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Sample records for l-name increases arachidonic

  1. Nitric oxide donors prevent while the nitric oxide synthase inhibitor L-NAME increases arachidonic acid plus CYP2E1-dependent toxicity

    International Nuclear Information System (INIS)

    Wu Defeng; Cederbaum, Arthur

    2006-01-01

    Polyunsaturated fatty acids such as arachidonic acid (AA) play an important role in alcohol-induced liver injury. AA promotes toxicity in rat hepatocytes with high levels of cytochrome P4502E1 and in HepG2 E47 cells which express CYP2E1. Nitric oxide (NO) participates in the regulation of various cell activities as well as in cytotoxic events. NO may act as a protectant against cytotoxic stress or may enhance cytotoxicity when produced at elevated concentrations. The goal of the current study was to evaluate the effect of endogenously or exogenously produced NO on AA toxicity in liver cells with high expression of CYP2E1 and assess possible mechanisms for its actions. Pyrazole-induced rat hepatocytes or HepG2 cells expressing CYP2E1 were treated with AA in the presence or absence of an inhibitor of nitric oxide synthase L-N G -Nitroarginine Methylester (L-NAME) or the NO donors S-nitroso-N-acetylpenicillamine (SNAP), and (Z)-1-[-(2-aminoethyl)-N-(2-aminoethyl)]diazen-1-ium-1,2-diolate (DETA-NONO). AA decreased cell viability from 100% to 48 ± 6% after treatment for 48 h. In the presence of L-NAME, viability was further lowered to 23 ± 5%, while, SNAP or DETA-NONO increased viability to 66 ± 8 or 71 ± 6%. The L-NAME potentiated toxicity was primarily necrotic in nature. L-NAME did not affect CYP2E1 activity or CYP2E1 content. SNAP significantly lowered CYP2E1 activity but not protein. AA treatment increased lipid peroxidation and lowered GSH levels. L-NAME potentiated while SNAP prevented these changes. Thus, L-NAME increased, while NO donors decreased AA-induced oxidative stress. Antioxidants prevented the L-NAME potentiation of AA toxicity. Damage to mitochondria by AA was shown by a decline in the mitochondrial membrane potential (MMP). L-NAME potentiated this decline in MMP in association with its increase in AA-induced oxidative stress and toxicity. NO donors decreased this decline in MMP in association with their decrease in AA-induced oxidative stress and

  2. Sildenafil preserves diastolic relaxation after reduction by L-NAME and increases phosphodiesterase-5 in the intercalated discs of cardiac myocytes and arterioles

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    Silvia Elaine Ferreira-Melo

    2011-01-01

    Full Text Available OBJECTIVES: We investigated the influence of sildenafil on cardiac contractility and diastolic relaxation and examined the distribution of phosphodiesterase-5 in the hearts of hypertensive rats that were treated with by NG-nitro-L-arginine methyl ester (L-NAME. METHODS: Male Wistar rats were treated with L-NAME and/or sildenafil for eight weeks. The Langendorff method was used to examine the effects of sildenafil on cardiac contractility and diastolic relaxation. The presence and location of phosphodiesterase-5 and phosphodiesterase-3 were assessed by immunohistochemistry, and cGMP plasma levels were measured by ELISA. RESULTS: In isolated hearts, sildenafil prevented the reduction of diastolic relaxation (dP/dt that was induced by L-NAME. In addition, phosphodiesterase-5 immunoreactivity was localized in the intercalated discs between the myocardial cells. The staining intensity was reduced by L-NAME, and sildenafil treatment abolished this reduction. Consistent with these results, the plasma levels of cGMP were decreased in the L-NAME-treated rats but not in rats that were treated with L-NAME + sildenafil. CONCLUSION: The sildenafil-induced attenuation of the deleterious hemodynamic and cardiac morphological effects of L-NAME in cardiac myocytes is mediated (at least in part by the inhibition of phosphodiesterase-5.

  3. Arachidonate metabolism increases as rat alveolar type II cells differentiate in vitro

    International Nuclear Information System (INIS)

    Lipchik, R.J.; Chauncey, J.B.; Paine, R.; Simon, R.H.; Peters-Golden, M.

    1990-01-01

    Rat type II alveolar epithelial cells are known to undergo morphological and functional changes when maintained in culture for several days. Having previously demonstrated that these cells can deacylate free arachidonic acid (AA) and metabolize it to products of the cyclooxygenase pathway, the present study was undertaken to determine whether in vitro differentiation was accompanied by alterations in the availability and metabolism of AA. We assessed the constitutive and ionophore A23187-induced deacylation and metabolism of endogenous AA, as well as the metabolism of exogenously supplied AA, in primary cultures of rat type II cells at days 2, 4, and 7 after isolation. Levels of free endogenous AA were increased at day 4, whereas eicosanoid synthesis, predominantly prostaglandin E2 and prostacyclin, increased markedly only at day 7. A similar time course of augmentation of prostanoid release was seen in response to exogenous AA. Type II cells cultured on fibronectin, intended to hasten cell flattening and spreading, demonstrated accelerated increases in available free AA in response to A23187; cells cultured on basement membrane derived from Engelbreth-Holm-Swarm mouse sarcoma, known to maintain the type II phenotype, exhibited diminished levels of available free AA. From these findings, we conclude that alterations in arachidonate metabolism are linked to alterations in cellular phenotype. The potentiation of eicosanoid synthesis accompanying in vitro differentiation suggests a possible role for the alveolar epithelium in the modulation of inflammation and fibrosis in the distal lung

  4. Raloxifene and hormone replacement therapy increase arachidonic acid and docosahexaenoic levels in postmenopausal women

    NARCIS (Netherlands)

    Giltay, E.J.; Duschek, E.J.J.; Katan, M.B.; Neele, S.J.; Netelenbos, J.C.; Zock, P.L.

    2004-01-01

    Estrogens may affect the essential n-6 and n-3 fatty acids arachidonic acid (AA; C20:4n-6) and docosahexaenoic acid (DHA; C22:6n-3). Therefore, we investigated the long-term effects of hormone replacement therapy and raloxifene, a selective estrogen-receptor modulator, in two randomized,

  5. Human milk arachidonic acid and docosahexaenoic acid contents increase following supplementation during pregnancy and lactation

    NARCIS (Netherlands)

    van Goor, Saskia A.; Dijick-Brouwer, D. A. Janneke; Hadders-Algra, Mijna; Doornbos, Bennard; Erwich, Jan Jaap H. M.; Schaafsma, Anne; Muskiet, Frits A. J.; Djick-Brouwer, D.A.J.

    Introduction: Docosahexaenoic acid (DHA) and arachidonic acid (AA) are important for neurodevelopment. Maternal diet influences milk DHA, whereas milk AA seems rather constant. We investigated milk AA, DHA and DHA/AA after supplementation of AA plus DHA, or DHA alone during pregnancy and lactation.

  6. Aryl hydrocarbon receptor–ligand axis mediates pulmonary fibroblast migration and differentiation through increased arachidonic acid metabolism

    International Nuclear Information System (INIS)

    Su, Hsiang-Han; Lin, Hsin-Ting; Suen, Jau-Ling; Sheu, Chau Chyun; Yokoyama, Kazunari K.; Huang, Shau-Ku; Cheng, Chih Mei

    2016-01-01

    Pulmonary fibroblast migration and differentiation are critical events in fibrogenesis; meanwhile, fibrosis characterizes the pathology of many respiratory diseases. The role of aryl hydrocarbon receptor (AhR), a unique cellular chemical sensor, has been suggested in tissue fibrosis, but the mechanisms through which the AhR-ligand axis influences the fibrotic process remain undefined. In this study, the potential impact of the AhR-ligand axis on pulmonary fibroblast migration and differentiation was analyzed using human primary lung fibroblasts HFL-1 and CCL-202 cells. Boyden chamber-based cell migration assay showed that activated AhR in HFL-1cells significantly enhanced cell migration in response to 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD), and a known AhR antagonist, CH223191, inhibited its migratory activity. Furthermore, the calcium mobilization and subsequent upregulated expression of arachidonic acid metabolizing enzymes, including cyclooxygenase2 (COX-2) and 5-lipoxygenase (5-LOX), were observed in TCDD-treated HFL-1 cells, concomitant with elevated levels of prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) secretion. Also, significantly increased expression of α-smooth muscle actin α-SMA), a fibroblast differentiation marker, was also noted in TCDD-treated HFL-1 cells (p < 0.05), resulting in a dynamic change in cytoskeleton protein levels and an increase in the nuclear translocation of the myocardin-related transcription factor. Moreover, the enhanced levels of α-SMA expression and fibroblast migration induced by TCDD, PGE2 and LTB4 were abrogated by selective inhibitors for COX-2 and 5-LOX. Knockdown of AhR by siRNA Completely diminished intracellular calcium uptake and reduced α-SMA protein verified by promoter-reporter assays and chromatin immunoprecipitation. Taken together, our results suggested the importance of the AhR-ligand axis in fibroblast migration and differentiation through its capacity in enhancing arachidonic acid metabolism.

  7. Improved mitochondrial function with diet-induced increase in either docosahexaenoic acid or arachidonic acid in membrane phospholipids.

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    Ramzi J Khairallah

    Full Text Available Mitochondria can depolarize and trigger cell death through the opening of the mitochondrial permeability transition pore (MPTP. We recently showed that an increase in the long chain n3 polyunsaturated fatty acids (PUFA docosahexaenoic acid (DHA; 22:6n3 and depletion of the n6 PUFA arachidonic acid (ARA; 20:4n6 in mitochondrial membranes is associated with a greater Ca(2+ load required to induce MPTP opening. Here we manipulated mitochondrial phospholipid composition by supplementing the diet with DHA, ARA or combined DHA+ARA in rats for 10 weeks. There were no effects on cardiac function, or respiration of isolated mitochondria. Analysis of mitochondrial phospholipids showed DHA supplementation increased DHA and displaced ARA in mitochondrial membranes, while supplementation with ARA or DHA+ARA increased ARA and depleted linoleic acid (18:2n6. Phospholipid analysis revealed a similar pattern, particularly in cardiolipin. Tetralinoleoyl cardiolipin was depleted by 80% with ARA or DHA+ARA supplementation, with linoleic acid side chains replaced by ARA. Both the DHA and ARA groups had delayed Ca(2+-induced MPTP opening, but the DHA+ARA group was similar to the control diet. In conclusion, alterations in mitochondria membrane phospholipid fatty acid composition caused by dietary DHA or ARA was associated with a greater cumulative Ca(2+ load required to induced MPTP opening. Further, high levels of tetralinoleoyl cardiolipin were not essential for normal mitochondrial function if replaced with very-long chain n3 or n6 PUFAs.

  8. Arachidonic acid containing phosphatidylcholine increases due to microglial activation in ipsilateral spinal dorsal horn following spared sciatic nerve injury.

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    Tomohiro Banno

    Full Text Available Peripheral nerve injury induces substantial molecular changes in the somatosensory system that leads to maladaptive plasticity and cause neuropathic pain. Understanding the molecular pathways responsible for the development of neuropathic pain is essential to the development of novel rationally designed therapeutics. Although lipids make up to half of the dry weight of the spinal cord, their relation with the development of neuropathic pain is poorly understood. We aimed to elucidate the regulation of spinal lipids in response to neuropathic peripheral nerve injury in mice by utilizing matrix-assisted laser desorption/ionization imaging mass spectrometry, which allows visualization of lipid distribution within the cord. We found that arachidonic acid (AA containing [PC(diacyl-16:0/20:4+K]+ was increased temporarily at superficial ipsilateral dorsal horn seven days after spared nerve injury (SNI. The spatiotemporal changes in lipid concentration resembled microglia activation as defined by ionized calcium binding adaptor molecule 1 (Iba1 immunohistochemistry. Suppression of microglial function through minocycline administration resulted in attenuation of hypersensitivity and reduces [PC(diacyl-16:0/20:4+K]+ elevation in the spinal dorsal horn. These data suggested that AA containing [PC(diacyl-16:0/20:4+K]+ is related to hypersensitivity evoked by SNI and implicate microglial cell activation in this lipid production.

  9. Significance of antioxidants in L-NAME-induced hypertension

    Czech Academy of Sciences Publication Activity Database

    Pecháňová, Olga; Kojšová, S.; Jendeková, L.; Paulis, L.; Janega, P.; Dovinová, I.; Dobešová, Zdenka; Šimko, F.; Babál, P.; Kuneš, Jaroslav; Zicha, Josef

    2006-01-01

    Roč. 24, č. S4 (2006), S341-S341 ISSN 0263-6352. [European Meeting on Hypertension /16./. 12.06.2006-15.06.2006, Madrid] Grant - others:VEGA(SK) 2/6148/26; VEGA(SK) 1/3429/06 Keywords : antioxidants * L-NAME * hypertension Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery

  10. Arachidonic acid is a chemoattractant for Dictyostelium discoideum

    Indian Academy of Sciences (India)

    Arachidonic acid is a chemoattractant for Dictyostelium discoideum cells ... Arachidonic acid; chemotaxis; fatty acids; iplA ... Previously, we have shown that arachidonic acid (AA) induces an increase in the cytosolic Ca2+ concentration by causing the release of Ca2+ from intracellular stores and activating influx of ...

  11. Dietary supplementation of tiger nut alters biochemical parameters relevant to erectile function in l-NAME treated rats.

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    Olabiyi, Ayodeji A; Carvalho, Fabiano B; Bottari, Nathieli B; Lopes, Thauan F; da Costa, Pauline; Stefanelo, Naiara; Morsch, Vera M; Akindahunsi, Afolabi A; Oboh, Ganiyu; Schetinger, Maria Rosa

    2018-07-01

    Tiger nut tubers have been reportedly used for the treatment of erectile dysfunction (ED) in folk medicine without scientific basis. Hence, this study evaluated the effect of tiger nut on erectile dysfunction by assessing biochemical parameters relevant to ED in male rats by nitric oxide synthase (NOS) inhibitor, Nω-nitro-l-arginine methyl ester hydrochloride (l-NAME) treatment. Rats were divided into five groups (n = 10) each: Control group; l-NAME plus basal diet; l-NAME plus Sildenafil citrate; diet supplemented processed tiger nut (20%) plus l-NAME;diet supplemented raw tiger nut (20%) plus l-NAME. l-NAME pre-treatment (40 mg/kg/day) lasted for 14 days. Arginase, acetycholinesterase (AChE) and adenosine deaminase (ADA) activities as well as nitric oxide levels (NO) in serum, brain and penile tissue were measured. l-NAME increased the activity of arginase, AChE and ADA and reduced NO levels. However, dietary supplementation with tiger nut caused a reduction on the activities of the above enzymes and up regulated nitric oxide levels when compared to the control group. The effect of tiger nut supplemented diet may be said to prevent alterations of the activities of the enzymes relevant in erectile function. Quercetin was revealed to be the most active component of tiger nut tuber by HPLC finger printing. Copyright © 2018. Published by Elsevier Ltd.

  12. Arbutus unedo prevents cardiovascular and morphological alterations in L-NAME-induced hypertensive rats Part I: cardiovascular and renal hemodynamic effects of Arbutus unedo in L-NAME-induced hypertensive rats.

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    Afkir, Saida; Nguelefack, Telesphore Benoit; Aziz, Mohamed; Zoheir, Johar; Cuisinaud, Guy; Bnouham, Mohamed; Mekhfi, Hassane; Legssyer, Abdelkhaleq; Lahlou, Saad; Ziyyat, Abderrahim

    2008-03-05

    Hypertension induced by nitric oxide synthase inhibition is associated with functional abnormalities of the heart and kidney. The aim of the present study was to investigate whether chronic treatment with Arbutus unedo leaf (AuL) or root (AuR) aqueous extracts can prevent these alterations. Six groups of rats were used: control group received tap water; N(G)-nitro-l-arginine methyl-ester (L-NAME) group treated with L-NAME at 40 mg/kg/day; AuL and AuR groups received simultaneously L-NAME (40 mg/kg/day) and Au leaves or roots extract at the same concentration 250 mg/kg/day; l-arginine and enalapril groups received simultaneously L-NAME (40 mg/kg/day) and l-arginine at 50mg/kg/day or enalapril at 15 mg/kg/day. Treatment of rats during 4 weeks with L-NAME caused an increase of the systolic blood pressure (SBP) accompanied by a ventricular hypertrophy, an impairment of endothelium-dependent vasorelaxation, an increase of the cardiac baroreflex sensitivity and a decrease of water, sodium and potassium excretion. The co-administration of AuL or AuR extracts with L-NAME reduces the development of increased SBP, ameliorates the vascular reactivity as well as the baroreflex sensitivity and normalizes the renal function. AuR reduces the ventricular hypertrophy but AuL do not. Enalapril associated with L-NAME reverses the majority of alterations induced by L-NAME while l-arginine only lightly ameliorates the vascular reactivity. These results show that chronic treatment with Arbutus extract regress the development of hypertension and ameliorate cardiovascular and renal functions in NO deficient hypertension.

  13. Resistance training controls arterial blood pressure in rats with L-NAME- induced hypertension.

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    Araujo, Ayslan Jorge Santos de; Santos, Anne Carolline Veríssimo dos; Souza, Karine dos Santos; Aires, Marlúcia Bastos; Santana-Filho, Valter Joviniano; Fioretto, Emerson Ticona; Mota, Marcelo Mendonça; Santos, Márcio Roberto Viana

    2013-04-01

    Arterial hypertension is a multifactorial chronic condition caused by either congenital or acquired factors. To evaluate the effects of Resistance Training (RT) on arterial pressure, and on vascular reactivity and morphology, of L-NAME-treated hypertensive rats. Male Wistar rats (200 - 250 g) were allocated into Sedentary Normotensive (SN), Sedentary Hypertensive (SH) and Trained Hypertensive (TH) groups. Hypertension was induced by adding L-NAME (40 mg/Kg) to the drinking water for four weeks. Arterial pressure was evaluated before and after RT. RT was performed using 50% of 1RM, 3 sets of 10 repetitions, 3 times per week for four weeks. Vascular reactivity was measured in rat mesenteric artery rings by concentration-response curves to sodium nitroprusside (SNP); phenylephrine (PHE) was also used for histological and stereological analysis. Resistance training inhibited the increase in mean and diastolic arterial pressures. Significant reduction was observed in Rmax (maximal response) and pD2 (potency) of PHE between SH and TH groups. Arteries demonstrated normal intima, media and adventitia layers in all groups. Stereological analysis demonstrated no significant difference in luminal, tunica media, and total areas of arteries in the SH and TH groups when compared to the SN group. Wall-to-lumen ratio of SH arteries was significantly different compared to SN arteries (parteries. RT was able to prevent an increase in blood pressure under the conditions in this study. This appears to involve a vasoconstrictor regulation mechanism and maintenance of luminal diameter in L-NAME induced hypertensive rats.

  14. Intake of Blueberry Fermented by Lactobacillus plantarum Affects the Gut Microbiota of L-NAME Treated Rats

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    Jie Xu

    2013-01-01

    Full Text Available Prebiotics, probiotics, or synbiotics can be used as means to regulate the microbiota to exert preventative or beneficial effects to the host. However, not much is known about the effect of the gut microbiota on hypertension which is a major risk factor of cardiovascular disease and also a symptom of the metabolic syndrome. The NG-nitro-L-arginine methyl ester (L-NAME induced hypertensive rats were used in order to test the effect of a synbiotic dietary supplement of Lactobacillus plantarum HEAL19 either together with fermented blueberry or with three phenolic compounds synthesized during fermentation. The experimental diets did not lower the blood pressure after 4 weeks. However, the fermented blueberries together with live L. plantarum showed protective effect on liver cells indicated by suppressed increase of serum alanine aminotransferase (ALAT levels. The diversity of the caecal microbiota was neither affected by L-NAME nor the experimental diets. However, inhibition of the nitric oxide synthesis by L-NAME exerted a selection pressure that led to a shift in the bacterial composition. The mixture of fermented blueberries with the bacterial strain altered the caecal microbiota in different direction compared to L-NAME, while the three phenolic compounds together with the bacteria eliminated the selection pressure from the L-NAME.

  15. The milk-derived peptides Val-Pro-Pro and Ile-Pro-Pro attenuate arterial dysfunction in L-NAME-treated rats.

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    Nonaka, Atsuko; Nakamura, Teppei; Hirota, Tatsuhiko; Matsushita, Akiko; Asakura, Masanori; Ohki, Kohji; Kitakaze, Masafumi

    2014-08-01

    Both endothelial dysfunction and arterial stiffness are surrogate markers of atherosclerosis and thus cardiovascular (CV) events. The milk-derived peptides Val-Pro-Pro (VPP) and Ile-Pro-Pro (IPP) inhibit angiotensin-converting enzyme, dilate blood vessels ex vivo and stimulate nitric oxide (NO) production in cells. In this study, we investigated the effects of either VPP or IPP on arterial function and on target organ damage in vivo. Male Wistar rats were treated with N(G)-nitro-L-arginine methyl ester hydrochloride (L-NAME, 1 g l(-1)), L-NAME+VPP (0.3 g l(-1)) or L-NAME+IPP (0.3 g l(-1)) in their drinking water for 8 weeks. Plasma nitrite and nitrate (NOx) levels were significantly increased in normal Wistar rats after supplementation with either VPP or IPP but not in rats that were chronically treated with L-NAME. Acetylcholine-induced vasorelaxation in the thoracic aorta ring was impaired by L-NAME, whereas vasorelaxation was significantly greater in mice treated with L-NAME+VPP for 1 or 4 weeks or L-NAME+IPP for 4 weeks than in mice treated with L-NAME alone. Four weeks of treatment with either VPP or IPP attenuated the increase in pulse wave velocity (PWV) that was induced by L-NAME. Cardiac and renal damage were observed after 8 weeks of treatment with L-NAME, and either VPP or IPP attenuated this damage. These results show that VPP or IPP attenuates arterial dysfunction and suggest that milk-derived peptides might prevent CV damage.

  16. Protective effects of long-term administration of Ziziphus jujuba fruit extract on cardiovascular responses in L-NAME hypertensive rats.

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    Mohebbati, Reza; Bavarsad, Kosar; Rahimi, Maryam; Rakhshandeh, Hasan; Khajavi Rad, Abolfazl; Shafei, Mohammad Naser

    2018-01-01

    Ziziphus jujuba stimulates the release of nitric oxide (NO). Because NO is involved in cardiovascular regulations, in this study the effects of hydroalcoholic extract of Z. jujuba on cardiovascular responses in acute NG-nitro-L-arginine methyl ester (L-NAME) hypertensive rats were evaluated. Rats were divided into 6 group (n=6): 1) saline, 2) L-NAME received (10mg/kg) intravenously, 3) sodium nitroprusside (SNP) (50µg/kg)+L-NAME group received SNP before L-NAME and 4-6) three groups of Z. jujuba (100, 200 and 400mg/kg) that treated for four weeks and on the 28 th day, L-NAME was injected. Femoral artery and vein were cannulated for recording cardiovascular responses and drug injection, respectively. Systolic blood pressure (SBP), Mean arterial pressure (MAP) and heart rate (HR) were recorded continuously. Maximal changes (∆) of SBP, MAP and HR were calculated and compared to control and L-NAME groups. In L-NAME group, maximal ΔSBP (L-NAME: 44.15±4.0 mmHg vs control: 0.71±2.1 mmHg) and ΔMAP (L-NAME: 40.8±4.0 mmHg vs control: 0.57±1.6 mmHg) significantly increased (p0.05). All doses of Z. jujuba attenuated maximal ∆SBP and ∆MAP induced by L-NAME but only the lowest dose (100 mg/kg) had significant effects (ΔSBP: 20.36±5.6 mmHg vs L-NAME: 44.1±4.0 mmHg and ΔMAP: 20.8±4.5 mmHg vs L-NAME: 40.8±3.8 mmHg (pL-NAME group (p>0.05). Because long-term consumption of Z. jujuba extract, especially its lowest dose, attenuated cardiovascular responses induced by L-NAME, we suggest that Z. jujuba has potential beneficial effects in prevention of hypertension induced by NO deficiency.

  17. The Effect of Nitric Oxide Synthetase Inhibitor (L-NAME on Prevention of Morphine Dependence in Rats

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    A. Rafati

    2004-10-01

    Full Text Available Prevention of dependency to morphine or delaying to it and decreasing of tendency to morphine craving and also decreasing in morphine induced hyperalgesia(tolerance were the aims of this study. Nitric oxide is one of the neurotransmitters, which involves in the Dopamine reuptake in striatum. Dopamine is one of the most important neurotransmitters in reward system in central nervous system and it has a critical role in morphine addiction and dependency, tendency and tolerance to it, so in this study we survied the role of L- NAME as a nitric oxide synthetase (NOS inhibitor on the prevention of morphine addiction in rats. In this study we evaluated behavioral changes such as morphine craving by self - administration as a criterion for tendency, dependency by observation of withdrawal syndrom signs (e.g Jumping, wet dog shaking and also responses to nociceptive condenced bim of light by using tail flick analgesia metric device in sham (consuming tap water, control (consuming increasing doses of morphine sulfate solution from 0.1mg/ml up to 0.4mg/ml and test (treated with 45 mg/kg of L- NAME 30 minutes before consuming of morphine sulfate solution per day groups. The results showed that pretreatment with L- NAME in test group lead to a significant decline in tendency to morphine craving, withdrawal signs and also a significant reversal of morphine induced hyperalgesia. We concluded that L- NAME is a potent agent in the prevention of morphine addiction.

  18. Different effect of l-NAME treatment on susceptibility to decompression sickness in male and female rats.

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    Mazur, Aleksandra; Buzzacott, Peter; Lambrechts, Kate; Wang, Qiong; Belhomme, Marc; Theron, Michael; Popov, Georgi; Distefano, Giovanni; Guerrero, Francois

    2014-11-01

    Vascular bubble formation results from supersaturation during inadequate decompression contributes to endothelial injuries, which form the basis for the development of decompression sickness (DCS). Risk factors for DCS include increased age, weight-fat mass, decreased maximal oxygen uptake, chronic diseases, dehydration, and nitric oxide (NO) bioavailability. Production of NO is often affected by diving and its expression-activity varies between the genders. Little is known about the influence of sex on the risk of DCS. To study this relationship we used an animal model of Nω-nitro-l-arginine methyl ester (l-NAME) to induce decreased NO production. Male and female rats with diverse ages and weights were divided into 2 groups: treated with l-NAME (in tap water; 0.05 mg·mL(-1) for 7 days) and a control group. To control the distribution of nitrogen among tissues, 2 different compression-decompression protocols were used. Results showed that l-NAME was significantly associated with increased DCS in female rats (p = 0.039) only. Weight was significant for both sexes (p = 0.01). The protocol with the highest estimated tissue pressures in the slower compartments was 2.6 times more likely to produce DCS than the protocol with the highest estimated tissue pressures in faster compartments. The outcome of this study had significantly different susceptibility to DCS after l-NAME treatment between the sexes, while l-NAME per se had no effect on the likelihood of DCS. The analysis also showed that for the appearance of DCS, the most significant factors were type of protocol and weight.

  19. Is arachidonic acid an endoschistosomicide?

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    Violette Said Hanna

    2018-05-01

    Full Text Available Schistosoma mansoni and Schistosoma haematobium are intravascular, parasitic flatworms that infect >250 million people in 70 developing countries, yet not all people of the same community and household are afflicted. Regarding laboratory rodents, mice but not rats are susceptible to infection with S. mansoni and hamsters but not mice are entirely permissive to infection with S. haematobium. A recent Brazilian publication has demonstrated that resistance of the water-rat, Nectomys squamipes to S. mansoni infection might be ascribed to stores of arachidonic acid (ARA-rich lipids in liver. Several reports have previously shown that ARA is a safe and effective schistosomicide in vitro, and in vivo in mice, hamsters and in children. Schistosoma haematobium appeared more sensitive than S. mansoni to ARA in in vitro and in vivo experiments. Accordingly, it was proposed that ARA increased levels might be predominantly responsible for natural attrition of S. mansoni and S. haematobium in resistant experimental rodents. Therefore, the levels of ARA in serum, lung, and liver of rats (resistant and mice (susceptible at 1, 2, 3, 4 and 6 weeks after infection with S. mansoni cercariae and between mice (semi-permissive and hamster (susceptible at 1, 2, 3, 4, and 12 weeks after infection with S. haematobium cercariae were compared and contrasted. Neutral triglycerides and ARA levels were assessed in serum using commercially available assays and in liver and lung sections by transmission electron microscopy, Oil Red O staining, and specific anti-ARA antibody-based immunohistochemistry assays. Significant (P < .05, consistent, and reproducible correlation was recorded between ARA content in serum, lung, and liver and rodent resistance to schistosome infection, thereby implicating ARA as an endoschistosomicide. Keywords: Schistosoma mansoni, Schistosoma haematobium, Rat schistosomiasis, Arachidonic acid, Oil Red O staining, Immunohistochemistry

  20. Acute and chronic antihypertensive effects of Cinnamomum zeylanicum stem bark methanol extract in L-NAME-induced hypertensive rats

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    Nyadjeu Paulin

    2013-01-01

    Full Text Available Abstract Background Previous study showed that the aqueous extract of the stem bark of Cinnamomum zeylanicum possesses antihypertensive and vasodilatory properties. The present work investigates the acute and chronic antihypertensive effects of the methanol extract of Cinnamomum zeylanicum stem bark (MECZ in L-NAME-induced hypertensive rats. Methods The acute antihypertensive effects of MECZ (5, 10 and 20 mg/kg administered intravenously were evaluated in rats in which acute arterial hypertension has been induced by intravenous administration of L-NAME (20 mg/kg. For chronic antihypertensive effects, animals were treated with L-NAME (40 mg/kg/day plus the vehicle or L-NAME (40 mg/kg/day in combination with captopril (20 mg/kg/day or MECZ (300 mg/kg/day and compared with control group receiving only distilled water. All drugs were administered per os and at the end of the experiment that lasted for four consecutive weeks, blood pressure was measured by invasive method and blood samples were collected for the determination of the lipid profile. The heart and aorta were collected, weighed and used for both histological analysis and determination of NO tissue content. Results Acute intravenous administration of C. zeylanicum extract (5, 10 and 20 mg/kg to L-NAME-induced hypertensive rats provoked a long-lasting decrease in blood pressure. Mean arterial blood pressure decreased by 12.5%, 26.6% and 30.6% at the doses of 5, 10 and 20 mg/kg, respectively. In chronic administration, MECZ and captopril significantly prevented the increase in blood pressure and organs’ weights, as well as tissue histological damages and were able to reverse the depletion in NO tissue’s concentration. The MECZ also significantly lower the plasma level of triglycerides (38.1%, total cholesterol (32.1% and LDL-cholesterol (75.3% while increasing that of HDL-cholesterol (58.4% with a significant low atherogenic index (1.4 versus 5.3 for L-NAME group. Conclusion MECZ

  1. Impact of angiotensin and endothelin converting enzymes and related bradykinin on renal functions in L-NAME hypertensive rats

    Science.gov (United States)

    Omar, Ali Zainal; Maulood, Ismail M.

    2017-09-01

    The renin-angiotensin system (RAS), one of the most important hormonal systems, controls the kidney functions by regulating fluid volume, and electrolyte balance. The current study included the effects of kinin-kallikrein system (KKS) and its interaction with both angiotensin converting enzyme (ACE) and endothelin converting enzyme (ECE) on some of kidney function test parameters. In the present experiment, rats were divided into six groups, the first group was infused with normal saline, the second group was L-NG-Nitroarginine methyl ester (L-NAME) treated rats, third group was bradykinin (BK), forth group was captopril (ACEi), fifth group was phosphoramidon (ECEi), sixth group was a combination of BK with phosphoramidon. L-NAME was intravenously infused for one hour to develop systematic hypertension in male rats. After one hour of infusion, the results showed that L-NAME significantly increased serum creatinine. While, it decreased glomerular filtration rate (GFR), and K+ excretion rate. Moreover, BK increased packed cell volume PCV%, serum creatinine and K+ ion concentration. While, it reduced GFR, serum Ca+2 ion concentration, K+ and Na+ excretion rates. On the other hand, captopril infusion showed its effect by reduction in GFR, serum Ca+2 ion and electrolyte excretion rates. Phosphoramidon an ECEi dramatically reduced serum Ca+2 ion, but it increased pH, GFR and Ca+2 excretion rate. The results suggested that BK and Captopril each alone severely reduces GFR value. Interestingly, inhibition of ET-1 production via phosphoramidon could markedly elevate GFR values.

  2. Potential Cardiovascular and Renal Protective Effects of Vitamin D and Coenzyme Q10 in l-NAME-Induced Hypertensive Rats.

    Science.gov (United States)

    Shamardl, Hanan A; El-Ashmony, Sahar M; Kamel, Hala F; Fatani, Sameer H

    2017-08-01

    Hypertension is one of the primary modifiable risk factors for cardiovascular disease. Adequate vitamin D (vit D) levels have been shown to reduce vascular smooth muscle contraction and to increase arterial compliance, which may be beneficial in hypertension. Further, coenzyme Q10 (COQ10) through its action to lower oxidative stress has been reported to have beneficial effects on hypertension and heart failure. This study examined the possible cardiac and renal protective effects of vit D and COQ10 both separately and in combination with an angiotensin II receptor blocker, valsartan (vals) in l-NAME hypertensive rats. Hypertension was induced in rats by l-NAME administration. Following induction of hypertension, the rats were assigned into the following 6 subgroups: an l-NAME alone group and treated groups receiving the following drugs intraperitoneally for 6 weeks; vals, vit D, COQ10 and combination of vals with either vit D or COQ10. A group of normotensive rats were used as negative controls. At the end of the treatment period, blood pressure, serum creatinine, blood urea nitrogen, lipids and serum, cardiac and renal parameters of oxidative stress were measured. Compared to the l-NAME only group, all treatments lowered systolic, diastolic, mean arterial pressure, total cholesterol, low-density lipoprotein cholesterol, and creatinine levels as well as TNF-α and malondialdehyde. Further, the agents increased serum, cardiac and renal total antioxidant capacity. Interestingly, the combination of agents had further effects on all the parameters compared to treatment with each single agent. The study suggests that the additive protective effects of vit D and COQ10 when used alone or concurrent with vals treatment in hypertensive rats may be due to their effects as antioxidants, anticytokines and blood pressure conservers. Copyright © 2017 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

  3. The Effects Of L-Arginine And L-Name On Coronary Flow And Oxidative Stress In Isolated Rat Hearts

    Directory of Open Access Journals (Sweden)

    Sobot Tanja

    2015-12-01

    Full Text Available The aim of this experimental study was to assess the effects of the acute administration of L-arginine alone and in combination with L-NAME (a non-selective NO synthase inhibitor on the coronary flow and oxidative stress markers in isolated rat hearts. The experimental study was performed on hearts isolated from Wistar albino rats (n=12, male, 8 weeks old, body mass of 180-200 g. Retrograde perfusion of the isolated preparations was performed using a modified method according to the Langendorff technique with a gradual increase in the perfusion pressure (40–120 cmH2O. The following values were measured in the collected coronary effluents: coronary flow, released nitrites (NO production marker, superoxide anion radical and the index of lipid peroxidation (measured as thiobarbiturate reactive substances. The experimental protocol was performed under controlled conditions, followed by the administration of L-arginine alone (1 mmol and L-arginine (1 mmol + L-NAME (30 μmol. The results indicated that L-arginine did not significantly increase the coronary flow or the release of NO, TBARS and the superoxide anion radical. These effects were partially blocked by the joint administration of L-arginine + L-NAME, which indicated their competitive effect. Hence, the results of our study do not demonstrate significant effects of L-arginine administration on the coronary flow and oxidative stress markers in isolated rat hearts.

  4. Hydrogen sulfide ameliorated L-NAME-induced hypertensive heart disease by the Akt/eNOS/NO pathway.

    Science.gov (United States)

    Jin, Sheng; Teng, Xu; Xiao, Lin; Xue, Hongmei; Guo, Qi; Duan, Xiaocui; Chen, Yuhong; Wu, Yuming

    2017-12-01

    Reductions in hydrogen sulfide (H 2 S) production have been implicated in the pathogenesis of hypertension; however, no studies have examined the functional role of hydrogen sulfide in hypertensive heart disease. We hypothesized that the endogenous production of hydrogen sulfide would be reduced and exogenous hydrogen sulfide would ameliorate cardiac dysfunction in N ω -nitro- L-arginine methyl ester ( L-NAME)-induced hypertensive rats. Therefore, this study investigated the cardioprotective effects of hydrogen sulfide on L-NAME-induced hypertensive heart disease and explored potential mechanisms. The rats were randomly divided into five groups: Control, Control + sodium hydrosulfide (NaHS), L-NAME, L-NAME + NaHS, and L-NAME + NaHS + glibenclamide (Gli) groups. Systolic blood pressure was monitored each week. In Langendorff-isolated rat heart, cardiac function represented by ±LV dP/dt max and left ventricular developing pressure was recorded after five weeks of treatment. Hematoxylin and Eosin and Masson's trichrome staining and myocardium ultrastructure under transmission electron microscopy were used to evaluate cardiac remodeling. The plasma nitric oxide and hydrogen sulfide concentrations, as well as nitric oxide synthases and cystathionine-γ-lyase activity in left ventricle tissue were determined. The protein expression of p-Akt, Akt, p-eNOS, and eNOS in left ventricle tissue was analyzed using Western blot. After five weeks of L-NAME treatment, there was a time-dependent hypertension, cardiac remodeling, and dysfunction accompanied by a decrease in eNOS phosphorylation, nitric oxide synthase activity, and nitric oxide concentration. Meanwhile, cystathionine-γ-lyase activity and hydrogen sulfide concentration were also decreased. NaHS treatment significantly increased plasma hydrogen sulfide concentration and subsequently promoted the Akt/eNOS/NO pathway which inhibited the development of hypertension and attenuated cardiac remodeling and

  5. Effect of aliskiren, telmisartan and torsemide on cardiac dysfunction in l-nitro arginine methyl ester (l-NAME induced hypertension in rats

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    Sawsan A. Sadek

    2015-11-01

    Full Text Available Comparative study of cardio protective effect of aliskiren, telmisartan, and torsemide was carried out on l-nitro arginine methyl ester (l-NAME induced hypertension in rats. The three drugs were given daily for 8 weeks simultaneously with l-NAME, with a control group for each drug and l-NAME. The degree of protection was assessed by measurement of systolic blood pressure and heart rate of animals every two weeks. At the end of the experimental period blood sampling was carried out for estimation of the level of NO2−/NO3−. After which animals were sacrificed for heart dissection to detect collagen types I and III gene expression. Histopathological study was done to evaluate the extension of collagen deposits. The study revealed that the three drugs decreased blood pressure significantly compared to l-NAME. There was no significant difference between aliskiren and telmisartan in all measurements, but there was significant decrease in measurements of both aliskiren and telmisartan treated groups compared to torsemide starting from 4th week. There were insignificant changes in pulse rate values between the three l-NAME treated groups through the experiment. The three drugs significantly increased NO compared to l-NAME. Collagen I and III gene expression was significantly decreased by the three drugs but the highest percentage of inhibition was with telmisartan compared to l-NAME. Comparing the percentage inhibition of cardiac fibrosis, there was insignificant difference between telmisartan and torsemide treated groups while both were superior to aliskiren. In conclusion, further experimental studies are required to elucidate the potential cardioprotective mechanisms of aliskiren, telmisartan and torsemide, and assess their efficacy in treatment of heart failure.

  6. The effect of L-NAME on intra- and inter-nephron synchronization

    DEFF Research Database (Denmark)

    Sosnovtseva, Olga; Pavlov, A. N.; Pavlova, O. N.

    2009-01-01

    to what extent these phenomena are reflected in the overall blood flow to the kidney and how they are affected by intravenous administration of nitro-l-arginine-methyl-ester (L-NAME), a potent NO synthesis inhibitor. Wavelet analysis is applied to detect rhythmic activity at the level of the renal artery...

  7. Structural alterations in rat myocardium induced by chronic l-arginine and l-NAME supplementation

    Directory of Open Access Journals (Sweden)

    Amal Abdussalam Ali A. Hmaid

    2018-03-01

    Full Text Available Structural changes affecting cardiomyocyte function may contribute to the pathophysiological remodeling underlying cardiac function impairment. Recent reports have shown that endogenous nitric oxide (NO plays an important role in this process. In order to examine the role of NO in cardiomyocyte remodeling, male rats were acclimated to room temperature (22 ± 1 °C or cold (4 ± 1 °C and treated with 2.25% l-arginine·HCl or 0.01% l-NAME (Nω-nitro-l-arginine methyl ester·HCl for 45 days. Untreated groups served as controls. Right heart ventricles were routinely prepared for light microscopic examination. Stereological estimations of volume densities of cardiomyocytes, surrounding blood vessels and connective tissue, as well as the morphometric measurements of cardiomyocyte diameters were performed. Tissue sections were also analyzed for structural alterations. We observed that both l-arginine and l-NAME supplementation induced cardiomyocyte hypertrophy, regardless of ambient temperature. However, cardiomyocyte hypertrophy was associated with fibrosis and extra collagen deposition only in the l-NAME treated group. Taken together, our results suggest that NO has a modulatory role in right heart ventricle remodeling by coordinating hypertrophy of cardiomyocytes and fibrous tissue preventing cardiac fibrosis. Keywords: Cardiomyocyte, Cardiac hypertrophy, l-Arginine, l-NAME, Myocardium

  8. Macrophage populations and cardiac sympathetic denervation during L-NAME-induced hypertension in rats

    DEFF Research Database (Denmark)

    Neves, S R S; Machado, C R S; Pinto, A M T

    2006-01-01

    The rat model of hypertension induced by prolonged treatment with Nomega-nitro-L-arginine methyl ester (L-NAME) has been extensively used. However, the effects on cardiac autonomic innervation are unknown. Here, the cardiac sympathetic innervation is analyzed in parallel with myocardial lesions a...

  9. Beneficial Effects of Different Flavonoids on Vascular and Renal Function in L-NAME Hypertensive Rats

    Directory of Open Access Journals (Sweden)

    M. Dolores Paredes

    2018-04-01

    Full Text Available Background: we have evaluated the antihypertensive effect of several flavonoid extracts in a rat model of arterial hypertension caused by chronic administration (6 weeks of the nitric oxide synthesis inhibitor, L-NAME. Methods: Sprague Dawley rats received L-NAME alone or L-NAME plus flavonoid-rich vegetal extracts (Lemon, Grapefruit + Bitter Orange, and Cocoa or purified flavonoids (Apigenin and Diosmin for 6 weeks. Results: L-NAME treatment resulted in a marked elevation of blood pressure, and treatment with Apigenin, Lemon Extract, and Grapefruit + Bitter Orange extracts significantly reduced the elevated blood pressure of these animals. Apigenin and some of these flavonoids also ameliorated nitric oxide-dependent and -independent aortic vasodilation and elevated nitrite urinary excretion. End-organ abnormalities such as cardiac infarcts, hyaline arteriopathy and fibrinoid necrosis in coronary arteries and aorta were improved by these treatments, reducing the end-organ vascular damage. Conclusions: the flavonoids included in this study, specially apigenin, may be used as functional food ingredients with potential therapeutic benefit in arterial hypertension.

  10. The effect of pre-eclampsia-like syndrome induced by L-NAME on learning and memory and hippocampal glucocorticoid receptor expression: A rat model.

    Science.gov (United States)

    Zhu, Hao; Zhu, Weimin; Hu, Rong; Wang, Huijun; Ma, Duan; Li, Xiaotian

    2017-02-01

    We aimed to study the impacts of pre-eclampsia on the cognitive and learning capabilities of adolescent rat offspring and to explore the possible underlying mechanisms at the molecular level. Pregnant rats were subcutaneously injected with saline solution (control) (n = 16) or NG-nitro-L-arginine methyl ester (L-NAME) (n = 16) from the 13th day of gestation until parturition. The brain tissues from fetal rats delivered by cesarean section were examined in both groups with hematoxylin and eosin (H&E) staining. Rats born vaginally in both groups were subjected to the Morris water maze test when 8-week-old and their hippocampi were analyzed for glucocorticoid receptor (GR) expression. A pre-eclampsia-like model was successfully built in pregnant rats by infusion of the NO synthase inhibitor L-NAME, including phenotypes as maternal hypertension and proteinuria, high stillbirth rate, and fetal growth retardation. Neuroepithelial cell proliferation was found in the hippocampus of fetal rats in the L-NAME group. Grown to 8-week-old, the L-NAME group showed significantly longer escape latency than the control group in the beginning as well as in the end of navigation trials. At the same time, the swimming distance achieved by the L-NAME group was significantly longer than that of the control group. Such differences in cognitive and learning capabilities between the two groups were not gender dependent. Besides, the 8-week-old rats in the L-NAME group had increased GR expression in the hippocampus than the control group. Pre-eclampsia would impair cognitive and learning capabilities in adolescent offspring, and the upregulated expression of hippocampal GR may be involved in the underlying mechanisms.

  11. Antihypertensive Effects of Roselle-Olive Combination in L-NAME-Induced Hypertensive Rats.

    Science.gov (United States)

    Abdel-Rahman, Rehab F; Hessin, Alyaa F; Abdelbaset, Marwan; Ogaly, Hanan A; Abd-Elsalam, Reham M; Hassan, Salah M

    2017-01-01

    This study aimed to evaluate the antihypertensive efficacy of a new combination therapy of Hibiscus sabdariffa and Olea europaea extracts (2 : 1; Roselle-Olive), using N(G)-nitro-L-arginine-methyl ester- (L-NAME-) induced hypertensive model. Rats received L-NAME (50 mg/kg/day, orally) for 4 weeks. Concurrent treatment with Roselle-Olive (500, 250, and 125 mg/kg/day for 4 weeks) resulted in a dose-dependent decrease in both systolic and diastolic blood pressure, reversed the L-NAME-induced suppression in serum nitric oxide (NO), and improved liver and kidney markers, lipid profile, and oxidative status. Furthermore, Roselle-Olive significantly lowered the elevated angiotensin-converting enzyme activity (ACE) and showed a marked genoprotective effect against oxidative DNA damage in hypertensive rats. Roselle-Olive ameliorated kidney and heart lesions and reduced aortic media thickness. Real-time PCR and immunohistochemistry showed an enhanced endothelial nitric oxide synthase (eNOS) gene and protein expression in both heart and kidney of Roselle-Olive-treated rats. To conclude, our data revealed that Roselle-Olive is an effective combination in which H. sabdariffa and O. europaea synergistically act to control hypertension. These effects are likely to be mediated by antioxidant and genoprotective actions, ACE inhibition, and eNOS upregulation by Roselle-Olive constituents. These findings provide evidences that Roselle-Olive combination affords efficient antihypertensive effect with a broad end-organ protective influence.

  12. Structural alterations in rat myocardium induced by chronic l-arginine and l-NAME supplementation.

    Science.gov (United States)

    Hmaid, Amal Abdussalam Ali A; Markelic, Milica; Otasevic, Vesna; Masovic, Sava; Jankovic, Aleksandra; Korac, Bato; Korac, Aleksandra

    2018-03-01

    Structural changes affecting cardiomyocyte function may contribute to the pathophysiological remodeling underlying cardiac function impairment. Recent reports have shown that endogenous nitric oxide (NO) plays an important role in this process. In order to examine the role of NO in cardiomyocyte remodeling, male rats were acclimated to room temperature (22 ± 1 °C) or cold (4 ± 1 °C) and treated with 2.25% l-arginine·HCl or 0.01% l-NAME (N ω -nitro-l-arginine methyl ester)·HCl for 45 days. Untreated groups served as controls. Right heart ventricles were routinely prepared for light microscopic examination. Stereological estimations of volume densities of cardiomyocytes, surrounding blood vessels and connective tissue, as well as the morphometric measurements of cardiomyocyte diameters were performed. Tissue sections were also analyzed for structural alterations. We observed that both l-arginine and l-NAME supplementation induced cardiomyocyte hypertrophy, regardless of ambient temperature. However, cardiomyocyte hypertrophy was associated with fibrosis and extra collagen deposition only in the l-NAME treated group. Taken together, our results suggest that NO has a modulatory role in right heart ventricle remodeling by coordinating hypertrophy of cardiomyocytes and fibrous tissue preventing cardiac fibrosis.

  13. Antihypertensive Effects of Roselle-Olive Combination in L-NAME-Induced Hypertensive Rats

    Directory of Open Access Journals (Sweden)

    Rehab F. Abdel-Rahman

    2017-01-01

    Full Text Available This study aimed to evaluate the antihypertensive efficacy of a new combination therapy of Hibiscus sabdariffa and Olea europaea extracts (2 : 1; Roselle-Olive, using N(G-nitro-L-arginine-methyl ester- (L-NAME- induced hypertensive model. Rats received L-NAME (50 mg/kg/day, orally for 4 weeks. Concurrent treatment with Roselle-Olive (500, 250, and 125 mg/kg/day for 4 weeks resulted in a dose-dependent decrease in both systolic and diastolic blood pressure, reversed the L-NAME-induced suppression in serum nitric oxide (NO, and improved liver and kidney markers, lipid profile, and oxidative status. Furthermore, Roselle-Olive significantly lowered the elevated angiotensin-converting enzyme activity (ACE and showed a marked genoprotective effect against oxidative DNA damage in hypertensive rats. Roselle-Olive ameliorated kidney and heart lesions and reduced aortic media thickness. Real-time PCR and immunohistochemistry showed an enhanced endothelial nitric oxide synthase (eNOS gene and protein expression in both heart and kidney of Roselle-Olive-treated rats. To conclude, our data revealed that Roselle-Olive is an effective combination in which H. sabdariffa and O. europaea synergistically act to control hypertension. These effects are likely to be mediated by antioxidant and genoprotective actions, ACE inhibition, and eNOS upregulation by Roselle-Olive constituents. These findings provide evidences that Roselle-Olive combination affords efficient antihypertensive effect with a broad end-organ protective influence.

  14. Vasoactive systems in L-NAME hypertension: the role of inducible nitric oxide synthase

    Czech Academy of Sciences Publication Activity Database

    Pecháňová, Olga; Dobešová, Zdenka; Čejka, Jakub; Kuneš, Jaroslav; Zicha, Josef

    2004-01-01

    Roč. 22, č. 1 (2004), s. 167-173 ISSN 0263-6352 R&D Projects: GA ČR GA305/03/0769; GA MŠk LN00A069 Grant - others:VEGA(SK) 2/3185/23; SAV(SK) APVT51-017902 Institutional research plan: CEZ:AV0Z5011922 Keywords : nitric oxide synthase * L-NAME hypertension * aminoguanidine Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 4.871, year: 2004

  15. Ellagic Acid Prevents L-NAME-Induced Hypertension via Restoration of eNOS and p47phox Expression in Rats

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    Thewarid Berkban

    2015-06-01

    Full Text Available The effect of ellagic acid on oxidative stress and hypertension induced by Nω-Nitro-l-arginine methyl ester hydrochloride (L-NAME was investigated. Male Sprague-Dawley rats were administrated with L-NAME (40 mg/kg/day for five weeks. L-NAME induced high systolic blood pressure (SBP and increased heart rate (HR, hindlimb vascular resistance (HVR and oxidative stress. Concurrent treatment with ellagic acid (7.5 or 15 mg/kg prevented these alterations. Co-treatment with ellagic acid was associated with up-regulation of endothelial nitric oxide synthase (eNOS protein production and alleviation of oxidative stress as indicated by decreased superoxide production in the vascular tissue, reduced plasma malondialdehyde levels, reduced NADPH oxidase subunit p47phox expression and increased plasma nitrate/nitrite levels. Our results indicate that ellagic acid attenuates hypertension by reducing NADPH oxidase subunit p47phox expression, which prevents oxidative stress and restores NO bioavailability.

  16. Synergistic Antihypertensive Effect of Carthamus tinctorius L. Extract and Captopril in l-NAME-Induced Hypertensive Rats via Restoration of eNOS and AT1R Expression

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    Putcharawipa Maneesai

    2016-02-01

    Full Text Available This study examined the effect of Carthamus tinctorius (CT extract plus captopril treatment on blood pressure, vascular function, nitric oxide (NO bioavailability, oxidative stress and renin-angiotensin system (RAS in Nω-Nitro-l-arginine methyl ester (l-NAME-induced hypertension. Rats were treated with l-NAME (40 mg/kg/day for five weeks and given CT extract (75 or 150 or 300 or 500 mg/kg/day: captopril (5 mg/kg/day or CT extract (300 mg/kg/day plus captopril (5 mg/kg/day for two consecutive weeks. CT extract reduced blood pressure dose-dependently, and the most effective dose was 300 mg/kg/day. l-NAME-induced hypertensive rats showed abnormalities including high blood pressure, high vascular resistance, impairment of acetylcholine-induced vasorelaxation in isolated aortic rings and mesenteric vascular beds, increased vascular superoxide production and plasma malondialdehyde levels, downregulation of eNOS, low level of plasma nitric oxide metabolites, upregulation of angiotensin II type 1 receptor and increased plasma angiotensin II. These abnormalities were alleviated by treatment with either CT extract or captopril. Combination treatment of CT extract and captopril normalized all the abnormalities found in hypertensive rats except endothelial dysfunction. These data indicate that there are synergistic antihypertensive effects of CT extract and captopril. These effects are likely mediated by their anti-oxidative properties and their inhibition of RAS.

  17. Activation and regulation of arachidonic acid release in rabbit peritoneal neutrophils

    International Nuclear Information System (INIS)

    Tao, W.

    1988-01-01

    Arachidonic acid release in rabbit neutrophils can be enhanced by the addition of chemotactic fMet-Leu-Phe, platelet-activating factor, PAF, or the calcium ionophore A23187. Over 80% of the release [ 3 H]arachidonic acid comes from phosphatidylcholine and phosphatidylinositol. The release is dose-dependent and increases with increasing concentration of the stimulus. The A23187-induced release increases with increasing time of the stimulation. [ 3 H]arachidonic acid release, but not the rise in the concentration of intracellular calcium, is inhibited in pertussis toxin-treated neutrophils stimulated with PAF. The [ 3 H]arachidonic acid released by A23187 is potentiated while that release by fMET-Leu-Phe or PAF is inhibited in phorbol 12-myristate 13-acetate, PMA, treated rabbit neutrophils. The protein kinase C inhibitor 1-(5-isoquinoline sulfonyl)-2-methylpiperazine, H-7, has no effect on the potentiation by PMA of the A23187-induced release, it prevents the inhibition by PMA of the release produced by PAF or fMet-Leu-Phe. In addition, PMA increases arachidonic acid release in H-7-treated cells stimulated with fMet-Leu-Phe. The diacylglycerol kinase inhibitor R59022 increases the level of diacylglycerol in neutrophils stimulated with fMet-Leu-Phe. Furthermore, R59022 potentiates [ 3 H] arachidonic acid release produced by fMet-Leu-Phe. This potentiation is not inhibited by H-7, in fact, it is increased in H-7-treated neutrophils

  18. Time-dependent alterations in serum NO concentration after oral administration of L-arginine, L-NAME, and allopurinol in intestinal ischemia/reperfusion

    Directory of Open Access Journals (Sweden)

    Amalia E Yanni

    2008-04-01

    Full Text Available Amalia E Yanni1, Eleutherios Margaritis2, Nikolaos Liarakos2, Alkisti Pantopoulou2, Maria Poulakou2, Maria Kostakis2, Despoina Perrea2, Alkis Kostakis31Department of Science of Dietetics and Nutrition, Harokopio University of Athens, Athens, Greece, 2Laboratory of Experimental Surgery and Surgical Research, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece, 32nd Department of Propedeutic Surgery, School of Medicine, National and Kapodistrian University of Athens, Athens, GreeceObjective: To study the effect of oral administration of a nitric oxide (NO donor L-arginine (L-Arg, a NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME and an inhibitor of xanthine oxidase, allopurinol (Allo, on serum NO concentration and catalase activity after intestinal ischemia/reperfusion (I/R in rats.Methods: Male Wistar rats received per os L-Arg (800 mg/kg or L-NAME (50 mg/kg or Allo (100 mg/kg 24 hrs, 12 hrs and 1 hr before underwent 1 hr occlusion of superior mesenteric artery followed by 1 hr of reperfusion (L-Arg(IR1, L-NAME(IR1 and Allo(IR1 respectively or 1 hr occlusion followed by 8 hrs of reperfusion (L-Arg(IR8, L-NAME(IR8 and Allo(IR8 respectively. There was one group underwent 1 hr occlusion (I, a group underwent 1 hr occlusion followed by 1 hr reperfusion (IR1, a group subjected to 1 hr occlusion followed by 8 hrs of reperfusion (IR8 and a last group that served as control (C. Serum NO concentration and catalase activity were measured.Results: After 1 hr of reperfusion serum NO concentration was elevated in IR1 and L-Arg(IR1 groups compared with group C but not in L-NAME(IR1 and Allo(IR1 group. Catalase activity was enhanced in L-NAME(IR1 group. Interestingly, serum NO concentration was increased after 8 hrs of reperfusion in all groups (IR8, L-Arg(IR8, L-NAME(IR8 and Allo(IR8 compared with control while catalase activity did not show significant difference in any group.Conclusions: The results of the

  19. Role of Lipoxygenase Metabolites of Arachidonic Acid in Enhanced Pulmonary Artery Contractions of Female Rabbits

    OpenAIRE

    Pfister, Sandra L.

    2011-01-01

    Pulmonary arterial hypertension is characterized by elevated pulmonary artery pressure and vascular resistance. In women the incidence is 4 fold greater than that in men. Studies suggest sustained vasoconstriction is a factor in increased vascular resistance. Possible vasoconstrictor mediators include arachidonic acid-derived lipoxygenase metabolites. Our studies in rabbits showed enhanced endothelium-dependent contractions to arachidonic acid in pulmonary arteries from females compared to ma...

  20. Antihypertensive mechanisms of chronic captopril (CPT) or N-Acetylcysteine (NAC) treatment in L-NAME hypertensive rats

    Czech Academy of Sciences Publication Activity Database

    Dobešová, Zdenka; Zicha, Josef; Pecháňová, Olga; Kuneš, Jaroslav

    2005-01-01

    Roč. 46, č. 4 (2005), s. 912-913 ISSN 0194-911X. [Annual Meeting of the European Council for Cardiovascular Research (ECCR) /10./. 14.10.2005-16.10.2005, La Colle sur Loup] R&D Projects: GA MZd(CZ) NR7786 Keywords : antihypertensive mechanism * captopril * N-Acetylcysteine * L-NAME hypertension Subject RIV: ED - Physiology

  1. Dietary arachidonic acid in perinatal nutrition

    DEFF Research Database (Denmark)

    Lauritzen, Lotte; Fewtrell, Mary; Agostoni, Carlo

    2015-01-01

    Arachidonic acid (AA) is supplied together with docosahexaenoic acid (DHA) in infant formulas, but we have limited knowledge about the effects of supplementation with either of these long-chain polyunsaturated fatty acids (LCPUFA) on growth and developmental outcomes. AA is present in similar lev...

  2. The effects of L-arginine, D-arginine, L-name and methylene blue on channa striatus-induced peripheral antinociception in mice.

    Science.gov (United States)

    Zakaria, Zainul Amiruddin; Sulaiman, Mohd Rosian; Somchit, Muhammad Nazrul; Jais, Abdul Manan Mat; Ali, Daud Israf

    2005-08-03

    To determine the involvement of nitric oxide/cyclic guanosine monophosphate (NO/cGMP) pathway in aqueous supernatant of haruan (Channa striatus) fillet (ASH) antinociception using the acetic acid-induced abdominal constriction test. The ASH was prepared by soaking fresh haruan fillet in chloroform:methanol (CM) (2/1 (v/v)) for 72 h followed by evaporation of the upper layer supernatant to remove any solvent residues. The supernatant was then subjected to a freeze-drying process (48 h) followed by doses preparation. Subcutaneous (SC) administration of ASH alone (0.170, 0.426 and 1.704 mg/kg) exhibited a dose-dependent antinociception. On the other hand, 20 mg/kg (SC) of L-arginine and MB exhibited a significant nociception and antinociception, while D-arginine and L-NAME did not produce any effect at all. Pre-treatment with L-arginine was found to significantly reverse the three respective doses of ASH antinociception; pre-treatment with D-arginine did not produce any significant change in the ASH activity; pre-treatment with L-NAME only significantly increased the 0.170 and 0.426 mg/kg ASH antinociception; and pre-treatment with MB significantly enhanced the respective doses of ASH antinociception, respectively. Furthermore, co-treatment with L-NAME significantly enhanced the L-arginine reversal effect on 0.426 mg/kg ASH antinociception. In addition, MB significantly reversed the L-arginine nociception on 0.426 mg/kg ASH. These finding suggest ASH antinociception involves the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) pathway. The presence of NO was found to reverse ASH antinociceptive activity while blocking of cGMP system enhanced it.

  3. The effect of endogenous essential and nonessential fatty acids on the uptake and subsequent agonist-induced release of arachidonate

    International Nuclear Information System (INIS)

    Furth, E.E.; Hurtubise, V.; Schott, M.A.; Laposata, M.

    1989-01-01

    We have demonstrated that the uptake and agonist-induced release of a pulse of arachidonate are influenced by the size and composition of preexisting endogenous fatty acid pools. EFD-1 cells, an essential fatty acid-deficient mouse fibrosarcoma cell line, were incubated with radiolabeled (14C or 3H) arachidonate, linoleate, eicosapentaenoate (EPA), palmitate, or oleate in concentrations of 0-33 microM for 24 h. After 24 h, the cells were pulsed with 0.67 microM radiolabeled (3H or 14C, opposite first label) arachidonate for 15 min and then stimulated with 10 microM bradykinin for 4 min. Because EFD-1 cells contain no endogenous essential fatty acids, we were able to create essential fatty acid-repleted cells for which the specific activity of the newly constructed endogenous essential fatty acid pool was known. Loading the endogenous pool with the essential fatty acids arachidonate, eicosapentaenoate, or linoleate (15-20 nmol of fatty acid incorporated/10(6) cells) decreased the uptake of a pulse of arachidonate from 200 to 100 pmol/10(6) cells but had no effect on palmitate uptake. The percent of arachidonate incorporated during the pulse which was released upon agonist stimulation increased 2-fold (4-8%) as the endogenous pool of essential fatty acids was increased from 0 to 15-20 nmol/10(6) cells. This 8% release was at least 3-fold greater than the percent release from the various endogenous essential fatty acid pools. In contrast, loading the endogenous pool with the nonessential fatty acids oleate or palmitate to more than 2-3 times their preexisting cellular level had no effect on the uptake of an arachidonate pulse. Like the essential fatty acids, increasing endogenous oleate increased (by 2-fold) the percent release of arachidonate incorporated during the pulse, whereas endogenous palmitate had no effect on subsequent agonist-induced release from this arachidonate pool

  4. Effects of Diclofenac, L-NAME, L-Arginine, and Pentadecapeptide BPC 157 on Gastrointestinal, Liver, and Brain Lesions, Failed Anastomosis, and Intestinal Adaptation Deterioration in 24 Hour-Short-Bowel Rats.

    Science.gov (United States)

    Lojo, Nermin; Rasic, Zarko; Zenko Sever, Anita; Kolenc, Danijela; Vukusic, Darko; Drmic, Domagoj; Zoricic, Ivan; Sever, Marko; Seiwerth, Sven; Sikiric, Predrag

    2016-01-01

    Stable gastric pentadecapeptide BPC 157 was previously used to ameliorate wound healing following major surgery and counteract diclofenac toxicity. To resolve the increasing early risks following major massive small bowel resectioning surgery, diclofenac combined with nitric oxide (NO) system blockade was used, suggesting therapy with BPC 157 and the nitric oxide synthase (NOS substrate) L-arginine, is efficacious. Immediately after anastomosis creation, short-bowel rats were untreated or administered intraperitoneal diclofenac (12 mg/kg), BPC 157 (10 μg/kg or 10 ng/kg), L-NG-nitroarginine methyl ester (L-NAME, 5 mg/kg), L-arginine (100 mg/kg) alone or combined, and assessed 24 h later. Short-bowel rats exhibited poor anastomosis healing, failed intestine adaptation, and gastrointestinal, liver, and brain lesions, which worsened with diclofenac. This was gradually ameliorated by immediate therapy with BPC 157 and L-arginine. Contrastingly, NOS-blocker L-NAME induced further aggravation and lesions gradually worsened. Specifically, rats with surgery alone exhibited mild stomach/duodenum lesions, considerable liver lesions, and severe cerebral/hippocampal lesions while those also administered diclofenac showed widespread severe lesions in the gastrointestinal tract, liver, cerebellar nuclear/Purkinje cells, and cerebrum/hippocampus. Rats subjected to surgery, diclofenac, and L-NAME exhibited the mentioned lesions, worsening anastomosis, and macro/microscopical necrosis. Thus, rats subjected to surgery alone showed evidence of deterioration. Furtheremore, rats subjected to surgery and administered diclofenac showed worse symptoms, than the rats subjected to surgery alone did. Rats subjected to surgery combined with diclofenac and L-NAME showed the worst deterioration. Rats subjected to surgery exhibited habitual adaptation of the remaining small intestine, which was markedly reversed in rats subjected to surgery and diclofenac, and those with surgery, diclofenac, and

  5. Chronic and acute effects of different antihypertensive drugs on femoral artery relaxations of L-NAME hypertensive rats

    Czech Academy of Sciences Publication Activity Database

    Sládková, M.; Kojšová, S.; Jendeková, L.; Pecháňová, Olga

    2007-01-01

    Roč. 56, Suppl.2 (2007), S85-S91 ISSN 0862-8408 Grant - others:VEGA(SK) 2/6148/26; VEGA(SK) 1/3429/06; -(SK) APVV-0586-06 Institutional research plan: CEZ:AV0Z50110509 Keywords : L-NAME induced hypertension * indapamide * hydrochlorothiazide * captopril Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 1.505, year: 2007

  6. Regression of L-NAME - induced hypertension: the role of NO-pathway and endothelium-derived constricting factor

    Czech Academy of Sciences Publication Activity Database

    Paulis, Ĺudovít; Zicha, Josef; Kuneš, Jaroslav; Hojná, Silvie; Kojšová, S.; Pecháňová, O.; Šimko, F.

    2006-01-01

    Roč. 24, č. S4 (2006), S7-S7 ISSN 0263-6352. [European Meeting on Hypertension /16./. 12.06.2006-15.06.2006, Madrid] R&D Projects: GA MZd(CZ) NR7786; GA ČR(CZ) GA305/03/0769 Grant - others:VEGA(SK) 1/3429/0; APVT(SK) 51-02704 Keywords : L-NAME * hypertension * nitric oxide Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery

  7. Effects of fluticasone propionate inhalation on levels of arachidonic acid metabolites in patients with chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Gert T. Verhoeven

    2001-01-01

    Full Text Available Background: In smoking COPD patients the bronchoalveolar lavage (BAL fluid contains high numbers of inflammatory cells. These cells might produce arachidonic acid (AA metabolites, which contribute to inflammation and an increased bronchomotor tone.

  8. Differential effects of Rho-kinase inhibitor and angiotensin II type-1 receptor antagonist on the vascular function in hypertensive rats induced by chronic l-NAME treatment

    Directory of Open Access Journals (Sweden)

    Bainian Chen

    2012-10-01

    Full Text Available Little attention has been paid to the effect of Rho-kinase inhibitor on the vascular dysfunction of nitric oxide-deficient hypertension. We aimed to investigate whether the Rho-kinase inhibitor fasudil showed beneficial effect on the vascular dysfunction of the NG-nitro-l-arginine methyl ester (l-NAME treated rat, as well as to compare the differential effects of fasudil and angiotensin II receptor antagonist valsartan on vascular function. In the present study, both valsartan and fasudil exerted antihypertensive action on the l-NAME-treated rats, while only valsartan attenuated the cardiac hypertrophy. Treatment with valsartan showed improvement on vascular reactivity to norepinephrine, KCl and CaCl2, whereas fasudil therapy showed little effect on vasoconstriction. Endothelium-dependent vasodilation to acetylcholine was reduced in the NO-deficient group but was normalized by the fasudil therapy. The increased expression of RhoA and Rho-kinase (ROCK in the vasculature was corrected well to normal level by either valsartan or fasudil administration, which seemed to be at least partially responsible for the beneficial effect of the drug infusion. These findings suggest that the angiotensin II receptor antagonist interferes more with the contractile response than Rho-kinase inhibitor, whereas inhibition of Rho-kinase activity exhibits a better improvement on vasorelaxation than blockade of angiotensin II receptor.

  9. EVALUATION OF SOME ANTIOXIDANTS TREATMENT ON KIDNEY FUNCTION AND LIPID PEROXIDATION STATUS IN HYPERTENSIVE RATS INDUCED WITH L-NAME

    International Nuclear Information System (INIS)

    MATTA, T.F.

    2008-01-01

    Hypertension, the disease known as the s ilent killer , is a common problem facing peoples today with million new cases being diagnosed each year. Although a great amount of money is spent annually for the treatment and detection of this disease and its complications, current conventional treatment have done little to reduce the number of patients with hypertension. Research has found a variety of alternative therapies to be successful in reducing high blood pressure including diet, exercise, stress management, supplements and herbs.In this study, the changes in some selected biochemical blood variables, which are thought to represent risk factors coincident with hypertension and kidney function, were compared between a group of normotensive male albino rats and other group suffered from hypertension induced artificially by N-nitro-L-arginine methyl ester (L-NAME). Also, this study investigated the effects of daily administration of some antioxidants nutrients for two weeks namely carnitine, coenzyme Q 1 0 , garlic oil and their mixture on the same variables in order to show to what extent these nutrients are valid to control the levels of these variables without any deleterious effects after treatment. Fifty mg of coenzyme Q 10 and 50 mg of carnitine were daily injected intraperitoneally for two weeks in two groups of hypertensive rats while 200 mg/kg b.wt was given to another group of hypertensive rats by oral intubation. A combination of all the above mentioned nutrients was given to the fourth group. Another hypertensive group was left without any treatment and served as a recovery group. Fasting blood samples were drawn and kidney tissues were taken at the terminal of treatments.The obtained results revealed that induced hypertension caused significant (P<0.05) increase of thiobarbeturic acid reactive substances (TBARs), malondialdehyde (MAD), parathormone (PTH), renin, blood urea, creatinine, phosphorus, sodium and potassium while glutathione (GSH), calcium

  10. The effect of cigarette smoke on the metabolism of arachidonic acid in isolated hamster lungs

    International Nuclear Information System (INIS)

    Maennistoe, J.; Toivonen, H.; Hartiala, J.; Bakhle, Y.S.; Uotila, P.

    1981-01-01

    The effects of cigarette smoke on the metabolism of exogenous arachidonic acid (AA) were investigated in isolated hamster lungs. Arachidonate was injected into the pulmonary circulation and the metabolites were analysed from the nonrecirculating perfusion effluent by thin layer chromatography. After the pulmonary injection of 66 nmol of 14C-AA about 20% of the injected radioactivity appeared in the perfusion effluent mostly as metabolites in six minutes. When isolated lungs were ventilated with cigarette smoke during the perfusion, the amounts of PGF2 alpha, PGE2 and two unidentified metabolite groups increased in the lung effluent. In two other experimental series hamsters were exposed to cigarette smoke before the lung perfusion either once for 30 min or during one hour daily for ten consecutive days. Neither pre-exposures caused any changes in the amounts of arachidonate metabolites in the lung effluent

  11. Class side effects: decreased pressure in the lower oesophageal and the pyloric sphincters after the administration of dopamine antagonists, neuroleptics, anti-emetics, L-NAME, pentadecapeptide BPC 157 and L-arginine.

    Science.gov (United States)

    Belosic Halle, Zeljka; Vlainic, Josipa; Drmic, Domagoj; Strinic, Dean; Luetic, Kresimir; Sucic, Mario; Medvidovic-Grubisic, Maria; Pavelic Turudic, Tatjana; Petrovic, Igor; Seiwerth, Sven; Sikiric, Predrag

    2017-05-17

    The ulcerogenic potential of dopamine antagonists and L-NAME in rats provides unresolved issues of anti-emetic neuroleptic application in both patients and experimental studies. Therefore, in a 1-week study, we examined the pressures within the lower oesophageal and the pyloric sphincters in rats [assessed manometrically (cm H 2 O)] after dopamine neuroleptics/prokinetics, L-NAME, L-arginine and stable gastric pentadecapeptide BPC 157 were administered alone and/or in combination. Medication (/kg) was given once daily intraperitoneally throughout the 7 days, with the last dose at 24 h before pressure assessment. Given as individual agents to healthy rats, all dopamine antagonists (central [haloperidol (6.25 mg, 16 mg, 25 mg), fluphenazine (5 mg), levomepromazine (50 mg), chlorpromazine (10 mg), quetiapine (10 mg), olanzapine (5 mg), clozapine (100 mg), sulpiride (160 mg), metoclopramide (25 mg)) and peripheral(domperidone (10 mg)], L-NAME (5 mg) and L-arginine (100 mg) decreased the pressure within both sphincters. As a common effect, this decreased pressure was rescued, dose-dependently, by BPC 157 (10 µg, 10 ng) (also note that L-arginine and L-NAME given together antagonized each other's responses). With haloperidol, L-NAME worsened both the lower oesophageal and the pyloric sphincter pressure, while L-arginine ameliorated lower oesophageal sphincter but not pyloric sphincter pressure, and antagonized L-NAME effect. With domperidone, L-arginine originally had no effect, while L-NAME worsened pyloric sphincter pressure. This effect was opposed by L-arginine. All these effects were further reversed towards a stronger beneficial effect, close to normal pressure values, by the addition of BPC 157. In addition, NO level was determined in plasma, sphincters and brain tissue. Thiobarbituric acid reactive substances (TBARS) were also assessed. Haloperidol increased NO levels (in both sphincters, the plasma and brain), consistently producing increased

  12. Involvement of arachidonate metabolism in neurotensin-induced prolactin release in vitro

    International Nuclear Information System (INIS)

    Canonico, P.L.; Speciale, C.; Sortino, M.A.; Scapagnini, U.

    1985-01-01

    Neurotensin increased in a concentration-dependent manner the level of hypophyseal [ 3 H]arachidonic acid in vitro as well as prolactin release from hemipituitary glands. The effect of 1 microM neurotensin on arachidonate release was already present at 2.5 min, maximal at 5, and disappeared after a 10-min incubation. Neurotensin analogues produced an enhancement of hypophyseal arachidonate similar to their relative potencies in other cellular systems, whereas other peptides (somatostatin and vasoactive intestinal peptide) were devoid of any effect on the concentration of the fatty acid in the pituitary. Seventy micromoles RHC 80267, a rather selective inhibitor of diacylglycerol lipase, completely prevented the neurotensin-stimulated prolactin release and decreased arachidonate release both in basal or in neurotensin-induced conditions. Similar results were obtained with 50 microM quinacrine, a phospholipase A2 inhibitor. To clarify whether arachidonate released by neurotensin requires a further metabolism through specific pathways to stimulate prolactin release, the authors used indomethacin and BW 755c, two blockers of cyclooxygenase and lipoxygenase pathways. Thirty micromoles indomethacin, a dose active to inhibit cyclooxygenase, did not affect unesterified arachidonate levels either in basal or in neurotensin-induced conditions; moreover, the drug did not modify basal prolactin release but slightly potentiated the stimulatory effect of neurotensin on the release of the hormone. On the other hand, 250 microM BW 755c, an inhibitor of both cyclooxygenase and lipoxygenase pathways, significantly inhibited both basal and neurotensin-stimulated prolactin release and further potentiated the increase of the fatty acid concentrations produced by 1 microM neurotensin

  13. Beneficial effects of Acer okamotoanum sap on L-NAME-induced hypertension-like symptoms in a rat model.

    Science.gov (United States)

    Yang, Hyun; Hwang, Inho; Koo, Tae-Hyoung; Ahn, Hyo-Jin; Kim, Sun; Park, Mi-Jin; Choi, Won-Sil; Kang, Ha-Young; Choi, In-Gyu; Choi, Kyung-Chul; Jeung, Eui-Bae

    2012-02-01

    The sap of Acer okamotoanum has been termed 'bone-benefit-water' in Korea owing to its mineral and sugar content. In particular, the calcium (Ca) and potassium (K) concentrations of the sap of Acer okamotoanum are 40- and 20-times higher, respectively, than commercial spring water. In the present study, we examined whether Acer okamotoanum sap improves or prevents hypertension-like symptoms in a rat model. Male Sprague-Dawley rats (8-weeks-old) were provided commercial spring water supplemented with 25, 50 or 100% Acer okamotoanum sap, 3% potassium ions (K+) or captopril, and treated daily for 2 weeks with NG-nitro-L-arginine methyl ester (L-NAME; 100 mg/kg/day) by subcutaneous injection, in order to induce hypertensive symptoms. Rats were euthanized 6 h following the final injection. To assess the effect of the sap on hypertension-like symptoms, we examined the mean blood pressure (BP), protein levels and localization of endothelial nitric oxide synthase (eNOS) in the descending aorta of the rats. BP levels were significantly lower in hypertensive rats received 25, 50 and 100% sap compared with rats who were administered only commercial spring water. Protein levels of eNOS were repressed in L-NAME-only-treated rats, but were elevated in the descending aorta of rats administered captopril, K+ water and Acer okamotoanum sap (25, 50 and 100%) up to the level of the sham group provided commercial spring water, and then injected with dimethyl sulfoxide for the same period of time. Localized eNOS protein was abundantly expressed in the perivascular descending aorta adipose tissue of the rats. Taken together, these results demonstrated that the sap of Acer okamotoanum ameliorated high BP induced by L-NAME treatment in a rat model.

  14. Effect of cyclosporine and l-name on skeletal muscle arteriole dilation to lipopolysaccharide in vivo

    International Nuclear Information System (INIS)

    Purton, B.J.; Hill, M.A.; Potocnik, S.J.

