Sample records for reduced thyroxine release

  1. Luteinizing hormone-releasing hormone induces thyroxine release together with testosterone in the neotenic axolotl Ambystoma mexicanum.

    Jacobs, G F; Kühn, E R


    In male neotenic axolotls Ambystoma mexicanum plasma concentrations of thyroxine (T4) and testosterone were increased following intravenous injection of 10 micrograms luteinizing hormone-releasing hormone. A dose of 50 micrograms influenced only plasma T4 levels. This observation suggests for the first time that a hypothalamic hormone is capable of stimulating the thyroidal axis in the neotenic axolotl.

  2. Cellular mechanisms of reduced sarcoplasmic reticulum Ca2+ content in L-thyroxin-induced rat ventricular hypertrophy

    Lai-jing SONG; Guan-lei WANG; Jie LIU; Qin-ying QIU; Jing-hua OU; Yong-yuan GUAN


    Aim:To examine how the sarcoplasmic reticulum (SR) Ca2+ content changes and the underlying mechanism in L-thyroxin-induced cardiac hypertrophy. Methods:Echocardiography was used to confirm the establishment of the cardiac hypertro-phy model. The confocal microscopy and fluorescent indicator Fluo-3 was ap-plied to examine the intracellular Ca2+ concentration ([Ca2+]I), the Ca2+ sparks, and the caffeine-induced Ca2+ transient in freshly isolated cardiac ventricular myocytes. The activity of sarcolemmal and SR Ca2+-ATPase 2a (SERCA2a) in the ventricular tissue was also measured, respectively. Results:L-thyroxin (1 mg/kg injection for 10 d) induces left ventricular cardiac hypertrophy with normal myocardial function. The decreased caffeine-induced Ca2+ transient in the Ca2+-free solution was detected. The spontaneous Ca2+ sparks in hypertrophied myocytes occurred more frequently than in normal cells, with similar duration and spatial spread, but smaller amplitude. Then the basal [Ca2+]I increase was observed in quiescent left ventricular myocytes from hyperthyroidism rats. The activity of sarcolemmal and SR Ca2+-ATPase was decreased in the hypertrophied ventricle tissue. Conclusion:The results suggested that the reduced SR Ca2+ content may be associated with an increased Ca2+ leak and reduced SERCA2a activity, contributing to abnormal intracellular Ca2+ handling during hypertrophy in hyperthyroidism rats.

  3. Triclosan exposure reduces thyroxine levels in pregnant and lactating rat dams and in directly exposed offspring

    Petersen, Marta Axelstad; Boberg, Julie; Vinggaard, Anne Marie


    Thyroid disrupting chemicals can potentially disrupt brain development. Two studies investigating the effect of the antibacterial compound triclosan on thyroxine (T4) levels in rats are reported. In the first, Wistar rat dams were gavaged with 75, 150 or 300 mg triclosan/kg bw/day throughout...... gestation and lactation. Total T4 serum levels were measured in dams and offspring, and all doses of triclosan significantly lowered T4 in dams, but no significant effects on T4 levels were seen in the offspring at the end of the lactation period. Since this lack of effect could be due to minimal exposure...... through maternal milk, a second study using direct per oral pup exposure from postnatal day 3–16 to 50 or 150 mg triclosan/kg bw/day was performed. This exposure pointed to significant T4 reductions in 16 day old offspring in both dose groups. These results corroborate previous studies showing...

  4. Triclosan exposure reduces thyroxine levels in pregnant and lactating rat dams and in directly exposed offspring.

    Axelstad, Marta; Boberg, Julie; Vinggaard, Anne Marie; Christiansen, Sofie; Hass, Ulla


    Thyroid disrupting chemicals can potentially disrupt brain development. Two studies investigating the effect of the antibacterial compound triclosan on thyroxine (T₄) levels in rats are reported. In the first, Wistar rat dams were gavaged with 75, 150 or 300 mg triclosan/kg bw/day throughout gestation and lactation. Total T₄ serum levels were measured in dams and offspring, and all doses of triclosan significantly lowered T₄ in dams, but no significant effects on T₄ levels were seen in the offspring at the end of the lactation period. Since this lack of effect could be due to minimal exposure through maternal milk, a second study using direct per oral pup exposure from postnatal day 3-16 to 50 or 150 mg triclosan/kg bw/day was performed. This exposure pointed to significant T₄ reductions in 16 day old offspring in both dose groups. These results corroborate previous studies showing that in rats lactational transfer of triclosan seems limited. Since an optimal study design for testing potential developmental neurotoxicants in rats, should include exposure during both the pre- and postnatal periods of brain development, we suggest that in the case of triclosan, direct dosing of pups may be the best way to obtain that goal.

