05) endometrial in vitro secretion of PGE2 and allantoic content of P4 than multiparous YL and ML sows. The allantoic content of E2 was also higher (P<0.05) in NYL sows than in multiparous ML sows only. The allantoic content of TGF-beta2 was lower (P<0.05) in multiparous ML than in multiparous YL only sows. Finally, in YL and NYL sows, folic acid+glycine supplement decreased (P<0.05) the endometrial

  2. Delayed translocation of NGFI-B/RXR in glutamate stimulated neurons allows late protection by 9-cis retinoic acid

    SciTech Connect

    Mathisen, Gro H.; Fallgren, Asa B.; Strom, Bjorn O.; Boldingh Debernard, Karen A.; Mohebi, Beata U.; Paulsen, Ragnhild E.

    2011-10-14

    Highlights: {yields} NGFI-B and RXR translocate out of the nucleus after glutamate treatment. {yields} Arresting NGFI-B/RXR in the nucleus protects neurons from excitotoxicity. {yields} Late protection by 9-cis RA is possible due to a delayed translocation of NGFI-B/RXR. -- Abstract: Nuclear receptor and apoptosis inducer NGFI-B translocates out of the nucleus as a heterodimer with RXR in response to different apoptosis stimuli, and therefore represents a potential pharmacological target. We found that the cytosolic levels of NGFI-B and RXR{alpha} were increased in cultures of cerebellar granule neurons 2 h after treatment with glutamate (excitatory neurotransmitter in the brain, involved in stroke). To find a time-window for potential intervention the neurons were transfected with gfp-tagged expressor plasmids for NGFI-B and RXR. The default localization of NGFI-Bgfp and RXRgfp was nuclear, however, translocation out of the nucleus was observed 2-3 h after glutamate treatment. We therefore hypothesized that the time-window between treatment and translocation would allow late protection against neuronal death. The RXR ligand 9-cis retinoic acid was used to arrest NGFI-B and RXR in the nucleus. Addition of 9-cis retinoic acid 1 h after treatment with glutamate reduced the cytosolic translocation of NGFI-B and RXR{alpha}, the cytosolic translocation of NGFI-Bgfp observed in live neurons, as well as the neuronal death. However, the reduced translocation and the reduced cell death were not observed when 9-cis retinoic acid was added after 3 h. Thus, late protection from glutamate induced death by addition of 9-cis retinoic acid is possible in a time-window after apoptosis induction.

  3. Biomarkers for Success: Using Neuroimaging to Predict Relapse and Develop Brain Stimulation Treatments for Cocaine-Dependent Individuals.

    PubMed

    Hanlon, C A; Dowdle, L T; Jones, J L

    2016-01-01

    Cocaine dependence is one of the most difficult substance use disorders to treat. While the powerful effects of cocaine use on behavior were documented in the 19th century, it was not until the late 20th century that we realized cocaine use was affecting brain tissue and function. Following a brief introduction (Section 1), this chapter will summarize our current knowledge regarding alterations in neural circuit function typically observed in chronic cocaine users (Section 2) and highlight an emerging body of literature which suggests that pretreatment limbic circuit activity may be a reliable predictor of clinical outcomes among individuals seeking treatment for cocaine (Section 3). Finally, as the field of addiction research strives to translate this neuroimaging data into something clinically meaningful, we will highlight several new brain stimulation approaches which utilize functional brain imaging data to design noninvasive brain stimulation interventions for individuals seeking treatment for substance dependence disorders (Section 4). PMID:27503451

  4. Acid treatment of melanoma cells selects for invasive phenotypes.

    PubMed

    Moellering, Raymond E; Black, Kvar C; Krishnamurty, Chetan; Baggett, Brenda K; Stafford, Phillip; Rain, Matthew; Gatenby, Robert A; Gillies, Robert J

    2008-01-01

    Solid tumors become acidic due to hypoxia and upregulated glycolysis. We have hypothesized that this acidosis leads to more aggressive invasive behavior during carcinogenesis (Nature Reviews Cancer 4:891-899, 2004). Previous work on this subject has shown mixed results. While some have observed an induction of metastasis and invasion with acid treatments, others have not. To investigate this, human melanoma cells were acclimated to low pH growth conditions. Significant cell mortality occurred during acclimation, suggesting that acidosis selected for resistant phenotypes. Cells maintained under acidic conditions exhibited a greater range of motility, a reduced capacity to form flank tumors in SCID mice and did not invade more rapidly in vitro, compared to non-selected control cells. However, re-acclimation of these selected cells to physiological pH gave rise to stable populations with significantly higher in vitro invasion. These re-acclimated cells maintained higher invasion and higher motility for multiple generations. Transcriptomic analyses of these three phenotypes revealed significant differences, including upregulation of relevant pathways important for tissue remodeling, cell cycle control and proliferation. These results reinforce the hypothesis that acidosis promotes selection of stable, more invasive phenotypes, rather than inductive changes, which would be reversible.

  5. Electrical stimulation promotes nerve cell differentiation on polypyrrole/poly (2-methoxy-5 aniline sulfonic acid) composites

    NASA Astrophysics Data System (ADS)

    Liu, Xiao; Gilmore, Kerry J.; Moulton, Simon E.; Wallace, Gordon G.

    2009-12-01

    The purpose of this work was to investigate for the first time the potential biomedical applications of novel polypyrrole (PPy) composites incorporating a large polyelectrolyte dopant, poly (2-methoxy-5 aniline sulfonic acid) (PMAS). The physical and electrochemical properties were characterized. The PPy/PMAS composites were found to be smooth and hydrophilic and have low electrical impedance. We demonstrate that PPy/PMAS supports nerve cell (PC12) differentiation, and that clinically relevant 250 Hz biphasic current pulses delivered via PPy/PMAS films significantly promote nerve cell differentiation in the presence of nerve growth factor (NGF). The capacity of PPy/PMAS composites to support and enhance nerve cell differentiation via electrical stimulation renders them valuable for medical implants for neurological applications.

  6. Andrographolide attenuates interleukin-1β-stimulated upregulation of chemokine CCL5 and glial fibrillary acidic protein in astrocytes.

    PubMed

    Wong, Siew-Ying; Chan, Su-Jing; Wong, W S Fred; Wong, Peter T-H; Lai, Mitchell K P

    2014-08-20

    Andrographolide is a bioactive molecule isolated from Andrographis paniculata with anticancer and anti-inflammatory activities. In this study, we tested the effects of andrographolide on astrocyte-mediated neuroinflammatory responses. Cultured rat primary astrocytes were treated with proinflammatory cytokine interleukin 1β with or without pretreatment with andrographolide, and then processed for measurements of chemokine C-C motif ligand 5 (CCL5) and glial fibrillary acidic protein. The activation status of nuclear factor-κB activation that may underlie CCL5 upregulation was also measured. Andrographolide pretreatment was found to attenuate the upregulation of CCL5 and glial fibrillary basic protein as well as reduce the phosphorylation of nuclear factor-κB p65 and IκBα after interleukin 1β stimulation. These data suggest that andrographolide should be evaluated further as a therapeutic for central nervous system diseases characterized by astrocyte-mediated neuroinflammatory processes.

  7. Relationship between stimulated phosphatidic acid production and inositol lipid hydrolysis in intestinal longitudinal smooth muscle from guinea pig.

    PubMed

    Mallows, R S; Bolton, T B

    1987-06-15

    Accumulation of [32P]phosphatidic acid (PA) and total [3H]inositol phosphates (IPs) was measured in the longitudinal smooth-muscle layer from guinea-pig small intestine. Stimulation with carbachol, histamine and substance P produced increases in accumulation of both [3H]IPs and [32P]PA over the same concentration range. The increase in [32P]PA accumulation in response to carbachol (1 microM-0.1 mM) was inhibited in the presence of atropine (0.5 microM). Buffering the external free [Ca2+] to 10 nM did not prevent the carbachol-stimulated increase in [32P]PA accumulation. Carbachol and Ca2+ appear to act synergistically to increase accumulation of [32P]PA. In contrast, although incubation with noradrenaline also increased accumulation of [3H]IPs, no increase in accumulation of [32P]PA could be detected. These results suggest that an increase in formation of IPs is not necessarily accompanied by an increase in PA formation, and imply the existence of receptor-modulated pathways regulating PA concentrations other than by phospholipase-C-catalysed inositol phospholipid hydrolysis.

  8. Vaccenic and elaidic acid modify plasma and splenocyte membrane phospholipids and mitogen-stimulated cytokine production in obese insulin resistant JCR: LA-cp rats.

    PubMed

    Ruth, Megan R; Wang, Ye; Yu, Howe-Ming; Goruk, Susan; Reaney, Martin J; Proctor, Spencer D; Vine, Donna F; Field, Catherine J

    2010-02-01

    This study assessed the long-term effects of dietary vaccenic acid (VA) and elaidic acid (EA) on plasma and splenocyte phospholipid (PL) composition and related changes in inflammation and splenocyte phenotypes and cytokine responses in obese/insulin resistant JCR:LA-cp rats. Relative to lean control (Ctl), obese Ctl rats had higher serum haptoglobin and impaired T-cell-stimulated cytokine responses. VA and EA diets improved T-cell-stimulated cytokine production; but, only VA normalized serum haptoglobin. However, EA- and VA-fed rats had enhanced LPS-stimulated cytokine responses. The changes elicited by VA were likely due changes in essential fatty acid composition in PL; whereas EA-induced changes may due to direct incorporation into membrane PL.

  9. Tactile stimulation as a complementary treatment of temporomandibular disorders in patients with fibromyalgia syndrome. A pilot study.

    PubMed

    Adiels, Anne-Marie; Helkimo, Martti; Magnusson, Tomas

    2005-01-01

    Pain of long duration is a common suffering in modern man. One such pain condition is fibromyalgia syndrome (FMS). Opinions about what treatment regimen that are to be used in these patients are diverging, and many of the treatments suggested are not, or only poorly, scientifically investigated. The aim of this pilot investigation was to evaluate if FMS patients with signs and symptoms of temporomandibular disorders (TMDs) refractory to conservative TMD treatment would respond positively to tactile stimulation in respect of local and/or general symptoms. Ten female patients fulfilling the inclusion criteria received such treatment once a week during a 10-week period. At the end of treatment, a positive effect on both clinical signs and subjective symptoms of TMD, as well as on general body pain, was registered. Eight out of 10 patients also perceived an improved quality of their sleep. At follow-ups after 3 and 6 months some relapse of both signs and symptoms could be seen, but there was still an improvement compared to the initial degree of local and general complaints. At the 6-months follow-up, half of the patients also reported a lasting improvement of their sleep quality. One hypothetical explanation to the positive treatment effect experienced by the tactile stimulation might be the resulting improvement of the patients' quality of sleep leading to increased serotonin levels. The results of the present pilot study are so encouraging that they warrant an extended, controlled study.

  10. Docosahexenoic acid treatment ameliorates cartilage degeneration via a p38 MAPK-dependent mechanism

    PubMed Central

    WANG, ZHENZHONG; GUO, AI; MA, LIFENG; YU, HAOMIAO; ZHANG, LIANG; MENG, HAI; CUI, YINPENG; YU, FEI; YANG, BO

    2016-01-01

    Osteoarthritis (OA) is a common chronic inflammatory disease, characterized by cartilage degradation. The aberrant expression of matrix metalloproteinase-13 (MMP-13) plays a vital role in the pathogenesis of OA. The anti-inflammatory property of docosahexenoic acid (DHA) was previously revealed and showed that DHA retards the progress of many types of inflammatory disease. To evaluate the prophylactic function of DHA in OA, the effect of DHA on cartilage degeneration was assessed in interleukin-1β (IL-1β) stimulated human chondrosarcoma SW1353 cells or a rat model of adjuvant-induced arthritis (AIA). The safe concentration range (0–50 µg/ml in vitro) of DHA was determined by flow cytometry and MTT assay. The inhibitory effects of DHA on MMP-13 mRNA and protein expression were confirmed by RT-qPCR, ELISA and western blotting. Furthermore, findings of an in vivo study showed that DHA can increase the thickness of articular cartilage and decrease MMP-13 expression in cartilage matrix in a rat AIA model. We also revealed the mechanism by which DHA ameliorates cartilage degeneration from OA. The DHA-mediated inhibition of MMP-13 expression was partially attributed to the inactivation of the p38 mitogen-activated protein kinases pathway by suppressing p-p38 in IL-1β-stimulated SW1353 cells and a rat AIA model. Our findings suggested that DHA is a promising therapeutic agent that may be used for the prevention and treatment of OA. PMID:27082436

  11. Stimulation of arachidonic acid metabolism in primary cultures of osteoblast-like cells by hormones and drugs

    SciTech Connect

    Feyen, J.H.; van der Wilt, G.; Moonen, P.; Di Bon, A.; Nijweide, P.J.

    1984-12-01

    The effects of parathyroid hormone (PTH), dihydroxycholecalciferol (1,25-(OH)2 D3), thrombin, epidermal growth factor (EGF) and 12-o-tetradecanoylphorbol-13-acetate (PMA) on the biosynthesis and release of arachidonic acid metabolites were studied in primary cultures of osteoblast-like cells isolated from 18-day-old chick embryo calvaria. Cells were labelled with (/sup 14/C)-arachidonic acid for 30 h. The radioactive eicosanoids were extracted from the cell culture media after a further 30 h stimulation period and analysed on a PRP-1 column by HPLC. The radioactive products were characterized by co-elution of (/sup 3/H) standard prostanoids. Osteoblasts showed a basal release of the prostanoids 6-keto-PGF1 alpha, TXB2, PGF2 alpha, PGE2, PGD2 and PGB2, the latter being the most abundant one. Indomethacin (10(-5) M) effectively inhibited the basal release, but not that of an as yet unidentified compound. The release of prostanoids was stimulated by PTH (2 U/ml), thrombin (0.4 NIH/ml), EGF (50 ng/ml) and PMA (25 ng/ml), the latter being by far the most potent one. 1,25-(OH)2D3 was found to slightly inhibit the prostanoid release. These results indicate: (1) primary cultures of osteoblasts synthesize several prostaglandins, thromboxane B2 and one unidentified product. (2) the action on bone of PTH and the various drugs tested may be, at least partly, mediated by an increased prostaglandin production by osteoblasts. Clearly this does not apply to 1,25-(OH)2D3.