    1999-01-01

    Full text: Allosteric sites are being recognised on a growing number of G protein-coupled receptors (GPCRs), in addition to the classical binding site recognised by agonists and antagonists. The muscarinic acetylcholine receptors (mAChRs) are the best-studied system of allosteric modulation at GPCRs, and the neuromuscular blocking agent, gallamine, has been demonstrated to exert a profound negative allosteric effect on agonist and antagonist binding affinities at all 5 mAChR subtypes (Christopoulos et al, 1998). In the present study, the effect of gallamine pretreatment on the steady-state expression of human M 2 mAChRs was investigated in transfected CHO cells. The hydrophilic radioligand, [ 3 H]N-methylscopolamine ([ 3 H]NMS) was used to quantify cell-surface receptors (BmaX = 4.49 ± 0.94 finoU10 cells; pK D 9.93 ± 0.15; n=6), whereas the lipophilic radioligand, [ 3 H]quinuclidinyl benzilate ([ 3 H]QNB) was used to quantify both cell-surface and internalised receptors (B max = 10.69 ± 2.61 fmol/10 5 cells; pK D = 10.86 ± 0.02; n=3). Pretreatment of the CHO cells for 24 h with the agonist, carbachol (1 mM), resulted in a significant receptor downregulation, whereas pretreatment with the antagonist, atropine (1 μM), or with gallamine (1 μM) resulted in receptor upregulation. In all instances, radioligand affinity was unaltered. The ability of gallamine to increase steady-state cell-surface mAChRs was also evident at pretreatment concentrations below the K D value for gallamine binding to the M 2 mAChR allosteric site. Subsequent experiments were undertaken to evaluate the time course of the phenomenon. Using [ 3 H]NMS, the same pattern of mAChR expression changes was found after a 90 min period of pretreatment with the three ligands as was seen after 24 h pretreatment. In contrast, [ 3 H]QNB B max values after 90 min pretreatment were no different to vehicle controls, indicating that changes in cell-surface levels during short ligand exposure times were most

  15. Treinamento resistido controla a pressão arterial de ratos hipertensos induzidos por l-NAME

    Directory of Open Access Journals (Sweden)

    Ayslan Jorge Santos de Araujo

    2013-04-01

    Full Text Available FUNDAMENTO: A hipertensão arterial é uma síndrome multifatorial, crônica, causada tanto por fatores congênitos ou adquiridos. OBJETIVO: Avaliar os efeitos do treinamento físico resistido (TR sobre pressão arterial, reatividade e morfologia vascular de ratos hipertensos induzidos por L-NAME. MÉTODOS: Ratos Wistar machos (200-250 g foram divididos em 3 grupos: normotenso sedentário (NS, hipertenso sedentário (HS e hipertenso treinado (HT. A hipertensão foi induzida pela administração de L-NAME (40 mg/kg na água de beber por 4 semanas. A pressão arterial foi avaliada antes e após o TR. O TR foi realizado utilizando 50% de 1RM, em 3 séries de 10 repetições, 3 vezes por semana, durante quatro semanas. A reatividade vascular foi mensurada em artéria mesentérica superior por curvas concentração resposta ao nitroprussiato de sódio (NPS e fenilefrina (FEN. Além disso, foram realizadas análises histológicas e estereológicas. RESULTADOS: O TR inibiu o aumento das pressões arteriais média e diastólica. Foi observada uma redução significativa na resposta máxima e na potência da FEN entre os grupos HS e HT. A análise histológica evidenciou aspecto normal para as túnicas íntima, média e adventícia em todos os grupos. Não houve diferença significativa nas áreas do lúmen, da túnica média e total das artérias dos grupos HS e HT em relação ao NS. A razão parede/lúmen arterial do grupo HS apresentou diferença significativa em relação ao NS (p < 0,05, mas esta não foi diferente do HT. CONCLUSÕES: O TR foi capaz de prevenir a elevação da pressão arterial sob as condições deste estudo. Este controle parece envolver a regulação de mecanismo vasoconstritor e a manutenção do diâmetro luminal de ratos hipertensos induzidos por L-NAME.

  16. BAY 41-2272 Treatment Improves Acetylcholine-Induced Aortic Relaxation in L-NAME Hypertensive Rats.

    Science.gov (United States)

    Prawez, Shahid; Ahanger, Azad Ahmad; Singh, Thakur Uttam; Mishra, Santosh Kumar; Sarkar, Souvendra Nath; Kumar, Dinesh

    2016-12-01

    Hypertension, an emerging problem of recent era, and many pathophysiological factors are participating to produce the disease. Nitric oxide (NO) is an important constituent to ameliorate hypertensive condition. Inhibition of endogenous NO synthase by L-N G -Nitroarginine methyl ester (L-NAME) was responsible for generating hypertension in rats. BAY 41-2272 (5-cyclopropyl-2-[1-(2-fluoro-benzyl)-1H-pyrazolo[3,4-b]pyridine-3-yl]-pyrimidin-4-ylamine), a soluble guanylyl cyclase activator, restricts rise of blood pressure and shows cardioprotective activity. The aim of the present study was to analyze effect of short-term BAY 41-2272 treatment on blood pressure and vascular function. Male Wistar rats were randomly divided into three groups such as control (group-A), hypertensive (group-B), and BAY 41-2272-treated hypertensive (group-C) rats. Normal saline was administered intramuscularly to control rats for last 3 days (days 40, 41, and 42) of total 42 days treatment, whereas rats of group-B and group-C were treated with L-NAME hydrochloride in drinking water at 50 mg/kg body weight daily for 42 days. Also, normal saline and BAY 41-2272 were administered for last 3 days at two different dosages at 1 and 3 mg/kg body weight/day intramuscularly to group-B and group-C rats, respectively. Administration of BAY 41-2272 for 3 days was not sufficient enough to decrease mean arterial pressure of hypertensive rats significantly. BAY at both the treatment dosages significantly ameliorate acetylcholine-induced maximal aortic relaxation compared with BAY-untreated hypertensive rats. Findings of the present study indicate that even shorter period of BAY 41-2272 treatment (3 days) improves vascular relaxation.

  17. Effect of selenium and vitamin E deficiencies on the fate of arachidonic acid in rat isolated lungs

    International Nuclear Information System (INIS)

    Uotila, P.; Puustinen, T.

    1985-01-01

    The fate of exogenous 14 C-arachidonic acid ( 14 C-AA) was investigated in the isolated lungs of rats fed selenium and vitamin E deficient diet or diets supplemented with selenium and/or vitamin E. When 80 nmol of 14 C-AA was infused into the pulmonary circulation most of the infused 14 C-AA was found in different phospholipid and neutral lipid fractions of the perfused lungs. Only less than ten percent of the infused radioactivity was recovered in the perfusion effluent. The amount of arachidonate metabolites in the perfusion effluent was negligible, and most of the radioactivity in the perfusion effluent consisted of unmetabolized arachidonate. Selenium deficiency had no significant effect on the distribution of 14 C-AA in different lung lipid fractions. However, in the lungs of vitamin E deficient rats the amount of radioactivity was slightly increased in the neutral lipid fraction, which was due to the increased amount of 14 C-AA in the diacylglycerols. The amount of radioactivity was increased especially in the 1,3-diacylglycerols. The amount of radioactivity was increased especially in the 1,3-diacylglycerols. The amount of 14 C-AA in the triacylglycerols and in different phospholipids was not significantly changed. The present study might indicate that selenium deficiency has no significant effect on the fate of exogenous arachidonic acid in isolated rat lungs, and that vitamin E deficiency would slightly increase the amount of arachidonic acid in the diacylglycerols

  18. Bacterial metabolism of human polymorphonuclear leukocyte-derived arachidonic acid.

    Science.gov (United States)

    Sorrell, T C; Muller, M; Sztelma, K

    1992-05-01

    Evidence for transcellular bacterial metabolism of phagocyte-derived arachidonic acid was sought by exposing human blood polymorphonuclear leukocytes, prelabelled with [3H]arachidonic acid, to opsonized, stationary-phase Pseudomonas aeruginosa (bacteria-to-phagocyte ratio of 50:1) for 90 min at 37 degrees C. Control leukocytes were stimulated with the calcium ionophore A23187 (5 microM) for 5 min. Radiochromatograms of arachidonic acid metabolites, extracted from A23187-stimulated cultures and then separated by reverse-phase high-performance liquid chromatography, revealed leukotriene B4, its omega-oxidation products, and 5-hydroxy-eicosatetraenoic acid. In contrast, two major metabolite peaks, distinct from known polymorphonuclear leukocyte arachidonic acid products by high-performance liquid chromatography or by thin-layer chromatography, were identified in cultures of P. aeruginosa with [3H]arachidonic acid-labelled polymorphonuclear leukocytes. Respective chromatographic characteristics of these novel products were identical to those of two major metabolite peaks produced by incubation of stationary-phase P. aeruginosa with [3H]arachidonic acid. Production of the metabolites was dependent upon pseudomonal viability. UV spectral data were consistent with a conjugated diene structure. Metabolism of arachidonic acid by P. aeruginosa was not influenced by the presence of catalase, superoxide dismutase, nordihydroguaiaretic acid, ethanol, dimethyl sulfoxide, or ferrous ions but was inhibited by carbon monoxide, ketoconazole, and 1,2-epoxy-3,3,3-trichloropropane. Our data suggest that pseudomonal metabolism of polymorphonuclear leukocyte-derived arachidonic acid occurs during phagocytosis, probably by enzymatic epoxidation and hydroxylation via an oxygenase. By this means, potential proinflammatory effects of arachidonic acid or its metabolites may be modulated by P. aeruginosa at sites of infection in vivo.

  19. A new model to study the role of arachidonic acid in colon cancer pathophysiology

    OpenAIRE

    Fan, Yang-Yi; Callaway, Evelyn; Monk, Jennifer M.; Goldsby, Jennifer S.; Yang, Peiying; Vincent, Logan; Chapkin, Robert S.

    2016-01-01

    A significant increase in cyclooxygenase 2 (COX2) gene expression has been shown to promote cylcooxygenase-dependent colon cancer development. Controversy associated with the role of COX2 inhibitors indicates that additional work is needed to elucidate the effects of arachidonic acid (AA) derived (cyclooxygenase and lipoxygenase) eicosanoids in cancer initiation, progression and metastasis. We have recently developed a novel Fads1 knockout mouse model, which allows for the investigation of AA...

  20. Arachidonic acid metabolites and endothelial dysfunction of portal hypertension.

    Science.gov (United States)

    Sacerdoti, David; Pesce, Paola; Di Pascoli, Marco; Brocco, Silvia; Cecchetto, Lara; Bolognesi, Massimo

    2015-07-01

    Increased resistance to portal flow and increased portal inflow due to mesenteric vasodilatation represent the main factors causing portal hypertension in cirrhosis. Endothelial cell dysfunction, defined as an imbalance between the synthesis, release, and effect of endothelial mediators of vascular tone, inflammation, thrombosis, and angiogenesis, plays a major role in the increase of resistance in portal circulation, in the decrease in the mesenteric one, in the development of collateral circulation. Reduced response to vasodilators in liver sinusoids and increased response in the mesenteric arterioles, and, viceversa, increased response to vasoconstrictors in the portal-sinusoidal circulation and decreased response in the mesenteric arterioles are also relevant to the pathophysiology of portal hypertension. Arachidonic acid (AA) metabolites through the three pathways, cyclooxygenase (COX), lipoxygenase, and cytochrome P450 monooxygenase and epoxygenase, are involved in endothelial dysfunction of portal hypertension. Increased thromboxane-A2 production by liver sinusoidal endothelial cells (LSECs) via increased COX-1 activity/expression, increased leukotriens, increased epoxyeicosatrienoic acids (EETs) (dilators of the peripheral arterial circulation, but vasoconstrictors of the portal-sinusoidal circulation), represent a major component in the increased portal resistance, in the decreased portal response to vasodilators and in the hyper-response to vasoconstrictors. Increased prostacyclin (PGI2) via COX-1 and COX-2 overexpression, and increased EETs/heme-oxygenase-1/K channels/gap junctions (endothelial derived hyperpolarizing factor system) play a major role in mesenteric vasodilatation, hyporeactivity to vasoconstrictors, and hyper-response to vasodilators. EETs, mediators of liver regeneration after hepatectomy and of angiogenesis, may play a role in the development of regenerative nodules and collateral circulation, through stimulation of vascular endothelial

  1. Arachidonic acid metabolism in silica-stimulated bovine alveolar macrophages

    International Nuclear Information System (INIS)

    Englen, M.D.

    1989-01-01

    The in vitro production of arachidonic acid (AA) metabolites in adherent bovine alveolar macrophages (BAM) incubated with silica was investigated. BAM were pre-labelled with 3 H-AA, and lipid metabolites released into the culture medium were analyzed by high performance liquid chromatography (HPLC). Lactate dehydrogenase (LDH) release was simultaneously assayed to provide an indication of cell injury. Increasing doses of silica selectively stimulated the 5-lipoxygenase pathway of AA metabolism, while cyclooxygenase metabolite output was suppressed. LDH release increased in a linear, dose-dependent fashion over the range of silica doses used. Moreover, within 15 min following addition of a high silica dose, a shift to the production of 5-lipoxygenase metabolites occurred, accompanied by a reduction in cyclooxygenase products. This rapid alteration in AA metabolism preceded cell injury. To examine the relationship between cytotoxicity and AA metabolite release by BAM exposed to silicas with different cytotoxic and fibrogenic activities, BAM were exposed to different doses of DQ-12, Minusil-5, and Sigma silicas, and carbonyl iron beads. The median effective dose (ED 50 ) of each particulate to stimulate the release of AA metabolites and LDH was calculated. The ED 50 values for DQ-12, Minusil-5, and Sigma silica showed that the relative cytotoxicities of the different silicas for BAM corresponded to the relative potencies of the silicas to elicit 5-lipoxygenase metabolites from BAM. These results indicate that the cytotoxic, and presumed fibrogenic potential, of a silica is correlated with the potency to stimulate the release of leukotrienes from AM

  2. Role of arachidonic acid metabolism in transcriptional induction of tumor necrosis factor gene expression by phorbol ester

    Energy Technology Data Exchange (ETDEWEB)

    Horiguchi, J.; Spriggs, D.; Imamura, K.; Stone, R.; Luebbers, R.; Kufe, D.

    1989-01-01

    The treatment of human HL-60 promyelocytic leukemia cells with 12-0 tetradecanoylphorbol-13-acetate (TPA) is associated with induction of tumor necrosis factor (TNF) transcripts. The study reported here has examined TPA-induced signaling mechanisms responsible for the regulation of TNF gene expression in these cells. Run-on assays demonstrated that TPA increases TNS mRNA levels by transcriptional activation of this gene. The induction of TNF transcripts by TPA was inhibited by the isoquinolinesulfonamide derivative H7 but not by HA1004, suggesting that this effect of TPA is mediated by activation of protein kinase C. TPA treatment also resulted in increased arachidonic acid release. Moreover, inhibitors of phospholipase, A/sub 2/ blocked both the increase in arachidonic acid release and the induction of TNF transcripts. These findings suggest that TPA induces TNF gene expression through the formation of arachidonic acid metabolites. Although indomethacin had no detectable effect on this induction of TNF transcripts, ketoconazole, an inhibitor of 5-lipoxygenase, blocked TPA-induced increases in TNF mRNA levels. Moreover, TNF mRNA levels were increased by the 5-lipoxygenase metabolite leukotriene B/sub 4/. In contrast, the cyclooxygenase metabolite prostaglandin E/sub 2/ inhibited the induction of TNF transcripts by TPA. Taken together, these results suggest that TPA induces TNF gene expression through the arachidonic acid cascade and that the level of TNF transcripts is regulated by metabolites of the pathway, leukotriene B/sub 4/ and prostaglandin E/sub 2/.

  3. Effects of Nitric Oxide Production Inhibitor Named, NG-Nitro-L-Arginine Methyl Ester (L-NAME, on Rat Mesenchymal Stem Cells Differentiation

    Directory of Open Access Journals (Sweden)

    E Arfaei

    2010-04-01

    Full Text Available Introduction & Objectives: Recently, the findings of some studies have shown that, nitric oxide (NO probably has an important role in differentiation of mesenchymal stem cells to osteoblasts. The aim of the present investigation was to study the effects of nitric oxide production inhibitor named, NG-nitro-L-arginine methyl ester (L-NAME, on rat mesenchymal stem cells differentiation to osteoblasts in vitro. Materials & Methods: This was an experimental study conducted at Hamedan University of Medical Sciences in 2009, in which rat bone marrow stem cells were isolated in an aseptic condition and cultured in vitro. After third passage, the cells were cultured in osteogenic differentiation medium. To study the effects of L-NAME on osteogenic differentiation, the L-NAME was added to the culture medium at a concentration of 125, 250, and 500 μM in some culture plates. During the culture procedure, the media were replaced with fresh ones, with a three days interval. After 28 days of culturing the mineralized matrix was stained using Alizarian red staining method. The gathered data were analyzed by SPSS software version 12 using one way ANOVA. Results: The findings of this study showed that in the presence of L-NAME, differentiation of bone marrow mesenchymal stem cells to osteoblasts was disordered and matrix mineralization significantly decreased in a dose dependent manner. Conclusion: This study revealed that, inhibition of nitric oxide production using L-NAME can prevent the differentiation of rat bone marrow mesenchymal stem cells to osteoblast. The results imply that NO is an important constituent in differentiation of mesenchymal stem cell to osteoblasts.

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

    International Nuclear Information System (INIS)

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

    2009-01-01

    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 2+ -independent, but not Ca 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 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.

  5. Mechanism for release of arachidonic acid during guinea pig platelet aggregation: a role for the diacylglycerol lipase inhibitor RHC 80267

    International Nuclear Information System (INIS)

    Amin, D.

    1986-01-01

    The mechanism of the release of arachidonic acid from phospholipids after the stimulation of guinea pig platelets with collagen, thrombin and platelet activating factor (PAF) was studied. RHC 80267, a diacylglycerol lipase inhibitor, and indomethacin, a cyclooxygenase inhibitor, were used. Various in vitro assays for enzymes involved in arachidonic acid release and metabolism were conducted. Platelet aggregation and simultaneous release of ADP from platelets were monitored using a Chrono-log Lumiaggregometer. Platelets were labeled with ( 14 C)arachidonic acid to facilitate sensitive determination of small changes in platelet phospholipids during platelet aggregation. In the present investigation it is shown that collagen, thrombin and PAF increased phospholipase C activity. It was also discovered that cyclooxygenase products were responsible for further stimulation (a positive feed-back) of phospholipase C activity, while diacylglycerol provided a negative feed-back control over receptor-stimulated phospholipase C activity and inhibited ADP release. The guinea pig platelet is an ideal model to study phospholipase C-diacylglycerol lipase pathway for the release of arachidonic acid from platelet phospholipids because it does not have any phospholipase A 2 activity. It was observed that cyclooxygenase products were responsible for collagen-induced guinea pig platelet aggregation. Indomethacin completely inhibited collagen-induced platelet aggregation, was less effective against thrombin, and had no effect on PAF-induced platelet aggregation. On the other hand, RHC 80267 was a powerful inhibitor of aggregation and ADP release induced by all three of these potent aggregating agents

  6. Effects of thyroid hormone status on metabolic pathways of arachidonic acid in mice and humans: A targeted metabolomic approach.

    Science.gov (United States)

    Yao, Xuan; Sa, Rina; Ye, Cheng; Zhang, Duo; Zhang, Shengjie; Xia, Hongfeng; Wang, Yu-cheng; Jiang, Jingjing; Yin, Huiyong; Ying, Hao

    2015-01-01

    Symptoms of cardiovascular diseases are frequently found in patients with hypothyroidism and hyperthyroidism. However, it is unknown whether arachidonic acid metabolites, the potent mediators in cardiovascular system, are involved in cardiovascular disorders caused by hyperthyroidism and hypothyroidism. To answer this question, serum levels of arachidonic acid metabolites in human subjects with hypothyroidism, hyperthyroidism and mice with hypothyroidism or thyroid hormone treatment were determined by a mass spectrometry-based method. Over ten arachidonic acid metabolites belonging to three catalytic pathways: cyclooxygenases, lipoxygenases, and cytochrome P450, were quantified simultaneously and displayed characteristic profiles under different thyroid hormone status. The level of 20-hydroxyeicosatetraenoic acid, a cytochrome P450 metabolite, was positively correlated with thyroid hormone level and possibly contributed to the elevated blood pressured in hyperthyroidism. The increased prostanoid (PG) I2 and decreased PGE2 levels in hypothyroid patients might serve to alleviate atherosclerosis associated with dyslipidemia. The elevated level of thromboxane (TX) A2, as indicated by TXB2, in hyperthyroid patients and mice treated with thyroid hormone might bring about pulmonary hypertension frequently found in hyperthyroid patients. In conclusion, our prospective study revealed that arachidonic acid metabolites were differentially affected by thyroid hormone status. Certain metabolites may be involved in cardiovascular disorders associated with thyroid diseases. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Histological evaluation of the rat dental pulp after indirect capping with sildenafil or L-NAME incorporated into a bioadhesive thermoresponsive system

    Directory of Open Access Journals (Sweden)

    Rogério Rodrigues Cupertino

    2016-06-01

    Full Text Available We evaluated the histological dental pulp state in vivo after indirect pulp capping using sildenafil or LG-nitro-L-arginine (L-NAME, incorporated into a new bioadhesive thermoresponsive system (BTS. Male Wistar rats were subjected to an upper and lower first molar class I cavity preparation followed by indirect pulp capping with sildenafil or L-NAME. Calcium hydroxide (CaOH2 was used as a control. The teeth and surrounding bone were properly dissected and processed for Nissl’s staining. Pulp state was evaluated considering the morphological aspects of the inflammatory response, type of inflammatory infiltrate, organization of the odontoblast layer, blood vessel condition, and presence of abscesses or necrosis. The results were expressed as average of observations. The most intense inflammatory response was observed 3 days after the cavity preparation. No identified changes were detected in the dental pulp response of the molars treated with L-NAME compared with those treated with CaOH2. A dual effect was observed in the teeth treated with sildenafil. While low sildenafil concentration (0.015% w w-1 promoted effects comparable to CaOH2, at a higher concentration (0.15% w w-1, sildenafil caused a severe inflammatory response and pulp necrosis. This pioneering suggest that NO pathway activity may be a determinant in the process of dental pulp healing.

  8. Arachidonic acid triggers an oxidative burst in leukocytes

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    Pompeia C.

    2003-01-01

    Full Text Available The change in cellular reducing potential, most likely reflecting an oxidative burst, was investigated in arachidonic acid- (AA stimulated leukocytes. The cells studied included the human leukemia cell lines HL-60 (undifferentiated and differentiated into macrophage-like and polymorphonuclear-like cells, Jurkat and Raji, and thymocytes and macrophages from rat primary cultures. The oxidative burst was assessed by nitroblue tetrazolium reduction. AA increased the oxidative burst until an optimum AA concentration was reached and the burst decreased thereafter. In the leukemia cell lines, optimum concentration ranged from 200 to 400 µM (up to 16-fold, whereas in rat cells it varied from 10 to 20 µM. Initial rates of superoxide generation were high, decreasing steadily and ceasing about 2 h post-treatment. The continuous presence of AA was not needed to stimulate superoxide generation. It seems that the NADPH oxidase system participates in AA-stimulated superoxide production in these cells since the oxidative burst was stimulated by NADPH and inhibited by N-ethylmaleimide, diphenyleneiodonium and superoxide dismutase. Some of the effects of AA on the oxidative burst may be due to its detergent action. There apparently was no contribution of other superoxide-generating systems such as xanthine-xanthine oxidase, cytochromes P-450 and mitochondrial electron transport chain, as assessed by the use of inhibitors. Eicosanoids and nitric oxide also do not seem to interfere with the AA-stimulated oxidative burst since there was no systematic effect of cyclooxygenase, lipoxygenase or nitric oxide synthase inhibitors, but lipid peroxides may play a role, as indicated by the inhibition of nitroblue tetrazolium reduction promoted by tocopherol.

  9. Role of lipoxygenase metabolites of arachidonic acid in enhanced pulmonary artery contractions of female rabbits.

    Science.gov (United States)

    Pfister, Sandra L

    2011-04-01

    Pulmonary arterial hypertension is characterized by elevated pulmonary artery pressure and vascular resistance. In women the incidence is 4-fold greater than that in men. Studies suggest that sustained vasoconstriction is a factor in increased vascular resistance. Possible vasoconstrictor mediators include arachidonic acid-derived lipoxygenase (LO) metabolites. Our studies in rabbits showed enhanced endothelium-dependent contractions to arachidonic acid in pulmonary arteries from females compared with males. Because treatment with a nonspecific LO inhibitor reduced contractions in females but not males, the present study identified which LO isoform contributes to sex-specific pulmonary artery vasoconstriction. The 15- and 5- but not 12-LO protein expressions were greater in females. Basal and A23187-stimulated release of 15-, 5-, and 12-hydroxyeicosatetraenoic acids (HETEs) from females and males were measured by liquid chromatography/mass spectrometry. Only 15-HETE synthesis was greater in females compared with males under both basal and stimulated conditions. Vascular contractions to 15-HETE were enhanced in females compared with males (maximal contraction: 44±6%versus 25±3%). The specific 15-LO inhibitor PD146176 (12 μmol/L) decreased arachidonic acid-induced contractions in females (maximal contraction: 93±4% versus 57±10%). If male pulmonary arteries were incubated with estrogen (1 μmol/L, 18 hours), protein expression of 15-LO and 15-HETE production increased. Mechanisms to explain the increased incidence of pulmonary hypertension in women are not known. Results suggest that the 15-LO pathway is different between females and males and is regulated by estrogen. Understanding this novel sex-specific mechanism may provide insight into the increased incidence of pulmonary hypertension in females.

  10. Tamoxifen and the Rafoxifene analog LY117018: their effects on arachidonic acid release from cells in culture and on prostaglandin I2 production by rat liver cells

    International Nuclear Information System (INIS)

    Levine, Lawrence

    2004-01-01

    Tamoxifen is being used successfully to treat breast cancer. However, tamoxifen also increases the risk of developing endometrial cancer in postmenopausal women. Raloxifene also decreases breast cancer in women at high risk and may have a lower risk at developing cancer of the uterus. Tamoxifen has been shown to stimulate arachidonic acid release from rat liver cells. I have postulated that arachidonic acid release from cells may be associated with cancer chemoprevention. Rat liver, rat glial, human colon carcinoma and human breast carcinoma cells were labelled with [ 3 H] arachidonic acid. The release of the radiolabel from these cells during incubation with tamoxifen and the raloxifene analog LY117018 was measured. The prostaglandin I 2 produced during incubation of the rat liver cells with μM concentrations of tamoxifen and the raloxifene analog was quantitatively estimated. Tamoxifen is about 5 times more effective than LY117018 at releasing arachidonic acid from all the cells tested. In rat liver cells only tamoxifen stimulates basal prostaglandin I 2 production and that induced by lactacystin and 12-O-tetradecanoyl-phorbol-13-acetate. LY117018, however, blocks the tamoxifen stimulated prostaglandin production. The stimulated prostaglandin I 2 production is rapid and not affected either by preincubation of the cells with actinomycin or by incubation with the estrogen antagonist ICI-182,780. Tamoxifen and the raloxifene analog, LY117018, may prevent estrogen-independent as well as estrogen-dependent breast cancer by stimulating phospholipase activity and initiating arachidonic acid release. The release of arachidonic acid and/or molecular reactions that accompany that release may initiate pathways that prevent tumor growth. Oxygenation of the intracellularly released arachidonic acid and its metabolic products may mediate some of the pharmacological actions of tamoxifen and raloxifene

  11. Hepatic arachidonic acid metabolism is disrupted after hexachlorobenzene treatment

    International Nuclear Information System (INIS)

    Billi de Catabbi, Silvia C.; Faletti, Alicia; Fuentes, Federico; San Martin de Viale, Leonor C.; Cochon, Adriana C.

    2005-01-01

    Hexaclorobenzene (HCB), one of the most persistent environmental pollutants, can cause a wide range of toxic effects including cancer in animals, and hepatotoxicity and porphyria both in humans and animals. In the present study, liver microsomal cytochrome P450 (CYP)-dependent arachidonic acid (AA) metabolism, hepatic PGE production, and cytosolic phospholipase A 2 (cPLA 2 ) activity were investigated in an experimental model of porphyria cutanea tarda induced by HCB. Female Wistar rats were treated with a single daily dose of HCB (100 mg kg -1 body weight) for 5 days and were sacrificed 3, 10, 17, and 52 days after the last dose. HCB treatment induced the accumulation of hepatic porhyrins from day 17 and increased the activities of liver ethoxyresorufin O-deethylase (EROD), methoxyresorufin O-demethylase (MROD), and aminopyrine N-demethylase (APND) from day 3 after the last dose. Liver microsomes from control and HCB-treated rats generated, in the presence of NADPH, hydroxyeicosatetraenoic acids (HETEs), epoxyeicosatrienoic acids (EETs), 11,12-Di HETE, and ω-OH/ω-1-OH AA. HCB treatment caused an increase in total NADPH CYP-dependent AA metabolism, with a higher response at 3 days after the last HCB dose than at the other time points studied. In addition, HCB treatment markedly enhanced PGE production and release in liver slices. This HCB effect was time dependent and reached its highest level after 10 days. At this time cPLA 2 activity was shown to be increased. Unexpectedly, HCB produced a significant decrease in cPLA 2 activity on the 17th and 52nd day. Our results demonstrated for the first time that HCB induces both the cyclooxygenase and CYP-dependent AA metabolism. The effects of HCB on AA metabolism were previous to the onset of a marked porphyria and might contribute to different aspects of HCB-induced liver toxicity such as alterations of membrane fluidity and membrane-bound protein function. Observations also suggested that a possible role of cPLA 2 in

  12. Metabolism and incorporation of orally administrated arachidonic acid in rats

    International Nuclear Information System (INIS)

    Magni, F.; Kikawa, Y.; Jedlinski, A.; Lands, W.E.M.

    1986-01-01

    50 mg 3 H 2 H-20: 4n-6 was administered by oral intubation to rats maintained on a normal diet. The distribution of radioactive arachidonate esterified in the various tissues was similar to that for EFA-deficient rats from their previous study. The amount incorporated in the tissues was 14% in normal rats and 16% in EFA-deficient rats. At 24 hrs, the relative radioactivity in PC was higher (and lower in PE) than after 20 days in the previous study. Urine had 3-4% of initial radioactivity in the first 12 hours and only 1% more by 24 hours. Urine components were analyzed as methyl ester-methoxime-t-butyldimethylsilyl ethers. Most of the arachidonate metabolites in urine reported in the literature have expected ECL values between 26 to 32, whereas they found 68% of radioactivity with ECL values below 26. This represents a substantial divergence from arachidonate metabolite patterns described for injected prostaglandins and indicates the need of examining the metabolites formed from endogenously formed eicosanoids

  13. Arachidonic acid assimilation by thrombocytes from white carneau pigeons

    International Nuclear Information System (INIS)

    Saxon, D.J.; Blankenship, T.

    1986-01-01

    The metabolism of arachidonic acid was investigated using thrombocyte-enriched-plasma from RBWC and WC-II white carneau pigeons, which differ genetically in their susceptibility to atherosclerosis. Thrombocytes were incubated at 42 C with [ 14 C] arachidonate in Puck's solution. After a 1 hour labeling period the WC-II cells had taken up 69% and RBWC 77% of the [ 14 C]arachidonate from the medium. When 8,11,14-eicosatrienoic acid or 5,8,11,14,17-eicosapentaenoic acid were added to incubation media the [ 14 C] uptake was reduced in each type cell, with WC-II exhibiting the greatest effect. Release of [ 14 C]molecules from cells labeled with [ 14 ]Carachidonate was studied using calcium ionophore and indomethacin. Indomethacin inhibited [ 14 C] molecule release similarly in both RBWC and WC-II cells. Calcium ionophore was twice as effective in stimulating [ 14 C]molecule release from WC-II than RBWC cells. Therefore, the WE-II cells (from pigeons greater in susceptibility to atherosclerosis) are more sensitive to calcium ionophore than the REWC cells

  14. Melatonin improves the restoration of endothelium-derived constricting factor signalling and inner diameter in the rat femoral artery after cessation of L-NAME treatment

    Czech Academy of Sciences Publication Activity Database

    Paulis, L.; Pecháňová, Olga; Zicha, Josef; Líšková, Silvia; Celec, P.; Müllerová, M.; Kollár, J.; Behuliak, M.; Kuneš, Jaroslav; Adamcová, M.; Šimko, F.

    2010-01-01

    Roč. 28, Suppl.1 (2010), S19-S24 ISSN 0263-6352 R&D Projects: GA AV ČR(CZ) IAA500110902 Grant - others:EC(XE) 2009-237834; VEGA(SK) 1/0187/09; VEGA(SK) 2/0178/09; APVV(SK) 0538-07; Univerzita Komenského(SK) 2006/24-UK-03 Institutional research plan: CEZ:AV0Z50110509 Keywords : L-NAME hypertension * melatonin * oxidative stress Subject RIV: ED - Physiology Impact factor: 3.980, year: 2010

  15. Pulmonary arachidonic acid metabolism following acute exposures to ozone and nitrogen dioxide

    International Nuclear Information System (INIS)

    Schlesinger, R.B.; Driscoll, K.E.; Gunnison, A.F.; Zelikoff, J.T.

    1990-01-01

    Ozone (O 3 ) and nitrogen dioxide (NO 2 ) are common air pollutants, and exposure to these gases has been shown to affect pulmonary physiology, biochemistry, and structure. This study examined their ability to modulate arachidonic acid metabolites (eicosanoids) in the lungs. Rabbits were exposed for 2 h to O 3 at 0.1, 0.3, or 1 ppm; NO 2 at 1, 3, or 10 ppm; or to a mixture of 0.3 ppm O 3 and 3 ppm NO 2 . Groups of animals sacrificed either immediately or 24 h after each exposure underwent broncho-pulmonary lavage. Selected eicosanoids were assessed in lavage fluid by radioimmunoassay. Increases in prostaglandins E2 (PGE2) and F2 alpha (PGF2 alpha) were found immediately after exposure to 1 ppm O 3 . Exposure to 10 ppm NO 2 resulted in a depression of 6-keto-PGF1 alpha, while thromboxane B2 (TxB2) was elevated after exposure to 1 ppm NO 2 and depressed following 3 and 10 ppm. The O 3 /NO 2 mixture resulted in synergistic increases in PGE2 and PGF2 alpha, with the response appearing to be driven by O 3 . This study has demonstrated that acute exposure to either O 3 or NO 2 can alter pulmonary arachidonic acid metabolism and that the responses to these oxidants differ, both quantitatively and qualitatively

  16. Lung, aorta, and platelet metabolism of 14C-arachidonic acid in vitamin E deficient rats

    International Nuclear Information System (INIS)

    Valentovic, M.A.; Gairola, C.; Lubawy, W.C.

    1982-01-01

    14 C-arachidonic acid metabolism was determined in aortas, platelets, and perfused lungs from rats pair fed a basal diet supplemented with 0 or 100 ppm vitamin E for 11 weeks. Spontaneous erythrocyte hemolysis tests showed 92% and 8% hemolysis for the 0 and 100 ppm vitamin E groups, respectively. Elevated lung homogenate levels of malonaldehyde in the 0 ppm group confirmed its deficient vitamin E status. Aortas from the vitamin E deficient group synthesized 54% less prostacyclin than aortas from the supplemented group (p less than 0.05). Although thromboxane generation by platelets from the vitamin E deficient group exhibited a 37% increase, this difference was not statistically significant compared to the supplemented animals. Greater amounts of PGE2, PGF2 alpha, TXB2, and 6-keto-PGF1 alpha were obtained in albumin buffer perfusates from lungs of vitamin E deficient rats than in those from supplemented rats. Significant differences (p less than 0.05) were noticed, however, only for PGE2 and PGF2 alpha. These studies indicate that vitamin E quantitatively alters arachidonic acid metabolism in aortic and lung tissue but its effect on thromboxane synthesis by platelets is less marked

  17. Chronic cigarette smoke exposure adversely alters 14C-arachidonic acid metabolism in rat lungs, aortas and platelets

    International Nuclear Information System (INIS)

    Lubawy, W.C.; Valentovic, M.A.; Atkinson, J.E.; Gairola, G.C.

    1983-01-01

    Male rats were exposed to freshly generated cigarette smoke once daily, 5 times a week for 10 weeks. Inhalation of smoke was verified by elevated carboxyhemoglobin in blood sampled immediately after smoke exposure and by increased lung aryl hydrocarbon hydroxylase activity 24 hours after the last smoke exposure. Aortic rings isolated from smoke-exposed rats synthesized less prostacyclin (PGI2) from 14 C-arachidonic acid than rings from sham rats. Platelets from smoke-exposed rats synthesized more thromboxane (TXA2) from 14 C-arachidonic acid than platelets from room controls but not those from sham rats. Lung microsomes from smoke-exposed rats synthesized more TXA2 and had a lower PGI2/TXA2 ratio than lung microsomes from room controls and shams. It is concluded that chronic cigarette smoke exposure alters arachidonic acid metabolism in aortas, platelets and lungs in a manner resulting in decreased PGI2 and increased TXA2, thereby creating a condition favoring platelet aggregation and a variety of cardiovascular diseases

  18. Efecto antihipertensivo del extracto de Piper aduncum ‘matico’ sobre la hipertensión inducida por L-NAME en ratones

    Directory of Open Access Journals (Sweden)

    Jorge Arroyo

    2012-10-01

    Full Text Available Introducción: El Piper aduncum es una planta conocida como matico. Se le atribuye efectos antihipertensivo, antiinflamatorio, cicatrizante. Objetivos: Determinar el efecto antihipertensivo del extracto de Piper aduncum ‘matico’, sobre la hipertensión inducida por L-NAME, en ratones. Diseño: Experimental. Lugar: Facultades de Medicina y de Farmacia y Bioquímica, Universidad Nacional Mayor de San Marcos, Lima, Perú. Material biológico: Extracto etanólico de las hojas de Piper aduncum y ratas. Intervenciones: Se utilizó seis grupos de seis ratones Muss musculus cada uno, uno sin hipertensión (control negativo y cuatro con hipertensión inducida por L-NAME: un control positivo y tres grupos para las dosis de 50, 150 y 300 mg/kg, respectivamente. El tratamiento se realizó por vía oral, una vez por día, durante 25 días. Las mediciones de la presión arterial sistólica (PAS, presión arterial diastólica (PAD y presión arterial media (PAM fueron realizadas dos veces por semana (martes y viernes y se consideró las mediciones entre los días 19 y 23 de iniciado el tratamiento. Principales medidas de resultados: Actividad antihipertensiva. Resultados: En los días 19 y 23 se observó los mejores niveles de presión arterial en el grupo control y los experimentales, correspondiendo a las mediciones 6 y 7. La eficacia antihipertensiva para enalapril fue 24,1 a 20,6%, respectivamente, seguida por matico, entre 24,9 y 13,7% (p<0,05. Conclusiones: En las condiciones experimentales, se demostró la actividad antihipertensiva del extracto etanólico de hojas de Piper aduncum ‘matico’.

  19. Oxidation of esterified arachidonate by rat liver microsomes

    International Nuclear Information System (INIS)

    Davis, H.W.; Suzuki, T.; Schenkman, J.B.

    1986-01-01

    The authors have previously demonstrated a relationship between phospholipid arachidonate in liver microsomes and malondialdehyde (MDA) formation during lipid peroxidation. In this study arachidonic acid (U- 14 C) was incorporated into rat liver microsomes and NADPH-supported peroxidation was carried out at 37 0 C for 15 minutes. The microsomes were pelleted by centrifugation and the labeled products in the supernatant were isolated by a solid phase method. Pellets were hydrolyzed with phospholipase A 2 and extracted with diethyl ether and the products from both fractions were separated by reverse phase HPLC. The results show that (1) oxidation occurs in all of the major phospholipids but that phosphatidylethanolamine is the most susceptible; (2) a linear correlation exists between MDA formation and supernatant radioactivity; (3) several different polar products are found in both the supernatant and the hydrolyzed pellet but that the ratios of product peaks in HPLC do not change during the peroxidation, indicating no secondary metabolism or propagation; and (4) cytochrome P-450 is not involved in the peroxidative reactions since no oxidation occurs in the absence of Fe 3+ and since product formation is unaffected in the presence of carbon monoxide

  20. Study of Arachidonic Acid Pathway in Human Bladder Tumor

    Directory of Open Access Journals (Sweden)

    Masahide Matsuyama

    2009-12-01

    Full Text Available Recent epidemiological studies and animal experiments have demonstrated that nonsteroidal anti-inflammatory drugs (NSAIDs reduce the incidence of colorectal carcinoma. Cyclooxygenase (COX is the principal target of NSAIDs. COX is the first oxidase in the process of prostaglandin production from arachidonic acid. COX enzyme may be involved in the initiation and/or the promotion of tumorigenesis due to NSAIDs inhibition of COX. Lipoxygenase (LOX is also an initial enzyme in the pathway for producing leukotrienes from arachidonic acid. Similar to COX, LOX enzyme may also be involved in the initiation and/or promotion of tumorigenesis. Peroxisome proliferator activator-receptor (PPAR-γ is a ligand-activated transcriptional factor belonging to the steroid receptor superfamily. PPAR-γ plays a role in both adipocyte differentiation and tumorigenesis. PPAR-γ is one target for cell growth modulation of NSAIDs. In this review, we report the expression of COX-2, LOX and PPAR-γ in human bladder tumor tissues as well as the effects of COX-2 and LOX inhibitors and PPAR-γ ligand.

  1. Study of Arachidonic Acid Pathway in Human Bladder Tumor

    Directory of Open Access Journals (Sweden)

    Masahide Matsuyama

    2009-01-01

    Full Text Available Recent epidemiological studies and animal experiments have demonstrated that nonsteroidal anti-inflammatory drugs (NSAIDs reduce the incidence of colorectal carcinoma. Cyclooxygenase (COX is the principal target of NSAIDs. COX is the first oxidase in the process of prostaglandin production from arachidonic acid. COX enzyme may be involved in the initiation and/or the promotion of tumorigenesis due to NSAIDs inhibition of COX. Lipoxygenase (LOX is also an initial enzyme in the pathway for producing leukotrienes from arachidonic acid. Similar to COX, LOX enzyme may also be involved in the initiation and/or promotion of tumorigenesis. Peroxisome proliferator activator-receptor (PPAR-γ is a ligand-activated transcriptional factor belonging to the steroid receptor superfamily. PPAR-γ plays a role in both adipocyte differentiation and tumorigenesis. PPAR-γ is one target for cell growth modulation of NSAIDs. In this review, we report the expression of COX-2, LOX and PPAR-γ in human bladder tumor tissues as well as the effects of COX-2 and LOX inhibitors and PPAR-γ ligand.

  2. Measurement of the incorporation of orally administered arachidonic acid into tissue lipids

    International Nuclear Information System (INIS)

    Kulmacz, R.J.; Sivarajan, M.; Lands, W.E.

    1986-01-01

    The applicability of a stable isotope method to monitor the mixing of dietary arachidonic acid with endogenous arachidonic acid in tissue lipids was evaluated. Rats were fed octadeuterated arachidonic acid during a 20-day period, and the entry of the dietary acid into lipid esters of various tissues was examined by gas chromatography-mass spectrometric (GC-MS) analysis of their fatty acids. The rats were maintained on a fat-free diet from weaning until 63 days old to enhance the ratio of the dietary acid to endogenous arachidonate. Three separate forms of eicosatetraenoic acid in the tissue lipids could be distinguished by GC-MS: octadeuterated arachidonic acid (recent dietary origin), unlabeled arachidonic acid (maternal origin) and unlabeled 4,7,10,13-eicosatetraenoic acid (originating from palmitoleic acid). The total eicosatetraenoic acid in the tissue lipids contained about 90% arachidonate from recent dietary origin in lung, kidney, heart and fat, 70% in muscle and liver and 27% in brain. The n-7 isomer of eicosatetraenoic acid was estimated to make up 6% or less of the total eicosatetraenoic acid in lung, kidney, brain, muscle and heart tissue lipids, but it comprised around 15% of the total eicosatetraenoic acid in liver. The unlabeled arachidonic acid of maternal origin thus comprised only about 10% of the eicosatetraenoic acid in all tissues examined except muscle and brain, where it was 24% and 70% of the eicosatetraenoic acid, respectively

  3. Effects of arachidonic acid and 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine on prolactin secretion from anterior pituitary cells

    International Nuclear Information System (INIS)

    Camoratto, A.M.

    1988-01-01

    The role of two lipids, arachidonic acid and 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine, as modulators or prolactin secretion has been examined. Stimulators of phospholipase A 2 activity, melittin and mastoparan, were found to increase prolactin release. Melittin also caused release of previously incorporated 3 H-arachidonic acid and this effect was associated with loss of radiolabel from the phospholipid fraction. Exogenous arachidonic acid also stimulated prolactin secretion. Conversely, inhibitors of phospholipase A 2 activity, dibromoacetophenone and U10029A, decreased basal and stimulated prolactin release. Prolactin release could also be lowered by ETYA, BW755C and NDGA, inhibitors of arachidonic acid metabolism. In the second series of experiments the effects of the biologically active phospholipid 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine (platelet activating factor, PAF) on prolactin release were examined. PAF is an ether-linked phospholipid known to stimulate granule release in a variety of cell types including both inflammatory and noninflammatory cells. PAF increased release of prolactin from dispersed rat anterior pituitary cells; stimulation was not due to cell lysis. PAF-induced prolactin release could be blocked by the dopaminergic agonists apomorphine and bromocriptine as well as by two PAF receptor antagonists, SRI 63-072 and L-652-731

  4. DMPD: Regulation of arachidonic acid release and cytosolic phospholipase A2activation. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 10080535 Regulation of arachidonic acid release and cytosolic phospholipase A2activ...on of arachidonic acid release and cytosolic phospholipase A2activation. PubmedID 10080535 Title Regulation ...of arachidonic acid release and cytosolic phospholipase A2activation. Authors Gij

  5. Novel metabolic pathways for linoleic and arachidonic acid metabolism.

    Science.gov (United States)

    Moghaddam, M; Motoba, K; Borhan, B; Pinot, F; Hammock, B D

    1996-08-13

    Mouse liver microsomes oxidized linoleic acid to form 9,10- or 12,13-epoxyoctadecenoate. These monoepoxides were subsequently hydrolyzed to their corresponding diols in the absence of the microsomal epoxide hydrolase inhibitor, 1,2-epoxy-3,3,3-trichloropropane. Furthermore, both 9,10- and 12,13-epoxyoctadecenoates were oxidized to diepoxyoctadecanoate at apparently identical rates by mouse liver microsomal P-450 epoxidation. Both epoxyoctadecanoates and diepoxyoctadecanoates were converted to tetrahydrofuran-diols by microsomes. Tetrahydroxides of linoleate were produced as minor metabolites. Arachidonic acid was metabolized to epoxyeicosatrienoates, dihydroxyeicosatrienoates, and monohydroxyeicosatetraenoates by the microsomes. Microsomes prepared from clofibrate (but not phenobarbital) -treated mice exhibited much higher production rates for epoxyeicosatrienoates and vic-dihydroxyeicosatrienoates. This indicated an induction of P-450 epoxygenase(s) and microsomal epoxide hydrolase in mice by clofibrate and not by phenobarbital. Incubation of synthetic epoxyeicosatrienoates with microsomes led to the production of diepoxyeicosadienoates. Among chemically generated diepoxyeicosadienoate isomers, three of them possessing adjacent diepoxides were hydrolyzed to their diol epoxides which cyclized to the corresponding tetrahydrofuran-diols by microsomes as well as soluble epoxide hydrolase at a much higher rate. Larger cyclic products from non-adjacent diepoxides were not observed. The results of our in vitro experiments suggest that linoleic and arachidonic acid can be metabolized to their tetrahydrofuran-diols by two consecutive microsomal cytochrome P-450 epoxidations followed by microsomal or soluble epoxide hydrolase catalyzed hydrolysis of the epoxides. Incubation experiments with the S-9 fractions indicate that the soluble epoxide hydrolase is more important in this conversion. This manuscript is the first report of techniques for the separation and

  6. Ultraviolet radiation stimulates the release of arachidonic acid from mammalian cells in culture

    International Nuclear Information System (INIS)

    De Leo, V.A.; Hanson, D.; Weinstein, I.B.; Harber, L.C.

    1985-01-01

    C3H 10T1/2 cells in culture were prelabelled with [ 3 H]arachidonic acid and exposed to UVB radiation. Almost immediately after irradiation cells released labelled arachidonate metabolites into media in a dose dependent manner. This release was inhibited by removing calcium ions from the system and by the addition of dexamethasone and parabromophenacyl bromide to the system. This suggests that the UVB stimulated release of arachidonic acid from membrane phospholipids is, in part, mediated by a phospholipase A 2 enzyme system. Thin layer chromatographic examination of media extracts revealed a dose dependent UVB stimulation of prostaglandin production by cultured cells. (author)

  7. Arachidonate 5-lipoxygenase (ALOX5) gene polymorphism is associated with Alzheimer's disease and body mass index

    Czech Academy of Sciences Publication Activity Database

    Šerý, Omar; Hlinecká, L.; Povová, J.; Bonczek, Ondřej; Zeman, T.; Janout, V.; Ambrož, P.; Khan, N. A.; Balcar, V. J.

    2016-01-01

    Roč. 362, č. 1 (2016), s. 27-32 ISSN 0022-510X Institutional support: RVO:67985904 Keywords : Arachidonic acid * genetics * inflammation * leukotrienes * curcumin Subject RIV: FH - Neurology Impact factor: 2.295, year: 2016

  8. Arachidonic acid metabolism in fibroblasts derived from canine myocardium

    International Nuclear Information System (INIS)

    Weber, D.R.; Prescott, S.M.

    1986-01-01

    Canine fibroblasts from normal or healing infarcted myocardium were grown in culture. The cells were morphologically indistinguishable, but the doubling time of cells from healing myocardium was 39.6 +/- 3.5 hr whereas that of normals was 24 +/- 3.7 (n=5, p 3 H]arachidonate (AA) into phospholipids. Calcium ionophore A23187 (10 μM) caused release and metabolism of [ 3 H] AA. A23187 or AA (10μM) induced production of 6-keto PGF1α, PGE2, and a hydroxy metabolite of AA. RIA of 6-keto PGF1α showed that subconfluent cells from healing myocardium produced 1202 +/- 354 pg/mg protein whereas that of normals was 551 +/- 222 (n=7, p 3 H]AA released but did not metabolize [ 3 H]AA. In coincubations, fibroblasts incorporated myocyte-derived AA. Subsequent stimulation of the fibroblasts with A23187 induced the synthesis of 6-keto PGF1α, PGE2 and a hydroxy metabolite. The fibroblast content of healing myocardium was 35-1000 times that of normal tissue (n=7). Thus even a moderate change in AA metabolism, amplified by the AA released from deteriorating myocytes, may be a significant physiologic or pathologic event

  9. Dietary arachidonic acid in perinatal nutrition: a commentary.

    Science.gov (United States)

    Lauritzen, Lotte; Fewtrell, Mary; Agostoni, Carlo

    2015-01-01

    Arachidonic acid (AA) is supplied together with docosahexaenoic acid (DHA) in infant formulas, but we have limited knowledge about the effects of supplementation with either of these long-chain polyunsaturated fatty acids (LCPUFA) on growth and developmental outcomes. AA is present in similar levels in breast milk throughout the world, whereas the level of DHA is highly diet dependent. Autopsy studies show similar diet-dependent variation in brain DHA, whereas AA is little affected by intake. Early intake of DHA has been shown to affect visual development, but the effect of LCPUFA on neurodevelopment remains to be established. Few studies have found any functional difference between infants supplemented with DHA alone compared to DHA+AA, but some studies show neurodevelopmental advantages in breast-fed infants of mothers supplemented with n-3 LCPUFA alone. It also remains to be established whether the AA/DHA balance could affect allergic and inflammatory outcomes later in life. Disentangling effects of genetic variability and dietary intake on AA and DHA-status and on functional outcomes may be an important step in the process of determining whether AA-intake is of any physiological or clinical importance. However, based on the current evidence we hypothesize that dietary AA plays a minor role on growth and development relative to the impact of dietary DHA.

  10. In vitro release of arachidonic acid and in vivo responses to respirable fractions of cotton dust

    International Nuclear Information System (INIS)

    Thomson, T.A.; Edwards, J.H.; Al-Zubaidy, T.S.; Brown, R.C.; Poole, A.; Nicholls, P.J.

    1986-01-01

    It was considered that the fall in lung function seen after exposure to cotton dust may be attributable in part to the activity of arachidonic acid metabolites, such as leucotrienes as well as to the more established release of histamine by cotton dust. However, we found that cotton and barley dusts elicited poor release of arachidonic acid from an established macrophage like cell line compared with that observed with other organic dusts. In the experimental animal, pulmonary cellular responses to both cotton and barley dust were similar to those evoked by moldy hay and pigeon dropping dusts, although after multiple doses a more severe response was seen to cotton and barley. Since both moldy hay and pigeon droppings elicit a greater arachidonic acid release than cotton or barley, a role for arachidonic acid in inducing the cellular response is less likely than other factors. There are limitations to our conclusions using this system, i.e., the arachidonic acid may be released in a nonmetabolized form, although it is noted that the two dusts with the greatest arachidonic acid release produce their clinical responses in humans largely by hypersensitivity mechanisms

  11. The Polyunsaturated Fatty Acids Arachidonic Acid and Docosahexaenoic Acid Induce Mouse Dendritic Cells Maturation but Reduce T-Cell Responses In Vitro

    Science.gov (United States)

    Carlsson, Johan A.; Wold, Agnes E.; Sandberg, Ann-Sofie; Östman, Sofia M.

    2015-01-01

    Long-chain polyunsaturated fatty acids (PUFAs) might regulate T-cell activation and lineage commitment. Here, we measured the effects of omega-3 (n-3), n-6 and n-9 fatty acids on the interaction between dendritic cells (DCs) and naïve T cells. Spleen DCs from BALB/c mice were cultured in vitro with ovalbumin (OVA) with 50 μM fatty acids; α-linolenic acid, arachidonic acid (AA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), linoleic acid or oleic acid and thereafter OVA-specific DO11.10 T cells were added to the cultures. Fatty acids were taken up by the DCs, as shown by gas chromatography analysis. After culture with arachidonic acid or DHA CD11c+ CD11b+ and CD11c+ CD11bneg DCs expressed more CD40, CD80, CD83, CD86 and PDL-1, while IAd remained unchanged. However, fewer T cells co-cultured with these DCs proliferated (CellTrace Violetlow) and expressed CD69 or CD25, while more were necrotic (7AAD+). We noted an increased proportion of T cells with a regulatory T cell (Treg) phenotype, i.e., when gating on CD4+ FoxP3+ CTLA-4+, CD4+ FoxP3+ Helios+ or CD4+ FoxP3+ PD-1+, in co-cultures with arachidonic acid- or DHA-primed DCs relative to control cultures. The proportion of putative Tregs was inversely correlated to T-cell proliferation, indicating a suppressive function of these cells. With arachidonic acid DCs produced higher levels of prostaglandin E2 while T cells produced lower amounts of IL-10 and IFNγ. In conclusion arachidonic acid and DHA induced up-regulation of activation markers on DCs. However arachidonic acid- and DHA-primed DCs reduced T-cell proliferation and increased the proportion of T cells expressing FoxP3, indicating that these fatty acids can promote induction of regulatory T cells. PMID:26619195

  12. Docosahexaenoic acid affects arachidonic acid uptake in megakaryocytes

    International Nuclear Information System (INIS)

    Schick, P.K.; Webster, P.

    1987-01-01

    Dietary omega 3 fatty acids are thought to prevent atherosclerosis, possibly by modifying platelet (PT) function and arachidonic acid (20:4) metabolism. The study was designed to determine whether omega 3 fatty acids primarily affect 20:4 metabolism in megakaryocytes (MK), bone marrow precursors of PT, rather than in circulating PT. MK and PT were isolated from guinea pigs and incubated with [ 14 C]-20:4 (0.13uM). Docosahexaenoic acid (22:6) is a major omega 3 fatty acid in marine oils. The incubation of MK with 22:6 (0.1, 1.0 uM) resulted in the decrease of incorporation of [ 14 C]-20:4 into total MK phospholipids, 16% and 41% respectively. Alpha-linolenic acid (18:3), a major omega 3 fatty acid present in American diets, had no effect on 20:4 uptake in MK. 22:6 primarily affected the uptake of [ 14 C]-20:4 into phosphatidylethanolamine (PE) and phosphatidylserine (PS) in MK. In MK, 22:6 (0.1, 1.0 uM) caused a decrease of incorporation of [ 14 C]-20:4 into PE, 21% and 55% respectively; a decrease into PS, 16% and 48% respectively; but only a decrease of 4% and 18%, respectively, into phosphatidylcholine; and a decrease of 3% and 21% into phosphatidylinositol 22:6 (3.0 uM) had no effect on the uptake of AA into PT phospholipids. The study shows that 22:6 has a selective effect on AA uptake in MK and that the acylation or transacylation of PE and PS are primarily affected. 22:6 and other marine omega 3 fatty acids appear to primarily affect megakaryocytes which may result in the production of platelets with abnormal content and compartmentalization of AA

  13. Hypersensitivity to norepinephrine in vasa deferentia from diabetic rats. Possible participation of metabolic products of arachidonic acid

    Energy Technology Data Exchange (ETDEWEB)

    Peredo, H; Agostini, M D; Gimeno, M F; Borda, E S

    1984-08-01

    Contractile responses to norepinephrine of the vas deferens isolated from normal and diabetic rats as well as tissue radio-conversion of exogenous arachidonic acid, were studied. Vasa deferentia from rats with acute streptozotocin-induced diabetes showed hypersensitivity to exogenous norepinephrine (NE). This increased contractile response was associated with the interaction of the agonist with alpha adrenoceptors. Inhibitors of cyclooxygenase increased and inhibitors of lipoxygenase(s) abolished the enhanced response to NE of diabetic vas deferens. Vasa deferentia from both normal and diabetic rats, converted (1-/sup 14/C)-arachidonic acid (AA) into PGF, PGE, PGD and thromboxane (TX) B2, but the % of AA metabolites formed was significantly higher in the diabetic than in the normal condition. Moreover, the predominant prostanoid generated by tissue preparations from diabetic animals was PGD2. Taken together the present experimental findings indicate that preparations from rats with acute streptozotocin-induced diabetes have an augmented reactivity towards NE, which appeared associated with changes in metabolites of AA generated via cyclooxygenase and lipoxygenase catalized pathways.

  14. The effect of the antipsoriatic drug metabolite etretin (Ro 10-1670) on UVB irradiation induced changes in the metabolism of arachidonic acid in human keratinocytes in culture

    International Nuclear Information System (INIS)

    Punnonen, Kari; Jansen, C.T.; Puustinen, Tapio

    1986-01-01

    [ 14 C]Arachidonic acid was avidly incorporated into human keratinocytes in culture and following exposure to UVB irradiation of 9 mJ/cm 2 (erythemally effective, EE) substantial amounts of 14 C-radiolabel were released from the cells. The release of radiolabel was accompanied by a decrease in the labelling of phosphatidylethanolamine whereas the labelling of triacylglycerols and cholesteryl esters was increased. Keratinocytes produced significant amounts of prostaglandin E 2 (PGE 2 ) and following UVB irradiation of 9 mJ/cm 2 (EE) the formation of prostaglandin E 2 was increased. Etretin (Ro 10-1670), the active metabolite of the antipsoriatic drug etretinate (Ro 10-9359), affected significantly neither the total release of radiolabel induced by UVB nor the formation of prostaglandin E 2 . However, in the presence of etretin the UVB irradiation induced transfer of [ 14 C]arachidonic acid into triacylglycerols and cholesteryl esters was not increased as much as in the corresponding experiments without etretin. On the basis of the present study it appears that etretin dose not interfere with the release of arachidonic acid in amounts which could be related to the therapeutic effects of the combination of retinoids with UVB irradiation (Re-UVB) in the treatment of psoriasis. (author)

  15. Roles of phospholipase A2 isoforms in swelling- and melittin-induced arachidonic acid release and taurine efflux in NIH3T3 fibroblasts

    DEFF Research Database (Denmark)

    Pedersen, Stine Helene Falsig; Poulsen, Kristian Arild; Lambert, Ian H.

    2006-01-01

    Osmotic swelling of NIH3T3 mouse fibroblasts activates a bromoenol lactone (BEL)-sensitive taurine efflux, pointing to the involvement of a Ca2+-independent phospholipase A2 (iPLA2) (Lambert IH. J Membr Biol 192: 19-32, 2003). We report that taurine efflux from NIH3T3 cells was not only increased...... by cell swelling but also decreased by cell shrinkage. Arachidonic acid release to the cell exterior was similarly decreased by shrinkage yet not detectably increased by swelling. NIH3T3 cells were found to express cytosolic calcium-dependent cPLA2-IVA, cPLA2-IVB, cPLA2-IVC, iPLA2-VIA, iPLA2-VIB......, and secretory sPLA2-V. Arachidonic acid release from swollen cells was partially inhibited by BEL and by the sPLA2-inhibitor manoalide. Cell swelling elicited BEL-sensitive arachidonic acid release from the nucleus, to which iPLA2-VIA localized. Exposure to the bee venom peptide melittin, to increase PLA2...

  16. A New Model to Study the Role of Arachidonic Acid in Colon Cancer Pathophysiology.

    Science.gov (United States)

    Fan, Yang-Yi; Callaway, Evelyn; M Monk, Jennifer; S Goldsby, Jennifer; Yang, Peiying; Vincent, Logan; S Chapkin, Robert

    2016-09-01

    A significant increase in cyclooxygenase 2 (COX2) gene expression has been shown to promote cylcooxygenase-dependent colon cancer development. Controversy associated with the role of COX2 inhibitors indicates that additional work is needed to elucidate the effects of arachidonic acid (AA)-derived (cyclooxygenase and lipoxygenase) eicosanoids in cancer initiation, progression, and metastasis. We have recently developed a novel Fads1 knockout mouse model that allows for the investigation of AA-dependent eicosanoid deficiency without the complication of essential fatty acid deficiency. Interestingly, the survival rate of Fads1-null mice is severely compromised after 2 months on a semi-purified AA-free diet, which precludes long-term chemoprevention studies. Therefore, in this study, dietary AA levels were titrated to determine the minimal level required for survival, while maintaining a distinct AA-deficient phenotype. Null mice supplemented with AA (0.1%, 0.4%, 0.6%, 2.0%, w/w) in the diet exhibited a dose-dependent increase (P sibling littermate control mice. These data indicate that (i) basal/minimal dietary AA supplementation (0.6%) expands the utility of the Fads1-null mouse model for long-term cancer prevention studies and (ii) that AA content in the colonic epithelium modulates colon cancer risk. Cancer Prev Res; 9(9); 750-7. ©2016 AACR. ©2016 American Association for Cancer Research.

  17. High expression of arachidonate 15-lipoxygenase and proinflammatory markers in human ischemic heart tissue

    International Nuclear Information System (INIS)

    Magnusson, Lisa U.; Lundqvist, Annika; Asp, Julia; Synnergren, Jane; Johansson, Cecilia Thalén; Palmqvist, Lars; Jeppsson, Anders; Hultén, Lillemor Mattsson

    2012-01-01

    Highlights: ► We found a 17-fold upregulation of ALOX15 in the ischemic heart. ► Incubation of human muscle cells in hypoxia showed a 22-fold upregulation of ALOX15. ► We observed increased levels of proinflammatory markers in ischemic heart tissue. ► Suggesting a link between ischemia and inflammation in ischemic heart biopsies. -- Abstract: A common feature of the ischemic heart and atherosclerotic plaques is the presence of hypoxia (insufficient levels of oxygen in the tissue). Hypoxia has pronounced effects on almost every aspect of cell physiology, and the nuclear transcription factor hypoxia inducible factor-1α (HIF-1α) regulates adaptive responses to low concentrations of oxygen in mammalian cells. In our recent work, we observed that hypoxia increases the proinflammatory enzyme arachidonate 15-lipoxygenase (ALOX15B) in human carotid plaques. ALOX15 has recently been shown to be present in the human myocardium, but the effect of ischemia on its expression has not been investigated. Here we test the hypothesis that ischemia of the heart leads to increased expression of ALOX15, and found an almost 2-fold increase in HIF-1α mRNA expression and a 17-fold upregulation of ALOX15 mRNA expression in the ischemic heart biopsies from patients undergoing coronary bypass surgery compared with non ischemic heart tissue. To investigate the effect of low oxygen concentration on ALOX15 we incubated human vascular muscle cells in hypoxia and showed that expression of ALOX15 increased 22-fold compared with cells incubated in normoxic conditions. We also observed increased mRNA levels of proinflammatory markers in ischemic heart tissue compared with non-ischemic controls. In summary, we demonstrate increased ALOX15 in human ischemic heart biopsies. Furthermore we demonstrate that hypoxia increases ALOX15 in human muscle cells. Our results yield important insights into the underlying association between hypoxia and inflammation in the human ischemic heart disease.

  18. Lowering dietary n-6 polyunsaturated fatty acids: interaction with brain arachidonic and docosahexaenoic acids.

    Science.gov (United States)

    Alashmali, Shoug M; Hopperton, Kathryn E; Bazinet, Richard P

    2016-02-01

    Arachidonic (ARA) and docosahexaenoic (DHA) acids are the most abundant polyunsaturated fatty acids (PUFA) in the brain, where they have many biological effects, including on inflammation, cell-signaling, appetite regulation, and blood flow. The Western diet contains a high ratio of n-6: n-3 PUFA. Although interest in lowering this ratio has largely focused on increasing intake of n-3 PUFA, few studies have examined lowering dietary n-6 PUFA. This review will evaluate the effect of lowering dietary n-6 PUFA on levels and metabolism of ARA and DHA in animal models and in humans, with a primary focus on the brain. In animal models, lowering dietary ARA or linoleic acid generally lowers levels of brain ARA and raises DHA. Lowering dietary n-6 PUFA can also modulate the levels of ARA and DHA metabolizing enzymes, as well as their associated bioactive mediators. Human studies examining changes in plasma fatty acid composition following n-6 PUFA lowering demonstrate no changes in levels of ARA and DHA, though there is evidence of alterations in their respective bioactive mediators. Lowering dietary n-6 PUFA, in animal models, can alter the levels and metabolism of ARA and DHA in the brain, but it remains to be determined whether these changes are clinically meaningful.

  19. Combination Therapy of PPAR Ligands and Inhibitors of Arachidonic Acid in Lung Cancer

    Directory of Open Access Journals (Sweden)

    Jordi Tauler

    2008-01-01

    Full Text Available Lung cancer is the leading cause of cancer death in the United States and five-year survival remains low. Numerous studies have shown that chronic inflammation may lead to progression of carcinogenesis. As a result of inflammatory stimulation, arachidonic acid (AA metabolism produces proliferation mediators through complex and dynamic interactions of the products of the LOX/COX enzymes. One important mediator in the activation of the AA pathways is the nuclear protein PPAR. Targeting LOX/COX enzymes and inducing activation of PPAR have resulted in significant reduction of cell growth in lung cancer cell lines. However, specific COX-inhibitors have been correlated with an increased cardiovascular risk. Clinical applications are still being explored with a novel generation of dual LOX/COX inhibitors. PPAR activation through synthetic ligands (TZDs has revealed a great mechanistic complexity since effects are produced through PPAR-dependent and -independent mechanisms. Furthermore, PPAR could also be involved in regulation of COX-2. Overexpression of PPAR has reported to play a role in control of invasion and differentiation. Exploring the function of PPAR, in this new context, may provide a better mechanistic model of its role in cancer and give an opportunity to design a more efficient therapeutic approach in combination with LOX/COX inhibitors.

  20. Influence of whole-body gamma irradiation upon arachidonic acid metabolism in rat platelets

    International Nuclear Information System (INIS)

    Lognonne, J.L.; Ducousso, R.; Rocquet, G.; Kergonou, J.F.

    1985-01-01

    The effects of whole-body gamma irradiation (8.4 Gy) were studied on arachidonic acid (AA) metabolism in rat's blood platelets, from day D + 1 to day D + 10 after irradiation. AA conversion into thromboxane B 2 (TxB 2 ) increased at D + 1 and then gradually decreased to very low values from D + 7 to D + 10. This decrease in the conversion of exogenous AA into TxB 2 was due to a lower AA incorporation into platelets and not to a decrease of cyclooxygenase and thromboxane-synthetase activities. AA incorporation into membrane phospholipids of blood platelets was much more decreased than AA incorporation into whole platelets; moreover, the lipid composition of the platelet membranes was markedly modified after irradiation, which must have resulted in structural and functional changes in these membranes; from these effects of whole-body gamma irradiation on platelets, the latter's membranes appeared as a major site of in vivo radiation damage in these cells

  1. The influence of arachidonic acid metabolites on cell division in the intestinal epithelium and in colonic tumors.

    Science.gov (United States)

    Petry, F M; Tutton, P J; Barkla, D H

    1984-09-01

    Various metabolites of arachidonic acid are now known to influence cell division. In this paper the effects on cell proliferation of arachidonic acid, some inhibitors of arachidonic acid metabolism and some analogs of arachidonic acid metabolites is described. The epithelial cell proliferation rate in the jejunum, in the descending colon and in dimethylhydrazine-induced tumors of rat colon was measured using a stathmokinetic technique. Administration of arachidonic acid resulted in retardation of cell proliferation in each of the tissues examined. A cyclooxygenase inhibitor (Flurbiprofen) prevented this effect of arachidonic acid in the jejunal crypts and in colonic tumors, but not in colonic crypts. In contrast, inhibitors of both cyclooxygenase and lipoxygenase (Benoxaprofen and BW755c) prevented the effect of arachidonic acid in the colonic crypts and reduced its effect on colonic tumours but did not alter its effect on the jejunum. An inhibitor of thromoboxane A2 synthetase (U51,605) was also able to prevent the inhibitory effect of arachidonic acid on colonic tumors. Treatment with 16,16-dimethyl PGE2 inhibited cell proliferation in jejunal crypts and in colonic tumors, as did a thromboxane A2 mimicking agent, U46619. Nafazatrom, an agent that stimulates prostacyclin synthesis and inhibits lypoxygenase, promoted cell proliferation in the jejunal crypts and colonic crypts, but inhibited cell proliferation in colonic tumours.

  2. Arachidonic acid metabolism by bovine placental tissue during the last month of pregnancy

    International Nuclear Information System (INIS)

    Hoedemaker, M.; Weston, P.G.; Wagner, W.C.

    1991-01-01

    Conversion of tritiated arachidonic acid (AA) into metabolites of the cyclo- and lipoxygenase pathways by bovine fetal placental tissue (200 mg) and fetal plus maternal placental tissue (400 mg) of Days 255, 265, 275 of gestation and at parturition (n = 5) during a 30 min incubation was measured using reverse-phase high pressure liquid chromatography. Fetal placental tissue produced 13,14-dihydro-15-keto-prostaglandin E2 (PGEM) as the major metabolite, the synthesis of which increased from Day 265 to Day 275 and parturition by 150% and 475%, respectively. In tissues collected at parturition, PGE2 synthesis was also detected. On Day 275 and at parturition fetal placental tissue synthesized the metabolite 12-hydroxyheptadecatrienoic acid (HHT), and throughout the experimental period the lipoxygenase product 15-HETE was detected with synthesis rates increasing over time of gestation. In addition, an unidentified metabolite was regularly found in the radiochromatograms which eluted at 1 h and 1 min (U101), between HHT and 15-HETE. The synthesis of this metabolite decreased as pregnancy progressed. Furthermore, various other polar and nonpolar metabolites pooled under the heading UNID were eluted, the production of which increased over time of gestation. The presence of maternal placental tissue did not influence the synthesis of PGEM, 15-HETE and U101, but the production of HHT was decreased when maternal tissue was present. Also, as pregnancy progressed, maternal placental tissue seemed to contribute to the pool of unidentified metabolites. In conclusion, fetal placental tissue seems to be the major source of the AA metabolites when compared with maternal placental tissue, and AA metabolism by bovine placental tissue is markedly increased throughout the last month of pregnancy, suggesting a role for AA metabolites in mechanisms controlling parturition

  3. Anti-inflammatory effects of chronic aspirin on brain arachidonic acid metabolites

    Science.gov (United States)

    Basselin, Mireille; Ramadan, Epolia; Chen, Mei; Rapoport, Stanley I.

    2010-01-01

    Pro-inflammatory and anti-inflammatory mediators derived from arachidonic acid (AA) modulate peripheral inflammation and its resolution. Aspirin (ASA) is a unique non-steroidal anti-inflammatory drug, which switches AA metabolism from prostaglandin E2 (PGE2) and thromboxane B2 (TXB2) to lipoxin A4 (LXA4) and 15-epi-LXA4. However it is unknown whether chronic therapeutic doses of ASA are anti-inflammatory in the brain. We hypothesized that ASA would dampen increases in brain concentrations of AA metabolites in a rat model of neuroinflammation, produced by a 6-day intracerebroventricular infusion of bacterial lipopolysaccharide (LPS). In rats infused with LPS (0.5 ng/h) and given ASA-free water to drink, concentrations in high-energy microwaved brain of PGE2, TXB2 and leukotriene B4 (LTB4) were elevated. In rats infused with artificial cerebrospinal fluid, 6 weeks of treatment with a low (10 mg/kg/day) or high (100 mg/kg/day) ASA dose in drinking water decreased brain PGE2, but increased LTB4, LXA4 and 15-epi-LXA4 concentrations. Both doses attenuated the LPS effects on PGE2, and TXB2. The increments in LXA4 and 15-epi-LXA4 caused by high-dose ASA were significantly greater in LPS-infused rats. The ability of ASA to increase anti-inflammatory LXA4 and 15-epi-LXA4 and reduce pro-inflammatory PGE2 and TXB2 suggests considering aspirin further for treating clinical neuroinflammation. PMID:20981485

  4. The Arachidonic Acid Metabolome Serves as a Conserved Regulator of Cholesterol Metabolism

    NARCIS (Netherlands)

    Demetz, Egon; Schroll, Andrea; Auer, Kristina; Heim, Christiane; Patsch, Josef R.; Eller, Philipp; Theurl, Markus; Theurl, Igor; Theurl, Milan; Seifert, Markus; Lener, Daniela; Stanzl, Ursula; Haschka, David; Asshoff, Malte; Dichtl, Stefanie; Nairz, Manfred; Huber, Eva; Stadlinger, Martin; Moschen, Alexander R.; Li, Xiaorong; Pallweber, Petra; Scharnagl, Hubert; Stojakovic, Tatjana; Maerz, Winfried; Kleber, Marcus E.; Garlaschelli, Katia; Uboldi, Patrizia; Catapano, Alberico L.; Stellaard, Frans; Rudling, Mats; Kuba, Keiji; Imai, Yumiko; Arita, Makoto; Schuetz, John D.; Pramstaller, Peter P.; Tietge, Uwe J. F.; Trauner, Michael; Norata, Giuseppe D.; Claudel, Thierry; Hicks, Andrew A.; Weiss, Guenter; Tancevski, Ivan

    2014-01-01

    Cholesterol metabolism is closely interrelated with cardiovascular disease in humans. Dietary supplementation with omega-6 polyunsaturated fatty acids including arachidonic acid (AA) was shown to favorably affect plasma LDL-C and HDL-C. However, the underlying mechanisms are poorly understood. By

  5. Arachidonic acid reduces the stress response of gilthead seabream Sparus aurata L.

    NARCIS (Netherlands)

    Anholt, R.D. van; Spanings, F.A.T.; Koven, WM; Nixon, O.; Wendelaar Bonga, S.E.

    2004-01-01

    In this study the influence of the dietary level of the fatty acid arachidonic acid (ArA, 20:4n-6) was determined on the acute stress response and osmoregulation of adult gilthead seabream Sparus aurata L. Seabream were fed a diet containing either 0.9% or 2.4% of total fatty acids as ArA for 18

  6. Intrauterine, postpartum and adult relationships between arachidonic acid (AA) and docosahexaenoic acid (DHA)

    NARCIS (Netherlands)

    Kuipers, Remko S.; Luxwolda, Martine F.; Dijck-Brouwer, D. A. Janneke; Muskiet, Frits A. J.

    Erythrocyte (RBC) fatty acid compositions from populations with stable dietary habits but large variations in RBC-arachidonic (AA) and RBC-docosahexaenoic acid (DHA) provided us with insight into relationships between DHA and AA. It also enabled us to estimate the maternal RBC-DHA (mRBC-DHA) status

  7. Group I mGlu receptors potentiate synaptosomal [3H]glutamate release independently of exogenously applied arachidonic acid

    International Nuclear Information System (INIS)

    Reid, M.E.; Toms, N.J.; Bedingfield, J.S.; Roberts, P.J.

    1999-01-01

    In the current study, we have characterized group I metabotropic glutamate (mGlu) receptor enhancement of 4-aminopyridine (4AP)-evoked [ 3 H]glutamate release from rat cerebrocortical synaptosomes. The broad spectrum mGlu receptor agonist (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid ((1S,3R)-ACPD, 10 μM) increased 4AP-evoked [ 3 H]glutamate release (143.32±2.73% control) only in the presence of exogenously applied arachidonic acid; an effect reversed by the inclusion of bovine serum albumin (BSA, fatty acid free). In contrast, the selective group I mGlu receptor agonist (S)-3,5-dihydroxyphenylglycine (DHPG) potentiated (EC 50 =1.60±0.25 μM; E max =147.61±10.96% control) 4AP-evoked [ 3 H]glutamate release, in the absence of arachidonic acid. This potentiation could be abolished by either the selective mGlu 1 receptor antagonist (R,S)-1-aminoindan-1,5-dicarboxylic acid (AIDA, 1 mM) or the selective PKC inhibitor (Ro 31-8220, 10 μM) and was BSA-insensitive. The selective mGlu 5 receptor agonist (R,S)-2-chloro-5-hydroxyphenylglycine (CHPG, 300μM) was without effect. DHPG (100 μM) also potentiated both 30 mM and 50 mM K + -evoked [ 3 H]glutamate release (121.60±12.77% and 121.50±4.45% control, respectively). DHPG (100 μM) failed to influence both 4AP-stimulated 45 Ca 2+ influx and 50 mM K + -induced changes in synaptosomal membrane potential. Possible group I mGlu receptor suppression of tonic adenosine A 1 receptor, group II/III mGlu receptors or GABA B receptor activity is unlikely since 4AP-evoked [ 3 H]glutamate release was insensitive to the selective inhibitory receptor antagonists 8-cyclopentyl-1,3-dimethylxanthine, (R,S)-α-cyclopropyl-4-phosphonophenylglycine or CGP55845A, respectively. These data suggest an 'mGlu 1 receptor-like' receptor potentiates [ 3 H]glutamate release from cerebrocortical synaptosomes in the absence of exogenously applied arachidonic acid. This PKC dependent effect is unlikely to be via modulation of synaptosomal membrane

  8. Early docosahexaenoic and arachidonic acid supplementation in extremely-low-birth-weight infants.

    Science.gov (United States)

    Robinson, Daniel T; Caplan, Michael; Carlson, Susan E; Yoder, Rachel; Murthy, Karna; Frost, Brandy

    2016-10-01

    Extremely-low-birth-weight (ELBW) infants accrue large deficits in docosahexaenoic acid (DHA) and arachidonic acid (ARA) and require improved supplementation strategies. We hypothesized that once daily DHA+ARA drops applied to buccal mucosa will increase blood levels. Thirty ELBW infants were randomized to receive DHA 20 mg/kg/d + ARA 40 or 60 mg/kg/d + ARA 120 mg/kg/d or placebo within 72 h of age for 8 wk duration. Red blood cell phospholipid levels of DHA (primary) and ARA (secondary) were measured at 2 and 8 wk of age. Twenty-eight survivors with a median birth weight of 806 g completed dosing and sampling. Red blood cell levels were similar between the three groups at 2 wk (DHA: 4.62 wt% (interquartile range (IQR) 4.1-5.5) for all, P = 0.29 between groups; ARA: 21.1 wt% (IQR 18.78-22.6) for all, P = 0.41 between groups) and 8 wk (DHA: 6.0 wt% (IQR 5.1-7.1) for all, P = 0.57 between groups; ARA: 20.1 wt% (IQR 18.3-23.1) for all, P = 0.63 between groups). DHA in all infants showed a median increase of 31% from 2 to 8 wk (P 0.6). Daily buccal DHA and ARA supplements did not affect fatty acid levels in ELBW infants.