  5. Comparison of preventive effect of T3 and T4 on thyroxine release from thyroid induced by endogeneous TSH after TRH injection.

    Kokesová, H; Langer, P; Gschwendtová, K; Sadlon, J; Bukovská, M


    Comparison of Preventive Effect of T3 and T4 on Thyroxine Release from Thyroid Induced by Endogenous TSH after TRH Injection. Endocrinologia Experimentalis 11, 91-98, 1977. The technique of frequent blood sampling through polyethylene tubings inserted into blood vessels while maintaining isovolemia was used in pentobarbiturate anaesthetized rats weighing 250--300 g. The animals were fed low iodine diet for 4 weeks and injected 125I- (5 microgram Ci per animal daily) for 6 days begining from 8th day before the experiment. The effect of 25 microgram TRH injected through a cannula inserted into carotid artery in cranial direction was evaluated as per cent increase of labelled thyroxine in plasma at 120 min after the injection compared to its level at 30 min. Moreover, the inhibitory effect of various doses of thyroxine (T4; 5, 20 and 80 nmol kg-1) and triiodothyronine (T3; 1.25 and 5 nmol kg-1) injected i.v. at the intervals of 10, 20, 30, 60 and 180 min prior to TRH was investigated. It was found that the effect was time dependent, being negligible after 10 or 20 min, while after 60 and 180 min the increase of labelled T4 after TRH was fully prevented by 20 and 80 nmol T4 kg-1 and by 5 nmol T3 kg-1. The other doses (i. e. 5 nmol T4 kg-1 and 1.25 nmol T3 kg-1) were without effect. Thus, T3 was found to be significantly more active than equimolar doses of T4.

  6. Thyroxine mimetics

    Randa F Salam


    Full Text Available Thyroid hormones influence heart rate, serum lipids, metabolic rate, body weight, and multiple aspects of lipid, carbohydrate, protein, and mineral metabolism. Although increased thyroid hormone levels can improve serum lipid profiles and reduce fat, these positive effects are counterbalanced by the harmful effects on the heart, muscle, and bone. Thus, attempts to use thyroid hormones for cholesterol-lowering and weight loss purposes have so far been limited. However, over the past decade, thyroid hormone analogs that are capable of uncoupling the beneficial effects from the deleterious effects have been developed. Such drugs could serve as powerful new tools to address two of the largest medical problems, namely atherosclerosis and obesity. Aggressive reduction in LDL-cholesterol by the use of statins is a cornerstone of preventive cardiovascular risk, but additional therapies to prevent atherosclerosis and its clinical sequelae are still needed. Thyromimetics selective for the liver or the thyroid hormone receptor isoform β1 constitute a novel approach to treat dyslipidemia. In preclinical studies, selective thyromimetics were clearly shown to reduce plasma cholesterol and protect from atherosclerosis through the upregulation of hepatic LDL receptor and promotion of the so-called reverse cholesterol transport. Notably, there is the first evidence from on-going clinical trials that selective thyromimetics may reduce plasma cholesterol in humans also. Most importantly, thyromimetics has a synergistic action when used in combination with 3-hydroxy-3-methylglutaryl CoA reductase inhibitors. Animal data have further suggested that thyromimetics might be useful in the treatment of obesity, hepatic steatosis, and atherosclerosis.

  7. [Thyroxine and triiodothyronine].

    Pinchera, A; Ambrosino, N; Mammoli, C


    The value of measurements of serum thyroxine (T4) and triiodothyronine (T3) concentrations in the clinical evaluation of thyroid function is well established. In the present report the properties of the methods currently available for the assessment of circulating thyroid hormones are examined. Recent data indicate that results of measurements of serum T4 by radioimmunoassay (RIA) or by displacement analysis are qualitatively and quantitatively similar. Evidence has been provided from this and other laboratories that elevated or subnormal serum levels of total tt4 may be observed in several euthyroid physiologicmal serum levels of total T4 may be observed in several euthyroid physiological or pathological conditions associated with altered capacity of the thyroxine-binding protein; in these cases a normal free thyroxine index is usually found indicating its importance in the evaluation of thyroid function. Several physiological observations and the recent recognition of clinical conditions associated with changes in the T4/T3 ratio, justify the present interest in the measurement of serum T3. The advantages of RIA methods with respect to displacement techniques in the determination of this hormone are well documented. The AA. report here their experience with a simple RIA method for total T3, using a single Sephadex G25 column for extraction of T3 from serum and for separation of bound from free hormone. The mean (+/-SD) values of serum T3 found in 78 normal, 23 hyperthyroid and 25 hypothyroid subjects were as follows:160+/37ng/dl, 604+/195ng/dl and 35+/23ng/dl respectively. High values were found in 19 pregnant women at delivery (236+/29ng/dl), but not in 5 subjects on contraceptives (156+/42ng/dl). A relatively large variability is noted when normal values reported from different laboratories are compared. This may be related at least in part to geographical and/or ethnical factors, but methodolgical differences may also be involved. The normal range of

  8. Difference of the in vivo responsiveness to thyrotropin stimulation between the neotenic and metamorphosed axolotl, Ambystoma mexicanum: failure of prolactin to block the thyrotropin-induced thyroxine release.