  12. Brain Stimulation in the Treatment of Chronic Neuropathic and Non-Cancerous Pain

    PubMed Central

    Plow, EB; Pascual-Leone, A; Machado, A

    2012-01-01

    Chronic neuropathic pain is one of the most prevalent and debilitating disorders. Conventional medical management, however, remains frustrating for both patients and clinicians owing to poor specificity of pharmacotherapy, delayed-onset of analgesia and extensive side-effects. Neuromodulation presents as a promising alternative, or at least an adjunct, as it is more specific in inducing analgesia without associated risks of pharmacotherapy. Here, we discuss common clinical and investigational methods of neuromodulation. Compared to clinical spinal cord stimulation (SCS), investigational techniques of cerebral neuromodulation, both invasive [deep brain stimulation (DBS) and motor cortical stimulation (MCS)] and noninvasive [repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS)], may be more advantageous. By adaptively targeting the multi-dimensional experience of pain, subtended by integrative pain circuitry in the brain, including somatosensory and thalamocortical, limbic and cognitive, cerebral methods may modulate the sensory-discriminative, affective-emotional and evaluative-cognitive spheres of the pain neuromatrix. Despite promise, the current state of results alludes to the possibility that cerebral neuromodulation has thus far not been effective in producing analgesia as intended in patients with chronic pain disorders. These techniques, thus, remain investigational and off-label. We discuss issues implicated in inadequate efficacy, variability of responsiveness and poor retention of benefit, while recommending design and conceptual refinements for future trials of cerebral neuromodulation in management of chronic neuropathic pain. PMID:22484179

  13. Ketoisocaproic acid, a metabolite of leucine, suppresses insulin-stimulated glucose transport in skeletal muscle cells in a BCAT2-dependent manner.

    PubMed

    Moghei, Mahshid; Tavajohi-Fini, Pegah; Beatty, Brendan; Adegoke, Olasunkanmi A J

    2016-09-01

    Although leucine has many positive effects on metabolism in multiple tissues, elevated levels of this amino acid and the other branched-chain amino acids (BCAAs) and their metabolites are implicated in obesity and insulin resistance. While some controversies exist about the direct effect of leucine on insulin action in skeletal muscle, little is known about the direct effect of BCAA metabolites. Here, we first showed that the inhibitory effect of leucine on insulin-stimulated glucose transport in L6 myotubes was dampened when other amino acids were present, due in part to a 140% stimulation of basal glucose transport (P < 0.05). Importantly, we also showed that α-ketoisocaproic acid (KIC), an obligatory metabolite of leucine, stimulated mTORC1 signaling but suppressed insulin-stimulated glucose transport (-34%, P < 0.05) in an mTORC1-dependent manner. The effect of KIC on insulin-stimulated glucose transport was abrogated in cells depleted of branched-chain aminotransferase 2 (BCAT2), the enzyme that catalyzes the reversible transamination of KIC to leucine. We conclude that although KIC can modulate muscle glucose metabolism, this effect is likely a result of its transamination back to leucine. Therefore, limiting the availability of leucine, rather than those of its metabolites, to skeletal muscle may be more critical in the management of insulin resistance and its sequelae. PMID:27488662

  14. Collagen Stimulators: Poly-L-Lactic Acid and Calcium Hydroxyl Apatite.

    PubMed

    Breithaupt, Andrew; Fitzgerald, Rebecca

    2015-11-01

    Over the last decade, many studies of the structural changes observed in the aging face (in bone, fat pads, facial ligaments, muscle, skin) have increased our understanding that facial rejuvenation is more complex and nuanced than simply filling lines and folds or cutting and lifting soft tissue and skin. This, in addition to the many new products introduced to the marketplace over the same period, has fueled the evolution of panfacial rejuvenation and restoration using fillers. This article discusses current techniques used with calcium hydroxylapatite and poly-l-lactic acid to safely and effectively address changes observed in the aging face. PMID:26505542

  15. Collagen Stimulators: Poly-L-Lactic Acid and Calcium Hydroxyl Apatite.

    PubMed

    Breithaupt, Andrew; Fitzgerald, Rebecca

    2015-11-01

    Over the last decade, many studies of the structural changes observed in the aging face (in bone, fat pads, facial ligaments, muscle, skin) have increased our understanding that facial rejuvenation is more complex and nuanced than simply filling lines and folds or cutting and lifting soft tissue and skin. This, in addition to the many new products introduced to the marketplace over the same period, has fueled the evolution of panfacial rejuvenation and restoration using fillers. This article discusses current techniques used with calcium hydroxylapatite and poly-l-lactic acid to safely and effectively address changes observed in the aging face.

  16. Triacontanol negatively modulates the jasmonic acid-stimulated proteinase inhibitors in tomato (Lycopersicon esculentum).

    PubMed

    Ramanarayan, Krishnamurthy; Swamy, Gangadharamurthy Sivakumar

    2004-04-01

    Triacontanol (TRIA), a long chain aliphatic alcohol (C30H61OH) reverses the effect of jasmonic acid (JA) in inducing proteinase inhibitors (PIs) in tomato leaves. Porcine pancreas trypsin and Spodoptera litura gut proteinases were inhibited in the presence of leaf proteins treated with JA, and TRIA partially reverses this effect. Spodoptera litura larvae fed with tomato leaves treated with JA were reduced in body weight and TRIA is able to partially reverse this JA-induced effect. These results reflect the partial reversal effect of TRIA in down regulating the JA-induced production of proteinase inhibitors.

  17. Vitamin B(12) deficiency stimulates osteoclastogenesis via increased homocysteine and methylmalonic acid.

    PubMed

    Vaes, Bart L T; Lute, Carolien; Blom, Henk J; Bravenboer, Nathalie; de Vries, Teun J; Everts, Vincent; Dhonukshe-Rutten, Rosalie A; Müller, Michael; de Groot, Lisette C P G M; Steegenga, Wilma T

    2009-05-01

    The risk of nutrient deficiencies increases with age in our modern Western society, and vitamin B(12) deficiency is especially prevalent in the elderly and causes increased homocysteine (Hcy) and methylmalonic acid (MMA) levels. These three factors have been recognized as risk factors for reduced bone mineral density and increased fracture risk, though mechanistic evidence is still lacking. In the present study, we investigated the influence of B(12), Hcy, and MMA on differentiation and activity of bone cells. B(12) deficiency did not affect the onset of osteoblast differentiation, maturation, matrix mineralization, or adipocyte differentiation from human mesenchymal stem cells (hMSCs). B(12) deficiency caused an increase in the secretion of Hcy and MMA into the culture medium by osteoblasts, but Hcy and MMA appeared to have no effect on hMSC osteoblast differentiation. We further studied the effect of B(12), Hcy, and MMA on the formation of multinucleated tartrate-resistant acid phosphatase-positive osteoclasts from mouse bone marrow. We observed that B(12) did not show an effect on osteoclastogenesis. However, Hcy as well as MMA were found to induce osteoclastogenesis in a dose-dependent manner. On the basis of these results, we conclude that B(12) deficiency may lead to decreased bone mass by increased osteoclast formation due to increased MMA and Hcy levels.

  18. Gibberellic Acid-Stimulated Arabidopsis6 Serves as an Integrator of Gibberellin, Abscisic Acid, and Glucose Signaling during Seed Germination in Arabidopsis1[OPEN

    PubMed Central

    Zhong, Chunmei; Xu, Hao; Ye, Siting; Wang, Shiyi; Li, Lingfei; Zhang, Shengchun; Wang, Xiaojing

    2015-01-01

    The DELLA protein REPRESSOR OF ga1-3-LIKE2 (RGL2) plays an important role in seed germination under different conditions through a number of transcription factors. However, the functions of the structural genes associated with RGL2-regulated germination are less defined. Here, we report the role of an Arabidopsis (Arabidopsis thaliana) cell wall-localized protein, Gibberellic Acid-Stimulated Arabidopsis6 (AtGASA6), in functionally linking RGL2 and a cell wall loosening expansin protein (Arabidopsis expansin A1 [AtEXPA1]), resulting in the control of embryonic axis elongation and seed germination. AtGASA6-overexpressing seeds showed precocious germination, whereas transfer DNA and RNA interference mutant seeds displayed delayed seed germination under abscisic acid, paclobutrazol, and glucose (Glc) stress conditions. The differences in germination rates resulted from corresponding variation in cell elongation in the hypocotyl-radicle transition region of the embryonic axis. AtGASA6 was down-regulated by RGL2, GLUCOSE INSENSITIVE2, and ABSCISIC ACID-INSENSITIVE5 genes, and loss of AtGASA6 expression in the gasa6 mutant reversed the insensitivity shown by the rgl2 mutant to paclobutrazol and the gin2 mutant to Glc-induced stress, suggesting that it is involved in regulating both the gibberellin and Glc signaling pathways. Furthermore, it was found that the promotion of seed germination and length of embryonic axis by AtGASA6 resulted from a promotion of cell elongation at the embryonic axis mediated by AtEXPA1. Taken together, the data indicate that AtGASA6 links RGL2 and AtEXPA1 functions and plays a role as an integrator of gibberellin, abscisic acid, and Glc signaling, resulting in the regulation of seed germination through a promotion of cell elongation. PMID:26400990

  19. Bile acids induce uncoupling protein 1-dependent thermogenesis and stimulate energy expenditure at thermoneutrality in mice.

    PubMed

    Zietak, Marika; Kozak, Leslie P

    2016-03-01

    It has been proposed that diet-induced obesity at thermoneutrality (TN; 29°C) is reduced by a UCP1-dependent thermogenesis; however, it has not been shown how UCP1-dependent thermogenesis can be activated in the absence of sympathetic activity. A recent study provides such a mechanism by showing that dietary bile acids (BAs) suppress obesity in mice fed a high-fat diet (HFD) by a mechanism dependent on type 2 deiodinase (DIO2); however, neither a role for UCP1 nor the influence of sympathetic activity was properly assessed. To test whether the effects of BAs on adiposity are independent of Ucp1 and cold-activated thermogenesis, obesity phenotypes were determined in C57BL6/J.(+)/(+) (WT) and C57BL6/J.Ucp1.(-)/(-) mice (Ucp1-KO) housed at TN and fed a HFD with or without 0.5% (wt/wt) cholic acid (CA) for 9 wk. CA in a HFD reduced adiposity and hepatic lipogenesis and improved glucose tolerance in WT but not in Ucp1-KO mice and was accompanied by increases in food intake and energy expenditure (EE). In iBAT, CA increased Ucp1 mRNA and protein levels 1.5- and twofold, respectively, and increased DIO2 and TGR5 protein levels in WT mice. Despite enhanced Dio2 expression in Ucp1-KO and Ucp1-KO-CA treated mice, this did not enhance the ability of BAs to reduce obesity. By comparing the effects of BAs on WT and Ucp1-KO mice at TN, our study showed that BAs suppress diet-induced obesity by increasing EE through a mechanism dependent on Ucp1 expression, which is likely independent of adrenergic signaling. PMID:26714852

  20. Indirect effects of UV radiation: Fe{sup 2+} enrichment stimulates picocyanobacterial growth in Clearwater acidic Shield lakes

    SciTech Connect

    Auclair, J.C.

    1995-12-31

    Ozone depletion and associated increases in UVB radiation could increase the photoreduction of iron in Shield lakes of the Boreal forest zone. Since photoreduced iron (I) is more soluble than iron (III), and the re-oxidation rate slower in acidic (pH = 5--6) lakes, phytoplankton growth and/or species composition may be altered where iron is growth limiting. The differential enrichment of UV{sub A+B} transparent herbivore-free (< 65 mu) lakewater enclosures ({approximately}500L) with phosphorus, phosphorus and Fe (II) and phosphorus, ammonium and Fe (II) revealed that the Spring phytoplankton abundance of an oligotrophic Clearwater acidic Canadian Shield lake was limited by herbivore grazing, rather than by a limiting nutrient. However, in the herbivore-free enriched enclosures the addition of Fe{sup 2+} greatly stimulated picocyanobacterial growth and grazing activity by mixotrophic species comprising the microbial food web of this lake. In spite of a 10-fold increase in the mixotrophic chrysophytes, the authors did not discern any strong competitive interactions among the mixotrophic organisms, strongly suggesting that the latter obtain most if not all of their iron quota from their picoplanktonic prey.

  1. An Open-Label Feasibility Trial of Repetitive Transcranial Magnetic Stimulation for Treatment-Resistant Major Depressive Episodes.

    PubMed

    Fujiwara, Masaki; Inagaki, Masatoshi; Higuchi, Yuji; Uchitomi, Yosuke; Terada, Seishi; Kodama, Masafumi; Kishi, Yoshiki; Yamada, Norihito

    2016-08-01

    Repetitive transcranial magnetic stimulation (rTMS) has been reported to be a new treatment option for treatment-resistant depression. In Japan, there has been limited research into its feasibility, efficacy, and tolerability. We have launched a trial of rTMS for treating medication-resistant major depressive disorder and bipolar depression. We are investigating low-frequency rTMS to the right dorsolateral prefrontal cortex and traditional high-frequency rTMS to the left dorsolateral prefrontal cortex, in 20 patients. The primary outcome of the study is the treatment completion rate. This study will provide new data on the usefulness of rTMS for treatment-resistant depression in Japan. PMID:27549679

  2. Efficient treatment of azo dye containing wastewater in a hybrid acidogenic bioreactor stimulated by biocatalyzed electrolysis.

    PubMed

    Wang, Hong-Cheng; Cheng, Hao-Yi; Wang, Shu-Sen; Cui, Dan; Han, Jing-Long; Hu, Ya-Ping; Su, Shi-Gang; Wang, Ai-Jie

    2016-01-01

    In this study, a novel scaled-up hybrid acidogenic bioreactor (HAB) was designed and adopted to evaluate the performance of azo dye (acid red G, ARG) containing wastewater treatment. Principally, HAB is an acidogenic bioreactor coupled with a biocatalyzed electrolysis module. The effects of hydraulic retention time (HRT) and ARG loading rate on the performance of HAB were investigated. In addition, the influent was switched from synthetic wastewater to domestic wastewater to examine the key parameters for the application of HAB. The results showed that the introduction of the biocatalyzed electrolysis module could enhance anoxic decolorization and COD (chemical oxygen demand) removal. The combined process of HAB-CASS presented superior performance compared to a control system without biocatalyzed electrolysis (AB-CASS). When the influent was switched to domestic wastewater, with an environment having more balanced nutrients and diverse organic matters, the ARG, COD and nitrogen removal efficiencies of HAB-CASS were further improved, reaching 73.3%±2.5%, 86.2%±3.8% and 93.5%±1.6% at HRT of 6 hr, respectively, which were much higher than those of AB-CASS (61.1%±4.7%, 75.4%±5.0% and 82.1%±2.1%, respectively). Moreover, larger TCV/TV (total cathode volume/total volume) for HAB led to higher current and ARG removal. The ARG removal efficiency and current at TCV/TV of 0.15 were 39.2%±3.7% and 28.30±1.48 mA, respectively. They were significantly increased to 62.1%±2.0% and 34.55±0.83 mA at TCV/TV of 0.25. These results show that HAB system could be used to effectively treat real wastewater. PMID:26899658

  3. Cardiovascular Risk of Stimulant Treatment in Pediatric Attention-Deficit/Hyperactivity Disorder: Update and Clinical Recommendations

    ERIC Educational Resources Information Center

    Hammerness, Paul G.; Perrin, James M.; Shelley-Abrahamson, Rachel; Wilens, Timothy E.