  9. A new model to study the role of arachidonic acid in colon cancer pathophysiology

    Science.gov (United States)

    Fan, Yang-Yi; Callaway, Evelyn; Monk, Jennifer M.; Goldsby, Jennifer S.; Yang, Peiying; Vincent, Logan; Chapkin, Robert S.

    2016-01-01

    A significant increase in cyclooxygenase 2 (COX2) gene expression has been shown to promote cylcooxygenase-dependent colon cancer development. Controversy associated with the role of COX2 inhibitors indicates that additional work is needed to elucidate the effects of arachidonic acid (AA) derived (cyclooxygenase and lipoxygenase) eicosanoids in cancer initiation, progression and metastasis. We have recently developed a novel Fads1 knockout mouse model, which allows for the investigation of AA-dependent eicosanoid deficiency without the complication of essential fatty acid deficiency. Interestingly, the survival rate of Fads1 null mice is severely compromised after 2 months on a semi-purified AA-free diet, which precludes long-term chemoprevention studies. Therefore, in this study, dietary AA levels were titrated to determine the minimal level required for survival, while maintaining a distinct AA-deficient phenotype. Null mice supplemented with AA (0.1, 0.4, 0.6, 2.0%, w/w) in the diet exhibited a dose-dependent increase (P diet were injected with a colon-specific carcinogen (azoxymethane) in order to assess cancer susceptibility. Null mice exhibited significantly (P < 0.05) reduced levels/multiplicity of aberrant crypt foci (ACF) as compared to wild type sibling littermate control mice. These data indicate that (i) basal/minimal dietary AA supplementation (0.6%) expands the utility of the Fads1 Null mouse model for long-term cancer prevention studies, and (ii) that AA content in the colonic epithelium modulates colon cancer risk. PMID:27339171

  10. Docosahexaenoic acid (DHA) and arachidonic acid (ARA) balance in developmental outcomes.

    Science.gov (United States)

    Colombo, John; Jill Shaddy, D; Kerling, Elizabeth H; Gustafson, Kathleen M; Carlson, Susan E

    2017-06-01

    The DHA Intake and Measurement of Neural Development (DIAMOND) trial represents one of only a few studies of the long-term dose-response effects of LCPUFA-supplemented formula feeding during infancy. The trial contrasted the effects of four formulations: 0.00% docosahexaenoic acid (DHA)/0.00% arachidonic acid (ARA), 0.32% DHA/0.64% ARA, 0.64% DHA/0.64% ARA, and 0.96% DHA/0.64% ARA against a control condition (0.00% DHA/0.00% ARA). The results of this trial have been published elsewhere, and show improved cognitive outcomes for infants fed supplemented formulas, but a common finding among many of the outcomes show a reduction of benefit for the highest DHA dose (i.e., 0.96%DHA/0.64% ARA, that is, a DHA: ARA ratio 1.5:1.0). The current paper gathers and summarizes the evidence for the reduction of benefit at this dose, and in an attempt to account for this reduced benefit, presents for the first time data from infants' red blood cell (RBC) assays taken at 4 and 12 months of age. Those assays indicate that blood DHA levels generally rose with increased DHA supplementation, although those levels tended to plateau as the DHA-supplemented level exceeded 0.64%. Perhaps more importantly, ARA levels showed a strong inverted-U function in response to increased DHA supplementation; indeed, infants assigned to the formula with the highest dose of DHA (and highest DHA/ARA ratio) showed a reduction in blood ARA relative to more intermediate DHA doses. This finding raises the possibility that reduced ARA may be responsible for the reduction in benefit on cognitive outcomes seen at this dose. The findings implicate the DHA/ARA balance as an important variable in the contribution of LCPUFAs to cognitive and behavioral development in infancy. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Arachidonic acid-mediated inhibition of a potassium current in the giant neurons of Aplysia

    International Nuclear Information System (INIS)

    Carlson, R.O.

    1990-01-01

    Biochemical and electrophysiological approaches were used to investigate the role of arachidonic acid (AA) in the modulation of an inwardly rectifying potassium current (I R ) in the giant neurons of the marine snail, Aplysia californica. Using [ 3 H]AA as tracer, the intracellular free AA pool in Aplysia ganglia was found to be in a state of constant and rapid turnover through deacylation and reacylation of phospholipid, primarily phosphatidyl-inositol. This constant turnover was accompanied by a constant release of free AA and eicosanoids into the extracellular medium. The effects of three pharmacological agents were characterized with regard to AA metabolism in Aplysia ganglia. 4-O-tetra-decanoylphorbol 13-acetate (TPA), an activator of protein kinase C, stimulated liberation of AA from phospholipid, and 4-bromophenacylbromide (BPB), an inhibitor of phospholipate A 2 , inhibited this liberation. Indomethacin at 250 μM was found to inhibit uptake of AA, likely through inhibition of acyl-CoA synthetase. These agents were also found to modulate I R in ways which were consistent with their biological effects: TPA inhibited I R , and both BPB and indomethacin stimulated I R . Modulation of I R by these substances was found not to involve cAMP metabolism. Acute application of exogenous AA did not affect I R ; however, I R in giant neurons was found to be inhibited after dialysis with AA or other unsaturated fatty acids. Also, after perfusion with BSA overnight, a treatment which strips the giant neurons of AA in lipid storage, I R was found to have increased over 2-fold. This perfusion-induced increase was inhibited by the presence of AA or by pretreatment of the giant neurons with BPB. These results suggest AA, provided through constant turnover from phospholipid, mediates constitutive inhibition of I R

  12. Vascular permeabilization by intravenous arachidonate in the rat peritoneal cavity: antagonism by ethamsylate.

    Science.gov (United States)

    Hannaert, Patrick; Alvarez-Guerra, Miriam; Hider, Hamida; Chiavaroli, Carlo; Garay, Ricardo P

    2003-04-11

    The hemostatic agent, ethamsylate, inhibits arachidonic acid metabolism by a mechanism independent of cyclooxygenase activity and blocks carrageenan-induced rat paw edema. Here, ethamsylate was investigated for (i) in vivo actions on the free radical-dependent, permeabilizing responses to arachidonic acid and (ii) its antioxidant potential in vitro. Vascular permeability was equated to the extravasation rate of Evans blue from plasma into the rat peritoneal cavity. Antioxidant potential was investigated by classical in vitro tests for superoxide radicals, hydroxyl radicals (OH(.)), and nitric oxide. Intravenous ethamsylate induced a very important and significant reduction of permeability responses to arachidonate, both when given preventively and cumulatively. Thus, (i) ethamsylate significantly reversed arachidonate-induced permeabilization, even at the lowest dose tested (44+/-5% at 10 mg/kg) and (ii) a maximal reversal (about 70%) was reached between 50 and 200 mg/kg ethamsylate. In contrast, ethamsylate (100 mg/kg) was unable to antagonize the vascular permeabilization induced by serotonin (5-HT). In antioxidant assays, ethamsylate showed scavenging properties against hydroxyl radicals generated by the Fenton reaction (H(2)O(2)/Fe(2+)) even at 0.1 microM (-20+/-3%). OH(.) scavenging by ethamsylate reached 42+/-8% at 10 microM and 57+/-7% at 1 mM and was comparable to that of reference compounds (vitamin E, troxerutin, and mannitol). Conversely, ethamsylate was a poor scavenger of superoxide and nitric oxide radicals. In conclusion, intravenous ethamsylate potently antagonized the peritoneal vascular permeabilization induced by arachidonate, an action likely due to its antioxidant properties, particularly against hydroxyl radical. Such a mechanism can explain previous observations that ethamsylate inhibits carrageenan-induced rat paw edema. Whether it also participates in the hemostatic action of ethamsylate deserves further investigation.

  13. Regulation of rat intrapulmonary arterial tone by arachidonic acid and prostaglandin E2 during hypoxia.

    Directory of Open Access Journals (Sweden)

    Gaoliang Yan

    Full Text Available Arachidonic acid (AA and its metabolites, prostaglandins (PG are known to be involved in regulation of vascular homeostasis including vascular tone and vessel wall tension, but their potential role in Hypoxic pulmonary vasoconstriction (HPV remains unclear. In this study, we examined the effects of AA and PGE2 on the hypoxic response in isolated rat intrapulmonary arteries (IPAs.We carried out the investigation on IPAs by vessel tension measurement. Isotetrandrine (20 µM significantly inhibited phase I, phase IIb and phase IIc of hypoxic vasoconstriction. Both indomethacin (100 µM and NS398 attenuated KPSS-induced vessel contraction and phase I, phase IIb and phase IIc of HPV, implying that COX-2 plays a primary role in the hypoxic response of rat IPAs. PGE2 alone caused a significant vasoconstriction in isolated rat IPAs. This constriction is mediated by EP4. Blockage of EP4 by L-161982 (1 µM significantly inhibited phase I, phase IIb and phase IIc of hypoxic vasoconstriction. However, AH6809 (3 µM, an antagonist of EP1, EP2, EP3 and DP1 receptors, exerted no effect on KPSS or hypoxia induced vessel contraction. Increase of cellular cAMP by forskolin could significantly reduce KPSS-induced vessel contraction and abolish phase I, phase II b and phase II c of HPV.Our results demonstrated a vasoconstrictive effect of PGE2 on rat IPAs and this effect is via activation of EP4. Furthermore, our results suggest that intracellular cAMP plays dual roles in regulation of vascular tone, depending on the spatial distribution of cAMP and its coupling with EP receptor and Ca(2+ channels.

  14. Enhancement of arachidonic acid signaling pathway by nicotinic acid receptor HM74A

    International Nuclear Information System (INIS)

    Tang, Yuting; Zhou, Lubing; Gunnet, Joseph W.; Wines, Pamela G.; Cryan, Ellen V.; Demarest, Keith T.

    2006-01-01

    HM74A is a G protein-coupled receptor for nicotinic acid (niacin), which has been used clinically to treat dyslipidemia for decades. The molecular mechanisms whereby niacin exerts its pleiotropic effects on lipid metabolism remain largely unknown. In addition, the most common side effect in niacin therapy is skin flushing that is caused by prostaglandin release, suggesting that the phospholipase A 2 (PLA 2 )/arachidonic acid (AA) pathway is involved. Various eicosanoids have been shown to activate peroxisome-proliferator activated receptors (PPAR) that play a diverse array of roles in lipid metabolism. To further elucidate the potential roles of HM74A in mediating the therapeutic effects and/or side effects of niacin, we sought to explore the signaling events upon HM74A activation. Here we demonstrated that HM74A synergistically enhanced UTP- and bradykinin-mediated AA release in a pertussis toxin-sensitive manner in A431 cells. Activation of HM74A also led to Ca 2+ -mobilization and enhanced bradykinin-promoted Ca 2+ -mobilization through Gi protein. While HM74A increased ERK1/2 activation by the bradykinin receptor, it had no effects on UTP-promoted ERK1/2 activation.Furthermore, UTP- and bradykinin-mediated AA release was significantly decreased in the presence of both MAPK kinase inhibitor PD 098059 and PKC inhibitor GF 109203X. However, the synergistic effects of HM74A were not dramatically affected by co-treatment with both inhibitors, indicating the cross-talk occurred at the receptor level. Finally, stimulation of A431 cells transiently transfected with PPRE-luciferase with AA significantly induced luciferase activity, mimicking the effects of PPARγ agonist rosiglitazone, suggesting that alteration of AA signaling pathway can regulate gene expression via endogenous PPARs

  15. Enhancement of arachidonic acid signaling pathway by nicotinic acid receptor HM74A

    Energy Technology Data Exchange (ETDEWEB)

    Tang, Yuting [Endocrine Therapeutics and Metabolic Disorders, Johnson and Johnson Pharmaceutical Research and Development, L.L.C., 1000 Rt. 202, Raritan, NJ 08869 (United States); Zhou, Lubing [Endocrine Therapeutics and Metabolic Disorders, Johnson and Johnson Pharmaceutical Research and Development, L.L.C., 1000 Rt. 202, Raritan, NJ 08869 (United States); Gunnet, Joseph W [Endocrine Therapeutics and Metabolic Disorders, Johnson and Johnson Pharmaceutical Research and Development, L.L.C., 1000 Rt. 202, Raritan, NJ 08869 (United States); Wines, Pamela G [Endocrine Therapeutics and Metabolic Disorders, Johnson and Johnson Pharmaceutical Research and Development, L.L.C., 1000 Rt. 202, Raritan, NJ 08869 (United States); Cryan, Ellen V [Endocrine Therapeutics and Metabolic Disorders, Johnson and Johnson Pharmaceutical Research and Development, L.L.C., 1000 Rt. 202, Raritan, NJ 08869 (United States); Demarest, Keith T [Endocrine Therapeutics and Metabolic Disorders, Johnson and Johnson Pharmaceutical Research and Development, L.L.C., 1000 Rt. 202, Raritan, NJ 08869 (United States)

    2006-06-23

    HM74A is a G protein-coupled receptor for nicotinic acid (niacin), which has been used clinically to treat dyslipidemia for decades. The molecular mechanisms whereby niacin exerts its pleiotropic effects on lipid metabolism remain largely unknown. In addition, the most common side effect in niacin therapy is skin flushing that is caused by prostaglandin release, suggesting that the phospholipase A{sub 2} (PLA{sub 2})/arachidonic acid (AA) pathway is involved. Various eicosanoids have been shown to activate peroxisome-proliferator activated receptors (PPAR) that play a diverse array of roles in lipid metabolism. To further elucidate the potential roles of HM74A in mediating the therapeutic effects and/or side effects of niacin, we sought to explore the signaling events upon HM74A activation. Here we demonstrated that HM74A synergistically enhanced UTP- and bradykinin-mediated AA release in a pertussis toxin-sensitive manner in A431 cells. Activation of HM74A also led to Ca{sup 2+}-mobilization and enhanced bradykinin-promoted Ca{sup 2+}-mobilization through Gi protein. While HM74A increased ERK1/2 activation by the bradykinin receptor, it had no effects on UTP-promoted ERK1/2 activation.Furthermore, UTP- and bradykinin-mediated AA release was significantly decreased in the presence of both MAPK kinase inhibitor PD 098059 and PKC inhibitor GF 109203X. However, the synergistic effects of HM74A were not dramatically affected by co-treatment with both inhibitors, indicating the cross-talk occurred at the receptor level. Finally, stimulation of A431 cells transiently transfected with PPRE-luciferase with AA significantly induced luciferase activity, mimicking the effects of PPAR{gamma} agonist rosiglitazone, suggesting that alteration of AA signaling pathway can regulate gene expression via endogenous PPARs.

  16. Lamotrigine blocks NMDA receptor-initiated arachidonic acid signalling in rat brain: Implications for its efficacy in bipolar disorder

    Science.gov (United States)

    Ramadan, Epolia; Basselin, Mireille; Rao, Jagadeesh S.; Chang, Lisa; Chen, Mei; Ma, Kaizong; Rapoport, Stanley I.

    2011-01-01

    An upregulated brain arachidonic acid (AA) cascade and a hyperglutamatergic state characterize bipolar disorder (BD). Lamotrigine (LTG), a mood stabilizer approved for treating BD, is reported to interfere with glutamatergic neurotransmission involving N-methyl-D-aspartate receptors (NMDARs). NMDARs allow extracellular calcium into the cell, thereby stimulating calcium-dependent cytosolic phospholipase A2 (cPLA2) to release arachidonic acid (AA) from membrane phospholipid. We hypothesized that LTG, like other approved mood stabilizers, would reduce NMDAR-mediated AA signaling in rat brain. An acute subconvulsant dose of NMDA (25 mg/kg) or saline was administered intraperitoneally to unanesthetized rats that had been treated p.o. daily for 42 days with vehicle or a therapeutically relevant dose of LTG (10 mg/kg/.d). Regional brain AA incorporation coefficients k* and rates Jin, AA signals, were measured using quantitative autoradiography after intravenous [1-14C]AA infusion, as were other AA cascade markers. In chronic vehicle-treated rats, acute NMDA compared to saline increased k* and Jin in widespread regions of the brain, as well as prostaglandin (PG)E2 and thromboxane B2 concentrations. Chronic LTG treatment compared to vehicle reduced brain cyclooxygenase (COX) activity, PGE2 concentration, and DNA binding activity of the COX-2 transcription factor, NF-κB. Pretreatment with chronic LTG blocked the acute NMDA effects on AA cascade markers. In summary, chronic LTG like other mood stabilizers blocks NMDA-mediated signaling involving the AA metabolic cascade. Since markers of the AA cascade and of NMDAR signaling are up-regulated in the postmortem BD brain, mood stabilizers generally may be effective in BD by dampening NMDAR signalling and the AA cascade. PMID:21733229

  17. Dietary effects of arachidonate-rich fungal oil and fish oil on murine hepatic and hippocampal gene expression

    Directory of Open Access Journals (Sweden)

    Mutch David M

    2002-10-01

    Full Text Available Abstract Background The functions, actions, and regulation of tissue metabolism affected by the consumption of long chain polyunsaturated fatty acids (LC-PUFA from fish oil and other sources remain poorly understood; particularly how LC-PUFAs affect transcription of genes involved in regulating metabolism. In the present work, mice were fed diets containing fish oil rich in eicosapentaenoic acid and docosahexaenoic acid, fungal oil rich in arachidonic acid, or the combination of both. Liver and hippocampus tissue were then analyzed through a combined gene expression- and lipid- profiling strategy in order to annotate the molecular functions and targets of dietary LC-PUFA. Results Using microarray technology, 329 and 356 dietary regulated transcripts were identified in the liver and hippocampus, respectively. All genes selected as differentially expressed were grouped by expression patterns through a combined k-means/hierarchical clustering approach, and annotated using gene ontology classifications. In the liver, groups of genes were linked to the transcription factors PPARα, HNFα, and SREBP-1; transcription factors known to control lipid metabolism. The pattern of differentially regulated genes, further supported with quantitative lipid profiling, suggested that the experimental diets increased hepatic β-oxidation and gluconeogenesis while decreasing fatty acid synthesis. Lastly, novel hippocampal gene changes were identified. Conclusions Examining the broad transcriptional effects of LC-PUFAs confirmed previously identified PUFA-mediated gene expression changes and identified novel gene targets. Gene expression profiling displayed a complex and diverse gene pattern underlying the biological response to dietary LC-PUFAs. The results of the studied dietary changes highlighted broad-spectrum effects on the major eukaryotic lipid metabolism transcription factors. Further focused studies, stemming from such transcriptomic data, will need to

  18. Participation of Arachidonic Acid Metabolism in the Aortic Aneurysm Formation in Patients with Marfan Syndrome

    Directory of Open Access Journals (Sweden)

    María E. Soto

    2018-02-01

    Full Text Available Marfan syndrome (MFS is a pleiotropic genetic disease involving the cardiovascular system where a fibrillin-1 mutation is present. This mutation is associated with accelerated activation of transforming growth factor β (TGFβ1 which contributes to the formation of aneurysms in the root of the aorta. There is an imbalance in the synthesis of thromboxane A2 (TXA2 and prostacyclin, that is a consequence of a differential protein expression of the isoforms of cyclooxygenases (COXs, suggesting an alteration of arachidonic acid (AA metabolism. The aim of this study was to analyze the participation of AA metabolism associated with inflammatory factors in the dilation and dissection of the aortic aneurysm in patients with MFS. A decrease in AA (p = 0.02, an increase in oleic acid (OA, TGFβ1, tumor necrosis factor alpha (TNFα, prostaglandin E2 (PGE2 (p < 0.05, and COXs activity (p = 0.002 was found. The expressions of phospholipase A2 (PLA2, cytochrome P450 (CYP450 4A, 5-lipoxygenase (5-LOX, COX2 and TXA2R (p < 0.05 showed a significant increase in the aortic aneurysm of patients with MFS compared to control subjects. COX1, 6-keto-prostaglandin 1 alpha (6-keto-PG1α and 8-isoprostane did not show significant changes. Histological examination of the aortas showed an increase of cystic necrosis, elastic fibers and collagen in MFS. The results suggest that there are inflammatory factors coupled to genetic factors that predispose to aortic endothelial dysfunction in the aortic tissue of patients with MFS. There is a decrease in the percentage of AA, associated with an increase of PLA2, COX2/TXA2R, CYP450 4A, and 5-LOX which leads to a greater synthesis of PGE2 than of 6-keto-PGF1α, thus contributing to the formation of the aortic aneurysm. The evident loss of the homeostasis in these mechanisms confirms that there is a participation of the AA pathway in the aneurysm progression in MFS.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  20. Regulation of the arachidonic acid mobilization in macrophages by combustion-derived particles

    Directory of Open Access Journals (Sweden)

    Weiss Carsten

    2011-08-01

    Full Text Available Abstract Background Acute exposure to elevated levels of environmental particulate matter (PM is associated with increasing morbidity and mortality rates. These adverse health effects, e.g. culminating in respiratory and cardiovascular diseases, have been demonstrated by a multitude of epidemiological studies. However, the underlying mechanisms relevant for toxicity are not completely understood. Especially the role of particle-induced reactive oxygen species (ROS, oxidative stress and inflammatory responses is of particular interest. In this in vitro study we examined the influence of particle-generated ROS on signalling pathways leading to activation of the arachidonic acid (AA cascade. Incinerator fly ash particles (MAF02 were used as a model for real-life combustion-derived particulate matter. As macrophages, besides epithelial cells, are the major targets of particle actions in the lung murine RAW264.7 macrophages and primary human macrophages were investigated. Results The interaction of fly ash particles with macrophages induced both the generation of ROS and as part of the cellular inflammatory responses a dose- and time-dependent increase of free AA, prostaglandin E2/thromboxane B2 (PGE2/TXB2, and 8-isoprostane, a non-enzymatically formed oxidation product of AA. Additionally, increased phosphorylation of the mitogen-activated protein kinases (MAPK JNK1/2, p38 and ERK1/2 was observed, the latter of which was shown to be involved in MAF02-generated AA mobilization and phosphorylation of the cytosolic phospolipase A2. Using specific inhibitors for the different phospolipase A2 isoforms the MAF02-induced AA liberation was shown to be dependent on the cytosolic phospholipase A2, but not on the secretory and calcium-independent phospholipase A2. The initiation of the AA pathway due to MAF02 particle exposure was demonstrated to depend on the formation of ROS since the presence of the antioxidant N-acetyl-cysteine (NAC prevented the MAF02

  1. A novel dioxygenation product of arachidonic acid possesses potent chemotactic activity for human polymorphonuclear leukocytes.

    Science.gov (United States)

    Shak, S; Perez, H D; Goldstein, I M

    1983-12-25

    We have found that a novel dioxygenation product of arachidonic acid, 8(S),15(S)-dihydroxy-5,11-cis-9,13-trans-eicosatetraenoic acid (8,15-diHETE), possesses chemotactic activity for human polymorphonuclear leukocytes comparable to that of leukotriene B4. Authentic 8,15-diHETE, identified by gas chromatography-mass spectrometry, was prepared by treating arachidonic acid with soybean lipoxygenase and was purified by reverse-phase high performance liquid chromatography. Using a "leading front" assay, 8,15-diHETE exhibited significant chemotactic activity at a concentration of 5.0 ng/ml. Maximum chemotactic activity was observed at a concentration of 30 ng/ml. The 8,15-diHETE generated by mixed human leukocytes after stimulation with arachidonic acid and the calcium ionophore, A23187, exhibited quantitatively similar chemotactic activity. Two synthetic all-trans conjugated isomers of 8,15-diHETE, however, were not chemotactic at concentrations up to 500 ng/ml. In contrast to its potent chemotactic activity, 8,15-diHETE (at concentrations up to 10 micrograms/ml) was relatively inactive with respect to its ability to provoke either degranulation or generation of superoxide anion radicals by cytochalasin B-treated leukocytes. Both leukotriene B4 and 8,15-diHETE may be important mediators of inflammation.

  2. Ultraviolet B irradiation induces changes in the distribution and release of arachidonic acid, dihomo-gamma-linolenic acid, and eicosapentaenoic acid in human keratinocytes in culture

    International Nuclear Information System (INIS)

    Punnonen, K.; Puustinen, T.; Jansen, C.T.

    1987-01-01

    There is increasing evidence that derivatives of 20-carbon polyunsaturated fatty acids, the eicosanoids, play an important role in the inflammatory responses of the human skin. To better understand the metabolic fate of fatty acids in the skin, the effect of ultraviolet B (UVB) irradiation (280-320 nm) on the distribution and release of 14 C-labeled arachidonic acid, dihomo-gamma-linolenic acid, and eicosapentaenoic acid in human keratinocytes in culture was investigated. Ultraviolet B irradiation induced the release of all three 14 C-labeled fatty acids from the phospholipids, especially from phosphatidylethanolamine, and this was accompanied by increased labeling of the nonphosphorus lipids. This finding suggests that UVB induces a significant liberation of eicosanoid precursor fatty acids from cellular phospholipids, but the liberated fatty acids are largely reincorporated into the nonphosphorus lipids. In conclusion, the present study suggests that not only arachidonic acid but also dihomo-gamma-linolenic acid, and eicosapentaenoic acid might be involved in the UVB irradiation-induced inflammatory reactions of human skin

  3. Application of a ω-3 Desaturase with an Arachidonic Acid Preference to Eicosapentaenoic Acid Production in Mortierella alpina

    Directory of Open Access Journals (Sweden)

    Chengfeng Ge

    2018-01-01

    Full Text Available In the industrial oleaginous fungus Mortierella alpina, the arachidonic acid (AA; C20:4; ω-6 fraction can reach 50% of the total fatty acids (TFAs in vivo. However, the eicosapentaenoic acid (EPA; C20:5; ω-3 fraction is less than 3% when this fungus is cultivated at a low temperature (12°C. Omega-3 fatty acid desaturase is a key enzyme in ω-3 long-chain polyunsaturated fatty acids biosynthesis pathways. To enhance EPA production, we transformed the ω-3 fatty acid desaturase (PaD17, which exhibits strong Δ-17 desaturase activity, into M. alpina, thus increasing the AA to EPA conversion rate to 49.8%. This PaD17-harboring M. alpina reconstruction strain produced 617 mg L−1 of EPA at room temperature in broth medium, this yield was increased to 1.73 g L−1 after culture medium optimization (i.e., about threefold higher than that under original culture conditions, with concomitant respective increases in dry cell weight and TFA content to 16.55 and 6.46 g L−1. These findings suggest a new platform for the future industrial production of EPA.

  4. Group I mGlu receptors potentiate synaptosomal [{sup 3}H]glutamate release independently of exogenously applied arachidonic acid

    Energy Technology Data Exchange (ETDEWEB)

    Reid, M.E.; Toms, N.J.; Bedingfield, J.S.; Roberts, P.J. [Department of Pharmacology, School of Medical Sciences, University of Bristol, University Walk, Bristol, BS8 1TD (United Kingdom)

    1999-04-01

    In the current study, we have characterized group I metabotropic glutamate (mGlu) receptor enhancement of 4-aminopyridine (4AP)-evoked [{sup 3}H]glutamate release from rat cerebrocortical synaptosomes. The broad spectrum mGlu receptor agonist (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid ((1S,3R)-ACPD, 10 {mu}M) increased 4AP-evoked [{sup 3}H]glutamate release (143.32{+-}2.73% control) only in the presence of exogenously applied arachidonic acid; an effect reversed by the inclusion of bovine serum albumin (BSA, fatty acid free). In contrast, the selective group I mGlu receptor agonist (S)-3,5-dihydroxyphenylglycine (DHPG) potentiated (EC{sub 50}=1.60{+-}0.25 {mu}M; E{sub max}=147.61{+-}10.96% control) 4AP-evoked [{sup 3}H]glutamate release, in the absence of arachidonic acid. This potentiation could be abolished by either the selective mGlu{sub 1} receptor antagonist (R,S)-1-aminoindan-1,5-dicarboxylic acid (AIDA, 1 mM) or the selective PKC inhibitor (Ro 31-8220, 10 {mu}M) and was BSA-insensitive. The selective mGlu{sub 5} receptor agonist (R,S)-2-chloro-5-hydroxyphenylglycine (CHPG, 300{mu}M) was without effect. DHPG (100 {mu}M) also potentiated both 30 mM and 50 mM K{sup +}-evoked [{sup 3}H]glutamate release (121.60{+-}12.77% and 121.50{+-}4.45% control, respectively). DHPG (100 {mu}M) failed to influence both 4AP-stimulated {sup 45}Ca{sup 2+} influx and 50 mM K{sup +}-induced changes in synaptosomal membrane potential. Possible group I mGlu receptor suppression of tonic adenosine A{sub 1} receptor, group II/III mGlu receptors or GABA{sub B} receptor activity is unlikely since 4AP-evoked [{sup 3}H]glutamate release was insensitive to the selective inhibitory receptor antagonists 8-cyclopentyl-1,3-dimethylxanthine, (R,S)-{alpha}-cyclopropyl-4-phosphonophenylglycine or CGP55845A, respectively. These data suggest an 'mGlu{sub 1} receptor-like' receptor potentiates [{sup 3}H]glutamate release from cerebrocortical synaptosomes in the absence of

  5. Diffusion of intracerebrally injected [1-14C]arachidonic acid and [2-3H]glycerol in the mouse brain. Effects of ischemia and electroconvulsive shock

    International Nuclear Information System (INIS)

    Pediconi, M.F.; Rodriguez de Turco, E.B.; Bazan, N.G.

    1982-01-01

    [2- 3 H]Glycerol and [1- 14 C]arachidonic acid were injected into the region of the frontal horn of the left ventricle of mice and were distributed rapidly throughout the brain. After 10 sec, most of the radioactive fatty acid was found in the hemisphere near the injection site; after 10 min, it was recovered in similar proportions in the cerebellum and brain stem. [2- 3 H]Glycerol showed a heterogeneous distribution, with most of the label remaining in the left hemisphere even after 10 min. On a fresh weight basis, cerebrum, cerebellum, and brain stem were found to contain similar amounts of labeled glycerol. However, the amount of [1- 14 C]arachidonate in cerebrum was only 50% of that recovered from cerebellum or brain stem. Brain ischemia or a single electroconvulsive shock reduced the spread of the label, producing an accumulation of radioactivity in the injected hemisphere, except for an increase in [2- 3 H]glycerol in the brain stem during ischemia. Despite the significant decrease in available precursor in the cerebellum and brain stem after electroshock, the amount of label incorporated into lipids was not altered in these areas and only slightly diminished in the cerebrum

  6. Arachidonic Acid and Eicosapentaenoic Acid Metabolism in Juvenile Atlantic Salmon as Affected by Water Temperature.

    Science.gov (United States)

    Norambuena, Fernando; Morais, Sofia; Emery, James A; Turchini, Giovanni M

    2015-01-01

    Salmons raised in aquaculture farms around the world are increasingly subjected to sub-optimal environmental conditions, such as high water temperatures during summer seasons. Aerobic scope increases and lipid metabolism changes are known plasticity responses of fish for a better acclimation to high water temperature. The present study aimed at investigating the effect of high water temperature on the regulation of fatty acid metabolism in juvenile Atlantic salmon fed different dietary ARA/EPA ratios (arachidonic acid, 20:4n-6/ eicosapentaenoic acid, 20:5n-3), with particular focus on apparent in vivo enzyme activities and gene expression of lipid metabolism pathways. Three experimental diets were formulated to be identical, except for the ratio EPA/ARA, and fed to triplicate groups of Atlantic salmon (Salmo salar) kept either at 10°C or 20°C. Results showed that fatty acid metabolic utilisation, and likely also their dietary requirements for optimal performance, can be affected by changes in their relative levels and by environmental temperature in Atlantic salmon. Thus, the increase in temperature, independently from dietary treatment, had a significant effect on the β-oxidation of a fatty acid including EPA, as observed by the apparent in vivo enzyme activity and mRNA expression of pparα -transcription factor in lipid metabolism, including β-oxidation genes- and cpt1 -key enzyme responsible for the movement of LC-PUFA from the cytosol into the mitochondria for β-oxidation-, were both increased at the higher water temperature. An interesting interaction was observed in the transcription and in vivo enzyme activity of Δ5fad-time-limiting enzyme in the biosynthesis pathway of EPA and ARA. Such, at lower temperature, the highest mRNA expression and enzyme activity was recorded in fish with limited supply of dietary EPA, whereas at higher temperature these were recorded in fish with limited ARA supply. In consideration that fish at higher water temperature

  7. Arachidonic Acid and Eicosapentaenoic Acid Metabolism in Juvenile Atlantic Salmon as Affected by Water Temperature.

    Directory of Open Access Journals (Sweden)

    Fernando Norambuena

    Full Text Available Salmons raised in aquaculture farms around the world are increasingly subjected to sub-optimal environmental conditions, such as high water temperatures during summer seasons. Aerobic scope increases and lipid metabolism changes are known plasticity responses of fish for a better acclimation to high water temperature. The present study aimed at investigating the effect of high water temperature on the regulation of fatty acid metabolism in juvenile Atlantic salmon fed different dietary ARA/EPA ratios (arachidonic acid, 20:4n-6/ eicosapentaenoic acid, 20:5n-3, with particular focus on apparent in vivo enzyme activities and gene expression of lipid metabolism pathways. Three experimental diets were formulated to be identical, except for the ratio EPA/ARA, and fed to triplicate groups of Atlantic salmon (Salmo salar kept either at 10°C or 20°C. Results showed that fatty acid metabolic utilisation, and likely also their dietary requirements for optimal performance, can be affected by changes in their relative levels and by environmental temperature in Atlantic salmon. Thus, the increase in temperature, independently from dietary treatment, had a significant effect on the β-oxidation of a fatty acid including EPA, as observed by the apparent in vivo enzyme activity and mRNA expression of pparα -transcription factor in lipid metabolism, including β-oxidation genes- and cpt1 -key enzyme responsible for the movement of LC-PUFA from the cytosol into the mitochondria for β-oxidation-, were both increased at the higher water temperature. An interesting interaction was observed in the transcription and in vivo enzyme activity of Δ5fad-time-limiting enzyme in the biosynthesis pathway of EPA and ARA. Such, at lower temperature, the highest mRNA expression and enzyme activity was recorded in fish with limited supply of dietary EPA, whereas at higher temperature these were recorded in fish with limited ARA supply. In consideration that fish at higher

  8. Arachidonic and oleic acid exert distinct effects on the DNA methylome

    DEFF Research Database (Denmark)

    Silva-Martínez, Guillermo A.; Rodríguez-Ríos, Dalia; Alvarado-Caudillo, Yolanda

    2016-01-01

    ABSTRACT: Abnormal fatty acid metabolism and availability are landmarks of metabolic diseases, which in turn are associated with aberrant DNA methylation profiles. To understand the role of fatty acids in disease epigenetics, we sought DNA methylation profiles specifically induced by arachidonic....... The divergent response to AA and OA was prominent within the gene body of target genes, where it correlated positively with transcription. AA-induced DNA methylation profiles were similar to the corresponding profiles described for palmitic acid, atherosclerosis, diabetes, obesity, and autism, but relatively...

  9. Production of arachidonic and linoleic acid metabolites by guinea pig tracheal epithelial cells

    International Nuclear Information System (INIS)

    Oosthuizen, M.J.; Engels, F.; Van Esch, B.; Henricks, P.A.; Nijkamp, F.P.

    1990-01-01

    Pulmonary epithelial cells may be responsible for regulating airway smooth muscle function, in part by release of fatty acid-derived mediators. Incubation of isolated guinea pig tracheal epithelial cells with radiolabeled arachidonic acid (AA) leads to the production of 5- and 15-hydroxyeicosatetraenoic acid (5- and 15-HETE) and smaller amounts of leukotriene (LT) B4 and C4 and 12-hydroxyheptadecatrienoic acid (HHT). Epithelial cells also are able to release linoleic acid (LA) metabolites. Incubation with radiolabeled linoleic acid leads to the formation of 9- and 13-hydroxyoctadecadienoic acid (9- and 13-HODE). The biological significance of these mediators produced by epithelial cells is discussed

  10. Effect of amiloride on arachidonic acid and histamine release from rat mast cells

    DEFF Research Database (Denmark)

    Linnebjerg, H.; Hansen, Harald S.; Jensen, B.

    1989-01-01

    The effect of a putative Na/H exchange inhibition on histamine and [C]arachidonic acid ([C]AA) release has been examined in rat peritoneal mast cells, using either addition of amiloride or removal of extracellular Na. The cells were stimulated by non-immunological agents, i.e. calcium ionophore A......23187, nerve growth factor (NGF), thapsigargin and compound 48/80. On the basis of the results obtained, a possible role for Na/H exchange in rat mast cell secretion is discussed....

  11. Maternal melatonin or N-acetylcysteine therapy regulates hydrogen sulfide-generating pathway and renal transcriptome to prevent prenatal NG-Nitro-L-arginine-methyl ester (L-NAME)-induced fetal programming of hypertension in adult male offspring.

    Science.gov (United States)

    Tain, You-Lin; Lee, Chien-Te; Chan, Julie Y H; Hsu, Chien-Ning

    2016-11-01

    Pregnancy is a critical time for fetal programming of hypertension. Nitric oxide deficiency during pregnancy causes hypertension in adult offspring. We examined whether maternal melatonin or N-acetylcysteine therapy can prevent N G -nitro-L-arginine-methyl ester-induced fetal programming of hypertension in adult offspring. Next, we aimed to identify potential gatekeeper pathways that contribute to N G -nitro-L-arginine-methyl ester -induced programmed hypertension using the next generation RNA sequencing technology. Pregnant Sprague-Dawley rats were assigned to 4 groups: control, N G -nitro-L-arginine-methyl ester, N G -nitro-L-arginine-methyl ester +melatonin, and N G -nitro-L-arginine-methyl ester+N-acetylcysteine. Pregnant rats received N G -nitro-L-arginine-methyl ester administration at 60 mg/kg/d subcutaneously during pregnancy alone, with additional 0.01% melatonin in drinking water, or with additional 1% N-acetylcysteine in drinking water during the entire pregnancy and lactation. Male offspring (n=8/group) were killed at 12 weeks of age. N G -nitro-L-arginine-methyl ester exposure during pregnancy induced programmed hypertension in adult male offspring, which was prevented by maternal melatonin or N-acetylcysteine therapy. Protective effects of melatonin and N-acetylcysteine against N G -nitro-L-arginine-methyl ester-induced programmed hypertension were associated with an increase in hydrogen sulfide-generating enzymes and hydrogen sulfide synthesis in the kidneys. Nitric oxide inhibition by N G -nitro-L-arginine-methyl ester in pregnancy caused >2000 renal transcripts to be modified during nephrogenesis stage in 1-day-old offspring kidney. Among them, genes belong to the renin-angiotensin system, and arachidonic acid metabolism pathways were potentially involved in the N G -nitro-L-arginine-methyl ester-induced programmed hypertension. However, melatonin and N-acetylcysteine reprogrammed the renin-angiotensin system and arachidonic acid pathway

  12. Relative turnover of [3H]arachidonic acid and [14C]eicosapentaenoic acid in stimulated human platelets

    International Nuclear Information System (INIS)

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

    1986-01-01

    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 [ 3 H]AA and [ 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 [ 3 H]AA/[ 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 [ 3 H]/[ 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

  13. The role of arachidonic acid metabolites in signal transduction in an identified neural network mediating presynaptic inhibition in Aplysia

    International Nuclear Information System (INIS)

    Shapiro, E.; Piomelli, D.; Feinmark, S.; Vogel, S.; Chin, G.; Schwartz, J.H.

    1988-01-01

    Neuromodulation is a form of signal transduction that results in the biochemical control of neuronal excitability. Many neurotransmitters act through second messengers, and the examination of biochemical cascades initiated by neurotransmitter-receptor interaction has advanced the understanding of how information is acquired and stored in the nervous system. For example, 5-HT and other facilitory transmitters increase cAMP in sensory neurons of Aplysia, which enhances excitability and facilitates transmitter output. The authors have examined the role of arachidonic acid metabolites in a neuronal circuit mediating presynaptic inhibition. L32 cells are a cluster of putative histaminergic neurons that each make dual-action synaptic potentials onto two follower neurons, L10 and L14. The synaptic connections, biophysical properties, and roles in behavior of the L10 and L14 follower cells have been well studied. The types of ion channels causing each component of the L32-L10 and L32-L14 dual actions have been characterized and application of histamine mimics the effects of stimulating L32 in both L10 and L14

  14. Docosahexaenoic acid (DHA) supplementation in pregnancy differentially modulates arachidonic acid and DHA status across FADS genotypes in pregnancy.

    Science.gov (United States)

    Scholtz, S A; Kerling, E H; Shaddy, D J; Li, S; Thodosoff, J M; Colombo, J; Carlson, S E

    2015-03-01

    Some FADS alleles are associated with lower DHA and ARA status assessed by the relative amount of arachidonic acid (ARA) and docosahexaenoic acid (DHA) in plasma and red blood cell (RBC) phospholipids (PL). We determined two FADS single nucleotide polymorphisms (SNPs) in a cohort of pregnant women and examined the relationship of FADS1rs174533 and FADS2rs174575 to DHA and ARA status before and after supplementation with 600mg per day of DHA. The 205 pregnant women studied were randomly assigned to placebo (mixed soy and corn oil) (n=96) or 600mg algal DHA (n=109) in 3 capsules per day for the last two trimesters of pregnancy. Women homozygous for the minor allele of FADS1rs174533 (but not FADS2rs174575) had lower DHA and ARA status at baseline. At delivery, minor allele homozygotes of FADS1rs174533 in the placebo group had lower RBC-DHA compared to major-allele carriers (P=0.031), while in the DHA-supplemented group, all genotypes had higher DHA status compared to baseline (P=0.001) and status did not differ by genotype (P=0.941). Surprisingly, DHA but not the placebo decreased ARA status of minor allele homozygotes of both FADS SNPs but not major allele homozygotes at delivery. Any physiological effects of changing the DHA to ARA ratio by increasing DHA intake appears to be greater in minor allele homozygotes of some FADS SNPs. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Valnoctamide, which reduces rat brain arachidonic acid turnover, is a potential non-teratogenic valproate substitute to treat bipolar disorder.

    Science.gov (United States)

    Modi, Hiren R; Ma, Kaizong; Chang, Lisa; Chen, Mei; Rapoport, Stanley I

    2017-08-01

    Valproic acid (VPA), used for treating bipolar disorder (BD), is teratogenic by inhibiting histone deacetylase. In unanaesthetized rats, chronic VPA, like other mood stabilizers, reduces arachidonic acid (AA) turnover in brain phospholipids, and inhibits AA activation to AA-CoA by recombinant acyl-CoA synthetase-4 (Acsl-4) in vitro. Valnoctamide (VCD), a non-teratogenic constitutional isomer of VPA amide, reported effective in BD, also inhibits recombinant Acsl-4 in vitro. VCD like VPA will reduce brain AA turnover in unanaesthetized rats. A therapeutically relevant (50mg/kg i.p.) dose of VCD or vehicle was administered daily for 30 days to male rats. AA turnover and related parameters were determined using our kinetic model, following intravenous [1- 14 C]AA in unanaesthetized rats for 10min, and measuring labeled and unlabeled lipids in plasma and high-energy microwaved brain. VCD, compared with vehicle, increased λ, the ratio of brain AA-CoA to unesterified plasma AA specific activities; and decreased turnover of AA in individual and total brain phospholipids. VCD's ability like VPA to reduce rat brain AA turnover and inhibit recombinant Acsl-4, and its efficacy in BD, suggest that VCD be further considered as a non-teratogenic VPA substitute for treating BD. Published by Elsevier B.V.

  16. Use of reversed-phase gel partition chromatography for the purification of chemically synthesized (5,6,8,9,11,12,14,15(n)) octadeuterium- and octatritium-labelled arachidonic acid

    Energy Technology Data Exchange (ETDEWEB)

    Wollard, P M; Lascelles, P T [Department of Chemical Pathology, Institute of Neurology, London, Great Britain; Hensby, C N [Hammersmith Hospital, London (UK). Postgraduate Medical School

    1978-12-11

    The development of a method is described for the preparation and purification of (5,6,8,9,11,12,14,15(n)-/sup 2/H)arachidonic acid (/sup 2/H/sub 8/-AA). The /sup 2/H/sub 8/-AA was chemically synthesised by the selective reduction of 5,8,11,14-eiconsatetraynoic acid (ETYA) with deuterium gas. Using reversed-phase partition chromatography on a Lipidex 5000 column support, it was shown that: (1) The reaction products could readily be separated from each other to yield /sup 2/H/sub 8/-AA of greater than 98% mass purity by gas chromatography. (2) Closely related C20 cis-ethylenic fatty acids differing only in the degree of unsaturation are efficiently separated. The resolution increases exponentially on saturation of double bonds. (3) Commercially available (5,6,8,9,11,12,14,15(n))octatritium-labelled arachidonic acid (/sup 3/H/sub 8/-AA) was readily purified. Both (/sup 3/H/sub 8/)- and (1-/sup 14/C)arachidonic acid (/sup 14/C-AA) co-chromatographed with /sup 2/H/sub 8/-AA. (4) The mass spectra of the methyl ester and trimethylsilyl ester of the purified /sup 2/H/sub 8/-AA showed molecular ions at m/e 326 and 384, respectively.

  17. The effects of the oral administration of fish oil concentrate on the release and the metabolism of [14C]arachidonic acid and [14C]eicosapentaenoic acid by human platelets

    International Nuclear Information System (INIS)

    Hirai, A.; Terano, T.; Hamazaki, T.

    1982-01-01

    It has been suggested by several investigators that eicosapentaenoic acid (C20:5 omega 3, EPA) might have anti-thrombotic effects. In this experiment, the effect of the oral administration of EPA rich fish oil concentrate on platelet aggregation and the release and the metabolism of [ 1 - 14 C]arachidonic acid and [(U)- 14 C]eicosapentaenoic acid by human platelets was studied. Eight healthy male subjects ingested 18 capsules of fish oil concentrate (EPA 1.4 g) per day for 4 weeks. Plasma and platelet concentrations of EPA markedly increased, while those of arachidonic acid (C20:4 omega 6, AA) and docosahexaenoic acid (C22:6 omega 3, DHA) did not change. Platelet aggregation induced by collagen and ADP was reduced. Collagen induced [ 14 C]thromboxane B2 (TXB2) formation from [ 14 C]AA prelabeled platelets decreased. There was no detectable formation of [ 14 C]TXB3 from [ 14 C]EPA prelabeled platelets, and the conversion of exogenous [ 14 C]EPA to [ 14 C]TXB3 was lower than that of [ 14 C]AA to [ 14 C]TXB2. The release of [ 14 C]AA from [ 14 C]AA prelabeled platelets by collagen was significantly decreased. These observations raise the possibility that the release of arachidonic acid from platelet lipids might be affected by the alteration of EPA content in platelets

  18. Arachidonic acid production by the oleaginous fungus Mortierella alpina 1S-4: A review

    Directory of Open Access Journals (Sweden)

    Hiroshi Kikukawa

    2018-05-01

    Full Text Available The filamentous fungus Mortierella alpina 1S-4 is capable of accumulating a large amount of triacylglycerol containing C20 polyunsaturated fatty acids (PUFAs. Indeed, triacylglycerol production by M. alpina 1S-4 can reach 20 g/L of culture broth, and the critical cellular signaling and structural PUFA arachidonic acid (ARA comprises 30%–70% of the total fatty acid. The demonstrated health benefits of functional PUFAs have in turn encouraged the search for rich sources of these compounds, including fungal strains showing enhanced production of specific PUFAs. Screening for mutants and targeted gene manipulation of M. alpina 1S-4 have elucidated the functions of various enzymes involved in PUFA biosynthesis and established lines with improved PUFA productivity. In some cases, these strains have been used for indistrial-scale production of PUFAs, including ARA. In this review, we described practical ARA production through mutant breeding, functional analyses of genes encoding enzymes involved in PUFA biosynthesis, and recent advances in the production of specific PUFAs through molecular breeding of M. alpina 1S-4. Keywords: Arachidonic acid, Mortierella alpina, Molecular breeding, Fatty acid desaturase

  19. mRNA levels of enzymes and receptors implicated in arachidonic acid metabolism in gliomas.

    Science.gov (United States)

    De Armas, Rafael; Durand, Karine; Guillaudeau, Angélique; Weinbreck, Nicolas; Robert, Sandrine; Moreau, Jean-Jacques; Caire, François; Acosta, Gisela; Pebet, Matias; Chaunavel, Alain; Marin, Benoît; Labrousse, François; Denizot, Yves

    2010-07-01

    Gliomas are tumors of the central nervous system derived from glial cells. They show cellular heterogeneity and lack specific diagnostic markers. Although a possible role for the eicosanoid cascade has been suggested in glioma tumorigenesis, the relationship between enzymes and receptors implicated in arachidonic acid metabolism, with histological tumor type has not yet been determined. Quantitative real-time reverse transcription-polymerase chain reaction was performed to measure and compare transcript levels of enzymes and receptors implicated in both lipoxygenase and cyclooxygenase pathways between oligodendrogliomas, astrocytomas, glioblastomas and mixed oligoastrocytomas. Arachidonic acid metabolism-related enzymes and receptor transcripts (i) were underexpressed in classical oligodendrogliomas compared to astrocytomas and/or glioblastomas, (ii) differed between astrocytomas and glioblastomas and (iii) had an intermediate expression in mixed oligoastrocytomas. mRNA levels of enzymes and receptors implicated both in lipoxygenase and cyclooxygenase pathways differed significantly in gliomas according to the histological type. Copyright 2010 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  20. Effect of ethanol amine plasmalogens on Fe-induced peroxidation of arachidonic acid in dipalmitoylphosphatidylcholine vesicles.

    Science.gov (United States)

    Omodeo Salè, M F; Rizzo, A M; Masserini, M

    2000-12-01

    We have investigated the influence of ethanolamine plasmalogens on iron-induced oxidation of arachidonic acid in dipalmitoylphosphatidylcholine (DPPC) vesicles. Lipoperoxidation was induced by the addition of 50 microM FeSO4 and studied above (50 degrees C) and below (15 degrees C) the gel-to liquid transition temperature of the vesicles, at two different pH values (7.4 or 6.4). The extent of peroxidation was measured as thiobarbituric reactive product formed and the influence exerted by ethanolamine plasmalogens (PEPL) in this process was compared to that of dipalmitoylphosphatidylethanolamine (DPPE) and diacylphosphatidylethanolamines (DAPE). The extent of peroxidation of arachidonic acid embedded in DPPC vesicles was similar at the two temperatures and greater at 50 degrees C under acidic conditions. However, the peroxidative process was significantly decreased at 50 degrees C in the presence of PEPL, but not of DPPE or DAPE and the inhibitory effect was enhanced at pH 6.4. The possibility that a different phase distribution of the phospholipids, namely a transition from a lamellar to a hexagonal phase, may play a role in the scavenger effect of ethanolamine plasmalogens is discussed.

  1. Arachidonic acid in health and disease with focus on hypertension and diabetes mellitus: A review

    Directory of Open Access Journals (Sweden)

    Undurti N. Das

    2018-05-01

    Full Text Available Arachidonic acid (AA 20:4n-6 is an essential component of cell membranes and modulates cell membrane fluidity. AA is metabolized by cyclo-oxygenase (COX, lipoxygenase (LOX and cytochrome P450 enzymes to form several metabolites that have important biological actions. Of all the actions, role of AA in the regulation of blood pressure and its ability to prevent both type 1 and type 2 diabetes mellitus seems to be interesting. Studies showed that AA and its metabolites especially, lipoxin A4 (LXA4 and epoxyeicosatrienoic acids (EETs, potent anti-inflammatory metabolites, have a crucial role in the pathobiology of hypertension and diabetes mellitus. AA, LXA4 and EETs regulate smooth muscle function and proliferation, voltage gated ion channels, cell membrane fluidity, membrane receptors, G-coupled receptors, PPARs, free radical generation, nitric oxide formation, inflammation, and immune responses that, in turn, participate in the regulation blood pressure and pathogenesis of diabetes mellitus. In this review, role of AA and its metabolites LXA4 and EETs in the pathobiology of hypertension, pre-eclampsia and diabetes mellitus are discussed. Based on several lines of evidences, it is proposed that a combination of aspirin and AA could be of benefit in the prevention and management of hypertension, pre-eclampsia and diabetes mellitus. Keywords: Arachidonic acid, Lipoxin A4, Hypertension, Pre-eclampsia, Diabetes mellitus, Inflammation, Cytokines, Free radicals, Nitric oxide

  2. Nitric oxide production from macrophages is regulated by arachidonic acid metabolites.

    Science.gov (United States)

    Imai, Y; Kolb, H; Burkart, V

    1993-11-30

    In activated macrophages the inducible form of the enzyme nitric oxide (NO) synthase generates high amounts of the toxic mediator NO. After 20 h of treatment with LPS rat peritoneal macrophages release 12-16 nmol NO2-/10(5) cells which is detectable in the culture supernatant by the Griess reaction as a measure of NO formation. The addition of aminoguanidine (1 mM), a preferential inhibitor of the inducible NO-synthase, completely abolished NO2-accumulation. Incubation with indomethacin or acetyl-salicylic acid, preferential inhibitors of the cyclooxygenase pathway of the arachidonic acid metabolism, did not influence NO2- levels. Nordihydro-guaiaretic acid (50 microM), a preferential inhibitor of the lipoxygenase pathway, caused strong reduction of NO2- accumulation to 1.9 +/- 0.3 nmol/200 microliter. Simultaneous inhibition of cyclo- and lipoxygenase by BW755c resulted in an intermediate effect (7.3 +/- 1.1 nmol/200 microliter NO2-). These results show that the induction of NO production in activated macrophages is regulated by products of the lipoxygenase-pathway of the arachidonic acid metabolism.

  3. Equine tracheal epithelial membrane strips - An alternate method for examining epithelial cell arachidonic acid metabolism

    International Nuclear Information System (INIS)

    Gray, P.R.; Derksen, F.J.; Robinson, N.E.; Peter-Golden, M.L.

    1990-01-01

    Arachidonic acid metabolism by tracheal epithelium can be studied using enzymatically dispersed cell suspensions or cell cultures. Both techniques require considerable tissue disruption and manipulation and may not accurately represent in vivo activity. The authors have developed an alternate method for obtaining strips of equine tracheal epithelium without enzymatic digestion. In the horse, a prominent elastic lamina supports the tracheal epithelium. By physical splitting this lamina, they obtained strips (≤12 x 1.5 cm) of pseudostratified columnar epithelium attached to a layer of elastic tissue 30-100 μm thick. Epithelial strips (1.2 x 0.5 cm) were attached to plexiglass rods and incubated with [ 3 H]arachidonic acid in M199 medium (0.5 μCi/ml) for 24 hours at 37C. The strips incorporated 36±4% (mean ± SEM) of the total radioactivity and released 8.0±1.2% of incorporated radioactivity when stimulated by 5.0 μM calcium ionophore A23187. The extracted supernatant was processed using HPLC, resulting in peaks of radioactivity that co-eluted with authentic PGE 2 , PGF 2 α, and 12-HETE standards. The greatest activity corresponded to the PGE 2 and PGF 2 α standards, which is a similar pattern to that reported for cultured human tracheal epithelium

  4. Food Polyphenol Apigenin Inhibits the Cytochrome P450 Monoxygenase Branch of the Arachidonic Acid Cascade.

    Science.gov (United States)

    Steuck, Maryvonne; Hellhake, Stefan; Schebb, Nils Helge

    2016-11-30

    The product of cytochrome P450 monooxygenase (P450) ω-hydroxylation of arachidonic acid (AA), 20- hydroxyeicosatetraenoic acid (HETE), is a potent vasoconstrictor. Utilizing microsomes as well as individual CYP4 isoforms we demonstrate here that flavonoids can block 20-HETE formation. Apigenin inhibits CYP4F2 with an IC 50 value of 4.6 μM and 20-HETE formation in human liver and kidney microsomes at 2.4-9.8 μM. Interestingly, the structurally similar naringenin shows no relevant effect on the formation of 20-HETE. Based on these in vitro data, it is impossible to evaluate if a relevant blockade of 20-HETE formation can result in humans from intake of polyphenols with the diet. However, the potency of apigenin is comparable to those of P450 inhibitors such as ketoconazole. Moreover, an IC 50 value in the micromolar range is also described for the inhibition of CYP-mediated drug metabolism leading to food-drug interactions. The modulation of the arachidonic acid cascade by food polyphenols therefore warrants further investigation.

  5. Hydrocortisone selectively inhibits IgE-dependent arachidonic acid release from rat peritoneal mast cells

    International Nuclear Information System (INIS)

    Heiman, A.S.; Crews, F.T.

    1984-01-01

    Purified rat mst cells were used to study the effects of antiinflammatory steroids on the release of [1-14C]-arachidonic acid ([1-14C]AA) and metabolites. Mast cell were incubated overnight with glucocorticoids, [1-14C]AA incorporated into cellular phospholipids and the release of [1-14C]AA, and metabolites determined using a variety of secretagogues. Release of [1-14C]AA and metabolites by concanavalin A, the antigen ovalbumin and anti-immunoglobulin E antibody was markedly reduced by glucocorticoid treatment. Neither the total incorporation of [1-14C]AA nor the distribution into phospholipids was altered by hydrocortisone pretreatment. Glucocorticoid pretreatment did not alter [1-14C]AA release stimulated by somatostatin, compound 48/80, or the calcium ionophore, A23187. These data indicate that antiinflammatory steroids selectively inhibit immunoglobulin dependent release of arachidonic acid from rat mast cells. These findings question the role of lipomodulin and macrocortin as general phospholipase inhibitors and suggest that they may be restricted to immunoglobulin stimuli

  6. Melatonin prevents maternal fructose intake-induced programmed hypertension in the offspring: roles of nitric oxide and arachidonic acid metabolites.

    Science.gov (United States)

    Tain, You-Lin; Leu, Steve; Wu, Kay L H; Lee, Wei-Chia; Chan, Julie Y H

    2014-08-01

    Fructose intake has increased globally and is linked to hypertension. Melatonin was reported to prevent hypertension development. In this study, we examined whether maternal high fructose (HF) intake causes programmed hypertension and whether melatonin therapy confers protection against the process, with a focus on the link to epigenetic changes in the kidney using next-generation RNA sequencing (NGS) technology. Pregnant Sprague-Dawley rats received regular chow or chow supplemented with HF (60% diet by weight) alone or with additional 0.01% melatonin in drinking water during the whole period of pregnancy and lactation. Male offspring were assigned to four groups: control, HF, control + melatonin (M), and HF + M. Maternal HF caused increases in blood pressure (BP) in the 12-wk-old offspring. Melatonin therapy blunted the HF-induced programmed hypertension and increased nitric oxide (NO) level in the kidney. The identified differential expressed gene (DEGs) that are related to regulation of BP included Ephx2, Col1a2, Gucy1a3, Npr3, Aqp2, Hba-a2, and Ptgs1. Of which, melatonin therapy inhibited expression and activity of soluble epoxide hydrolase (SEH, Ephx2 gene encoding protein). In addition, we found genes in arachidonic acid metabolism were potentially involved in the HF-induced programmed hypertension and were affected by melatonin therapy. Together, our data suggest that the beneficial effects of melatonin are attributed to its ability to increase NO level in the kidney, epigenetic regulation of genes related to BP control, and inhibition of SEH expression. The roles of DEGs by the NGS in long-term epigenetic changes in the adult offspring kidney require further clarification. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. Carbon monoxide is not responsible for the cigarette smokeinduced changes in the pulmonary metabolism of arachidonic acid and prostaglandin E2

    International Nuclear Information System (INIS)

    Maennistoe, J.; Puustinen, T.; Uotila, P.

    1985-01-01

    Cigarette smoke is known to interfere with the pulmonary metabolism of arachidomic acid and prostaglandin E 2 (PGE 2 ). We investigated the possible role of carbon monoxide in these cigarette smoke-infuced alterations. 4 C-Arachidonic acid (50 nmol) was indused into the pulmonary circulation of isolated perfused hamster lungs and the radioactive metabolites in the perfusion effluent, as well as the distribution of incorporated radioactive arachidonic acid within the lung lipids, were analysed. Carbon monoxide, added into the ventilatory air, had no effect on the oxidative metabolism of arachidonic acid or on the distribution of radioactive arachidonic acid within the lung. In addition, carbon monoxide had no effect on the metabolism of PGE 2 following infusion of 100 nmol of 14 C-PGE 2 into the rat pulmonary circulation. The present study suggests that carbon monoxide is not responsible for the cigarette smoke-induced changes in the pulmonary metabolism of arachidonic acid and PGE 2 . (author)

  8. Effect of supplementation of arachidonic acid (AA) or a combination of AA plus docosahexaenoic acid on breastmilk fatty acid composition

    NARCIS (Netherlands)

    Smit, EN; Koopmann, M; Boersma, ER; Muskiet, FAJ

    We investigated whether supplementation with arachidonic acid (20:4 omega 6; AA), ora combination of AA and docosahexaenoic acid (22:6 omega 3; DHA) would affect human milk polyunsaturated fatty acid (PUFA) composition. Ten women were daily supplemented with 300 mg AA, eight with 300 mg AA, 110 mg

  9. Prenatal long-chain polyunsaturated fatty acid status : the importance of a balanced intake of docosahexaenoic acid and arachidonic acid

    NARCIS (Netherlands)

    Hadders-Algra, Mijna

    2008-01-01

    This review addresses the effect of prenatal long-chain polyunsaturated fatty acid (LCPUFA) status on neuro-developmental outcome. It focuses on the major LPCUFA doxosahexaenoic acid (DNA; 22:6 omega 3) and arachidonic acid (AA; 20:4 omega 6). Due to enzymatic competition high DHA intake results in

  10. The influence of supplemental docosahexaenoic and arachidonic acids during pregnancy and lactation on neurodevelopment at eighteen months

    NARCIS (Netherlands)

    van Goor, Saskia A.; Dijck-Brouwer, D. A. Janneke; Erwich, Jan Jaap H. M.; Schaafsma, Anne; Hadders-Algra, Mijna

    2011-01-01

    Docosahexaenoic acid (DHA) and arachidonic acid (AA) are important for neurodevelopment. The effects of DHA (220 mg/day, n=41), DHA+AA (220 mg/day, n=39) or placebo (n=34) during pregnancy and lactation on neurodevelopment at 18 months, and the relations between umbilical cord DHA, AA and Mead acid

  11. Ethanolic extract of Piper betle Linn. leaves reduces nociception via modulation of arachidonic acid pathway.

    Science.gov (United States)

    De, Soumita; Maroo, Niteeka; Saha, Piu; Hazra, Samik; Chatterjee, Mitali

    2013-01-01

    The objective of this study was to evaluate the peripheral analgesic effect of Piper betle leaf extract (PBE) along with establishing its putative mechanism of action. Male Swiss albino mice after pre-treatment (1 h) with different doses of PBE were injected 0.8% (v/v) acetic acid i.p.; the onset and number of writhes were noted up to 15 min. To evaluate the mechanism of action, the murine peritoneal exudate was incubated with PBE for 1 h, followed by exposure to arachidonic acid (AA) and generation of reactive oxygen species (ROS) was measured by flow cytometry using 2',7'-dichlorodihydrofluorescein diacetate. PBE in a dose dependent manner significantly reduced acetic acid induced writhing response in mice (P < 0.001). In peritoneal exudates, PBE significantly inhibited AA induced generation of ROS, P < 0.01. The present study indicates that PBE has promising analgesic activity, worthy of future pharmacological consideration.

  12. Glutamate signalling and secretory phospholipase A2 modulate the release of arachidonic acid from neuronal membranes

    DEFF Research Database (Denmark)

    Rodriguez De Turco, Elena B; Jackson, Fannie R; DeCoster, Mark A

    2002-01-01

    The lipid mediators generated by phospholipases A(2) (PLA(2)), free arachidonic acid (AA), eicosanoids, and platelet-activating factor, modulate neuronal activity; when overproduced, some of them become potent neurotoxins. We have shown, using primary cortical neuron cultures, that glutamate...... and secretory PLA(2) (sPLA(2)) from bee venom (bv sPLA(2)) and Taipan snake venom (OS2) elicit synergy in inducing neuronal cell death. Low concentrations of sPLA(2) are selective ligands of cell-surface sPLA(2) receptors. We investigated which neuronal arachidonoyl phospholipids are targeted by glutamate......) and in minor changes in other phospholipids. A similar profile, although of greater magnitude, was observed 20 hr posttreatment. Glutamate (80 microM) induced much less mobilization of (3)H-AA than did sPLA(2) and resulted in a threefold greater degradation of (3)H-AA PE than of (3)H-AA PC by 20 hr...

  13. Effects of Arachidonic Acid Supplementation on Acute Anabolic Signaling and Chronic Functional Performance and Body Composition Adaptations.

    Directory of Open Access Journals (Sweden)

    Eduardo O De Souza

    Full Text Available The primary purpose of this investigation was to examine the effects of arachidonic acid (ARA supplementation on functional performance and body composition in trained males. In addition, we performed a secondary study looking at molecular responses of ARA supplementation following an acute exercise bout in rodents.Thirty strength-trained males (age: 20.4 ± 2.1 yrs were randomly divided into two groups: ARA or placebo (i.e. CTL. Then, both groups underwent an 8-week, 3-day per week, non-periodized training protocol. Quadriceps muscle thickness, whole-body composition scan (DEXA, muscle strength, and power were assessed at baseline and post-test. In the rodent model, male Wistar rats (~250 g, ~8 weeks old were pre-fed with either ARA or water (CTL for 8 days and were fed the final dose of ARA prior to being acutely strength trained via electrical stimulation on unilateral plantar flexions. A mixed muscle sample was removed from the exercised and non-exercised leg 3 hours post-exercise.Lean body mass (2.9%, p<0.0005, upper-body strength (8.7%, p<0.0001, and peak power (12.7%, p<0.0001 increased only in the ARA group. For the animal trial, GSK-β (Ser9 phosphorylation (p<0.001 independent of exercise and AMPK phosphorylation after exercise (p-AMPK less in ARA, p = 0.041 were different in ARA-fed versus CTL rats.Our findings suggest that ARA supplementation can positively augment strength-training induced adaptations in resistance-trained males. However, chronic studies at the molecular level are required to further elucidate how ARA combined with strength training affect muscle adaptation.

  14. Inhibitors of the 5-lipoxygenase arachidonic acid pathway induce ATP release and ATP-dependent organic cation transport in macrophages.

    Science.gov (United States)

    da Silva-Souza, Hercules Antônio; Lira, Maria Nathalia de; Costa-Junior, Helio Miranda; da Cruz, Cristiane Monteiro; Vasconcellos, Jorge Silvio Silva; Mendes, Anderson Nogueira; Pimenta-Reis, Gabriela; Alvarez, Cora Lilia; Faccioli, Lucia Helena; Serezani, Carlos Henrique; Schachter, Julieta; Persechini, Pedro Muanis

    2014-07-01

    We have previously described that arachidonic acid (AA)-5-lipoxygenase (5-LO) metabolism inhibitors such as NDGA and MK886, inhibit cell death by apoptosis, but not by necrosis, induced by extracellular ATP (ATPe) binding to P2X7 receptors in macrophages. ATPe binding to P2X7 also induces large cationic and anionic organic molecules uptake in these cells, a process that involves at least two distinct transport mechanisms: one for cations and another for anions. Here we show that inhibitors of the AA-5-LO pathway do not inhibit P2X7 receptors, as judged by the maintenance of the ATPe-induced uptake of fluorescent anionic dyes. In addition, we describe two new transport phenomena induced by these inhibitors in macrophages: a cation-selective uptake of fluorescent dyes and the release of ATP. The cation uptake requires secreted ATPe, but, differently from the P2X7/ATPe-induced phenomena, it is also present in macrophages derived from mice deficient in the P2X7 gene. Inhibitors of phospholipase A2 and of the AA-cyclooxygenase pathway did not induce the cation uptake. The uptake of non-organic cations was investigated by measuring the free intracellular Ca(2+) concentration ([Ca(2+)]i) by Fura-2 fluorescence. NDGA, but not MK886, induced an increase in [Ca(2+)]i. Chelating Ca(2+) ions in the extracellular medium suppressed the intracellular Ca(2+) signal without interfering in the uptake of cationic dyes. We conclude that inhibitors of the AA-5-LO pathway do not block P2X7 receptors, trigger the release of ATP, and induce an ATP-dependent uptake of organic cations by a Ca(2+)- and P2X7-independent transport mechanism in macrophages. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. Peroxisome proliferation activation receptor alpha modulation of Ca2+-regulated exocytosis via arachidonic acid in guinea-pig antral mucous cells.

    Science.gov (United States)

    Sawabe, Yukinori; Shimamoto, Chikao; Sakai, Akiko; Kuwabara, Hiroko; Saad, Adel H; Nakano, Takashi; Takitani, Kimitaka; Tamai, Hiroshi; Mori, Hiroshi; Marunaka, Yoshinori; Nakahari, Takashi

    2010-08-01

    Indomethacin (IDM, 10 microm), not aspirin (ASA; 10 microm), enhanced the Ca(2+)-regulated exocytosis stimulated by 1 microm acetylcholine (ACh) in guinea-pig antral mucous cells. Indomethacin inhibits prostaglandin G/H (PGG/H) and 15R-hydroperoxy-eicosatetraenoic acid (15R-HPETE) production from arachidonic acid (AA), while ASA inhibits PGG/H production but accelerates 15R-HPETE production. This suggests that IDM accumulates AA. Arachidonic acid (2 microm) enhanced Ca(2+)-regulated exocytosis in antral mucous cells to a similar extent to IDM. Moreover, a stable analogue of AA, arachidonyltrifluoromethyl ketone (AACOCF(3)), also enhanced Ca(2+)-regulated exocytosis, indicating that AA, not products from AA, enhances Ca(2+)-regulated exocytosis. We hypothesized that AA activates peroxisome proliferation activation receptor alpha (PPARalpha), because AA is a natural ligand for PPARalpha. A PPARalpha agonist (WY14643; 1 microm) enhanced Ca(2+)-regulated exocytosis, and a PPARalpha blocker (MK886; 50 microm) abolished the enhancement of Ca(2+)-regulated exocytosis induced by AA, IDM, AACOCF(3) and WY14643. Western blotting and immunohistochemical examinations demonstrated that PPARalpha exists in antral mucous cells. Moreover, MK886 decreased the frequency of Ca(2+)-regulated exocytosis activated by 1 microm ACh or 2 microm thapsigargin alone by 25-30%. Thus, ACh stimulates AA accumulation via an [Ca(2+)](i) increase, which activates PPARalpha, leading to enhancement of Ca(2+)-regulated exocytosis in antral mucous cells. A novel autocrine mechanism mediated via PPARalpha enhances Ca(2+)-regulated exocytosis in guinea-pig antral mucous cells.

  16. Effects of sexually dimorphic growth hormone secretory patterns on arachidonic acid metabolizing enzymes in rodent heart

    International Nuclear Information System (INIS)

    Zhang, Furong; Yu, Xuming; He, Chunyan; Ouyang, Xiufang; Wu, Jinhua; Li, Jie; Zhang, Junjie; Duan, Xuejiao; Wan, Yu; Yue, Jiang

    2015-01-01

    The arachidonic acid (AA) metabolizing enzymes are the potential therapeutic targets of cardiovascular diseases (CVDs). As sex differences have been shown in the risk and outcome of CVDs, we investigated the regulation of heart AA metabolizing enzymes (COXs, LOXs, and CYPs) by sex-dependent growth hormone (GH) secretory patterns. The pulsatile (masculine) GH secretion at a physiological concentration decreased CYP1A1 and CYP2J3 mRNA levels more efficiently in the H9c2 cells compared with the constant (feminine) GH secretion; however, CYP1B1 mRNA levels were higher following the pulsatile GH secretion. Sex differences in CYP1A1, CYP1B1, and CYP2J11 mRNA levels were observed in both the wild-type and GHR deficient mice. No sex differences in the mRNA levels of COXs, LOXs, or CYP2E1 were observed in the wild-type mice. The constant GH infusion induced heart CYP1A1 and CYP2J11, and decreased CYP1B1 in the male C57/B6 mice constantly infused with GH (0.4 μg/h, 7 days). The activity of rat Cyp2j3 promoter was inhibited by the STAT5B protein, but was activated by C/EBPα (CEBPA). Compared with the constant GH administration, the levels of the nuclear phosphorylated STAT5B protein and its binding to the rat Cyp2j3 promoter were higher following the pulsatile GH administration. The constant GH infusion decreased the binding of the nuclear phosphorylated STAT5B protein to the mouse Cyp2j11 promoter. The data suggest the sexually dimorphic transcription of heart AA metabolizing enzymes, which might alter the risk and outcome of CVDs. GHR-STAT5B signal transduction pathway may be involved in the sex difference in heart CYP2J levels. - Highlights: • The transcription of heart Cyp1a1, Cyp1b1 and Cyp2j genes is sexually dimorphic. • There are no sex differences in the mRNA levels of heart COXs, LOXs, or CYP2E1. • GHR-STAT5B pathway is involved in sexually dimorphic transcription of heart Cpy2j genes. • Heart CYPs-mediated metabolism pathway of arachidonic acid may be sex

  17. Effects of sexually dimorphic growth hormone secretory patterns on arachidonic acid metabolizing enzymes in rodent heart

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Furong; Yu, Xuming [Department of Pharmacology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071 (China); He, Chunyan [Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071 (China); Ouyang, Xiufang; Wu, Jinhua; Li, Jie; Zhang, Junjie; Duan, Xuejiao [Department of Pharmacology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071 (China); Wan, Yu [Department of Physiology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071 (China); Yue, Jiang, E-mail: yuejiang@whu.edu.cn [Department of Pharmacology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071 (China)

    2015-12-15

    The arachidonic acid (AA) metabolizing enzymes are the potential therapeutic targets of cardiovascular diseases (CVDs). As sex differences have been shown in the risk and outcome of CVDs, we investigated the regulation of heart AA metabolizing enzymes (COXs, LOXs, and CYPs) by sex-dependent growth hormone (GH) secretory patterns. The pulsatile (masculine) GH secretion at a physiological concentration decreased CYP1A1 and CYP2J3 mRNA levels more efficiently in the H9c2 cells compared with the constant (feminine) GH secretion; however, CYP1B1 mRNA levels were higher following the pulsatile GH secretion. Sex differences in CYP1A1, CYP1B1, and CYP2J11 mRNA levels were observed in both the wild-type and GHR deficient mice. No sex differences in the mRNA levels of COXs, LOXs, or CYP2E1 were observed in the wild-type mice. The constant GH infusion induced heart CYP1A1 and CYP2J11, and decreased CYP1B1 in the male C57/B6 mice constantly infused with GH (0.4 μg/h, 7 days). The activity of rat Cyp2j3 promoter was inhibited by the STAT5B protein, but was activated by C/EBPα (CEBPA). Compared with the constant GH administration, the levels of the nuclear phosphorylated STAT5B protein and its binding to the rat Cyp2j3 promoter were higher following the pulsatile GH administration. The constant GH infusion decreased the binding of the nuclear phosphorylated STAT5B protein to the mouse Cyp2j11 promoter. The data suggest the sexually dimorphic transcription of heart AA metabolizing enzymes, which might alter the risk and outcome of CVDs. GHR-STAT5B signal transduction pathway may be involved in the sex difference in heart CYP2J levels. - Highlights: • The transcription of heart Cyp1a1, Cyp1b1 and Cyp2j genes is sexually dimorphic. • There are no sex differences in the mRNA levels of heart COXs, LOXs, or CYP2E1. • GHR-STAT5B pathway is involved in sexually dimorphic transcription of heart Cpy2j genes. • Heart CYPs-mediated metabolism pathway of arachidonic acid may be sex

  18. 2-hydroxy arachidonic acid: a new non-steroidal anti-inflammatory drug.

    Directory of Open Access Journals (Sweden)

    Daniel H Lopez

    Full Text Available BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs are a family of COX1 and COX2 inhibitors used to reduce the synthesis of pro-inflammatory mediators. In addition, inflammation often leads to a harmful generation of nitric oxide. Efforts are being done in discovering safer NSAIDs molecules capable of inhibiting the synthesis of pro-inflammatory lipid mediators and nitric oxide to reduce the side effects associated with long term therapies. METHODOLOGY/PRINCIPAL FINDINGS: The analogue of arachidonic acid (AA, 2-hydroxy-arachidonic acid (2OAA, was designed to inhibit the activities of COX1 and COX2 and it was predicted to have similar binding energies as AA for the catalytic sites of COX1 and COX2. The interaction of AA and 2OAA with COX1 and COX2 was investigated calculating the free energy of binding and the Fukui function. Toxicity was determined in mouse microglial BV-2 cells. COX1 and COX2 (PGH2 production activities were measured in vitro. COX1 and COX2 expression in human macrophage-like U937 cells were carried out by Western blot, immunocytochemistry and RT-PCR analysis. NO production (Griess method and iNOS (Western blot were determined in mouse microglial BV-2 cells. The comparative efficacy of 2OAA, ibuprofen and cortisone in lowering TNF-α serum levels was determined in C57BL6/J mice challenged with LPS. We show that the presence of the -OH group reduces the likelihood of 2OAA being subjected to H* abstraction in COX, without altering significantly the free energy of binding. The 2OAA inhibited COX1 and COX2 activities and the expression of COX2 in human U937 derived macrophages challenged with LPS. In addition, 2OAA inhibited iNOS expression and the production of NO in BV-2 microglial cells. Finally, oral administration of 2OAA decreased the plasma TNF-α levels in vivo. CONCLUSION/SIGNIFICANCE: These findings demonstrate the potential of 2OAA as a NSAID.