    Darras, V M; Kühn, E R


    Basal and TSH-induced plasma concentrations of T4 have been measured by radioimmunoassay in the neotenic and metamorphosed male axolotl Ambystoma mexicanum both before and after an ovine prolactin pretreatment. All injections are made into the vena abdominalis. Basal levels of T4 are low in neotenes (85 +/- 19 pg/ml) and somewhat higher in metamorphosed Ambystoma (171 +/- 39 pg/ml), but are increased during metamorphosis (1094 +/- 138 pg/ml). Following injection of 5 mU bovine TSH circulating levels of T4 are raised about 4 times in neotenes, but more than 50 times in metamorphose animals. Three intravenous injections, each of 640 mU prolactin and given, respectively, 24 and 13 hr before and simultaneously with 5 mU TSH, do not inhibit the TSH-induced release in both experimental groups. In the metamorphosed Ambystoma again a more than 50-fold T4 increase is present, whereas in neotenes a 10-fold TSH-induced T4 release is seen, which is more pronounced than before the prolactin treatment. It is concluded that in A. mexicanum ovine prolactin does not block a TSH-induced T4 release and that any antagonistic action with thyroid hormones is not mediated through the thyroid gland.

  9. Corticotropin-releasing hormone-mediated metamorphosis in the neotenic axolotl Ambystoma mexicanum: synergistic involvement of thyroxine and corticoids on brain type II deiodinase.

    Kühn, Eduard R; De Groef, Bert; Van der Geyten, Serge; Darras, Veerle M


    In the present study, morphological changes leading to complete metamorphosis have been induced in the neotenic axolotl Ambystoma mexicanum using a submetamorphic dose of T(4) together with an injection of corticotropin-releasing hormone (CRH). An injection of CRH alone is ineffective in this regard presumably due to a lack of thyrotropic stimulation. Using this low hormone profile for induction of metamorphosis, the deiodinating enzymes D2 and D3 known to be present in amphibians were measured in liver and brain 24h following an intraperitoneal injection. An injection of T(4) alone did not influence liver nor brain D2 and D3, but dexamethasone (DEX) or CRH alone or in combination with T(4) decreased liver D2 and D3. Brain D2 activity was slightly increased with a higher dose of DEX, though CRH did not have this effect. A profound synergistic effect occurred when T(4) and DEX or CRH were injected together, in the dose range leading to metamorphosis, increasing brain D2 activity more than fivefold. This synergistic effect was not found in the liver. It is concluded that brain T(3) availability may play an important role for the onset of metamorphosis in the neotenic axolotl.

  10. Experimental Study of Contaminant Release from Reducing Grout

    Waiting D.J.


    Full Text Available A column experiment was conducted to study the release behavior of technetium, uranium, and selenium initially sequestered in reducing grout similar in composition to Savannah River Site (SRS saltstone, a cementitious waste form made by mixing salt solution from SRS liquid waste storage tanks with a dry mix containing blast furnace slag, fly ash, and Portland cement. The data suggest that uranium was retained in the grout possibly as a CaUO4 phase, whereas most of the selenium was released. Technetium release initially was relatively constant, and then increased significantly after 26 pore volumes. The increase in technetium release was slightly delayed relative to the observed Eh increase. The system Eh-pH started under conditions in which technetium solubility is low, constrained by Tc3O4 solubility, but eventually transitioned into the stability field of the pertechnetate ion. The delay in technetium release relative to the Eh increase was possibly due to slow oxidation of technetium at depth within the grout particles, which in turn was likely controlled by O2 diffusion into the particles. In contrast to technetium and uranium, selenium release was not solubility limited and selenium likely was present in the pore solution initially as a HSe− species.