    2011-01-01

    Objective: This review provides an update on the cardiovascular impact of therapeutic stimulant-class medication for children and adolescents with attention-deficit/hyperactivity disorder (ADHD). Method: Relevant clinical literature was ascertained using PubMed searches limited to human studies and the English language as of May 2011. Current…

  4. Transcranial Magnetic Stimulation in the investigation and treatment of schizophrenia: a review.

    PubMed

    Haraldsson, H Magnus; Ferrarelli, Fabio; Kalin, Ned H; Tononi, Giulio

    2004-11-01

    Transcranial Magnetic Stimulation (TMS) is a non-invasive method of stimulating the brain that is increasingly being used in neuropsychiatric research and clinical psychiatry. This review examines the role of TMS in schizophrenia research as a diagnostic and a therapeutic resource. After a brief overview of TMS, we describe the application of TMS to schizophrenia in studies of cortical excitability and inhibition, and we discuss the potential confounding role of neuroleptic medications. Based on these studies, it appears that some impairment of cortical inhibition may be present in schizophrenic subjects. We then review attempts to employ TMS for treating different symptoms of schizophrenia. Some encouraging results have been obtained, such as the reduction of auditory hallucinations after slow TMS over auditory cortex and an improvement of psychotic symptoms after high frequency TMS over left prefrontal cortex. However, these results need to be confirmed using better placebo conditions. Future studies are likely to employ TMS in combination with functional brain imaging to examine the effects produced by the stimulated area on activity in other brain regions. Such studies may reveal impaired effective connectivity between specific brain areas, which could identify these regions as targets for selective stimulation with therapeutic doses of TMS.

  5. Transcranial cortical stimulation in the treatment of obsessive-compulsive disorders: efficacy studies.

    PubMed

    Saba, Ghassen; Moukheiber, Albert; Pelissolo, Antoine

    2015-05-01

    Repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) are non-invasive brain stimulation methods that became widely used as therapeutic tools during the past two decades especially in cases of depression and schizophrenia. Low frequency rTMS and cathodal effect of tDCS inhibits cortical functioning while high frequency and anodal effect of tDCS have the opposite effect. Prolonged and repetitive application of either methods leads to changes in excitability of the human cortex that outlast the period of stimulation. Both rTMS and tDCS induce functional changes in the brain-modulating neural activity at cortical level. This paper reviews rTMS and tDCS effects in clinical trials for obsessive-compulsive disorder (OCD). Low frequency rTMS, particularly targeting the supplementary motor area and the orbital frontal cortex, seems to be the most promising in terms of therapeutic efficacy while older studies targeting the prefrontal dorsal cortex were not as successful. tDCS clearly needs to be investigated in large scale and sufficiently powered randomized control studies. From a general point of view, these non-invasive techniques hold promise as novel therapeutic tools for OCD patients. PMID:25825002

  6. The Analysis and Treatment of Problem Behavior Evoked by Auditory Stimulation

    ERIC Educational Resources Information Center

    Devlin, Sarah; Healy, Olive; Leader, Geraldine; Reed, Phil

    2008-01-01

    The current study aimed to identify specific stimuli associated with music that served as an establishing operation (EO) for the problem behavior of a 6-year-old child with a diagnosis of autism. Specific EOs for problem behavior evoked by auditory stimulation could be identified. A differential negative reinforcement procedure was implemented for…

  7. Apelin Treatment Increases Complete Fatty Acid Oxidation, Mitochondrial Oxidative Capacity, and Biogenesis in Muscle of Insulin-Resistant Mice

    PubMed Central

    Attané, Camille; Foussal, Camille; Le Gonidec, Sophie; Benani, Alexandre; Daviaud, Danièle; Wanecq, Estelle; Guzmán-Ruiz, Rocío; Dray, Cédric; Bezaire, Veronic; Rancoule, Chloé; Kuba, Keiji; Ruiz-Gayo, Mariano; Levade, Thierry; Penninger, Josef; Burcelin, Rémy; Pénicaud, Luc; Valet, Philippe; Castan-Laurell, Isabelle

    2012-01-01

    Both acute and chronic apelin treatment have been shown to improve insulin sensitivity in mice. However, the effects of apelin on fatty acid oxidation (FAO) during obesity-related insulin resistance have not yet been addressed. Thus, the aim of the current study was to determine the impact of chronic treatment on lipid use, especially in skeletal muscles. High-fat diet (HFD)-induced obese and insulin-resistant mice treated by an apelin injection (0.1 μmol/kg/day i.p.) during 4 weeks had decreased fat mass, glycemia, and plasma levels of triglycerides and were protected from hyperinsulinemia compared with HFD PBS-treated mice. Indirect calorimetry experiments showed that apelin-treated mice had a better use of lipids. The complete FAO, the oxidative capacity, and mitochondrial biogenesis were increased in soleus of apelin-treated mice. The action of apelin was AMP-activated protein kinase (AMPK) dependent since all the effects studied were abrogated in HFD apelin-treated mice with muscle-specific inactive AMPK. Finally, the apelin-stimulated improvement of oxidative capacity led to decreased levels of acylcarnitines and enhanced insulin-stimulated glucose uptake in soleus. Thus, by promoting complete lipid use in muscle of insulin-resistant mice through mitochondrial biogenesis and tighter matching between FAO and the tricarboxylic acid cycle, apelin treatment could contribute to insulin sensitivity improvement. PMID:22210322

  8. Diastereomeric mixture of calophyllic acid and isocalophyllic acid stimulates glucose uptake in skeletal muscle cells: involvement of PI-3-kinase- and ERK1/2-dependent pathways.

    PubMed

    Prasad, Janki; Maurya, Chandan Kumar; Pandey, Jyotsana; Jaiswal, Natasha; Madhur, Gaurav; Srivastava, Arvind Kumar; Narender, Tadigoppula; Tamrakar, Akhilesh Kumar

    2013-05-01

    The diastereomeric mixture of calophyllic acid and isocalophyllic acid (F015) isolated from the leaves of Calophyllum inophyllum was investigated for the metabolic effect on glucose transport in skeletal muscle cells. In L6 myotubes, F015 dose-dependently stimulated glucose uptake by increasing translocation of glucose transporter4 (GLUT4) to plasma membrane without affecting their gene expression. The effects on glucose uptake were additive to insulin. Inhibitors analyses revealed that F015-induced glucose uptake was dependent on the activation of phosphatidylinositol-3-kinase (PI-3-K) and extracellular signal-regulated kinases 1 and 2 (ERK1/2), while independent to the activation of 5'AMP-activated kinase (AMPK). F015 significantly increased the phosphorylation of AKT, AS160 and ERK1/2, account for the augmented glucose transport capacity in L6 myotubes. Furthermore, F015 improved glucose tolerance and enhanced insulin sensitivity in skeletal muscle of dexamethasone-induced insulin resistant mice. Our findings demonstrate that F015 activates glucose uptake in skeletal muscle cells through PI-3-K- and EKR1/2-dependent mechanisms and can be a potential lead for the management of diabetes and obesity.

  9. An efficient and green pretreatment to stimulate short-chain fatty acids production from waste activated sludge anaerobic fermentation using free nitrous acid.

    PubMed

    Li, Xiaoming; Zhao, Jianwei; Wang, Dongbo; Yang, Qi; Xu, Qiuxiang; Deng, Yongchao; Yang, Weiqiang; Zeng, Guangming

    2016-02-01

    Short-chain fatty acid (SCFA) production from waste activated sludge (WAS) anaerobic fermentation is often limited by the slow hydrolysis rate and poor substrate availability, thus a long fermentation time is required. This paper reports a new pretreatment approach, i.e., using free nitrous acid (FNA) to pretreat sludge, for significantly enhanced SCFA production. Experimental results showed the highest SCFA production occurred at 1.8 mg FNA/L with time of day 6, which was 3.7-fold of the blank at fermentation time of day 12. Mechanism studies revealed that FNA pretreatment accelerated disruption of both extracellular polymeric substances and cell envelope. It was also found that FNA pretreatment benefited hydrolysis and acidification processes but inhibited the activities of methanogens, thereby promoting the yield of SCFA. In addition, the FNA pretreatment substantially stimulated the activities of key enzymes responsible for hydrolysis and acidification, which were consistent with the improvement of solubilization, hydrolysis and acidification of WAS anaerobic fermentation.

  10. Effects of high pressure-dependent leakoff and high process-zone stress in coal-stimulation treatments

    SciTech Connect

    Ramurthy, M.; Lyons, B.; Hendrickson, R.B.; Barree, R.D.; Magill, D.R.

    2009-08-15

    Hydraulic fracturing in coals has been studied extensively over the last two decades; however, there are factors that were often ignored or incorrectly diagnosed, resulting in screenouts. Assuming that a majority of the perforations are open and there are no problems with the stimulation fluids, screenouts during coal hydraulic-fracture treatments can be attributed to either high pressure-dependent leakoff (PDL), high process-zone stress (PZS) or in some cases both. The objective of this work is to discuss, help identify, and present solutions to address these reservoir-related issues such that screenouts can be avoided in optimized refracture treatments and new well stimulations. The tools for identifying these reservoir-related parameters include a diagnostic fracture-injection test (DFIT) and a grid-oriented fully functional 3D fracture simulator with shear decoupling. An example for each respective case is presented in this paper. In the first example, in which high PZS was considered to be the dominant reason for screenout or pressure out, the well was restimulated successfully by implementing the solutions presented in this paper. In the second example, in which high PDL was considered to be the main reason for screenout, there were several wells in the same project area that exhibited the same behavior resulting in screenouts. After implementing the solutions presented in this paper to address high PDL, all new wells were stimulated successfully without any issues.

  11. Polarographic determination of metyrosine through treatment with nitrous acid.

    PubMed

    Aly, F A; Belal, F; el-Brashy, A

    1993-10-15

    A simple and sensitive polarographic method is described for the determination of metyrosine through treatment with nitrous acid. The different experimental parameters affecting the derivatization process, as well as the polarographic analysis were studied. The derivatization product was found to be reducible at the dropping mercury electrode over the whole pH range in Britton Robinson buffers. At pH 5, a well-defined diffusion-controlled cathodic wave was produced. The limiting current versus the concentration plot was linear over the range 8-80 mumol/l in the direct current mode with a detection limit of 0.2 mumol/l. The method was then applied to the determination of metyrosine capsules, and the results obtained were in good agreement with those given by the USP method.

  12. Phosphatidylcholine is a major source of phosphatidic acid and diacylglycerol in angiotensin II-stimulated vascular smooth-muscle cells.

    PubMed

    Lassègue, B; Alexander, R W; Clark, M; Akers, M; Griendling, K K

    1993-06-01

    In cultured vascular smooth-muscle cells, angiotensin II produces a sustained formation of diacylglycerol (DG) and phosphatidic acid (PtdOH). Since the fatty acid composition of these molecules is likely to determine their efficacy as second messengers, it is important to ascertain the phospholipid precursors and the biochemical pathways from which they are produced. Our experiments suggest that phospholipase D (PLD)-mediated phosphatidylcholine (PtdCho) hydrolysis is the major source of both DG and PtdOH during the late signalling phase. First, in cells labelled with [3H]myristate, which preferentially labels PtdCho, formation of [3H]PtdOH precedes formation of [3H]DG. Second, in contrast with phospholipase C (PLC) activation, DG mass accumulation is dependent on extracellular Ca2+. Similarly, DG mass accumulation is not attenuated by protein kinase C activation, which we have previously shown to inhibit the phosphoinositide-specific PLC. Third, the fatty acid composition of late-phase DG and PtdOH more closely resembles that of PtdCho than that of phosphatidylinositol. Finally, in cells labelled for a short time with [3H]glycerol, the radioactivity incorporated into [3H]DG and PtdOH was greater than that incorporated into PtdIns, but not into PtdCho. We found no evidence that synthesis de novo or phosphatidylethanolamine breakdown contributes to sustained DG and PtdOH formation. Thus, in angiotensin II-stimulated cultured vascular smooth-muscle cells, PLD-mediated PtdCho hydrolysis is the major source of sustained DG and PtdOH, whereas phosphoinositide breakdown is a minor contributor. Furthermore, PtdOH phosphohydrolase, which determines the relative levels of DG and PtdOH, appears to be regulated by protein kinase C. These results have important implications for the role of these second messengers in growth and contraction.