  19. Synergy by secretory phospholipase A2 and glutamate on inducing cell death and sustained arachidonic acid metabolic changes in primary cortical neuronal cultures

    DEFF Research Database (Denmark)

    Kolko, M; DeCoster, M A; de Turco, E B

    1996-01-01

    glutamate and sPLA2 from bee venom. sPLA2, at concentrations eliciting low neurotoxicity (acid into triacylglycerols. Free [3H]arachidonic acid accumulated at higher enzyme concentrations......, from Taipan snake venom. The NMDA receptor antagonist MK-801 blocked glutamate effects and partially inhibited sPLA2 OS2 but not sPLA2 from bee venom-induced arachidonic acid release. Thus, the synergy with glutamate and very low concentrations of exogenously added sPLA2 suggests a potential role......Secretory and cytosolic phospholipases A2 (sPLA2 and cPLA2) may contribute to the release of arachidonic acid and other bioactive lipids, which are modulators of synaptic function. In primary cortical neuron cultures, neurotoxic cell death and [3H]arachidonate metabolism was studied after adding...

  20. Supplementation of DHA but not DHA with arachidonic acid during pregnancy and lactation influences general movement quality in 12-week-old term infants

    NARCIS (Netherlands)

    van Goor, Saskia A.; Dijck-Brouwer, D. A. Janneke; Doornbos, Bennard; Erwich, Jan Jaap H. M.; Schaafsma, Anne; Muskiet, Frits A. J.; Hadders-Algra, Mijna

    2010-01-01

    DHA and arachidonic acid (AA) are important for neurodevelopment. A traditional neonatal neurological examination and the evaluation of general movement quality are sensitive techniques for assessing neurodevelopment in young infants. Mildly abnormal general movement,,; at 3 months have been

  1. Ultrastructural autoradiographic localization of exogenous arachidonic acid in cultured endothelial and smooth muscle cells

    International Nuclear Information System (INIS)

    Tasca, S.I.; Galis, Z.

    1988-01-01

    The uptake and intracellular localization of exogenous arachidonic acid (AA) were investigated in cultured endothelial (EC) and smooth muscle cells (SMC) isolated from bovine aorta. The [ 14 C]AA uptake was assessed biochemically and by light and electron microscopic autoradiography. The highest values of silver grain surface density were associated with the mitochondria, lysosomes, and the Golgi apparatus of the EC. The grain linear density was greater on the nuclear envelope than on plasmalemma. On SMC, the grain density was highest on lipid droplets whereas the linear densities of the nuclear envelope and plasmalemma were similar. The share of each subcellular compartment in the AA distribution was estimated as the percentage of the individual silver grain count out of the total cell-associated radioactivity. The results showed that cytoplasm (including endoplasmic reticulum, ribosomes, and small vesicles) made the main contribution followed by the nucleus and at lower values by other organelles. These subcompartments may represent the intracellular sites from which AA could be mobilized for prostanoid synthesis by EC and SMC. (author)

  2. IMAGING BRAIN SIGNAL TRANSDUCTION AND METABOLISM VIA ARACHIDONIC AND DOCOSAHEXAENOIC ACID IN ANIMALS AND HUMANS

    Science.gov (United States)

    Basselin, Mireille; Ramadan, Epolia; Rapoport, Stanley I.

    2012-01-01

    The polyunsaturated fatty acids (PUFAs), arachidonic acid (AA, 20:4n-6) and docosahexaenoic acid (DHA, 22:6n-3), important second messengers in brain, are released from membrane phospholipid following receptor-mediated activation of specific phospholipase A2 (PLA2) enzymes. We developed an in vivo method in rodents using quantitative autoradiography to image PUFA incorporation into brain from plasma, and showed that their incorporation rates equal their rates of metabolic consumption by brain. Thus, quantitative imaging of unesterified plasma AA or DHA incorporation into brain can be used as a biomarker of brain PUFA metabolism and neurotransmission. We have employed our method to image and quantify effects of mood stabilizers on brain AA/DHA incorporation during neurotransmission by muscarinic M1,3,5, serotonergic 5-HT2A/2C, dopaminergic D2-like (D2, D3, D4) or glutamatergic N-methyl-D-aspartic acid (NMDA) receptors, and effects of inhibition of acetylcholinesterase, of selective serotonin and dopamine reuptake transporter inhibitors, of neuroinflammation (HIV-1 and lipopolysaccharide) and excitotoxicity, and in genetically modified rodents. The method has been extended for the use with positron emission tomography (PET), and can be employed to determine how human brain AA/DHA signaling and consumption are influenced by diet, aging, disease and genetics. PMID:22178644

  3. Characterization of arachidonate 5-lipoxygenase and leukotriene A4 synthetase from RBL-1 cells

    International Nuclear Information System (INIS)

    Cook, M.; Hogaboom, G.K.; Sarau, H.M.; Foley, J.J.; Crooke, S.T.

    1986-01-01

    5-lipoxygenase (LO) and leukotriene (LT) A4 synthetase from RBL-1 high speed (105,000 x g for 60 min) supernatants were partially purified by protein-high performance liquid chromatography (HPLC) and characterized in detail. The partially purified preparation contained only 5-LO and LTA4 synthetase and was isolated from 12-LO, peroxidase and LTA4 hydrolase activities. Reaction products were separated by reversed phase HPLC and quantitated by absorption spectrophotometry and radiochemical detection. The enzyme preparation rapidly converted [ 14 C]arachidonate to [ 14 C]5-hydroperoxyeicosatetraenoic acid (HPETE) and [ 14 C]5,12-dihydroperoxyeicosatetraenoic acids (diHETEs). The 5,12-diHETEs were primarily non-enzymatic breakdown products of LTA4 (e.g., 6-trans-LTB4 and 6-trans-12-epi-LTB4). Both the 5-LO and LTA4 synthetase activities were Ca 2+- and ATP-dependent. For both enzyme activities, the CA 2+ stimulation required the presence of ATP. The fatty acid hydroperoxides, 5-,12-, and 15-HPETE, both stimulated ([ 3 μM]) 5-LO and LTA4 synthetase activities. The rapid isolation and subsequent characterization of 5-LO and LTA4 synthetase provide the bases for the further understanding of the role of the LO pathway in biological processes

  4. Monoglyceride lipase as a drug target: At the crossroads of arachidonic acid metabolism and endocannabinoid signaling.

    Science.gov (United States)

    Grabner, Gernot F; Zimmermann, Robert; Schicho, Rudolf; Taschler, Ulrike

    2017-07-01

    Monoglyerides (MGs) are short-lived, intermediary lipids deriving from the degradation of phospho- and neutral lipids, and monoglyceride lipase (MGL), also designated as monoacylglycerol lipase (MAGL), is the major enzyme catalyzing the hydrolysis of MGs into glycerol and fatty acids. This distinct function enables MGL to regulate a number of physiological and pathophysiological processes since both MGs and fatty acids can act as signaling lipids or precursors thereof. The most prominent MG species acting as signaling lipid is 2-arachidonoyl glycerol (2-AG) which is the most abundant endogenous agonist of cannabinoid receptors in the body. Importantly, recent observations demonstrate that 2-AG represents a quantitatively important source for arachidonic acid, the precursor of prostaglandins and other inflammatory mediators. Accordingly, MGL-mediated 2-AG degradation affects lipid signaling by cannabinoid receptor-dependent and independent mechanisms. Recent genetic and pharmacological studies gave important insights into MGL's role in (patho-)physiological processes, and the enzyme is now considered as a promising drug target for a number of disorders including cancer, neurodegenerative and inflammatory diseases. This review summarizes the basics of MG (2-AG) metabolism and provides an overview on the therapeutic potential of MGL. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. The TIP30 protein complex, arachidonic acid and coenzyme A are required for vesicle membrane fusion.

    Directory of Open Access Journals (Sweden)

    Chengliang Zhang

    Full Text Available Efficient membrane fusion has been successfully mimicked in vitro using artificial membranes and a number of cellular proteins that are currently known to participate in membrane fusion. However, these proteins are not sufficient to promote efficient fusion between biological membranes, indicating that critical fusogenic factors remain unidentified. We have recently identified a TIP30 protein complex containing TIP30, acyl-CoA synthetase long-chain family member 4 (ACSL4 and Endophilin B1 (Endo B1 that promotes the fusion of endocytic vesicles with Rab5a vesicles, which transport endosomal acidification enzymes vacuolar (H⁺-ATPases (V-ATPases to the early endosomes in vivo. Here, we demonstrate that the TIP30 protein complex facilitates the fusion of endocytic vesicles with Rab5a vesicles in vitro. Fusion of the two vesicles also depends on arachidonic acid, coenzyme A and the synthesis of arachidonyl-CoA by ACSL4. Moreover, the TIP30 complex is able to transfer arachidonyl groups onto phosphatidic acid (PA, producing a new lipid species that is capable of inducing close contact between membranes. Together, our data suggest that the TIP30 complex facilitates biological membrane fusion through modification of PA on membranes.

  6. Systematic Analysis Reveals that Cancer Mutations Converge on Deregulated Metabolism of Arachidonate and Xenobiotics

    Directory of Open Access Journals (Sweden)

    Francesco Gatto

    2016-07-01

    Full Text Available Mutations are the basis of the clonal evolution of most cancers. Nevertheless, a systematic analysis of whether mutations are selected in cancer because they lead to the deregulation of specific biological processes independent of the type of cancer is still lacking. In this study, we correlated the genome and transcriptome of 1,082 tumors. We found that nine commonly mutated genes correlated with substantial changes in gene expression, which primarily converged on metabolism. Further network analyses circumscribed the convergence to a network of reactions, termed AraX, that involves the glutathione- and oxygen-mediated metabolism of arachidonic acid and xenobiotics. In an independent cohort of 4,462 samples, all nine mutated genes were consistently correlated with the deregulation of AraX. Among all of the metabolic pathways, AraX deregulation represented the strongest predictor of patient survival. These findings suggest that oncogenic mutations drive a selection process that converges on the deregulation of the AraX network.

  7. Effect of oxygen deprivation on metabolism of arachidonic acid by cultures of rat heart cells

    International Nuclear Information System (INIS)

    Freyss-Beguin, M.; Millanvoye-van Brussel, E.; Duval, D.

    1989-01-01

    To investigate the mechanisms responsible for the impairment of phospholipid metabolism observed in ischemic cells, we have studied the effect of conditions simulating ischemia on the metabolism of arachidonic acid (AA) by muscle (M-) and nonmuscle (F-) cells isolated from newborn rat hearts and cultured separately. In muscle cells, oxygen deprivation induces a significant stimulation of the release of [ 14 C]AA from prelabeled cells associated with a preferential redistribution of [ 14 C]AA into cell triglycerides but not formation of radioactive prostaglandins. Moreover, the fatty acid content of phospholipids, as measured by capillary gas chromatography, appears markedly reduced in ischemic myocardial cells. This fact may be related to phospholipase stimulation during ischemia as suggested by the antagonistic effect of mepacrine or p-bromophenacyl bromide. In contrast, oxygen deprivation failed to induce any significant alteration of AA metabolism in fibroblast-like heart cells. Our results indicate that these cultures of newborn rat heart cells, which exhibit many of the features observed in intact organ during ischemia, may represent a useful experimental model to investigate the pharmacological control of the membrane phospholipid turnover

  8. Phospholipid sources for adrenic acid mobilization in RAW 264.7 macrophages. Comparison with arachidonic acid.

    Science.gov (United States)

    Guijas, Carlos; Astudillo, Alma M; Gil-de-Gómez, Luis; Rubio, Julio M; Balboa, María A; Balsinde, Jesús

    2012-11-01

    Cells metabolize arachidonic acid (AA) to adrenic acid (AdA) via 2-carbon elongation reactions. Like AA, AdA can be converted into multiple oxygenated metabolites, with important roles in various physiological and pathophysiological processes. However, in contrast to AA, there is virtually no information on how the cells regulate the availability of free AdA for conversion into bioactive products. We have used a comparative lipidomic approach with both gas chromatography and liquid chromatography coupled to mass spectrometry to characterize changes in the levels of AA- and AdA-containing phospholipid species in RAW 264.7 macrophage-like cells. Incubation of the cells with AA results in an extensive conversion to AdA but both fatty acids do not compete with each other for esterification into phospholipids. AdA but not AA, shows preference for incorporation into phospholipids containing stearic acid at the sn-1 position. After stimulation of the cells with zymosan, both AA and AdA are released in large quantities, albeit AA is released to a greater extent. Finally, a variety of phosphatidylcholine and phosphatidylinositol molecular species contribute to AA; however, AdA is liberated exclusively from phosphatidylcholine species. Collectively, these results identify significant differences in the cellular utilization of AA and AdA by the macrophages, suggesting non-redundant biological actions for these two fatty acids. Copyright © 2012 Elsevier B.V. All rights reserved.

  9. Arachidonic acid metabolites in normal and autoimmune mice do not influence lymphocyte-high endothelial venule interactions.

    Science.gov (United States)

    Manolios, N; Bakiera, B; Geczy, C L; Schrieber, L

    1991-02-01

    In peripheral lymphoid organs the number of lymphocytes and the proportion of functional lymphocyte subsets are regulated by multiple factors including the control of lymphocyte migration by selective lymphocyte-high endothelial venule (HEV) interactions. In this study, prostaglandin E2 (PGE2) levels from normal and autoimmune mouse lymph node cells were measured. The contribution of eicosanoids to lymphocyte-HEV interactions in normal (CBA/T6) and autoimmune (MRL/n) mice was examined. There was no association between PGE2 production in normal or autoimmune mice and the age of onset of disease activity in the latter strains. Arachidonic acid metabolites, in particular PGE2 and leukotriene B4 (LTB4), did not have any effects on lymphocyte-HEV binding. Likewise, lymphocytes treated in vivo and/or in vitro with arachidonic acid metabolite inhibitors (acetyl salicylic acid, indomethacin, BW755C) did not alter lymphocyte-HEV binding interactions in both normal and autoimmune mice. No clinical significance could be attributed to lymph node PGE2 production and the age of onset of autoimmune disease. In summary, these findings cast doubt on the role of arachidonic acid metabolites in lymphocyte-HEV binding interactions.

  10. D-2 dopamine receptor activation reduces free [3H]arachidonate release induced by hypophysiotropic peptides in anterior pituitary cells

    International Nuclear Information System (INIS)

    Canonico, P.L.

    1989-01-01

    Dopamine reduces the stimulation of intracellular [ 3 H]arachidonate release produced by the two PRL-stimulating peptides angiotensin-II and TRH. This effect is concentration dependent and is mediated by stimulation of D-2 dopamine receptors. D-2 receptor agonists (bromocriptine, dihydroergocryptine, and dihydroergocristine) inhibit the release of fatty acid induced by angiotensin-II with a potency that parallels their ability to inhibit PRL release in vitro. Conversely, the selective D-2 receptor antagonist L-sulpiride completely prevents dopamine's effect, whereas SCH 23390 (a D-1 receptor antagonist) is ineffective. The inhibitory action of dopamine does not seem to be consequent to an action on the adenylate cyclase-cAMP system, as 8-bromo-cAMP (1 mM) does not affect either basal or dopamine-inhibited [ 3 H]arachidonate release. However, a 24-h pertussis toxin pretreatment significantly reduces the action of dopamine on fatty acid release. Collectively, these results suggest that D-2 dopamine receptor-mediated inhibition of intracellular [ 3 H]arachidonate release requires the action of a GTP-binding protein, but is not a consequence of an inhibitory action on cAMP levels

  11. Arachidonic acid and other unsaturated fatty acids and some of their metabolites function as endogenous antimicrobial molecules: A review

    Directory of Open Access Journals (Sweden)

    Undurti N. Das

    2018-05-01

    Full Text Available Our body is endowed with several endogenous anti-microbial compounds such as interferon, cytokines, free radicals, etc. However, little attention has been paid to the possibility that lipids could function as antimicrobial compounds. In this short review, the antimicrobial actions of various polyunsaturated fatty acids (PUFAs, mainly free acids and their putative mechanisms of action are described. In general, PUFAs kill microbes by their direct action on microbial cell membranes, enhancing generation of free radicals, augmenting the formation of lipid peroxides that are cytotoxic, and by increasing the formation of their bioactive metabolites, such as prostaglandins, lipoxins, resolvins, protectins and maresins that enhance the phagocytic action of leukocytes and macrophages. Higher intakes of α-linolenic and cis-linoleic acids (ALA and LA respectively and fish (a rich source of eicosapentaenoic acid and docosahexaenoic acid might reduce the risk pneumonia. Previously, it was suggested that polyunsaturated fatty acids (PUFAs: linoleic, α-linolenic, γ-linolenic (GLA, dihomo-GLA (DGLA, arachidonic (AA, eicosapentaenoic (EPA, and docosahexaenoic acids (DHA function as endogenous anti-bacterial, anti-fungal, anti-viral, anti-parasitic, and immunomodulating agents. A variety of bacteria are sensitive to the growth inhibitory actions of LA and ALA in vitro. Hydrolyzed linseed oil can kill methicillin-resistant Staphylococcus aureus. Both LA and AA have the ability to inactivate herpes, influenza, Sendai, and Sindbis virus within minutes of contact. AA, EPA, and DHA induce death of Plasmodium falciparum both in vitro and in vivo. Prostaglandin E1 (PGE1 and prostaglandin A (PGA, derived from DGLA, AA, and EPA inhibit viral replication and show anti-viral activity. Oral mucosa, epidermal cells, lymphocytes and macrophages contain and release significant amounts of PUFAs on stimulation. PUFAs stimulate NADPH-dependent superoxide production by

  12. Arachidonic Acid Metabolism Pathway Is Not Only Dominant in Metabolic Modulation but Associated With Phenotypic Variation After Acute Hypoxia Exposure

    Directory of Open Access Journals (Sweden)

    Chang Liu

    2018-03-01

    Full Text Available Background: The modulation of arachidonic acid (AA metabolism pathway is identified in metabolic alterations after hypoxia exposure, but its biological function is controversial. We aimed at integrating plasma metabolomic and transcriptomic approaches to systematically explore the roles of the AA metabolism pathway in response to acute hypoxia using an acute mountain sickness (AMS model.Methods: Blood samples were obtained from 53 enrolled subjects before and after exposure to high altitude. Ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry and RNA sequencing were separately performed for metabolomic and transcriptomic profiling, respectively. Influential modules comprising essential metabolites and genes were identified by weighted gene co-expression network analysis (WGCNA after integrating metabolic information with phenotypic and transcriptomic datasets, respectively.Results: Enrolled subjects exhibited diverse response manners to hypoxia. Combined with obviously altered heart rate, oxygen saturation, hemoglobin, and Lake Louise Score (LLS, metabolomic profiling detected that 36 metabolites were highly related to clinical features in hypoxia responses, out of which 27 were upregulated and nine were downregulated, and could be mapped to AA metabolism pathway significantly. Integrated analysis of metabolomic and transcriptomic data revealed that these dominant molecules showed remarkable association with genes in gas transport incapacitation and disorders of hemoglobin metabolism pathways, such as ALAS2, HEMGN. After detailed description of AA metabolism pathway, we found that the molecules of 15-d-PGJ2, PGA2, PGE2, 12-O-3-OH-LTB4, LTD4, LTE4 were significantly up-regulated after hypoxia stimuli, and increased in those with poor response manner to hypoxia particularly. Further analysis in another cohort showed that genes in AA metabolism pathway such as PTGES, PTGS1, GGT1, TBAS1 et al. were excessively

  13. Targeting arachidonic acid pathway by natural products for cancer prevention and therapy.

    Science.gov (United States)

    Yarla, Nagendra Sastry; Bishayee, Anupam; Sethi, Gautam; Reddanna, Pallu; Kalle, Arunasree M; Dhananjaya, Bhadrapura Lakkappa; Dowluru, Kaladhar S V G K; Chintala, Ramakrishna; Duddukuri, Govinda Rao

    2016-10-01

    Arachidonic acid (AA) pathway, a metabolic process, plays a key role in carcinogenesis. Hence, AA pathway metabolic enzymes phospholipase A 2 s (PLA 2 s), cyclooxygenases (COXs) and lipoxygenases (LOXs) and their metabolic products, such as prostaglandins and leukotrienes, have been considered novel preventive and therapeutic targets in cancer. Bioactive natural products are a good source for development of novel cancer preventive and therapeutic drugs, which have been widely used in clinical practice due to their safety profiles. AA pathway inhibitory natural products have been developed as chemopreventive and therapeutic agents against several cancers. Curcumin, resveratrol, apigenin, anthocyans, berberine, ellagic acid, eugenol, fisetin, ursolic acid, [6]-gingerol, guggulsteone, lycopene and genistein are well known cancer chemopreventive agents which act by targeting multiple pathways, including COX-2. Nordihydroguaiaretic acid and baicalein can be chemopreventive molecules against various cancers by inhibiting LOXs. Several PLA 2 s inhibitory natural products have been identified with chemopreventive and therapeutic potentials against various cancers. In this review, we critically discuss the possible utility of natural products as preventive and therapeutic agents against various oncologic diseases, including prostate, pancreatic, lung, skin, gastric, oral, blood, head and neck, colorectal, liver, cervical and breast cancers, by targeting AA pathway. Further, the current status of clinical studies evaluating AA pathway inhibitory natural products in cancer is reviewed. In addition, various emerging issues, including bioavailability, toxicity and explorability of combination therapy, for the development of AA pathway inhibitory natural products as chemopreventive and therapeutic agents against human malignancy are also discussed. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Arachidonic Acid Metabolite as a Novel Therapeutic Target in Breast Cancer Metastasis

    Directory of Open Access Journals (Sweden)

    Thaiz F. Borin

    2017-12-01

    Full Text Available Metastatic breast cancer (BC (also referred to as stage IV spreads beyond the breast to the bones, lungs, liver, or brain and is a major contributor to the deaths of cancer patients. Interestingly, metastasis is a result of stroma-coordinated hallmarks such as invasion and migration of the tumor cells from the primary niche, regrowth of the invading tumor cells in the distant organs, proliferation, vascularization, and immune suppression. Targeted therapies, when used as monotherapies or combination therapies, have shown limited success in decreasing the established metastatic growth and improving survival. Thus, novel therapeutic targets are warranted to improve the metastasis outcomes. We have been actively investigating the cytochrome P450 4 (CYP4 family of enzymes that can biosynthesize 20-hydroxyeicosatetraenoic acid (20-HETE, an important signaling eicosanoid involved in the regulation of vascular tone and angiogenesis. We have shown that 20-HETE can activate several intracellular protein kinases, pro-inflammatory mediators, and chemokines in cancer. This review article is focused on understanding the role of the arachidonic acid metabolic pathway in BC metastasis with an emphasis on 20-HETE as a novel therapeutic target to decrease BC metastasis. We have discussed all the significant investigational mechanisms and put forward studies showing how 20-HETE can promote angiogenesis and metastasis, and how its inhibition could affect the metastatic niches. Potential adjuvant therapies targeting the tumor microenvironment showing anti-tumor properties against BC and its lung metastasis are discussed at the end. This review will highlight the importance of exploring tumor-inherent and stromal-inherent metabolic pathways in the development of novel therapeutics for treating BC metastasis.

  15. Arachidonic acid-induced Ca2+ entry and migration in a neuroendocrine cancer cell line.

    Science.gov (United States)

    Goswamee, Priyodarshan; Pounardjian, Tamar; Giovannucci, David R

    2018-01-01

    Store-operated Ca 2+ entry (SOCE) has been implicated in the migration of some cancer cell lines. The canonical SOCE is defined as the Ca 2+ entry that occurs in response to near-maximal depletion of Ca 2+ within the endoplasmic reticulum. Alternatively, arachidonic acid (AA) has been shown to induce Ca 2+ entry in a store-independent manner through Orai1/Orai3 hetero-multimeric channels. However, the role of this AA-induced Ca 2+ entry pathway in cancer cell migration has not been adequately assessed. The present study investigated the involvement of AA-induced Ca 2+ entry in migration in BON cells, a model gastro-enteropancreatic neuroendocrine tumor (GEPNET) cell line using pharmacological and gene knockdown methods in combination with live cell fluorescence imaging and standard migration assays. We showed that both the store-dependent and AA-induced Ca 2+ entry modes could be selectively activated and that exogenous administration of AA resulted in Ca 2+ entry that was pharmacologically distinct from SOCE. Also, whereas homomeric Orai1-containing channels appeared to largely underlie SOCE, the AA-induced Ca 2+ entry channel required the expression of Orai3 as well as Orai1. Moreover, we showed that AA treatment enhanced the migration of BON cells and that this migration could be abrogated by selective inhibition of the AA-induced Ca 2+ entry. Taken together, these data revealed that an alternative Orai3-dependent Ca 2+ entry pathway is an important signal for GEPNET cell migration.

  16. Pharmacological inhibition of arachidonate 15-lipoxygenase (ALOX15) protects human spermatozoa against oxidative stress.

    Science.gov (United States)

    Walters, Jessica L H; De Iuliis, Geoffry N; Dun, Matthew D; Aitken, Robert John; McLaughlin, Eileen A; Nixon, Brett; Bromfield, Elizabeth G

    2018-03-13

    One of the leading causes of male infertility is defective sperm function, a pathology that commonly arises from oxidative stress in the germline. Lipid peroxidation events in the sperm plasma membrane result in the generation of cytotoxic aldehydes such as 4-hydroxynonenal (4HNE), which accentuate the production of reactive oxygen species (ROS) and cause cellular damage. One of the key enzymes involved in the metabolism of polyunsaturated fatty acids to 4HNE in somatic cells is arachidonate 15-lipoxygenase (ALOX15). Although ALOX15 has yet to be characterized in human spermatozoa, our previous studies have revealed a strong link between ALOX15 activity and the levels of oxidative stress and 4HNE in mouse germ cell models. In view of these data, we sought to assess the function of ALOX15 in mature human spermatozoa and determine whether the pharmacological inhibition of this enzyme could influence the level of oxidative stress experienced by these cells. By driving oxidative stress in vitro with exogenous H2O2, our data reveal that 6,11-dihydro[1]benzothiopyrano[4,3-b]indole (PD146176; a selective ALOX15 inhibitor), was able to significantly reduce several deleterious, oxidative insults in spermatozoa. Indeed, PD146176 attenuated the production of ROS, as well as membrane lipid peroxidation and 4HNE production in human spermatozoa. Accordingly, ALOX15 inhibition also protected the functional competence of these cells to acrosome react and bind homologous human zonae pellucidae. Together, these results implicate ALOX15 in the propagation of an oxidative stress cascade within human spermatozoa and offer insight into potential therapeutic avenues to address male fertility that arises from oxidative stress.

  17. Differentiation of U937 cells induced by 5,8,11,14-eicosatetraynoic acid, a competitive inhibitor of arachidonic acid metabolism

    International Nuclear Information System (INIS)

    Ondrey, F.; Anderson, K.; Hoeltgen, D.; Harris, J.

    1988-01-01

    5,8,11,14-Eicosatetraynoic acid, a competitive inhibitor of arachidonic acid metabolism, rapidly and reversibly inhibited DNA synthesis in U937 cells. This inhibition was not due to cytotoxicity, as judged by studies with trypan blue, release of 51 Cr-labeled proteins, and its reversibility. When cells were cultured in the presence of ETYA for several days, morphologic, enzymatic, and functional changes consistent with differentiation occurred. The cells enlarged, the ratio of cytoplasm to nuclei increased, secretory granules and vacuoles developed, the apparent activity of nonspecific esterase rose, and ingestion of latex particles increased. A morphology consistent with that of an immature monocyte was evident by electron microscopy. When cells differentiated by ETYA were cultured in media free of the inhibitor, DNA synthesis reinitiated and the cell number increased; differentiation was phenotypic and not genotypic. To examine whether ETYA-induced differentiation was obligatorily related to its suppression of DNA synthesis, cells were incubated in 50 μM hydroxyurea and DNA synthesis was inhibited for 24 to 36 h without morphologic evidence of cellular differentiation. However, addition of ETYA to cells prevented from dividing by hydroxyurea and subsequent culture for 72 h induced morphologic evidence of differentiation. The effects of ETYA on cell division and cell differentiation are closely related but can be dissociated

  18. Prostaglandin E2 and the protein kinase A pathway mediate arachidonic acid induction of c-fos in human prostate cancer cells

    Science.gov (United States)

    Chen, Y.; Hughes-Fulford, M.

    2000-01-01

    Arachidonic acid (AA) is the precursor for prostaglandin E2 (PGE2) synthesis and increases growth of prostate cancer cells. To further elucidate the mechanisms involved in AA-induced prostate cell growth, induction of c-fos expression by AA was investigated in a human prostate cancer cell line, PC-3. c-fos mRNA was induced shortly after addition of AA, along with a remarkable increase in PGE2 production. c-fos expression and PGE2 production induced by AA was blocked by a cyclo-oxygenase inhibitor, flurbiprofen, suggesting that PGE2 mediated c-fos induction. Protein kinase A (PKA) inhibitor H-89 abolished induction of c-fos expression by AA, and partially inhibited PGE2 production. Protein kinase C (PKC) inhibitor GF109203X had no significant effect on c-fos expression or PGE2 production. Expression of prostaglandin (EP) receptors, which mediate signal transduction from PGE2 to the cells, was examined by reverse transcription polymerase chain reaction in several human prostate cell lines. EP4 and EP2, which are coupled to the PKA signalling pathway, were expressed in all cells tested. Expression of EP1, which activates the PKC pathway, was not detected. The current study showed that induction of the immediate early gene c-fos by AA is mediated by PGE2, which activates the PKA pathway via the EP2/4 receptor in the PC-3 cells.

  19. Effects of different arachidonic acid supplementation on psychomotor development in very preterm infants; a randomized controlled trial.

    Science.gov (United States)

    Alshweki, Ayham; Muñuzuri, Alejandro Pérez; Baña, Ana M; de Castro, Ma José; Andrade, Fernando; Aldamiz-Echevarría, Luís; de Pipaón, Miguel Sáenz; Fraga, José M; Couce, María L

    2015-09-30

    Nutritional supplementation with polyunsaturated fatty acids is important in preterm infants neurodevelopment, but it is not known if the omega-6/omega-3 ratio affects this process. This study was designed to determine the effects of a balanced contribution of arachidonic acid in very preterm newborns fed with formula milk. This was a randomized trial, in which newborns psychomotor development was assessed using the Brunet Lézine scale at 24 months corrected age. A control group, for comparison of Brunet Lézine score, was made up of 25 newborns from the SEN1500 project, who were fed exclusively with breast milk. At 12 months, arachidonic acid values were significantly higher in group A than in group B (6.95 ± 1.55% vs. 4.55 ± 0.78%), as were polyunsaturated fatty acids (41.02 ± 2.09% vs. 38.08 ± 2.32%) achieved a higher average. Group A achieved a higher average Brunet Lézine score at 24 months than group B (99.9 ± 9 vs. 90.8 ± 11, p =0.028). The Brunet Lézine results from group A were compared with the control group results, with very similar scores registered between the two groups (99.9 ± 9 vs. 100.5 ± 7). There were no significant differences in growth or evoked potentials between the two formula groups. Very preterm infants who received formula with an ω-6/ω-3 ratio of 2/1 had higher blood levels of essential fatty acids during the first year of life, and better psychomotor development, compared with very preterm newborns who consumed formula with an ω-6/ω-3 of 1/1. Therefore, formula milk with an arachidonic acid quantity double that of docosahexaenoic acid should be considered for feeding very preterm infants. ClinicalTrials.gov Identifier NCT02503020.

  20. Acyl-CoA synthetase activity links wild-type but not mutant a-Synuclein to brain arachidonate metabolism

    DEFF Research Database (Denmark)

    Golovko, Mikhail; Rosenberger, Thad; Færgeman, Nils J.

    2006-01-01

    Because alpha-synuclein (Snca) has a role in brain lipid metabolism, we determined the impact that the loss of alpha-synuclein had on brain arachidonic acid (20:4n-6) metabolism in vivo using Snca-/- mice. We measured [1-(14)C]20:4n-6 incorporation and turnover kinetics in brain phospholipids using......, our data demonstrate that alpha-synuclein has a major role in brain 20:4n-6 metabolism through its modulation of endoplasmic reticulum-localized acyl-CoA synthetase activity, although mutant forms of alpha-synuclein fail to restore this activity....

  1. A human dietary arachidonic acid supplementation study conducted in a metabolic research unit: rationale and design.

    Science.gov (United States)

    Nelson, G J; Kelley, D S; Emken, E A; Phinney, S D; Kyle, D; Ferretti, A

    1997-04-01

    While there are many reports of studies that fed arachidonic acid (AA) to animals, there are very few reports of AA feeding to humans under controlled conditions. This 130-d study was conceived as a controlled, symmetrical crossover design with healthy, adult male volunteers. They lived in the metabolic research unit (MRU) of the Western Human Nutrition Research (WHNRC) for the entire study. All food was prepared by the WHNRC kitchen. The basal (low-AA) diet consisted of natural foods (30 en% fat, 15 en% protein, and 55 en% carbohydrate), containing 210 mg/d of AA, and met the recommended daily allowance for all nutrients. The high-AA (intervention) diet was similar except that 1.5 g/d of AA in the form of a triglyceride containing 50% AA replaced an equal amount of high-oleic safflower oil in the basal diet. The subjects (ages 20 to 39) were within -10 to +20% of ideal body weight, nonsmoking, and not allowed alcohol in the MRU. Their exercise level was constant, and their body weights were maintained within 2% of entry level. Subjects were initially fed the low-AA diet for 15 d. On day 16, half of the subjects (group A) wee placed on the high-AA diet, and the other group (B) remained on the low-AA diets. On day 65, the two groups switched diets. On day 115, group B returned to the low-AA diet. This design, assuming no carryover effect, allowed us to merge the data from the two groups, with the data comparison days being 65 (low-AA) and 115 (high-AA) for group B and 130 (low-AA) and 65 (high-AA) for group A. The main indices studied were the fatty acid composition of the plasma, red blood cells, platelets, and adipose tissue; in vitro platelet aggregation, bleeding times, clotting factors; immune response as measured by delayed hypersensitivity skin tests, cellular proliferation of peripheral blood mononuclear cells in response to various mitogens and antigens, natural killer cell activity, and response to measles/mumps/rubella and influenza vaccines; the

  2. Thiyl radical-induced cis-trans-isomerization of arachidonic acid inhibits prostaglandin metabolism

    International Nuclear Information System (INIS)

    Kratzsch, S.; Droessler, K.; Sprinz, H.; Brede, O.

    2002-01-01

    Complete text of publication follows. Thiyl radicals radiolytically generated from thiophenol in methanolic solution are known to isomerise double bonds of poly-unsaturated fatty acids (PUFA). γ-irradiating of such a system containing all-cis 5,8,11,14 eicosatetraenoic acid (arachidonic acid, AA) with low doses (0.1-0.8 kGy) results in a mixture of 8 to 32% mono-trans-isomers. Here we report about the influence of mono-trans-AA on the primary steps of AA-metabolism and prostaglandin synthesis, catalysed by cyclooxygenase (COX). In the cell-free model system the reaction of COX-1 with AA was analysed by controlling the oxygen level during the enzymatic reaction. As an example, a mixture of a low quantity of mono-trans-isomerized AA (10%) and 90% all-cis-isomer exhibits a marked reduced oxygen consumption by 45%. As further proofs - the yield of reactive oxygen species (ROS) generated by the COX-coupled peroxidase reaction was detected, - and the COX-1 activity in presence of different amounts of trans-AA was characterized using a photometric assay based on the oxidation of TMPD. All these methods indicated semiquantitatively a reduced activity of COX-1, depending on the trans-isomer yield. Therefore, an inhibition of COX-1 activity by only one trans-double-bond in AA could be concluded. Furthermore, in vitro cell-line experiments were performed analysing the influence of mono-trans-isomerized AA on the activity of the cell-own COX-2. Hence, VD 3 -differentiated and LPS-stimulated monocyte-like cells were incubated with mono-trans-AA and ROS-production was detected by the chemiluminescence measurements mentioned above. Compared to the reaction with all-cis-AA we found a considerable lowered formation of ROS. Likewise, we obtained a reduced PGE 2 -expression between 15 and 40% for cells treated with 8 to 29% trans-AA. The model as well as in vivo experiments demonstrate an inhibition effect of mono-trans-AA and give rise for postulating an enzyme blocking mechanism

  3. Chronic dietary n-6 PUFA deprivation leads to conservation of arachidonic acid and more rapid loss of DHA in rat brain phospholipids.

    Science.gov (United States)

    Lin, Lauren E; Chen, Chuck T; Hildebrand, Kayla D; Liu, Zhen; Hopperton, Kathryn E; Bazinet, Richard P

    2015-02-01

    To determine how the level of dietary n-6 PUFA affects the rate of loss of arachidonic acid (ARA) and DHA in brain phospholipids, male rats were fed either a deprived or adequate n-6 PUFA diet for 15 weeks postweaning, and then subjected to an intracerebroventricular infusion of (3)H-ARA or (3)H-DHA. Brains were collected at fixed times over 128 days to determine half-lives and the rates of loss from brain phospholipids (J out). Compared with the adequate n-6 PUFA rats, the deprived n-6-PUFA rats had a 15% lower concentration of ARA and an 18% higher concentration of DHA in their brain total phospholipids. Loss half-lives of ARA in brain total phospholipids and fractions (except phosphatidylserine) were longer in the deprived n-6 PUFA rats, whereas the J out was decreased. In the deprived versus adequate n-6 PUFA rats, the J out of DHA was higher. In conclusion, chronic n-6 PUFA deprivation decreases the rate of loss of ARA and increases the rate of loss of DHA in brain phospholipids. Thus, a low n-6 PUFA diet can be used to target brain ARA and DHA metabolism. Copyright © 2015 by the American Society for Biochemistry and Molecular Biology, Inc.

  4. Suppression of Remodeling Behaviors with Arachidonic Acid Modification for Enhanced in vivo Antiatherogenic Efficacies of Lovastatin-loaded Discoidal Recombinant High Density Lipoprotein.

    Science.gov (United States)

    He, Hongliang; Zhang, Mengyuan; Liu, Lisha; Zhang, Shuangshuang; Liu, Jianping; Zhang, Wenli

    2015-10-01

    A series of in vitro evaluation in our previous studies had proved that arachidonic acid (AA) modification could suppress the remodeling behaviors of lovastatin-loaded discoidal reconstituted high density lipoprotein (LT-d-rHDL) by restraining the reactivity with lecithin cholesterol acyltransferase (LCAT) for reducing undesired drug leakage. This study focuses on the investigation of AA-modified LT-d-rHDL (AA-LT-d-rHDL) in atherosclerotic New Zealand White (NZW) rabbit models to explore whether AA modification could enhance drug targeting delivery and improve antiatherogenic efficacies in vivo. After pharmacokinetics of AA-LT-d-rHDL modified with different AA amount were investigated in atherosclerotic NZW rabbits, atherosclerotic lesions targeting property was assessed by ex vivo imaging of aortic tree and drug distribution. Furthermore, their antiatherogenic efficacies were elaborately evaluated and compared by typical biochemical indices. With AA modification amount augmenting, circulation time of AA-LT-d-rHDL was prolonged, and drug accumulation in the target locus was increased, eventually the significant appreciation in antiatherogenic efficacies were further supported by lower level of bad cholesterol, decreased atherosclerotic lesions areas and mean intima-media thickness (MIT), markedly attenuated matrix metalloproteinase-9 (MMP-9) protein expression and macrophage infiltration. This proof-of-concept study demonstrated that AA-LT-d-rHDL could enhance drug accumulation in atherosclerotic lesion and impede atherosclerosis progression more effectively.

  5. Incorporation and distribution of dihomo-gamma-linolenic acid, arachidonic acid, and eicosapentaenoic acid in cultured human keratinocytes

    International Nuclear Information System (INIS)

    Punnonen, K.; Puustinen, T.; Jansen, C.T.

    1986-01-01

    Human keratinocytes in culture were labelled with 14 C-dihomo-gamma-linolenic acid, 14 C-arachidonic acid or 14 C-eicosapentaenoic acid. All three eicosanoid precursor fatty acids were effectively incorporated into the cells. In phospholipids most of the radioactivity was recovered, in neutral lipids a substantial amount, and as free unesterified fatty acids only a minor amount. Most of the radioactivity was found in phosphatidylethanolamine which was also the major phospholipid as measured by phosphorous assay. The incorporation of dihomo-gamma-linolenic acid and arachidonic acid into lipid subfractions was essentially similar. Eicosapentaenoic acid was, however, much less effectively incorporated into phosphatidylinositol + phosphatidylserine and, correspondingly, more effectively into triacylglycerols as compared to the two other precursor fatty acids. Once incorporated, the distribution of all three precursor fatty acids was relatively stable, and only minor amounts of fatty acids were released into the culture medium during short term culture (two days). Our study demonstrates that eicosanoid precursor fatty acids are avidly taken up by human keratinocytes and esterified into membrane lipids. The clinical implication of this finding is that dietary manipulations might be employed to cause changes in the fatty acid composition of keratinocytes

  6. Increased activity of 5-lipoxygenase in polymorphonuclear leukocytes from asthmatic patients

    International Nuclear Information System (INIS)

    Mita, H.; Yui, Y.; Taniguchi, N.; Yasueda, H.; Shida, T.

    1985-01-01

    The formation of 5-lipoxygenase products of arachidonic acid, 5-HETE and 5,12-diHETE, was determined in 100,000 x g supernatant of polymorphonuclear leukocytes from 17 healthy subjects, 17 patients with extrinsic asthma and 15 patients with intrinsic asthma. After the supernatant was incubated with 14 C-arachidonic acid in the presence of calcium and indomethacin, the lipoxygenase products of arachidonic acid were separated by thin layer chromatography. The results were expressed as the percentage conversion of 14 C-arachidonic acid into the product per 10 7 cells. The formation of 5,12-diHETE, but not of the 5-HETE, was significantly increased in the cells from the group of patients with extrinsic asthma (4.38 +/- 0.78%, mean +/- S.E.; p 14 C-arachidonic acid into 5-HETE and 5,12-diHETE. The percentage conversion in normal subjects was 4.19 +/- 0.39%, 6.24 +/- 0.84% for 17 patients with extrinsic asthma (p < 0.05), and 8.59 +/- 1.29% for 15 patients with intrinsic asthma (p < 0.01). There was no significant difference between these asthmatic groups. These results indicate that 5-lipoxygenase activity is increased in patients with bronchial asthma. 22 references, 3 figures

  7. Indomethacin increases the formation of lipoxygenase products in calcium ionophore stimulated human neutrophils.

    Science.gov (United States)

    Docherty, J C; Wilson, T W

    1987-10-29

    Arachidonic acid metabolism in human neutrophils stimulated in vitro with the calcium ionophore A23187 was studied using combined HPLC and radioimmunoassays. Indomethacin (0.1 and 1.0 microM) caused a 300% increase in LTB4 formation in neutrophils stimulated with A23187. 5-, 12- and 15-HETE levels were also increased. In the presence of exogenous arachidonic acid 1.0 microM Indomethacin caused a 37% increase in LTB4 formation. Acetyl Salicylic Acid and Ibuprofen had no effect on the formation of lipoxygenase metabolites. The effect of indomethacin on LTB4 formation does not appear to be due to a simple redirection of substrate arachidonic acid from the cyclooxygenase to the lipoxygenase pathways.

  8. Ausencia de correlación entre las cifras tensionales, el daño de órgano blanco y la presencia de retinopatía en el modelo animal de hipertensión con L-NAME: ¿Son necesarios nuevos modelos animales en hipertensión arterial?

    OpenAIRE

    Jorge Hernán Ramírez; Mauricio Palacios; Hugo Ocampo; Claudia Zuluaga; Oscar Gutiérrez

    2006-01-01

    La comunidad científica nacional e internacional utiliza ampliamente modelos animales de hipertensión para el estudio de posibles fármacos antihipertensivos. Sin embargo, algunas de las complicaciones de la hipertensión arterial no se expresan por completo en los modelos animales. En este artículo se presenta la falta de correlación de las cifras tensionales con la retinopatía, en el modelo de ratas hipertensas por L-NAME. Además, plantea interrogantes con respecto al desarrollo de nuevos mod...

  9. Pregnancy duration and the ratio of long-chain n-3 fatty acids to arachidonic acid in erythrocytes from Faroese women

    DEFF Research Database (Denmark)

    Olsen, S.F.; Hansen, Harald S.; Jensen, B.

    1989-01-01

    of long-chain n-3 FA to arachidonic acid (the (3/6) ratio) was used as the most relevant single measure of exposure. In 18 women with certain gestational age and with spontaneous onset of delivery, gestational age was significantly associated with the (3/6) ratio quantified in PC (correlation coefficient......Dietary long-chain n-3 fatty acids (FA) may prolong gestation by inhibiting formation of prostaglandins from arachidonic acid. FA were quantified in phosphatidylcholine (PC), phosphatidylethanolamine (PE), and total lipids (TL) of red cells sampled during pregnancy from 29 Faroese women. The ratio...

  10. Impact of arachidonic versus eicosapentaenoic acid on exotonin-induced lung vascular leakage: relation to 4-series versus 5-series leukotriene generation.

    Science.gov (United States)

    Grimminger, F; Wahn, H; Mayer, K; Kiss, L; Walmrath, D; Seeger, W

    1997-02-01

    Escherichia coli hemolysin (HlyA) is a proteinaceous pore-forming exotoxin that is implicated as a significant pathogenicity factor in extraintestinal E. coli infections including sepsis. In perfused rabbit lungs, subcytolytic concentrations of the toxin evoke thromboxane-mediated vasoconstriction and prostanoid-independent protracted vascular permeability increase (11). In the present study, the influence of submicromolar concentrations of free arachidonic acid (AA) and eicosapentaenoic acid (EPA) on the HlyA-induced leakage response was investigated. HlyA at concentration from 0.02 to 0.06 hemolytic units/ml provoked a dose-dependent, severalfold increase in the capillary filtration coefficient (Kfc), accompanied by the release of leukotriene(LT)B4, LTC4, and LTE4 into the recirculating buffer fluid. Simultaneous application of 100 nmol/L AA markedly augmented the HlyA-elicited leakage response, concomitant with an amplification of LTB4 release and a change in the kinetics of cysteinyl-LT generation. In contrast, 50 to 200 nmol/L EPA suppressed in a dose-dependent manner the HlyA-induced increase in Kfc values. This was accompanied by a blockage of 4-series LT generation and a dose-dependent appearance of LTB5, LTC5, and LTE5. In addition, EPA fully antagonized the AA-induced amplification of the HlyA-provoked Kfc increase, again accompanied by a shift from 4-series to 5-series LT generation. We conclude that the vascular leakage provoked by HlyA in rabbit lungs is differentially influenced by free AA versus free EPA, related to the generation of 4- versus 5-series leukotrienes. The composition of lipid emulsions used for parenteral nutrition may thus influence inflammatory capillary leakage.

  11. Identification of rabbit cytochromes P450 2C1 and 2C2 as arachidonic acid epoxygenases.

    Science.gov (United States)

    Laethem, R M; Koop, D R

    1992-12-01

    Microsomes prepared from COS-1 cells transiently expressing rabbit cytochromes P450 2C1 and 2C2 catalyzed the metabolism of arachidonic acid to predominantly 11,12- and 14,15-epoxyeicosatrienoic acids (EETs) when microsomal epoxide hydrolase activity was inhibited by 0.2 mM 1,2-epoxy-3,3,3-trichloropropane. P450 2C2 catalyzed the formation of 11,12-EET and 14,15-EET at a ratio of 3.0 and also produced 19-hydroxyeicosatetraenoic acid (19-HETE). The 11,12-EET, 14,15-EET, and 19-HETE represented 48.3, 15.9, and 12.8%, respectively, of the total metabolites formed. P450 2C1 produced a similar but distinct ratio of 11,12-EET to 14,15-EET (2.0) and did not produce any detectable 19-HETE. The 11,12-EET and 14,15-EET represented 63.0 and 31.1%, respectively, of the total metabolites formed. The 8,9- and 5,6-EETs were not detected with either enzyme. The ratio of the 11,12-EET to 14,15-EET was 1.5 with P450 2CAA, a P450 arachidonic acid epoxygenase (P450 2CAA) that had an amino-terminal sequence identical to that of P450 2C2 [J. Biol. Chem. 267:5552-5559 (1992)]. P450 2C1, 2C2, and 2CAA metabolized lauric acid. The ratio of omega-1- to omega-hydroxylated laurate was 3.6, 3.4, and 2.4 for P450 2CAA, P450 2C2, and P450 2C1, respectively. Purified P450 2CAA had a slightly greater apparent molecular weight than expressed P450 2C2 on sodium dodecyl sulfate-polyacrylamide gels. The results clearly establish that rabbit P450 2C1 and 2C2 are arachidonic acid epoxygenases, and they suggest that P450 2CAA and 2C2 are very similar but may not be identical isoforms.

  12. Receptor-mediated inhibition of adenylate cyclase and stimulation of arachidonic acid release in 3T3 fibroblasts. Selective susceptibility to islet-activating protein, pertussis toxin

    International Nuclear Information System (INIS)

    Murayama, T.; Ui, M.

    1985-01-01

    Thrombin exhibited diverse effects on mouse 3T3 fibroblasts. It (a) decreased cAMP in the cell suspension, (b) inhibited adenylate cyclase in the Lubrol-permeabilized cell suspension in a GTP-dependent manner, increased releases of (c) arachidonic acid and (d) inositol from the cell monolayer prelabeled with these labeled compounds, (e) increased 45 Ca 2+ uptake into the cell monolayer, and (f) increased 86 Rb + uptake into the cell monolayer in a ouabain-sensitive manner. Most of the effects were reproduced by bradykinin, platelet-activating factor, and angiotensin II. The receptors for these agonists are thus likely to be linked to three separate effector systems: the adenylate cyclase inhibition, the phosphoinositide breakdown leading to Ca 2+ mobilization and phospholipase A2 activation, and the Na,K-ATPase activation. Among the effects of these agonists, (a), (b), (c), and (e) were abolished, but (d) and (f) were not, by prior treatment of the cells with islet-activating protein (IAP), pertussis toxin, which ADP-ribosylates the Mr = 41,000 protein, the alpha-subunit of the inhibitory guanine nucleotide regulatory protein (Ni), thereby abolishing receptor-mediated inhibition of adenylate cyclase. The effects (a), (c), (d), and (e) of thrombin, but not (b), were mimicked by A23187, a calcium ionophore. The effects of A23187, in contrast to those of receptor agonists, were not affected by the treatment of cells with IAP. Thus, the IAP substrate, the alpha-subunit of Ni, or the protein alike, may play an additional role in signal transduction arising from the Ca 2+ -mobilizing receptors, probably mediating process(es) distal to phosphoinositide breakdown and proximal to Ca 2+ gating

  13. Modulation of hypericin photodynamic therapy by pretreatment with 12 various inhibitors of arachidonic acid metabolism in colon adenocarcinoma HT-29 cells

    Czech Academy of Sciences Publication Activity Database

    Kleban, J.; Mikeš, J.; Szilárdiová, B.; Koval, J.; Sačková, V.; Solár, P.; Horváth, Viktor; Hofmanová, Jiřina; Kozubík, Alois; Fedoročko, P.

    2007-01-01

    Roč. 83, č. 5 (2007), s. 1174-1185 ISSN 0031-8655 R&D Projects: GA AV ČR(CZ) 1QS500040507 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : hypericin * photodynamic therapy * arachidonic acid inhibitors Subject RIV: BO - Biophysics Impact factor: 2.172, year: 2007

  14. Decreased arachidonic acid content and metabolism in tissues of NZB/W F1 females fed a diet containing 0.45% dehydroisoandrosterone (DHA)

    International Nuclear Information System (INIS)

    Matsunaga, A.; Cottam, G.L.

    1987-01-01

    A diet containing 0.45% DHA fed to NZB/W mice, a model of systemic lupus erythematosus, delays the time of onset, improves survival and decreases the formation of antibodies to ds-DNA. Essential fatty acid-deficient diets or inclusion of eicosapentaenoic acid have similar beneficial effects and led them to investigate arachidonic acid metabolism in response to feeding DHA. The arachidonic acid content of plasma cholesteryl ester decreased from 37.4 +/- 2.2 to 28.2 +/- 1.3 mg%. In total liver phospholipid the value decreased from 18.1 +/- 0.52 to 13.7 +/- 1.3 mg%, in total kidney phospholipid the value decreased from 24.10 +/- 0.87 to 20.7 +/- 0.32 mg% and in resident peritoneal macrophages the value decreased from 15.4 +/- 4.6 to 3.6 +/- 1.4 mg%. The metabolism of exogenous [1- 14 C]arachidonic acid by resident peritoneal macrophages in response to Zymosan stimulation for 2 hr was examined by extraction of metabolites and separation by HPLC. Cells isolated from DHA-fed animals produced less PGE2 than controls, yet similar amounts of 6-keto PGF1α were produced. Arachidonic acid metabolites have significant effects on the immune system and may be a mechanism involved in the benefits obtained by inclusion of DHA in the diet

  15. Evaluation of a subchronic (13-week) oral toxicity study, preceded by an in utero exposure phase, with arachidonic acid oil derived from Mortierella alpina in rats

    NARCIS (Netherlands)

    Hempenius, R.A.; Lina, B.A.R.; Haggitt, R.C.

    2000-01-01

    Arachidonic acid oil (ARA-oil) derived from the fungus Mortierella alpina for use in infant nutrition was tested in a subchronic (13-week) oral toxicity study in rats, preceded by an in utero exposure phase. The ARA-oil was administered as admixture to the rodent diet at dose levels of 3000 ppm,

  16. The relation between the omega-3 index and arachidonic acid is bell shaped : Synergistic at low EPA plus DHA status and antagonistic at high EPA plus DHA status

    NARCIS (Netherlands)

    Luxwolda, Martine F.; Kuipers, Remko S.; Smit, Ella N.; Velzing-Aarts, Francien V.; Dijck-Brouwer, D. A. Janneke; Muskiet, Frits A. J.

    2011-01-01

    Introduction: The relation between docosahexaenoic (DHA) and eicosapentaenoic (EPA) vs. arachidonic acid (AA) seems characterized by both synergism and antagonism. Materials and methods: Investigate the relation between EPA + DHA and AA in populations with a wide range of EPA + DHA status and across

  17. Maternal and fetal brain contents of docosahexaenoic acid (DHA) and arachidonic acid (AA) at various essential fatty acid (EFA), DHA and AA dietary intakes during pregnancy in mice

    NARCIS (Netherlands)

    van Goor, Saskia A; Dijck-Brouwer, D A Janneke; Fokkema, M Rebecca; van der Iest, Theo Hans; Muskiet, Frits A J

    We investigated essential fatty acids (EFA) and long-chain polyunsaturated fatty acids (LCP) in maternal and fetal brain as a function of EFA/LCP availability to the feto-maternal unit in mice. Diets varying in parent EFA, arachidonic acid (AA), and docosahexaenoic acid (DHA) were administered from

  18. Subchronic (13-week) oral toxicity study, preceded by an in utero exposure phase, with arachidonate-enriched triglyceride oil (SUNTGA40S) in rats

    NARCIS (Netherlands)

    Lina, B.A.R.; Wolterbeek, A.P.M.; Suwa, Y.; Fujikawa, S.; Ishikura, Y.; Tsuda, S.; Dohnalek, M.

    2006-01-01

    Polyunsaturated fatty acids (PUFAs), such as arachidonic acid (ARA) and docosahexaenoic acid (DHA) are natural constituents found in human milk, fish oil or egg yolk. Until recently, infant formulas, though providing the essential fatty acid precursors for these PUFAs, did not contain preformed ARA

  19. High contents of both docosahexaenoic and arachidonic acids in milk of women consuming fish from lake Kitangiri (Tanzania) : targets for infant formulae close to our ancient diet?

    NARCIS (Netherlands)

    Kuipers, RS; Fokkema, MR; Smit, EN; van der Meulen, J; Boersma, ER; Muskiet, FAJ

    Current recommendations for arachidonic (AA) and docosahexaenoic (DHA) acids in infant formulae are based on milk of Western mothers. Validity may be questioned in view of the profound dietary changes in the past 100 years, as opposed to our slowly adapting genome. Hominin evolution occurred in the

  20. Essential function of linoleic acid esterified in acylglucosylceramide and acylceramide in maintaining the epidermal water permeability barrier. Evidence from feeding studies with oleate, linoleate, arachidonate, columbinate and a-linolenate

    DEFF Research Database (Denmark)

    Hansen, Harald S.; Jensen, B.

    1985-01-01

    sphingolipids. These rats showed increased evaporation which was comparable to that of essential fatty acid-deficient rats. We interpret these results as strong evidence for a very specific and essential function of linoleic acid in maintaining the integrity of the epidermal water permeability barrier......Essential fatty acid-deficient rats were supplemented with 300 mg per day of pure fatty acid esters: oleate (O), linoleate (L), arachidonate (A), and columbinate (C) for 10 days. During this period, the rats in groups L, A, and C all showed a decrease in their initially high trans-epidermal water...... loss, a classical essential fatty acid-deficiency symptom, to a level seen in non-deficient rats (group N). The trans-epidermal water loss in rats of group O was unaffected by the supplementation. Fatty acid composition of two epidermal sphingolipids, acylglucosylceramide and acylceramide, from...

  1. Effect of extra virgin olive oil components on the arachidonic acid cascade, colorectal cancer and colon cancer cell proliferation

    International Nuclear Information System (INIS)

    Storniolo, C.E.; Moreno, J.J.

    2016-01-01

    The mediterranean diet (MD) reduced the risk of colorectal cancer (CRC), and olive oil, the primary source of fat in the MD, has also been found to have a protective effect. However, animals fed with oleic acid present a high number of intestinal tumours, suggesting that oleic acid and olive oil consumption can exert different effects on CRC. Considering that extra virgin olive oil (EVOO) is a complex mix of fatty acids and minor compounds such as polyphenols, hydrocarbons, phytosterols and triterpenes; and that these compounds have antioxidant activity and consequently they can modulate the arachidonic acid (AA) cascade and eicosanoid synthesis. This review analyzes the state of the art of olive oil components on the AA cascade and cellular mechanism involved in CRC such as intestinal epithelial cell growth/apoptosis, to understand the fact that the consumption of seed oils with high oleic content or EVOO will probably have different effects on CRC development. [es

  2. Effect of extra virgin olive oil components on the arachidonic acid cascade, colorectal cancer and colon cancer cell proliferation

    Directory of Open Access Journals (Sweden)

    C. E. Storniolo

    2016-12-01

    Full Text Available The mediterranean diet (MD reduced the risk of colorectal cancer (CRC, and olive oil, the primary source of fat in the MD, has also been found to have a protective effect. However, animals fed with oleic acid present a high number of intestinal tumours, suggesting that oleic acid and olive oil consumption can exert different effects on CRC. Considering that extra virgin olive oil (EVOO is a complex mix of fatty acids and minor compounds such as polyphenols, hydrocarbons, phytosterols and triterpenes; and that these compounds have antioxidant activity and consequently they can modulate the arachidonic acid (AA cascade and eicosanoid synthesis. This review analyzes the state of the art of olive oil components on the AA cascade and cellular mechanism involved in CRC such as intestinal epithelial cell growth/apoptosis, to understand the fact that the consumption of seed oils with high oleic content or EVOO will probably have different effects on CRC development.

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

    Energy Technology Data Exchange (ETDEWEB)

    Nigam, S.; Fiore, S.; Luscinskas, F.W.; Serhan, C.N. (Brigham and Women' s Hospital, Boston, MA (USA))

    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.

  4. Clinical implications of eicosapentaenoic acid/arachidonic acid ratio (EPA/AA) in adult patients with congenital heart disease.

    Science.gov (United States)

    Kanoh, Miki; Inai, Kei; Shinohara, Tokuko; Tomimatsu, Hirofumi; Nakanishi, Toshio

    2017-12-01

    Recent studies showed that a low ratio between the levels of eicosapentaenoic acid and those of arachidonic acid (EPA/AA) is associated with higher incidence of coronary artery disease and poor prognosis of heart failure, arrhythmia, and cardiac sudden death. However, the clinical implications of EPA/AA in adult patients with congenital heart disease remain unclear. We aimed to assess the prognostic value of EPA/AA regarding cardiac events in adult patients with congenital heart disease. We measured the serum levels of eicosapentaenoic acid and arachidonic acid in 130 adult patients (median age, 31 years) stratified into two groups according to their EPA/AA (low, ≤0.22; high, >0.22). We prospectively analyzed the association between EPA/AA and incidence of cardiac events during a mean observation period of 15 months, expressed in terms of hazard ratio (HR) with 95% confidence interval (95% CI). In the subgroup of patients with biventricular circulation (2VC) (n = 76), we analyzed the same clinical endpoints. In our study population, EPA/AA was not associated with the incidence of arrhythmic events (HR, 1.52; 95% CI, 0.82-2.85; p = 0.19), but low EPA/AA was a predictor of heart failure hospitalization (HR, 2.83; 95% CI, 1.35-6.30; p AA of ≤0.25 was associated with a significantly higher risk of arrhythmic events (HR, 2.55; 95% CI, 1.11-6.41; p = 0.03) and heart failure hospitalization (HR, 5.20; 95% CI, 1.78-18.1; p AA represents a useful predictor of cardiac events in adult patients with congenital heart disease.

  5. Developmental Outcomes at 24 Months of Age in Toddlers Supplemented with Arachidonic Acid and Docosahexaenoic Acid: Results of a Double Blind Randomized, Controlled Trial

    Directory of Open Access Journals (Sweden)

    Angela M. Devlin

    2017-09-01

    Full Text Available Little is known about arachidonic acid (ARA and docosahexaenoic acid (DHA requirements in toddlers. A longitudinal, double blind, controlled trial in toddlers (n = 133 age 13.4 ± 0.9 months (mean ± standard deviation, randomized to receive a DHA (200 mg/day and ARA (200 mg/day supplement (supplement or a corn oil supplement (control until age 24 months determined effects on neurodevelopment. We found no effect of the supplement on the Bayley Scales of Infant and Toddler Development 3rd Edition (Bayley-III cognitive and language composites and Beery–Buktenica Developmental Test of Visual–Motor Integration (Beery VMI at age 24 months. Supplemented toddlers had higher RBC phosphatidylcholine (PC, phosphatidylethanolamine (PE, and plasma DHA and ARA compared to placebo toddlers at age 24 months. A positive relationship between RBC PE ARA and Bayley III Cognitive composite (4.55 (0.21–9.00, B (95% CI, p = 0.045 in supplemented boys, but not in control boys, was observed in models adjusted for baseline fatty acid, maternal non-verbal intelligence, and BMI z-score at age 24 months. A similar positive relationship between RBC PE ARA and Bayley III Language composite was observed for supplemented boys (11.52 (5.10–17.94, p < 0.001 and girls (11.19 (4.69–17.68, p = 0.001. These findings suggest that increasing the ARA status in toddlers is associated with better neurodevelopment at age 24 months.

  6. Safflower and olive oil dietary treatments rescue aberrant embryonic arachidonic acid and nitric oxide metabolism and prevent diabetic embryopathy in rats.

    Science.gov (United States)

    Higa, R; White, V; Martínez, N; Kurtz, M; Capobianco, E; Jawerbaum, A

    2010-04-01

    Aberrant arachidonic acid and nitric oxide (NO) metabolic pathways are involved in diabetic embryopathy. Previous works have found diminished concentrations of PGE(2) and PGI(2) in embryos from diabetic rats, and that PGI(2) is capable of increasing embryonic PGE(2) concentrations through the activation of the nuclear receptor PPARdelta. PPARdelta activators are lipid molecules such as oleic and linoleic acids, present in high concentrations in olive and safflower oils, respectively. The aim of this study was to analyze the capability of dietary supplementation with either 6% olive or 6% safflower oils to regulate PGE(2), PGI(2) and NO concentrations in embryos and deciduas from control and diabetic rats during early organogenesis. Diabetes was induced by a single injection of streptozotocin (55 mg/kg) 1 week before mating. Animals were fed with the oil-supplemented diets from Days 0.5 to 10.5 of gestation. PGI(2) and PGE(2) were measured by EIA and NO through the evaluation of its stable metabolites nitrates-nitrites in 10.5 day embryos and deciduas. We found that the olive and safflower oil-supplemented treatments highly reduced resorption and malformation rates in diabetic animals, and that they were able to prevent maternal diabetes-induced alterations in embryonic and decidual PGI(2) and PGE(2) concentrations. Moreover, these dietary treatments prevented NO overproduction in embryos and deciduas from diabetic rats. These data indicate that in maternal diabetes both the embryo and the decidua benefit from the olive and safflower oil supplementation probably through mechanisms that involve the rescue of aberrant prostaglandin and NO generation and that prevent developmental damage during early organogenesis.

  7. Developmental Outcomes at 24 Months of Age in Toddlers Supplemented with Arachidonic Acid and Docosahexaenoic Acid: Results of a Double Blind Randomized, Controlled Trial

    Science.gov (United States)

    Devlin, Angela M.; Chau, Cecil M. Y.; Matheson, Julie; McCarthy, Deanna; Yurko-Mauro, Karin; Innis, Sheila M.; Grunau, Ruth E.

    2017-01-01

    Little is known about arachidonic acid (ARA) and docosahexaenoic acid (DHA) requirements in toddlers. A longitudinal, double blind, controlled trial in toddlers (n = 133) age 13.4 ± 0.9 months (mean ± standard deviation), randomized to receive a DHA (200 mg/day) and ARA (200 mg/day) supplement (supplement) or a corn oil supplement (control) until age 24 months determined effects on neurodevelopment. We found no effect of the supplement on the Bayley Scales of Infant and Toddler Development 3rd Edition (Bayley-III) cognitive and language composites and Beery–Buktenica Developmental Test of Visual–Motor Integration (Beery VMI) at age 24 months. Supplemented toddlers had higher RBC phosphatidylcholine (PC), phosphatidylethanolamine (PE), and plasma DHA and ARA compared to placebo toddlers at age 24 months. A positive relationship between RBC PE ARA and Bayley III Cognitive composite (4.55 (0.21–9.00), B (95% CI), p = 0.045) in supplemented boys, but not in control boys, was observed in models adjusted for baseline fatty acid, maternal non-verbal intelligence, and BMI z-score at age 24 months. A similar positive relationship between RBC PE ARA and Bayley III Language composite was observed for supplemented boys (11.52 (5.10–17.94), p < 0.001) and girls (11.19 (4.69–17.68), p = 0.001). These findings suggest that increasing the ARA status in toddlers is associated with better neurodevelopment at age 24 months. PMID:28878181

  8. Maternal dietary n-6 polyunsaturated fatty acid deprivation does not exacerbate post-weaning reductions in arachidonic acid and its mediators in the mouse hippocampus.

    Science.gov (United States)

    Alashmali, Shoug M; Kitson, Alex P; Lin, Lin; Lacombe, R J Scott; Bazinet, Richard P

    2017-09-13

    The present study examines how lowering maternal dietary n-6 polyunsaturated fatty acids (PUFA) (starting from pregnancy) compared to offspring (starting from post-weaning) affect the levels of n-6 and n-3 fatty acids in phospholipids (PL) and lipid mediators in the hippocampus of mice. Pregnant mice were randomly assigned to consume either a deprived or an adequate n-6 PUFA diet during pregnancy and lactation (maternal exposure). On postnatal day (PND) 21, half of the male pups were weaned onto the same diet as their dams, and the other half were switched to the other diet for 9 weeks (offspring exposure). At PND 84, upon head-focused high-energy microwave irradiation, hippocampi were collected for PL fatty acid and lipid mediator analyses. Arachidonic acid (ARA) concentrations were significantly decreased in both total PL and PL fractions, while eicosapentaenoic acid (EPA) concentrations were increased only in PL fractions upon n-6 PUFA deprivation of offspring, regardless of maternal exposure. Several ARA-derived eicosanoids were reduced, while some of the EPA-derived eicosanoids were elevated by n-6 PUFA deprivation in offspring. There was no effect of diet on docosahexaenoic acid (DHA) or DHA-derived docosanoids concentrations under either maternal or offspring exposure. These results indicate that the maternal exposure to dietary n-6 PUFA may not be as important as the offspring exposure in regulating hippocampal ARA and some lipid mediators. Results from this study will be helpful in the design of experiments aimed at testing the significance of altering brain ARA levels over different stages of life.

  9. Immunoregulation of antitumor response; differential secretion of arachidonic acid metabolites by macrophages during stimulation ''in vitro'' with BCG and ''Corynebacterium parvum''

    International Nuclear Information System (INIS)

    Tomecki, Jaroslaw; Sukiennik, Jadwiga; Kordowiak, Anna

    1993-01-01

    The level of arachidonic acid (AA) metabolites in the supernatants of cultures peritoneal exudate cells (PEC) were studied under various conditions using BCG and ''Corynebacterium parvum'' as stimulators. The metabolite levels were analyzed by thin layer chromatography (TLC). The degree of macrophage cytotoxic/cytostatic activity was dependent on the dose and character of stimulators used and the source of macrophages. The application of micro cytotoxicity assay for the evaluation of tumor cell lysis (lung sarcoma SaL-1) ''in vitro'' revealed that peritoneal macrophages from healthy and tumor bearing BALB/c mice may affect the degree of antitumor response. In the supernatants of cultured PEC from tumor bearing mice AA level increased (by 10-fold) in comparison with PEC from healthy mice. Stimulation with BCG induced over a double level of AA in PEC isolated from tumor bearing mice non-stimulated or stimulated with ''C.parvum''. A lower level of prostaglandins (PGs) was found in the supernatants of cultured PEC isolated from healthy mice (stimulated and non-stimulated), but the highest level of PGs was observed in the supernatants of cultured PEC isolated from tumor bearing mice stimulated with BCG. The unique metabolite of AA was found only in the supernatants form non-stimulated PEC from tumor bearing mice. PEC from tumor bearing mice produced metabolites of AA which were not detected in control group. These results suggest that macrophages also play a regulatory role by secretion of AA. This process can be modified by bacterial antigens. (author). 21 refs, 7 figs

  10. cPLA2a-evoked formation of arachidonic acid and lysophospholipids is required for exocytosis in mouse pancreatic ß-cells

    DEFF Research Database (Denmark)

    Juhl, Kirstine; Høy, Marianne; Olsen, Hervør L.

    2003-01-01

    Using capacitance measurements, we investigated the effects of intracellularly applied recombinant human cytosolic phospholipase A2 (cPLA2 ) and its lipolytic products arachidonic acid and lysophosphatidylcholine on Ca2+-dependent exocytosis in single mouse pancreatic -cells. cPLA2 dose dependently......–80 to 280–300. cPLA2 -stimulated exocytosis was antagonized by the specific cPLA2 inhibitor AACOCF3. Ca2+-evoked exocytosis was reduced by 40% in cells treated with AACOCF3 or an antisense oligonucleotide against cPLA2 . The action of cPLA2 was mimicked by a combination of arachidonic acid...... and lysophosphatidylcholine (470% stimulation) in which each compound alone doubled the exocytotic response. Priming of insulin-containing secretory granules has been reported to involve Cl- uptake through ClC-3 Cl- channels. Accordingly, the stimulatory action of cPLA2 was inhibited by the Cl- channel inhibitor DIDS...

  11. cPLA2alpha-evoked formation of arachidonic acid and lysophospholipids is required for exocytosis in mouse pancreatic beta-cells

    DEFF Research Database (Denmark)

    Juhl, Kirstine; Høy, Marianne; Olsen, Hervør L

    2003-01-01

    Using capacitance measurements, we investigated the effects of intracellularly applied recombinant human cytosolic phospholipase A2 (cPLA2alpha) and its lipolytic products arachidonic acid and lysophosphatidylcholine on Ca2+-dependent exocytosis in single mouse pancreatic beta-cells. cPLA2alpha...... from 70-80 to 280-300. cPLA2alpha-stimulated exocytosis was antagonized by the specific cPLA2 inhibitor AACOCF3. Ca2+-evoked exocytosis was reduced by 40% in cells treated with AACOCF3 or an antisense oligonucleotide against cPLA2alpha. The action of cPLA2alpha was mimicked by a combination...... of arachidonic acid and lysophosphatidylcholine (470% stimulation) in which each compound alone doubled the exocytotic response. Priming of insulin-containing secretory granules has been reported to involve Cl- uptake through ClC-3 Cl- channels. Accordingly, the stimulatory action of cPLA2alpha was inhibited...

  12. Food sources of arachidonic acid (PFA 20:4), listed in descending order by percentages of their contribution to intake, based on data from the National Health and Nutrition Examination Survey 2005-2006

    Science.gov (United States)

    Food sources of arachidonic acid (PFA 20:4), listed in descending order by percentages of their contribution to intake, based on data from the National Health and Nutrition Examination Survey 2005-2006

  13. An updated review of worldwide levels of docosahexaenoic and arachidonic acid in human breast milk by region.

    Science.gov (United States)

    Fu, Yuanqing; Liu, Xin; Zhou, Bing; Jiang, Alice C; Chai, Lingying

    2016-10-01

    We aimed to evaluate the DHA and arachidonic acid (AA) levels in human breast milk worldwide by country, region and socio-economic status. Descriptive review conducted on English publications reporting breast-milk DHA and AA levels. We systematically searched and identified eligible literature in PubMed from January 1980 to July 2015. Data on breast-milk DHA and AA levels from women who had given birth to term infants were included. Seventy-eight studies from forty-one countries were included with 4163 breast-milk samples of 3746 individuals. Worldwide mean levels of DHA and AA in breast milk were 0·37 (sd 0·11) % and 0·55 (sd 0·14) % of total fatty acids, respectively. The breast-milk DHA levels from women with accessibility to marine foods were significantly higher than those from women without accessibility (0·35 (sd 0·20) % v. 0·25 (sd 0·14) %, Pworldwide variation in breast-milk DHA and AA levels and underlines the need for future population- or region-specific investigations.

  14. Coordination of gene expression of arachidonic and docosahexaenoic acid cascade enzymes during human brain development and aging.

    Science.gov (United States)

    Ryan, Veronica H; Primiani, Christopher T; Rao, Jagadeesh S; Ahn, Kwangmi; Rapoport, Stanley I; Blanchard, Helene

    2014-01-01

    The polyunsaturated arachidonic and docosahexaenoic acids (AA and DHA) participate in cell membrane synthesis during neurodevelopment, neuroplasticity, and neurotransmission throughout life. Each is metabolized via coupled enzymatic reactions within separate but interacting metabolic cascades. AA and DHA pathway genes are coordinately expressed and underlie cascade interactions during human brain development and aging. The BrainCloud database for human non-pathological prefrontal cortex gene expression was used to quantify postnatal age changes in mRNA expression of 34 genes involved in AA and DHA metabolism. Expression patterns were split into Development (0 to 20 years) and Aging (21 to 78 years) intervals. Expression of genes for cytosolic phospholipases A2 (cPLA2), cyclooxygenases (COX)-1 and -2, and other AA cascade enzymes, correlated closely with age during Development, less so during Aging. Expression of DHA cascade enzymes was less inter-correlated in each period, but often changed in the opposite direction to expression of AA cascade genes. Except for the PLA2G4A (cPLA2 IVA) and PTGS2 (COX-2) genes at 1q25, highly inter-correlated genes were at distant chromosomal loci. Coordinated age-related gene expression during the brain Development and Aging intervals likely underlies coupled changes in enzymes of the AA and DHA cascades and largely occur through distant transcriptional regulation. Healthy brain aging does not show upregulation of PLA2G4 or PTGS2 expression, which was found in Alzheimer's disease.

  15. Metabolism of arachidonic acid in 1 yr old New Zealand white (NZW) and watanabe heritable hyperlipidemic (WHHL) rabbit aortas

    International Nuclear Information System (INIS)

    Pfister, S.L.; Schmitz, J.M.; Willerson, J.T.; Campbell, W.B.

    1986-01-01

    This study was designed to characterize the metabolism of arachidonic acid (AA) in normal and atherosclerotic aortas. Segments of aortas were obtained from 1 yr old NZW rabbits, and WHHL rabbits, a genetic model of athero-sclerosis resembling familial hypercholesterolemia. Aortas were incubated at 37 0 C for 15 min with 14 C-AA (5 x 10 -5 M) during stimulation by A23187. The media was extracted using octadecylsilica columns and resolved into metabolites by reverse-phase HPLC. Prostaglandins (PGs) were identified by comigration of 14 C-metabolites with standards. The monoxygenated metabolites of AA (HETEs) were resolved by normal-phase HPLC, and their structures confirmed by GC-MS. In extracts from NZW and WHHL aortas, approximately 14% and 6% of the total radioactivity was converted to PGs and HETEs, respectively. The major PG produced by NZW and WHHL aortas was 6-keto PGF/sub 1α/ with lesser amounts of PGE 2 . Similarly, NZW and WHHL aortas produced primarily 12- and 15-HETE with lesser amounts of 11-, 9-, 8-, and 5-HETE. There were no qualitative differences between NZW and WHHL aortas in PG and HETE production. Therefore, despite extensive atherosclerosis in aortas of WHHL rabbits, the vessels maintain the ability to synthesize PGs and HETEs

  16. Coordination of gene expression of arachidonic and docosahexaenoic acid cascade enzymes during human brain development and aging.