  13. Maleic acid treatment of biologically detoxified corn stover liquor.

    PubMed

    Kim, Daehwan; Ximenes, Eduardo A; Nichols, Nancy N; Cao, Guangli; Frazer, Sarah E; Ladisch, Michael R

    2016-09-01

    Elimination of microbial and enzyme inhibitors from pretreated lignocellulose is critical for effective cellulose conversion and yeast fermentation of liquid hot water (LHW) pretreated corn stover. In this study, xylan oligomers were hydrolyzed using either maleic acid or hemicellulases, and other soluble inhibitors were eliminated by biological detoxification. Corn stover at 20% (w/v) solids was LHW pretreated LHW (severity factor: 4.3). The 20% solids (w/v) pretreated corn stover derived liquor was recovered and biologically detoxified using the fungus Coniochaeta ligniaria NRRL30616. After maleic acid treatment, and using 5 filter paper units of cellulase/g glucan (8.3mg protein/g glucan), 73% higher cellulose conversion from corn stover was obtained for biodetoxified samples compared to undetoxified samples. This corresponded to 87% cellulose to glucose conversion. Ethanol production by yeast of pretreated corn stover solids hydrolysate was 1.4 times higher than undetoxified samples, with a reduction of 3h in the fermentation lag phase. PMID:27262718

  14. Corticosteroid and hyaluronic acid treatments in equine degenerative joint disease. A review.

    PubMed

    Nizolek, D J; White, K K

    1981-10-01

    Degenerative arthrosis is perhaps the most common debilitating disease of performance horses. Treatment should be based upon a knowledge of the anatomy and physiology of normal joints and upon an understanding of the processes of degeneration and repair. These topics are briefly reviewed. Although rest is probably, the most beneficial therapy, physical and pharmaceutical treatments are often employed in an effort to speed recovery. The effects and relative benefits of intrasynovial injections of corticosteroids, hyaluronica cid, and Arteparon are considered in detail. Although local corticosteroid therapy is inexpensive and is effective in reducing lameness caused by degenerative joint disease, it is rarely indicated. Septic arthritis and "steroid arthropathy" are two serious sequelae. Whereas the incidence of the former may be avoided through careful technique, the latter effect is inherent in the action of the drug. The accelerated rate of joint destruction observed in steroid arthropathy is due to suppression of chondrocyte metabolism and thus the processes of cartilage maintenance and repair. Hyaluronic acid is present in the synovial fluid and within the matrix of cartilage. The commercial preparation is no approved for use in the United States, but it is commonly obtained from other countries. Although hyaluronate apparently does not function in the lubrication of cartilage surfaces, it may improve lubrication of soft tissues thus decreasing resistance to joint movement and lessening pain. Reports substantiate the effectiveness of hyaluronic acid in treating early cases of degenerative arthrosis despite the fact that the drug does not significantly promote cartilage healing. Arteparon, a polysulfated glycosaminoglycan, has been used in Europe for two decades in the treatment of degeneration joint disease and is currently being tested in this country. The drug is deposited within diseased cartilage and improves the functional properties of the cartilage as

  15. Raf-1 kinase possesses distinct binding domains for phosphatidylserine and phosphatidic acid. Phosphatidic acid regulates the translocation of Raf-1 in 12-O-tetradecanoylphorbol-13-acetate-stimulated Madin-Darby canine kidney cells.

    PubMed

    Ghosh, S; Strum, J C; Sciorra, V A; Daniel, L; Bell, R M

    1996-04-01

    Previous studies demonstrated that the cysteine-rich amino-terminal domain of Raf-1 kinase interacts selectively with phosphatidylserine (Ghosh, S., Xie, W. Q., Quest, A. F. G., Mabrouk, G. M., Strum, J. C., and Bell, R. M. (1994) J. Biol. Chem. 269, 10000-10007). Further analysis showed that full-length Raf-1 bound to both phosphatidylserine and phosphatidic acid (PA). Specifically, a carboxyl-terminal domain of Raf-1 kinase (RafC; residues 295 648 of human Raf-1) interacted strongly with phosphatidic acid. The binding of RafC to PA displayed positive cooperativity with Hill numbers between 3.3 and 6.2; the apparent Kd ranged from 4.9 +/- 0.6 to 7.8 +/- 0.9 mol % PA. The interaction of RafC with PA displayed a pH dependence distinct from the interaction between the cysteine-rich domain of Raf-1 and PA. Also, the RafC-PA interaction was unaffected at high ionic strength. Of all the lipids tested, only PA and cardiolipin exhibited high affinity binding; other acidic lipids were either ineffective or weakly effective. By deletion mutagenesis, the PA binding site within RafC was narrowed down to a 35-amino acid segment between residues 389 and 423. RafC did not bind phosphatidyl alcohols; also, inhibition of PA formation in Madin-Darby canine kidney cells by treatment with 1% ethanol significantly reduced the translocation of Raf-1 from the cytosol to the membrane following stimulation with 12-O-tetradecanoylphorbol-13-acetate. These results suggest a potential role of the lipid second messenger, PA, in the regulation of translocation and subsequent activation of Raf-1 in vivo.

  16. Acidic fibroblast growth factor and keratinocyte growth factor stimulate fetal rat pulmonary epithelial growth.

    PubMed

    Deterding, R R; Jacoby, C R; Shannon, J M

    1996-10-01

    We have shown that pulmonary epithelial growth and differentiation can occur if pulmonary mesenchyme is replaced with a mixture of growth factors [total growth medium (TGM)] that consists of adult rat bronchoalveolar lavage fluid, insulin, epidermal growth factor (EGF), cholera toxin (CT), acidic fibroblast growth factor (aFGF), and fetal bovine serum. In the present study, we have defined the importance of specific components of TGM. Day 14 fetal rat distal lung epithelium, devoid of mesenchyme, was enrobed in growth factor-depleted Matrigel and cultured for 5 days in various soluble factors. We found that deleting aFGF or CT from TGM significantly reduced DNA synthesis. Epithelial proliferation was not significantly different when keratinocyte growth factor (KGF) replaced aFGF in TGM. KGF, however, required the presence of a basal medium containing CT, insulin, and serum for optimal proliferation. We then added specific growth factors to the basal medium and showed that aFGF and KGF were more potent mitogens than EGF, transforming growth factor-alpha, and hepatocyte growth factor. Additionally, basal medium + KGF also allowed progression to a distal alveolar phenotype. We conclude that aFGF and KGF may be important mediators in epithelial-mesenchymal interactions. PMID:8897895

  17. A Comparative Study Between Two Sensory Stimulation Strategies After Two Weeks Treatment on Older Patients with Oropharyngeal Dysphagia.

    PubMed

    Ortega, Omar; Rofes, Laia; Martin, Alberto; Arreola, Viridiana; López, Irene; Clavé, Pere

    2016-10-01

    Oropharyngeal dysphagia (OD) is a prevalent geriatric syndrome. Treatment is based on compensatory strategies to avoid complications. New treatments based on sensory stimulation to promote the recovery of the swallowing function have proved effective in acute studies but prolonged treatment needs further research. Our aim was to evaluate and compare the effect of two, longer-term sensory treatment strategies on older patients with OD. 38 older patients (≥70 years) were studied with videofluoroscopy (pre/posttreatment) and randomized into two 10-day treatment groups: Group A-transient receptor potential vanilloid 1 (TRPV1) agonist (capsaicin 1 × 10(-5) M) and Group B-transcutaneous sensory electrical stimulation (TSES) (Intelect VitalStim, biphasic pulses, 300 μs, 80 Hz). Patients were analyzed for treatment response. Patients were old (80.47 ± 5.2 years), with comorbidities (3.11 ± 1.59 Charlson Index), polymedication (8.92 ± 3.31 drugs/patient), and mild functional impairment (86.84 ± 17.84 Barthel Index), and 28.9 % were at risk of malnutrition (MNA-sf). Overall, all patients had videofluoroscopic signs of impaired safety of swallow (ISS) with delayed oropharyngeal swallow response (OSR). After sensory stimulation, prevalence of ISS decreased to 68.42 % in both groups (P = 0.019). There were 68.42 % responders in Group A (TRPV1) and 42.11 % in Group B (TSES). Group A responders showed an improvement in the penetration-aspiration scale (PAS, 5.23 ± 2.04 to 3 ± 1.47; P = 0.002), and the same was true for those of Group B (4.63 ± 1.41 to 2.13 ± 0.64; P = 0.007). 10-day sensory stimulation with either therapy improved safety of swallow and OSR in older patients with OD, reducing the severity of OD in a significant subgroup of these patients. PMID:27503566

  18. A Comparative Study Between Two Sensory Stimulation Strategies After Two Weeks Treatment on Older Patients with Oropharyngeal Dysphagia.

    PubMed

    Ortega, Omar; Rofes, Laia; Martin, Alberto; Arreola, Viridiana; López, Irene; Clavé, Pere

    2016-10-01

    Oropharyngeal dysphagia (OD) is a prevalent geriatric syndrome. Treatment is based on compensatory strategies to avoid complications. New treatments based on sensory stimulation to promote the recovery of the swallowing function have proved effective in acute studies but prolonged treatment needs further research. Our aim was to evaluate and compare the effect of two, longer-term sensory treatment strategies on older patients with OD. 38 older patients (≥70 years) were studied with videofluoroscopy (pre/posttreatment) and randomized into two 10-day treatment groups: Group A-transient receptor potential vanilloid 1 (TRPV1) agonist (capsaicin 1 × 10(-5) M) and Group B-transcutaneous sensory electrical stimulation (TSES) (Intelect VitalStim, biphasic pulses, 300 μs, 80 Hz). Patients were analyzed for treatment response. Patients were old (80.47 ± 5.2 years), with comorbidities (3.11 ± 1.59 Charlson Index), polymedication (8.92 ± 3.31 drugs/patient), and mild functional impairment (86.84 ± 17.84 Barthel Index), and 28.9 % were at risk of malnutrition (MNA-sf). Overall, all patients had videofluoroscopic signs of impaired safety of swallow (ISS) with delayed oropharyngeal swallow response (OSR). After sensory stimulation, prevalence of ISS decreased to 68.42 % in both groups (P = 0.019). There were 68.42 % responders in Group A (TRPV1) and 42.11 % in Group B (TSES). Group A responders showed an improvement in the penetration-aspiration scale (PAS, 5.23 ± 2.04 to 3 ± 1.47; P = 0.002), and the same was true for those of Group B (4.63 ± 1.41 to 2.13 ± 0.64; P = 0.007). 10-day sensory stimulation with either therapy improved safety of swallow and OSR in older patients with OD, reducing the severity of OD in a significant subgroup of these patients.

  19. Noninvasive brain stimulation by radioelectric asymmetric conveyor in the treatment of agoraphobia: open-label, naturalistic study

    PubMed Central

    Mannu, Piero; Rinaldi, Salvatore; Fontani, Vania; Castagna, Alessandro; Margotti, Matteo Lotti

    2011-01-01

    Background Agoraphobia is considered to be the most serious complication of panic disorder. It involves progressive development of debilitating anxiety symptoms related to being in situations where one would be extremely embarrassed and could not be rescued in the case of a panic attack. This study aimed to investigate the efficacy of noninvasive brain stimulation using a radioelectric asymmetric conveyor (REAC) for agoraphobia. Patients and methods Twenty-three patients (3 males and 20 females) suffering from agoraphobia and without a history of panic disorder were evaluated by a psychiatrist using the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, and the Agoraphobia Scale (AS). The patients were subjected to two 18-session cycles of noninvasive brain stimulation with the REAC, according to an established therapeutic protocol called neuropsycho-physical optimization. Results Analyzing the anxiety and avoidance parameters of the AS after the first and second cycles of REAC treatment revealed variation in levels of response to treatment, including weak (AS item 7), moderate (AS items 10 and 13), and good responses (AS items 1–6, 8, 9, 11, 12, and 14–20). Conclusion These results highlight the potential of the REAC to treat complex clinical situations such as agoraphobia, which is typically resistant to pharmacologic treatments. Furthermore, these data show the advantages of REAC treatment, even compared with modern cognitive behavioral therapy, including a relatively rapid and “stable” clinical response (just over 6 months) and economic cost. PMID:22163156

  20. [Experimental study of non-invasive percutaneous electrical stimulator for treatment of obstructive sleep apnea syndrome and its clinical effect].

    PubMed

    Hu, Lianggang; Xu, Xiaomei; Gong, Yongsheng; Fan, Xiaofang; Wang, Liangxing

    2006-08-01

    To study the stimulation of the genioglossus with percutaneous biphasic current pulses as a new therapeutical method to treat the obstructive sleep apnea syndrome (OSAS), polysomnography (PSG) was used to synchronously monitor the patient. When OSAS was occurring, the stimulation with the optimal parameter was given in time to make the tongue move forward, the glossopharyngeal airway dilated, the resistance of the upper respiratory tract reduced, the hypoxia at night to be improved and the sleeping structure to be ameliorated because of the function of the dilated muscle of the upper airway. The results of the clinical therapeutic effect indicated that 17 of 22 patients with OSAS had cured effects, 2 of whom improved and 3 of whom were without effect. The effective rate was 77.27%. It is preliminarily proved that this is a new method in the treatment of patients suffered from OSAS. PMID:17002124

  1. Perturbative treatments of photo-stimulated desorption and dissociation on metal surfaces induced by single and multiple electronic transitions

    NASA Astrophysics Data System (ADS)

    Guo, Hua; Liu, Li

    1997-02-01

    Photo-stimulated desorption and dissociation of small molecules adsorbed on metals are investigated in both the DIET and DIMET limits. A theoretical model is developed based on a perturbative treatment of substrate-mediated transitions. In this model, the system evolves according to the time-dependent Schrödinger equation except for transitions between the neutral and ionic states, which are induced by a series of delta pulses delayed by a pre-specified time (τ). Two examples are studied: the photo-stimulated substrate-mediated desorption of nitric oxide and the dissociative electron attachment of methyl bromide. Translational energy distributions and product yields in both the DIET and DIMET limits are calculated and compared. The influence of the time delay between the excitation and deexcitation is explored.

  2. [Experimental study of non-invasive percutaneous electrical stimulator for treatment of obstructive sleep apnea syndrome and its clinical effect].

    PubMed

    Hu, Lianggang; Xu, Xiaomei; Gong, Yongsheng; Fan, Xiaofang; Wang, Liangxing

    2006-08-01

    To study the stimulation of the genioglossus with percutaneous biphasic current pulses as a new therapeutical method to treat the obstructive sleep apnea syndrome (OSAS), polysomnography (PSG) was used to synchronously monitor the patient. When OSAS was occurring, the stimulation with the optimal parameter was given in time to make the tongue move forward, the glossopharyngeal airway dilated, the resistance of the upper respiratory tract reduced, the hypoxia at night to be improved and the sleeping structure to be ameliorated because of the function of the dilated muscle of the upper airway. The results of the clinical therapeutic effect indicated that 17 of 22 patients with OSAS had cured effects, 2 of whom improved and 3 of whom were without effect. The effective rate was 77.27%. It is preliminarily proved that this is a new method in the treatment of patients suffered from OSAS.

  3. Stimulation of pyruvate transport in metabolizing mitochondria through changes in the transmembrane pH gradient induced by glucagon treatment of rats.

    PubMed

    Halestrap, A P

    1978-06-15

    Glucagon treatment of rats allowed the isolation of liver mitochondria with enhanced rates of pyruvate metabolism measured in either sucrose or KCl media. No change in the activity of the pyruvate carrier itself was apparent, but under metabolizing conditions, use of the inhibitor of pyruvate transport, alpha-cyano-4-hydroxycinnamate, demonstrated that pyruvate transport limited the rate of pyruvate metabolism. The maximum rate of transport under metabolizing conditions was enhanced by glucagon treatment. Problems involved in measuring the transmembrane pH gradient under metabolizing conditions are discussed and a variety of techniques are used to estimate the matrix pH. From the distribution of methylamine, ammonia and D-lactate and the Ki for inhibition by alpha-cyano-4-hydroxycinnamate it is concluded that the matrix is more acid than the medium and that the pH of the matrix rises after glucagon treatment. The increase in matrix pH stimulates pyruvate transport. The membrane potential, ATP concentration and O2 uptake were also increased under metabolizing conditions in glucagon-treated mitochondria. These changes were correlated with a stimulation of the respiratory chain which can be observed in uncoupled mitochondria [Yamazaki (1975) J. Biol. Chem. 250, 7924--7930]. The mitochondrial Mg2+ content (mean +/- S.E.M.) was increased from 38.8 +/- 1.2 (n = 26) to 47.5 +/- 2.0 (n = 26) ng-atoms/mg by glucagon and the K+ content from 126.7 +/- 10.3 (n = 19) ng-atoms/mg. This may represent a change in membrane potential induced by glucagon in vivo. The physiological significance of these results in the control of gluconeogenesis is discussed. PMID:28727

  4. Two weeks of metformin treatment induces AMPK-dependent enhancement of insulin-stimulated glucose uptake in mouse soleus muscle

    PubMed Central

    Kristensen, Jonas Møller; Treebak, Jonas T.; Schjerling, Peter; Goodyear, Laurie

    2014-01-01

    Metformin-induced activation of the 5′-AMP-activated protein kinase (AMPK) has been associated with enhanced glucose uptake in skeletal muscle, but so far no direct causality has been examined. We hypothesized that an effect of in vivo metformin treatment on glucose uptake in mouse skeletal muscles is dependent on AMPK signaling. Oral doses of metformin or saline treatment were given to muscle-specific kinase dead (KD) AMPKα2 mice and wild-type (WT) littermates either once or chronically for 2 wk. Soleus and extensor digitorum longus muscles were used for measurements of glucose transport and Western blot analyses. Chronic treatment with metformin enhanced insulin-stimulated glucose uptake in soleus muscles of WT (∼45%, P < 0.01) but not of AMPK KD mice. Insulin signaling at the level of Akt protein expression or Thr308 and Ser473 phosphorylation was not changed by metformin treatment. Insulin signaling at the level of Akt and TBC1D4 protein expression as well as Akt Thr308/Ser473 and TBC1D4 Thr642/Ser711 phosphorylation were not changed by metformin treatment. Also, protein expressions of Rab4, GLUT4, and hexokinase II were unaltered after treatment. The acute metformin treatment did not affect glucose uptake in muscle of either of the genotypes. In conclusion, we provide novel evidence for a role of AMPK in potentiating the effect of insulin on glucose uptake in soleus muscle in response to chronic metformin treatment. PMID:24644243

  5. Geothermal-Reservoir Well-Stimulation Program. Program status report

    SciTech Connect

    Not Available

    1982-05-01

    Seven experimental fracture stimulation treatments completed to date and the laboratory work performed to develop the stimulation technology are described. A discussion of the pre-stimulation and post-stimulation data and their evaluation is provided for each experiment. Six of the seven stimulation experiments were at least technically successful in stimulating the wells. The two fracture treatments in East Mesa 58-30 more than doubled the producing rate of the previously marginal producer. The two fracture treatments in Raft River and the two in Baca were all successful in obtaining significant production from previously nonproductive intervals. However, these treatments failed to establish commercial production due to deficiencies in either fluid temperature or flow rate. The acid etching treatment in the well at The Geysers did not have any material effect on producing rate.

  6. Alveolar macrophage phagocytic activity is enhanced with LPS priming, and combined stimulation of LPS and lipoteichoic acid synergistically induce pro-inflammatory cytokines in pigs.

    PubMed

    Islam, Mohammad Ariful; Pröll, Maren; Hölker, Michael; Tholen, Ernst; Tesfaye, Dawit; Looft, Christian; Schellander, Karl; Cinar, Mehmet Ulas

    2013-12-01

    The objective of the present study was to investigate LPS and lipoteichoic acid (LTA)-induced TLRs, associated signaling molecules and inflammatory mediators, as well as to compare their combined effect in porcine alveolar macrophages. Macrophages were incubated for 24 h with various concentrations of LPS, LTA, LPS + LTA or control. Multiple concentrations of LPS elicited marked up-regulation in mRNA for TLR2 and TLR4, CD14, MD2, MyD88, IRAK-4 and TRAF6 compared with the control. LTA had no effect on TLR4 and MD2; only higher doses up-regulated TLR2, CD14, MyD88, IRAK-4 and TRAF6 mRNA. LPS-activated cells released IL1-β, IL12-β, TNF-α, IL-6, IL-8, IFN-γ and IL-10 in a dose-dependent manner, while LTA had no effect on IL-1β, IL-6 and IFN-γ. Higher doses of LTA induced IL-12β, TNF-α, IL-8 and IL-10. Combined stimulation augmented TLR2, CD14 and MyD88 mRNA, and subsequently produced elevated levels of IL-6, TNF-α and IL-8 when compared with LPS and LTA alone. Additionally, phagocytosis of macrophages was significantly increased following low concentration of LPS treatment. Only low levels of NO (nitric oxide) were detected in the LPS group. Overall, compared with LPS, LTA was a relatively weak inducer, and co-stimulation accelerated gene and cytokine production associated with pulmonary innate immune function.

  7. Short-Chain Fatty Acid Acetate Stimulates Adipogenesis and Mitochondrial Biogenesis via GPR43 in Brown Adipocytes.

    PubMed

    Hu, Jiamiao; Kyrou, Ioannis; Tan, Bee K; Dimitriadis, Georgios K; Ramanjaneya, Manjunath; Tripathi, Gyanendra; Patel, Vanlata; James, Sean; Kawan, Mohamed; Chen, Jing; Randeva, Harpal S

    2016-05-01

    Short-chain fatty acids play crucial roles in a range of physiological functions. However, the effects of short-chain fatty acids on brown adipose tissue have not been fully investigated. We examined the role of acetate, a short-chain fatty acid formed by fermentation in the gut, in the regulation of brown adipocyte metabolism. Our results show that acetate up-regulates adipocyte protein 2, peroxisomal proliferator-activated receptor-γ coactivator-1α, and uncoupling protein-1 expression and affects the morphological changes of brown adipocytes during adipogenesis. Moreover, an increase in mitochondrial biogenesis was observed after acetate treatment. Acetate also elicited the activation of ERK and cAMP response element-binding protein, and these responses were sensitive to G(i/o)-type G protein inactivator, Gβγ-subunit inhibitor, phospholipase C inhibitor, and MAPK kinase inhibitor, indicating a role for the G(i/o)βγ/phospholipase C/protein kinase C/MAPK kinase signaling pathway in these responses. These effects of acetate were mimicked by treatment with 4-chloro-α-(1-methylethyl)-N-2-thiazolylbenzeneacetamide, a synthetic G protein-coupled receptor 43 (GPR43) agonist and were impaired in GPR43 knockdown cells. Taken together, our results indicate that acetate may have important physiological roles in brown adipocytes through the activation of GPR43. PMID:26990063

  8. Effects of gas atmospheres on poly(lactic acid) film in acrylic acid plasma treatment

    NASA Astrophysics Data System (ADS)

    Zhao, Yun; Fina, Alberto; Venturello, Alberto; Geobaldo, Francesco

    2013-10-01

    Plasma polymerized acrylic acid (AA) coatings were deposited on poly(lactic acid) (PLA) films in various gas atmospheres during the pre-treatment of PLA and the deposition of AA, respectively. Therefore, this work was twofold: the argon pretreated PLA films followed by a deposition in argon were investigated against the mixture of argon and oxygen pretreated ones under the same deposition conditions; the plasma deposition of AA operating in different atmospheres (argon, oxygen and nitrogen) was employed to modify the pretreated PLA in oxygen. Chemical and physical changes on the plasma-treated surfaces were examined using contact angle, X-ray photoelectron spectroscopy (XPS), field emission scanning electron microscopy (FE-SEM) and attenuated total reflection infrared (ATR-FTIR) analysis. The results showed that the discharge gas can have a significant influence on the chemical composition of the PLA surfaces: oxygen plasmas introduced oxygen-containing groups in company with surface etching in pretreatment and deposition, while argon discharges was able to achieve much better hydrophilic behavior and high retention ratio of poly(acrylic acid) (PAA) coating before and after washing in water.

  9. Enhancement of cell viability after treatment with polyunsaturated fatty acids.

    PubMed

    Bartl, J; Walitza, S; Grünblatt, E

    2014-01-24

    Attention-deficit/hyperactivity disorder (ADHD) is highly prevalent in children and adolescents and both environmental and genetic factors play major roles. Polyunsaturated fatty acids (PUFAs) are postulated to contribute to the development of the infant brain and an imbalance in these may increase the risk of ADHD. In recent clinical studies, supplementation with PUFAs improved symptoms of ADHD in some cases. Similarly, some beneficial effects were observed with PUFA treatment in neuronal cell cultures. Therefore, in this study, we hypothesized that a specific PUFA combination (available on the market as Equazen™ [Vifor Pharma, Switzerland]) along with iron, zinc, or vitamin B5 (vitB5) would produce an additive beneficial effect on the viability of rat pheochromocytoma-12 dopaminergic cells. The specific PUFA combination alone, as well as added to each of the three nutrients, was tested in a dose-response manner. The specific PUFAs significantly improved cell viability, starting at very low doses (100pM) from 60h up to 90h; while the combined treatment with vitB5 and minerals did not provide additional benefit. Our results confirmed the beneficial effect of the specific PUFAs on neuronal cell viability; although supplementation with minerals and vitB5 did not enhance this effect.

  10. Transcranial magnetic stimulation of the brain: guidelines for pain treatment research

    PubMed Central

    Klein, Max M.; Treister, Roi; Raij, Tommi; Pascual-Leone, Alvaro; Park, Lawrence; Nurmikko, Turo; Lenz, Fred; Lefaucheur, Jean-Pascal; Lang, Magdalena; Hallett, Mark; Fox, Michael; Cudkowicz, Merit; Costello, Ann; Carr, Daniel B.; Ayache, Samar S.; Oaklander, Anne Louise

    2015-01-01

    Abstract Recognizing that electrically stimulating the motor cortex could relieve chronic pain sparked development of noninvasive technologies. In transcranial magnetic stimulation (TMS), electromagnetic coils held against the scalp influence underlying cortical firing. Multiday repetitive transcranial magnetic stimulation (rTMS) can induce long-lasting, potentially therapeutic brain plasticity. Nearby ferromagnetic or electronic implants are contraindications. Adverse effects are minimal, primarily headaches. Single provoked seizures are very rare. Transcranial magnetic stimulation devices are marketed for depression and migraine in the United States and for various indications elsewhere. Although multiple studies report that high-frequency rTMS of the motor cortex reduces neuropathic pain, their quality has been insufficient to support Food and Drug Administration application. Harvard's Radcliffe Institute therefore sponsored a workshop to solicit advice from experts in TMS, pain research, and clinical trials. They recommended that researchers standardize and document all TMS parameters and improve strategies for sham and double blinding. Subjects should have common well-characterized pain conditions amenable to motor cortex rTMS and studies should be adequately powered. They recommended standardized assessment tools (eg, NIH's PROMIS) plus validated condition-specific instruments and consensus-recommended metrics (eg, IMMPACT). Outcomes should include pain intensity and qualities, patient and clinician impression of change, and proportions achieving 30% and 50% pain relief. Secondary outcomes could include function, mood, sleep, and/or quality of life. Minimum required elements include sample sources, sizes, and demographics, recruitment methods, inclusion and exclusion criteria, baseline and posttreatment means and SD, adverse effects, safety concerns, discontinuations, and medication-usage records. Outcomes should be monitored for at least 3 months after

  11. Transcranial magnetic stimulation of the brain: guidelines for pain treatment research.

    PubMed

    Klein, Max M; Treister, Roi; Raij, Tommi; Pascual-Leone, Alvaro; Park, Lawrence; Nurmikko, Turo; Lenz, Fred; Lefaucheur, Jean-Pascal; Lang, Magdalena; Hallett, Mark; Fox, Michael; Cudkowicz, Merit; Costello, Ann; Carr, Daniel B; Ayache, Samar S; Oaklander, Anne Louise

    2015-09-01

    Recognizing that electrically stimulating the motor cortex could relieve chronic pain sparked development of noninvasive technologies. In transcranial magnetic stimulation (TMS), electromagnetic coils held against the scalp influence underlying cortical firing. Multiday repetitive transcranial magnetic stimulation (rTMS) can induce long-lasting, potentially therapeutic brain plasticity. Nearby ferromagnetic or electronic implants are contraindications. Adverse effects are minimal, primarily headaches. Single provoked seizures are very rare. Transcranial magnetic stimulation devices are marketed for depression and migraine in the United States and for various indications elsewhere. Although multiple studies report that high-frequency rTMS of the motor cortex reduces neuropathic pain, their quality has been insufficient to support Food and Drug Administration application. Harvard's Radcliffe Institute therefore sponsored a workshop to solicit advice from experts in TMS, pain research, and clinical trials. They recommended that researchers standardize and document all TMS parameters and improve strategies for sham and double blinding. Subjects should have common well-characterized pain conditions amenable to motor cortex rTMS and studies should be adequately powered. They recommended standardized assessment tools (eg, NIH's PROMIS) plus validated condition-specific instruments and consensus-recommended metrics (eg, IMMPACT). Outcomes should include pain intensity and qualities, patient and clinician impression of change, and proportions achieving 30% and 50% pain relief. Secondary outcomes could include function, mood, sleep, and/or quality of life. Minimum required elements include sample sources, sizes, and demographics, recruitment methods, inclusion and exclusion criteria, baseline and posttreatment means and SD, adverse effects, safety concerns, discontinuations, and medication-usage records. Outcomes should be monitored for at least 3 months after initiation

  12. Solid Lipid Nanoparticles Loaded with Retinoic Acid and Lauric Acid as an Alternative for Topical Treatment of Acne Vulgaris.