    Directory of Open Access Journals (Sweden)

    Veronica H Ryan

    Full Text Available The polyunsaturated arachidonic and docosahexaenoic acids (AA and DHA participate in cell membrane synthesis during neurodevelopment, neuroplasticity, and neurotransmission throughout life. Each is metabolized via coupled enzymatic reactions within separate but interacting metabolic cascades.AA and DHA pathway genes are coordinately expressed and underlie cascade interactions during human brain development and aging.The BrainCloud database for human non-pathological prefrontal cortex gene expression was used to quantify postnatal age changes in mRNA expression of 34 genes involved in AA and DHA metabolism.Expression patterns were split into Development (0 to 20 years and Aging (21 to 78 years intervals. Expression of genes for cytosolic phospholipases A2 (cPLA2, cyclooxygenases (COX-1 and -2, and other AA cascade enzymes, correlated closely with age during Development, less so during Aging. Expression of DHA cascade enzymes was less inter-correlated in each period, but often changed in the opposite direction to expression of AA cascade genes. Except for the PLA2G4A (cPLA2 IVA and PTGS2 (COX-2 genes at 1q25, highly inter-correlated genes were at distant chromosomal loci.Coordinated age-related gene expression during the brain Development and Aging intervals likely underlies coupled changes in enzymes of the AA and DHA cascades and largely occur through distant transcriptional regulation. Healthy brain aging does not show upregulation of PLA2G4 or PTGS2 expression, which was found in Alzheimer's disease.

  17. 12(R)-hydroxyicosatetraenoic acid: a cytochrome P450-dependent arachidonate metabolite that inhibits Na+, K+-ATPase in the cornea

    International Nuclear Information System (INIS)

    Schwartzman, M.L.; Balazy, M.; Masferrer, J.; Abraham, N.G.; McGiff, J.C.; Murphy, R.C.

    1987-01-01

    When corneal microsomes were incubated with arachidonic acid in the presence of an NADPH-generating system, four polar metabolites (compounds A-D) were formed. Synthesis of these metabolites could be inhibited by carbon monoxide, SKF 525A, and anti-cytochrome c reductase antibodies. One of the metabolites, compound C, was found to inhibit partially purified Na + , K + -ATPase from the corneal epithelium in a dose-dependent manner. After compound C was purified by TLC and HPLC, it was found to have a UV absorption spectrum with a maximum absorbance at 236 nm suggesting the presence of a conjugated diene. Mass spectrometric analysis using positive- and negative-ionization modes was carried out on derivatized compound C. Abundant fragment ions were consistent with compound C being a monooxygenated derivative of arachidonic acid with a hydroxyl substituent at carbon-12 of the icosanoid backbone; all deuterium atoms from [ 2 H 8 ]arachidonate were retained in the structure. Compound C was characterized as a 12-hydroxyicosatetraenoic acid. However, only 12(R) isomer was found to be an inhibitor of the Na + , K + -ATPase from the corneal epithelium, suggesting that the biologically active compound C was 12(R)-hydroxyy-5,8,10,14-icosatetraenoic acid. Such an inhibitor of Na + , K + -ATPase synthesized in the cornea may have an important role in regulating ocular transparency and aqueous human secretion

  18. 12(R)-hydroxyicosatetraenoic acid: a cytochrome P450-dependent arachidonate metabolite that inhibits Na/sup +/, K/sup +/-ATPase in the cornea

    Energy Technology Data Exchange (ETDEWEB)

    Schwartzman, M.L.; Balazy, M.; Masferrer, J.; Abraham, N.G.; McGiff, J.C.; Murphy, R.C.

    1987-11-01

    When corneal microsomes were incubated with arachidonic acid in the presence of an NADPH-generating system, four polar metabolites (compounds A-D) were formed. Synthesis of these metabolites could be inhibited by carbon monoxide, SKF 525A, and anti-cytochrome c reductase antibodies. One of the metabolites, compound C, was found to inhibit partially purified Na/sup +/, K/sup +/-ATPase from the corneal epithelium in a dose-dependent manner. After compound C was purified by TLC and HPLC, it was found to have a UV absorption spectrum with a maximum absorbance at 236 nm suggesting the presence of a conjugated diene. Mass spectrometric analysis using positive- and negative-ionization modes was carried out on derivatized compound C. Abundant fragment ions were consistent with compound C being a monooxygenated derivative of arachidonic acid with a hydroxyl substituent at carbon-12 of the icosanoid backbone; all deuterium atoms from (/sup 2/H/sub 8/)arachidonate were retained in the structure. Compound C was characterized as a 12-hydroxyicosatetraenoic acid. However, only 12(R) isomer was found to be an inhibitor of the Na/sup +/, K/sup +/-ATPase from the corneal epithelium, suggesting that the biologically active compound C was 12(R)-hydroxyy-5,8,10,14-icosatetraenoic acid. Such an inhibitor of Na/sup +/, K/sup +/-ATPase synthesized in the cornea may have an important role in regulating ocular transparency and aqueous human secretion.

  19. Hydroxyurea Therapy Mobilises Arachidonic Acid from Inner Cell Membrane Aminophospholipids in Patients with Homozygous Sickle Cell Disease

    Directory of Open Access Journals (Sweden)

    A. A. Daak

    2011-01-01

    Full Text Available The cytotoxic compound hydroxyurea (HU is effective therapy for sickle cell disease. However, its effect on unsaturated membrane lipids is unknown. Red cell fatty acids were investigated in HU-treated (n=19 and HU-untreated (n=17 sickle cell patients and controls (n=20. The HU-treated compared with the HU-untreated patients had lower arachidonic (AA acid level in ethanolamine, physphoglycerids (EPG (22.9±1.2   versus   24.0±1.1%,  P<0.05 serine SPG (22.13±2.2   versus   24.9±2.3%,  P<0.01 phosphoglycerides. The treated patients and controls had comparable levels of docosahexaenoic (DHA and total n-3 fatty acids in EPG and choline phosphoglycerides (CPG. In contrast, the untreated group had significantly (P<0.05 lower DHA and total n-3 compared with the controls in EPG (2.7±0.4   versus   3.2±0.6% and 4.6±0.5   versus   5.2±0.7% and CPG (0.7±0.2   versus   1.0±0.2% and 1.2±0.2   versus   1.4±0.3. HU is known to activate cytosolic phospholipase A2 and cyclooxygenase 2, and from this study, it appears to induce mobilisation of AA from the inner cell membrane EPG and SPG. Hence, eicosanoids generated from the released AA may play a role in clinical improvements which occur in HU-treated patients.

  20. Arachidonic acid metabolomic study of BPH in rats and the interventional effects of Zishen pill, a traditional Chinese medicine.

    Science.gov (United States)

    Bian, Qiaoxia; Wang, Weihui; Wang, Nannan; Peng, Yan; Ma, Wen; Dai, Ronghua

    2016-09-05

    Zishen pill (ZSP) is a traditional Chinese medicine (TCM) used to treat benign prostatic hyperplasia (BPH). The study used a metabolomic approach based on UHPLC-MS/MS to profile arachidonic acid (AA) metabolic changes and to investigate the interventional mechanisms of ZSP in testosterone- induced BPH rats. In order to explore the potential therapeutic effect of ZSP, rat models were constructed and orally administrated with ZSP. Plasma and urine samples were collected after four weeks and then eleven potential biomarkers (15-HETE, 12-HETE, TXA2, 5-HETE, AA, PGI2, PGF2α, 8-HETE, PGD2, PGE2 and LTB4) were identified and quantified by UHPLC-MS/MS. The chromatographic separation was carried out with gradient elution using a mobile phase comprised of 0.05% formic acid aqueous solution (pH=3.3) (A) and acetonitrile: methanol (80:20, V/V) (B), and each AA metabolites was measured using electrospray ionization source with negative mode and multiple reaction monitoring. The eleven biomarkers in BPH group rat plasma and urine were significant higher than those in sham group rats. Using the potential biomarkers as a screening index, the results suggest that ZSP can potentially reverse the process of BPH by partially regulating AA metabolism through refrain the expression of cyclooxygenase (COX) and lipoxygenase (LOX). This study demonstrates that a metabolomic strategy is useful for identifying potential BPH biomarkers and investigating the underlying mechanisms of a TCM in BPH treatment. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Anti-inflammatory effects of benfotiamine are mediated through the regulation of the arachidonic acid pathway in macrophages.

    Science.gov (United States)

    Shoeb, Mohammad; Ramana, Kota V

    2012-01-01

    Benfotiamine, a lipid-soluble analogue of vitamin B1, is a potent antioxidant that is used as a food supplement for the treatment of diabetic complications. Our recent study (U.C. Yadav et al., Free Radic. Biol. Med. 48:1423-1434, 2010) indicates a novel role for benfotiamine in the prevention of bacterial endotoxin, lipopolysaccharide (LPS)-induced cytotoxicity and inflammatory response in murine macrophages. Nevertheless, it remains unclear how benfotiamine mediates anti-inflammatory effects. In this study, we investigated the anti-inflammatory role of benfotiamine in regulating arachidonic acid (AA) pathway-generated inflammatory lipid mediators in RAW264.7 macrophages. Benfotiamine prevented the LPS-induced activation of cPLA2 and release of AA metabolites such as leukotrienes, prostaglandin E2, thromboxane 2 (TXB2), and prostacyclin (PGI2) in macrophages. Further, LPS-induced expression of AA-metabolizing enzymes such as COX-2, LOX-5, TXB synthase, and PGI2 synthase was significantly blocked by benfotiamine. Furthermore, benfotiamine prevented the LPS-induced phosphorylation of ERK1/2 and expression of transcription factors NF-κB and Egr-1. Benfotiamine also prevented the LPS-induced oxidative stress and protein-HNE adduct formation. Most importantly, compared to specific COX-2 and LOX-5 inhibitors, benfotiamine significantly prevented LPS-induced macrophage death and monocyte adhesion to endothelial cells. Thus, our studies indicate that the dual regulation of the COX and LOX pathways in AA metabolism could be a novel mechanism by which benfotiamine exhibits its potential anti-inflammatory response. Copyright © 2011 Elsevier Inc. All rights reserved.

  2. Anti-Inflammatory Effects of Benfotiamine are Mediated Through the Regulation of Arachidonic Acid Pathway in Macrophages

    Science.gov (United States)

    Shoeb, Mohammad; Ramana, Kota V

    2011-01-01

    Benfotiamine, a lipid-soluble analogue of vitamin B1, is a potent anti-oxidant that is used as a food supplement for the treatment of diabetic complications. Our recent study indicates a novel role of benfotiamine in the prevention of bacterial endotoxin, lipopolysaccharide (LPS)-induced cytotoxicity and inflammatory response in murine macrophages. Nevertheless, it remains unclear how benfotiamine mediates anti-inflammatory effects. In this study, we investigated the anti-inflammatory role of benfotiamine in regulating the arachidonic acid (AA) pathway generated inflammatory lipid mediators in RAW 264.7 macrophages. Benfotiamine prevented the LPS-induced activation of cPLA2 and release of AA metabolites such as leukotrienes (LTB4), prostaglandin E2 (PGE2), thromboxanes 2 (TXB2) and prostacyclin (PGI2) in macrophages. Further, LPS-induced expressions of AA metabolizing enzymes such as COX-2, LOX-5, TXB synthase and PGI2 synthase were significantly blocked by benfotiamine. Furthermore, benfotiamine prevented the LPS-induced phosphorylation of ERK1/2 and expression of transcription factors NF-kB, and Egr-1. Benfotiamine also prevented the LPS-induced oxidative stress and protein-HNE adducts formation. Most importantly, as compared to specific COX-2 and LOX-5 inhibitors, benfotiamine significantly prevented the LPS-induced macrophage death and monocytes adhesion to endothelial cells. Thus, our studies indicate that the dual regulation of COX and LOX pathways in AA metabolism could be a novel mechanism by which benfotiamine exhibits its potential anti-inflammatory response. PMID:22067901

  3. Platelet Arachidonic Acid Deficiency May Contribute to Abnormal Platelet Function During Parenteral Fish Oil Monotherapy in a Piglet Model.

    Science.gov (United States)

    Turner, Justine M; Field, Catherine J; Goruk, Sue; Wizzard, Pamela; Dicken, Bryan J; Bruce, Aisha; Wales, Paul W

    2016-05-01

    Fish oil monotherapy has been an advance for treating intestinal failure-associated liver disease (IFALD). However, such patients are at risk of bleeding complications from liver disease and because fish oil can inhibit thrombosis. We have previously reported abnormal platelet function in neonatal piglets given fish oil monotherapy during parenteral nutrition (PN). The purpose of this study was to determine if abnormal fatty acid composition of the platelets could explain the prior observed antiplatelet effect. Neonatal piglets were assigned to 2 treatments: PN with fish oil monotherapy (FO; n = 4) or PN with soy oil (SO; n = 5). On day 14, plasma was collected and platelets isolated by centrifuging. The fatty acid content in plasma and platelet plug were measured using gas liquid chromatography and compared with controls (CON; n = 5). The arachidonic acid (AA) content in the FO group was on average half that of the SO group, in both the platelets (FO, 3.5% vs SO, 7.6%; P = .021; CON, 4.5%-11%) and the plasma (FO, 3.8% vs SO, 9.2%; P = .002; CON, 6.1%-9.5%). No bleeding complications were observed for any piglets during PN treatment. Using platelet mapping, we have previously shown that neonatal piglets given fish oil monotherapy have abnormal platelet function in the AA pathway. This report demonstrates that such an abnormality can be explained by platelet AA deficiency. Platelet mapping and platelet fatty acid analysis should be undertaken in human infants treated with fish oil monotherapy during PN. © 2015 American Society for Parenteral and Enteral Nutrition.

  4. Arachidonic Acid-Induced Expression of the Organic Solute and Steroid Transporter-beta (Ost-beta) in a Cartilaginous Fish Cell Line

    Science.gov (United States)

    Hwang, Jae-Ho; Parton, Angela; Czechanski, Anne; Ballatori, Nazzareno; Barnes, David

    2008-01-01

    The organic solute and steroid transporter (OST/Ost) is a unique membrane transport protein heterodimer composed of subunits designated alpha and beta, that transports conjugated steroids and prostaglandin E2 across the plasma membrane. Ost was first identified in the liver of the cartilaginous fish Leucoraja erinacea, the little skate, and subsequently was found in many other species, including humans and rodents. The present study describes the isolation of a new cell line, LEE-1, derived from an early embryo of L. erinacea, and characterizes the expression of Ost in these cells. The mRNA size and amino acid sequence of Ost-beta in LEE-1 was identical to that previously reported for Ost-beta from skate liver, and the primary structure was identical to that of the spiny dogfish shark (Squalus acanthias) with the exception of a single amino acid. Ost-beta was found both on the plasma membrane and intracellularly in LEE-1 cells, consistent with its localization in other cell types. Interestingly, arachidonic acid, the precursor to eiconsanoids, strongly induced Ost-beta expression in LEE-1 cells and a lipid mixture containing arachidonic acid also induced Ost-alpha. Overall, the present study describes the isolation of a novel marine cell line, and shows that this cell line expresses relatively high levels of Ost when cultured in the presence of arachidonic acid. Although the function of this transport protein in embryo-derived cells is unknown, it may play a role in the disposition of eicosanoids or steroid-derived molecules. PMID:18407792

  5. Increasing the Fungicidal Action of Amphotericin B by Inhibiting the Nitric Oxide-Dependent Tolerance Pathway

    Directory of Open Access Journals (Sweden)

    Kim Vriens

    2017-01-01

    Full Text Available Amphotericin B (AmB induces oxidative and nitrosative stresses, characterized by production of reactive oxygen and nitrogen species, in fungi. Yet, how these toxic species contribute to AmB-induced fungal cell death is unclear. We investigated the role of superoxide and nitric oxide radicals in AmB’s fungicidal activity in Saccharomyces cerevisiae, using a digital microfluidic platform, which enabled monitoring individual cells at a spatiotemporal resolution, and plating assays. The nitric oxide synthase inhibitor L-NAME was used to interfere with nitric oxide radical production. L-NAME increased and accelerated AmB-induced accumulation of superoxide radicals, membrane permeabilization, and loss of proliferative capacity in S. cerevisiae. In contrast, the nitric oxide donor S-nitrosoglutathione inhibited AmB’s action. Hence, superoxide radicals were important for AmB’s fungicidal action, whereas nitric oxide radicals mediated tolerance towards AmB. Finally, also the human pathogens Candida albicans and Candida glabrata were more susceptible to AmB in the presence of L-NAME, pointing to the potential of AmB-L-NAME combination therapy to treat fungal infections.

  6. Long-term aerobic exercise increases redox-active iron through nitric oxide in rat hippocampus.

    Science.gov (United States)

    Chen, Qian; Xiao, De-Sheng

    2014-01-30

    Adult hippocampus is highly vulnerable to iron-induced oxidative stress. Aerobic exercise has been proposed to reduce oxidative stress but the findings in the hippocampus are conflicting. This study aimed to observe the changes of redox-active iron and concomitant regulation of cellular iron homeostasis in the hippocampus by aerobic exercise, and possible regulatory effect of nitric oxide (NO). A randomized controlled study was designed in the rats with swimming exercise treatment (for 3 months) and/or an unselective inhibitor of NO synthase (NOS) (L-NAME) treatment. The results from the bleomycin-detectable iron assay showed additional redox-active iron in the hippocampus by exercise treatment. The results from nonheme iron content assay, combined with the redox-active iron content, showed increased storage iron content by exercise treatment. NOx (nitrate plus nitrite) assay showed increased NOx content by exercise treatment. The results from the Western blot assay showed decreased ferroportin expression, no changes of TfR1 and DMT1 expressions, increased IRP1 and IRP2 expression, increased expressions of eNOS and nNOS rather than iNOS. In these effects of exercise treatment, the increased redox-active iron content, storage iron content, IRP1 and IRP2 expressions were completely reversed by L-NAME treatment, and decreased ferroportin expression was in part reversed by L-NAME. L-NAME treatment completely inhibited increased NOx and both eNOS and nNOS expression in the hippocampus. Our findings suggest that aerobic exercise could increase the redox-active iron in the hippocampus, indicating an increase in the capacity to generate hydroxyl radicals through the Fenton reactions, and aerobic exercise-induced iron accumulation in the hippocampus might mainly result from the role of the endogenous NO. Copyright © 2013 Elsevier Inc. All rights reserved.

  7. Fabp1 gene ablation inhibits high-fat diet-induced increase in brain endocannabinoids.

    Science.gov (United States)

    Martin, Gregory G; Landrock, Danilo; Chung, Sarah; Dangott, Lawrence J; Seeger, Drew R; Murphy, Eric J; Golovko, Mikhail Y; Kier, Ann B; Schroeder, Friedhelm

    2017-01-01

    The endocannabinoid system shifts energy balance toward storage and fat accumulation, especially in the context of diet-induced obesity. Relatively little is known about factors outside the central nervous system that may mediate the effect of high-fat diet (HFD) on brain endocannabinoid levels. One candidate is the liver fatty acid binding protein (FABP1), a cytosolic protein highly prevalent in liver, but not detected in brain, which facilitates hepatic clearance of fatty acids. The impact of Fabp1 gene ablation (LKO) on the effect of high-fat diet (HFD) on brain and plasma endocannabinoid levels was examined and data expressed for each parameter as the ratio of high-fat diet/control diet. In male wild-type mice, HFD markedly increased brain N-acylethanolamides, but not 2-monoacylglycerols. LKO blocked these effects of HFD in male mice. In female wild-type mice, HFD slightly decreased or did not alter these endocannabinoids as compared with male wild type. LKO did not block the HFD effects in female mice. The HFD-induced increase in brain arachidonic acid-derived arachidonoylethanolamide in males correlated with increased brain-free and total arachidonic acid. The ability of LKO to block the HFD-induced increase in brain arachidonoylethanolamide correlated with reduced ability of HFD to increase brain-free and total arachidonic acid in males. In females, brain-free and total arachidonic acid levels were much less affected by either HFD or LKO in the context of HFD. These data showed that LKO markedly diminished the impact of HFD on brain endocannabinoid levels, especially in male mice. © 2016 International Society for Neurochemistry.

  8. Arachidonic acid/docosahexaenoic acid-supplemented diet in early life reduces body weight gain, plasma lipids, and adiposity in later life in ApoE*3 Leiden mice

    NARCIS (Netherlands)

    Wielinga, P.Y.; Harthoorn, L.F.; Verschuren, L.; Schoemaker, M.H.; Jouni, Z.E.; Tol, E.A.F. van; Kleemann, R.; Kooistra, T.

    2012-01-01

    Scope: This study addresses whether early life arachidonic acid (ARA)/docosahexaenoic acid (DHA) supplementation or eicosapentaenoic acid (EPA)/DHA (Omacor) supplementation affects body weight gain, lipid metabolism, and adipose tissue quantity and quality in later life in ApoE*3Leiden-transgenic

  9. The effect of non-steroidal anti-inflammatory drugs on the metabolism of /sup 14/C-arachidonic acid by human gingival tissue in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Elattar, T.M.; Lin, H.S.; Tira, D.E.

    1983-09-01

    We investigated the effect of non-steroidal anti-inflammatory drugs on prostaglandins (PGs) and 12-hydroxyeicosatetraenoic acid (12-HETE) formation by inflamed human gingival tissues. Gingival tissue homogenates were incubated with /sup 14/C-arachidonic acid in the presence of indomethacin, piroxicam, or ibuprofen, and the organic solvent extracts were chromatographed on silica gel plates with standards for radiometric assay. There was a significant negative trend between the doses (10(-7)-10(-3) M) of each of indomethacin, piroxicam, and ibuprofen, and the amounts of PGF2 alpha, PGE2, PGD2, and 15-keto-PGE2 produced. All three drugs have a significant inhibitory effect on PGs and 12-HETE production at 10(-3) M when compared with the control. The rank order effectiveness of the drugs, at 10(-3) M, on PG inhibition was indomethacin greater than piroxicam greater than ibuprofen, and on 12-HETE inhibition was indomethacin greater than ibuprofen greater than piroxicam.

  10. The effect of non-steroidal anti-inflammatory drugs on the metabolism of 14C-arachidonic acid by human gingival tissue in vitro

    International Nuclear Information System (INIS)

    Elattar, T.M.; Lin, H.S.; Tira, D.E.

    1983-01-01

    We investigated the effect of non-steroidal anti-inflammatory drugs on prostaglandins (PGs) and 12-hydroxyeicosatetraenoic acid (12-HETE) formation by inflamed human gingival tissues. Gingival tissue homogenates were incubated with 14 C-arachidonic acid in the presence of indomethacin, piroxicam, or ibuprofen, and the organic solvent extracts were chromatographed on silica gel plates with standards for radiometric assay. There was a significant negative trend between the doses (10(-7)-10(-3) M) of each of indomethacin, piroxicam, and ibuprofen, and the amounts of PGF2 alpha, PGE2, PGD2, and 15-keto-PGE2 produced. All three drugs have a significant inhibitory effect on PGs and 12-HETE production at 10(-3) M when compared with the control. The rank order effectiveness of the drugs, at 10(-3) M, on PG inhibition was indomethacin greater than piroxicam greater than ibuprofen, and on 12-HETE inhibition was indomethacin greater than ibuprofen greater than piroxicam

  11. Effect of dietary arachidonic acid, eicosapentaenoic acid and docosahexaenoic acid on survival, growth and pigmentation in larvae of common sole ( Solea solea L.)

    DEFF Research Database (Denmark)

    Lund, Ivar; Steenfeldt, Svend Jørgen; Hansen, B.W.

    2007-01-01

    Evidence confirms that polyunsaturated fatty acids (PUFAs), arachidonic acid (ARA), eicosapentaenoic acid (EPA) and docosahexaenoic acid, DHA are involved in growth as well in pigmentation of marine fish larvae. In the present study we examined the performance of common sole larvae reared...... on Artemia enriched with 10 formulated emulsions, differing in inclusions of ARA, EPA, and DHA. The specific growth rate of the sole larvae until late metamorphosis, 21 days after hatching (dah) was 20 to 27% d(-1). Even though the relative tissue essential fatty acid (EFA) concentrations significantly...... reflected dietary composition, neither standard growth nor larval survival were significantly related to the absolute concentrations of ARA, EPA and DHA or their ratios. This suggests low requirements for essential polyunsaturated fatty acids (PUFAs) in common sole. Malpigmentation was significantly related...

  12. Studies of insulin secretory responses and of arachidonic acid incorporation into phospholipids of stably transfected insulinoma cells that overexpress group VIA phospholipase A2 (iPLA2beta ) indicate a signaling rather than a housekeeping role for iPLA2beta.

    Science.gov (United States)

    Ma, Z; Ramanadham, S; Wohltmann, M; Bohrer, A; Hsu, F F; Turk, J

    2001-04-20

    A cytosolic 84-kDa group VIA phospholipase A(2) (iPLA(2)beta) that does not require Ca(2+) for catalysis has been cloned from several sources, including rat and human pancreatic islet beta-cells and murine P388D1 cells. Many potential iPLA(2)beta functions have been proposed, including a signaling role in beta-cell insulin secretion and a role in generating lysophosphatidylcholine acceptors for arachidonic acid incorporation into P388D1 cell phosphatidylcholine (PC). Proposals for iPLA(2)beta function rest in part on effects of inhibiting iPLA(2)beta activity with a bromoenol lactone (BEL) suicide substrate, but BEL also inhibits phosphatidate phosphohydrolase-1 and a group VIB phospholipase A(2). Manipulation of iPLA(2)beta expression by molecular biologic means is an alternative approach to study iPLA(2)beta functions, and we have used a retroviral construct containing iPLA(2)beta cDNA to prepare two INS-1 insulinoma cell clonal lines that stably overexpress iPLA(2)beta. Compared with parental INS-1 cells or cells transfected with empty vector, both iPLA(2)beta-overexpressing lines exhibit amplified insulin secretory responses to glucose and cAMP-elevating agents, and BEL substantially attenuates stimulated secretion. Electrospray ionization mass spectrometric analyses of arachidonic acid incorporation into INS-1 cell PC indicate that neither overexpression nor inhibition of iPLA(2)beta affects the rate or extent of this process in INS-1 cells. Immunocytofluorescence studies with antibodies directed against iPLA(2)beta indicate that cAMP-elevating agents increase perinuclear fluorescence in INS-1 cells, suggesting that iPLA(2)beta associates with nuclei. These studies are more consistent with a signaling than with a housekeeping role for iPLA(2)beta in insulin-secreting beta-cells.

  13. Decreased Polyunsaturated Fatty Acid Content Contributes to Increased Survival in Human Colon Cancer

    Directory of Open Access Journals (Sweden)

    Manuela Oraldi

    2009-01-01

    Full Text Available Among diet components, some fatty acids are known to affect several stages of colon carcinogenesis, whereas others are probably helpful in preventing tumors. In light of this, our aim was to determine the composition of fatty acids and the possible correlation with apoptosis in human colon carcinoma specimens at different Duke's stages and to evaluate the effect of enriching human colon cancer cell line with the possible reduced fatty acid(s. Specimens of carcinoma were compared with the corresponding non-neoplastic mucosa: a significant decrease of arachidonic acid, PPARα, Bad, and Bax and a significant increase of COX-2, Bcl-2, and pBad were found. The importance of arachidonic acid in apoptosis was demonstrated by enriching a Caco-2 cell line with this fatty acid. It induced apoptosis in a dose- and time-dependent manner via induction of PPARα that, in turn, decreased COX-2. In conclusion, the reduced content of arachidonic acid is likely related to carcinogenic process decreasing the susceptibility of cancer cells to apoptosis.

  14. Isoliquiritigenin induces growth inhibition and apoptosis through downregulating arachidonic acid metabolic network and the deactivation of PI3K/Akt in human breast cancer

    International Nuclear Information System (INIS)

    Li, Ying; Zhao, Haixia; Wang, Yuzhong; Zheng, Hao; Yu, Wei; Chai, Hongyan; Zhang, Jing; Falck, John R.; Guo, Austin M.; Yue, Jiang; Peng, Renxiu; Yang, Jing

    2013-01-01

    Arachidonic acid (AA)-derived eicosanoids and its downstream pathways have been demonstrated to play crucial roles in growth control of breast cancer. Here, we demonstrate that isoliquiritigenin, a flavonoid phytoestrogen from licorice, induces growth inhibition and apoptosis through downregulating multiple key enzymes in AA metabolic network and the deactivation of PI3K/Akt in human breast cancer. Isoliquiritigenin diminished cell viability, 5-bromo-2′-deoxyuridine (BrdU) incorporation, and clonogenic ability in both MCF-7 and MDA-MB-231cells, and induced apoptosis as evidenced by an analysis of cytoplasmic histone-associated DNA fragmentation, flow cytometry and hoechst staining. Furthermore, isoliquiritigenin inhibited mRNA expression of multiple forms of AA-metabolizing enzymes, including phospholipase A2 (PLA2), cyclooxygenases (COX)-2 and cytochrome P450 (CYP) 4A, and decreased secretion of their products, including prostaglandin E 2 (PGE 2 ) and 20-hydroxyeicosatetraenoic acid (20-HETE), without affecting COX-1, 5-lipoxygenase (5-LOX), 5-lipoxygenase activating protein (FLAP), and leukotriene B 4 (LTB 4 ). In addition, it downregulated the levels of phospho-PI3K, phospho-PDK (Ser 241 ), phospho-Akt (Thr 308 ), phospho-Bad (Ser 136 ), and Bcl-x L expression, thereby activating caspase cascades and eventually cleaving poly(ADP-ribose) polymerase (PARP). Conversely, the addition of exogenous eicosanoids, including PGE 2 , LTB 4 and a 20-HETE analog (WIT003), and caspase inhibitors, or overexpression of constitutively active Akt reversed isoliquiritigenin-induced apoptosis. Notably, isoliquiritigenin induced growth inhibition and apoptosis of MDA-MB-231 human breast cancer xenografts in nude mice, together with decreased intratumoral levels of eicosanoids and phospho-Akt (Thr 308 ). Collectively, these data suggest that isoliquiritigenin induces growth inhibition and apoptosis through downregulating AA metabolic network and the deactivation of PI3K/Akt in

  15. Pro-oxidant activity of indicaxanthin from Opuntia ficus indica modulates arachidonate metabolism and prostaglandin synthesis through lipid peroxide production in LPS-stimulated RAW 264.7 macrophages

    OpenAIRE

    M. Allegra; F. D’Acquisto; L. Tesoriere; A. Attanzio; M.A. Livrea

    2014-01-01

    Macrophages come across active prostaglandin (PG) metabolism during inflammation, shunting early production of pro-inflammatory towards anti-inflammatory mediators terminating the process. This work for the first time provides evidence that a phytochemical may modulate the arachidonate (AA) metabolism in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages, promoting the ultimate formation of anti-inflammatory cyclopentenone 15deoxy-PGJ2. Added 1 h before LPS, indicaxanthin from Opuntia ...

  16. Transient postnatal fluoxetine decreases brain concentrations of 20-HETE and 15-epi-LXA4, arachidonic acid metabolites in adult mice.

    Science.gov (United States)

    Yuan, Zhi-Xin; Rapoport, Stanley I

    2015-10-01

    Transient postnatal exposure of rodents to the selective serotonin (5-HT) reuptake inhibitor (SSRI) fluoxetine alters behavior and brain 5-HT neurotransmission during adulthood, and also reduces brain arachidonic (ARA) metabolic consumption and protein level of the ARA metabolizing enzyme, cytochrome P4504A (CYP4A). Brain 20-hydroxyeicosatetraenoic acid (20-HETE), converted by CYP4A from ARA, will be reduced in adult mice treated transiently and postnatally with fluoxetine. Male mice pups were injected i.p. daily with fluoxetine (10mg/kg) or saline during P4-P21. At P90 their brain was high-energy microwaved and analyzed for 20-HETE and six other ARA metabolites by enzyme immunoassay. Postnatal fluoxetine vs. saline significantly decreased brain concentrations of 20-HETE (-70.3%) and 15-epi-lipoxin A4 (-60%) in adult mice, but did not change other eicosanoid concentrations. Behavioral changes in adult mice treated postnatally with fluoxetine may be related to reduced brain ARA metabolism involving CYP4A and 20-HETE formation. Published by Elsevier Ltd.

  17. Prostacyclin production in rabbit arteries in situ: inhibition by arachidonic acid-induced endothelial cell damage or by low-dose aspirin.

    Science.gov (United States)

    Ingerman-Wojenski, C; Silver, M J; Smith, J B; Nissenbaum, M; Sedar, A W

    1981-04-01

    The central artery of the rabbit ear was perfused in situ and effluent fractions from the artery were assayed for 6-keto-prostaglandin F1 alpha (6-K-PGF1 alpha) and thromboxane B2 (TxB2), the stable metabolites of prostacyclin (PGI2) and TxA2, using specific radioimmunoassays. These metabolites of arachidonic acid (AA) were not detected in the effluent during infusion of Tyrode's solution but both metabolites were detected when small amounts of AA were infused into the artery. Examination of the arteries by scanning electron microscopy revealed that high concentrations of AA which caused a short burst of 6-K-PGF1 alpha and TxB2 production damaged the endothelial cells while lower concentrations which stimulated continuous production did not cause damage. When a non-damaging concentration of AA was infused into an artery that had previously received a damaging concentration, PG production was greatly reduced. Pretreatment of the rabbits with 4 mg/kg acetyl-salicylic acid (ASA) inhibited 6-K-PGF1 alpha production by the rabbit ear artery in response to AA and 70% inhibition was still evident 18 hours after ASA.

  18. The role of the arachidonic acid cascade in the species-specific X-ray-induced inflammation of the rabbit eye

    International Nuclear Information System (INIS)

    Bito, L.Z.; Klein, E.M.

    1982-01-01

    To identify the mediator(s) of the apparently species-specific X-ray-induced inflammation of the rabbit eye, inhibitors of the synthesis and/or release of known or putative mediators of ocular inflammation were administered prior to irradiation. The X-ray-induced ocular inflammation, particularly the rise in intraocular pressure, was found to be inhibited by intravenous pretreatment of rabbits with flurbiprofen, indomethacin, or imidazole (1, 10, and 100 mg/kg i.v., respectively), or by combined intravitreal and topical administration of flurbiprofen. Systemic, intravitreal, and/or topical pretreatment with prednisolone or disodium cromoglycate or the retrobulbar injection of ethyl alcohol or capsaicin failed to block the inflammatory response, whereas vitamin E apparently exerted some protective effect. These findings show that the X-ray-induced inflammation of the rabbit eye is mediated, at least in part, by prostaglandins (PGs) and/or related autacoids. In addition, these results suggest that the unique sensitivity of the rabbit eye to X-ray-induced inflammation is due either to the presence in this species of a unique or uniquely effective triggering mechanism for the release of PG precursors or to the greater sensitivity of this species to the ocular inflammatory effects of PGs. Thus the rabbit eye may provide a unique model for studying some aspects of arachidonic acid release or ocular PG effects, but extreme caution must be exercised in generalizing such findings to other species

  19. On methods for the detection of reactive oxygen species generation by human spermatozoa: analysis of the cellular responses to catechol oestrogen, lipid aldehyde, menadione and arachidonic acid.

    Science.gov (United States)

    Aitken, R J; Smith, T B; Lord, T; Kuczera, L; Koppers, A J; Naumovski, N; Connaughton, H; Baker, M A; De Iuliis, G N

    2013-03-01

    Oxidative stress is known to have a major impact on human sperm function and, as a result, there is a need to develop sensitive methods for measuring reactive oxygen species (ROS) generation by these cells. A variety of techniques have been developed for this purpose including chemiluminescence (luminol and lucigenin), flow cytometry (MitoSOX Red, dihydroethidium, 4,5-diaminofluorescein diacetate and 2',7'-dichlorodihydrofluorescein diacetate) and spectrophotometry (nitroblue tetrazolium). The relative sensitivity of these assays and their comparative ability to detect ROS generated in different subcellular compartments of human spermatozoa, have not previously been investigated. To address this issue, we have compared the performance of these assays when ROS generation was triggered with a variety of reagents including 2-hydroxyestradiol, menadione, 4-hydroxynonenal and arachidonic acid. The results revealed that menadione predominantly induced release of ROS into the extracellular space where these metabolites could be readily detected by luminol-peroxidase and, to a lesser extent, 2',7'-dichlorodihydrofluorescein. However, such sensitivity to extracellular ROS meant that these assays were particularly vulnerable to interference by leucocytes. The remaining reagents predominantly elicited ROS generation by the sperm mitochondria and could be optimally detected by MitoSOX Red and DHE. Examination of spontaneous ROS generation by defective human spermatozoa revealed that MitoSOX Red was the most effective indicator of oxidative stress, thereby emphasizing the general importance of mitochondrial dysregulation in the aetiology of defective sperm function. © 2013 American Society of Andrology and European Academy of Andrology.

  20. Comparison of the effect of timegadine, levamisole, and D-penicillamine on human neutrophil metabolism of endogenous arachidonic acid and chemotaxis

    Energy Technology Data Exchange (ETDEWEB)

    Nielsen, O.H.; Ahnfelt-Roenne, I. Department of Pharmacology, Leo Pharmaceutical Products, Ballerup; Elmgreen, J.

    1988-01-01

    The effect of timegadine, a novel experimental antirheumatic drug, on human neutrophil (PMN) 5-lipoxygenase activity and leukotriene B/sub 4/ (LTB/sub 4/) chemotaxis was compared with that of two second-line antiinflammatory drugs, D-penicillamine and levamisole. 1-/sup 14/C-Arachidonic acid (AA) was incorporated into the purified cells until steady state conditions were obtained. After preincubation with serial dilutions of the three drugs, AA release and metabolism was stimulated with calcium ionophore A23187. The radioactive eicosanoids released were extracted and separated by thinlayer chromatography, followed by autoradiography and quantitative laser densitometry. Chemotaxi of PMNs towards LTB/sub 4/ was measured in a modified Boyden chamber. Timegardine showed dose-dependent inhibition of both the 5-lipoxygenase pathway (IC50 3.4 x 10/sup -5/ M), and of chemotaxis (IC50 3 x 10/sup -4/ M). Inhibition of the release of AA from phospholipids, however, occurred only at therapeutically irrelevant doses (millimolar concentrations). Levamisole and D-penicillamine did not inhibit any of the cell functions investigated. Inhibition of both neutrophil motility and cellular synthesis of pro-inflammatory eicosanoids, may thus contribute to the clinical effects of timegadine in rheumatoid arthritis.

  1. Arachidonic acid and DHA status in pregnant women is not associated with cognitive performance of their children at 4 or 6-7 years.

    Science.gov (United States)

    Crozier, Sarah R; Sibbons, Charlene M; Fisk, Helena L; Godfrey, Keith M; Calder, Philip C; Gale, Catharine R; Robinson, Sian M; Inskip, Hazel M; Baird, Janis; Harvey, Nicholas C; Cooper, Cyrus; Burdge, Graham C

    2018-06-01

    Arachidonic acid (ARA) and DHA, supplied primarily from the mother, are required for early development of the central nervous system. Thus, variations in maternal ARA or DHA status may modify neurocognitive development. We investigated the relationship between maternal ARA and DHA status in early (11·7 weeks) or late (34·5 weeks) pregnancy on neurocognitive function at the age of 4 years or 6-7 years in 724 mother-child pairs from the Southampton Women's Survey cohort. Plasma phosphatidylcholine fatty acid composition was measured in early and late pregnancy. ARA concentration in early pregnancy predicted 13 % of the variation in ARA concentration in late pregnancy (β=0·36, PDHA concentration in early pregnancy predicted 21 % of the variation in DHA concentration in late pregnancy (β=0·46, PDHA nor ARA concentrations in early or late pregnancy were associated significantly with neurocognitive function in children at the age of 4 years or the age of 6-7 years. These findings suggest that ARA and DHA status during pregnancy in the range found in this cohort are unlikely to have major influences on neurocognitive function in healthy children.

  2. Associations between dietary n-6 and n-3 fatty acids and arachidonic acid compositions in plasma and erythrocytes in young and elderly Japanese volunteers

    Directory of Open Access Journals (Sweden)

    Kawabata Terue

    2011-08-01

    Full Text Available Abstract Background We reported that the compositions of arachidonic acid (ARA in erythrocytes and plasma phospholipids (PL in the elderly were lower than those in the young, though the ARA intake was nearly identical. Objective We further analyzed data in four study groups with different ages and sexes, and determined that the blood ARA levels were affected by the kinds of dietary fatty acids ingested. Methods One hundred and four healthy young and elderly volunteers were recruited. Dietary records together with photographic records from 28 consecutive days were reviewed and the fatty acid composition in plasma lipid fractions and erythrocyte PL was analyzed. Results No correlations for ARA between dietary fatty acids and blood lipid fractions were observed. A significant negative correlation between eicosapentaenoic acid (EPA + docosahexaenoic acid (DHA intake and ARA composition in erythrocyte PL was observed. ARA composition in erythrocyte PL was significantly lower in elderly subjects than in young subjects, because EPA and DHA intake in elderly subjects was higher than in young subjects. However, after removing the effect of dietary EPA+DHA intake, the ARA composition in erythrocyte PL in elderly subjects was significantly lower than that in young subjects. Conclusions Changes in physical conditions with aging influenced the low ARA composition of erythrocyte in elderly subjects in addition to the effects of dietary EPA and DHA.

  3. Arachidonic acid alters tomato HMG expression and fruit growth and induces 3-hydroxy-3-methylglutaryl coenzyme A reductase-independent lycopene accumulation

    Energy Technology Data Exchange (ETDEWEB)

    Rodriguez-Concepcion, M.; Gruissem, W. [Univ. of California, Berkeley, CA (United States). Dept. of Plant and Microbial Biology

    1999-01-01

    Regulation of isoprenoid end-product synthesis required for normal growth and development in plants is not well understood. To investigate the extent to which specific genes for the enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) are involved in end-product regulation, the authors manipulated expression of the HMG1 and HMG2 genes in tomato (Lycopersicon esculentum) fruit using arachidonic acid (AA). In developing young fruit AA blocked fruit growth, inhibited HMG1, and activated HMG2 expression. These results are consistent with other reports indicating that HMG1 expression is closely correlated with growth processes requiring phytosterol production. In mature-green fruit AA strongly induced the expression of HMG2, PSY1 (the gene for phytoene synthase), and lycopene accumulation before the normal onset of carotenoid synthesis and ripening. The induction of lycopene synthesis was not blocked by inhibition of HMGR activity using mevinolin, suggesting that cytoplasmic HMGR is not required for carotenoid synthesis. Their results are consistent with the function of an alternative plastid isoprenoid pathway (the Rohmer pathway) that appears to direct the production of carotenoids during tomato fruit ripening.

  4. Evidence for the essentiality of arachidonic and docosahexaenoic acid in the postnatal maternal and infant diet for the development of the infant's immune system early in life.

    Science.gov (United States)

    Richard, Caroline; Lewis, Erin D; Field, Catherine J

    2016-05-01

    Long-chain polyunsaturated fatty acids (LCPUFA), especially the balance between arachidonic (AA) and docosahexaenoic (DHA) acids are known to have important immunomodulatory roles during the postnatal period when the immune system is rapidly developing. AA and DHA are required in infant formula in many countries but are optional in North America. The rationale for adding these LCPUFA to full-term formula is based on their presence in breast milk and randomized controlled studies that suggest improved cognitive function in preterm infants, but results are more variable in full-term infants. Recently, the European Food Safety Authority has proposed, based on a lack of functional evidence, that AA is not required in infant formula for full-term infants during the first year of life but DHA should remain mandatory. The purpose of this review is to review the evidence from epidemiological and intervention studies regarding the essentiality of AA and DHA in the postnatal infant and maternal diet (breast-feeding) for the immune system development early in life. Although studies support the essentiality of DHA for the immune system development, more research is needed to rule out the essentiality of AA. Nevertheless, intervention studies have demonstrated improvement in many markers of immune function in infants fed formula supplemented with AA and DHA compared with unsupplemented formula, which appears to consistently result in beneficial health outcomes including reduction in the risk of developing allergic and atopic disease early in life.

  5. ABA suppresses Botrytis cinerea elicited NO production in tomato to influence H2O2 generation and increase host susceptibility

    Directory of Open Access Journals (Sweden)

    Anushen eSivakumaran

    2016-05-01

    Full Text Available Abscisic acid (ABA production has emerged a susceptibility factor in plant-pathogen interactions. This work examined the interaction of ABA with NO in tomato following challenge with the ABA-synthesising pathogen, Botrytis cinerea. Trace gas detection using a quantum cascade laser detected NO production within minutes of challenge with B. cinerea whilst photoacoustic laser detection detected ethylene production – an established mediator of defence against this pathogen - occurring after 6 h. Application of the NO generation inhibitor N-Nitro-L-arginine methyl ester (L-NAME suppressed both NO and ethylene production and resistance against B. cinerea. The tomato mutant sitiens fails to accumulate ABA (abscisic acid, shows increased resistance to B. cinerea and we noted exhibited elevated NO and ethylene production. Exogenous application of L-NAME or ABA reduced NO production in sitiens and reduced resistance to B. cinerea. Increased resistance to B. cinerea in sitiens have previously been linked to increased reactive oxygen species (ROS generation but this was reduced in both L-NAME and ABA treated sitiens. Taken together, our data suggests that ABA can decreases resistance to B. cinerea via reduction of NO production which also suppresses both ROS and ethylene production.

  6. Arachidonic acid and lipoxin A4 attenuate alloxan-induced cytotoxicity to RIN5F cells in vitro and type 1 diabetes mellitus in vivo.

    Science.gov (United States)

    Gundala, Naveen K V; Naidu, Vegi G M; Das, Undurti N

    2017-03-01

    We studied whether polyunsaturated fatty acids (PUFAs) can protect rat insulinoma (RIN5F) cells against alloxan-induced apoptosis in vitro and type 1 diabetes mellitus (type 1 DM) in vivo and if so, mechanism of this beneficial action. In vitro study was conducted using RIN5F cells while in vivo study was performed in Wistar rats. The effect of PUFAs, cyclo-oxygenase and lipoxygenase inhibitors, various eicosanoids and PUFAs metabolites: lipoxin A4 (LXA4), resolvin D2 and protectin against alloxan-induced cytotoxicity to RIN5F cells and type 1 DM was studied. Expression of PDX1, P65 NF-kB and IKB in RIN5F cells and Nrf2, GLUT2, COX2, iNOS protein levels in the pancreatic tissue and plasma glucose, insulin and tumor necrosis factor-α and antioxidants, lipid peroxides and nitric oxide were measured. Of all, arachidonic acid (AA) was found to be the most effective against alloxan-induced cytotoxicity to RIN5F cells and preventing type 1 DM. Both cyclo-oxygenase and lipoxygenase inhibitors did not block the beneficial actions of AA in vitro and in vivo. Alloxan inhibited LXA4 production by RIN5F cells and in alloxan-induced type 1 DM Wistar rats. AA-treatment restored LXA4 levels to normal both in vitro and in vivo. LXA4 protected RIN5F cells against alloxan-induced cytotoxicity and prevented type 1 DM and restored expression of Nrf2, Glut2, COX2, and iNOS genes and abnormal antioxidants to near normal. AA seems to bring about its beneficial actions against alloxan-induced cytotoxicity and type 1 DM by enhancing the production of LXA4. © 2016 BioFactors, 43(2):251-271, 2017. © 2016 International Union of Biochemistry and Molecular Biology.

  7. Arachidonic acid-and docosahexaenoic acid-enriched formulas modulate antigen-specific T cell responses to influenza virus in neonatal piglets.

    Science.gov (United States)

    Bassaganya-Riera, Josep; Guri, Amir J; Noble, Alexis M; Reynolds, Kathryn A; King, Jennifer; Wood, Cynthia M; Ashby, Michael; Rai, Deshanie; Hontecillas, Raquel

    2007-03-01

    Whereas the immunomodulatory effects of feeding either arachidonic acid (AA) or docosahexaenoic acid (DHA) separately have been previously investigated, little is known about the immunomodulatory efficacy of AA or DHA when they are fed in combination as infant formula ingredients. The objective of this study was to investigate the ability of AA- and DHA(AA/DHA)-enriched infant formula to modulate immune responses in the neonate in response to an inactivated influenza virus vaccine. Neonatal piglets (n = 48) were weaned on day 2 of age and distributed into 16 blocks of 3 littermate piglets each. Within each block, piglets were randomly assigned to a control formula, AA/DHA-enriched formula (0.63% AA and 0.34% DHA), or sow milk for 30 d. On day 9, 8 blocks of piglets were immunized with an inactivated influenza virus vaccine. On days 0, 9, 16, 23, and 30 after weaning, we measured influenza virus-specific T cell proliferation and phenotype of T subsets in peripheral blood. A delayed-type hypersensitivity reaction test was administered on day 28. Cytokine messenger RNA expression was determined by quantitative real time reverse transcriptase-polymerase chain reaction on day 30. The influenza virus-specific CD4(+) and CD8(+) T cell ex vivo lymphoproliferative responses were significantly lower on day 23 after immunization in piglets receiving dietary AA/DHA supplementation and sow milk than in those receiving the unsupplemented control formula. The immunomodulatory effects of AA/DHA-enriched formulas were consistent with up-regulation of interleukin 10 in peripheral blood mononuclear cells. Overall, it appears that the AA/DHA-enriched formula modulated antigen-specific T cell responses in part through an interleukin 10-dependent mechanism.

  8. Autoradiographic observations of the induced vascular injuries by arachidonic acid in rabbit's brain and lung using 111In-oxine labeled platelets

    International Nuclear Information System (INIS)

    Fujimoto, Tsukasa; Fukushima, Yoshiharu; Suzuki, Hidenori; Kuroiwa, Kyoko; Tanoue, Kenjiro; Yamazaki, Hiroh.

    1985-01-01

    Autoradiography using 111 In-oxine labeled autologous platelets was performed to observe the behavior of platelets in induced vascular injury by activated platelets in rabbit's brain and lung. Cerebrovascular injuries were induced by injection of arachidonic acid (AA) (0.7 mg/kg) into right internal carotid artery. Fourteen animals were pretreated with antiplatelet drug, ticlopidine (200 mg/kg) and 10 were controls. Before the AA injection, 111 In-oxine (300 μCi) labeled platelets were injected intravenously. Evans blue was given as a marker of disturbances of blood brain barrier. Sixty min after the AA injection, brains were removed and autoradiographic and electron microscopic studies were done. In the nontreated animals and some of the treated animals whose platelet aggregability was not suppressed, blue staining were seen in the cerebral hemisphere of injection side and hot radioactivity in autoradiogram were revealed in corresponding area. In the treated animals whose platelet aggregability was remarkably suppressed, no or slight blue staining or radioactivity were recognized. Only in hot radioactive area, platelet thrombi and vascular injuries were seen. Vascular injuries of lung were produced by decompression after keeping animals under hyperbalic condition (6 atomosphere absolute for 40 min). Before this procedure, 111 In-oxine labeled platelets were injected. Lungs of both 4 control and 4 decompression sickness animals were removed and autoradiographic and lightmicroscopic observations were performed. In lungs of decompression sickness animals remarkable spotty high radioactivity and prominent platelet aggregates in the vessels were seen. These findings were not seen in control animals. Our results suggested important roles of platelets in induced vascular injuries. And this autoradiographic approach seemed to be quite useful for observation of platelet's behavior in injured vessels and evaluation of antiplatelet drugs. (author)

  9. The IL1B-511 Polymorphism (rs16944 AA Genotype) Is Increased in Aspirin-Exacerbated Respiratory Disease in Mexican Population

    OpenAIRE

    Falf?n-Valencia, Ramc?s; Pav?n-Romero, Gandhi F.; Camarena, Angel; Garc?a, Mar?a de la Luz; Galicia-Negrete, Gustavo; Negrete-Garc?a, Mar?a Cristina; Teran, Luis Manuel

    2011-01-01

    Aspirin exacerbated respiratory disease (AERD) is characterized by chronic hyperplastic rhinosinusitis, nasal polyposis, asthma, and aspirin sensitivity. The mechanisms which produce these manifestations of intolerance are not fully defined, current research focuses on cyclooxygenase 1 (COX-1) inhibition, metabolism of arachidonic acid, and the COX pathway to the lipoxygenase (LO) route, inducing increased synthesis of leukotrienes (LT). The biological plausibility of this model has led to th...

  10. The influence of dietary concentrations of arachidonic acid and eicosapentaenoic acid at various stages of larval ontogeny on eye migration, pigmentation and prostaglandin content of common sole larvae ( Solea solea L.)

    DEFF Research Database (Denmark)

    Lund, Ivar; Steenfeldt, Svend Jørgen; Banta, G.

    2008-01-01

    Dietary manipulations of arachidonic acid, ARA and eicosapentaenoic acid, EPA may have an influence on pigmentation in common sole larvae (Solea solea L., Linnaeus 1758) which may be related to a "pigmentation window". This is a specific period in the larval ontogeny where nutritional factors...... metamorphosis. Initiation of metamorphosis (i.e. start of eye migration) was related to the size of larvae and not related to ARA or EPA content. Dietary EPA or DHA did not retard the advance of eye migration. More than 90 % of highly malpigmented juveniles, (i.e. "albinos") had a permanent aberrant eye...

  11. Consumption of Red Meat, but Not Cooking Oils High in Polyunsaturated Fat, Is Associated with Higher Arachidonic Acid Status in Singapore Chinese Adults

    Directory of Open Access Journals (Sweden)

    Jowy Yi Hoong Seah

    2017-01-01

    Full Text Available High arachidonic acid (AA; 20:4 n − 6 status may have adverse effects on inflammation and risk of cardiovascular diseases. Concerns about high intake of n − 6 polyunsaturated fatty acids (PUFAs are based on the premise that endogenous conversion from linoleic acid (LA; 18:2 n − 6 is an important source of AA, but few population-based studies have investigated dietary determinants of AA status. In this study, we examined habitual food consumption in relation to plasma concentrations of AA and other PUFAs in population-based studies. We used cross-sectional data from 269 healthy, ethnic Chinese participants (25–80 years old with contrasting intakes of fish and red meat from the Singapore Prospective Study Program and 769 healthy participants (44–74 years old from the Singapore Chinese Health Study as a validation set. Multivariable linear regression was used to examine PUFA intake (% energy and food sources of PUFA (fish, red meat, poultry, soy and cooking oils in relation to plasma PUFAs (AA, LA, dihomo-gamma-linolenic acid (DGLA; 20:3 n − 6, alpha-linolenic acid (ALA; 18:3 n − 3, eicosapentaenoic acid (EPA; 20:5 n − 3, and docosahexaenoic acid (DHA; 22:6 n − 3 concentrations. Higher intake of red meat was associated with higher plasma AA concentrations. High intake of PUFA or PUFA-rich oils was associated with higher plasma ALA but not with plasma AA. Higher intakes of soy were associated with higher ALA and fish with higher DHA and EPA concentrations. These associations were statistically significant (p < 0.05 in both studies. Red meat consumption, but not PUFA or PUFA-rich cooking oil, was associated with circulating AA suggesting that intake of pre-formed AA rather than LA is an important determinant of AA status. A diet high in fish, soy products and polyunsaturated cooking oil, and low in red meat may be associated with an optimal plasma profile of PUFA in this Chinese population.

  12. THE PARTICIPATION OF THE NITRERGIC PATHWAY IN INCREASED RATE OF TRANSITORY RELAXATION OF LOWER ESOPHAGEAL SPHINCTER INDUCED BY RECTAL DISTENSION IN DOGS

    Directory of Open Access Journals (Sweden)

    Michel Santos PALHETA

    2014-04-01

    Full Text Available Context The rectal distension in dogs increases the rate of transitory lower esophageal sphincter relaxation considered the main factor causing gastroesophageal reflux. Objectives The aim of this study was evaluate the participation of the nitrergic pathway in the increased transitory lower esophageal sphincter relaxation rate induced by rectal distension in anesthetized dogs. Methods Male mongrel dogs (n = 21, weighing 10-15 kg, were fasted for 12 hours, with water ad libitum. Thereafter, they were anesthetized (ketamine 10 mg.Kg-1 + xylazine 20 mg.Kg-1, so as to carry out the esophageal motility evaluation protocol during 120 min. After a 30-minute basal period, the animals were randomly intravenous treated whith: saline solution 0.15M (1ml.Kg-1, L-NAME (3 mg.Kg-1, L-NAME (3 mg.Kg-1 + L-Arginine (200 mg.Kg-1, glibenclamide (1 mg.Kg-1 or methylene blue (3 mg.Kg-1. Forty-five min after these pre-treatments, the rectum was distended (rectal distension, 5 mL.Kg-1 or not (control with a latex balloon, with changes in the esophageal motility recorded over 45 min. Data were analyzed using ANOVA followed by Student Newman-Keuls test. Results In comparison to the respective control group, rectal distension induces an increase in transitory lower esophageal sphincter relaxation. Pre-treatment with L-NAME or methylene blue prevents (P<0.05 this phenomenon, which is reversible by L-Arginine plus L-NAME. However, pretreating with glibenclamide failed to abolish this process. Conclusions Therefore, these experiments suggested, that rectal distension increases transitory lower esophageal sphincter relaxation in dogs via through nitrergic pathways.

  13. A solid dietary fat containing fish oil redistributes lipoprotein subclasses without increasing oxidative stress in men

    DEFF Research Database (Denmark)

    Tholstrup, T.; Hellgren, Lars; Petersen, M.

    2004-01-01

    , a solid dietary fat containing (n-3) PUFA decreased plasma TAG, VLDL, and IDL cholesterol, and redistributed lipoprotein subclasses in LDL and HDL, with a higher concentration of the larger and less atherogenic subfractions. These changes took place without an increase in oxidative stress as measured...... of F than O fat (P oxidation measured as the ratio of plasma isoprostanes F-2 to arachidonic acid and urinary isoprostanes, whereas the vitamin E activity/plasma total lipids ratio was higher after intake of F than O (P = 0.008). In conclusion...

  14. Melatonin interactions with blood pressure and vascular function during l-NAME-induced hypertension

    Czech Academy of Sciences Publication Activity Database

    Paulis, L.; Pecháňová, Olga; Zicha, Josef; Barta, A.; Gardlik, R.; Celec, P.; Kuneš, Jaroslav; Šimko, F.

    2010-01-01

    Roč. 48, č. 2 (2010), s. 102-108 ISSN 0742-3098 R&D Projects: GA AV ČR(CZ) IAA500110902 Grant - others:VEGA(SK) 1/0187/09; VEGA(SK) 2/0178/09; APVV(SK) 0538-07; EC(XE) 2009-237834 Institutional research plan: CEZ:AV0Z50110509 Keywords : endothelium-derived constricting factor * melatonin * nitric oxide Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 5.855, year: 2010

  15. Influence of pertussis toxin pretreatment on the development of L-NAME-induced hypertension

    Czech Academy of Sciences Publication Activity Database

    Zicha, Josef; Kuneš, Jaroslav; Vranková, S.; Jendeková, L.; Dobešová, Zdenka; Pintérová, Mária; Pecháňová, Olga

    2009-01-01

    Roč. 58, č. 5 (2009), s. 751-755 ISSN 0862-8408 R&D Projects: GA ČR(CZ) GA305/08/0139; GA MŠk(CZ) 1M0510 Institutional research plan: CEZ:AV0Z50110509 Keywords : sympathetic nervous system * nitric oxide * inhibitory G proteins Subject RIV: ED - Physiology Impact factor: 1.430, year: 2009

  16. Blood fatty acid composition of pregnant and nonpregnant Korean women: red cells may act as a reservoir of arachidonic acid and docosahexaenoic acid for utilization by the developing fetus.

    Science.gov (United States)

    Ghebremeskel, K; Min, Y; Crawford, M A; Nam, J H; Kim, A; Koo, J N; Suzuki, H

    2000-05-01

    Relative fatty acid composition of plasma and red blood cell (RBC) choline phosphoglycerides (CPG), and RBC ethanolamine phosphoglycerides (EPG) of pregnant (n = 40) and nonpregnant, nonlactating (n = 40), healthy Korean women was compared. The two groups were of the same ethnic origin and comparable in age and parity. Levels of arachidonic (AA) and docosahexaenoic (DHA) acids were lower (P mothers were mobilizing membrane AA and DHA to meet the high fetal requirement for these nutrients. It may also suggest that RBC play a role as a potential store of AA and DHA and as a vehicle for the transport of these fatty acids from maternal circulation to the placenta to be utilized by the developing fetus.

  17. Price increase

    CERN Multimedia

    2006-01-01

    Please take note that after five years of stable prices at Restaurant No 1 a price increase will come into force on 1st January 2006. This increase has been agreed after discussions between the CSR (Comité de Surveillance des Restaurants) and the catering company Novae and will reflect the inflation rate of the last few years. In addition, a new children's menu will be introduced, as well as 'Max Havelaar' fair-trade coffee at a price of 1.70 CHF.

  18. Price increase

    CERN Multimedia

    2005-01-01

    Please take note that after five years of stable prices at Restaurant No 1 a price increase will come into force on 1st January 2006. This increase has been agreed after discussions between the CSR (Comité de Surveillance des Restaurants) and the catering company Novae and will reflect the inflation rate of the last few years. In addition, a new children's menu will be introduced as well as 'Max Havelaar' fair-trade coffee at a price of 1.70 CHF.

  19. Increased synthesis of high-molecular-weight cPLA2 mediates early UV-induced PGE2 in human skin.

    Science.gov (United States)

    Gresham, A; Masferrer, J; Chen, X; Leal-Khouri, S; Pentland, A P

    1996-04-01

    Ultraviolet light (UV) B-induced inflammation is characterized by dramatic increases in prostaglandin E2 (PGE2) synthesis due to enhanced arachidonate deacylation from the membrane. Therefore, the effect of UV on sythesis, mass, and distribution of the high-molecular-weight phospholipase A2 (cPLA2) in cultured human keratinocytes and human skin was studied. The 105-kDa cPLA2 was demonstrated to be the critical enzyme in UV-induced PGE2 synthesis and erythema in the first 6 h postirradiation. Immunoprecipitation of 35S-labeled protein showed cPLA2 synthesis increased three- to fourfold 6 h after irradiation. Immunoprecipitated 32P-labeled cPLA2 demonstrated phosphorylation of cPLA2 was concurrently induced, suggesting that UV also activates cPLA2. This increase in cPLA2 synthesis and activation also closely correlated with increased PGE2 synthesis and [3H]arachidonic acid release and was effectively blocked by both an S-oligonucleotide antisense to cPLA2 and methyl arachidonate fluorophosphate, a specific inhibitor of cPLA2. Biopsy and histochemical examination of erythematous sites expressed increased amounts of cPLA2 whereas nonerythematous irradiated sites did not. In contrast, cyclooxygenase-1 and -2 in cultures and skin explants were unaffected 6 h post-UV, and no change in cyclooxygenase activity was observed at this time. These results suggest that increased cPLA2 synthesis occurs only when skin is exposed to UV doses that are sufficient to cause erythema and indicate expression of cPLA2 participates in acute UV inflammation.

  20. Post-Weaning Protein Malnutrition Increases Blood Pressure and Induces Endothelial Dysfunctions in Rats

    Science.gov (United States)

    Siman, Fabiana D. M.; Silveira, Edna A.; Meira, Eduardo F.; da Costa, Carlos P.; Vassallo, Dalton V.; Padilha, Alessandra S.

    2012-01-01

    Malnutrition during critical periods in early life may increase the subsequent risk of hypertension and metabolic diseases in adulthood, but the underlying mechanisms are still unclear. We aimed to evaluate the effects of post-weaning protein malnutrition on blood pressure and vascular reactivity in aortic rings (conductance artery) and isolated-perfused tail arteries (resistance artery) from control (fed with Labina®) and post-weaning protein malnutrition rats (offspring that received a diet with low protein content for three months). Systolic and diastolic blood pressure and heart rate increased in the post-weaning protein malnutrition rats. In the aortic rings, reactivity to phenylephrine (10−10–3.10−4 M) was similar in both groups. Endothelium removal or L-NAME (10−4 M) incubation increased the response to phenylephrine, but the L-NAME effect was greater in the aortic rings from the post-weaning protein malnutrition rats. The protein expression of the endothelial nitric oxide isoform increased in the aortic rings from the post-weaning protein malnutrition rats. Incubation with apocynin (0.3 mM) reduced the response to phenylephrine in both groups, but this effect was higher in the post-weaning protein malnutrition rats, suggesting an increase of superoxide anion release. In the tail artery of the post-weaning protein malnutrition rats, the vascular reactivity to phenylephrine (0.001–300 µg) and the relaxation to acetylcholine (10−10–10−3 M) were increased. Post-weaning protein malnutrition increases blood pressure and induces vascular dysfunction. Although the vascular reactivity in the aortic rings did not change, an increase in superoxide anion and nitric oxide was observed in the post-weaning protein malnutrition rats. However, in the resistance arteries, the increased vascular reactivity may be a potential mechanism underlying the increased blood pressure observed in this model. PMID:22529948

  1. Increased peripheral vascular disease risk progressively constrains perfusion adaptability in the skeletal muscle microcirculation

    Science.gov (United States)

    Butcher, Joshua T.; Frisbee, Stephanie J.; Olfert, I. Mark; Chantler, Paul D.; Tabone, Lawrence E.; d'Audiffret, Alexandre C.; Shrader, Carl D.; Goodwill, Adam G.; Stapleton, Phoebe A.; Brooks, Steven D.; Brock, Robert W.; Lombard, Julian H.

    2015-01-01

    To determine the impact of progressive elevations in peripheral vascular disease (PVD) risk on microvascular function, we utilized eight rat models spanning “healthy” to “high PVD risk” and used a multiscale approach to interrogate microvascular function and outcomes: healthy: Sprague-Dawley rats (SDR) and lean Zucker rats (LZR); mild risk: SDR on high-salt diet (HSD) and SDR on high-fructose diet (HFD); moderate risk: reduced renal mass-hypertensive rats (RRM) and spontaneously hypertensive rats (SHR); high risk: obese Zucker rats (OZR) and Dahl salt-sensitive rats (DSS). Vascular reactivity and biochemical analyses demonstrated that even mild elevations in PVD risk severely attenuated nitric oxide (NO) bioavailability and caused progressive shifts in arachidonic acid metabolism, increasing thromboxane A2 levels. With the introduction of hypertension, arteriolar myogenic activation and adrenergic constriction were increased. However, while functional hyperemia and fatigue resistance of in situ skeletal muscle were not impacted with mild or moderate PVD risk, blood oxygen handling suggested an increasingly heterogeneous perfusion within resting and contracting skeletal muscle. Analysis of in situ networks demonstrated an increasingly stable and heterogeneous distribution of perfusion at arteriolar bifurcations with elevated PVD risk, a phenomenon that was manifested first in the distal microcirculation and evolved proximally with increasing risk. The increased perfusion distribution heterogeneity and loss of flexibility throughout the microvascular network, the result of the combined effects on NO bioavailability, arachidonic acid metabolism, myogenic activation, and adrenergic constriction, may represent the most accurate predictor of the skeletal muscle microvasculopathy and poor health outcomes associated with chronic elevations in PVD risk. PMID:26702145

  2. Mildly abnormal general movement quality in infants is associated with higher Mead acid and lower arachidonic acid and shows a U-shaped relation with the DHA/AA ratio.

    Science.gov (United States)

    van Goor, S A; Schaafsma, A; Erwich, J J H M; Dijck-Brouwer, D A J; Muskiet, F A J

    2010-01-01

    We showed that docosahexaenoic acid (DHA) supplementation during pregnancy and lactation was associated with more mildly abnormal (MA) general movements (GMs) in the infants. Since this finding was unexpected and inter-individual DHA intakes are highly variable, we explored the relationship between GM quality and erythrocyte DHA, arachidonic acid (AA), DHA/AA and Mead acid in 57 infants of this trial. MA GMs were inversely related to AA, associated with Mead acid, and associated with DHA/AA in a U-shaped manner. These relationships may indicate dependence of newborn AA status on synthesis from linoleic acid. This becomes restricted during the intrauterine period by abundant de novo synthesis of oleic and Mead acids from glucose, consistent with reduced insulin sensitivity during the third trimester. The descending part of the U-shaped relation between MA GMs and DHA/AA probably indicates DHA shortage next to AA shortage. The ascending part may reflect a different developmental trajectory that is not necessarily unfavorable. Copyright 2009 Elsevier Ltd. All rights reserved.

  3. Resistance of essential fatty acid-deficient rats to endotoxin-induced increases in vascular permeability

    International Nuclear Information System (INIS)

    Li, E.J.; Cook, J.A.; Spicer, K.M.; Wise, W.C.; Rokach, J.; Halushka, P.V.

    1990-01-01

    Resistance to endotoxin in essential fatty acid-deficient (EFAD) rats is associated with reduced synthesis of certain arachidonic acid metabolites. It was hypothesized that EFAD rats would manifest decreased vascular permeability changes during endotoxemia as a consequence of reduced arachidonic acid metabolism. To test this hypothesis, changes in hematocrit (HCT) and mesenteric localization rate of technetium-labeled human serum albumin (99mTc-HSA) and red blood cells (99mTc-RBC) were assessed in EFAD and normal rats using gamma-camera imaging. Thirty minutes after Salmonella enteritidis endotoxin, EFAD rats exhibited less hemoconcentration as determined by % HCT than normal rats. Endotoxin caused a less severe change in permeability index in the splanchnic region in EFAD rats than in normal rats (1.2 +/- 0.6 x 10(-3)min-1 vs. 4.9 +/- 1.7 x 10(-3)min-1 respectively, P less than 0.05). In contrast to 99mTc-HSA, mesenteric localization of 99mTc-RBC was not changed by endotoxin in control or EFAD rats. Supplementation with ethyl-arachidonic acid did not enhance susceptibility of EFAD rats to endotoxin-induced splanchnic permeability to 99mTc-HSA. Leukotrienes have been implicated as mediators of increased vascular permeability in endotoxin shock. Since LTC3 formation has been reported to be increased in EFA deficiency, we hypothesized that LTC3 may be less potent than LTC4. Thus the effect of LTC3 on mean arterial pressure and permeability was compared to LTC4 in normal rats. LTC3-induced increases in peak mean arterial pressure were less than LTC4 at 10 micrograms/kg (39 +/- 5 mm Hg vs. 58 +/- 4 mm Hg respectively, P less than 0.05) and at 20 micrograms/kg (56 +/- 4 mm Hg vs. 75 +/- 2 mm Hg respectively, P less than 0.05). LY171883 (30 mg/kg), an LTD4/E4 receptor antagonist, attenuated the pressor effect of LTC4, LTD4, and LTC3

  4. Cigarette smoke exposure alters [14C]arachidonic acid metabolism in aortas and platelets of rats fed various levels of selenium and vitamin E

    International Nuclear Information System (INIS)

    Valentovic, M.A.; Gairola, C.; Lubawy, W.C.

    1985-01-01

    Rats were placed on a basal diet supplemented with 0, 0.03, or 3 ppm selenium and 0 or 20 ppm vitamin E for 41-43 wk. Selenium deficiency decreased hepatic glutathione peroxidase activity and lowered both aortic prostacyclin (PGI2) and platelet thromboxane (TXA2) production compared to selenium- and vitamin E-supplemented animals. Vitamin E deficiency increased hepatic lipid peroxidation and decreased aortic PGI2 synthesis. Rats exposed daily for 31-32 wk to fresh smoke from a UK 2R1 reference cigarette had carboxyhemoglobin levels of 0.75 +/- 0.12 and 4.73 +/- 0.12% in sham- and smoke-exposed groups, respectively. Animals chronically exposed to cigarette smoke displayed a nearly twofold increase in pulmonary arylhydrocarbon hydroxylase activity. Smoke exposure produced a 26-33% decrease in aortic PGI2 synthesis compared to shams in the Se3E20, Se0.03E20, and Se3E0 groups. Smoking also increased platelet thromboxane 91% and 98% in the Se3E20 and Se3E0 groups compared to shams. It is concluded that cigarette-smoke exposure and selenium or vitamin E deficiency alter aortic PGI2 and platelet TXA2 production

  5. Alpha-synuclein gene ablation increases docosahexaenoic acid incorporation and turnover in brain phospholipids

    DEFF Research Database (Denmark)

    Golovko, Mikhail Y; Rosenberger, Thad A; Feddersen, Søren

    2007-01-01

    Previously, we demonstrated that ablation of alpha-synuclein (Snca) reduces arachidonate (20:4n-6) turnover in brain phospholipids through modulation of an endoplasmic reticulum-localized acyl-CoA synthetase (Acsl). The effect of Snca ablation on docosahexaenoic acid (22:6n-3) metabolism is unknown...... and turnover in ethanolamine glycerophospholipid, phosphatidylserine, and phosphatidylinositol pools. Increased 22:6n-3-CoA mass was not the result of altered Acsl activity, which was unaffected by the absence of Snca. While Snca bound 22:6n-3, Kd = 1.0 +/- 0.5 micromol/L, it did not bind 22:6n-3-Co...

  6. Pro-oxidant activity of indicaxanthin from Opuntia ficus indica modulates arachidonate metabolism and prostaglandin synthesis through lipid peroxide production in LPS-stimulated RAW 264.7 macrophages.

    Science.gov (United States)

    Allegra, M; D'Acquisto, F; Tesoriere, L; Attanzio, A; Livrea, M A

    2014-01-01

    Macrophages come across active prostaglandin (PG) metabolism during inflammation, shunting early production of pro-inflammatory towards anti-inflammatory mediators terminating the process. This work for the first time provides evidence that a phytochemical may modulate the arachidonate (AA) metabolism in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages, promoting the ultimate formation of anti-inflammatory cyclopentenone 15deoxy-PGJ2. Added 1 h before LPS, indicaxanthin from Opuntia Ficus Indica prevented activation of nuclear factor-κB (NF-κB) and over-expression of PGE2 synthase-1 (mPGES-1), but up-regulated cyclo-oxygenase-2 (COX-2) and PGD2 synthase (H-PGDS), with final production of the anti-inflammatory cyclopentenone. The effects were positively related with concentration between 50 and 100 µM. Indicaxanthin did not have any effect in the absence of LPS. A kinetic study investigating the redox status of LPS-stimulated macrophages between 0.5 and 12 h, either in the absence or in the presence of 50-100 µM indicaxanthin, revealed a differential control of ROS production, with early (0.5-3 h) modest inhibition, followed by a progressive (3-12 h) concentration-dependent enhancement over the level induced by LPS alone. In addition, indicaxanthin caused early (0.5-3 h) concentration-dependent elevation of conjugated diene lipid hydroperoxides, and production of hydroxynonenal-protein adducts, over the amount induced by LPS. In LPS-stimulated macrophages indicaxanthin did not affect PG metabolism when co-incubated with either an inhibitor of NADPH oxidase or vitamin E. It is concluded that LPS-induced pro-oxidant activity of indicaxanthin at the membrane level allows formation of signaling intermediates whose accumulation modulates PG biosynthetic pathway in inflamed macrophages.

  7. Liver conversion of docosahexaenoic and arachidonic acids from their 18-carbon precursors in rats on a DHA-free but α-LNA-containing n-3 PUFA adequate diet.

    Science.gov (United States)

    Gao, Fei; Kim, Hyung-Wook; Igarashi, Miki; Kiesewetter, Dale; Chang, Lisa; Ma, Kaizong; Rapoport, Stanley I

    2011-01-01

    The long-chain polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid (EPA, 20:5n-3), docosahexaenoic acid (DHA, 22:6n-3), and arachidonic acid (AA, 20:4n-6), are critical for health. These PUFAs can be synthesized in liver from their plant-derived precursors, α-linolenic acid (α-LNA, 18:3n-3) and linoleic acid (LA, 18:2n-6). Vegetarians and vegans may have suboptimal long-chain n-3 PUFA status, and the extent of the conversion of α-LNA to EPA and DHA by the liver is debatable. We quantified liver conversion of DHA and other n-3 PUFAs from α-LNA in rats fed a DHA-free but α-LNA (n-3 PUFA) adequate diet, and compared results to conversion of LA to AA. [U-(13)C]LA or [U-(13)C]α-LNA was infused intravenously for 2h at a constant rate into unanesthetized rats fed a DHA-free α-LNA adequate diet, and published equations were used to calculate kinetic parameters. The conversion coefficient k(⁎) of DHA from α-LNA was much higher than for AA from LA (97.2×10(-3) vs. 10.6×10(-3)min(-1)), suggesting that liver elongation-desaturation is more selective for n-3 PUFA biosynthesis on a per molecule basis. The net daily secretion rate of DHA, 20.3μmol/day, exceeded the reported brain DHA consumption rate by 50-fold, suggesting that the liver can maintain brain DHA metabolism with an adequate dietary supply solely of α-LNA. This infusion method could be used in vegetarians or vegans to determine minimal daily requirements of EPA and DHA in humans. Published by Elsevier B.V.

  8. Tributyltin chloride increases phenylephrine-induced contraction and vascular stiffness in mesenteric resistance arteries from female rats

    International Nuclear Information System (INIS)

    Ribeiro Júnior, Rogério Faustino; Marques, Vinicius Bermond; Nunes, Dieli Oliveira; Ronconi, Karoline de Sousa; Araújo, Julia F.P. de; Rodrigues, Paula Lopes; Padilha, Alessandra Simão; Vassallo, Dalton Valentim; Graceli, Jones B.; Stefanon, Ivanita

    2016-01-01

    Tributyltin chloride (TBT) is an organotin compound that reduces estrogen levels in female rats. We aimed to investigate the effects of TBT exposure on vascular tonus and vascular remodelling in the resistance arteries of female rats. Rats were treated daily with TBT (500 ng/kg) for 15 days. TBT did not change arterial blood pressure but did modify some morpho-physiological parameters of third-order mesenteric resistance arteries in the following ways: (1) decreased lumen and external diameters; (2) increased wall/lm ratio and wall thickness; (3) decreased distensibility and increased stiffness; (4) increased collagen deposition; and (5) increased pulse wave velocity. TBT exposure increased the phenylephrine-induced contractile response in mesenteric resistance arteries. However, vasodilatation responses induced by acetylcholine and sodium nitroprusside were not modified by TBT. It is suggested that TBT exposure reduces vascular nitric oxide (NO) production, because:(1) L-NAME incubation did not cause a leftward shift in the concentration–response curve for phenylephrine; (2) both eNOS protein expression; (3) in situ NO production were reduced. Incubation with L-NAME; and (4) SOD shifted the phenylephrine response curve to the left in TBT rats. Tiron, catalase, ML-171 and VAS2870 decreased vascular reactivity to phenylephrine only in TBT rats. Moreover, increased superoxide anion production was observed in the mesenteric resistance arteries of TBT rats accompanied by an increase in gp91phox, catalase, AT 1 receptor and total ERK1/2 protein expression. In conclusion, these findings show that TBT induced alterations are most likely due to a reduction of NO production combined with increased O 2 − production derived from NADPH oxidase and ERK1/2 activation. These findings offer further evidence that TBT is an environmental risk factor for cardiovascular disease. - Highlights: • Tributyltin chloride reduces estrogen levels in female rats. • Treatment with TBT

  9. Berberine inhibits the chemotherapy-induced repopulation by suppressing the arachidonic acid metabolic pathway and phosphorylation of FAK in ovarian cancer.