    PubMed

    Silva, Elton Luiz; Carneiro, Guilherme; De Araújo, Lidiane Advíncula; Trindade, Mariana de Jesus Vaz; Yoshida, Maria Irene; Oréfice, Rodrigo Lambert; Farias, Luis de Macêdo; De Carvalho, Maria Auxiliadora Roque; Dos Santos, Simone Gonçalves; Goulart, Gisele Assis Castro; Alves, Ricardo José; Ferreira, Lucas Antônio Miranda

    2015-01-01

    Topical therapy is the first choice for the treatment of mild to moderate acne and all-trans retinoic acid is one of the most used drugs. The combination of retinoids and antimicrobials is an innovative approach for acne therapy. Recently, lauric acid, a saturated fatty acid, has shown strong antimicrobial activity against Propionibacterium acnes. However, topical application of retinoic acid is followed by high incidence of side-effects, including erythema and irritation. Solid lipid nanoparticles represent an alternative to overcome these side-effects. This work aims to develop solid lipid nanoparticles loaded with retinoic acid and lauric acid and evaluate their antibacterial activity. The influence of lipophilic stearylamine on the characteristics of solid lipid nanoparticles was investigated. Solid lipid nanoparticles were characterized for size, zeta potential, encapsulation efficiency, differential scanning calorimetry and X-ray diffraction. The in vitro inhibitory activity of retinoic acid-lauric acid-loaded solid lipid nanoparticles was evaluated against Propionibacterium acnes, Staphylococcus aureus and Staphylococcus epidermidis. High encapsulation efficiency was obtained at initial time (94 ± 7% and 100 ± 4% for retinoic acid and lauric acid, respectively) and it was demonstrated that lauric acid-loaded-solid lipid nanoparticles provided the incorporation of retinoic acid. However, the presence of stearylamine is necessary to ensure stability of encapsulation. Moreover, retinoic acid-lauric acid-loaded solid lipid nanoparticles showed growth inhibitory activity against Staphylococcus epidermidis, Propionibacterium acnes and Staphylococcus aureus, representing an interesting alternative for the topical therapy of acne vulgaris. PMID:26328443

  13. Chemotherapy stimulates syndecan-1 shedding: A potentially negative effect of treatment that may promote tumor relapse

    PubMed Central

    Ramani, Vishnu C.; Sanderson, Ralph D.

    2015-01-01

    In patients with multiple myeloma, the heparan sulfate proteoglycan syndecan-1 (CD138) is shed from the surface of tumor cells and accumulates in the serum and within the extracellular matrix of the bone marrow where it promotes tumor growth and metastasis. In the present study we discovered that commonly used anti-myeloma drugs stimulate syndecan-1 shedding both in vitro and in animals bearing myeloma tumors. Enhanced shedding is accompanied by increased syndecan-1 synthesis prior to drug induced tumor cell death. Addition of a caspase inhibitor blocks the drug-induced shedding of syndecan-1 in vitro indicating that shedding is linked to the onset of apoptosis. ADAMs inhibitors or siRNA targeting ADAMs blocked drug-induced shedding suggesting that up regulation or activation of ADAMs is responsible for cleaving syndecan-1 from the tumor cell surface. These results reveal that myeloma chemotherapy stimulates synthesis and shedding of syndecan-1, a potentially negative side effect that may lead to accumulation of high levels of syndecan-1 to establish a microenvironment that nurtures relapse and promotes tumor progression. Interestingly, we also found that chemotherapeutic drugs stimulated syndecan-1 shedding from pancreatic cancer cells as well, indicating that drug-induced shedding of syndecan-1 may occur in many cancer types. Overall, our results indicate that use of metalloproteinase inhibitors (to inhibit syndecan-1 shedding) in combination with chemotherapy may represent a novel therapeutic strategy to prevent re-establishment of a microenvironment conducive for tumor relapse. PMID:24145151

  14. Soluble Guanylate Cyclase Stimulators: a Novel Treatment Option for Heart Failure Associated with Cardiorenal Syndromes?

    PubMed

    Dubin, Ruth F; Shah, Sanjiv J

    2016-06-01

    Heart failure in the setting of chronic kidney disease (CKD) is an increasingly common scenario and carries a poor prognosis. Clinicians lack tools for primary or secondary heart failure prevention in patients with cardiorenal syndromes. In patients without CKD, angiotensin-converting enzyme inhibitors (ACE-I) or angiotensin receptor blockers (ARB) and statins mitigate cardiovascular risk in large part due to salutary effects on the endothelium. In the setting of CKD, use of these therapies is limited by adverse effects of hyperkalemia in pre-dialysis CKD (ACE-I/ARB), or potential increased risk of stroke in end-stage renal disease (statins). The soluble guanylate cyclase (sGC) stimulators are a novel class of medications that promote endothelial and myocardial function with no known risk of hyperkalemia or stroke. In this review, we discuss the evidence emerging from recent clinical trials of sGC stimulators in pulmonary hypertension and heart failure, the diseased pathways involved in cardiorenal syndromes likely to be restored by sGC stimulators, and several strategies for designing future clinical trials of cardiorenal syndromes that might shorten the timeline for discovery and approval of effective cardiovascular therapies in these high-risk patients. PMID:27118234

  15. Subcutaneous Peripheral Nerve Field Stimulation for the Treatment of Chronic Back Pain: Patient Selection and Technical Aspects.

    PubMed

    Winkelmueller, Matthias; Kolodziej, Malgorzata Anna; Welke, Wolfgang; Koulousakis, Athanasios; Martinez, Ramon

    2016-01-01

    A wide variety of therapeutic options are available for the treatment of chronic back pain, a very common condition in Western countries with high related social and economic costs. Nevertheless, it is not always possible to achieve adequate long-term pain relief in spite of intensive analgesic therapies. Subcutaneous peripheral nerve field stimulation (sPNFS) is a newly approved neuromodulative treatment for back pain. In previously reported case series, it has provided encouraging results on long-term pain relief, improvement in quality of life, and a reduced need for analgesic drugs. Although the surgical technique is simple, there is neither consensus for patient management nor a standardized procedure for the implantation procedure. After consideration of our personal experience and the published literature, a basic recommendation has now been developed. This represents the first step toward planning prospective studies and standardization of this treatment and will permit comparison of this technique and the results with sPNFS.

  16. Spinal cord stimulation for long-term treatment of severe angina pectoris: what does the evidence say?

    PubMed

    Börjesson, Mats; Andréll, Paulin; Mannheimer, Clas

    2011-11-01

    Patients who continue to suffer from severe and disabling angina pectoris, despite optimum treatment in terms of conventional pharmacological therapy and/or revascularization procedures, have been termed as having refractory angina pectoris. The future group of patients with refractory angina pectoris will be different from today's patients and represent a 'moving target' as risk factors, efficacy of treatment and indications continue to change. Spinal cord stimulation (SCS) is today considered as first-line treatment of refractory angina pectoris, by the European Society of Cardiology, with an anti-ischemic effect. There is strong evidence for SCS giving symptomatic benefits (decrease in anginal attacks), improved quality of life and improvement of functional status. In addition, SCS seems to be cost effective with a 'break-even' after approximately 15-16 months.

  17. Pain Reduction in Myofascial Pain Syndrome by Anodal Transcranial Direct Current Stimulation Combined with Standard Treatment: A Randomized Controlled Study

    PubMed Central

    Sakrajai, Piyaraid; Janyacharoen, Taweesak; Jensen, Mark P.; Sawanyawisuth, Kittisak; Auvichayapat, Narong; Tunkamnerdthai, Orathai; Keeratitanont, Keattichai; Auvichayapat, Paradee

    2014-01-01

    Background Myofascial pain syndrome (MPS) in the shoulder is among the most prevalent pain problems in the middle-aged population worldwide. Evidence suggests that peripheral and central sensitization may play an important role in the development and maintenance of shoulder MPS. Given previous research supporting the potential efficacy of anodal transcranial direct current stimulation (tDCS) for modulating pain-related brain activity in individuals with refractory central pain, we hypothesized that anodal tDCS when applied over the primary motor cortex (M1) combined with standard treatment will be more effective for reducing pain in patients with MPS than standard treatment alone. Method Study participants were randomized to receive either (1) standard treatment with 5-consecutive days of 1 mA anodal tDCS over M1 for 20 min or (2) standard treatment plus sham tDCS. Measures of pain intensity, shoulder passive range of motion, analgesic medication use, and self-reported physical functioning were administered before treatment and again at post-treatment and 1-, 2-, 3-and 4-week follow-up. Results Thirty-one patients with MPS were enrolled. Participants assigned to the active tDCS condition reported significantly more pre- to post-treatment reductions in pain intensity that were maintained at 1-week post-treatment, and significant improvement in shoulder adduction PROM at 1-week follow-up than participants assigned to the sham tDCS condition. Conclusion 5 consecutive days of anodal tDCS over M1 combined with standard treatment appears to reduce pain intensity, and may improve PROM, faster than standard treatment alone. Further tests of the efficacy and duration of effects of tDCS in the treatment of MPS are warranted. PMID:25373724

  18. Fever-range whole-body heat treatment stimulates antigen-specific T-cell responses in humans.

    PubMed

    Kobayashi, Yasunobu; Ito, Yusuke; Ostapenko, Valentina V; Sakai, Mayuko; Matsushita, Norimasa; Imai, Kenichiro; Shimizu, Koichi; Aruga, Atsushi; Tanigawa, Keishi

    2014-11-01

    Increase in body temperature has been thought to play an important role in the regulation of immune responses, although its precise mechanisms are still under investigation. Here, we examined the effects of physiologically relevant thermal stress on the cytokine production from human peripheral T cells. Volunteers were heated using a whole-body hyperthermia device, the rectal temperature was maintained above 38.5 °C for more than 60 min, and peripheral blood mononuclear cells (PBMCs) were obtained before and after the treatment. When T cells were stimulated with anti-CD3/CD28 antibodies, marked increases in the production of interferon-γ (IFN-γ) and interleukin-2 were observed in PBMCs prepared immediately after and 24h after the treatment. Similarly, enhanced production of IFN-γ in response to the tuberculin purified protein derivative or antigenic viral peptides was also observed immediately after and 24h after the treatment. Fluorescence photo-bleaching analyses showed heat-induced increase of membrane fluidity in T cells, which probably enables them to induce rapid and efficient cluster formation of molecules involved in antigen recognition and signal transduction for T-cell stimulation. We concluded that physiologically relevant thermal stress could efficiently modify T-cell responsiveness to various stimuli, including enhanced responses to specific antigens.

  19. Exploratory study of the association of steroid profiles in stimulated ovarian follicular fluid with outcomes of IVF treatment.

    PubMed

    Kushnir, Mark M; Naessén, Tord; Wanggren, Kjell; Hreinsson, Julius; Rockwood, Alan L; Meikle, A Wayne; Bergquist, Jonas

    2016-09-01

    Steroid concentrations in stimulated follicular fluid (sFF) samples have been linked to the quality of oocytes used in IVF treatments. Most of the published studies focused on evaluating the association of the IVF outcomes with only a few of the steroids, measured by immunoassays (IA). We performed a treatment outcome, prospective cohort study using stimulated FF sampled from 14 infertile women undergoing IVF treatment; single oocyte was used per IVF cycle. Fourteen endogenous steroids were analyzed in 22 ovarian follicle aspirations, which corresponded to the embryos used in the IVF. Ten oocytes were associated with live birth (LB) and 12 with no pregnancy (NP). Steroids were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods. Differences in distribution of concentrations in association with the pregnancy outcome (LB or NP), and receiver operating characteristic (ROC) curves analysis were performed for the entire cohort and for within-women data. The predominant androgen and estrogen in stimulated sFF were androstenedione (A4) and estradiol (E2), respectively. Lower concentrations of pregnenolone (Pr), lower ratios of A4/ dehydroepiandrosterone (DHEA), testosterone (Te)/DHEA, and greater ratios of E2/Te, and estrone/A4 were observed in sFF samples associated with LB. Among the oocytes associated with NP, in four out of 12 samples total concentration of androgens was above the distribution of the concentrations in the oocytes corresponding to the LB group. Observations of the study indicated increased consumption of precursors and increased biosynthesis of estrogens in the follicles associated with LB. Our data suggest that potentially steroid profiles in sFF obtained during oocyte retrieval may serve as biomarkers for selection of the best embryo to transfer after IVF.

  20. The Safety of Erythropoiesis-Stimulating Agents for the Treatment of Anemia Resulting from Chronic Kidney Disease.

    PubMed

    Robles, Nicolas Roberto

    2016-06-01

    Chronic kidney disease (CKD) anemia treatment was revolutionized in the late 1980s with the introduction of recombinant human erythropoietin. This and related erythropoiesis-stimulating agents (ESAs) greatly benefited patients by decreasing debilitating symptoms, improving their quality of life, and freeing them from dependence on blood transfusions with their associated complications such as infections, sensitization impeding transplantation, and secondary iron overload. However, even in the initial studies, untoward effects were noted in patients receiving ESAs, including worsening hypertension, seizures, and dialysis access clotting. Later, increased mortality, malignancy progression and even stroke were reported in renal patients. This review focuses on the safety issues of ESAs in CKD patients.

  1. The Safety of Erythropoiesis-Stimulating Agents for the Treatment of Anemia Resulting from Chronic Kidney Disease.

    PubMed

    Robles, Nicolas Roberto

    2016-06-01

    Chronic kidney disease (CKD) anemia treatment was revolutionized in the late 1980s with the introduction of recombinant human erythropoietin. This and related erythropoiesis-stimulating agents (ESAs) greatly benefited patients by decreasing debilitating symptoms, improving their quality of life, and freeing them from dependence on blood transfusions with their associated complications such as infections, sensitization impeding transplantation, and secondary iron overload. However, even in the initial studies, untoward effects were noted in patients receiving ESAs, including worsening hypertension, seizures, and dialysis access clotting. Later, increased mortality, malignancy progression and even stroke were reported in renal patients. This review focuses on the safety issues of ESAs in CKD patients. PMID:26894799

  2. Towards energy positive wastewater treatment by sludge treatment using free nitrous acid.

    PubMed

    Wang, Qilin; Hao, Xiaodi; Yuan, Zhiguo

    2016-02-01

    Free nitrous acid (FNA i.e. HNO2) was revealed to be effective in enhancing biodegradability of secondary sludge. Also, nitrite-oxidizing bacteria were found to be more susceptible to FNA than ammonium-oxidizing bacteria. Based on these findings, a novel FNA-based sludge treatment technology is proposed to enhance energy recovery from wastewater/sludge. Energy analysis indicated that the FNA-based technology would make wastewater treatment become an energy generating process (yielding energy at 4 kWh/PE/y; kWh/PE/y: kilowatt hours per population equivalent per year), rather than being a large energy consumer that it is today (consuming energy at 24 kWh/PE/y). Importantly, FNA required for the sludge treatment could be produced as a by-product of wastewater treatment. This proposed FNA-based technology is economically and environmentally attractive, and can be easily implemented in any wastewater treatment plants. It only involves the installation of a simple sludge mixing tank. This article presents the concept of the FNA-based technology.