    Science.gov (United States)

    Zhao, Yawei; Cui, Lianzhi; Pan, Yue; Shao, Dan; Zheng, Xiao; Zhang, Fan; Zhang, Hansi; He, Kan; Chen, Li

    2017-12-01

    Cytotoxic chemotherapy is an effective and traditional treatment of ovarian cancer. However, chemotherapy-induced apoptosis may also trigger and ultimately accelerate the repopulation of the small number of adjacent surviving cells. This study mainly focused on the tumour cell repopulation caused by chemotherapy in ovarian cancer and the adjunctive/synergistic effect of Berberine on the prevention of tumour repopulation. The transwell system was used to mimic the co-culture of surviving ovarian cancer cells in the microenvironment of cytotoxic chemotherapy-treated dying cells. Tumour cell proliferation was observed by crystal violet staining. AA and PGE 2 levels were measured by ELISA, and changes of protein expression were analysed by Western blot. Chemotherapy drug VP16 treatment triggered AA pathway, leading to the elevated PGE 2 level, and ultimately enhanced the repopulation of ovarian cancer cells. Berberine can block the caspase 3-iPLA 2 -AA-COX-2-PGE 2 pathway by inhibiting the expression of iPLA 2 and COX-2. Berberine can also reverse the increased phosphorylation of FAK caused by abnormal PGE 2 level and thus reverse the repopulation of ovarian cancer cells after VP16 treatment. Our observation suggested that Berberine could inhibit the chemotherapy-induced repopulation of ovarian cancer cells by suppressing the AA pathway and phosphorylation of FAK. And these findings implicated a novel combined use of Berberine and chemotherapeutics, which might prevent ovarian cancer recurrence by abrogating early tumour repopulation. © 2017 John Wiley & Sons Ltd.

  10. Sodium nitrite attenuates hypertension-in-pregnancy and blunts increases in soluble fms-like tyrosine kinase-1 and in vascular endothelial growth factor.

    Science.gov (United States)

    Gonçalves-Rizzi, Victor Hugo; Possomato-Vieira, Jose Sergio; Sales Graça, Tamiris Uracs; Nascimento, Regina Aparecida; Dias-Junior, Carlos A

    2016-07-01

    Preeclampsia is a pregnancy-associated disorder characterized by hypertension with uncertain pathogenesis. Increases in antiangiogenic soluble fms-like tyrosine kinase-1 (sFlt-1) and reductions in nitric oxide (NO) bioavailability have been observed in preeclamptic women. However, the specific mechanisms linking these detrimental changes to the hypertension-in-pregnancy are not clearly understood. In this regard, while recent findings have suggested that nitrite-derived NO formation exerts antihypertensive and antioxidant effects, no previous study has examined these responses to orally administered nitrite in hypertension-in-pregnancy. We then hypothesized restoring NO bioavailability with sodium nitrite in pregnant rats upon NO synthesis inhibition with N(omega)-nitro-l-arginine methyl ester (L-NAME) attenuates hypertension and high circulating levels of sFlt-1. Number and weight of pups and placentae were recorded to assess maternal-fetal interface. Plasma sFlt-1, vascular endothelial growth factor (VEGF) and biochemical determinants of NO formation and of antioxidant function were measured. We found that sodium nitrite blunts the hypertension-in-pregnancy and restores the NO bioavailability, and concomitantly prevents the L-NAME-induced high circulating sFlt-1 and VEGF levels. Also, our results suggest that nitrite-derived NO protected against reductions in litter size and placental weight caused by L-NAME, improving number of viable and resorbed fetuses and antioxidant function. Therefore, the present findings are consistent with the hypothesis that nitrite-derived NO may possibly be the driving force behind the maternal and fetal beneficial effects observed with sodium nitrite during hypertension-in-pregnancy. Certainly further investigations are required in preeclampsia, since counteracting the damages to the mother and fetal sides resulting from hypertension and elevated sFlt-1 levels may provide a great benefit in this gestational hypertensive disease

  11. Tributyltin chloride increases phenylephrine-induced contraction and vascular stiffness in mesenteric resistance arteries from female rats.

    Science.gov (United States)

    Ribeiro Júnior, Rogério Faustino; Marques, Vinicius Bermond; Nunes, Dieli Oliveira; Ronconi, Karoline de Sousa; de Araújo, Julia F P; Rodrigues, Paula Lopes; Padilha, Alessandra Simão; Vassallo, Dalton Valentim; Graceli, Jones B; Stefanon, Ivanita

    2016-03-15

    Tributyltin chloride (TBT) is an organotin compound that reduces estrogen levels in female rats. We aimed to investigate the effects of TBT exposure on vascular tonus and vascular remodelling in the resistance arteries of female rats. Rats were treated daily with TBT (500 ng/kg) for 15 days. TBT did not change arterial blood pressure but did modify some morpho-physiological parameters of third-order mesenteric resistance arteries in the following ways: (1) decreased lumen and external diameters; (2) increased wall/lm ratio and wall thickness; (3) decreased distensibility and increased stiffness; (4) increased collagen deposition; and (5) increased pulse wave velocity. TBT exposure increased the phenylephrine-induced contractile response in mesenteric resistance arteries. However, vasodilatation responses induced by acetylcholine and sodium nitroprusside were not modified by TBT. It is suggested that TBT exposure reduces vascular nitric oxide (NO) production, because:(1) L-NAME incubation did not cause a leftward shift in the concentration-response curve for phenylephrine; (2) both eNOS protein expression; (3) in situ NO production were reduced. Incubation with L-NAME; and (4) SOD shifted the phenylephrine response curve to the left in TBT rats. Tiron, catalase, ML-171 and VAS2870 decreased vascular reactivity to phenylephrine only in TBT rats. Moreover, increased superoxide anion production was observed in the mesenteric resistance arteries of TBT rats accompanied by an increase in gp91phox, catalase, AT1 receptor and total ERK1/2 protein expression. In conclusion, these findings show that TBT induced alterations are most likely due to a reduction of NO production combined with increased O2(-) production derived from NADPH oxidase and ERK1/2 activation. These findings offer further evidence that TBT is an environmental risk factor for cardiovascular disease. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. The time-dependent effect of provinolsTM on brain NO synthase activity in L-NAME-induced hypertension

    Czech Academy of Sciences Publication Activity Database

    Jendeková, L.; Kojšová, S.; Andriantsitohaina, R.; Pecháňová, Olga

    2006-01-01

    Roč. 55, č. S1 (2006), S31-S37 ISSN 0862-8408 Grant - others:VEGA(SK) 2/6148/26; VEGA(SK) 1/342906 Institutional research plan: CEZ:AV0Z50110509 Keywords : red wine polyphenols * oxidative damage * nitric oxide synthase Subject RIV: ED - Physiology Impact factor: 2.093, year: 2006

  13. Effect of arachidonic acid supplementation and cyclooxygenase/lipoxygenase inhibition on the development of early bovine embryos Influência do ácido araquidónico e da inibição da ciclo-oxigenase ou lipo-oxigenase no desenvolvimento inicial de embriões bovinos

    Directory of Open Access Journals (Sweden)

    Rosa Maria Pereira

    2006-04-01

    Full Text Available The effect of arachidonic acid (AA cascade on bovine embryo development in a granulosa cell co-culture system was studied. Arachidonic acid (100 µM was supplemented from 1-cell to 8-16 cell block stage (first three days of co-culture and from 1-cell to hatching. Specific cyclooxygenase (indomethacin, 28 µM and lipoxygenase (nordihydroguaiaretic acid - NDGA, 28 µM inhibitors were used from 1-cell to 8-16 cell block stage with AA. Embryo development was assessed by cleavage, day 7-day 8 and hatched embryo rates and by measuring growth rates through development stages found in days 7-10 of culture (day 0 = insemination day. Embryo quality was scored at day 8. A 6.5-10.4% increase on cleavage rate after AA supplementation was found. This AA supplementation from 1-cell to hatching delayed embryo growth rate beyond day 7 and a reduction on hatching rate was detected. When AA supplementation was restricted to the first three days of co-culture those negative effects were overcome. Also, indomethacin and NDGA prevented the positive effect of AA and induced a significant reduction on cleavage, respectively. NDGA further decreased day 7 embryo rate and quality. Results suggest that AA has a two-phase action on bovine embryos, promoting early development and impairing embryo growth from day 7 onwards and hatching rates. Both cyclooxygenase and lipoxygenase were found to be important pathways to promote cleavage.Estudou-se a influência da cascata do ácido araquidónico (AA no desenvolvimento de embriões bovinos produzidos in vitro em co-cultura com células da granulosa. Os embriões foram suplementados com AA (100 µM desde o estádio de 1 célula até 8-16 células (primeiros três dias de co-cultura ou até a eclosão. Introduziram-se inibidores específicos da ciclo-oxigenase (indometacina, 28 µM e da lipo-oxigenase (ácido nordihidroguaiarético - NDGA, 28 µM, juntamente com o ácido araquidónico, desde o estádio de 1 célula até 8-16 c

  14. Synthesis of (9Z, 12E-, (9E, 12Z-[1-14C]-linoleic acid, (9Z, 12Z, 15E-, (9E, 12Z, 15Z-[1-14C]-linolenic acid and (5Z, 8Z, 11Z, 14E-[1-14C]-arachidonic acid

    Directory of Open Access Journals (Sweden)

    Enard, Thierry

    1996-04-01

    Full Text Available Trans polyunsaturated fatty acids are produced in vegetable oils during heat treatment (240-250 °C.ln order to study the metabolic pathway of 9c, 12t and 9t, 12c linoleic acid and 9c, 12c, 15t and 9t, 12c, 15c linolenic acid, these products were prepared labelled with carbon 14 in the carboxylic position. 5c, 8c, 11c, 14t-Arachidonic acid was also labelled on the carboxylic position with carbon 14 in order to study its physiological effects. To introduce the labelling (E-bromo precursors with a 17 carbons chain or a 19 carbon chain were needed. The different syntheses were done by elongation steps and creation of cis double bonds via highly stereospecific Wittig reactions. The radioactive carbon atom was introduced from [14C]-potassium cyanide. The final radioactive fatty acids had a specific activity greater than 50 mCi/mmol and a radioactive purity better than 99 % for linoleic and linolenic and better than 98.6 % for arachidonic acid.

  15. Arachidonic acid and lipoxinA4 attenuate streptozotocin-induced cytotoxicity to RIN5 F cells in vitro and type 1 and type 2 diabetes mellitus in vivo.

    Science.gov (United States)

    Gundala, Naveen K V; Naidu, Vegi G M; Das, Undurti N

    2017-03-01

    The aim of this study was to observe whether polyunsaturated fatty acids (PUFAs) can protect rat insulinoma (RIN5 F) cells against streptozotocin (STZ)-induced apoptosis in vitro and type 1 diabetes mellitus (T1DM) and type 2 DM (T2DM) in vivo and if so, what would be the mechanism of this action. RIN5 F cells were used for the in vitro study, whereas the in vivo study was performed in Wistar rats. STZ was used to induce apoptosis of RIN5 F cells in vitro and T1- and T2DM in vivo. The effect of PUFAs: γ-linolenic acid (GLA), arachidonic acid (AA) of ω-6 series, and eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) of ω-3 series; cyclooxygenase (COX) and lipoxygenase (LOX) inhibitors and antiinflammatory metabolite of AA and DHA, lipoxin A4 (LXA4), and resolvin D2 and protectin, respectively against STZ-induced cytotoxicity to RIN5 F cells in vitro and LXA4 against T1- and T2DM in vivo was studied. Changes in the antioxidant content, lipid peroxides, nitric oxide, and expression of PDX1, P65, nuclear factor-κb (NF-κb), and IKB genes in STZ-treated RIN5 F cells in vitro and Nrf2, GLUT2, COX2, iNOS protein levels in the pancreatic tissue of T1- and T2DM and LPCLN2 (lipocalin 2), NF-κb, IKB I in adipose tissue of T2DM after LXA4 treatment were studied. Plasma glucose, insulin, and tumor necrosis factor (TNF)-α levels also were measured in STZ-induced T1- and T2DM Wistar rats. Among all PUFAs tested, AA and EPA are the most effective against STZ-induced cytotoxicity to RIN5 F cells in vitro. Neither COX nor LOX inhibitors blocked the cytoprotective action of AA in vitro and T1- and T2DM by STZ. LXA4 production by RIN5 F cells in vitro and plasma LXA4 levels in STZ-induced T1- and T2DM animals were decreased by STZ that reverted to normal after AA treatment. AA prevented both T1- and T2DM induced by STZ. Antiinflammatory metabolite of AA and LXA4 prevented both T1- and T2DM induced by STZ. The expression of Pdx1, NF-κb, IKB genes in the

  16. Cross-validated stable-isotope dilution GC-MS and LC-MS/MS assays for monoacylglycerol lipase (MAGL) activity by measuring arachidonic acid released from the endocannabinoid 2-arachidonoyl glycerol.

    Science.gov (United States)

    Kayacelebi, Arslan Arinc; Schauerte, Celina; Kling, Katharina; Herbers, Jan; Beckmann, Bibiana; Engeli, Stefan; Jordan, Jens; Zoerner, Alexander A; Tsikas, Dimitrios

    2017-03-15

    2-Arachidonoyl glycerol (2AG) is an endocannabinoid that activates cannabinoid (CB) receptors CB1 and CB2. Monoacylglycerol lipase (MAGL) inactivates 2AG through hydrolysis to arachidonic acid (AA) and glycerol, thus modulating the activity at CB receptors. In the brain, AA released from 2AG by the action of MAGL serves as a substrate for cyclooxygenases which produce pro-inflammatory prostaglandins. Here we report stable-isotope GC-MS and LC-MS/MS assays for the reliable measurement of MAGL activity. The assays utilize deuterium-labeled 2AG (d 8 -2AG; 10μM) as the MAGL substrate and measure deuterium-labeled AA (d 8 -AA; range 0-1μM) as the MAGL product. Unlabelled AA (d 0 -AA, 1μM) serves as the internal standard. d 8 -AA and d 0 -AA are extracted from the aqueous buffered incubation mixtures by ethyl acetate. Upon solvent evaporation the residue is reconstituted in the mobile phase prior to LC-MS/MS analysis or in anhydrous acetonitrile for GC-MS analysis. LC-MS/MS analysis is performed in the negative electrospray ionization mode by selected-reaction monitoring the mass transitions [M-H] - →[M-H - CO 2 ] - , i.e., m/z 311→m/z 267 for d 8 -AA and m/z 303→m/z 259 for d 0 -AA. Prior to GC-MS analysis d 8 -AA and d 0 -AA were converted to their pentafluorobenzyl (PFB) esters by means of PFB-Br. GC-MS analysis is performed in the electron-capture negative-ion chemical ionization mode by selected-ion monitoring the ions [M-PFB] - , i.e., m/z 311 for d 8 -AA and m/z 303 for d 0 -AA. The GC-MS and LC-MS/MS assays were cross-validated. Linear regression analysis between the concentration (range, 0-1μM) of d 8 -AA measured by LC-MS/MS (y) and that by GC-MS (x) revealed a straight line (r 2 =0.9848) with the regression equation y=0.003+0.898x, indicating a good agreement. In dog liver, we detected MAGL activity that was inhibitable by the MAGL inhibitor JZL-184. Exogenous eicosatetraynoic acid is suitable as internal standard for the quantitative determination

  17. Evolution from increased cardiac mechanical function towards cardiomyopathy in the obese rat due to unbalanced high fat and abundant equilibrated diets

    Directory of Open Access Journals (Sweden)

    Mourmoura Evangelia

    2015-07-01

    Full Text Available The aim of our study was to know whether high dietary energy intake (HDEI with equilibrated and unbalanced diets in term of lipid composition modify the fatty acid profile of cardiac phospholipids and function of various cardiac cells and to know if the changes in membrane lipid composition can explain the modifications of cellular activity. Wistar rats were fed either a control or high-fat (HF diet for 12 weeks and Zucker diabetic fatty (ZDF rats as well as their lean littermate (ZL a control diet between week 7 to 11 of their life. Energy intake and abdominal obesity was increased in HF-fed and ZDF rats. Circulating lipids were also augmented in both strains although hyperglycemia was noticed only in ZDF rats. HDEI induced a decrease in linoleate and increase in arachidonate in membrane phospholipids which was more pronounced in the ZDF rats compared to the HF-fed rats. In vivo cardiac function (CF was improved in HF-fed rats whereas ex vivo cardiac function was unchanged, suggesting that environmental factors such as catecholamines stimulated the in vivo CF. The unchanged ex vivo CF was associated with an increased cardiac mass which indicated development of fibrosis and/or hypertrophy. The increased in vivo CF was sustained by an augmented coronary reserve which was related to the cyclooxygenase pathway and accumulation of arachidonate in membrane phospholipids. In conclusion, before triggering a diabetic cardiomyopathy, HDEI stimulated the CF. The development of cardiomyopathy seems to result from fibrosis and/or hypertrophy which augments myocardial stiffness and decreases contractility.

  18. Solute concentration affects bradykinin-mediated increases in renal prostaglandin E2

    International Nuclear Information System (INIS)

    Zenser, T.V.; Davis, E.S.; Rapp, N.S.; Davis, B.B.

    1981-01-01

    The effects of solute concentration on the bradykinin-mediated increase in inner medullary slice prostaglandin E2 (PGE2) synthesis were investigated. PG content was determined by specific RIA. Bradykinin stimulation was prevented by the addition of the following solutes to Krebs buffer: 1.0 M urea, 0.5 or 1.0 M NaCl, 0.5 or 1.0 M mannitol, 1.0 M urea plus 0.5 M NaCl, or 1.0 M mannitol plus 0.5 M NaCl. By contrast, basal PGE2 synthesis was increased by 1.0 M mannitol or by 1.0 M mannitol plus 0.5 M NaCl, but decreased by 1.0 M urea. Urea elicited a concentration-dependent, reversible inhibition of bradykinin stimulation, with 0.01 M urea being the lowest effective concentration. By contrast, basal PGE2 synthesis was only reduced at a urea concentration greater than 0.6 M. Arachidonic acid-mediated increases in both PGE2 and PGF2 alpha synthesis were not prevented by 1.0 M urea. The latter suggests that neither PG endoperoxide synthetase nor PG endoperoxide E isomerase are inhibited by urea. The data indicate that different hypertonic solutions have different effects on basal PG production, but all inhibit bradykinin stimulation

  19. Dietary omega-6 fatty acid lowering increases bioavailability of omega-3 polyunsaturated fatty acids in human plasma lipid pools.

    Science.gov (United States)

    Taha, Ameer Y; Cheon, Yewon; Faurot, Keturah F; Macintosh, Beth; Majchrzak-Hong, Sharon F; Mann, J Douglas; Hibbeln, Joseph R; Ringel, Amit; Ramsden, Christopher E

    2014-05-01

    Dietary linoleic acid (LA, 18:2n-6) lowering in rats reduces n-6 polyunsaturated fatty acid (PUFA) plasma concentrations and increases n-3 PUFA (eicosapentaenoic (EPA) and docosahexaenoic acid (DHA)) concentrations. To evaluate the extent to which 12 weeks of dietary n-6 PUFA lowering, with or without increased dietary n-3 PUFAs, alters unesterified and esterified plasma n-6 and n-3 PUFA concentrations in subjects with chronic headache. Secondary analysis of a randomized trial. Subjects with chronic headache were randomized for 12 weeks to (1) average n-3, low n-6 (L6) diet; or (2) high n-3, low n-6 LA (H3-L6) diet. Esterified and unesterified plasma fatty acids were quantified at baseline (0 weeks) and after 12 weeks on a diet. Compared to baseline, the L6 diet reduced esterified plasma LA and increased esterified n-3 PUFA concentrations (nmol/ml), but did not significantly change plasma arachidonic acid (AA, 20:4n-6) concentration. In addition, unesterified EPA concentration was increased significantly among unesterified fatty acids. The H3-L6 diet decreased esterified LA and AA concentrations, and produced more marked increases in esterified and unesterified n-3 PUFA concentrations. Dietary n-6 PUFA lowering for 12 weeks significantly reduces LA and increases n-3 PUFA concentrations in plasma, without altering plasma AA concentration. A concurrent increase in dietary n-3 PUFAs for 12 weeks further increases n-3 PUFA plasma concentrations and reduces AA. Published by Elsevier Ltd.

  20. Tributyltin chloride disrupts aortic vascular reactivity and increases reactive oxygen species production in female rats.

    Science.gov (United States)

    Ximenes, Carolina Falcão; Rodrigues, Samya Mere Lima; Podratz, Priscila Lang; Merlo, Eduardo; de Araújo, Julia Fernandez Puñal; Rodrigues, Lívia Carla Melo; Coitinho, Juliana Barbosa; Vassallo, Dalton Valentim; Graceli, Jones Bernardes; Stefanon, Ivanita

    2017-11-01

    Organotin compounds, such as tributyltin (TBT), are environment contaminants that induce bioaccumulation and have potential toxic effects on marine species and mammals. TBT have been banned by the International Maritime Organization in 2003. However, the assessment of butyltin and metal contents in marine sediments has demonstrated high residual levels of TBT in some cases exceeding 7000 ng Sn g -1 . The acceptable daily intake (ADI) level for TBT established by the World Health Organization is 0.5 μg/kg bw/day is based on genotoxicity, reproduction, teratogenicity, immunotoxicity, and mainly neurotoxicity. However, their effect on the cardiovascular system is not well understood. In this study, female rats were exposed to 0.5 μg/kg/day of TBT for 15 days with the goal of understanding the effect of TBT on vascular function. Female Wistar rats were treated daily by gavage and divided into control (n = 10) and TBT (n = 10) groups. The aortic rings were incubated with phenylephrine in both the presence and absence of endothelium. The phenylephrine concentration-response curves were generated by exposing endothelium-intact samples to N G -nitro-L-arginine methyl ester (L-NAME), apocynin, superoxide dismutase (SOD), catalase, tiron, and allopurinol. Acetylcholine (ACh) and sodium nitroprusside (SNP) were used to evaluate the relaxation response. Exposure to TBT reduced serum 17β-estradiol E 2 levels and increased vascular reactivity. After incubation with L-NAME, the vascular reactivity to phenylephrine was significantly higher. Apocynin, SOD, catalase, and tiron decreased the vascular reactivity to phenylephrine to a significantly greater extent in TBT-treated rats than in the control rat. The relaxation induced by ACh and SNP was significantly reduced in TBT rats. Exposure to TBT induced aortic wall atrophy and increased superoxide anion production and collagen deposition. These results provide evidence that exposing rats to the current ADI for TBT (0.5

  1. Tributyltin chloride increases phenylephrine-induced contraction and vascular stiffness in mesenteric resistance arteries from female rats

    Energy Technology Data Exchange (ETDEWEB)

    Ribeiro Júnior, Rogério Faustino, E-mail: rogeriofaustinoribeiro@hotmail.com [Department of Physiological Sciences, Federal University of Espirito Santo, Vitoria, ES (Brazil); Marques, Vinicius Bermond; Nunes, Dieli Oliveira; Ronconi, Karoline de Sousa [Department of Physiological Sciences, Federal University of Espirito Santo, Vitoria, ES (Brazil); Araújo, Julia F.P. de [Department of Morphology, Federal University of Espírito Santo (Brazil); Rodrigues, Paula Lopes; Padilha, Alessandra Simão; Vassallo, Dalton Valentim [Department of Physiological Sciences, Federal University of Espirito Santo, Vitoria, ES (Brazil); Graceli, Jones B. [Department of Morphology, Federal University of Espírito Santo (Brazil); Stefanon, Ivanita [Department of Physiological Sciences, Federal University of Espirito Santo, Vitoria, ES (Brazil)

    2016-03-15

    Tributyltin chloride (TBT) is an organotin compound that reduces estrogen levels in female rats. We aimed to investigate the effects of TBT exposure on vascular tonus and vascular remodelling in the resistance arteries of female rats. Rats were treated daily with TBT (500 ng/kg) for 15 days. TBT did not change arterial blood pressure but did modify some morpho-physiological parameters of third-order mesenteric resistance arteries in the following ways: (1) decreased lumen and external diameters; (2) increased wall/lm ratio and wall thickness; (3) decreased distensibility and increased stiffness; (4) increased collagen deposition; and (5) increased pulse wave velocity. TBT exposure increased the phenylephrine-induced contractile response in mesenteric resistance arteries. However, vasodilatation responses induced by acetylcholine and sodium nitroprusside were not modified by TBT. It is suggested that TBT exposure reduces vascular nitric oxide (NO) production, because:(1) L-NAME incubation did not cause a leftward shift in the concentration–response curve for phenylephrine; (2) both eNOS protein expression; (3) in situ NO production were reduced. Incubation with L-NAME; and (4) SOD shifted the phenylephrine response curve to the left in TBT rats. Tiron, catalase, ML-171 and VAS2870 decreased vascular reactivity to phenylephrine only in TBT rats. Moreover, increased superoxide anion production was observed in the mesenteric resistance arteries of TBT rats accompanied by an increase in gp91phox, catalase, AT{sub 1} receptor and total ERK1/2 protein expression. In conclusion, these findings show that TBT induced alterations are most likely due to a reduction of NO production combined with increased O{sub 2}{sup −} production derived from NADPH oxidase and ERK1/2 activation. These findings offer further evidence that TBT is an environmental risk factor for cardiovascular disease. - Highlights: • Tributyltin chloride reduces estrogen levels in female rats.

  2. Increased SRP reactor power

    International Nuclear Information System (INIS)

    MacAfee, I.M.

    1983-01-01

    Major changes in the current reactor hydraulic systems could be made to achieve a total of about 1500 MW increase of reactor power for P, K, and C reactors. The changes would be to install new, larger heat exchangers in the reactor buildings to increase heat transfer area about 24%, to increase H 2 O flow about 30% per reactor, to increase D 2 O flow 15 to 18% per reactor, and increase reactor blanket gas pressure from 5 psig to 10 psig. The increased reactor power is possible because of reduced inlet temperature of reactor coolant, increased heat removal capacity, and increased operating pressure (larger margin from boiling). The 23% reactor power increase, after adjustment for increased off-line time for reactor reloading, will provide a 15% increase of production from P, K, and C reactors. Restart of L Reactor would increase SRP production 33%

  3. Altered contractile response due to increased beta3-adrenoceptor stimulation in diabetic cardiomyopathy: the role of nitric oxide synthase 1-derived nitric oxide.

    Science.gov (United States)

    Amour, Julien; Loyer, Xavier; Le Guen, Morgan; Mabrouk, Nejma; David, Jean-Stéphane; Camors, Emmanuel; Carusio, Nunzia; Vivien, Benoît; Andriantsitohaina, Ramaroson; Heymes, Christophe; Riou, Bruno

    2007-09-01

    In the diabetic heart, the positive inotropic response to beta-adrenoceptor stimulation is altered and beta1 and beta2 adrenoceptors are down-regulated, whereas beta3 adrenoceptor is up-regulated. In heart failure, beta3-adrenoceptor stimulation induces a negative inotropic effect that results from endothelial nitric oxide synthase (NOS3)-derived nitric oxide production. The objective of our study was to investigate the role of beta3-adrenoceptor in diabetic cardiomyopathy. beta-Adrenergic responses were investigated in vivo (dobutamine echocardiography) and in vitro (left ventricular papillary muscle) in healthy and streptozotocin-induced diabetic rats. The effect of beta3-adrenoceptor inhibition on the inotropic response was studied in vitro. Immunoblots and NOS activities were performed in heart homogenates (electron paramagnetic resonance) and isolated cardiomyocytes. Data are mean percentage of baseline +/- SD. The impaired positive inotropic effect was confirmed in diabetes both in vivo (121 +/- 15% vs. 160 +/- 16%; P < 0.05) and in vitro (112 +/- 5% vs. 179 +/- 15%; P < 0.05). In healthy rat, the positive inotropic effect was not significantly modified in presence of beta3-adrenoceptor antagonist (174 +/- 20%), nonselective NOS inhibitor (N -nitro-l-arginine methylester [l-NAME]; 183 +/- 19%), or selective NOS1 inhibitor (vinyl-l-N-5-(1-imino-3-butenyl)-l-ornithine [l-VNIO]; 172 +/- 13%). In diabetes, in parallel with the increase in beta3-adrenoceptor protein expression, the positive inotropic effect was partially restored by beta3-adrenoceptor antagonist (137 +/- 8%; P < 0.05), l-NAME (133 +/- 11%; P < 0.05), or l-VNIO (130 +/- 13%; P < 0.05). Nitric oxide was exclusively produced by NOS1 within diabetic cardiomyocytes. NOS2 and NOS3 proteins were undetectable. beta3-Adrenoceptor is involved in altered positive inotropic response to beta-adrenoceptor stimulation in diabetic cardiomyopathy. This effect is mediated by NOS1-derived nitric oxide in diabetic

  4. Phospholipase D1 increases Bcl-2 expression during neuronal differentiation of rat neural stem cells.

    Science.gov (United States)

    Park, Shin-Young; Ma, Weina; Yoon, Sung Nyo; Kang, Min Jeong; Han, Joong-Soo

    2015-01-01

    We studied the possible role of phospholipase D1 (PLD1) in the neuronal differentiation, including neurite formation of neural stem cells. PLD1 protein and PLD activity increased during neuronal differentiation. Bcl-2 also increased. Downregulation of PLD1 by transfection with PLD1 siRNA or a dominant-negative form of PLD1 (DN-PLD1) inhibited both neurite outgrowth and Bcl-2 expression. PLD activity was dramatically reduced by a PLCγ (phospholipase Cγ) inhibitor (U73122), a Ca(2+)chelator (BAPTA-AM), and a PKCα (protein kinase Cα) inhibitor (RO320432). Furthermore, treatment with arachidonic acid (AA) which is generated by the action of PLA2 (phospholipase A2) on phosphatidic acid (a PLD1 product), increased the phosphorylation of p38 MAPK and CREB, as well as Bcl-2 expression, indicating that PLA2 is involved in the differentiation process resulting from PLD1 activation. PGE2 (prostaglandin E2), a cyclooxygenase product of AA, also increased during neuronal differentiation. Moreover, treatment with PGE2 increased the phosphorylation of p38 MAPK and CREB, as well as Bcl-2 expression, and this effect was inhibited by a PKA inhibitor (Rp-cAMP). As expected, inhibition of p38 MAPK resulted in loss of CREB activity, and when CREB activity was blocked with CREB siRNA, Bcl-2 production also decreased. We also showed that the EP4 receptor was required for the PKA/p38MAPK/CREB/Bcl-2 pathway. Taken together, these observations indicate that PLD1 is activated by PLCγ/PKCα signaling and stimulate Bcl-2 expression through PLA2/Cox2/EP4/PKA/p38MAPK/CREB during neuronal differentiation of rat neural stem cells.

  5. Ovariectomy increases the participation of hyperpolarizing mechanisms in the relaxation of rat aorta.

    Directory of Open Access Journals (Sweden)

    Ana Sagredo

    Full Text Available This study examines the downstream NO release pathway and the contribution of different vasodilator mediators in the acetylcholine-induced response in rat aorta 5-months after the loss of ovarian function. Aortic segments from ovariectomized and control female Sprague-Dawley rats were used to measure: the levels of superoxide anion, the superoxide dismutases (SODs activity, the cGMP formation, the cGMP-dependent protein kinase (PKG activity and the involvement of NO, cGMP, hydrogen peroxide and hyperpolarizing mechanisms in the ACh-induced relaxation. The results showed that ovariectomy did not alter ACh-induced relaxation; incubation with L-NAME, a NO synthase inhibitor, decreased the ACh-induced response to a lesser extent in aorta from ovariectomized than from control rats, while ODQ, a guanylate cyclase inhibitor, decreased that response to a similar extent; the blockade of hyperpolarizing mechanisms, by precontracting arteries with KCl, decreased the ACh-induced response to a greater extent in aortas from ovariectomized than those from control rats; catalase, that decomposes hydrogen peroxide, decreased the ACh-induced response only in aorta from ovariectomized rats. In addition, ovariectomy increased superoxide anion levels and SODs activity, decreased cGMP formation and increased PKG activity. Despite the increased superoxide anion and decreased cGMP in aorta from ovariectomized rats, ACh-induced relaxation is maintained by the existence of hyperpolarizing mechanisms in which hydrogen peroxide participates. The greater contribution of hydrogen peroxide in ACh-induced relaxation is due to increased SOD activity, in an attempt to compensate for increased superoxide anion formation. Increased PKG activity could represent a redundant mechanism to ensure vasodilator function in the aorta of ovariectomized rats.

  6. Increasing Public Expenditure

    Directory of Open Access Journals (Sweden)

    Ammar Ben Zaed

    2017-04-01

    Full Text Available This article aims to analyze and interpret the phenomenon of increased public expenditures and test explanatory theories as well as to analyze Abstract the relationship between public spending and GDP in the short and long term where you see the Wagner hypothesis that causal heading of GDP to government spending while there is a causal relationship analysis positive trending of government spending to GDP according to the Keynesian hypothesis in this study will be used descriptive analytical method to validate these hypotheses. Results in the short and long term made it clear that there is a difference in the outcome of Applied Studies where we find that each supports a relationship Wagner in the sense that the causal trending of real GDP to government spending and more precisely to increase the economic growth lead to increased aggregate demand which leads in turn increasing the need to increase government spending and to increase the resources available to the government sector to finance the increase in spending by the additional resources resulting from the economic growth while others opines opposes the existence of the relationship.

  7. Increasing income inequality

    DEFF Research Database (Denmark)

    Frederiksen, Anders; Poulsen, Odile

    In recent decades most developed countries have experienced an increase in income inequality. In this paper, we use an equilibrium search framework to shed additional light on what is causing an income distribution to change. The major benefit of the model is that it can accommodate shocks...... that shocks to the employees' relative productivity, i.e., skill-biased technological change, are unlikely to have caused the increase in income inequality....

  8. Increased Angiotensin II Sensitivity Contributes to Microvascular Dysfunction in Women Who Have Had Preeclampsia.

    Science.gov (United States)

    Stanhewicz, Anna E; Jandu, Sandeep; Santhanam, Lakshmi; Alexander, Lacy M

    2017-08-01

    Women who have had preeclampsia have increased cardiovascular disease risk; however, the mechanism(s) responsible for this association remain unclear. Microvascular damage sustained during a preeclamptic pregnancy may persist postpartum. The putative mechanisms mediating this dysfunction include a reduction in NO-dependent dilation and an increased sensitivity to angiotensin II. In this study, we evaluated endothelium-dependent dilation, angiotensin II sensitivity, and the therapeutic effect of angiotensin II receptor blockade (losartan) on endothelium-dependent dilation in vivo in the microvasculature of women with a history of preeclampsia (n=12) and control women who had a healthy pregnancy (n=12). We hypothesized that preeclampsia would have (1) reduced endothelium-dependent dilation, (2) reduced NO-mediated dilation, and (3) increased sensitivity to angiotensin II. We further hypothesized that localized losartan would increase endothelium-dependent vasodilation in preeclampsia. We assessed microvascular endothelium-dependent vasodilator function by measurement of cutaneous vascular conductance responses to graded infusion of acetylcholine (acetylcholine; 10 -7 -102 mmol/L) and a standardized local heating protocol in control sites and sites treated with 15 mmol/L L-NAME ( N G -nitro-l-arginine methyl ester; NO-synthase inhibitor) or 43 µmol/L losartan. Further, we assessed microvascular vasoconstrictor sensitivity to angiotensin II (10 -20 -10 -4 mol/L). Preeclampsia had significantly reduced endothelium-dependent dilation (-0.3±0.5 versus -1.0±0.4 log EC50 ; P Preeclampsia also had augmented vasoconstrictor sensitivity to angiotensin II (-10.2±1.3 versus -8.3±0.5; P =0.006). Angiotensin II type I receptor inhibition augmented endothelium-dependent vasodilation and NO-dependent dilation in preeclampsia but had no effect in healthy pregnancy. These data suggest that women who have had preeclampsia have persistent microvascular dysfunction postpartum

  9. Meeting increased demand.

    Science.gov (United States)

    Blair, Andrew

    2004-07-01

    New Zealand is a little country with a little economy but with a population that's rapidly aging. New Zealand's population is only 4.3 million people. It's GDP is only $US58.6 billion (2002). New Zealand's expenditure on health as a percentage of GDP is not out of line with that of other countries. As a nation we have been increasing expenditure on health over recent years. In 1990 we spent 7% of GDP on health. In 1995 that increased to 7.65% and is now 8.3%. However, in per capita terms our expenditure on health does not compare so well with like countries. The size of New Zealand's economy is restricting what our country spends on health. Health is already the second highest demand on the New Zealand tax dollar. The tolerance of New Zealanders would be challenged if a Government attempted to increase taxes further to meet the growing demands for expenditure on health, but at the same time the population's expectations are increasing. This is the challenging situation we face today. What lies ahead? Like all industrialized countries New Zealand is facing an aging population. The population below age 40 is decreasing, but it is increasing significantly over that age. 16% of the population is currently aged over 60. By 2051 this proportion will almost double to just over 31%. Coupled with the aging population is increased awareness and expectations, as access to options for treatment and technology becomes readily accessible to the population through such media as the internet. The extent of the impact of the aging population can be clearly represented by focusing on one specialty such as orthopaedics. The New Zealand Orthopaecic Association undertook a study in July 2003 which concluded (among other things) that as a result of the projected aging of the population, over the next 50 years: Musculo-skeletal operations will increase by over 30%. The number of hip replacements will nearly double. The incidence of osteoporosis will increase by a massive 201%. The number

  10. Increased urinary orosomucoid excretion

    DEFF Research Database (Denmark)

    Christiansen, M S; Iversen, K; Larsen, C T

    2009-01-01

    , impaired left ventricular function and endothelial dysfunction in patients with type 2 diabetes. MATERIAL AND METHODS: We performed a cross-sectional study of 41 patients with type 2 diabetes (17 patients with normal UOER and 24 with increased UOER) with no history of cardiovascular disease and 21 healthy...

  11. Integrated engineering increases flexibility

    International Nuclear Information System (INIS)

    Smith, Ray

    1991-01-01

    Integrated Engineering (IE) can be used to describe the best use of increasingly rare good engineering talent in an increasingly competive world. A number of organisations are now moving towards IE without any general agreement on a precise definition. The engineering division of British Nuclear Fuels (BNFL) is one such organisation. This feature covers the reasoning behind the decision, and our experience to date. BNFL engineering division is responsible primarily for the provision of major facilities on BNFL operational sites. This provision includes feasibility, front end and detailed design, procurement, installation and commissioning. Task force working has been used for some of the large projects. But the future workload is expected to comprise many more smaller projects. At the same time, equipment is becoming more complex and the need for mutual understanding and appreciation between disciplines is increasing. To meet this increasing need for flexibility, BNFL has decided to move to the matrix structure of project management and functional departments described in the article. (Author)

  12. Hypercholesterolemia increases plasma saturated and n-6 fatty acids altering prostaglandin homeostasis and promotes endothelial dysfunction in rabbits.

    Science.gov (United States)

    Medina, M; Alberto, M R; Sierra, L; Van Nieuwenhove, C; Saad, S; Isla, M I; Jerez, S

    2014-07-01

    The present study evaluated the plasma fatty acid levels and the vascular prostaglandin (PG) release in a rabbit model of early hypercholesterolemia with endothelial dysfunction. Rabbits were fed either a control diet (CD) or a diet containing 1 % cholesterol (HD) for 5-6 weeks. The level of fatty acids was measured in plasma. The levels of PG and nitric oxide (NO) released from the aorta were also determined. Vascular morphology of the aorta was characterized by intima and media thickness measurements. The rabbits fed with HD had higher levels of arachidonic acid (ARA) and lower levels of oleic acid. The linoleic acid level was unchanged. PGI(2) and NO were diminished and PGF(2α) levels, the PGI(2)/TXA(2) ratio and the intima/media ratio were increased in rabbits fed with HD. In conclusion, feeding HD for a short period increased ARA plasma levels and unbalanced release of vasodilator/vasoconstrictor PG redirected the pathway to vasoconstrictor metabolite release. These lipid metabolism alterations in addition to the reduced NO levels and the moderate changes in the vascular morphology contributed to the endothelial dysfunction in this animal model. Therefore, the present findings support the importance of early correction or prevention of high cholesterol levels to disrupt the endothelial dysfunction process that leads to cardiovascular disease.

  13. High population increase rates.

    Science.gov (United States)

    1991-09-01

    In addition to its economic and ethnic difficulties, the USSR faces several pressing demographic problems, including high population increase rates in several of its constituent republics. It has now become clear that although the country's rigid centralized planning succeeded in covering the basic needs of people, it did not lead to welfare growth. Since the 1970s, the Soviet economy has remained sluggish, which as led to increase in the death and birth rates. Furthermore, the ideology that held that demography could be entirely controlled by the country's political and economic system is contradicted by current Soviet reality, which shows that religion and ethnicity also play a significant role in demographic dynamics. Currently, Soviet republics fall under 2 categories--areas with high or low natural population increase rates. Republics with low rates consist of Christian populations (Armenia, Moldavia, Georgia, Byelorussia, Russia, Lithuania, Estonia, Latvia, Ukraine), while republics with high rates are Muslim (Tadzhikistan, Uzbekistan, Turkmenistan, Kirgizia, Azerbaijan Kazakhstan). The later group has natural increase rates as high as 3.3%. Although the USSR as a whole is not considered a developing country, the later group of republics fit the description of the UNFPA's priority list. Another serious demographic issue facing the USSR is its extremely high rate of abortion. This is especially true in the republics of low birth rates, where up to 60% of all pregnancies are terminated by induced abortions. Up to 1/5 of the USSR's annual health care budget is spent on clinical abortions -- money which could be better spent on the production of contraceptives. Along with the recent political and economic changes, the USSR is now eager to deal with its demographic problems.

  14. Global Increases in Individualism.

    Science.gov (United States)

    Santos, Henri C; Varnum, Michael E W; Grossmann, Igor

    2017-09-01

    Individualism appears to have increased over the past several decades, yet most research documenting this shift has been limited to the study of a handful of highly developed countries. Is the world becoming more individualist as a whole? If so, why? To answer these questions, we examined 51 years of data on individualist practices and values across 78 countries. Our findings suggest that individualism is indeed rising in most of the societies we tested. Despite dramatic shifts toward greater individualism around the world, however, cultural differences remain sizable. Moreover, cultural differences are primarily linked to changes in socioeconomic development, and to a lesser extent to shifts in pathogen prevalence and disaster frequency.

  15. ORIC Beam Energy Increase

    CERN Document Server

    Mallory, Merrit L; Dowling, Darryl; Hudson, Ed; Lord, Dick; Tatum, Alan

    2005-01-01

    The detection of and solution to a beam interference problem in the Oak Ridge Isochronous Cyclotron (ORIC) extraction system has yielded a 20% increase in the proton beam energy. The beam from ORIC was designed to be extracted before the nu r equal one resonance. Most cyclotrons extract after the nu r equal one resonance, thus getting more usage of the magnetic field for energy acceleration. We have now determined that the electrostatic deflector septum interferes with the last accelerated orbit in ORIC, with the highest extraction efficiency obtained near the maximum nu r value. This nu r provides a rotation in the betatron oscillation amplitude that is about the same length as the electrostatic septum thus allowing the beam to jump over the interference problem with the septum. With a thinned septum we were able to tune the beam through the nu r equal one resonance and achieve a 20% increase in beam energy. This nu r greater than one extraction method may be desirable for very high field cyclotrons since it...

  16. Influencia del α-tocoferol en la incorporación y peroxidación del ácido araquidónico en alevines parr de salmón del Atlántico (Salmo salar L. Influence of α-tocopherol on arachidonic acid deposition and peroxidation in Atlantic salmon (Salmo salar L. fingerlings

    Directory of Open Access Journals (Sweden)

    Patricio Dantagnan

    2012-09-01

    Full Text Available Se evaluó el efecto sinérgico del ácido araquidónico (ARA (20:4n-6 y el α-tocoferol en la acumulación de estos nutrientes y su peroxidación en el músculo e hígado en juveniles de salmón del Atlántico (Salmo salar. Grupos por triplicado se alimentaron por 12 semanas con ocho dietas experimentales que contenían diferentes niveles de ácido araquidónico y α-tocoferol. Los parámetros productivos no se vieron afectados (P > 0,05 por las dietas suministradas. La acumulación del ARA en el músculo e hígado mostró diferencias significativas (P The synergistic effect of arachidonic acid (ARA (20:4n-6 and α-tocopherol on the accumulation of fatty acids and the peroxidation of lipids in liver and muscle was evaluated in Atlantic salmon (Salmo salar juveniles. Triplicate groups were fed during 12 weeks with eight experimental diets with different levels of ARA and α-tocopherol. In all experimental diets the productive parameters were not affected (P > 0.05. ARA accumulation in muscle and liver showed significant differences (P < 0.05 between treatments. The synergic relationship between ARAAx4ocopherol was influenced (P < 0.05 only in the liver, showing that high levels of α-tocopherol and ARA favored the fatty acids accumulation in this organ. Results indicate that a dietary concentration up to 0.6% ARA, the increment of α-tocopherol is not necessary. The data obtained in this study demonstrated that the interaction between the ARA and α-tocopherol influenced the accumulation of fatty acids in the liver.

  17. Dietary omega-6 fatty acid lowering increases bioavailability of omega-3 polyunsaturated fatty acids in human plasma lipid pools

    Science.gov (United States)

    Taha, Ameer Y.; Cheon, Yewon; Faurot, Keturah F.; MacIntosh, Beth; Majchrzak-Hong, Sharon F.; Mann, J. Douglas; Hibbeln, Joseph R.; Ringel, Amit; Ramsden, Christopher E.

    2014-01-01

    Background Dietary linoleic acid (LA, 18:2n-6) lowering in rats reduces n-6 polyunsaturated fatty acid (PUFA) plasma concentrations and increases n-3 PUFA (eicosapentaenoic (EPA) and docosahexaenoic acid (DHA)) concentrations. Objective To evaluate the extent to which 12 weeks of dietary n-6 PUFA lowering, with or without increased dietary n-3 PUFAs, change unesterified and esterified plasma n-6 and n-3 PUFA concentrations in subjects with chronic headache. Design Secondary analysis of a randomized trial. Subjects with chronic headache were randomized for 12 weeks to: (1) average n-3, low n-6 (L6) diet; or (2) high n-3, low n-6 LA (H3-L6) diet. Esterified and unesterified plasma fatty acids were quantified at baseline (0 weeks) and after 12 weeks on a diet. Results Compared to baseline, the L6 diet reduced esterified plasma LA and increased esterified n-3 PUFA concentrations (nmol/ml), but did not significantly change plasma arachidonic acid (AA, 20:4n-6) concentration. In addition, unesterified EPA concentration was increased significantly among unesterified fatty acids. The H3-L6 diet decreased esterified LA and AA concentrations, and produced more marked increases in esterified and unesterified n-3 PUFA concentrations. Conclusion Dietary n-6 PUFA lowering for 12 weeks significantly reduces LA and increases n-3 PUFA concentrations in plasma, without altering plasma AA concentration. A concurrent increase in dietary n-3 PUFA for 12 weeks further increases n-3 PUFA plasma concentrations, but also reduces AA. PMID:24675168

  18. Damage-associated molecular pattern activated Toll-like receptor 4 signalling modulates blood pressure in L-NAME-induced hypertension

    Czech Academy of Sciences Publication Activity Database

    Sollinger, D.; Eissler, R.; Lorenz, S.; Strand, S.; Chmielewski, S.; Aoqui, C.; Schmaderer, Ch.; Bluyssen, H.; Zicha, Josef; Witzke, O.; Scherer, E.; Lutz, J.; Heemann, U.; Baumann, M.

    2014-01-01

    Roč. 101, č. 3 (2014), s. 464-472 ISSN 0008-6363 R&D Projects: GA ČR(CZ) GA305/09/0336 Institutional research plan: CEZ:AV0Z50110509 Institutional support: RVO:67985823 Keywords : innate immunity * Toll-like receptors * reactive oxygen species * vascular contractility Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 5.940, year: 2014

  19. MULTIPLEXED IMMUNOASSAYS FOR SIMULTANEOUS QUANTIFICATION OF CARDIOVASCULAR BIOMARKERS IN THE MODEL OF H-G-NITRO-L-ARGININE METHYLESTER (L-NAME) HYPERTENSIVE RAT

    Czech Academy of Sciences Publication Activity Database

    Adamcova, M.; Růžičková, Šárka; Simko, F.

    2013-01-01

    Roč. 64, č. 2 (2013), s. 211-217 ISSN 0867-5910 Institutional research plan: CEZ:AV0Z50520701 Keywords : cardiac biomarkers * multiplex assay * cardiac troponin Subject RIV: ED - Physiology Impact factor: 2.720, year: 2013

  20. Gas revenue increasingly significant

    International Nuclear Information System (INIS)

    Megill, R.E.

    1991-01-01

    This paper briefly describes the wellhead prices of natural gas compared to crude oil over the past 70 years. Although natural gas prices have never reached price parity with crude oil, the relative value of a gas BTU has been increasing. It is one of the reasons that the total amount of money coming from natural gas wells is becoming more significant. From 1920 to 1955 the revenue at the wellhead for natural gas was only about 10% of the money received by producers. Most of the money needed for exploration, development, and production came from crude oil. At present, however, over 40% of the money from the upstream portion of the petroleum industry is from natural gas. As a result, in a few short years natural gas may become 50% of the money revenues generated from wellhead production facilities

  1. Omeprazole increases the efficacy of a soluble epoxide hydrolase inhibitor in a PGE2 induced pain model

    International Nuclear Information System (INIS)

    Goswami, Sumanta Kumar; Inceoglu, Bora; Yang, Jun; Wan, Debin; Kodani, Sean D.; Trindade da Silva, Carlos Antonio; Morisseau, Christophe; Hammock, Bruce D.

    2015-01-01

    Epoxyeicosatrienoic acids (EETs) are potent endogenous analgesic metabolites produced from arachidonic acid by cytochrome P450s (P450s). Metabolism of EETs by soluble epoxide hydrolase (sEH) reduces their activity, while their stabilization by sEH inhibition decreases both inflammatory and neuropathic pain. Here, we tested the complementary hypothesis that increasing the level of EETs through induction of P450s by omeprazole (OME), can influence pain related signaling by itself, and potentiate the anti-hyperalgesic effect of sEH inhibitor. Rats were treated with OME (100 mg/kg/day, p.o., 7 days), sEH inhibitor TPPU (3 mg/kg/day, p.o.) and OME (100 mg/kg/day, p.o., 7 days) + TPPU (3 mg/kg/day, p.o., last 3 days of OME dose) dissolved in vehicle PEG400, and their effect on hyperalgesia (increased sensitivity to pain) induced by PGE 2 was monitored. While OME treatment by itself exhibited variable effects on PGE 2 induced hyperalgesia, it strongly potentiated the effect of TPPU in the same assay. The significant decrease in pain with OME + TPPU treatment correlated with the increased levels of EETs in plasma and increased activities of P450 1A1 and P450 1A2 in liver microsomes. The results show that reducing catabolism of EETs with a sEH inhibitor yielded a stronger analgesic effect than increasing generation of EETs by OME, and combination of both yielded the strongest pain reducing effect under the condition of this study. - Highlights: • The soluble epoxide hydrolase (sEH) inhibitor TPPU is anti-hyperalgesic. • Omeprazole potentiates the anti-hyperalgesic actions of TPPU. • This potentiation is associated with increased P450 activity. • The potentiation is associated with an increase in fatty acid epoxide/diol ratio. • Joint use of sEH inhibitors and P450 inducers could result in drug–drug interactions.

  2. Low mercury concentration produces vasoconstriction, decreases nitric oxide bioavailability and increases oxidative stress in rat conductance artery.

    Directory of Open Access Journals (Sweden)

    Núbia Belem Lemos

    Full Text Available Mercury is an environmental pollutant that reduces nitric oxide (NO bioavailability and increases oxidative stress, having a close link with cardiovascular diseases, as carotid atherosclerosis, myocardial infarction, coronary heart disease and hypertension. One of the main sites affected by oxidative stress, which develops atherosclerosis, is the aorta. Under acute exposure to low mercury concentrations reactive oxygen species (ROS production were only reported for resistance vessels but if low concentrations of mercury also affect conductance arteries it is still unclear. We investigated the acute effects of 6 nM HgCl(2 on endothelial function of aortic rings measuring the reactivity to phenylephrine in rings incubated, or not, with HgCl(2 for 45 min, the protein expression for cyclooxygenase 2 (COX-2 and the AT1 receptor. HgCl(2 increased Rmax and pD2 to phenylephrine without changing the vasorelaxation induced by acetylcholine and sodium nitroprusside. Endothelial damage abolished the increased reactivity to phenylephrine. The increase of Rmax and pD2 produced by L-NAME was smaller in the presence of HgCl(2. Enalapril, losartan, indomethacin, furegrelate, the selective COX-2 inhibitor NS 398, superoxide dismutase and the NADPH oxidase inhibitor apocynin reverted HgCl(2 effects on the reactivity to phenylephrine, COX-2 protein expression was increased, and AT1 expression reduced. At low concentration, below the reference values, HgCl(2 increased vasoconstrictor activity by reducing NO bioavailability due to increased ROS production by NADPH oxidase activity. Results suggest that this is due to local release of angiotensin II and prostanoid vasoconstrictors. Results also suggest that acute low concentration mercury exposure, occurring time to time could induce vascular injury due to endothelial oxidative stress and contributing to increase peripheral resistance, being a high risk factor for public health.

  3. Increasing paternal responsibility.

    Science.gov (United States)

    Cutright, P

    1985-01-01

    Increasing numbers of fathers of children born out of wedlock are not contributing to these children's economic support. In 1981, a tiny minority (14%) of the 1.7 million never-married mothers living with a child with an absent father had a child-support award, and of these, just 112,000 actually received some payment in 1981. The high rates of noncompliance, and the low level of legal efforts to enforce child support, are the result of attempts to collect payments through inefficient traditional methods, not the inability of fathers to pay, a Wisconsin study has shown. A basic problem with collecting child support under the present system is that it relies on fathers to control their expenditures and voluntarily to send the payment on a weekly, biweekly or monthly basis, year after year. As a Wisconsin study shows, full compliance with court-ordered payments dropped from 38% in the 1st year to below 20% by the 5th year among 163 ex-husbands tracked. A proposal by researchers at the University of Wisconsin's Institute for Research on Poverty calls for an "absent-parent tax." The Wisconsin Plan, as it is known, is simply a withholding tax based on the father's gross income and the number of his absent children. If his income falls below a certain level, payments will stop automatically, but will resume if and when it rises above the cutoff point. The Wisconsin plan removes all judicial discretion and lawyer's skill as factors in child-support awards, thus eliminating erratic awards. It also insures that support payments will be maintained during periods of conflict between the father and mother. However, before the Wisconsin Plan can effectively protect children both out of wedlock, a feature needs to be added that will establish paternity at birth. Imposing a real child-support obligation on fathers of children born outside of marriage will introduce a potentially powerful economic incentive for responsible male reproductive and parental behavior.

  4. Fatty acid amide hydrolase (FAAH) regulates hypercapnia/ischemia-induced increases in n-acylethanolamines in mouse brain.

    Science.gov (United States)

    Lin, Lin; Metherel, Adam H; Jones, Peter J; Bazinet, Richard P

    2017-09-01

    N-acylethanolamines (NAEs) are endogenous lipid ligands for several receptors including cannabinoid receptors and peroxisome proliferator-activated receptor-alpha (PPAR-α), which regulate numerous physiological functions. Fatty acid amide hydrolase (FAAH) is largely responsible for the degradation of NAEs. However, at high concentrations of ethanolamines and unesterified fatty acids, FAAH can also catalyze the reverse reaction, producing NAEs. Several brain insults such as ischemia and hypoxia increase brain unesterified fatty acids. Because FAAH can catalyze the synthesis of NAE, we aimed to test whether FAAH was necessary for CO 2 -induced hypercapnia/ischemia increases in NAE. To test this, we examined levels of NAEs, 1- and 2-arachidonoylglycerols as well as their corresponding fatty acid precursors in wild-type and mice lacking FAAH (FAAH-KO) with three Kill methods: (i) head-focused, high-energy microwave irradiation (microwave), (ii) 5 min CO 2 followed by microwave irradiation (CO 2 + microwave), and (iii) 5 min CO 2 only (CO 2 ). Both CO 2 -induced groups increased, to a similar extent, brain levels of unesterified oleic, arachidonic, and docosahexaenoic acid and 1- and 2-arachidonoylglycerols compared to the microwave group in both wild-type and FAAH-KO mice. Oleoylethanolamide (OEA), arachidonoylethanolamide (AEA), and docosahexaenoylethanolamide (DHEA) levels were about 8-, 7-, and 2.5-fold higher, respectively, in the FAAH-KO mice compared with the wild-type mice. Interestingly, the concentrations of OEA, AEA, and DHEA increased 2.5- to 4-fold in response to both CO 2 -induced groups in wild-type mice, but DHEA increased only in the CO 2 group in FAAH-KO mice. Our study demonstrates that FAAH is necessary for CO 2 - induced increases in OEA and AEA but not DHEA. Targeting brain FAAH could impair the production of NAEs in response to brain injuries. © 2017 International Society for Neurochemistry.

  5. Increased PUFA Content and 5-Lipoxygenase Pathway Expression Are Associated with Subcutaneous Adipose Tissue Inflammation in Obese Women with Type 2 Diabetes

    Directory of Open Access Journals (Sweden)

    Mattijs M. Heemskerk

    2015-09-01

    Full Text Available Obese women with type 2 diabetes mellitus (T2DM have more inflammation in their subcutaneous white adipose tissue (sWAT than age-and-BMI similar obese women with normal glucose tolerance (NGT. We aimed to investigate whether WAT fatty acids and/or oxylipins are associated with the enhanced inflammatory state in WAT of the T2DM women. Fatty acid profiles were measured in both subcutaneous and visceral adipose tissue (vWAT of 19 obese women with NGT and 16 age-and-BMI similar women with T2DM. Oxylipin levels were measured in sWAT of all women. Arachidonic acid (AA and docosahexaenoic acid (DHA percentages were higher in sWAT, but not vWAT of the T2DM women, and AA correlated positively to the gene expression of macrophage marker CD68. We found tendencies for higher oxylipin concentrations of the 5-LOX leukotrienes in sWAT of T2DM women. Gene expression of the 5-LOX leukotriene biosynthesis pathway was significantly higher in sWAT of T2DM women. In conclusion, AA and DHA content were higher in sWAT of T2DM women and AA correlated to the increased inflammatory state in sWAT. Increased AA content was accompanied by an upregulation of the 5-LOX pathway and seems to have led to an increase in the conversion of AA into proinflammatory leukotrienes in sWAT.

  6. Effect of extra virgin olive oil components on the arachidonic acid cascade, colorectal cancer and colon cancer cell proliferation; Efecto de los componentes del aceite de oliva virgen extra en la cascada del ácido araquidónico, el cáncer colorrectal y la proliferación de células de cáncer de colon.

    Energy Technology Data Exchange (ETDEWEB)

    Storniolo, C.E.; Moreno, J.J.

    2016-07-01

    The mediterranean diet (MD) reduced the risk of colorectal cancer (CRC), and olive oil, the primary source of fat in the MD, has also been found to have a protective effect. However, animals fed with oleic acid present a high number of intestinal tumours, suggesting that oleic acid and olive oil consumption can exert different effects on CRC. Considering that extra virgin olive oil (EVOO) is a complex mix of fatty acids and minor compounds such as polyphenols, hydrocarbons, phytosterols and triterpenes; and that these compounds have antioxidant activity and consequently they can modulate the arachidonic acid (AA) cascade and eicosanoid synthesis. This review analyzes the state of the art of olive oil components on the AA cascade and cellular mechanism involved in CRC such as intestinal epithelial cell growth/apoptosis, to understand the fact that the consumption of seed oils with high oleic content or EVOO will probably have different effects on CRC development. [Spanish] La dieta Mediterranea (DM) y el aceite de oliva reducen el riesgo de cáncer colorrectal (CCR). Sin embargo, animales alimentados con dietas ricas en ácido oleico presentan un elevado número de tumores intestinales, lo que sugiere que el consumo de ácido oleico y aceite de oliva pueden tener efectos diferentes sobre el desarrollo de CCR. Considerando que el aceite de oliva extra virgen (AOEV) es una compleja mezcla de ácidos grasos y compuestos minoritarios como polifenoles, lignanos, hidrocarburos, fitoesteroles y triterpenos; y que algunos de estos compuestos son antioxidantes y modulan la cascada del ácido araquidónico (AA) y la producción de eicosanoides. Analizamos la información existente sobre el efecto de los componentes del AOEV sobre la cascada del AA y los mecanismos implicados en el CCR como el crecimiento de las células epiteliales intestinales/apoptosis, lo que nos permitirá entender por qué el consumo de aceites de semillas altos en oleico o AOEV probablemente tendr

  7. Low Penetrance Alleles in Colorectal Cancer: the arachidonic acid pathway

    NARCIS (Netherlands)

    C.L.E. Siezen

    2006-01-01

    textabstractIn summary, we can conclude that we have successfully identified low penetrance alleles in the PPAR., PLA2G2A and ALOX15 genes, conferring differential colorectal adenoma risk, and two such alleles in the PTGS2 gene, one of which is also involved in colorectal cancer risk. These

  8. Arachidonic acid is a chemoattractant for Dictyostelium discoideum ...

    Indian Academy of Sciences (India)

    SEARCHU

    binding proteins and calmodulin-dependent phosphorylation linked to calmodulin-dependent chemotaxis to folic and cAMP in Dictyostelium; Cell Signal 13 575–584. Gerisch G and Hess B 1974 Cyclic-AMP-controlled oscillations in suspended Dictyostelium cells: Their relation to morphogenetic cell interactions; Proc. Natl.

  9. Fructose intake exacerbates the contractile response elicited by norepinephrine in mesenteric vascular bed of rats via increased endothelial prostanoids.

    Science.gov (United States)

    Sousa, Glauciene J; Oliveira, Phablo Wendell C; Nogueira, Breno V; Melo, Antônio F; Faria, Thaís de Oliveira; Meira, Eduardo Frizera; Mill, José G; Bissoli, Nazaré S; Baldo, Marcelo P

    2017-10-01

    Chronic fructose intake induces major cardiovascular and metabolic disturbances and is associated with the development of hypertension due to changes in vascular function. We hypothesized that high fructose intake for 6 weeks would cause metabolic syndrome and lead to initial vascular dysfunction. Male Wistar rats were assigned to receive fructose (FRU, 10%) or drinking water (CON) for 6 weeks. Systolic blood pressure was evaluated by tail plethysmography. Fasting glucose, insulin and glucose tolerance were measured at the end of the follow-up. Mesenteric vascular bed reactivity was tested before and after pharmacological blockade. Western blot analysis was performed for iNOS, eNOS, Nox2 and COX-2. DHE staining was used for vascular superoxide anion detection. Vessel structure was evaluated by optical and electronic microscopy. Fructose intake did not alter blood pressure, but did increase visceral fat deposition and fasting glucose as well as impair insulin and glucose tolerance. Fructose increased NE-induced vasoconstriction compared with CON, and this difference was abrogated by indomethacin perfusion as well as endothelium removal. ACh-induced relaxation was preserved, and the NO modulation tested after L-NAME perfusion was similar between groups. SNP-induced relaxation was not altered. Inducible NOS was increased; however, there were no changes in eNOS, Nox2 or COX-2 protein expression. Basal or stimulated superoxide anion production was not changed by fructose intake. In conclusion, high fructose intake increased NE-induced vasoconstriction through the endothelial prostanoids even in the presence of a preserved endothelium-mediated relaxation. No major changes in vessel structure were detected. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Increased platelet expression of glycoprotein IIIa following aspirin treatment in aspirin-resistant but not aspirin-sensitive subjects

    Science.gov (United States)

    Floyd, Christopher N; Goodman, Timothy; Becker, Silke; Chen, Nan; Mustafa, Agnesa; Schofield, Emma; Campbell, James; Ward, Malcolm; Sharma, Pankaj; Ferro, Albert

    2014-01-01

    Aims Aspirin is widely used as an anti-platelet agent for cardiovascular prophylaxis. Despite aspirin treatment, many patients experience recurrent thrombotic events, and aspirin resistance may contribute to this. We examined the prevalence of aspirin resistance in a healthy population, and investigated whether the platelet proteome differed in aspirin-resistant subjects. Methods Ninety-three healthy subjects received aspirin 300 mg daily for 28 days. Before and at the end of treatment, urine was taken to determine 11-dehydrothromboxane B2, and blood was taken to measure arachidonic acid (AA)-induced aggregation of platelet-rich plasma and to interrogate the platelet proteome by mass spectrometric analysis with further confirmation of findings using Western blotting. Results In two of the 93 subjects, neither AA-induced aggregation nor urinary 11-dehydrothromboxane B2 was effectively suppressed by aspirin, despite measurable plasma salicylate concentrations, suggesting the presence of true aspirin resistance. Despite no detectable differences in the platelet proteome at baseline, following aspirin a marked increase was seen in platelet glycoprotein IIIa expression in the aspirin-resistant but not aspirin-sensitive subjects. An increase in platelet glycoprotein IIIa expression with aspirin resistance was confirmed in a separate cohort of 17 patients with stable coronary artery disease on long term aspirin treatment, four of whom exhibited aspirin resistance. Conclusions In a healthy population, true aspirin resistance is uncommon but exists. Resistance is associated with an increase in platelet glycoprotein IIIa expression in response to aspirin. These data shed new light on the mechanism of aspirin resistance, and provide the potential to identify aspirin-resistant subjects using a novel biomarker. PMID:25099258

  11. Obligatory Role of EP1 Receptors in the Increase in Cerebral Blood Flow Produced by Hypercapnia in the Mice.

    Directory of Open Access Journals (Sweden)

    Ken Uekawa

    Full Text Available Hypercapnia induces potent vasodilation in the cerebral circulation. Although it has long been known that prostanoids participate in the cerebrovascular effects of hypercapnia, the role of prostaglandin E2 (PGE2 and PGE2 receptors have not been fully investigated. In this study, we sought to determine whether cyclooxygenase-1 (COX-1-derived PGE2 and EP1 receptors are involved in the cerebrovascular response induced by hypercapnia. Cerebral blood flow (CBF was recorded by laser-Doppler flowmetry in the somatosenasory cortex of anesthetized male EP1-/- mice and wild type (WT littermates. In WT mice, neocortical application of the EP1 receptor antagonist SC-51089 attenuated the increase in CBF elicited by systemic hypercapnia (pCO2 = 50-60 mmHg. SC-51089 also attenuated the increase in CBF produced by neocortical treatment of arachidonic acid or PGE2. These CBF responses were also attenuated in EP1-/- mice. In WT mice, the COX-1 inhibitor SC-560, but not the COX-2 inhibitor NS-398, attenuated the hypercapnic CBF increase. Neocortical application of exogenous PGE2 restored the attenuation in resting CBF and the hypercapnic response induced by SC-560. In contrast, exogenous PGE2 failed to rescue the attenuation both in WT mice induced by SC-51089 and EP1-/- mice, attesting to the obligatory role of EP1 receptors in the response. These findings indicate that the hypercapnic vasodilatation depends on COX-1-derived PGE2 acting on EP1 receptors and highlight the critical role that COX-1-derived PGE2 and EP1 receptors play in the hypercapnic regulation of the cerebral circulation.

  12. The IL1B-511 Polymorphism (rs16944 AA Genotype) Is Increased in Aspirin-Exacerbated Respiratory Disease in Mexican Population.

    Science.gov (United States)

    Falfán-Valencia, Ramcés; Pavón-Romero, Gandhi F; Camarena, Angel; García, María de la Luz; Galicia-Negrete, Gustavo; Negrete-García, María Cristina; Teran, Luis Manuel

    2012-01-01

    Aspirin exacerbated respiratory disease (AERD) is characterized by chronic hyperplastic rhinosinusitis, nasal polyposis, asthma, and aspirin sensitivity. The mechanisms which produce these manifestations of intolerance are not fully defined, current research focuses on cyclooxygenase 1 (COX-1) inhibition, metabolism of arachidonic acid, and the COX pathway to the lipoxygenase (LO) route, inducing increased synthesis of leukotrienes (LT). The biological plausibility of this model has led to the search for polymorphisms in genes responsible for proinflammatory cytokines synthesis, such as IL1B and IL8. We performed a genetic association study between IL8-251 (rs4073) and IL1B-511 (rs16944) polymorphisms in AERD, aspirin-tolerant asthma (ATA), and healthy control subjects. Using allelic discrimination by real-time PCR, we found statistically nonsignificant associations between AERD, ATA, and healthy control subjects for the GG and GA genotypes of IL1B (rs16944). Interestingly, the AA genotype showed an increased frequency in the AERD patients versus the ATA group (GF = 0.19 versus 0.07, p = 0.018, OR 2.98, and 95% CI 1.17-7.82). This is the first observation that IL1B polymorphisms are involved in AERD. Thus, future studies must investigate whether interleukin-1β is released in the airways of AERD patients and whether it relates to genetic polymorphisms in the IL1B gene.

  13. Increasing Northern Hemisphere water deficit

    Science.gov (United States)

    McCabe, Gregory J.; Wolock, David M.

    2015-01-01

    A monthly water-balance model is used with CRUTS3.1 gridded monthly precipitation and potential evapotranspiration (PET) data to examine changes in global water deficit (PET minus actual evapotranspiration) for the Northern Hemisphere (NH) for the years 1905 through 2009. Results show that NH deficit increased dramatically near the year 2000 during both the cool (October through March) and warm (April through September) seasons. The increase in water deficit near 2000 coincides with a substantial increase in NH temperature and PET. The most pronounced increases in deficit occurred for the latitudinal band from 0 to 40°N. These results indicate that global warming has increased the water deficit in the NH and that the increase since 2000 is unprecedented for the 1905 through 2009 period. Additionally, coincident with the increase in deficit near 2000, mean NH runoff also increased due to increases in P. We explain the apparent contradiction of concurrent increases in deficit and increases in runoff.

  14. Increasing instruction time in school does increase learning

    DEFF Research Database (Denmark)

    Andersen, Simon Calmar; Humlum, Maria; Nandrup, Anne Brink

    2016-01-01

    Increasing instruction time in school is a central element in the attempts of many governments to improve student learning, but prior research—mainly based on observational data—disputes the effect of this approach and points out the potential negative effects on student behavior. Based on a large......-scale, cluster-randomized trial, we find that increasing instruction time increases student learning and that a general increase in instruction time is at least as efficient as an expert-developed, detailed teaching program that increases instruction with the same amount of time. These findings support the value...... of increased instruction time....

  15. Efeito do lipopolissacarídio bacteriano sobre o esvaziamento gástrico de ratos: avaliação do pré-tratamento com Nw-nitro-L-arginine methyl ester (L-NAME The effect of bacterial lipopolysaccharide on the gastric emptying of rats: a pretreatment evaluation using Nw-nitro-L-arginine methyl ester (L-NAME

    Directory of Open Access Journals (Sweden)

    Edgard Ferro Collares

    2006-09-01

    Full Text Available RACIONAL: Há evidências de que o óxido nítrico participa do mecanismo de retardo do esvaziamento gástrico determinado pelo lipopolissacarídio bacteriano. OBJETIVO: Avaliar o efeito do pré-tratamento com Nw-nitro-L-arginine methyl ester, um inibidor competitivo das óxido nítrico-sintetases, sobre o fenômeno. MATERIAL E MÉTODOS: Utilizaram-se ratos, Wistar, machos, SPF ("specific-pathogen free", adultos, adaptados às condições do laboratório, que após 24 horas de jejum alimentar foram pré-tratados endovenosamente com veículo (salina ou Nw-nitro-L-arginine methyl ester nas doses de 0,5, 1, 2,5 e 5 mg/kg. No tratamento, administrou-se endovenosamente veículo (salina ou lipopolissacarídio (50 µg/kg. O intervalo entre o pré-tratamento e o tratamento foi de 10 minutos, e entre este e a avaliação do esvaziamento gástrico foi de 60 minutos. O esvaziamento gástrico foi avaliado indiretamente através da determinação da retenção gástrica da solução salina marcada com fenol vermelho 10 minutos após administração por via orogástrica. RESULTADOS: Entre os animais pré-tratados com veículo, o tratamento com lipopolissacarídio determinou elevação significativa da retenção gástrica (média = 57% em relação aos tratados com veículo (38,1%. O pré-tratamento com as diferentes doses de Nw-nitro-L-arginine methyl ester não modificou a retenção gástrica nos animais controles do tratamento. O pré-tratamento com Nw-nitro-L-arginine methyl ester com a dose de 1 mg/kg determinou redução discreta, mas significativa, na retenção gástrica (52% nos animais tratados com lipopolissacarídio, em relação ao observado naqueles com pré-tratamento e tratamento com veículo (35,9%. Nos animais pré-tratados com 2,5 e 5 mg/kg de Nw-nitro-L-arginine methyl ester e tratados com lipopolissacarídio, houve aumento significante da retenção gástrica (74,7% e 80,5%, respectivamente em relação aos seus controles pré-tratados com as mesmas doses do inibidor das óxido nítrico-sintetases e tratados com veículo (40,5% e 38,7%, respectivamente e àqueles pré-tratados com veículo e tratados com a mesma toxina. CONCLUSÃO: O pré-tratamento com Nw-nitro-L-arginine methyl ester numa dose baixa (1 mg/kg determinou redução discreta no efeito de retardo do esvaziamento gástrico determinado pelo lipopolissacarídio in vivo e aumento significativo do retardo com doses mais elevadas (2,5 e 5 mg/kg, doses estas que, per se, não interferem no esvaziamento.BACKGROUND: There is evidence that nitric oxide plays a role in the decrease in gastric emptying induced by bacterial lipopolysaccharide. AIM: To evaluate the effect of pretreatment with Nw-nitro-L-arginine methyl to ester, one competitive inhibitor of the nitric oxide syntases, on the gastric emptying delay induced by lipopolysaccharide. MATERIAL AND METHODS: Male Wistar rats, SPF, were used after 24 h fast and 1 h-water withdrawn. The pretreatment was done intravenously with vehicle (saline or Nw-nitro-L-arginine methyl to ester in the doses of 0.5, 1, 2.5 e 5 mg/kg. After 10 min, the animals were treated iv with lipopolysaccharide (50 mg/kg or received vehicle (saline. The gastric emptying was evaluated 1 h after the lipopolysaccharide administration. A saline solution containing phenol red was used as the test meal. The gastric emptying was indirectly assessed by the determination of percent gastric retention of the test meal 10 min after orogastric administration. RESULTS: The animals pretreated with vehicle and treatment with lipopolysaccharide have significant rise of the gastric retention (average = 57% in comparison with the controls receiving only vehicle (38.1%. The pretreatment with the different doses of Nw-nitro-L-arginine methyl to ester did not modify per se the gastric retention in comparison with the animals pretreated with vehicle. Pretreatment with Nw-nitro-L-arginine methyl to ester with the dose of 1 mg/kg determined a discrete but significant reduction in the gastric retention (52% of animals treated with lipopolysaccharide in comparison with vehicle-pretreated rats. Paradoxically, animals pretreated with 2.5 or 5 mg of Nw-nitro-L-arginine methyl to ester/kg followed by treatment with lipopolysaccharide displayed a significantly higher gastric retention (74.7% and 80.5%, respectively as compared to their controls, pretreated with the same doses of the inhibitor and treated with vehicle (40.5% and 38.7%, respectively and to those pretreated with vehicle and treated with the same toxin. CONCLUSION: The pretreatment with Nw-nitro-L-arginine methyl to ester at low dose (1 mg/kg resulted in a discrete inhibition of the gastric emptying delay induced by lipopolysaccharide. Nevertheless, Nw-nitro-L-arginine methyl to ester at higher doses (2.5 and 5 mg/kg induced an enhancement of the lipopolysaccharide effect on gastric emptying, despite not interfering with the gastric emptying per se.

  16. Aspirin provocation increases 8-iso-PGE2 in exhaled breath condensate of aspirin-hypersensitive asthmatics.

    Science.gov (United States)

    Mastalerz, Lucyna; Januszek, Rafał; Kaszuba, Marek; Wójcik, Krzysztof; Celejewska-Wójcik, Natalia; Gielicz, Anna; Plutecka, Hanna; Oleś, Krzysztof; Stręk, Paweł; Sanak, Marek

    2015-09-01

    Isoprostanes are bioactive compounds formed by non-enzymatic oxidation of polyunsaturated fatty acids, mostly arachidonic, and markers of free radical generation during inflammation. In aspirin exacerbated respiratory disease (AERD), asthmatic symptoms are precipitated by ingestion of non-steroid anti-inflammatory drugs capable for pharmacologic inhibition of cyclooxygenase-1 isoenzyme. We investigated whether aspirin-provoked bronchoconstriction is accompanied by changes of isoprostanes in exhaled breath condensate (EBC). EBC was collected from 28 AERD subjects and 25 aspirin-tolerant asthmatics before and after inhalatory aspirin challenge. Concentrations of 8-iso-PGF2α, 8-iso-PGE2, and prostaglandin E2 were measured using gas chromatography/mass spectrometry. Leukotriene E4 was measured by immunoassay in urine samples collected before and after the challenge. Before the challenge, exhaled 8-iso-PGF2α, 8-iso-PGE2, and PGE2 levels did not differ between the study groups. 8-iso-PGE2 level increased in AERD group only (p=0.014) as a result of the aspirin challenge. Urinary LTE4 was elevated in AERD, both in baseline and post-challenge samples. Post-challenge airways 8-iso-PGE2 correlated positively with urinary LTE4 level (p=0.046), whereas it correlated negatively with the provocative dose of aspirin (p=0.027). A significant increase of exhaled 8-iso-PGE2 after inhalatory challenge with aspirin was selective and not present for the other isoprostane measured. This is a novel finding in AERD, suggesting that inhibition of cyclooxygenase may elicit 8-iso-PGE2 production in a specific mechanism, contributing to bronchoconstriction and systemic overproduction of cysteinyl leukotrienes. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Soy-based infant formula supplemented with DHA and ARA supports growth and increases circulating levels of these fatty acids in infants.

    Science.gov (United States)

    Hoffman, Dennis; Ziegler, Ekhard; Mitmesser, Susan H; Harris, Cheryl L; Diersen-Schade, Deborah A

    2008-01-01

    Healthy term infants (n = 244) were randomized to receive: (1) control, soy-based formula without supplementation or (2) docosahexaenoic acid-arachidonic acid (DHA + ARA), soy-based formula supplemented with at least 17 mg DHA/100 kcal (from algal oil) and 34 mg ARA/100 kcal (from fungal oil) in a double-blind, parallel group trial to evaluate safety, benefits, and growth from 14 to 120 days of age. Anthropometric measurements were taken at 14, 30, 60, 90, and 120 days of age and 24-h dietary and tolerance recall were recorded at 30, 60, 90, and 120 days of age. Adverse events were recorded throughout the study. Blood samples were drawn from subsets of 25 infants in each group. Capillary column gas chromatography was used to analyze the percentages of fatty acids in red blood cell (RBC) lipids and plasma phospholipids. Compared with the control group, percentages of fatty acids such as DHA and ARA in total RBC and plasma phospholipids were significantly higher in infants in the DHA + ARA group at 120 days of age (P soy-based formula supplemented with DHA and ARA from single cell oil sources at concentrations similar to human milk significantly increased circulating levels of DHA and ARA when compared with the control group. Both formulas supported normal growth and were well tolerated.

  18. Strong increase of solar panels

    International Nuclear Information System (INIS)

    Segers, R.; Janssen, S.

    2012-01-01

    The number of installed solar panels in 2011 has increased again. 40 megawatt of new panels have been installed. This increase is twice as high as the year before. The production of solar power increased to 90 million kWh in 2011 as a result of this expansion. However, the share of solar power in total energy use is still very limited. [nl

  19. Increasing tobacco taxes : A cheap tool to increase public health

    NARCIS (Netherlands)

    van Baal, Pieter H. M.; Brouwer, Werner B. F.; Hoogenveen, Rudolf T.; Feenstra, Talitha L.

    Introduction: Several studies have estimated health effects resulting from tobacco tax increases. However, studies on the cost effectiveness of tobacco taxes are scarce. The aim of this study was to estimate the cost effectiveness of tobacco tax increases from a health care perspective, explicitly

  20. N-3 fatty acids reduced trans fatty acids retention and increased docosahexaenoic acid levels in the brain.

    Science.gov (United States)

    Lavandera, Jimena Verónica; Saín, Juliana; Fariña, Ana Clara; Bernal, Claudio Adrián; González, Marcela Aída

    2017-09-01

    The levels of docosahexaenoic acid (DHA, 22:6n-3) and arachidonic acid (AA, 20:4n-6) are critical for the normal structure and function of the brain. Trans fatty acids (TFA) and the source of the dietary fatty acids (FA) interfere with long-chain polyunsaturated fatty acids (LC-PUFA) biosynthesis. The aim of this study was to investigate the effect of TFA supplementation in diets containing different proportions of n-9, n-6, and n-3 FA on the brain FA profile, including the retention of TFA, LC-PUFA levels, and n-6/n-3 PUFA ratios. These parameters were also investigated in the liver, considering that LC-PUFA are mainly bioconverted from their dietary precursors in this tissue and transported by serum to the brain. Also, stearoyl-CoA desaturase-1 (SCD1) and sterol regulatory element-binding protein-1c (SREBP-1c) gene expressions were evaluated. Male CF1 mice were fed (16 weeks) diets containing different oils (olive, corn, and rapeseed) with distinct proportions of n-9, n-6, and n-3 FA (55.2/17.2/0.7, 32.0/51.3/0.9, and 61.1/18.4/8.6), respectively, substituted or not with 0.75% of TFA. FA composition of the brain, liver, and serum was assessed by gas chromatography. TFA were incorporated into, and therefore retained in the brain, liver, and serum. However, the magnitude of retention was dependent on the tissue and type of isomer. In the brain, total TFA retention was lower than 1% in all diets. Dietary n-3 PUFA decreased TFA retention and increased DHA accretion in the brain. The results underscore the importance of the type of dietary FA on the retention of TFA in the brain and also on the changes of the FA profile.

  1. Unsaturated free fatty acids increase benzodiazepine receptor agonist binding depending on the subunit composition of the GABAA receptor complex.

    Science.gov (United States)

    Witt, M R; Westh-Hansen, S E; Rasmussen, P B; Hastrup, S; Nielsen, M

    1996-11-01

    It has been shown previously that unsaturated free fatty acids (FFAs) strongly enhance the binding of agonist benzodiazepine receptor ligands and GABAA receptor ligands in the CNS in vitro. To investigate the selectivity of this effect, recombinant human GABAA/benzodiazepine receptor complexes formed by different subunit compositions (alpha x beta y gamma 2, x = 1, 2, 3, and 5; y = 1, 2, and 3) were expressed using the baculovirus-transfected Sf9 insect cell system. At 10(-4) M, unsaturated FFAs, particularly arachidonic (20:4) and docosahexaenoic (22:6) acids, strongly stimulated (> 200% of control values) the binding of [3H]flunitrazepam ([3H]FNM) to the alpha 3 beta 2 gamma 2 receptor combination in whole cell preparations. No effect or small increases in levels of unsaturated FFAs on [3H]FNM binding to alpha 1 beta x gamma 2 and alpha 2 beta x gamma 2 receptor combinations were observed, and weak effects (130% of control values) were detected using the alpha 5 beta 2 gamma 2 receptor combination. The saturated FFAs, stearic and palmitic acids, were without effect on [3H]FNM binding to any combination of receptor complexes. The hydroxylated unsaturated FFAs, ricinoleic and ricinelaidic acids, were shown to decrease the binding of [3H]FNM only if an alpha 1 beta 2 gamma 2 receptor combination was used. Given the heterogeneity of the GABAA/ benzodiazepine receptor subunit distribution in the CNS, the effects of FFAs on the benzodiazepine receptor can be assumed to vary at both cellular and regional levels.

  2. Increasing diversity in radiologic technology.

    Science.gov (United States)

    Carwile, Laura

    2003-01-01

    Diversity is increasingly important in the radiologic technology workplace. For significant changes to occur in work force diversity, educators must first recruit and retain students from a wide variety of backgrounds. This article examines personality, race and gender as factors affecting career choice and how educators can use these factors to increase diversity in their programs. An overview of the ASRT's efforts to improve diversity within the profession is presented, along with suggestions for developing effective recruitment and retention plans to increase diversity.

  3. Increasing Access to Special Collections

    Directory of Open Access Journals (Sweden)

    Ricky Erway

    2012-01-01

    Full Text Available In an environment where we increasingly have access to a collective collection of digitized books, special collections will become increasingly invisible if they are not accessible online. In an era of increasing expectations and decreasing budgets, finding ways to streamline some of our processes is the best way to enable us to do more with less. This report details a number of investigations into how access to special collections can be increased. It includes guidance running the gamut from digitization and rights management to policies and procedures.

  4. Assessing and Increasing Physical Activity

    Science.gov (United States)

    Van Camp, Carole M.; Hayes, Lynda B.

    2012-01-01

    Increasing physical activity is a crucial component of any comprehensive approach to combat the growing obesity epidemic. This review summarizes recent behavioral research on the measurement of physical activity and interventions aimed at increasing physical activity and provides directions for future research.

  5. Omeprazole increases the efficacy of a soluble epoxide hydrolase inhibitor in a PGE{sub 2} induced pain model

    Energy Technology Data Exchange (ETDEWEB)

    Goswami, Sumanta Kumar; Inceoglu, Bora; Yang, Jun; Wan, Debin; Kodani, Sean D. [Department of Entomology and Nematology, UC Davis Comprehensive Cancer Center, University of California, Davis, CA (United States); Trindade da Silva, Carlos Antonio [Department of Entomology and Nematology, UC Davis Comprehensive Cancer Center, University of California, Davis, CA (United States); Department of Genetics and Biochemistry, Federal University of Uberlandia, MG (Brazil); Morisseau, Christophe [Department of Entomology and Nematology, UC Davis Comprehensive Cancer Center, University of California, Davis, CA (United States); Hammock, Bruce D., E-mail: bdhammock@ucdavis.edu [Department of Entomology and Nematology, UC Davis Comprehensive Cancer Center, University of California, Davis, CA (United States)

    2015-12-15

    Epoxyeicosatrienoic acids (EETs) are potent endogenous analgesic metabolites produced from arachidonic acid by cytochrome P450s (P450s). Metabolism of EETs by soluble epoxide hydrolase (sEH) reduces their activity, while their stabilization by sEH inhibition decreases both inflammatory and neuropathic pain. Here, we tested the complementary hypothesis that increasing the level of EETs through induction of P450s by omeprazole (OME), can influence pain related signaling by itself, and potentiate the anti-hyperalgesic effect of sEH inhibitor. Rats were treated with OME (100 mg/kg/day, p.o., 7 days), sEH inhibitor TPPU (3 mg/kg/day, p.o.) and OME (100 mg/kg/day, p.o., 7 days) + TPPU (3 mg/kg/day, p.o., last 3 days of OME dose) dissolved in vehicle PEG400, and their effect on hyperalgesia (increased sensitivity to pain) induced by PGE{sub 2} was monitored. While OME treatment by itself exhibited variable effects on PGE{sub 2} induced hyperalgesia, it strongly potentiated the effect of TPPU in the same assay. The significant decrease in pain with OME + TPPU treatment correlated with the increased levels of EETs in plasma and increased activities of P450 1A1 and P450 1A2 in liver microsomes. The results show that reducing catabolism of EETs with a sEH inhibitor yielded a stronger analgesic effect than increasing generation of EETs by OME, and combination of both yielded the strongest pain reducing effect under the condition of this study. - Highlights: • The soluble epoxide hydrolase (sEH) inhibitor TPPU is anti-hyperalgesic. • Omeprazole potentiates the anti-hyperalgesic actions of TPPU. • This potentiation is associated with increased P450 activity. • The potentiation is associated with an increase in fatty acid epoxide/diol ratio. • Joint use of sEH inhibitors and P450 inducers could result in drug–drug interactions.

  6. Mechanisms whereby insulin increases diacylglycerol in BC3H-1 myocytes.

    Science.gov (United States)

    Farese, R V; Cooper, D R; Konda, T S; Nair, G; Standaert, M L; Davis, J S; Pollet, R J

    1988-01-01

    /PE labelling by [3H]arachidonic acid, [3H]myristic acid, and [14C]choline. Phenylephrine, ionophore A23187 and phorbol esters did not increase [2-3H]glycerol incorporation into DAG or other glycerolipids in 2-h-prelabelling experiments; thus activation of the phospholipase C which hydrolyses phosphatidylinositol, its mono- and bis-phosphate, Ca2+ mobilization, and protein kinase C activation, appear to be ruled out as mechanisms to explain the insulin effect on synthesis de novo of PA, DAG and PC.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:3146971

  7. Employee benefits or wage increase?

    Directory of Open Access Journals (Sweden)

    Jiří Duda

    2011-01-01

    Full Text Available The paper comes from a survey done during the years 2007–2009. It focused on employee satisfaction with the provision of employee benefits. The research included 21 companies, 7 companies were from the engineering sector, 7 companies from the food industry, 3 companies represented the budgetary sphere, 3 companies the services sector and one company operates in pharmaceutical industry.The questionnaire survey consisted of 14 questions, including 5 identification-questions. The paper presents results of the questions on dealing with employees’ awareness of employee benefits and on choosing between employees’ preferences of wage increase or increase in value of benefits provided.Employees are informed about all options of providing employee benefits. Only in 3 cases employees stated dissatisfaction with information. This answer was related with the responses to the second monitored question. Employees of these companies preferred pay increases before benefits’ increases. There was no effect of gender of the respondents, neither the influence of the sector of operation, in the preference of increases in wages or in benefits. Exceptions were the employees of companies operating in the financial sector, who preferred employee benefits before a wage increase. It was found that employees of companies who participated in research in 2009, preferred wage increases before the extension of employee benefits, although the value of the net wage increase is lower than the monetary value of benefits increase.The paper is a part of solution of the research plan MSM 6215648904 The Czech economy in the process of integration and globalization, and the development of agricultural sector and the sector of services under the new conditions of the integrated European market.

  8. Increasing sales by reducing procrastination

    OpenAIRE

    Gjedrem, William Gilje

    2012-01-01

    Master's thesis in Finance In this paper I analyze whether an intervention program increases productivity and sales, by reducing potential procrastination problems that employees face at work. The intervention was introduced to stores in a large retail chain in Norway, and contained different tools that could lead to lower perceived costs of higher effort. In a difference-in-differences analysis I find that the intervention increases sales after a 14 weeks long implementation period. Fu...

  9. Increased Materialistic Trends Among Youth

    OpenAIRE

    Shama Mazahir, Afsheen Masood, Rubab Musarrat

    2016-01-01

    The goal of this qualitative research is to investigate the increased sense of materialism among youth. The main research question is to identify the factors which are causing materialism among youth. The sample of this research included 25 people, age group 18-25 years obtained from students that are enrolled in universities. The interpretive phenomenological approach was taken which was based on semi-structured interviews. The findings revealed that materialistic trends are increasing among...

  10. Increased Materialistic Trends among Youth

    OpenAIRE

    Afsheen Masood; Rubab Musarrat; Shama Mazahir

    2016-01-01

    The goal of this qualitative research is to investigate the increased sense of materialism among youth. The main research question is to identify the factors which are causing materialism among youth. The sample of this research included 25 people, age group 18-25 years obtained from students that are enrolled in universities. The interpretive phenomenological approach was taken which was based on semi-structured interviews. The findings revealed that materialistic trends are increasing among...

  11. Increasing incidence of pyogenic spondylodiscitis

    DEFF Research Database (Denmark)

    Kehrer, Michala; Pedersen, Court; Jensen, Thøger G

    2014-01-01

    Smaller studies indicate that the incidence of pyogenic spondylodiscitis is increasing, possible related to a growing elderly population. Data supporting this is sparse, and we therefore studied patient characteristics and changes in spondylodiscitis incidence 1995-2008.......Smaller studies indicate that the incidence of pyogenic spondylodiscitis is increasing, possible related to a growing elderly population. Data supporting this is sparse, and we therefore studied patient characteristics and changes in spondylodiscitis incidence 1995-2008....

  12. Requests for body computed tomography: increasing workload, increasing indications and increasing age

    International Nuclear Information System (INIS)

    Toms, A.P.; Cash, C.J.C.; Dixon, A.K.; Linton, S.J.

    2001-01-01

    Increasing numbers of increasingly elderly patients were being examined in our Body CT department. At the same time, some of our clinical colleagues perceived that their patients might be discriminated against on the basis of their age when allocating CT time. We therefore studied the population trends in our department over a 10-year period. The ages of patients attending the Body CT department were collected from the hospital's computer information system from 1995 to 2000 and from handwritten logbooks for the months of September 1988 and 1998. Comparison was made with population trends within the hospital and local demographic data. There has been an average increase of 11% per annum in the number of examinations performed in the Body CT unit. The average age of patients examined increased from 52.7 years in 1988 to 58.9 years in 1998. The largest increase occurred in the over 75-year population (18% rise per annum). Hospital and local demographic population profiles changed little during the same period. We are performing increasing numbers of body CT examinations on increasingly elderly patients. This is probably due to an increased willingness to investigate and treat elderly patients, rather than changes in the local population. There is no evidence of a general discriminatory policy on the basis of age. (orig.)

  13. Increased dietary long-chain polyunsaturated fatty acids alter serum fatty acid concentrations and lower risk of urine stone formation in cats.

    Directory of Open Access Journals (Sweden)

    Jean A Hall

    Full Text Available The lifespan of cats with non-obstructive kidney stones is shortened compared with healthy cats indicating a need to reduce stone formation and minimize chronic kidney disease. The purpose of this study was to investigate the effects of increasing dietary polyunsaturated fatty acids (PUFA on urine characteristics. Domestic-short-hair cats (n = 12; mean age 5.6 years were randomized into two groups and fed one of two dry-cat foods in a cross-over study design. For one week before study initiation, all cats consumed control food that contained 0.07% arachidonic acid (AA, but no eicosapentaenoic acid (EPA or docosahexaenoic acid (DHA. Group 1 continued eating control food for 56 days. Group 2 was fed test food for 56 days, which was control food plus fish oil and high-AA oil. Test food contained 0.17% AA, 0.09% EPA and 0.18% DHA. After 56 days, cats were fed the opposite food for another 56 days. At baseline and after each feeding period, serum was analyzed for fatty acid concentrations, and urine for specific gravity, calcium concentration, relative-super-saturation for struvite crystals, and a calcium-oxalate-titrimetric test was performed. After consuming test food, cats had increased (all P<0.001 serum concentrations of EPA (173%, DHA (61%, and AA (35%; decreased urine specific gravity (P = 0.02; decreased urine calcium concentration (P = 0.06; decreased relative-super-saturation for struvite crystals (P = 0.03; and increased resistance to oxalate crystal formation (P = 0.06 compared with cats consuming control food. Oxalate crystal formation was correlated with serum calcium concentration (r = 0.41; P<0.01. These data show benefits for reducing urine stone formation in cats by increasing dietary PUFA.

  14. Pilot clinical study of the effects of ginger root extract on eicosanoids in colonic mucosa of subjects at increased risk for colorectal cancer.

    Science.gov (United States)

    Zick, Suzanna M; Turgeon, D Kim; Ren, Jianwei; Ruffin, Mack T; Wright, Benjamin D; Sen, Ananda; Djuric, Zora; Brenner, Dean E

    2015-09-01

    Colorectal cancer (CRC) remains a significant cause of mortality. Inhibitors of cyclooxygenase (COX) and thus prostaglandin E2, are promising CRC preventives, but have significant toxicities. Ginger has been shown to inhibit COX, to decrease the incidence and multiplicity of adenomas, and decrease PGE2 concentrations in subjects at normal risk for CRC. This study was conducted to determine the effects of 2.0 g/d of ginger given orally on the levels of PGE2, leukotriene B4 (LTB4), 13-hydroxy-octadecadienoic acids, and 5-, 12-, & 15-hydroxyeicosatetraenoic acid, in the colonic mucosa of subjects at increased risk for CRC. We randomized 20 subjects to 2.0 g/d ginger or placebo for 28 d. At baseline and Day 28, a flexible sigmoidoscopy was used to obtain colon biopsies. A liquid chromatography mass spectrometry method was used to determine eicosanoid levels in the biopsies, and levels were expressed per amount of protein or free arachidonic acid (AA). There was a significant decrease in AA between baseline and Day 28 (P = 0.05) and significant increase in LTB4 (P = 0.04) when normalized to protein, in subjects treated with ginger versus placebo. No other changes in eicosanoids were observed. There was no difference between the groups in total adverse events (AE; P = 0.06). Ginger lacks the ability to decrease eicosanoid levels in people at increased risk for CRC. Ginger did appear to be both tolerable and safe; and could have chemopreventive effects through other mechanisms. Further investigation should focus on other markers of CRC risk in those at increased CRC risk. © 2014 Wiley Periodicals, Inc.

  15. Aerobic training increases skin perfusion by a nitric oxide mechanism in type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Sheri R Colberg

    2010-08-01

    Full Text Available Sheri R Colberg1, Laura C Hill2, Henri K Parson3, Kathleen S Thomas1, Aaron I Vinik31Old Dominion University, Norfolk; 2State University of New York at Cortland, New York; 3Eastern Virginia Medical School, Norfolk, VirginiaAbstract: It is well known that a number of locally released vasodilatory and ­vasoconstrictive ­compounds can affect skin perfusion. This study investigated the effects of aerobic training on the contribution of nitric oxide (NO, prostaglandins (PG, and endothelial-derived ­hyperpolarizing factor (EDHF in stimulated dorsal foot skin perfusion in individuals with type 2 diabetes (T2DM. Ten previously sedentary, older individuals with T2DM (57.0 ± 3.1 years and nine sedentary controls (53.5 ± 3.2 years were tested before and after undertaking six months of moderate a­erobic training three times weekly in a supervised setting. All subjects underwent measurement of ­baseline (32°C and heat-stimulated (40°C and 44°C dorsal foot skin perfusion starting one hour after ­ingestion of a single, oral 325 mg dose of aspirin, a known inhibitor of PG synthesis. Before aspirin ­ingestion, a subcutaneous microdialysis probe was inserted into each foot dorsum to administer either saline (PG pathway only blocked by aspirin in the left foot or L-NAME (N(G-nitro-l-arginine methyl ester; thereby inhibiting both PG and NO pathways in the right foot. Normative data collected previously on subjects undergoing saline administration via ­microdialysis without aspirin ingestion served as a control group. Significantly lower responsiveness of maximal perfusion was found with the EDHF pathway alone unblocked compared with NO and EDHF unblocked after training. Maximal suppression attributable directly to NO, PG, and EDHF was not significantly different when examined by subject group and training status. However, ­contributions of NO, PG, and EDHF to maximal perfusion were significantly increased, decreased, and unchanged by aerobic training

  16. Pulsed electric field increases reproduction.

    Science.gov (United States)

    Panagopoulos, Dimitris J

    2016-01-01

    Purpose To study the effect of pulsed electric field - applied in corona discharge photography - on Drosophila melanogaster reproduction, possible induction of DNA fragmentation, and morphological alterations in the gonads. Materials and methods Animals were exposed to different field intensities (100, 200, 300, and 400 kV/m) during the first 2-5 days of their adult lives, and the effect on reproductive capacity was assessed. DNA fragmentation during early- and mid-oogenesis was investigated by application of the TUNEL (Terminal deoxynucleotide transferase dUTP Nick End Labeling) assay. Sections of follicles after fixation and embedding in resins were observed for possible morphological/developmental abnormalities. Results The field increased reproduction by up to 30% by increasing reproductive capacity in both sexes. The effect increased with increasing field intensities. The rate of increase diminished at the strongest intensities. Slight induction of DNA fragmentation was observed exclusively in the nurse (predominantly) and follicle cells, and exclusively at the two most sensitive developmental stages, i.e., germarium and predominantly stage 7-8. Sections of follicles from exposed females at stages of early and mid-oogennesis other than germarium and stages 7-8 did not reveal abnormalities. Conclusions (1) The specific type of electric field may represent a mild stress factor, inducing DNA fragmentation and cell death in a small percentage of gametes, triggering the reaction of the animal's reproductive system to increase the rate of gametogenesis in order to compensate the loss of a small number of gametes. (2) The nurse cells are the most sensitive from all three types of egg chamber cells. (3) The mid-oogenesis checkpoint (stage 7-8) is more sensitive to this field than the early oogenesis one (germarium) in contrast to microwave exposure. (4) Possible therapeutic applications, or applications in increasing fertility, should be investigated.

  17. Food allergy: is prevalence increasing?

    Science.gov (United States)

    Tang, Mimi L K; Mullins, Raymond J

    2017-03-01

    It is generally accepted that the prevalence of food allergy has been increasing in recent decades, particularly in westernised countries, yet high-quality evidence that is based on challenge confirmed diagnosis of food allergy to support this assumption is lacking because of the high cost and potential risks associated with conducting food challenges in large populations. Accepting this caveat, the use of surrogate markers for diagnosis of food allergy (such as nationwide data on hospital admissions for food anaphylaxis or clinical history in combination with allergen-specific IgE (sIgE) measurement in population-based cohorts) has provided consistent evidence for increasing prevalence of food allergy at least in western countries, such as the UK, United States and Australia. Recent reports that children of East Asian or African ethnicity who are raised in a western environment (Australia and United States respectively) have an increased risk of developing food allergy compared with resident Caucasian children suggest that food allergy might also increase across Asian and African countries as their economies grow and populations adopt a more westernised lifestyle. Given that many cases of food allergy persist, mathematical principles would predict a continued increase in food allergy prevalence in the short to medium term until such time as an effective treatment is identified to allow the rate of disease resolution to be equal to or greater than the rate of new cases. © 2017 Royal Australasian College of Physicians.

  18. Increased chromosome radiosensitivity during pregnancy

    International Nuclear Information System (INIS)

    Ricoul, Michelle; Sabatier, Laure; Dutrillaux, Bernard

    1997-01-01

    It was necessary to consider the risks of exposure of pregnant women, not only in relation to the child, but also in relation to their own hypersensitivity. We have demonstrated that pregnancy increases radiosensitivity of chromosome in the mouse at the end of gestation. This is of importance since it may have implications on radioprotection of pregnant women and give experimental guidelines to the problems of hypersensitivity to drugs and cancer aggravation during pregnancy. Blood obtained from women at various times of pregnancy was exposed to ionizing radiations. By comparison to non-pregnant women, an increase in chromosome breakage was observed in metaphases from lymphocytes, after short-term culture in the presence of the serum of the same donor. Immediately after delivery, this increase in radiosensitivity disappeared. In a prospective study, serial analyses showed a very strong correlation between the amount of pregnancy hormones, progesterone in particular, and the increase in radiosensitivity. Pregnant women may have an increased sensitivity to ionizing radiation during the second half of their pregnancy. This study provides the first evidence in human that radiosensitivity may vary in relation to physiological conditions

  19. Increasing work-time influence

    DEFF Research Database (Denmark)

    Nabe-Nielsen, Kirsten; Garde, Anne Helene; Aust, Birgit

    2012-01-01

    This quasi-experimental study investigated how an intervention aiming at increasing eldercare workers' influence on their working hours affected the flexibility, variability, regularity and predictability of the working hours. We used baseline (n = 296) and follow-up (n = 274) questionnaire data......), or discussion of working hours (subgroup C). Only computerised self-scheduling changed the working hours and the way they were planned. These changes implied more flexible but less regular working hours and an experience of less predictability and less continuity in the care of clients and in the co...... that while increasing the individual flexibility, increasing work-time influence may also result in decreased regularity of the working hours and less continuity in the care of clients and co-operation with colleagues....

  20. Increased Materialistic Trends among Youth

    Directory of Open Access Journals (Sweden)

    Afsheen Masood

    2016-12-01

    Full Text Available The goal of this qualitative research is to investigate the increased sense of materialism among youth. The main research question is to identify the factors which are causing materialism among youth. The sample of this research included 25 people, age group 18-25 years obtained from students that are enrolled in universities. The interpretive phenomenological approach was taken which was based on semi-structured interviews. The findings revealed that materialistic trends are increasing among youth nowadays. Because thought patterns of youth and societal demands have changed totally. Factors that are increasing materialism include social media, brand consciousness; self-centeredness; fake personality development and desire to be socially accepted. The implications indicate that materialistic trend should stop by controlling the social media possession among youth which is the primary source of enhancing materialism among youth.

  1. Increased burnup of fuel elements

    International Nuclear Information System (INIS)

    Ahlf, J.

    1983-01-01

    The specialists' group for fuel elements of the Kerntechnische Gesellschaft e.V. held a meeting on ''Increased Burnup of Fuel Elements'' on 9th and 10th of November 1982 at the GKSS Research Center Geesthacht. Most papers dealt with the problems of burnup increase of fuel elements for light water reactors with respect to fuel manufacturing, power plant operation and reprocessing. Review papers were given on the burnup limits for high temperature gas cooled reactors and sodium fast breeder reactors. The meeting ended with a presentation of the technical equipment of the hot laboratory of the GKSS and the programs which are in progress there. (orig.) [de

  2. Big increase in US ethanol

    Energy Technology Data Exchange (ETDEWEB)

    1981-07-10

    US ethanol capacity is expected to reach 600 million US gal/year by the end of 1982, according to a report from the AIChE. Although this is a six-fold increase over capacity installed in 1979 it is still less than 1% of US domestic motor fuel supply.

  3. Crop diversity for yield increase.

    Directory of Open Access Journals (Sweden)

    Chengyun Li

    2009-11-01

    Full Text Available Traditional farming practices suggest that cultivation of a mixture of crop species in the same field through temporal and spatial management may be advantageous in boosting yields and preventing disease, but evidence from large-scale field testing is limited. Increasing crop diversity through intercropping addresses the problem of increasing land utilization and crop productivity. In collaboration with farmers and extension personnel, we tested intercropping of tobacco, maize, sugarcane, potato, wheat and broad bean--either by relay cropping or by mixing crop species based on differences in their heights, and practiced these patterns on 15,302 hectares in ten counties in Yunnan Province, China. The results of observation plots within these areas showed that some combinations increased crop yields for the same season between 33.2 and 84.7% and reached a land equivalent ratio (LER of between 1.31 and 1.84. This approach can be easily applied in developing countries, which is crucial in face of dwindling arable land and increasing food demand.

  4. Electromigration early resistance increase measurements

    NARCIS (Netherlands)

    Niehof, J.; Flinn, P.A.; Maloney, T.J.

    1993-01-01

    An early resistance change measurement set-up, using an AC bridge technique, has been developed, and measurements have been performed. Large sample-to-sample variations occur. The characteristic time for the resistance change curve is shorter for resistance increase (under current stress) than for

  5. Effects of increased biofuel utilization

    International Nuclear Information System (INIS)

    Bahr, J.; Blad, B.; Hillring, B.

    1996-01-01

    This report is a compilation of present knowledge regarding the effects of an increased use of biomass fuels. Main areas treated are: Availability of raw materials; Effects on forestry and agriculture; Transportation; Areas of use; Cost and price formation; Emission to the atmosphere, and effect on the climate; and Effect on employment and regional aspects. 29 tabs

  6. INCREASED RELIABILITY OF ELECTRIC BLASTING

    OpenAIRE

    Kashuba, Oleh Ivanovych; Skliarov, L I; Skliarov, A L

    2017-01-01

    The problems of improving reliability of an electric blasting method using electric detonators with nichrome filament bridges. It was revealed that in the calculation of the total resistance of the explosive network it is necessary to increase to 24% of the nominal value

  7. Carbohydrase and protease supplementation increased ...

    African Journals Online (AJOL)

    A trial was conducted to evaluate whether the addition of commercial enzyme preparations containing carbohydrases and a protease would increase the available metabolizable energy (ME) of maize-soya-based broiler diets. Seven thousand five hundred and sixty (7560) day-old Ross 788 chicks were randomly allocated ...

  8. How To Increase Advertising Revenue.

    Science.gov (United States)

    Mitchell, Carmen

    1995-01-01

    Describes advertising sales strategies to help faculty advisers of community college newspapers increase revenues. Argues that sales representatives should know their product well and maintain demographic information on the paper's readership. Includes strategies for organizing advertising staff, searching for potential clients, and taking charge…

  9. Increased NMDA receptor inhibition at an increased Sevoflurane MAC

    Directory of Open Access Journals (Sweden)

    Brosnan Robert J

    2012-06-01

    Full Text Available Abstract Background Sevoflurane potently enhances glycine receptor currents and more modestly decreases NMDA receptor currents, each of which may contribute to immobility. This modest NMDA receptor antagonism by sevoflurane at a minimum alveolar concentration (MAC could be reciprocally related to large potentiation of other inhibitory ion channels. If so, then reduced glycine receptor potency should increase NMDA receptor antagonism by sevoflurane at MAC. Methods Indwelling lumbar subarachnoid catheters were surgically placed in 14 anesthetized rats. Rats were anesthetized with sevoflurane the next day, and a pre-infusion sevoflurane MAC was measured in duplicate using a tail clamp method. Artificial CSF (aCSF containing either 0 or 4 mg/mL strychnine was then infused intrathecally at 4 μL/min, and the post-infusion baseline sevoflurane MAC was measured. Finally, aCSF containing strychnine (either 0 or 4 mg/mL plus 0.4 mg/mL dizocilpine (MK-801 was administered intrathecally at 4 μL/min, and the post-dizocilpine sevoflurane MAC was measured. Results Pre-infusion sevoflurane MAC was 2.26%. Intrathecal aCSF alone did not affect MAC, but intrathecal strychnine significantly increased sevoflurane requirement. Addition of dizocilpine significantly decreased MAC in all rats, but this decrease was two times larger in rats without intrathecal strychnine compared to rats with intrathecal strychnine, a statistically significant (P  Conclusions Glycine receptor antagonism increases NMDA receptor antagonism by sevoflurane at MAC. The magnitude of anesthetic effects on a given ion channel may therefore depend on the magnitude of its effects on other receptors that modulate neuronal excitability.

  10. Economic inequality increases risk taking.

    Science.gov (United States)

    Payne, B Keith; Brown-Iannuzzi, Jazmin L; Hannay, Jason W

    2017-05-02

    Rising income inequality is a global trend. Increased income inequality has been associated with higher rates of crime, greater consumer debt, and poorer health outcomes. The mechanisms linking inequality to poor outcomes among individuals are poorly understood. This research tested a behavioral account linking inequality to individual decision making. In three experiments ( n = 811), we found that higher inequality in the outcomes of an economic game led participants to take greater risks to try to achieve higher outcomes. This effect of unequal distributions on risk taking was driven by upward social comparisons. Next, we estimated economic risk taking in daily life using large-scale data from internet searches. Risk taking was higher in states with greater income inequality, an effect driven by inequality at the upper end of the income distribution. Results suggest that inequality may promote poor outcomes, in part, by increasing risky behavior.

  11. Heavier smoking increases coffee consumption

    DEFF Research Database (Denmark)

    Bjørngaard, Johan H; Nordestgaard, Ask Tybjærg; Taylor, Amy E

    2017-01-01

    Background: There is evidence for a positive relationship between cigarette and coffee consumption in smokers. Cigarette smoke increases metabolism of caffeine, so this may represent a causal effect of smoking on caffeine intake. Methods: We performed Mendelian randomization analyses in the UK...... Biobank ( N  = 114 029), the Norwegian HUNT study ( N  = 56 664) and the Copenhagen General Population Study (CGPS) ( N  = 78 650). We used the rs16969968 genetic variant as a proxy for smoking heaviness in all studies and rs4410790 and rs2472297 as proxies for coffee consumption in UK Biobank and CGPS....... Analyses were conducted using linear regression and meta-analysed across studies. Results: Each additional cigarette per day consumed by current smokers was associated with higher coffee consumption (0.10 cups per day, 95% CI: 0.03, 0.17). There was weak evidence for an increase in tea consumption per...

  12. Price Increases from Online Privacy

    OpenAIRE

    Ward, Michael R.; Chen, Yu-Ching

    2001-01-01

    Consumers value keeping some information about them private from potential marketers. E-commerce dramatically increases the potential for marketers to accumulate otherwise private information about potential customers. Online marketers claim that this information enables them to better market their products. Policy makers are currently drafting rules to regulate the way in which these marketers can collect, store, and share this information. However, there is little evidence yet either of con...

  13. Increase Productivity Through Knowledge Management

    OpenAIRE

    Gavrikova, Nadezhda Aleksandrovna; Dolgikh, Irina Nikolaevna; Dyrina, E. N.

    2016-01-01

    Increase in competition level requires companies to improve the efficiency of work force use characterized by labor productivity. Professional knowledge of staff and its experience play the key role in it. The results of Extrusion Line operator's working time analysis are performed in this article. The analysis revealed that the reasons of working time ineffective use connected with inadequate information exchange and knowledge management in the company. Authors suggest the way to solve this ...

  14. Mod increases AGR boiler output

    International Nuclear Information System (INIS)

    Jones, W.K.C.; Rider, G.; Taylor, D.E.

    1986-01-01

    During the commissioning runs of the first reactor units at Heysham I and Hartlepool Advanced Gas-cooled Reactors (AGRs), non-uniform temperature distributions were observed across individual boiler units which were more severe than those predicted from the design analysis. This article describes the re-orificing (referruling) of the boilers to overcome this problem. The referruling has reduced boiler sensitivity and resulted in an increase of load of 7 or 8%. (U.K.)

  15. Is surgical workforce diversity increasing?

    Science.gov (United States)

    Andriole, Dorothy A; Jeffe, Donna B; Schechtman, Kenneth B

    2007-03-01

    We sought to determine the extent to which recent increases in levels of gender and racial diversity in the overall resident-physician workforce were evident among core-surgical specialty resident workforces. Chi-square tests for trend assessed the importance of changes from 1996 to 2004 in proportions of women and African Americans in the surgery-resident workforce. Surgery-resident trends were compared with overall resident workforce trends using two-tailed t-tests to compare regression slopes that quantified rates of change over time. Chi-square tests assessed differences between proportions of women and African Americans in the current overall board-certified workforce and their proportions in the surgery board-certified workforce. From 1996 to 2004, proportions of women increased in all seven surgical specialties studied. Compared with the overall trend toward increasing proportions of women in the resident workforce, the trend in one surgical specialty was larger (obstetrics/gynecology, p 0.05), and two were smaller (each p 0.05). Proportions of African Americans decreased in three specialties (each p workforce, except obstetrics/gynecology, remained lower than in the overall board-certified workforce (each p workforces have persisted since 1996 and will likely perpetuate ongoing surgery board-certified workforce disparities.

  16. High Heels Increase Women's Attractiveness.

    Science.gov (United States)

    Guéguen, Nicolas

    2015-11-01

    Research has found that the appearance of women's apparel helps increase their attractiveness as rated by men and that men care more about physical features in potential opposite-sex mates. However, the effect of sartorial appearance has received little interest from scientists. In a series of studies, the length of women's shoe heels was examined. A woman confederate wearing black shoes with 0, 5, or 9 cm heels asked men for help in various circumstances. In Study 1, she asked men to respond to a short survey on gender equality. In Study 2, the confederate asked men and women to participate in a survey on local food habit consumption. In Study 3, men and women in the street were observed while walking in back of the female confederate who dropped a glove apparently unaware of her loss. It was found that men's helping behavior increased as soon as heel length increased. However, heel length had no effect on women's helping behavior. It was also found that men spontaneously approached women more quickly when they wore high-heeled shoes (Study 4). Change in gait, foot-size judgment, and misattribution of sexiness and sexual intent were used as possible explanations.

  17. Does milk increase mucus production?

    Science.gov (United States)

    Bartley, Jim; McGlashan, Susan Read

    2010-04-01

    Excessive milk consumption has a long association with increased respiratory tract mucus production and asthma. Such an association cannot be explained using a conventional allergic paradigm and there is limited medical evidence showing causality. In the human colon, beta-casomorphin-7 (beta-CM-7), an exorphin derived from the breakdown of A1 milk, stimulates mucus production from gut MUC5AC glands. In the presence of inflammation similar mucus overproduction from respiratory tract MUC5AC glands characterises many respiratory tract diseases. beta-CM-7 from the blood stream could stimulate the production and secretion of mucus production from these respiratory glands. Such a hypothesis could be tested in vitro using quantitative RT-PCR to show that the addition of beta-CM-7 into an incubation medium of respiratory goblet cells elicits an increase in MUC5AC mRNA and by identifying beta-CM-7 in the blood of asthmatic patients. This association may not necessarily be simply cause and effect as the person has to be consuming A1 milk, beta-CM-7 must pass into the systemic circulation and the tissues have to be actively inflamed. These prerequisites could explain why only a subgroup of the population, who have increased respiratory tract mucus production, find that many of their symptoms, including asthma, improve on a dairy elimination diet. (c) 2009 Elsevier Ltd. All rights reserved.

  18. Integrated outages increase Surry's availability

    International Nuclear Information System (INIS)

    Harms, S.R.; Downs, J.L.

    1995-01-01

    This article describes how, through Virginia Power's and Westinghouse's goal-oriented planning philosophy, teamwork and commitment, average outage duration has decreased significantly. During the past 10 years Virginia Power and its nuclear steam supply system (NSSS) services vendor, Westinghouse Electric Corp., have developed a working partnership with one goal in mind: increasing the availability and capacity factors of the North Anna and Surry nuclear power stations while driving down the operating costs of the plants. The outage integration program, steam generator maintenance agreement (SGMA), and integrated radiological services program form the core of this relationship and helped Virginia Power complete one of the most successful outages in Surry Power Station's operating history

  19. Adrenomedullin increased the short-circuit current in the pig oviduct through chloride channels via the CGRP receptor: mediation by cAMP and calcium ions but not by nitric oxide.

    Science.gov (United States)

    Liao, S B; Cheung, K H; Cheung, M P L; To, Y T; O, W S; Tang, F

    2013-10-01

    The oviduct serves as a site for the fertilization of the ovum and the transport of the conceptus down to the uterus for implantation. In this study, we investigated the presence of adrenomedullin (ADM) and its receptor component proteins in the pig oviduct. The effect of ADM on oviductal secretion, the specific receptor, and the mechanisms involved were also investigated. The presence of ADM and its receptor component proteins in the pig oviduct were confirmed using immunostaining. Short-circuit current (I(sc)) technique was employed to study chloride ion secretion in the oviductal epithelium. ADM increased I(sc) through cAMP- and calcium-activated chloride channels, and this effect could be inhibited by the CGRP receptor antagonist, hCGRP8-37. In contrast, the nitric oxide synthase inhibitor, L-NG-nitroarginine methyl ester (L-NAME), could not block the effect of ADM on I(sc). In summary, ADM may increase oviductal fluid secretion via chloride secretion independent of the nitric oxide pathway for the transport of sperm and the conceptus.

  20. Implications of increased ethanol production

    International Nuclear Information System (INIS)

    1992-06-01

    The implications of increased ethanol production in Canada, assuming a 10% market penetration of a 10% ethanol/gasoline blend, are evaluated. Issues considered in the analysis include the provision of new markets for agricultural products, environmental sustainability, energy security, contribution to global warming, potential government cost (subsidies), alternative options to ethanol, energy efficiency, impacts on soil and water of ethanol crop production, and acceptance by fuel marketers. An economic analysis confirms that ethanol production from a stand-alone plant is not economic at current energy values. However, integration of ethanol production with a feedlot lowers the break-even price of ethanol by about 35 cents/l, and even further reductions could be achieved as technology to utilize lignocellulosic feedstock is commercialized. Ethanol production could have a positive impact on farm income, increasing cash receipts to grain farmers up to $53 million. The environmental impact of ethanol production from grain would be similar to that from crop production in general. Some concerns about ethanol/gasoline blends from the fuel industry have been reduced as those blends are now becoming recommended in some automotive warranties. However, the concerns of the larger fuel distributors are a serious constraint on an expansion of ethanol use. The economics of ethanol use could be improved by extending the federal excise tax exemption now available for pure alcohol fuels to the alcohol portion of alcohol/gasoline blends. 9 refs., 10 tabs

  1. Social Power Increases Interoceptive Accuracy

    Directory of Open Access Journals (Sweden)

    Mehrad Moeini-Jazani

    2017-08-01

    Full Text Available Building on recent psychological research showing that power increases self-focused attention, we propose that having power increases accuracy in perception of bodily signals, a phenomenon known as interoceptive accuracy. Consistent with our proposition, participants in a high-power experimental condition outperformed those in the control and low-power conditions in the Schandry heartbeat-detection task. We demonstrate that the effect of power on interoceptive accuracy is not explained by participants’ physiological arousal, affective state, or general intention for accuracy. Rather, consistent with our reasoning that experiencing power shifts attentional resources inward, we show that the effect of power on interoceptive accuracy is dependent on individuals’ chronic tendency to focus on their internal sensations. Moreover, we demonstrate that individuals’ chronic sense of power also predicts interoceptive accuracy similar to, and independent of, how their situationally induced feeling of power does. We therefore provide further support on the relation between power and enhanced perception of bodily signals. Our findings offer a novel perspective–a psychophysiological account–on how power might affect judgments and behavior. We highlight and discuss some of these intriguing possibilities for future research.

  2. MAPK pathway activation by chronic lead-exposure increases vascular reactivity through oxidative stress/cyclooxygenase-2-dependent pathways

    Energy Technology Data Exchange (ETDEWEB)

    Simões, Maylla Ronacher, E-mail: yllars@hotmail.com [Dept. of Physiological Sciences, Federal University of Espirito Santo, Vitória, ES CEP 29040-091 (Brazil); Department of Pharmacology, Universidad Autonoma de Madrid, Instituto de Investigación Hospital Universitario La Paz (IdiPAZ), Madrid (Spain); Aguado, Andrea [Department of Pharmacology, Universidad Autonoma de Madrid, Instituto de Investigación Hospital Universitario La Paz (IdiPAZ), Madrid (Spain); Fiorim, Jonaína; Silveira, Edna Aparecida; Azevedo, Bruna Fernandes; Toscano, Cindy Medice [Dept. of Physiological Sciences, Federal University of Espirito Santo, Vitória, ES CEP 29040-091 (Brazil); Zhenyukh, Olha; Briones, Ana María [Department of Pharmacology, Universidad Autonoma de Madrid, Instituto de Investigación Hospital Universitario La Paz (IdiPAZ), Madrid (Spain); Alonso, María Jesús [Dept. of Biochemistry, Physiology and Molecular Genetics, Universidad Rey Juan Carlos, Alcorcón (Spain); Vassallo, Dalton Valentim [Dept. of Physiological Sciences, Federal University of Espirito Santo, Vitória, ES CEP 29040-091 (Brazil); Health Science Center of Vitória-EMESCAM, Vitória, ES CEP 29045-402 (Brazil); Salaices, Mercedes, E-mail: mercedes.salaices@uam.es [Department of Pharmacology, Universidad Autonoma de Madrid, Instituto de Investigación Hospital Universitario La Paz (IdiPAZ), Madrid (Spain)

    2015-03-01

    Chronic exposure to low lead concentration produces hypertension; however, the underlying mechanisms remain unclear. We analyzed the role of oxidative stress, cyclooxygenase-2-dependent pathways and MAPK in the vascular alterations induced by chronic lead exposure. Aortas from lead-treated Wistar rats (1st dose: 10 μg/100 g; subsequent doses: 0.125 μg/100 g, intramuscular, 30 days) and cultured aortic vascular smooth muscle cells (VSMCs) from Sprague Dawley rats stimulated with lead (20 μg/dL) were used. Lead blood levels of treated rats attained 21.7 ± 2.38 μg/dL. Lead exposure increased systolic blood pressure and aortic ring contractile response to phenylephrine, reduced acetylcholine-induced relaxation and did not affect sodium nitroprusside relaxation. Endothelium removal and L-NAME left-shifted the response to phenylephrine more in untreated than in lead-treated rats. Apocynin and indomethacin decreased more the response to phenylephrine in treated than in untreated rats. Aortic protein expression of gp91(phox), Cu/Zn-SOD, Mn-SOD and COX-2 increased after lead exposure. In cultured VSMCs lead 1) increased superoxide anion production, NADPH oxidase activity and gene and/or protein levels of NOX-1, NOX-4, Mn-SOD, EC-SOD and COX-2 and 2) activated ERK1/2 and p38 MAPK. Both antioxidants and COX-2 inhibitors normalized superoxide anion production, NADPH oxidase activity and mRNA levels of NOX-1, NOX-4 and COX-2. Blockade of the ERK1/2 and p38 signaling pathways abolished lead-induced NOX-1, NOX-4 and COX-2 expression. Results show that lead activation of the MAPK signaling pathways activates inflammatory proteins such as NADPH oxidase and COX-2, suggesting a reciprocal interplay and contribution to vascular dysfunction as an underlying mechanisms for lead-induced hypertension. - Highlights: • Lead-exposure increases oxidative stress, COX-2 expression and vascular reactivity. • Lead exposure activates MAPK signaling pathway. • ROS and COX-2 activation by

  3. Ego involvement increases doping likelihood.

    Science.gov (United States)

    Ring, Christopher; Kavussanu, Maria

    2018-08-01

    Achievement goal theory provides a framework to help understand how individuals behave in achievement contexts, such as sport. Evidence concerning the role of motivation in the decision to use banned performance enhancing substances (i.e., doping) is equivocal on this issue. The extant literature shows that dispositional goal orientation has been weakly and inconsistently associated with doping intention and use. It is possible that goal involvement, which describes the situational motivational state, is a stronger determinant of doping intention. Accordingly, the current study used an experimental design to examine the effects of goal involvement, manipulated using direct instructions and reflective writing, on doping likelihood in hypothetical situations in college athletes. The ego-involving goal increased doping likelihood compared to no goal and a task-involving goal. The present findings provide the first evidence that ego involvement can sway the decision to use doping to improve athletic performance.

  4. Propofol directly increases tau phosphorylation.

    Directory of Open Access Journals (Sweden)

    Robert A Whittington

    2011-01-01

    Full Text Available In Alzheimer's disease (AD and other tauopathies, the microtubule-associated protein tau can undergo aberrant hyperphosphorylation potentially leading to the development of neurofibrillary pathology. Anesthetics have been previously shown to induce tau hyperphosphorylation through a mechanism involving hypothermia-induced inhibition of protein phosphatase 2A (PP2A activity. However, the effects of propofol, a common clinically used intravenous anesthetic, on tau phosphorylation under normothermic conditions are unknown. We investigated the effects of a general anesthetic dose of propofol on levels of phosphorylated tau in the mouse hippocampus and cortex under normothermic conditions. Thirty min following the administration of propofol 250 mg/kg i.p., significant increases in tau phosphorylation were observed at the AT8, CP13, and PHF-1 phosphoepitopes in the hippocampus, as well as at AT8, PHF-1, MC6, pS262, and pS422 epitopes in the cortex. However, we did not detect somatodendritic relocalization of tau. In both brain regions, tau hyperphosphorylation persisted at the AT8 epitope 2 h following propofol, although the sedative effects of the drug were no longer evident at this time point. By 6 h following propofol, levels of phosphorylated tau at AT8 returned to control levels. An initial decrease in the activity and expression of PP2A were observed, suggesting that PP2A inhibition is at least partly responsible for the hyperphosphorylation of tau at multiple sites following 30 min of propofol exposure. We also examined tau phosphorylation in SH-SY5Y cells transfected to overexpress human tau. A 1 h exposure to a clinically relevant concentration of propofol in vitro was also associated with tau hyperphosphorylation. These findings suggest that propofol increases tau phosphorylation both in vivo and in vitro under normothermic conditions, and further studies are warranted to determine the impact of this anesthetic on the acceleration of

  5. Phosphodiesterase inhibitor KMUP-3 displays cardioprotection via protein kinase G and increases cardiac output via G-protein-coupled receptor agonist activity and Ca2+ sensitization

    Directory of Open Access Journals (Sweden)

    Chung-Pin Liu

    2016-02-01

    Full Text Available KMUP-3 (7-{2-[4-(4-nitrobenzene piperazinyl]ethyl}-1, 3-dimethylxanthine displays cardioprotection and increases cardiac output, and is suggested to increase cardiac performance and improve myocardial infarction. To determine whether KMUP-3 improves outcomes in hypoperfused myocardium by inducing Ca2+ sensitization to oppose protein kinase (PKG-mediated Ca2+ blockade, we measured left ventricular systolic blood pressure, maximal rates of pressure development, mean arterial pressure and heart rate in rats, and measured contractility and expression of PKs/RhoA/Rho kinase (ROCKII in beating guinea pig left atria. Hemodynamic changes induced by KMUP-3 (0.5–3.0 mg/kg, intravenously were inhibited by Y27632 [(R-(+-trans-4-1-aminoethyl-N-(4-Pyridyl cyclohexane carboxamide] and ketanserin (1 mg/kg, intravenously. In electrically stimulated left guinea pig atria, positive inotropy induced by KMUP-3 (0.1–100μM was inhibited by the endothelial NO synthase (eNOS inhibitors N-nitro-l-arginine methyl ester (L-NAME and 7-nitroindazole, cyclic AMP antagonist SQ22536 [9-(terahydro-2-furanyl-9H-purin-6-amine], soluble guanylyl cyclase (sGC antagonist ODQ (1H-[1,2,4] oxadiazolo[4,3-a] quinoxalin-1-one, RhoA inhibitor C3 exoenzyme, β-blocker propranolol, 5-hydroxytryptamine 2A antagonist ketanserin, ROCK inhibitor Y27632 and KMUP-1 (7-{2-[4-(2-chlorobenzene piperazinyl]ethyl}-1, 3-dimethylxanthine at 10μM. Western blotting assays indicated that KMUP-3 (0.1–10μM increased PKA, RhoA/ROCKII, and PKC translocation and CIP-17 (an endogenous 17-kDa inhibitory protein activation. In spontaneous right atria, KMUP-3 induced negative chronotropy that was blunted by 7-nitroindazole and atropine. In neonatal myocytes, L-NAME inhibited KMUP-3-induced eNOS phosphorylation and RhoA/ROCK activation. In H9c2 cells, Y-27632 (50μM and PKG antagonist KT5823 [2,3,9,10,11,12-hexahydro-10R- methoxy-2,9-dimethyl-1-oxo-9S,12R-epoxy-1H-diindolo(1,2,3-fg:3′,2′,1

  6. Dividing Attention Increases Operational Momentum

    Directory of Open Access Journals (Sweden)

    Koleen McCrink

    2017-12-01

    Full Text Available When adding or subtracting two quantities, adults often compute an estimated outcome that is larger or smaller, respectively, than the actual outcome, a bias referred to as “operational momentum”. The effects of attention on operational momentum were investigated. Participants viewed a display in which two arrays of objects were added, or one array was subtracted from another array, and judged whether a subsequent outcome (probe array contained the correct or incorrect number of objects. In a baseline condition, only the arrays to be added or subtracted were viewed. In divided attention conditions, participants simultaneously viewed a sequence of colors or shapes, and judged which color (a non-spatial judgment or shape (a spatial judgment was repeated. Operational momentum occurred in all conditions, but was higher in divided attention conditions than in the baseline condition, primarily for addition problems. This pattern suggests that dividing attention, rather than decreasing operational momentum by decreasing attentional shifts, actually increased operational momentum. These results are consistent with a heightened use of arithmetic heuristics under conditions of divided attention.

  7. Job stress and productivity increase.

    Science.gov (United States)

    Adaramola, Samson Sunday

    2012-01-01

    This paper examines mental and physical pressures that workers bear at work. The authors discuss how on the-job stress affects a person's capabilities and productivity, and how such pressures lend to higher incidences of accidents at work. The paper also discuss methods of reducing job-related stress and increasing productivity. An intervention was conducted amongst workers in a private firm. It shows mental and emotional pressure can affect performance and productivity of a worker on the job. One of the biggest influences of today's worker is on the-job stress. Job stress occurs when the requirements of the job do not match the capabilities, resources, or needs of the worker. This consequently affects how a person would normally deal with customer service problems, grievances, violence, conflict, and decisions on the job. Stress is an inevitable part of everyday life, and is therefore a distinct part of a person's job. To properly control the outcome of stress, there are certain precautions and methods that should be taken that will boost productivity.

  8. Increasing Possibilities of Nano suspension

    International Nuclear Information System (INIS)

    Sutradhar, K.B.; Khatun, S.; Luna, I.P.

    2013-01-01

    Nowadays, a very large proportion of new drug candidates emerging from drug discovery programmes are water insoluble and thus poorly bioavailable. To avoid this problem, nano technology for drug delivery has gained much interest as a way to improve the solubility problems. Nano refers to particles size range of 1-1000 nm. The reduction of drug particles into the submicron range leads to a significant increase in the dissolution rate and therefore enhances bioavailability. Nanosuspensions are part of nano technology. This interacts with the body at subcellular (i.e., molecular) scales with a high degree of specificity and can be potentially translated into targeted cellular and tissue-specific clinical applications designed to achieve maximal therapeutic efficacy with minimal side effects. Production of drugs as nanosuspensions can be developed for drug delivery systems as an oral formulation and no noral administration. Here, this review describes the methods of pharmaceutical nano suspension production including advantages and disadvantages, potential benefits, characterization tests, and pharmaceutical applications in drug delivery

  9. Turkey's Increasing Role in Afghanistan

    Directory of Open Access Journals (Sweden)

    Muharrem Eksi

    2010-07-01

    Full Text Available This paper is briefly dealing with the current situation in Afghanistan within the context of Turkey’s increasing role in Afghanistan. Turkish-Afghani relations are examined in terms of politics and economy while Turkish foreign policies towards Afghanistan and the Turkish-Pakistani-Afghani triple summit attempts are analyzed. Additionally, Turkey’s security and socio-economic contributions in Afghanistan are emphasized. Turkey’s unwillingness to send troops to Afghanistanfor operational purposes that is frequently debated in national and international circles has been evaluated by stating the advantages and disadvantages of such decision. Turkey’s quiet approach between 2001 and 2004 towards Afghanistan, which have been energizing since 2005 and Foreign Minister Ahmet Davutoğlu’s visit to Afghanistan on June 2009 have been dealt as well. By considering Davutoglu’s policies, aiming to introduce Turkey as a global actor and as the term President of the UNSC (the UN Security Council, it seems that Turkey is preparing to play a more active role in Afghanistan.

  10. Scientific progress as increasing verisimilitude.

    Science.gov (United States)

    Niiniluoto, Ilkka

    2014-06-01

    According to the foundationalist picture, shared by many rationalists and positivist empiricists, science makes cognitive progress by accumulating justified truths. Fallibilists, who point out that complete certainty cannot be achieved in empirical science, can still argue that even successions of false theories may progress toward the truth. This proposal was supported by Karl Popper with his notion of truthlikeness or verisimilitude. Popper's own technical definition failed, but the idea that scientific progress means increasing truthlikeness can be expressed by defining degrees of truthlikeness in terms of similarities between states of affairs. This paper defends the verisimilitude approach against Alexander Bird who argues that the "semantic" definition (in terms of truth or truthlikeness alone) is not sufficient to define progress, but the "epistemic" definition referring to justification and knowledge is more adequate. Here Bird ignores the crucial distinction between real progress and estimated progress, explicated by the difference between absolute (and usually unknown) degrees of truthlikeness and their evidence-relative expected values. Further, it is argued that Bird's idea of returning to the cumulative model of growth requires an implausible trick of transforming past false theories into true ones.

  11. Laboratory facilities increased by gifts

    International Nuclear Information System (INIS)

    1968-01-01

    As a result of gifts from two Member States facilities at the Agency's research centre at Seibersdorf, Austria, have been increased. New equipment has been provided by France and Romania. The French equipment is a coincidence counter to be operated in conjunction with a computer and is valued at $35 000. It can give automatically an exact measurement of radioactivity in a chemical solution containing radioisotopes. This means that a sample of the solution can be sent to another laboratory to be used for calibrating instruments and checking results of research work. Since 1963 nearly 8 000 radioactive solutions to be used as standards have been sent from Seibersdorf to research laboratories and hospitals in 56 countries. The demand continues to grow, and in order to meet it the equipment was developed by the Saclay Research Centre of the Commissariat a l'Energie Atomique in collaboration with Seibersdorf. From Romania have come six electronic measuring instruments worth $6 000 to assist nuclear research, surveying and prospecting. Three are electronic scalers for experimental work involving the counting of radioactive emissions, and three are survey meters for detecting the presence of radioactivity in geological samples. (author)

  12. The increasing burden of depression

    Directory of Open Access Journals (Sweden)

    Lépine J-P

    2011-05-01

    Full Text Available Jean-Pierre Lépine1, Mike Briley21Hôpital Lariboisière Fernand Widal, Assistance Publique Hôpitaux de Paris Unité INSERM 705 CNRS UMR 8206, Université Paris Diderot, Paris, France; 2NeuroBiz Consulting and Communication, Castres, FranceAbstract: Recent epidemiological surveys conducted in general populations have found that the lifetime prevalence of depression is in the range of 10% to 15%. Mood disorders, as defined by the World Mental Health and the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, have a 12-month prevalence which varies from 3% in Japan to over 9% in the US. A recent American survey found the prevalence of current depression to be 9% and the rate of current major depression to be 3.4%. All studies of depressive disorders have stressed the importance of the mortality and morbidity associated with depression. The mortality risk for suicide in depressed patients is more than 20-fold greater than in the general population. Recent studies have also shown the importance of depression as a risk factor for cardiovascular death. The risk of cardiac mortality after an initial myocardial infarction is greater in patients with depression and related to the severity of the depressive episode. Greater severity of depressive symptoms has been found to be associated with significantly higher risk of all-cause mortality including cardiovascular death and stroke. In addition to mortality, functional impairment and disability associated with depression have been consistently reported. Depression increases the risk of decreased workplace productivity and absenteeism resulting in lowered income or unemployment. Absenteeism and presenteeism (being physically present at work but functioning suboptimally have been estimated to result in a loss of $36.6 billion per year in the US. Worldwide projections by the World Health Organization for the year 2030 identify unipolar major depression as the leading cause of disease burden

  13. Percoll gradient-centrifuged capacitated mouse sperm have increased fertilizing ability and higher contents of sulfogalactosylglycerolipid and docosahexaenoic acid-containing phosphatidylcholine compared to washed capacitated mouse sperm.

    Science.gov (United States)

    Furimsky, Anna; Vuong, Ngoc; Xu, Hongbin; Kumarathasan, Premkumari; Xu, Min; Weerachatyanukul, Wattana; Bou Khalil, Maroun; Kates, Morris; Tanphaichitr, Nongnuj

    2005-03-01

    Although Percoll gradient centrifugation has been used routinely to prepare motile human sperm, its use in preparing motile mouse sperm has been limited. Here, we showed that Percoll gradient-centrifuged (PGC) capacitated mouse sperm had markedly higher fertilizing ability (sperm-zona pellucida [ZP] binding and in vitro fertilization) than washed capacitated mouse sperm. We also showed that the lipid profiles of PGC capacitated sperm and washed capacitated sperm differed significantly. The PGC sperm had much lower contents of cholesterol and phospholipids. This resulted in relative enrichment of male germ cell-specific sulfogalactosylglycerolipid (SGG), a ZP-binding ligand, in PGC capacitated sperm, and this would explain, in part, their increased ZP-binding ability compared with that of washed capacitated sperm. Analyses of phospholipid fatty acyl chains revealed that PGC capacitated sperm were enriched in phosphatidylcholine (PC) molecular species containing highly unsaturated fatty acids (HUFAs), with docosahexaenoic acid (DHA; C22: 6n-3) being the predominant HUFA (42% of total hydrocarbon chains of PC). In contrast, the level of PC-HUFAs comprising arachidonic acid (20:4n-6), docosapentaenoic acid (C22:5n-6), and DHA in washed capacitated sperm was only 27%. Having the highest unsaturation degree among all HUFAs in PC, DHA would enhance membrane fluidity to the uppermost. Therefore, membranes of PGC capacitated sperm would undergo fertilization-related fusion events at higher rates than washed capacitated sperm. These results suggested that PGC mouse sperm should be used in fertilization experiments and that SGG and DHA should be considered to be important biomarkers for sperm fertilizing ability.

  14. Ptp1b deletion in pro-opiomelanocortin neurons increases energy expenditure and impairs endothelial function via TNF-α dependent mechanisms.

    Science.gov (United States)

    Bruder-Nascimento, Thiago; Kennard, Simone; Antonova, Galina; Mintz, James D; Bence, Kendra K; Belin de Chantemèle, Eric J

    2016-06-01

    Protein tyrosine phosphatase 1b (Ptp1b) is a negative regulator of leptin and insulin-signalling pathways. Its targeted deletion in proopiomelanocortin (POMC) neurons protects mice from obesity and diabetes by increasing energy expenditure. Inflammation accompanies increased energy expenditure. Therefore, the present study aimed to determine whether POMC-Ptp1b deletion increases energy expenditure via an inflammatory process, which would impair endothelial function. We characterized the metabolic and cardiovascular phenotypes of Ptp1b+/+ and POMC-Ptp1b-/- mice. Clamp studies revealed that POMC-Ptp1b deletion reduced body fat and increased energy expenditure as evidenced by a decrease in feed efficiency and an increase in oxygen consumption and respiratory exchange ratio. POMC-Ptp1b deletion induced a 2.5-fold increase in plasma tumour necrosis factor α (TNF-α) levels and elevated body temperature. Vascular studies revealed an endothelial dysfunction in POMC-Ptp1b-/- mice. Nitric oxide synthase inhibition [N-nitro-L-arginine methyl ester (L-NAME)] reduced relaxation to a similar extent in Ptp1b+/+ and POMC-Ptp1b-/- mice. POMC-Ptp1b deletion decreased ROS-scavenging enzymes [superoxide dismutases (SODs)] whereas it increased ROS-generating enzymes [NADPH oxidases (NOXs)] and cyclooxygenase-2 (COX-1) expression, in aorta. ROS scavenging or NADPH oxidase inhibition only partially improved relaxation whereas COX-2 inhibition and thromboxane-A2 (TXA2) antagonism fully restored relaxation in POMC-Ptp1b-/- mice Chronic treatment with the soluble TNF-α receptor etanercept decreased body temperature, restored endothelial function and reestablished aortic COX-2, NOXs and SOD expression to their baseline levels in POMC-Ptp1b-/- mice. However, etanercept promoted body weight gain and decreased energy expenditure in POMC-Ptp1b-/- mice. POMC-Ptp1b deletion increases plasma TNF-α levels, which contribute to body weight regulation via increased energy expenditure and impair

  15. Increased VLDL in nephrotic patients results from a decreased catabolism while increased LDL results from increased synthesis

    NARCIS (Netherlands)

    de Sain-van der Velden, M; Kaysen, GA; Barrett, HA; Stellaard, F; Gadellaa, MM; Voorbij, HA; Reijngoud, DJ; Rabelink, TJ

    Increased very low density lipoprotein (VLDL) in nephrotic patients results from a decreased catabolism while increased low density lipoprotein (LDL) results from increased synthesis. Hyperlipidemias a hallmark of nephrotic syndrome that has been associated with increased risk for ischemic heart

  16. Nitric oxide prevents alveolar senescence and emphysema in a mouse model.

    Directory of Open Access Journals (Sweden)

    Amanda E Boe

    Full Text Available Nω-nitro-L-arginine methyl ester (L-NAME treatment induces arteriosclerosis and vascular senescence. Here, we report that the systemic inhibition of nitric oxide (NO production by L-NAME causes pulmonary emphysema. L-NAME-treated lungs exhibited both the structural (alveolar tissue destruction and functional (increased compliance and reduced elastance characteristics of emphysema development. Furthermore, we found that L-NAME-induced emphysema could be attenuated through both genetic deficiency and pharmacological inhibition of plasminogen activator inhibitor-1 (PAI-1. Because PAI-1 is an important contributor to the development of senescence both in vitro and in vivo, we investigated whether L-NAME-induced senescence led to the observed emphysematous changes. We found that L-NAME treatment was associated with molecular and cellular evidence of premature senescence in mice, and that PAI-1 inhibition attenuated these increases. These findings indicate that NO serves to protect and defend lung tissue from physiological aging.

  17. Dairy fat blends high in α-linolenic acid are superior to n-3 fatty-acid-enriched palm oil blends for increasing DHA levels in the brains of young rats.

    Science.gov (United States)

    Du, Qin; Martin, Jean-Charles; Agnani, Genevieve; Pages, Nicole; Leruyet, Pascale; Carayon, Pierre; Delplanque, Bernadette

    2012-12-01

    Achieving an appropriate docosahexaenoic acid (DHA) status in the neonatal brain is an important goal of neonatal nutrition. We evaluated how different dietary fat matrices improved DHA content in the brains of both male and female rats. Forty rats of each gender were born from dams fed over gestation and lactation with a low α-linolenic acid (ALA) diet (0.4% of fatty acids) and subjected for 6 weeks after weaning to a palm oil blend-based diet (10% by weight) that provided either 1.5% ALA or 1.5% ALA and 0.12% DHA with 0.4% arachidonic acid or to an anhydrous dairy fat blend that provided 1.5% or 2.3% ALA. Fatty acids in the plasma, red blood cells (RBCs) and whole brain were determined by gas chromatography. The 1.5% ALA dairy fat was superior to both the 1.5% ALA palm oil blends for increasing brain DHA (14.4% increase, PDHA due to a gender-to-diet interaction, with dairy fats attenuating the gender effect. Brain DHA was predicted with a better accuracy by some plasma and RBC fatty acids when used in combination (R(2) of 0.6) than when used individually (R(2)=0.47 for RBC n-3 docosapentaenoic acid at best). In conclusion, dairy fat blends enriched with ALA appear to be an interesting strategy for achieving optimal DHA levels in the brain of postweaning rats. Human applications are worth considering. Copyright © 2012 Elsevier Inc. All rights reserved.

  18. Worldwide Increasing Incidences of Cutaneous Malignant Melanoma

    International Nuclear Information System (INIS)

    Godar, D. E.

    2011-01-01

    The incidence of cutaneous malignant melanoma (CMM) has been increasing at a steady rate in fair-skinned populations around the world for decades. Scientists are not certain why CMM has been steadily increasing, but strong, intermittent UVB (290-320 nm) exposures, especially sunburn episodes, probably initiate, CMM, while UVA (321-400 nm) passing through glass windows in offices and cars probably promotes it. The CMM incidence may be increasing at an exponential rate around the world, but it definitely decreases with increasing latitude up to∼ 50 degree N where it reverses and increases with the increasing latitude. The inversion in the incidence of CMM may occur because there is more UVA relative to UVB for most of the year at higher latitudes. If windows, allowing UVA to enter our indoor-working environment and cars, are at least partly responsible for the increasing incidence of CMM, then UV filters can be applied to reduce the rate of increase worldwide.

  19. 3 Ways to Increase Positive Emotions

    Science.gov (United States)

    ... Search English Español 3 Ways to Increase Positive Emotions KidsHealth / For Teens / 3 Ways to Increase Positive ... to give yourself a boost. Track Your Positive Emotions Name the positive emotions you're already familiar ...

  20. Increasing millet production in South Asia

    International Development Research Centre (IDRC) Digital Library (Canada)

    Asia, which has put the emphasis on cash crops and cereals ... aims to increase production and consumption of minor ... practices. They will then develop sustainable agriculture tool kits to help farmers to increase millet production in these.

  1. Absence of systemic oxidative stress and increased CSF prostaglandin F2α in progressive MS

    DEFF Research Database (Denmark)

    Lam, Magda A.; Maghzal, Ghassan J.; Khademi, Mohsen

    2016-01-01

    Objective: We aimed to investigate the role of oxidative stress in the progression of multiple sclerosis (MS).  Methods: We determined by liquid chromatography-tandem mass spectrometry nonenzymatic (F2-isoprostanes) and enzymatic oxidation products of arachidonic acid (prostaglandin F2α [PGF2α......]) in plasma and CSF of 45 controls (other neurologic disease [OND] with no signs of inflammation) and 62 patients with MS. Oxidation products were correlated with disease severity and validated biomarkers of inflammation (chemokine ligand 13; matrix metalloproteinase-9; osteopontin) and axonal damage...... with natalizumab and methylprednisolone treatment and was unaffected by the use of nonsteroidal anti-inflammatory drug in secondary progressive MS. CSF PGF2α did not associate with validated CSF markers of inflammation and axonal damage that themselves did not associate with the Expanded Disability Status Scale...

  2. Taurine increases hippocampal neurogenesis in aging mice

    Directory of Open Access Journals (Sweden)

    Elias Gebara

    2015-05-01

    Full Text Available Aging is associated with increased inflammation and reduced hippocampal neurogenesis, which may in turn contribute to cognitive impairment. Taurine is a free amino acid found in numerous diets, with anti-inflammatory properties. Although abundant in the young brain, the decrease in taurine concentration with age may underlie reduced neurogenesis. Here, we assessed the effect of taurine on hippocampal neurogenesis in middle-aged mice. We found that taurine increased cell proliferation in the dentate gyrus through the activation of quiescent stem cells, resulting in increased number of stem cells and intermediate neural progenitors. Taurine had a direct effect on stem/progenitor cells proliferation, as observed in vitro, and also reduced activated microglia. Furthermore, taurine increased the survival of newborn neurons, resulting in a net increase in adult neurogenesis. Together, these results show that taurine increases several steps of adult neurogenesis and support a beneficial role of taurine on hippocampal neurogenesis in the context of brain aging.

  3. Increased muscle glucose uptake during contractions

    DEFF Research Database (Denmark)

    Ploug, Thorkil; Galbo, Henrik; Richter, Erik

    1984-01-01

    We reinvestigated the prevailing concept that muscle contractions only elicit increased muscle glucose uptake in the presence of a so-called "permissive" concentration of insulin (Berger et al., Biochem. J. 146: 231-238, 1975; Vranic and Berger, Diabetes 28: 147-163, 1979). Hindquarters from rats...... in severe ketoacidosis were perfused with a perfusate containing insulin antiserum. After 60 min perfusion, electrical stimulation increased glucose uptake of the contracting muscles fivefold. Also, subsequent contractions increased glucose uptake in hindquarters from nondiabetic rats perfused for 1.5 h......-methylglucose uptake increased during contractions and glucose uptake was negative at rest and zero during contractions. An increase in muscle transport and uptake of glucose during contractions does not require the presence of insulin. Furthermore, glucose transport in contracting muscle may only increase if glycogen...

  4. Increase of internal energy due to measurement

    International Nuclear Information System (INIS)

    Daboul, J.

    1991-01-01

    We argue that the internal energy E=(H) of a macroscopic system in thermal equilibrium must increase, if we measure an observable A which does not commute with the Hamiltonian H. We derive an expression for calculating a lower bound for this increase in E. We then generalize the above result, and show that under certain conditions the expectation value (C) of an observable C should increase by the measurement of another observable A, if A and C do not commute. (author)

  5. Charcot's osteoarthropathy: An increased awareness of this ...

    African Journals Online (AJOL)

    Charcot's osteoarthropathy: An increased awareness of this condition may help in enabling an earlier diagnosis, instituting appropriate treatment, and preventing severe deformity and disability. T Johnson ...

  6. The increased importance of sector switching

    DEFF Research Database (Denmark)

    Frederiksen, Anders; Hansen, Jesper Rosenberg

    2017-01-01

    Sector switching is an important phenomenon that casts light on public–private differences. Yet our knowledge about its prevalence and trends is limited. We study sector switching using unique Danish register-based employer–employee data covering more than 25 years. We find that sector switching...... constitutes 18.5% of all job-to-job mobility, and the trend is increasing both from public to private and from private to public. Sector switching is also generally increasing for middle managers, but for administrative professionals only the flows from private to public increase and for top managers only...... the flows from public to private increase....

  7. Medicaid prospective payment: Case-mix increase

    Science.gov (United States)

    Baker, Samuel L.; Kronenfeld, Jennie J.

    1990-01-01

    South Carolina Medicaid implemented prospective payment by diagnosis-related group (DRG) for inpatient care. The rate of complications among newborns and deliveries doubled immediately. The case-mix index for newborns increased 66.6 percent, which increased the total Medicaid hospital expenditure 5.5 percent. Outlier payments increased total expenditure further. DRG distribution change among newborns has a large impact on spending because newborn complication DRGs have high weights. States adopting a DRG-based payment system for Medicaid should anticipate a greater increase in case mix than Medicare experienced. PMID:10113463

  8. Environmental effects of increased atmospheric carbon dioxide

    International Nuclear Information System (INIS)

    Soon, W.; Baliunas, S.L.; Robinson, A.B.; Robinson, Z.W.

    1999-01-01

    A review of the literature concerning the environmental consequences of increased levels of atmospheric carbon dioxide leads to the conclusion that increases during the 20th century have produced no deleterious effects upon global climate or temperature. Increased carbon dioxide has, however, markedly increased plant growth rates as inferred from numerous laboratory and field experiments. There is no clear evidence, nor unique attribution, of the global effects of anthropogenic CO 2 on climate. Meaningful integrated assessments of the environmental impacts of anthropogenic CO 2 are not yet possible because model estimates of global and regional climate changes on interannual, decadal and centennial timescales remain highly uncertain.(author)

  9. Increase nuclear safety of WWER-440

    International Nuclear Information System (INIS)

    Nochev, T.; Sabinov, S.

    2000-01-01

    A complete program for increasing nuclear safety has been made at NPP Kozloduy with the participation of German, French, Russian and American specialists. This effort cost greater than 100 mil $. This report includes the methods of increasing nuclear safety. The style of management in NPP Kozloduy has been changed for the last seven years. (authors)

  10. A Work Schedule to Increase Productivity.

    Science.gov (United States)

    Atwood, Caleb S.

    1979-01-01

    Outlines a technique for making a tight economy and energy shortages more palatable by supplementing employee wage increases with benefits such as alternative three and four day "weekends" without loss of regular pay and by enabling business to increase profits. (Author/IRT)

  11. Effect of increasing truck weight on bridges.

    Science.gov (United States)

    2010-09-01

    Legislation has been proposed that will allow a 17,000 lb increase in the maximum gross vehicle : weight on the Interstate Highway System. This projects main goal is quantify the effect of this : increase on the internal forces to which typical sl...

  12. Increased greenhouse effect substantiated through measurements

    International Nuclear Information System (INIS)

    Skartveit, Arvid

    2001-01-01

    The article presents studies on the greenhouse effect which substantiates the results from satellite measurements during the period 1970 - 1997. These show an increased effect due to increase in the concentration of the climatic gases CO 2 , methane, CFC-11 and CFC-12 in the atmosphere

  13. increases in cross-sectional samples

    African Journals Online (AJOL)

    1971-03-27

    Mar 27, 1971 ... TABLE Ill. PERCE 'TAGE INCREASES IN BODY M EASU REM ENTS .... population means (polynomials) for calculating total per- ... with age in males, except for very small increases in Bantu. ..... this applies at high levels of energy expenditure is another .... available for adults of all 4 populations studied.

  14. Dihydrotestostenone increase the gene expression of androgen ...

    African Journals Online (AJOL)

    HNTEP cells were grown in basal medium and treated with DHT in different conditions. HNTEP cells under treatment with DHT (10-13 M) induced an increase in FHL-2 expression. In turn, high DHT concentrations (10-8 M) induced an increase in the expression SHP-1. The present data suggest that the SHP-1 and FHL-2 ...

  15. Effective Strategies for Increasing Citation Frequency

    Science.gov (United States)

    Ebrahim, Nader Ale; Salehi, Hadi; Embi, Mohamed Amin; Tanha, Farid Habibi; Gholizadeh, Hossein; Motahar, Seyed Mohammad; Ordi, Ali

    2013-01-01

    Due to the effect of citation impact on The Higher Education (THE) world university ranking system, most of the researchers are looking for some helpful techniques to increase their citation record. This paper by reviewing the relevant articles extracts 33 different ways for increasing the citations possibilities. The results show that the article…

  16. Worldwide Increasing Incidences of Cutaneous Malignant Melanoma

    Directory of Open Access Journals (Sweden)

    Dianne E. Godar

    2011-01-01

    Full Text Available The incidence of cutaneous malignant melanoma (CMM has been increasing at a steady rate in fair-skinned populations around the world for decades. Scientists are not certain why CMM has been steadily increasing, but strong, intermittent UVB (290–320 nm exposures, especially sunburn episodes, probably initiate, CMM, while UVA (321–400 nm passing through glass windows in offices and cars probably promotes it. The CMM incidence may be increasing at an exponential rate around the world, but it definitely decreases with increasing latitude up to ~50°N where it reverses and increases with the increasing latitude. The inversion in the incidence of CMM may occur because there is more UVA relative to UVB for most of the year at higher latitudes. If windows, allowing UVA to enter our indoor-working environment and cars, are at least partly responsible for the increasing incidence of CMM, then UV filters can be applied to reduce the rate of increase worldwide.