  3. Towards energy positive wastewater treatment by sludge treatment using free nitrous acid.

    PubMed

    Wang, Qilin; Hao, Xiaodi; Yuan, Zhiguo

    2016-02-01

    Free nitrous acid (FNA i.e. HNO2) was revealed to be effective in enhancing biodegradability of secondary sludge. Also, nitrite-oxidizing bacteria were found to be more susceptible to FNA than ammonium-oxidizing bacteria. Based on these findings, a novel FNA-based sludge treatment technology is proposed to enhance energy recovery from wastewater/sludge. Energy analysis indicated that the FNA-based technology would make wastewater treatment become an energy generating process (yielding energy at 4 kWh/PE/y; kWh/PE/y: kilowatt hours per population equivalent per year), rather than being a large energy consumer that it is today (consuming energy at 24 kWh/PE/y). Importantly, FNA required for the sludge treatment could be produced as a by-product of wastewater treatment. This proposed FNA-based technology is economically and environmentally attractive, and can be easily implemented in any wastewater treatment plants. It only involves the installation of a simple sludge mixing tank. This article presents the concept of the FNA-based technology. PMID:26539712

  4. Implementation of a smartphone wireless accelerometer platform for establishing deep brain stimulation treatment efficacy of essential tremor with machine learning.

    PubMed

    LeMoyne, Robert; Tomycz, Nestor; Mastroianni, Timothy; McCandless, Cyrus; Cozza, Michael; Peduto, David

    2015-01-01

    Essential tremor (ET) is a highly prevalent movement disorder. Patients with ET exhibit a complex progressive and disabling tremor, and medical management often fails. Deep brain stimulation (DBS) has been successfully applied to this disorder, however there has been no quantifiable way to measure tremor severity or treatment efficacy in this patient population. The quantified amelioration of kinetic tremor via DBS is herein demonstrated through the application of a smartphone (iPhone) as a wireless accelerometer platform. The recorded acceleration signal can be obtained at a setting of the subject's convenience and conveyed by wireless transmission through the Internet for post-processing anywhere in the world. Further post-processing of the acceleration signal can be classified through a machine learning application, such as the support vector machine. Preliminary application of deep brain stimulation with a smartphone for acquisition of a feature set and machine learning for classification has been successfully applied. The support vector machine achieved 100% classification between deep brain stimulation in `on' and `off' mode based on the recording of an accelerometer signal through a smartphone as a wireless accelerometer platform. PMID:26737848

  5. A Sustainable Approach for Acid Rock Drainage Treatment using Clinoptilolite

    NASA Astrophysics Data System (ADS)

    Li, L. Y.; Xu, W.; Grace, J. R.

    2009-04-01

    Problems related to acid rock drainage (ARD) occur along many highways of British Columbia. The ARD problem at Pennask Creek along Highway 97C in the Thompson-Okanagan region is an ideal site for pilot study to investigate a possible remediation solution. The highway was opened in 1991. An ARD problem was identified in 1997. Both sides of Highway 97C are producing acidified runoff from both cut rock surface and a fractured ditch. This runoff eventually enters Pennask Creek, the largest spawning source of rainbow trout in British Columbia. The current remediation technique using limestone for ARD treatment appears to be unnecessarily expensive, to generate additional solid waste and to not be optimally effective. A soil mineral natural zeolite - clinoptilolite - which is inexpensive and locally available, has a high metal adsorption capacity and a significant buffering capacity. Moreover, the clinoptilolite materials could be back-flushed and reused on site. An earlier batch adsorption study from our laboratory demonstrated that clinoptilolite has a high adsorption capacity for Cu, Zn, Al, with adsorption concentrations 131, 158 and 215 mg/kg clinoptilolite, respectively, from ARD of pH 3.3. Removal of metals from the loaded clinoptilolite by back-flushing was found to depend on the pH, with an optimum pH range for extraction of 2.5 to 4.0 for a contact time of one hour. The rank of desorption effectiveness was EDTA > NaCl > NaNO3 > NaOAC > NaHCO3 > Na2CO3 > NaOH > Ca(OH)2. A novel process involving cyclic adsorption on clinoptilolite followed by regeneration of the sorbent by desorption is examined for the removal of heavy metals from acid rock drainage. Experimental results show that the adsorption of zinc and copper depends on the pH and on external mass transfer. Desorption is assisted by adding NaCl to the water. A slurry bubble column was able to significantly reduce the time required for both adsorption and desorption in batch tests. XRD analysis indicated

  6. Surgical approaches to treatment of gastroparesis: gastric electrical stimulation, pyloroplasty, total gastrectomy and enteral feeding tubes.

    PubMed

    Sarosiek, Irene; Davis, Brian; Eichler, Evelin; McCallum, Richard W

    2015-03-01

    Gastric electrical stimulation (GES) is neurostimulation; its mechanism of action is affecting central control of nausea and vomiting and enhancing vagal function. GES is a powerful antiemetic available for patients with refractory symptoms of nausea and vomiting from gastroparesis of idiopathic and diabetic causes. GES is not indicated as a way of reducing abdominal pain in gastroparetic patients. The need for introducing a jejunal feeding tube means intensive medical therapies are failing, and is an indication for the implantation of the GES system, which should always be accompanied by a pyloroplasty to guarantee accelerated gastric emptying.

  7. Lactoferrin Combined with Retinoic Acid Stimulates B1 Cells to Express IgA Isotype and Gut-homing Molecules.

    PubMed

    Kang, Seong-Ho; Jin, Bo-Ra; Kim, Hyeon-Jin; Seo, Goo-Young; Jang, Young-Saeng; Kim, Sun-Jin; An, Sun-Jin; Park, Seok-Rae; Kim, Woan-Sub; Kim, Pyeung-Hyeun

    2015-02-01

    It is well established that TGF-β1 and retinoic acid (RA) cause IgA isotype switching in mice. We recently found that lactoferrin (LF) also has an activity of IgA isotype switching in spleen B cells. The present study explored the effect of LF on the Ig production by mouse peritoneal B cells. LF, like TGF-β1, substantially increased IgA production in peritoneal B1 cells but little in peritoneal B2 cells. In contrast, LF increased IgG2b production in peritoneal B2 cells much more strongly than in peritoneal B1 cells. LF in combination with RA further enhanced the IgA production and, interestingly, this enhancement was restricted to IgA isotype and B1 cells. Similarly, the combination of the two molecules also led to expression of gut homing molecules α4β7 and CCR9 on peritoneal B1 cells, but not on peritoneal B2 cells. Thus, these results indicate that LF and RA can contribute to gut IgA response through stimulating IgA isotype switching and expression of gut-homing molecules in peritoneal B1 cells.

  8. Fatty acid-induced mitochondrial uncoupling in adipocytes is not a promising target for treatment of insulin resistance unless adipocyte oxidative capacity is increased.

    PubMed

    Frayn, K N; Langin, D; Karpe, F

    2008-03-01

    The release of fatty acids from white adipose tissue is regulated at several levels. We have examined the suggestion that fatty acid release might be diminished by upregulation of mitochondrial fatty acid oxidation in the adipocyte, through increasing mitochondrial uncoupling. The intrinsic oxidative capacity of white adipose tissue is low, and older studies suggest that there is little fatty acid oxidation in white adipocytes, human or rodent. We have examined data on fatty acid metabolism and O(2) consumption in human white adipose tissue in vivo, and conclude that increasing fatty acid oxidation within the oxidative capacity of the tissue would produce only small changes (a few percent) in fatty acid release. The major locus of control of fatty acid release beyond the stimulation of lipolysis is the pathway of fatty acid esterification, already probably targeted by the thiazolidinedione insulin-sensitising agents. An alternative approach would be to upregulate the mitochondrial capacity of the adipocyte. We review proof-of-concept studies in which the phenotype of the white adipocyte has been changed to resemble that of the brown adipocyte by expression of peroxisome proliferator-activated receptor coactivator-1alpha. This increases oxidative capacity and also leads to fatty acid retention through upregulation of glycerol-3-phosphate production, and hence increased fatty acid re-esterification. We conclude that prevention or treatment of insulin resistance through alteration of adipocyte fatty acid handling will require more than a simple alteration of the activity of mitochondrial beta-oxidation within normal limits.

  9. A Pilot Study of Safety and Efficacy of Cranial Electrotherapy Stimulation in Treatment of Bipolar II Depression.

    PubMed

    McClure, Deimante; Greenman, Samantha C; Koppolu, Siva Sundeep; Varvara, Maria; Yaseen, Zimri S; Galynker, Igor I

    2015-11-01

    This double-blind, sham-controlled study sought to investigate the effectiveness of cranial electrotherapy stimulation (CES) for the treatment of bipolar II depression (BD II). After randomization, the active group participants (n = 7) received 2 mA CES treatment for 20 minutes five days a week for 2 weeks, whereas the sham group (n = 9) had the CES device turned on and off. Symptom non-remitters from both groups received an additional 2 weeks of open-label active treatment. Active CES treatment but not sham treatment was associated with a significant decrease in the Beck Depression Inventory (BDI) scores from baseline to the second week (p = 0.003) maintaining significance until week 4 (p = 0.002). There was no difference between the groups in side effects frequency. The results of this small study indicate that CES may be a safe and effective treatment for BD II suggesting that further studies on safety and efficacy of CES may be warranted.

  10. Resting-state fMRI study of acute migraine treatment with kinetic oscillation stimulation in nasal cavity.

    PubMed

    Li, Tie-Qiang; Wang, Yanlu; Hallin, Rolf; Juto, Jan-Erik

    2016-01-01

    Kinetic oscillatory stimulation (KOS) in the nasal cavity is a non-invasive cranial nerve stimulation method with promising efficacy for acute migraine and other inflammatory disorders. For a better understanding of the underlying neurophysiological mechanisms of KOS treatment, we conducted a resting-state functional magnetic resonance imaging (fMRI) study of 10 acute migraine patients and 10 normal control subjects during KOS treatment in a 3 T clinical MRI scanner. The fMRI data were first processed using a group independent component analysis (ICA) method and then further analyzed with a voxel-wise 3-way ANOVA modeling and region of interest (ROI) of functional connectivity metrics. All migraine participants were relieved from their acute migraine symptoms after 10-20 min KOS treatment and remained migraine free for 3-6 months. The resting-state fMRI result indicates that migraine patients have altered intrinsic functional activity in the anterior cingulate, inferior frontal gyrus and middle/superior temporal gyrus. KOS treatment gave rise to up-regulated intrinsic functional activity for migraine patients in a number of brain regions involving the limbic and primary sensory systems, while down regulating temporally the activity for normal controls in a few brain areas, such as the right dorsal posterior insula and inferior frontal gyrus. The result of this study confirms the efficacy of KOS treatment for relieving acute migraine symptoms and reducing attack frequency. Resting-state fMRI measurements demonstrate that migraine is associated with aberrant intrinsic functional activity in the limbic and primary sensory systems. KOS in the nasal cavity gives rise to the adjustment of the intrinsic functional activity in the limbic and primary sensory networks and restores the physiological homeostasis in the autonomic nervous system. PMID:27622142

  11. Hepcidin as a predictive factor and therapeutic target in erythropoiesis-stimulating agent treatment for anemia of chronic disease in rats.

    PubMed

    Theurl, Milan; Nairz, Manfred; Schroll, Andrea; Sonnweber, Thomas; Asshoff, Malte; Haschka, David; Seifert, Markus; Willenbacher, Wolfgang; Wilflingseder, Doris; Posch, Wilfried; Murphy, Anthony T; Witcher, Derrick R; Theurl, Igor; Weiss, Günter

    2014-09-01

    Anemia of chronic disease is a multifactorial disorder, resulting mainly from inflammation-driven reticuloendothelial iron retention, impaired erythropoiesis, and reduced biological activity of erythropoietin. Erythropoiesis-stimulating agents have been used for the treatment of anemia of chronic disease, although with varying response rates and potential adverse effects. Serum concentrations of hepcidin, a key regulator of iron homeostasis, are increased in patients with anemia of chronic disease and linked to the pathogenesis of this disease, because hepcidin blocks cellular iron egress, thus limiting availability of iron for erythropoiesis. We tested whether serum hepcidin levels can predict and affect the therapeutic efficacy of erythropoiesis-stimulating agent treatment using a well-established rat model of anemia of chronic disease. We found that high pre-treatment hepcidin levels correlated with an impaired hematologic response to an erythropoiesis-stimulating agent in rats with anemia of chronic disease. Combined treatment with an erythropoiesis-stimulating agent and an inhibitor of hepcidin expression, LDN-193189, significantly reduced serum hepcidin levels, mobilized iron from tissue stores, increased serum iron levels and improved hemoglobin levels more effectively than did the erythropoiesis-stimulating agent or LDN-193189 monotherapy. In parallel, both the erythropoiesis-stimulating agent and erythropoiesis-stimulating agent/LDN-193189 combined reduced the expression of cytokines known to inhibit erythropoiesis. We conclude that serum hepcidin levels can predict the hematologic responsiveness to erythropoiesis-stimulating agent therapy in anemia of chronic disease. Pharmacological inhibition of hepcidin formation improves the erythropoiesis-stimulating agent's therapeutic efficacy, which may favor a reduction of erythropoiesis-stimulating agent dosages, costs and side effects.

  12. Increasing Production from Low-Permeability Gas Reservoirs by Optimizing Zone Isolation for Successful Stimulation Treatments

    SciTech Connect

    Fred Sabins

    2005-03-31

    Maximizing production from wells drilled in low-permeability reservoirs, such as the Barnett Shale, is determined by cementing, stimulation, and production techniques employed. Studies show that cementing can be effective in terms of improving fracture effectiveness by 'focusing' the frac in the desired zone and improving penetration. Additionally, a method is presented for determining the required properties of the set cement at various places in the well, with the surprising result that uphole cement properties in wells destined for multiple-zone fracturing is more critical than those applied to downhole zones. Stimulation studies show that measuring pressure profiles and response during Pre-Frac Injection Test procedures prior to the frac job are critical in determining if a frac is indicated at all, as well as the type and size of the frac job. This result is contrary to current industry practice, in which frac jobs are designed well before the execution, and carried out as designed on location. Finally, studies show that most wells in the Barnett Shale are production limited by liquid invasion into the wellbore, and determinants are presented for when rod or downhole pumps are indicated.