  17. Reading Instruction That Increases Thinking Abilities.

    Science.gov (United States)

    Collins, Cathy

    1991-01-01

    Analyzes the effects of eight reading and writing lessons designed to increase adolescent thinking ability. Finds that the lessons increased thinking abilities and scholastic achievement of middle school students. Notes that the lessons positively affect students' self-esteem and communication skills. (RS)

  18. Cyberbullying: An Increasing Challenge for Schools

    Science.gov (United States)

    von Marees, Nandoli; Petermann, Franz

    2012-01-01

    The use of information and communication technology (ICT) has not only brought advantages to mankind. One downside is the emergence and increase of cyberbullying in schools. Affecting students of all ages, teachers, parents, and other educators, this special form of bullying is an increasing challenge for schools. This article offers an overview…

  19. Exercising self-control increases approach motivation.

    Science.gov (United States)

    Schmeichel, Brandon J; Harmon-Jones, Cindy; Harmon-Jones, Eddie

    2010-07-01

    The present research tested the hypothesis that exercising self-control causes an increase in approach motivation. Study 1 found that exercising (vs. not exercising) self-control increases self-reported approach motivation. Study 2a identified a behavior--betting on low-stakes gambles--that is correlated with approach motivation but is relatively uncorrelated with self-control, and Study 2b observed that exercising self-control temporarily increases this behavior. Last, Study 3 found that exercising self-control facilitates the perception of a reward-relevant symbol (i.e., a dollar sign) but not a reward-irrelevant symbol (i.e., a percent sign). Altogether, these results support the hypothesis that exercising self-control temporarily increases approach motivation. Failures of self-control that follow from prior efforts at self-control (i.e., ego depletion) may be explained in part by increased approach motivation.

  20. Nuclear programs see a qualified increase

    International Nuclear Information System (INIS)

    Anon.

    1995-01-01

    This March 1995 Nuclear News article is a review of the proposed DOE budget for nuclear energy activities. This proposed budget increases spending by 32.7% and includes increases in nearly every individual program except civilian reactor development. Isotope production and distribution receive the largest increase, followed by termination costs for certain federal reactor projects. There is a 61.9% proposed increase (to $199M) for waste management activities, but with funding from other Departments, the actual budget would be $612M. The majority of this money would go toward Yucca Mountain activities. Except for the cancellation of the Advanced Neutron Source, the Science and Technology portion of the budget shows an overall small increase

  1. Are increases in cigarette taxation regressive?

    Science.gov (United States)

    Borren, P; Sutton, M

    1992-12-01

    Using the latest published data from Tobacco Advisory Council surveys, this paper re-evaluates the question of whether or not increases in cigarette taxation are regressive in the United Kingdom. The extended data set shows no evidence of increasing price-elasticity by social class as found in a major previous study. To the contrary, there appears to be no clear pattern in the price responsiveness of smoking behaviour across different social classes. Increases in cigarette taxation, while reducing smoking levels in all groups, fall most heavily on men and women in the lowest social class. Men and women in social class five can expect to pay eight and eleven times more of a tax increase respectively, than their social class one counterparts. Taken as a proportion of relative incomes, the regressive nature of increases in cigarette taxation is even more pronounced.

  2. Employee responses to health insurance premium increases.

    Science.gov (United States)

    Goldman, Dana P; Leibowitz, Arleen A; Robalino, David A

    2004-01-01

    To determine the sensitivity of employees' health insurance decisions--including the decision to not choose health maintenance organization or fee-for-service coverage--during periods of rapidly escalating healthcare costs. A retrospective cohort study of employee plan choices at a single large firm with a "cafeteria-style" benefits plan wherein employees paid all the additional cost of purchasing more generous insurance. We modeled the probability that an employee would drop coverage or switch plans in response to employee premium increases using data from a single large US company with employees across 47 states during the 3-year period of 1989 through 1991, a time of large premium increases within and across plans. Premium increases induced substantial plan switching. Single employees were more likely to respond to premium increases by dropping coverage, whereas families tended to switch to another plan. Premium increases of 10% induced 7% of single employees to drop or severely cut back on coverage; 13% to switch to another plan; and 80% to remain in their existing plan. Similar figures for those with family coverage were 11%, 12%, and 77%, respectively. Simulation results that control for known covariates show similar increases. When faced with a dramatic increase in premiums--on the order of 20%--nearly one fifth of the single employees dropped coverage compared with 10% of those with family coverage. Employee coverage decisions are sensitive to rapidly increasing premiums, and single employees may be likely to drop coverage. This finding suggests that sustained premium increases could induce substantial increases in the number of uninsured individuals.

  3. Atrial natriuretic factor increases vascular permeability

    International Nuclear Information System (INIS)

    Lockette, W.; Brennaman, B.

    1990-01-01

    An increase in central blood volume in microgravity may result in increased plasma levels of atrial natriuretic factor (ANF). Since elevations in plasma ANF are found in clinical syndromes associated with edema, and since space motion sickness induced by microgravity is associated with an increase in central blood volume and facial edema, we determined whether ANF increases capillary permeability to plasma protein. Conscious, bilaterally nephrectomized male rats were infused with either saline, ANF + saline, or hexamethonium + saline over 2 h following bolus injections of 125I-albumin and 14C-dextran of similar molecular size. Blood pressure was monitored and serial determinations of hematocrits were made. Animals infused with 1.0 micrograms.kg-1.min-1 ANF had significantly higher hematocrits than animals infused with saline vehicle. Infusion of ANF increased the extravasation of 125I-albumin, but not 14C-dextran from the intravascular compartment. ANF also induced a depressor response in rats, but the change in blood pressure did not account for changes in capillary permeability to albumin; similar depressor responses induced by hexamethonium were not accompanied by increased extravasation of albumin from the intravascular compartment. ANF may decrease plasma volume by increasing permeability to albumin, and this effect of ANF may account for some of the signs and symptoms of space motion sickness

  4. Increasing trends of herpes zoster in Australia.

    Directory of Open Access Journals (Sweden)

    Raina MacIntyre

    Full Text Available Increasing trends in incidence of herpes zoster (HZ have been reported in Australia and internationally. This may reflect the impact of childhood VZV vaccination programs introduced universally in Australia in late 2005. The objective of this study was to evaluate changes in incidence of HZ and PHN in Australia over time, and associated healthcare resource utilisation.Australian data on general practice (GP encounters for HZ, specific antiviral prescribing data from the pharmaceutical benefits scheme, emergency department presentations from the states of NSW and Victoria and national hospitalisation data for HZ were analysed for time trends using regression models. Two time periods (2000-2006 and 2006-2013 were compared which correspond broadly with the pre- and post- universal VZV vaccination period.All data sources showed increasing rates of HZ with age and over time. The GP database showed a significant annual increase in encounters for HZ of 2.5 per 100,000 between 1998 and 2013, and the rates of prescriptions for HZ increased by 4.2% per year between 2002 and 2012. In the 60+ population HZ incidence was estimated to increase from 11.9 to 15.4 per 1,000 persons using GP data or from 12.8 to 14.2 per 1,000 persons using prescription data (p<0.05, between the two periods. Hospitalisation data did not show the same increasing trend over time, except for the age group ≥80 years. Most emergency visits for HZ were not admitted, and showed significant increases over time.The burden of HZ in Australia is substantial, and continues to increase over time. This increase is seen both pre- and post-universal VZV vaccination in 2005, and is most prominent in the older population. The substantial burden of HZ, along with ageing of the Australian population and the importance of healthy ageing, warrants consideration of HZ vaccination for the elderly.

  5. Idaho Power's reverses decline with employee increase

    International Nuclear Information System (INIS)

    Anon.

    1990-01-01

    Following several years of decline, the number of full-time Idaho Power employees increased to 1,528 at the end of 1989, up from 1,500 in 1988. The increase reversed a steady decline that began in 1984 when the company had a peak employment of 1,725. Last year's increase in the work force in part reflects recent additions in customers served and the electric demands of an expanding economy in the service area, as well as new regulatory requirements, the company said

  6. FEASIBILITY OF INCREASING THE ENERGY OF RHIC

    International Nuclear Information System (INIS)

    MACKAY, W.W.; JAIN, A.; LUCCIO, A.U.; PILAT, F.; ROSER, T.; TEPIKIAN, S.; TROBOJEVIC, D.

    2001-01-01

    In this paper we discuss the possibility of increasing the energy of beams in RHIC by as much as 30% with a modest trade-off in luminosity. The arc dipoles and quadrupoles were designed with considerable margin. For higher energies (>100 GeV/nucleon) the minimum β* may be required to increase as the interaction region triplets saturate. The separator magnets (DX) have the least margin for increased field, so we consider three scenarios: allowing for a small crossing angle with the present DX magnets, upgrading the DX magnets to higher strength, and permitting a crossing angle of ∼1degree by removing the DX magnets altogether

  7. Increasing atmospheric carbon dioxide and its consequences

    Energy Technology Data Exchange (ETDEWEB)

    Lockwood, J G

    1982-09-16

    The effects of increasing CO/sub 2/ concentrations in the atmosphere are estimated using general circulation models (GCMs), which have the ability to portray many of the nonlinear feedback processes which serve to regulate atmospheric (and hence climatic) changes. GCMs predict that a doubling of atmospheric CO/sub 2/ would result in a 2-3 k increase of globally averaged surface air temperature. The largest warming will occur in the winter in high latitudes. Detection studies are now being directed towards isolating those parts of observed climate fluctuations that are attributable to increasing atmospheric CO/sub 2/. (KRM)

  8. The Aging Kidney: Increased Susceptibility to Nephrotoxicity

    Science.gov (United States)

    Wang, Xinhui; Bonventre, Joseph V.; Parrish, Alan R.

    2014-01-01

    Three decades have passed since a series of studies indicated that the aging kidney was characterized by increased susceptibility to nephrotoxic injury. Data from these experimental models is strengthened by clinical data demonstrating that the aging population has an increased incidence and severity of acute kidney injury (AKI). Since then a number of studies have focused on age-dependent alterations in pathways that predispose the kidney to acute insult. This review will focus on the mechanisms that are altered by aging in the kidney that may increase susceptibility to injury, including hemodynamics, oxidative stress, apoptosis, autophagy, inflammation and decreased repair. PMID:25257519

  9. Who Benefits from a Minimum Wage Increase?

    OpenAIRE

    John W. Lopresti; Kevin J. Mumford

    2015-01-01

    This paper addresses the question of how a minimum wage increase affects the wages of low-wage workers. Most studies assume that there is a simple mechanical increase in the wage for workers earning a wage between the old and the new minimum wage, with some studies allowing for spillovers to workers with wages just above this range. Rather than assume that the wages of these workers would have remained constant, this paper estimates how a minimum wage increase impacts a low-wage worker's wage...

  10. Reduced Dietary Sodium Intake Increases Heart Rate

    DEFF Research Database (Denmark)

    Graudal, Niels A; Hubeck-Graudal, Thorbjørn; Jürgens, Gesche

    2016-01-01

    Reduced dietary sodium intake (sodium reduction) increases heart rate in some studies of animals and humans. As heart rate is independently associated with the development of heart failure and increased risk of premature death a potential increase in heart rate could be a harmful side......-effect of sodium reduction. The purpose of the present meta-analysis was to investigate the effect of sodium reduction on heart rate. Relevant studies were retrieved from an updated pool of 176 randomized controlled trials (RCTs) published in the period 1973-2014. Sixty-three of the RCTs including 72 study...... populations reported data on heart rate. In a meta-analysis of these data sodium reduction increased heart rate with 1.65 beats per minute [95% CI: 1.19, 2.11], p heart rate. This effect was independent of baseline blood pressure. In conclusion sodium reduction...

  11. Worldwide trends show oropharyngeal cancer rates increasing

    Science.gov (United States)

    NCI scientists report that the incidence of oropharyngeal cancer significantly increased during the period 1983-2002 among people in countries that are economically developed. Oropharyngeal cancer occurs primarily in the middle part of the throat behind t

  12. Ethanologenic bacteria with increased resistance to furfural

    Science.gov (United States)

    Miller, Elliot Norman; Jarboe, Laura R.; Yomano, Lorraine P.; York, Sean W.; Shanmugam, Keelnatham; Ingram, Lonnie O'Neal

    2015-10-06

    The invention relates to bacterium that have increased resistance to furfural and methods of preparation. The invention also relates to methods of producing ethanol using the bacterium and corresponding kits.

  13. Determination of hormonal combination for increased multiplication ...

    African Journals Online (AJOL)

    ACSS

    production; such methods include tissue culture and ... NAA and Vitamins has been reported to increase the ... is a new technique in seed potato production ... Napthalene acetic acid (NAA) were ... to analysis of variance (ANOVA), using.

  14. Big increase in Spanish reseach funding

    CERN Document Server

    Bosch, X

    1998-01-01

    The Spanish government plans to increase spending on civilian science research and development by between 8 and 10 per cent. The exact figure is unclear since it has been included in the budget along with military research projects (1 page).

  15. Aged mice have increased inflammatory monocyte concentration ...

    Indian Academy of Sciences (India)

    monocytes from old as compared with those from young mice. The increased classic .... several instances where the isotype control antibodies stained in a similar position but at a ..... responses in young and older adults. J. Infect. Dis. 195.

  16. Increased backcrossing has reduced the usefulness of ...

    African Journals Online (AJOL)

    Increased backcrossing has reduced the usefulness of morphological and allozyme data for identifying Oreochromis niloticus , O. mossambicus (Teleostei: Cichlidae) and their hybrids in the Pafuri reach of the Luvuvhu River in the Kruger National Park, South Africa.

  17. Writing autobiographical narratives increases political conservatism

    NARCIS (Netherlands)

    Lammers, J.; Proulx, T.

    2013-01-01

    Two experiments show that writing chronological autobiographical narratives increases political conservatism, defined as an ideology of resistance to social change. When writing chronological autobiographical narratives, we hypothesized that people would re-experience the events of their life in a

  18. The ways of SOFC systems efficiency increasing

    Energy Technology Data Exchange (ETDEWEB)

    Demin, A.K.; Timofeyeva, N.

    1996-04-01

    The efficiency of solid oxide fuel cells (SOFCs) is described. This paper considers methods to lift the fuel utilization and/or the average cell voltage with the goal of increasing the cell efficiency by improved cell designs.

  19. Does Movie Violence Increase Violent Crime?

    OpenAIRE

    Gordon Dahl; Stefano DellaVigna

    2007-01-01

    Laboratory experiments in psychology find that media violence increases aggression in the short run. We analyze whether media violence affects violent crime in the field. We exploit variation in the violence of blockbuster movies from 1995 to 2004, and study the effect on same-day assaults. We find that violent crime decreases on days with larger theater audiences for violent movies. The effect is partly due to voluntary incapacitation: between 6PM and 12AM, a one million increase in the audi...

  20. Calming Meditation Increases Altruism, Decreases Parochialism

    OpenAIRE

    Frost, Karl

    2017-01-01

    It has been proposed that cultivating calm will increase altruism and decrease parochialism, where altruism is defined as self-sacrifice in support of others, regardless of group affiliation or identity, and parochialism is defined as prosocial self-sacrifice restricted to fellow members of a group. Such could be the case with a calming meditation practice. An alternate hypothesis, coming from the study of ritual, proposes that shared practices lead to bonding, increasing parochialism, but no...

  1. Increase of hydroelectric power plant operation reliability

    International Nuclear Information System (INIS)

    Koshumbaev, M.B.

    2006-01-01

    The new design of the turbine of hydroelectric power plant (HPP) is executed in the form of a pipe with plates. Proposed solution allows increasing the hydroelectric power plant capacity at existing head and water flow. At that time the HPP turbine reliability is increase, its operation performances are improving. Design efficiency is effective mostly for small-scale and micro-HPP due to reliable operation, low-end technology, and harmless ecological application. (author)

  2. Increased ionization rate in laser enrichment

    International Nuclear Information System (INIS)

    Janes, G.S.; Pike, G.T.

    1977-01-01

    A system employing multiple, upper excitation levels in a technique for isotopically selective ionization to improve the ionization efficiency is described. Laser radiation is employed to excite particles with isotopic selectivity. Excitation is produced to a plurality of excited states below the ionization level with the result of increasing the number of available excited particles for ionization and thereby increasing the ionization cross section for improved system efficiency

  3. Increasing incidence of diabetes after gestational diabetes

    DEFF Research Database (Denmark)

    Lauenborg, Jeannet; Hansen, Torben; Jensen, Dorte Møller

    2004-01-01

    To study the incidence of diabetes among women with previous diet-treated gestational diabetes mellitus (GDM) in the light of the general increasing incidence of overweight and diabetes and to identify risk factors for the development of diabetes.......To study the incidence of diabetes among women with previous diet-treated gestational diabetes mellitus (GDM) in the light of the general increasing incidence of overweight and diabetes and to identify risk factors for the development of diabetes....

  4. Islamic Caring Model on Increase Patient Satisfaction

    OpenAIRE

    Abdurrouf, Muh; Nursalam, Nursalam; Purwaningsih, Purwaningsih

    2013-01-01

    Introduction: Patient satisfaction was important aspect that must be considered by health service providers, patients who were not satisfied will leave the hospital and be a competitor's customers so be able caused a decrease in sales of products/services and in turn could reduce and even loss of profit, therefore, the hospital must provided the best service so that it could increase patient satisfaction. The purpose of this study was to exams the effect of Islamic caring model on increase pa...

  5. Tourism: a Soft Touch for Increased Taxation

    OpenAIRE

    McMahon, Frank

    1999-01-01

    This paper reviews the changes which are taking place internationally in the taxation of the tourism industry and the reasons why tourism is especially susceptible to increased taxation. It compares VAT rates in European countries and assesses the relationship between those rates and increases in international tourism receipts, concluding that there is not the direct, negative relationship which hotel associations frequently cited in their submissions to government. The canons of taxation, fi...

  6. Do childcare policies increase maternal employment?

    OpenAIRE

    Vuri, Daniela

    2016-01-01

    Women’s labor force participation has rapidly increased in most countries, but mothers still struggle to achieve a satisfactory work−life balance. Childcare allows the primary caregiver, usually the mother, to take time away from childrearing for employment. Family policies that subsidize childcare and increase its availability have different effects on female labor supply across countries. For policymakers to determine how well these policies work, they should consider that policy effectiven...

  7. Increasing the Brightness of Light Sources

    OpenAIRE

    Fu, Ling

    2006-01-01

    In modern illumination systems, compact size and high brightness are important features. Light recycling allows an increase of the spectral radiance (brightness) emitted by a light source for the price of reducing the total radiant power. Light recycling means returning part of the emitted light to the source where part of it will escape absorption. As a result, the output brightness can be increased in a restricted phase space, ...

  8. Increased bone radiotracer uptake in renal osteodystrophy

    Energy Technology Data Exchange (ETDEWEB)

    de Graaf, P.; Schicht, I.M.; de Graeff, J.; te Velde, J.; Kleiverda, K.; Pauwels, E.K.J.

    1982-04-01

    Bone radiotracer uptake in renal osteodystrophy was investigated in 35 dialysis patients by correlating the results of quantitative bone scintigraphy with those of biochemical and bone morphometric studies. There were highly significant correlations (P < 0.001) between the total skeletal activity and the biochemical (iPTH and alkaline phosphatase), and histologic parameters of hyperparathyroidism. These clinical results strongly suggest that increased bone turnover i.e. hyperparathyroidism, rather than osteomalacia is the major cause of increased skeletal uptake in renal osteodystrophy.

  9. Energy in China: Coping with increasing demand

    International Nuclear Information System (INIS)

    Sandklef, Kristina

    2004-11-01

    Sustaining the increasing energy consumption is crucial to future economic growth in China. This report focuses on the current and future situation of energy production and consumption in China and how China is coping with its increasing domestic energy demand. Today, coal is the most important energy resource, followed by oil and hydropower. Most energy resources are located in the inland, whereas the main demand for energy is in the coastal areas, which makes transportation and transmission of energy vital. The industrial sector is the main driver of the energy consumption in China, but the transport sector and the residential sector will increase their share of consumption in China, but the transport sector and the residential sector will increase their share of consumption by 2020. China's energy intensity decreased during the 1990s, but it is still high in a global comparison. China is projected to increase its energy consumption at least two times between 2000 and 2025. The government has an equal focus on energy conservation and to develop the current energy resources. Coal will continue to be the most important fuel, but the demand for oil, hydropower, natural gas and nuclear power will also increase. The main future challenges are transportation of energy resources within China and securing oil supply, both domestic and imports

  10. Increasing nursing treatment for pediatric procedural pain.

    Science.gov (United States)

    Bice, April A; Gunther, Mary; Wyatt, Tami

    2014-03-01

    Procedural pain management is an underused practice in children. Despite the availability of efficacious treatments, many nurses do not provide adequate analgesia for painful interventions. Complementary therapies and nonpharmacologic interventions are additionally essential to managing pain. Owing to the increasing awareness of inadequate nursing utilization of pharmacologic measures for procedural pain, this paper focuses only on analgesic treatments. The aim of this review was to examine how varying degrees of quality improvement affect nursing utilization of treatments for routine pediatric procedural pain. A comprehensive search of databases including Cinahl, Medline/Pubmed, Web of Science, Google Scholar, Psycinfo, and Cochrane Library was performed. Sixty-two peer-reviewed research articles were examined. Ten articles focusing on quality improvement in pediatric pain management published in English from 2001 to 2011 were included. Three themes emerged: 1) increasing nursing knowledge; 2) nursing empowerment; and 3) protocol implementation. Research critique was completed with the use of guidelines and recommendations from Creswell (2009) and Garrard (2011). The literature reveals that nurses still think that pediatric pain management is essential. Quality improvement increases nursing utilization of procedural pain treatments. Although increasing nursing knowledge improves pediatric pain management, it appears that nursing empowerment and protocol implementation increase nursing compliance more than just education alone. Nurses providing pain management can enhance their individual practice with quality improvement measures that may increase nursing adherence to institutional and nationally recommended pediatric procedural pain management guidelines. Copyright © 2014 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.

  11. Isoflurane increases cardiorespiratory coordination in rats

    Science.gov (United States)

    Kabir, Muammar M.; Beig, Mirza I.; Nalivaiko, Eugene; Abbott, Derek; Baumert, Mathias

    2008-12-01

    Anesthetics such as isoflurane adversely affect heart rate. In this study we analysed the interaction between heart rhythm and respiration at different concentrations of isoflurane and ventilation rates. In two rats, the electrocardiogram (ECG) and respiratory signals were recorded under the influence of isoflurane. For the assessment of cardiorespiratory coordination, we analysed the phase locking between heart rate, computed from the R-R intervals of body surface ECG, and respiratory rate, computed from impedance changes, using Hilbert transform. The changes in heart rate, percentage of synchronization and duration of synchronized epochs at different isoflurane concentrations and ventilation rates were assessed using linear regression model. From this study it appears that the amount of phase locking between cardiac and respiratory rates increases with the increase in concentration of isoflurane. Heart rate and duration of synchronized epochs increased significantly with the increase in the level of isoflurane concentration while respiratory rate was not significantly affected. Cardiorespiratory coordination also showed a considerable increase at the ventilation rates of 50- 55 cpm in both the rats, suggesting that the phase-locking between the cardiac and respiratory oscillators can be increased by breathing at a particular respiratory frequency.

  12. Precipitation variability increases in a warmer climate.

    Science.gov (United States)

    Pendergrass, Angeline G; Knutti, Reto; Lehner, Flavio; Deser, Clara; Sanderson, Benjamin M

    2017-12-21

    Understanding changes in precipitation variability is essential for a complete explanation of the hydrologic cycle's response to warming and its impacts. While changes in mean and extreme precipitation have been studied intensively, precipitation variability has received less attention, despite its theoretical and practical importance. Here, we show that precipitation variability in most climate models increases over a majority of global land area in response to warming (66% of land has a robust increase in variability of seasonal-mean precipitation). Comparing recent decades to RCP8.5 projections for the end of the 21 st century, we find that in the global, multi-model mean, precipitation variability increases 3-4% K -1 globally, 4-5% K -1 over land and 2-4% K -1 over ocean, and is remarkably robust on a range of timescales from daily to decadal. Precipitation variability increases by at least as much as mean precipitation and less than moisture and extreme precipitation for most models, regions, and timescales. We interpret this as being related to an increase in moisture which is partially mitigated by weakening circulation. We show that changes in observed daily variability in station data are consistent with increased variability.

  13. Insulin Increases Ceramide Synthesis in Skeletal Muscle

    Directory of Open Access Journals (Sweden)

    M. E. Hansen

    2014-01-01

    Full Text Available Aims. The purpose of this study was to determine the effect of insulin on ceramide metabolism in skeletal muscle. Methods. Skeletal muscle cells were treated with insulin with or without palmitate for various time periods. Lipids (ceramides and TAG were isolated and gene expression of multiple biosynthetic enzymes were quantified. Additionally, adult male mice received daily insulin injections for 14 days, followed by muscle ceramide analysis. Results. In muscle cells, insulin elicited an increase in ceramides comparable to palmitate alone. This is likely partly due to an insulin-induced increase in expression of multiple enzymes, particularly SPT2, which, when knocked down, prevented the increase in ceramides. In mice, 14 days of insulin injection resulted in increased soleus ceramides, but not TAG. However, insulin injections did significantly increase hepatic TAG compared with vehicle-injected animals. Conclusions. This study suggests that insulin elicits an anabolic effect on sphingolipid metabolism in skeletal muscle, resulting in increased ceramide accumulation. These findings reveal a potential mechanism of the deleterious consequences of the hyperinsulinemia that accompanies insulin resistance and suggest a possible novel therapeutic target to mitigate its effects.

  14. Wind increases leaf water use efficiency.

    Science.gov (United States)

    Schymanski, Stanislaus J; Or, Dani

    2016-07-01

    A widespread perception is that, with increasing wind speed, transpiration from plant leaves increases. However, evidence suggests that increasing wind speed enhances carbon dioxide (CO2 ) uptake while reducing transpiration because of more efficient convective cooling (under high solar radiation loads). We provide theoretical and experimental evidence that leaf water use efficiency (WUE, carbon uptake per water transpired) commonly increases with increasing wind speed, thus improving plants' ability to conserve water during photosynthesis. Our leaf-scale analysis suggests that the observed global decrease in near-surface wind speeds could have reduced WUE at a magnitude similar to the increase in WUE attributed to global rise in atmospheric CO2 concentrations. However, there is indication that the effect of long-term trends in wind speed on leaf gas exchange may be compensated for by the concurrent reduction in mean leaf sizes. These unintuitive feedbacks between wind, leaf size and water use efficiency call for re-evaluation of the role of wind in plant water relations and potential re-interpretation of temporal and geographic trends in leaf sizes. © 2015 The Authors. Plant, Cell & Environment published by John Wiley & Sons Ltd.

  15. Reversal of reflex pulmonary vasoconstriction induced by main pulmonary arterial distension.

    Science.gov (United States)

    Juratsch, C E; Grover, R F; Rose, C E; Reeves, J T; Walby, W F; Laks, M M

    1985-04-01

    Distension of the main pulmonary artery (MPA) induces pulmonary hypertension, most probably by neurogenic reflex pulmonary vasoconstriction, although constriction of the pulmonary vessels has not actually been demonstrated. In previous studies in dogs with increased pulmonary vascular resistance produced by airway hypoxia, exogenous arachidonic acid has led to the production of pulmonary vasodilator prostaglandins. Hence, in the present study, we investigated the effect of arachidonic acid in seven intact anesthetized dogs after pulmonary vascular resistance was increased by MPA distention. After steady-state pulmonary hypertension was established, arachidonic acid (1.0 mg/min) was infused into the right ventricle for 16 min; 15-20 min later a 16-mg bolus of arachidonic acid was injected. MPA distension was maintained throughout the study. Although the infusion of arachidonic acid significantly lowered the elevated pulmonary vascular resistance induced by MPA distension, the pulmonary vascular resistance returned to control levels only after the bolus injection of arachidonic acid. Notably, the bolus injection caused a biphasic response which first increased the pulmonary vascular resistance transiently before lowering it to control levels. In dogs with resting levels of pulmonary vascular resistance, administration of arachidonic acid in the same manner did not alter the pulmonary vascular resistance. It is concluded that MPA distension does indeed cause reflex pulmonary vasoconstriction which can be reversed by vasodilator metabolites of arachidonic acid. Even though this reflex may help maintain high pulmonary vascular resistance in the fetus, its function in the adult is obscure.

  16. Analysis of sharpness increase by image noise

    Science.gov (United States)

    Kurihara, Takehito; Aoki, Naokazu; Kobayashi, Hiroyuki

    2009-02-01

    Motivated by the reported increase in sharpness by image noise, we investigated how noise affects sharpness perception. We first used natural images of tree bark with different amounts of noise to see whether noise enhances sharpness. Although the result showed sharpness decreased as noise amount increased, some observers seemed to perceive more sharpness with increasing noise, while the others did not. We next used 1D and 2D uni-frequency patterns as stimuli in an attempt to reduce such variability in the judgment. The result showed, for higher frequency stimuli, sharpness decreased as the noise amount increased, while sharpness of the lower frequency stimuli increased at a certain noise level. From this result, we thought image noise might reduce sharpness at edges, but be able to improve sharpness of lower frequency component or texture in image. To prove this prediction, we experimented again with the natural image used in the first experiment. Stimuli were made by applying noise separately to edge or to texture part of the image. The result showed noise, when added to edge region, only decreased sharpness, whereas when added to texture, could improve sharpness. We think it is the interaction between noise and texture that sharpens image.

  17. Smoking prevalence increases following Canterbury earthquakes.

    Science.gov (United States)

    Erskine, Nick; Daley, Vivien; Stevenson, Sue; Rhodes, Bronwen; Beckert, Lutz

    2013-01-01

    A magnitude 7.1 earthquake hit Canterbury in September 2010. This earthquake and associated aftershocks took the lives of 185 people and drastically changed residents' living, working, and social conditions. To explore the impact of the earthquakes on smoking status and levels of tobacco consumption in the residents of Christchurch. Semistructured interviews were carried out in two city malls and the central bus exchange 15 months after the first earthquake. A total of 1001 people were interviewed. In August 2010, prior to any earthquake, 409 (41%) participants had never smoked, 273 (27%) were currently smoking, and 316 (32%) were ex-smokers. Since the September 2010 earthquake, 76 (24%) of the 316 ex-smokers had smoked at least one cigarette and 29 (38.2%) had smoked more than 100 cigarettes. Of the 273 participants who were current smokers in August 2010, 93 (34.1%) had increased consumption following the earthquake, 94 (34.4%) had not changed, and 86 (31.5%) had decreased their consumption. 53 (57%) of the 93 people whose consumption increased reported that the earthquake and subsequent lifestyle changes as a reason to increase smoking. 24% of ex-smokers resumed smoking following the earthquake, resulting in increased smoking prevalence. Tobacco consumption levels increased in around one-third of current smokers.

  18. Import of electric power increased by 19 %

    International Nuclear Information System (INIS)

    Anon.

    2000-01-01

    The import of electric power increased by 19% in 1999. Due to the decrease in the electric power export the net import of electric power increased even more. Electric power import from Sweden was 6000 GWh, import from Russia 5200 GWh and import from Norway 100 GWh. The electric power export in 1999 was only 200 GWh. The generation of nuclear power increased 5% and the consumption of wood-based fuels by 3%. The increase in nuclear power generation is based on increment of the power output capacities of the power plants. The consumption of peat decreased by 12% and the production of hydroelectric power by 15%. The decrement of the peat consumption is based on the changes in energy taxation. The production of hydroelectric power decreased to the normal level after the rainy year 1998. Oil consumption remained nearly the same as in 1998 even though the national product increased in 1999 by 3.5%. The wind power generation was doubled in 1999. The share of it is still only about 0.01% of the total energy consumption. Carbon dioxide emissions from coal and peat, decreased by 1.0 million tons, down to 56 million tons. The present emissions are now only about 2 million tons higher than during the reference year 1990. The emissions have decreased by 5 million tons since 1996 when they were at their highest

  19. Increased Mercury Bioaccumulation Follows Water Quality Improvement

    Energy Technology Data Exchange (ETDEWEB)

    Bogle, M.A.; Peterson, M.J.; Smith, J.G.; Southworth, G.R.

    1999-09-15

    Changes in physical and chemical characteristics of aquatic habitats made to reduce or eliminate ecological risks can sometimes have unforeseen consequences. Environmental management activities on the U.S. Dept. of Energy reservation in Oak Ridge, Tennessee,have succeeded in improving water quality in streams impacted by discharges fi-om industrial facilities and waste disposal sites. The diversity and abundance of pollution-sensitive components of the benthic macroinvertebrate communities of three streams improved after new waste treatment systems or remedial actions reduced inputs of various toxic chemicals. Two of the streams were known to be mercury-contaminated from historical spills and waste disposal practices. Waterborne mercury concentrations in the third were typical of uncontaminated systems. In each case, concentrations of mercury in fish, or the apparent biological availability of mercury increased over the period during which ecological metrics indicated improved water quality. In the system where waterborne mercury concentrations were at background levels, increased mercury bioaccumulation was probably a result of reduced aqueous selenium concentrations; however, the mechanisms for increased mercury accumulation in the other two streams remain under investigation. In each of the three systems, reduced inputs of metals and inorganic anions was followed by improvements in the health of aquatic invertebrate communities. However, this reduction in risk to aquatic invertebrates was accompanied by increased risk to humans and piscivorous wildlife related to increased mercury concentrations in fish.

  20. Antibiotic resistance increases with local temperature

    Science.gov (United States)

    MacFadden, Derek R.; McGough, Sarah F.; Fisman, David; Santillana, Mauricio; Brownstein, John S.

    2018-06-01

    Bacteria that cause infections in humans can develop or acquire resistance to antibiotics commonly used against them1,2. Antimicrobial resistance (in bacteria and other microbes) causes significant morbidity worldwide, and some estimates indicate the attributable mortality could reach up to 10 million by 20502-4. Antibiotic resistance in bacteria is believed to develop largely under the selective pressure of antibiotic use; however, other factors may contribute to population level increases in antibiotic resistance1,2. We explored the role of climate (temperature) and additional factors on the distribution of antibiotic resistance across the United States, and here we show that increasing local temperature as well as population density are associated with increasing antibiotic resistance (percent resistant) in common pathogens. We found that an increase in temperature of 10 °C across regions was associated with an increases in antibiotic resistance of 4.2%, 2.2%, and 2.7% for the common pathogens Escherichia coli, Klebsiella pneumoniae and Staphylococcus aureus. The associations between temperature and antibiotic resistance in this ecological study are consistent across most classes of antibiotics and pathogens and may be strengthening over time. These findings suggest that current forecasts of the burden of antibiotic resistance could be significant underestimates in the face of a growing population and climate change4.

  1. Increased Mercury Bioaccumulation Follows Water Quality Improvement

    International Nuclear Information System (INIS)

    Bogle, M.A.; Peterson, M.J.; Smith, J.G.; Southworth, G.R.

    1999-01-01

    Changes in physical and chemical characteristics of aquatic habitats made to reduce or eliminate ecological risks can sometimes have unforeseen consequences. Environmental management activities on the U.S. Dept. of Energy reservation in Oak Ridge, Tennessee,have succeeded in improving water quality in streams impacted by discharges fi-om industrial facilities and waste disposal sites. The diversity and abundance of pollution-sensitive components of the benthic macroinvertebrate communities of three streams improved after new waste treatment systems or remedial actions reduced inputs of various toxic chemicals. Two of the streams were known to be mercury-contaminated from historical spills and waste disposal practices. Waterborne mercury concentrations in the third were typical of uncontaminated systems. In each case, concentrations of mercury in fish, or the apparent biological availability of mercury increased over the period during which ecological metrics indicated improved water quality. In the system where waterborne mercury concentrations were at background levels, increased mercury bioaccumulation was probably a result of reduced aqueous selenium concentrations; however, the mechanisms for increased mercury accumulation in the other two streams remain under investigation. In each of the three systems, reduced inputs of metals and inorganic anions was followed by improvements in the health of aquatic invertebrate communities. However, this reduction in risk to aquatic invertebrates was accompanied by increased risk to humans and piscivorous wildlife related to increased mercury concentrations in fish

  2. Increasing vaccine production using pulsed ultrasound waves.

    Directory of Open Access Journals (Sweden)

    Jida Xing

    Full Text Available Vaccination is a safe and effective approach to prevent deadly diseases. To increase vaccine production, we propose that a mechanical stimulation can enhance protein production. In order to prove this hypothesis, Sf9 insect cells were used to evaluate the increase in the expression of a fusion protein from hepatitis B virus (HBV S1/S2. We discovered that the ultrasound stimulation at a frequency of 1.5 MHz, intensity of 60 mW/cm2, for a duration of 10 minutes per day increased HBV S1/S2 by 27%. We further derived a model for transport through a cell membrane under the effect of ultrasound waves, tested the key assumptions of the model through a molecular dynamics simulation package, NAMD (Nanoscale Molecular Dynamics program and utilized CHARMM force field in a steered molecular dynamics environment. The results show that ultrasound waves can increase cell permeability, which, in turn, can enhance nutrient / waste exchange thus leading to enhanced vaccine production. This finding is very meaningful in either shortening vaccine production time, or increasing the yield of proteins for use as vaccines.

  3. Are rates of pediatric bipolar disorder increasing?

    DEFF Research Database (Denmark)

    Kessing, Lars Vedel; Vradi, Eleni; Andersen, Per Kragh

    2014-01-01

    Studies from the USA suggest that rates of pediatric bipolar disorder have increased since the mid-90s, but no study outside the USA has been published on the rates of pediatric bipolar disorder. Further, it is unclear whether an increase in rates reflects a true increase in the illness or more...... diagnostic attention. Using nationwide registers of all inpatients and outpatients contacts to all psychiatric hospitals in Denmark, we investigated (1) gender-specific rates of incident pediatric mania/bipolar disorder during a period from 1995 to 2012, (2) whether age and other characteristics...... for pediatric mania/bipolar disorder changed during the calendar period (1995 to 2003 versus 2004 to 2012), and (3) whether the diagnosis is more often made at first psychiatric contact in recent time compared to earlier according to gender. Totally, 346 patients got a main diagnosis of a manic episode (F30...

  4. Is Eurasian October snow cover extent increasing?

    International Nuclear Information System (INIS)

    Brown, R D; Derksen, C

    2013-01-01

    A number of recent studies present evidence of an increasing trend in Eurasian snow cover extent (SCE) in the October snow onset period based on analysis of the National Oceanic and Atmospheric Administration (NOAA) historical satellite record. These increases are inconsistent with fall season surface temperature warming trends across the region. Using four independent snow cover data sources (surface observations, two reanalyses, satellite passive microwave retrievals) we show that the increasing SCE is attributable to an internal trend in the NOAA CDR dataset to chart relatively more October snow cover extent over the dataset overlap period (1982–2005). Adjusting the series for this shift results in closer agreement with other independent datasets, stronger correlation with continentally-averaged air temperature anomalies, and a decrease in SCE over 1982–2011 consistent with surface air temperature warming trends over the same period. (letter)

  5. Increased transvascular lipoprotein transport in diabetes

    DEFF Research Database (Denmark)

    Jensen, Jan Skov; Feldt-Rasmussen, Bo; Borch-Johnsen, Knut

    2005-01-01

    CONTEXT: Diabetes is associated with a highly increased risk of atherosclerosis, especially if hypertension or albuminuria is present. OBJECTIVE: We hypothesized that the increased transvascular lipoprotein transport in diabetes may be further accelerated if hypertension or albuminuria is present...... of transvascular transport. RESULTS: Transvascular LDL transport was 1.8 (1.6-2.0), 2.3 (2.0-2.6), and 2.6 (1.3-4.0)%/[h x (liter/m2)] in healthy controls, diabetic controls, and diabetes patients with systolic hypertension or albuminuria, respectively (P = 0.013; F = 4.5; df =2; ANOVA). These differences most...... likely were not caused by altered hepatic LDL receptor expression, glycosylation of LDL, small LDL size, or medicine use. CONCLUSIONS: Transvascular LDL transport is increased in patients with diabetes mellitus, especially if systolic hypertension or albuminuria is present. Accordingly, lipoprotein flux...

  6. Platelet-Rich Plasma Increases Pigmentation.

    Science.gov (United States)

    Uysal, Cagri A; Ertas, Nilgun Markal

    2017-11-01

    Platelet-rich plasma (PRP) is an autologous solution of plasma containing 4 to 7 times the baseline concentration of human platelets. Platelet-rich plasma has been widely popular in facial rejuvenation to attenuate wrinkles and has been practically used. The authors have been encountering various patients of increased hiperpigmentation following PRP applications that were performed to attenuate the postinflammatory hiperpigmentation especially after laser treatment. The authors have been using PRP for facial rejuvenation in selected patients and in 1 patient the authors have encountered increased pigmentation over the pigmented skin lesions that were present before the application. The authors recommend that the PRP might increase pigmentation especially in the face region and precautions might be taken before and after the application. Platelet-rich plasma should not be used for the treatment of post inflammatory hiperpigmentation.

  7. Poor Semen Quality Predicts Increased Mortality

    DEFF Research Database (Denmark)

    Jensen, Tina Kold; Bostofte, Erik; Jacobsen, Rune

    Objective: Over recent decades a possible decrease in semen quality and an increase in the incidence of testicular cancer have been reported. In addition, men with poor semen quality have been reported to be at increased risk of developing testicular cancer whereas the risk of other cancers...... is not increased. The long-term survival of men with poor semen quality is, however, unknown. We therefore studied the associations between semen characteristics and subsequent mortality. Back to Top Material and Methods: The Copenhagen Sperm Analysis Laboratory is one of several public semen analysis laboratories...... in Denmark and examines semen samples mostly from men in the area of Copenhagen. Men are referred to the clinic by general practitioners and urologists, and the investigations are paid for through the public health system. A total of 34.442 men had a semen analysis done at the laboratory during 1963 to 1995...

  8. Increased skeletal muscle capillarization enhances insulin sensitivity

    DEFF Research Database (Denmark)

    Åkerström, Thorbjörn; Laub, Lasse; Vedel, Kenneth

    2014-01-01

    Increased skeletal muscle capillarization is associated with improved glucose tolerance and insulin sensitivity. However, a possible causal relationship has not previously been identified. We therefore investigated whether increased skeletal muscle capillarization increases insulin sensitivity....... Skeletal muscle specific angiogenesis was induced by adding the α1-adrenergic receptor antagonist Prazosin to the drinking water of Sprague Dawley rats (n=33) while 34 rats served as controls. Insulin sensitivity was measured ≥40 h after termination of the 3-week Prazosin treatment, which ensured...... that Prazosin was cleared from the blood stream. Whole-body insulin sensitivity was measured in conscious, unrestrained rats by hyperinsulinemic euglycemic clamp. Tissue specific insulin sensitivity was assessed by administration of 2-deoxy-[(3)H]-Glucose during the plateau phase of the clamp. Whole...

  9. Increased health care utilisation in international adoptees

    DEFF Research Database (Denmark)

    Graff, Heidi Jeannet; Siersma, Volkert Dirk; Kragstrup, Jakob

    2015-01-01

    comprised internationallyadopted children (n = 6,820), adopted between 1994 and2005, and all non-adopted children (n = 492,374) who couldbe matched with the adopted children on sex, age, municipalityand family constellation at the time of adoption. Results: International adoption increased the use......Introduction: Several studies have documented thatinternational adoptees have an increased occurrence ofhealth problems and contacts to the health-care systemafter arriving to their new country of residence. This maybe explained by pre-adoption adversities, especially for theperiod immediately...... after adoption. Our study aimed to theassess health-care utilisation of international adoptees inprimary and secondary care for somatic and psychiatricdiagnoses in a late post-adoption period. Is there an increaseduse of the health-care system in this period, evenwhen increased morbidity in the group...

  10. Nutrient enrichment increases mortality of mangroves.

    Directory of Open Access Journals (Sweden)

    Catherine E Lovelock

    Full Text Available Nutrient enrichment of the coastal zone places intense pressure on marine communities. Previous studies have shown that growth of intertidal mangrove forests is accelerated with enhanced nutrient availability. However, nutrient enrichment favours growth of shoots relative to roots, thus enhancing growth rates but increasing vulnerability to environmental stresses that adversely affect plant water relations. Two such stresses are high salinity and low humidity, both of which require greater investment in roots to meet the demands for water by the shoots. Here we present data from a global network of sites that documents enhanced mortality of mangroves with experimental nutrient enrichment at sites where high sediment salinity was coincident with low rainfall and low humidity. Thus the benefits of increased mangrove growth in response to coastal eutrophication is offset by the costs of decreased resilience due to mortality during drought, with mortality increasing with soil water salinity along climatic gradients.

  11. STRATEGIES FOR INCREASING PRODUCTIVITY IN PRODUCTION SYSTEMS

    Directory of Open Access Journals (Sweden)

    Diego Pacheco

    2014-05-01

    Full Text Available The main objective of this article is to point a set of practical strategies that can be adopted to increase the capacity of constraints resources on production systems, when the constraint is inside the factory and not is in the market. To serve this purpose will be presented strategies based on best practices of the Theory of Constraints, Lean Manufacturing and Total Productive Maintenance. This article also presents the mains tools for the deployment of these methodologies. The survey results have provided an objective set of practical strategy that can be used to increase the capacity and productivity of production systems according to the needs of each manufacturing system.

  12. Increasing dominance of IT in ICT convergence

    DEFF Research Database (Denmark)

    Henten, Anders; Tadayoni, Reza

    The aim of the paper is to examine the increasing dominance of IT companies in the converging ICT industry and, on the basis of this development, to contribute to extending the theoretical understanding of market and industry convergence in the ICT area.......The aim of the paper is to examine the increasing dominance of IT companies in the converging ICT industry and, on the basis of this development, to contribute to extending the theoretical understanding of market and industry convergence in the ICT area....

  13. Licensing process for the power increase

    International Nuclear Information System (INIS)

    Perez P, R.; Mamani A, Y.R.; Salgado G, J.R.

    2006-01-01

    The licensing process for the power increase of a nuclear power station is presented, this includes the description of the effective normative framework, the attributions of the one Mexican regulator organism in nuclear matter, the definition and importance of the power level of a nuclear reactor for the safety studies. Also, the types of power increase according to its magnitude, and the regulator process that it includes the scope and the detail of the required information that it should be evaluated by the one regulator organism are discussed. Finally it offers a summary of the experience that one has in Mexico for this type of processes. (Author)

  14. Alanine increases blood pressure during hypotension

    Science.gov (United States)

    Conlay, L. A.; Maher, T. J.; Wurtman, R. J.

    1990-01-01

    The effect of L-alanine administration on blood pressure (BP) during haemorrhagic shock was investigated using anesthetized rats whose left carotid arteries were cannulated for BP measurement, blood removal, and drug administration. It was found that L-alanine, in doses of 10, 25, 50, 100, and 200 mg/kg, increased the systolic BP of hypotensive rats by 38 to 80 percent (while 100 mg/kg pyruvate increased BP by only 9.4 mmhg, not significantly different from saline). The results suggest that L-alanine might influence cardiovascular function.

  15. Hanford Waste Vitrification Plant capacity increase options

    International Nuclear Information System (INIS)

    Larson, D.E.

    1996-04-01

    Studies are being conducted by the Hanford Waste Vitrification Plant (HWVP) Project on ways to increase the waste processing capacity within the current Vitrification Building structural design. The Phase 1 study on remote systems concepts identification and extent of capacity increase was completed. The study concluded that the HWVP capacity could be increased to four times the current capacity with minor design adjustments to the fixed facility design, and the required design changes would not impact the current footprint of the vitrification building. A further increase in production capacity may be achievable but would require some technology development, verification testing, and a more systematic and extensive engineering evaluation. The primary changes included a single advance melter with a higher capacity, new evaporative feed tank, offgas quench collection tank, ejector venturi scrubbers, and additional inner canister closure station,a smear test station, a new close- coupled analytical facility, waste hold capacity of 400,000 gallon, the ability to concentrate out-of-plant HWVP feed to 90 g/L waste oxide concentration, and limited changes to the current base slab construction package

  16. Using Mobile Phones to Increase Classroom Interaction

    Science.gov (United States)

    Cobb, Stephanie; Heaney, Rose; Corcoran, Olivia; Henderson-Begg, Stephanie

    2010-01-01

    This study examines the possible benefits of using mobile phones to increase interaction and promote active learning in large classroom settings. First year undergraduate students studying Cellular Processes at the University of East London took part in a trial of a new text-based classroom interaction system and evaluated their experience by…

  17. Increasing security in inter-chip communication

    Science.gov (United States)

    Edwards, Nathan J; Hamlet, Jason; Bauer, Todd; Helinski, Ryan

    2014-10-28

    An apparatus for increasing security in inter-chip communication includes a sending control module, a communication bus, and a receiving control module. The communication bus is coupled between the sending control module and the receiving control module. The sending control module operates to send data on the communication bus, disable the communication bus when threats are detected, or both.

  18. SIRTF thermal design modifications to increase lifetime

    Science.gov (United States)

    Petrick, S. W.

    1993-01-01

    An effort was made to increase the predicted lifetime of the SIRTF dewar by lowering the exterior shell temperature, increasing the radiated energy from the vapor cooled shields and reconfiguring the vapor cooled shields. The lifetime increases can be used to increase the scientific return from the mission and as a trade-off against mass and cost. This paper describes the configurations studied, the steady state thermal model used, the analytical methods and the results of the analysis. Much of the heat input to the outside dewar shell is radiative heat transfer from the solar panel. To lower the shell temperature, radiative cooled shields were placed between the solar panel and the dewar shell and between the bus and the dewar shell. Analysis showed that placing a radiator on the outer vapor cooled shield had a significant effect on lifetime. Lengthening the distance between the outer shell and the point where the vapor cooled shields are attached to the support straps also improved lifetime.

  19. Increased cooperation through immediate post contractual negotiation

    NARCIS (Netherlands)

    Meijers, Stephan; Doree, Andries G.; Boes, Johan

    2014-01-01

    Traditional contracting has been largely shown to cause adversarial relationships between client and contractor in the construction sector. This leads to claims during construction by contractors, which increase transaction costs for both parties in the form of policing and enforcement costs. In

  20. Increasing Influenza Vaccine Uptake. A Comprehensive Approach

    NARCIS (Netherlands)

    Looijmans - van den Akker, I.

    2009-01-01

    General introduction: To prevent influenza virus infection, immunization against influenza has been recommended for individuals with increased risk of complications. These groups comprise individuals of 60 years and older, individuals with risk-elevating co-morbid conditions, residents of nursing

  1. SHORT COMMUNICATION Challenges to increased Snail ...

    African Journals Online (AJOL)

    The commercial production of snails has not kept pace with the demand for it in Ibarapa Local Government Areas (ILGA) of Oyo State, Nigeria. A study was carried out to characterize the snail farmers, identify challenges to an increased snail production and suggest measures for sustainable snail production. Structured ...

  2. Island Species Richness Increases with Habitat Diversity

    NARCIS (Netherlands)

    Hortal, J.; Triantis, K.A.; Meiri, S.; Thebault, E.M.C.; Sfenthourakis, S.

    2009-01-01

    Species richness is commonly thought to increase with habitat diversity. However, a recent theoretical model aiming to unify niche and island biogeography theories predicted a hump-shaped relationship between richness and habitat diversity. Given the contradiction between model results and previous

  3. Hypospadias and increased risk for neurodevelopmental disorders

    OpenAIRE

    Butwicka, Agnieszka; Lichtenstein, Paul; Landén, Mikael; Nordenvall, Anna; Nordenström, Anna; Nordenskjöld, Agneta; Frisén, Louise

    2014-01-01

    BACKGROUND: Hypospadias (aberrant opening of the urethra on the underside of the penis) occurs in 1 per 300 newborn boys. It has been previously unknown whether this common malformation is associated with increased psychiatric morbidity later in life. Studies of individuals with hypospadias also provide an opportunity to examine whether difference in androgen signaling is related to neurodevelopmental disorders. To elucidate the mechanisms behind ...

  4. Goal Setting to Increase Student Academic Performance

    Science.gov (United States)

    Dotson, Ronnie

    2016-01-01

    Over the past two years, the teachers and students in Carter County, Kentucky have been utilizing goal setting. As a result, the district has shown tremendous growth on not only state assessments, but also on local assessments. Additionally, the number of students meeting benchmarks for college and career readiness has increased significantly. The…

  5. Motivating Students by Increasing Student Choice

    Science.gov (United States)

    Birdsell, Becky S.; Ream, Sarah M.; Seyller, Ann M.; Zobott, Pam L.

    2009-01-01

    The purpose of this study was to increase motivation in 7th grade students. Four teacher researchers examined the change in motivational levels as a result of choice strategies. They gathered data from four different classes, 101 students in all, to track levels of motivation. They monitored their levels of observable behavioral patterns with a…

  6. Increasing Access and Relevance in Distance Education

    Science.gov (United States)

    Mendenhall, Robert W.

    2009-01-01

    Access to higher education is subject to many factors including affordability, time and geography. Distance education can deliver education to those that live far from a campus. Some of that distance education may be synchronous, or live, requiring students to be available at certain times. Flexibility and access are increased when the instruction…

  7. Sex Equity: Increasing Girls' Use of Computers.

    Science.gov (United States)

    Lockheed, Marlaine E.; Frakt, Steven B.

    1984-01-01

    Indicates that although computer science has been free of male domination, the stereotype of computers as male machines is emerging with increasing growth in microcomputer use by children. Factors that account for this development and some strategies teachers can adopt to equalize computer use by boys and girls are presented. (MBR)

  8. Age Increases Monocyte Adhesion on Collagen

    Science.gov (United States)

    Khalaji, Samira; Zondler, Lisa; Kleinjan, Fenneke; Nolte, Ulla; Mulaw, Medhanie A.; Danzer, Karin M.; Weishaupt, Jochen H.; Gottschalk, Kay-E.

    2017-05-01

    Adhesion of monocytes to micro-injuries on arterial walls is an important early step in the occurrence and development of degenerative atherosclerotic lesions. At these injuries, collagen is exposed to the blood stream. We are interested whether age influences monocyte adhesion to collagen under flow, and hence influences the susceptibility to arteriosclerotic lesions. Therefore, we studied adhesion and rolling of human peripheral blood monocytes from old and young individuals on collagen type I coated surface under shear flow. We find that firm adhesion of monocytes to collagen type I is elevated in old individuals. Pre-stimulation by lipopolysaccharide increases the firm adhesion of monocytes homogeneously in older individuals, but heterogeneously in young individuals. Blocking integrin αx showed that adhesion of monocytes to collagen type I is specific to the main collagen binding integrin αxβ2. Surprisingly, we find no significant age-dependent difference in gene expression of integrin αx or integrin β2. However, if all integrins are activated from the outside, no differences exist between the age groups. Altered integrin activation therefore causes the increased adhesion. Our results show that the basal increase in integrin activation in monocytes from old individuals increases monocyte adhesion to collagen and therefore the risk for arteriosclerotic plaques.

  9. Increasing Sales by Developing Production Consortiums.

    Science.gov (United States)

    Smith, Christopher A.; Russo, Robert

    Intended to help rehabilitation facility administrators increase organizational income from manufacturing and/or contracted service sources, this document provides a decision-making model for the development of a production consortium. The document consists of five chapters and two appendices. Chapter 1 defines the consortium concept, explains…

  10. Pharmacovigilance: Tiens Slimming Tea Causes Increased Blood ...

    African Journals Online (AJOL)

    ... possible link between the constituents of the slimming tea and increased blood pressure and also provide evidence of other possible harmful effects that may occur with the use of the slimming tea. Keywords: Pharmacovigilance, hypertension, slimming tea. West African Journal of Pharmacology and Drug Research Vol.

  11. GERD: Can Certain Medications Increase Severity?

    Science.gov (United States)

    ... increase severity? I've heard that some medications can aggravate the symptoms of GERD. Can you tell me more? Answers from Michael F. Picco, M.D. Certain medications and dietary supplements can irritate the lining of your esophagus, causing heartburn ...

  12. Increasing Household Protein Consumption Through Minilivestock ...

    African Journals Online (AJOL)

    Mini-livestock production can be a major contributor of a more balanced diet for both rural and urban settlements. The attributes of mini-livestock gives it the potential of increasing household protein consumption as well as being a source of income. Mini-livestock production can be practiced in rural and urban settlements ...

  13. ICT in higher education: increased student engagement.

    NARCIS (Netherlands)

    Zweekhorst, M.B.M.; Maas, J.

    2015-01-01

    Purpose – In general, active participation increases learning outcomes. The purpose of this paper is to explore how: information and communication technologies (ICT) can be used to improve the participation of students during lectures and the effect of ICT on the learning outcomes of students.

  14. FORUM Models for increasing the health workforce

    African Journals Online (AJOL)

    stewardship of the anticipated growth of private education and services ... The Global Health Workforce Alliance3 recognises the importance of increasing ... Action 2010 - 2014 to advance economic growth and development, to be realised by ... of the private higher education sector must be better understood and supported.

  15. Power Curve Measurements, quantify the production increase

    DEFF Research Database (Denmark)

    Gómez Arranz, Paula; Vesth, Allan

    The purpose of this report is to quantify the production increase on a given turbine with respect to another given turbine. The used methodology is the “side by side” comparison method, provided by the client. This method involves the use of two neighboring turbines and it is based...

  16. Robotic Bipedal Running : Increasing disturbance rejection

    NARCIS (Netherlands)

    Karssen, J.G.D.

    2013-01-01

    The goal of the research presented in this thesis is to increase the understanding of the human running gait. The understanding of the human running gait is essential for the development of devices, such as prostheses and orthoses, that enable disabled people to run or that enable able people to

  17. BUSINESS MODELS FOR INCREASING TECHNOLOGICAL TRANSFER EFFECTIVENESS

    Directory of Open Access Journals (Sweden)

    Simina FULGA

    2016-05-01

    Full Text Available The present paper is devoted to analyze the appropriate recommendations to increase the effectiveness of technology transfer organizations (centers from ReNITT, by using the specific instruments of Business Model Canvas, associated to the technological transfer value chain for the value added services addressed to their clients and according to a continuously improved competitive strategy over competition analysis.

  18. Does trade liberalization increase global pollution?

    International Nuclear Information System (INIS)

    Beladi, Hamid; Oladi, Reza

    2011-01-01

    In this paper we consider a simple duopoly market in which a home firm and a foreign firm use labor to produce an identical product and supply it to the home market. Firms emit pollution as a by-product of production. We show conditions under which international trade liberalization decreases (increases) the global pollution. (author)

  19. Increasing the lifetime of fuel cell catalysts

    NARCIS (Netherlands)

    Latsuzbaia, R.

    2015-01-01

    In this thesis, I discuss a novel idea of fuel cell catalyst regeneration to increase lifetime of the PEM fuel cell electrode/catalyst operation and, therefore, reduce the catalyst costs. As many of the catalyst degradation mechanisms are difficult to avoid, the regeneration is alternative option to

  20. Increasing Incidence of Juvenile Thyrotoxicosis in Denmark

    DEFF Research Database (Denmark)

    Kjær, R. H.; Andersen, M. S.; Hansen, D.

    2015-01-01

    Aim: The aim of this study was to determine in a Danish nationwide study whether the incidence rate (IR) of thyrotoxicosis in children below 15 years of age has increased between 1998 and 2012 and to compare the results with previously published national data from 1982 to 1988. Furthermore, we...

  1. Increased thyrotropin binding in hyperfunctioning thyroid nodules.

    Science.gov (United States)

    Müller-Gärtner, H W; Schneider, C; Bay, V; Tadt, A; Rehpenning, W; de Heer, K; Jessel, M

    1987-08-01

    The object of this study was to investigate TSH receptors in hyperfunctioning thyroid nodules (HFN). In HFN, obtained from seven patients, 125-I-TSH binding as determined by equilibrium binding analysis on particulate membrane preparations, was found to be significantly increased as compared with normal thyroid tissues (five patients; P less than 0.001). Scatchard analysis of TSH-binding revealed two kinds of binding sites for both normal thyroid tissue and HFN, and displayed significantly increased association constants of high- and low-affinity binding sites in HFN (Ka = 11.75 +/- 6.8 10(9) M-1, P less than 0.001 and Ka = 2.1 +/- 1.0 10(7) M-1, P less than 0.025; x +/- SEM) as compared with normal thyroid tissue (Ka = 0.25 +/- 0.06 10(9) M-1, Ka = 0.14 +/- 0.03 10(7) M-1; x +/- SEM). The capacity of the high-affinity binding sites in HFN was found to be decreased (1.8 +/- 1.1 pmol/mg protein, x +/- SEM) in comparison with normal thyroid tissue (4.26 +/- 1.27 pmol/mg protein; x +/- SEM). TSH-receptor autoradiography applied to cryostatic tissue sections confirmed increased TSH binding of the follicular epithelium in HFN. These data suggest that an increased affinity of TSH-receptor sites in HFN in iodine deficient areas may be an important event in thyroid autonomy.

  2. Precritical increase of particle collision rates

    International Nuclear Information System (INIS)

    Muenchow, L.

    1990-01-01

    In quantum kinetics the collision integral follows from the imaginary part of the mass operator. Using this connection it is shown that the coupling of single particle motion to precritical density fluctuations causes a strong increase of the collision integral near the point of phase instability. 13 refs

  3. Thalidomide increases human keratinocyte migration and proliferation.

    Science.gov (United States)

    Nasca, M R; O'Toole, E A; Palicharla, P; West, D P; Woodley, D T

    1999-11-01

    Thalidomide is reported to have therapeutic utility in the treatment of pyoderma gangrenosum, Behçet's disease, aphthous ulcers, and skin wounds. We investigated the effect of thalidomide on human keratinocyte proliferation and migration, two early and critical events in the re-epithelialization of skin wounds. Thalidomide at concentrations less than 1 microM did not affect keratinocyte viability. Using a thymidine incorporation assay, we found that thalidomide, at therapeutic concentrations, induced more than a 2. 5-fold increase in the proliferative potential of the cells. Keratinocyte migration was assessed by two independent motility assays: a colloidal gold assay and an in vitro scratch assay. At optimal concentrations, thalidomide increased keratinocyte migration on a collagen matrix more than 2-fold in the colloidal gold assay and more than 3-fold in the scratch assay over control. Although pro-migratory, thalidomide did not alter the level of metalloproteinase-9 secreted into culture medium. Thalidomide did, however, induce a 2-4-fold increase in keratinocyte-derived interleukin-8, a pro-migratory cellular autocrine factor. Human keratinocyte migration and proliferation are essential for re-epithelialization of skin wounds. Interleukin-8 increases human keratinocyte migration and proliferation and is chemotactic for keratinocytes. Therefore, thalidomide may modulate keratinocyte proliferation and motility by a chemokine-dependent pathway.

  4. Optimal diversity: Increasing returns versus recombinant innovation

    NARCIS (Netherlands)

    van den Bergh, J.C.J.M.; Zeppini Rossi, P.

    2008-01-01

    Choices regarding diversity play an important role in economics and innovation management, but often remain implicit. Once made explicit, the objectives of efficiency and diversity are usually posed as in conflict, as efficiency relates positively and diversity negatively to various increasing

  5. Potential transgenic routes to increase tree biomass.

    Science.gov (United States)

    Dubouzet, Joseph G; Strabala, Timothy J; Wagner, Armin

    2013-11-01

    Biomass is a prime target for genetic engineering in forestry because increased biomass yield will benefit most downstream applications such as timber, fiber, pulp, paper, and bioenergy production. Transgenesis can increase biomass by improving resource acquisition and product utilization and by enhancing competitive ability for solar energy, water, and mineral nutrients. Transgenes that affect juvenility, winter dormancy, and flowering have been shown to influence biomass as well. Transgenic approaches have increased yield potential by mitigating the adverse effects of prevailing stress factors in the environment. Simultaneous introduction of multiple genes for resistance to various stress factors into trees may help forest trees cope with multiple or changing environments. We propose multi-trait engineering for tree crops, simultaneously deploying multiple independent genes to address a set of genetically uncorrelated traits that are important for crop improvement. This strategy increases the probability of unpredictable (synergistic or detrimental) interactions that may substantially affect the overall phenotype and its long-term performance. The very limited ability to predict the physiological processes that may be impacted by such a strategy requires vigilance and care during implementation. Hence, we recommend close monitoring of the resultant transgenic genotypes in multi-year, multi-location field trials. Copyright © 2013 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  6. Increasing Student Engagement through Paired Technologies

    Science.gov (United States)

    Basko, Lynn; Hartman, Jillian

    2017-01-01

    This article highlights efficient ways to combine tech tools, such as Remind and video conferencing, to increase student engagement and faculty/student communication. Using Remind is a great way to provide information to students outside of LoudCloud, and video conferencing is a tool for having synchronous meetings and conferences with students.…

  7. Towards an increase of respiratory allergies

    International Nuclear Information System (INIS)

    Anon.

    2009-01-01

    An increase in the prevalence and severity of asthma and pollinoses is one of the predictable health consequences of climate change, as this article, based on data from numerous scientific reports, unambiguously demonstrates. It is one more reason for the health field to enlist in the fight against global warming, while its scale and speed can still be controlled. (author)

  8. Profit sharing for increased training investments

    NARCIS (Netherlands)

    Gielen, A. C.

    2011-01-01

    This article investigates whether paying a profit-related wage stimulates training investments. The results point to increased worker effort and wage flexibility as two channels through which profit sharing enhances investments in training. While both effects are found for young workers, for older

  9. Integrated engineering increases flexibility. [At BNFL

    Energy Technology Data Exchange (ETDEWEB)

    Smith, Ray [British Nuclear Fuels plc, London (UK)

    1991-05-01

    Integrated Engineering (IE) can be used to describe the best use of increasingly rare good engineering talent in an increasingly competive world. A number of organisations are now moving towards IE without any general agreement on a precise definition. The engineering division of British Nuclear Fuels (BNFL) is one such organisation. This feature covers the reasoning behind the decision, and our experience to date. BNFL engineering division is responsible primarily for the provision of major facilities on BNFL operational sites. This provision includes feasibility, front end and detailed design, procurement, installation and commissioning. Task force working has been used for some of the large projects. But the future workload is expected to comprise many more smaller projects. At the same time, equipment is becoming more complex and the need for mutual understanding and appreciation between disciplines is increasing. To meet this increasing need for flexibility, BNFL has decided to move to the matrix structure of project management and functional departments described in the article. (Author).

  10. Ontogeny of 6-keto-PGF/sub 1α/ synthesis in rabbit aorta and the effect of premature weaning

    International Nuclear Information System (INIS)

    Bydlowski, S.P.; Yunker, R.L.; Subbiah, M.T.R.

    1987-01-01

    A systematic study of the ontogeny of aortic 6-ketoprostaglandin F/sub 1α/ synthesis from birth to adult life and the effect of premature weaning on this process was investigated in rabbits. Prostacyclin (PGI 2 ) synthesis by both endogenous and exogenous arachidonic acid and its relation to aortic arachidonic acid content was determined. It was found that 1) PGI 2 synthesis from endogenous arachidonic acid increased with age, whereas 2) PGI 2 synthesis from exogenous arachidonic acid decreased. This correlated with a decrease in the incorporation of [ 14 C]arachidonic acid into phospholipids with age. Aortic arachidonic acid concentration did not change from birth until 3 wk of life but increased markedly by 5 wk of age. Premature weaning caused a decrease in the synthesis of aortic PGI 2 and in aortic arachidonic acid concentration initially, but the changes did not persist in later life. These studies suggest that the utilization of exogenous arachidonic acid by aorta decreases after birth perhaps due to maturity of the enzyme systems that synthesize and utilize endogenous substrates

  11. Increased heart rate variability during nondirective meditation.

    Science.gov (United States)

    Nesvold, Anders; Fagerland, Morten W; Davanger, Svend; Ellingsen, Øyvind; Solberg, Erik E; Holen, Are; Sevre, Knut; Atar, Dan

    2012-08-01

    Meditation practices are in use for relaxation and stress reduction. Some studies indicate beneficial cardiovascular health effects of meditation. The effects on the autonomous nervous system seem to vary among techniques. The purpose of the present study was to identify autonomic nerve activity changes during nondirective meditation. Heart rate variability (HRV), blood pressure variability (BPV), and baroreflex sensitivity (BRS) were monitored in 27 middle-aged healthy participants of both genders, first during 20 min regular rest with eyes closed, thereafter practising Acem meditation for 20 min. Haemodynamic and autonomic data were collected continuously (beat-to-beat) and non-invasively. HRV and BPV parameters were estimated by power spectral analyses, computed by an autoregressive model. Spontaneous activity of baroreceptors were determined by the sequence method. Primary outcomes were changes in HRV, BPV, and BRS between rest and meditation. HRV increased in the low-frequency (LF) and high-frequency (HF) bands during meditation, compared with rest (p = 0.014, 0.013, respectively). Power spectral density of the RR-intervals increased as well (p = 0.012). LF/HF ratio decreased non-significantly, and a reduction of LF-BPV power was observed during meditation (p < 0.001). There was no significant difference in BRS. Respiration and heart rates remained unchanged. Blood pressure increased slightly during meditation. There is an increased parasympathetic and reduced sympathetic nerve activity and increased overall HRV, while practising the technique. Hence, nondirective meditation by the middle aged may contribute towards a reduction of cardiovascular risk.

  12. Increased cerebral water content in hemodialysis patients.

    Directory of Open Access Journals (Sweden)

    Kathrin Reetz

    Full Text Available Little information is available on the impact of hemodialysis on cerebral water homeostasis and its distribution in chronic kidney disease. We used a neuropsychological test battery, structural magnetic resonance imaging (MRI and a novel technique for quantitative measurement of localized water content using 3T MRI to investigate ten hemodialysis patients (HD on a dialysis-free day and after hemodialysis (2.4±2.2 hours, and a matched healthy control group with the same time interval. Neuropsychological testing revealed mainly attentional and executive cognitive dysfunction in HD. Voxel-based-morphometry showed only marginal alterations in the right inferior medial temporal lobe white matter in HD compared to controls. Marked increases in global brain water content were found in the white matter, specifically in parietal areas, in HD patients compared to controls. Although the global water content in the gray matter did not differ between the two groups, regional increases of brain water content in particular in parieto-temporal gray matter areas were observed in HD patients. No relevant brain hydration changes were revealed before and after hemodialysis. Whereas longer duration of dialysis vintage was associated with increased water content in parieto-temporal-occipital regions, lower intradialytic weight changes were negatively correlated with brain water content in these areas in HD patients. Worse cognitive performance on an attention task correlated with increased hydration in frontal white matter. In conclusion, long-term HD is associated with altered brain tissue water homeostasis mainly in parietal white matter regions, whereas the attentional domain in the cognitive dysfunction profile in HD could be linked to increased frontal white matter water content.

  13. Increased cerebral water content in hemodialysis patients.

    Science.gov (United States)

    Reetz, Kathrin; Abbas, Zaheer; Costa, Ana Sofia; Gras, Vincent; Tiffin-Richards, Frances; Mirzazade, Shahram; Holschbach, Bernhard; Frank, Rolf Dario; Vassiliadou, Athina; Krüger, Thilo; Eitner, Frank; Gross, Theresa; Schulz, Jörg Bernhard; Floege, Jürgen; Shah, Nadim Jon

    2015-01-01

    Little information is available on the impact of hemodialysis on cerebral water homeostasis and its distribution in chronic kidney disease. We used a neuropsychological test battery, structural magnetic resonance imaging (MRI) and a novel technique for quantitative measurement of localized water content using 3T MRI to investigate ten hemodialysis patients (HD) on a dialysis-free day and after hemodialysis (2.4±2.2 hours), and a matched healthy control group with the same time interval. Neuropsychological testing revealed mainly attentional and executive cognitive dysfunction in HD. Voxel-based-morphometry showed only marginal alterations in the right inferior medial temporal lobe white matter in HD compared to controls. Marked increases in global brain water content were found in the white matter, specifically in parietal areas, in HD patients compared to controls. Although the global water content in the gray matter did not differ between the two groups, regional increases of brain water content in particular in parieto-temporal gray matter areas were observed in HD patients. No relevant brain hydration changes were revealed before and after hemodialysis. Whereas longer duration of dialysis vintage was associated with increased water content in parieto-temporal-occipital regions, lower intradialytic weight changes were negatively correlated with brain water content in these areas in HD patients. Worse cognitive performance on an attention task correlated with increased hydration in frontal white matter. In conclusion, long-term HD is associated with altered brain tissue water homeostasis mainly in parietal white matter regions, whereas the attentional domain in the cognitive dysfunction profile in HD could be linked to increased frontal white matter water content.

  14. Increasing Vaccination: Putting Psychological Science Into Action.

    Science.gov (United States)

    Brewer, Noel T; Chapman, Gretchen B; Rothman, Alexander J; Leask, Julie; Kempe, Allison

    2017-12-01

    Vaccination is one of the great achievements of the 20th century, yet persistent public-health problems include inadequate, delayed, and unstable vaccination uptake. Psychology offers three general propositions for understanding and intervening to increase uptake where vaccines are available and affordable. The first proposition is that thoughts and feelings can motivate getting vaccinated. Hundreds of studies have shown that risk beliefs and anticipated regret about infectious disease correlate reliably with getting vaccinated; low confidence in vaccine effectiveness and concern about safety correlate reliably with not getting vaccinated. We were surprised to find that few randomized trials have successfully changed what people think and feel about vaccines, and those few that succeeded were minimally effective in increasing uptake. The second proposition is that social processes can motivate getting vaccinated. Substantial research has shown that social norms are associated with vaccination, but few interventions examined whether normative messages increase vaccination uptake. Many experimental studies have relied on hypothetical scenarios to demonstrate that altruism and free riding (i.e., taking advantage of the protection provided by others) can affect intended behavior, but few randomized trials have tested strategies to change social processes to increase vaccination uptake. The third proposition is that interventions can facilitate vaccination directly by leveraging, but not trying to change, what people think and feel. These interventions are by far the most plentiful and effective in the literature. To increase vaccine uptake, these interventions build on existing favorable intentions by facilitating action (through reminders, prompts, and primes) and reducing barriers (through logistics and healthy defaults); these interventions also shape behavior (through incentives, sanctions, and requirements). Although identification of principles for changing

  15. Constant Fiber Number During Skeletal Muscle Atrophy and Modified Arachidonate Metabolism During Hypertrophy

    Science.gov (United States)

    Templeton, G.

    1985-01-01

    A previously documented shift from Type I to IIA predominance of the soleus muscle during rat suspension was further investigated to determine if this shift was by selective reduction of a single fiber type, simultaneous reduction and formation of fibers with different fiber types, or a transformation of fiber type by individual fibers. By partial acid digestion and dissection, average total soleus fiber number was found to be 3022 + or - 80 (SE) and 3008 + or - 64 before and after four-week suspension (n=12). Another area of current research was based on previous studies which indicate that prostaglandins are biosynthesized by skeletal muscle and evoke protein synthesis and degradation.

  16. Dietary fatty acids and the stress response of fish. Arachidonic acid in seabream and tilapia

    NARCIS (Netherlands)

    Anholt, R.D. van

    2004-01-01

    A key factor in the production of fish in commercial aquaculture is the optimization of the artificial diets, not only to achieve optimal growth, but also to maximize fish health. Evidence is accumulating that dietary lipids, particularly the fatty acid composition, can have a direct effect on the

  17. Multiple biological effects of inhibitors of arachidonic acid metabolism on human keratinocytes

    Czech Academy of Sciences Publication Activity Database

    Pacherník, Jiří; Hampl, Aleš; Souček, Karel; Kovaříková, Martina; Andrysík, Zdeněk; Hofmanová, Jiřina; Kozubík, Alois

    2002-01-01

    Roč. 293, č. 12 (2002), s. 626-633 ISSN 0340-3696 R&D Projects: GA ČR GA524/99/0694; GA AV ČR IBS5004009; GA ČR GA524/98/0190 Institutional research plan: CEZ:AV0Z5004920 Keywords : lipoxygenase * keratinocytes * cell cycle Subject RIV: BO - Biophysics Impact factor: 1.452, year: 2002

  18. How dietary arachidonic- and docosahexaenoic- acid rich oils differentially affect the murine hepatic transcriptome

    OpenAIRE

    Roberts Matthew A; Berger Alvin; Hoff Bruce

    2006-01-01

    Introduction Herein, we expand our previous work on the effects of long chain polyunsaturated fatty acids (LC-PUFA) on the murine hepatic transcriptome using novel statistical and bioinformatic approaches for evaluating microarray data. The analyses focuses on key differences in the transcriptomic response that will influence metabolism following consumption of FUNG (rich in 20:4n6), FISH (rich in 20:5n3, 22:5n3, and 22:6n3) and COMB, the combination of the two. Results Using a variance-stab...

  19. How dietary arachidonic- and docosahexaenoic- acid rich oils differentially affect the murine hepatic transcriptome

    Directory of Open Access Journals (Sweden)

    Roberts Matthew A

    2006-04-01

    Full Text Available Introduction Herein, we expand our previous work on the effects of long chain polyunsaturated fatty acids (LC-PUFA on the murine hepatic transcriptome using novel statistical and bioinformatic approaches for evaluating microarray data. The analyses focuses on key differences in the transcriptomic response that will influence metabolism following consumption of FUNG (rich in 20:4n6, FISH (rich in 20:5n3, 22:5n3, and 22:6n3 and COMB, the combination of the two. Results Using a variance-stabilized F-statistic, 371 probe sets (out of 13 K probe sets in the Affymetrix Mu11K chip set were changed by dietary treatment (P Conclusion Distinct transcriptomic, signaling cascades, and predicted affects on murine liver metabolism have been elucidated for 20:4n6-rich dietary oils, 22:6n3-rich oils, and a surprisingly distinct set of genes were affected by the combination of the two. Our results emphasize that the balance of dietary n6 and n3 LC-PUFA provided for infants and in nutritional and neutraceutical applications could have profoundly different affects on metabolism and cell signaling, beyond that previously recognized.

  20. The Arachidonic Acid Pathway: a potential application in the diagnosis and prognosis of prostate cancer

    NARCIS (Netherlands)

    G.A. Rodríguez-Blanco (Giovanny)

    2017-01-01

    markdownabstractProstate cancer (PCa) is the most common cancer in men, and in 2012 more than 400,000 cases were diagnosed in Europe. Although the introduction of the PSA test improved the management of the disease, its low specificity has led to overdiagnosis and unnecessary treatments for men