  13. Transcranial magnetic stimulation: potential treatment for co-occurring alcohol, traumatic brain injury and posttraumatic stress disorders

    PubMed Central

    Herrold, Amy A.; Kletzel, Sandra L.; Harton, Brett C.; Chambers, R. Andrew; Jordan, Neil; Pape, Theresa Louise-Bender

    2014-01-01

    Alcohol use disorder (AUD), mild traumatic brain injury (mTBI), and posttraumatic stress disorder (PTSD) commonly co-occur (AUD + mTBI + PTSD). These conditions have overlapping symptoms which are, in part, reflective of overlapping neuropathology. These conditions become problematic because their co-occurrence can exacerbate symptoms. Therefore, treatments must be developed that are inclusive to all three conditions. Repetitive transcranial magnetic stimulation (rTMS) is non-invasive and may be an ideal treatment for co-occurring AUD + mTBI + PTSD. There is accumulating evidence on rTMS as a treatment for people with AUD, mTBI, and PTSD each alone. However, there are no published studies to date on rTMS as a treatment for co-occurring AUD + mTBI + PTSD. This review article advances the knowledge base for rTMS as a treatment for AUD + mTBI + PTSD. This review provides background information about these co-occurring conditions as well as rTMS. The existing literature on rTMS as a treatment for people with AUD, TBI, and PTSD each alone is reviewed. Finally, neurobiological findings in support of a theoretical model are discussed to inform TMS as a treatment for co-occurring AUD + mTBI + PTSD. The peer-reviewed literature was identified by targeted literature searches using PubMed and supplemented by cross-referencing the bibliographies of relevant review articles. The existing evidence on rTMS as a treatment for these conditions in isolation, coupled with the overlapping neuropathology and symptomology of these conditions, suggests that rTMS may be well suited for the treatment of these conditions together. PMID:25422632

  14. Deep Brain Stimulation for Obsessive-Compulsive Disorder: A Meta-Analysis of Treatment Outcome and Predictors of Response

    PubMed Central

    Alonso, Pino; Cuadras, Daniel; Gabriëls, Loes; Denys, Damiaan; Goodman, Wayne; Greenberg, Ben D.; Jimenez-Ponce, Fiacro; Kuhn, Jens; Lenartz, Doris; Mallet, Luc; Nuttin, Bart; Real, Eva; Segalas, Cinto; Schuurman, Rick; Tezenas du Montcel, Sophie; Menchon, Jose M.

    2015-01-01

    Background Deep brain stimulation (DBS) has been proposed as an alternative to ablative neurosurgery for severe treatment-resistant Obsessive-Compulsive Disorder (OCD), although with partially discrepant results probably related to differences in anatomical targetting and stimulation conditions. We sought to determine the efficacy and tolerability of DBS in OCD and the existence of clinical predictors of response using meta-analysis. Methods We searched the literature on DBS for OCD from 1999 through January 2014 using PubMed/MEDLINE and PsycINFO. We performed fixed and random-effect meta-analysis with score changes (pre-post DBS) on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) as the primary-outcome measure, and the number of responders to treatment, quality of life and acceptability as secondary measures. Findings Thirty-one studies involving 116 subjects were identified. Eighty-three subjects were implanted in striatal areas—anterior limb of the internal capsule, ventral capsule and ventral striatum, nucleus accumbens and ventral caudate—27 in the subthalamic nucleus and six in the inferior thalamic peduncle. Global percentage of Y-BOCS reduction was estimated at 45.1% and global percentage of responders at 60.0%. Better response was associated with older age at OCD onset and presence of sexual/religious obsessions and compulsions. No significant differences were detected in efficacy between targets. Five patients dropped out, but adverse effects were generally reported as mild, transient and reversible. Conclusions Our analysis confirms that DBS constitutes a valid alternative to lesional surgery for severe, therapy-refractory OCD patients. Well-controlled, randomized studies with larger samples are needed to establish the optimal targeting and stimulation conditions and to extend the analysis of clinical predictors of outcome. PMID:26208305

  15. Increase in c-Fos and Arc protein in retrosplenial cortex after memory-improving lateral hypothalamic electrical stimulation treatment.

    PubMed

    Kádár, Elisabeth; Vico-Varela, Eva; Aldavert-Vera, Laura; Huguet, Gemma; Morgado-Bernal, Ignacio; Segura-Torres, Pilar

    2016-02-01

    Post-training Intracranial self-stimulation (ICSS) of the lateral hypothalamus (LH), a kind of rewarding deep-brain stimulation, potentiates learning and memory and increases c-Fos protein expression in specific memory-related brain regions. In a previous study, Aldavert-Vera et al. (2013) reported that post-acquisition LH-ICSS improved 48 h retention of a delay two-way active avoidance conditioning (TWAA) and induced c-Fos expression increase in CA3 at 90 min after administration. Nevertheless, this c-Fos induction was only observed after the acquisition session and not after the retention test at 48 h, when the ICSS improving effect was observed on memory. This current study aims to examine the hypothesis that post-training ICSS treatment may stimulate c-Fos expression at the time of the TWAA retention test in retrosplenial cortex (RSC), a hippocampus-related brain region more closely related with long-lasting memory storage. Effects of ICSS on Arc protein, a marker of memory-associated synaptic plasticity, were also measured by immunohistochemistry in granular and agranular RSC. The most innovative results are that the ICSS treatment potentiates the c-Fos induction across TWAA conditions (no conditioning, acquisition and retention), specifically in layer V of the granular RSC, along with increases of Arc protein levels in the granular but not in agranular areas of RSC ipsilaterally few hours after ICSS. This leads us to suggest that plasticity-related protein activation in the granular RSC could be involved in the positive modulatory effects of ICSS on TWAA memory consolidation, opening a new approach for future research in ICSS memory facilitation.

  16. Increase in c-Fos and Arc protein in retrosplenial cortex after memory-improving lateral hypothalamic electrical stimulation treatment.

    PubMed

    Kádár, Elisabeth; Vico-Varela, Eva; Aldavert-Vera, Laura; Huguet, Gemma; Morgado-Bernal, Ignacio; Segura-Torres, Pilar

    2016-02-01

    Post-training Intracranial self-stimulation (ICSS) of the lateral hypothalamus (LH), a kind of rewarding deep-brain stimulation, potentiates learning and memory and increases c-Fos protein expression in specific memory-related brain regions. In a previous study, Aldavert-Vera et al. (2013) reported that post-acquisition LH-ICSS improved 48 h retention of a delay two-way active avoidance conditioning (TWAA) and induced c-Fos expression increase in CA3 at 90 min after administration. Nevertheless, this c-Fos induction was only observed after the acquisition session and not after the retention test at 48 h, when the ICSS improving effect was observed on memory. This current study aims to examine the hypothesis that post-training ICSS treatment may stimulate c-Fos expression at the time of the TWAA retention test in retrosplenial cortex (RSC), a hippocampus-related brain region more closely related with long-lasting memory storage. Effects of ICSS on Arc protein, a marker of memory-associated synaptic plasticity, were also measured by immunohistochemistry in granular and agranular RSC. The most innovative results are that the ICSS treatment potentiates the c-Fos induction across TWAA conditions (no conditioning, acquisition and retention), specifically in layer V of the granular RSC, along with increases of Arc protein levels in the granular but not in agranular areas of RSC ipsilaterally few hours after ICSS. This leads us to suggest that plasticity-related protein activation in the granular RSC could be involved in the positive modulatory effects of ICSS on TWAA memory consolidation, opening a new approach for future research in ICSS memory facilitation. PMID:26774022

  17. Treatment of acne vulgaris with the retinoic acid derivative Ro 11-1430. A controlled clinical trial against retinoic acid.

    PubMed

    Christiansen, J; Holm, P; Reymann, F

    1976-01-01

    In a double-blind, randomized, group-comparative clinical trial, 31 patients with acne vulgaris received topical treatment for 6-8 weeks with a lotion containing either 0.05% retinoic acid or 0.1% of the retinoic acid derivative Ro 11-1430. The side-effects erythema, desquamation and burning were significantly less frequent with Ro 11-1430 than with retinoic acid. The treatments appeared to be approximately equally effective in reducing the number of acne elements, but due to the limited number of patients studied, the trial was admittedly not sufficient to detect differences with regard to therapeutic efficacy.

  18. Applications of transcranial magnetic stimulation and magnetic seizure therapy in the study and treatment of disorders related to cerebral aging.

    PubMed

    Luber, Bruce; McClintock, Shawn M; Lisanby, Sarah H

    2013-03-01

    Transcranial magnetic stimulation (TMS) can be used to probe cortical function and treat neuropsychiatric illnesses. TMS has demonstrated neuroplastic effects akin to long-term potentiation and long-term depression, and therapeutic applications are in development for post-stroke recovery, Alzheimer's disease, and depression in seniors. Here, we discuss two new directions of TMS research relevant to cerebral aging and cognition. First, we introduce a paradigm for enhancing cognitive reserve, based on our research in sleep deprivation. Second, we discuss the use of magnetic seizure therapy (MST) to spare cognitive functions relative to conventional electroconvulsive therapy, and as a means of providing a more potent antidepressant treatment when subconvulsive TMS has shown modest efficacy in seniors. Whether in the enhancement of cognition as a treatment goal, or in the reduction of amnesia as a side effect, these approaches to the use of TMS and MST merit further exploration regarding their clinical potential.

  19. Pallidal deep brain stimulation for the treatment of DYT6 dystonia: a case report and review of literature

    PubMed Central

    Miri, Shahnaz; Shahidi, Gholam Ali; Parvaresh, Mansour; Rohani, Mohammad

    2014-01-01

    Little is known about the results of pallidal deep brain stimulation (DBS) in DYT6 dystonia. This will be the first report of DYT6 dystonia treated with pallidal DBS from Iran. A 21 years old male patient with DYT6 dystonia underwent bilateral deep brain stimulation. The target of DBS was the sensorimotor region of the posteroventral globus pallidus internus (GPi). DBS parameters included an amplitude of 2.7 V, frequency of 160 Hz, and pulse width of 90 μs which were adjusted according to the patient's response 12 months after surgery. Treatment outcome was measured by the patient’s Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) score. Before surgery, the patient's BFMDRS score was 32. However, BFMDRS score reduced to 7 at one year follow up after surgery (78% improvement of total score). Dystonic symptoms of extremities and mouth completely resolved. Also speech and swallowing function significantly improved. Although previous observations reported a poor to moderate response in speech, we found DBS as an effective treatment not only for dystonic features, but also for speech improvement of DYT6 dystonia. PMID:25250280

  20. ADHD, stimulant treatment in childhood and subsequent substance abuse in adulthood - a naturalistic long-term follow-up study.

    PubMed

    Dalsgaard, Søren; Mortensen, Preben Bo; Frydenberg, Morten; Thomsen, Per Hove

    2014-01-01

    The purpose of the study was to estimate the risk of substance use disorder (SUD) and alcohol abuse in adulthood among children and adolescents with attention-deficit hyperactivity disorder (ADHD) compared to the background population. Furthermore, to examine whether the age at initiation and duration of stimulant treatment in childhood predicts SUD and alcohol abuse in adulthood. 208 youths with ADHD (183 boys; 25 girls) were followed prospectively. Diagnoses of SUD and alcohol abuse were obtained from The Danish Psychiatric Central Register. The relative risk (RR) of SUD and alcohol abuse for cases with ADHD, compared to the background population was 7.7 (4.3-13.9) and 5.2 (2.9-9.4), respectively. Female gender, conduct disorder in childhood and older age at initiation of stimulant treatment increased the risk of later SUD and alcohol abuse. Our results warrant increased focus on the possibly increased risk of substance abuse in females with ADHD compared to males with ADHD.

  1. Post-Traumatic, Drug-Resistant Epilepsy and Review of Seizure Control Outcomes from Blinded, Randomized Controlled Trials of Brain Stimulation Treatments for Drug-Resistant Epilepsy

    PubMed Central

    Meyer, R. Michael; Szuflita, Nicholas S; Severson, Meryl A; Levine, Zachary T

    2016-01-01

    Background: Many post-traumatic epilepsy (PTE) patients become resistant to medications. Nervous stimulation as a treatment for drug-resistant epilepsy (DRE) is an active area of clinical investigation. Objective: To summarize methods, reported seizure control outcome measures, and adverse events from blinded, randomized control trials (RCTs) for selected invasive brain stimulation (IBS) and non-invasive brain stimulation (NIBS) treatment options in patients with DRE. Methods: PubMed was searched for articles from 1995-2014, using search terms related to the topics of interest. Available relevant articles reporting the outcomes of interest were identified and data was extracted. Articles in the reference lists of relevant articles and clinicaltrials.gov were also referenced. Results: Eleven articles were analyzed with a total of 795 patients identified. Studies showed that select nervous stimulation treatments significantly reduced seizure frequency in patients with DRE.  PMID:27672534

  2. Post-Traumatic, Drug-Resistant Epilepsy and Review of Seizure Control Outcomes from Blinded, Randomized Controlled Trials of Brain Stimulation Treatments for Drug-Resistant Epilepsy

    PubMed Central

    Meyer, R. Michael; Szuflita, Nicholas S; Severson, Meryl A; Levine, Zachary T

    2016-01-01

    Background: Many post-traumatic epilepsy (PTE) patients become resistant to medications. Nervous stimulation as a treatment for drug-resistant epilepsy (DRE) is an active area of clinical investigation. Objective: To summarize methods, reported seizure control outcome measures, and adverse events from blinded, randomized control trials (RCTs) for selected invasive brain stimulation (IBS) and non-invasive brain stimulation (NIBS) treatment options in patients with DRE. Methods: PubMed was searched for articles from 1995-2014, using search terms related to the topics of interest. Available relevant articles reporting the outcomes of interest were identified and data was extracted. Articles in the reference lists of relevant articles and clinicaltrials.gov were also referenced. Results: Eleven articles were analyzed with a total of 795 patients identified. Studies showed that select nervous stimulation treatments significantly reduced seizure frequency in patients with DRE. 

  3. Positive Affect Stimulation and Sustainment (PASS) Module for Depressed Mood: A preliminary investigation of treatment-related effects.

    PubMed

    McMakin, Dana L; Siegle, Greg J; Shirk, Stephen R

    2011-06-01

    Positive affective functioning (PAF) is critical to the development, course and treatment of depressive symptoms. Targeting key features of PAF during treatment may provide a new angle through which to improve affective functioning and reduce symptoms. The current study was a treatment development trial for the Positive Affect Stimulation and Sustainment (PASS) Module. PASS is conceptualized as a means of capitalizing on positive events (e.g. planned through behavioral activation) by enhancing and sustaining positive affective states through savoring, and establishing positive attributions and expectancies. Participants were 27 female college students with dysphoric symptoms. There was a moderate effect of PASS on depressive symptoms. There was also a significant within session increase in positive affect from pre to post session among the PASS group, relative to active control; and a significant decrease in positive affect from pre (baseline) to post (follow-up) treatment among the c