  11. Effects of thyroxine and dexamethasone on rat submandibular glands

    Sagulin, G.B.; Roomans, G.M. (Karolinska Institutet, Huddinge (Sweden))


    Glucocorticoids and thyroxine are known to have a marked effect on the flow rate and protein composition of rat parotid saliva in hormonally intact animals. In the present study, the effects of a one-week treatment of male rats with dexamethasone and thyroxine were studied by electron microscopy and x-ray micro-analysis, and by measurement of the flow rate and determination of the chemical composition of pilocarpine-induced submandibular saliva. Thyroxine had the most extensive effects on the submandibular gland. The acinar cells were enlarged and filled with mucus; the cellular calcium concentration was significantly increased. The flow rate of the submandibular saliva was significantly reduced compared with that in saline-injected control animals. Thyroxine caused an increase in the concentrations of protein, total calcium, and potassium in the saliva. Dexamethasone had no significant effects on gland ultrastructure or on the elemental composition of the acinar cells; flow rate was not affected, but the concentrations of protein, calcium, and potassium were significantly increased. The effects of dexamethasone and thyroxine on the flow rate and protein composition of pilocarpine-induced rat submandibular saliva differ from those reported earlier for rat parotid saliva after simultaneous stimulation with pilocarpine and isoproterenol.

  12. Radioimmunoassay of thyroxine in saliva

    Putz, Z.; Vanuga, A.; Veleminsky, J. (Institute of Clinical Endocrinology, Lubochna (Czechoslovakia))


    A simple radioimmunoassay (RIA) for thyroxine (T/sub 4/) in saliva has been described. Fifty euthyroid control subjects, 14 euthyroid pregnant women, 23 thyreotoxic and 10 hypothyroid patients were examined. Serum T/sub 3/, T/sub 4/, thyroxine binding globulin (TBG) and TSH were measured simultaneously. The mean level of T/sub 4/ in saliva in controls was 1.10 +- 0.07 nmol/l. There was a good correlation between the saliva and serum T/sub 4/ concentrations (r = 0.74) and between saliva T/sub 4/ values and the T/sub 4//TBG ratio (r = 0.83). The saliva T/sub 4/ levels, like serum free T/sub 4/, were not dependent on fluctuations of serum TBG concentrations. In euthyroid pregnant women, saliva T/sub 4/ levels were within the normal range while the serum T/sub 4/ and TBG were increased. There was a good agreement of saliva T/sub 4/ values with the functional state of the thyroid. Thus, the RIA of saliva T/sub 4/ could replace the laborious determination of serum free T/sub 4/. It can especially be useful in instances with abnormal values of TBG, as it is in pregnancy, in congenital deficiency of serum TBG or in subjects with hereditary elevated TBG levels.

  13. Plasma immersion ion implantation for reducing metal ion release

    Diaz, C.; Garcia, J. A.; Maendl, S.; Pereiro, R.; Fernandez, B.; Rodriguez, R. J. [Centro de Ingenieria Avanzada de Superficies AIN, 31191, Cordovilla-Pamplona (Spain); Leibniz-Institut fuer Oberflaechenmodifizierung, 04318 Leipzig (Germany); Universidad de Oviedo, Departamento Quimica Fisica y Analitica (Spain); Centro de Ingenieria Avanzada de Superficies AIN, 31191, Cordovilla-Pamplona (Spain)


    Plasma immersion ion implantation of Nitrogen and Oxygen on CoCrMo alloys was carried out to improve the tribological and corrosion behaviors of these biomedical alloys. In order to optimize the implantation results we were carried experiments at different temperatures. Tribocorrosion tests in bovine serum were used to measure Co, Cr and Mo releasing by using Inductively Coupled Plasma Mass Spectrometry analysis after tests. Also, X-ray Diffraction analysis were employed in order to explain any obtained difference in wear rate and corrosion tests. Wear tests reveals important decreases in rate of more than one order of magnitude for the best treatment. Moreover decreases in metal release were found for all the implanted samples, preserving the same corrosion resistance of the unimplanted samples. Finally this paper gathers an analysis, in terms of implantation parameters and achieved properties for industrial implementation of these treatments.

  14. Reduced computational models of serotonin synthesis, release, and reuptake.

    Flower, Gordon; Wong-Lin, KongFatt


    Multiscale computational models can provide systemic evaluation and prediction of neuropharmacological drug effects. To date, little computational modeling work has been done to bridge from intracellular to neuronal circuit level. A complex model that describes the intracellular dynamics of the presynaptic terminal of a serotonergic neuron has been previously proposed. By systematically perturbing the model's components, we identify the slow and fast dynamical components of the model, and the reduced slow or fast mode of the model is computationally significantly more efficient with accuracy not deviating much from the original model. The reduced fast-mode model is particularly suitable for incorporating into neurobiologically realistic spiking neuronal models, and hence for large-scale realistic computational simulations. We also develop user-friendly software based on the reduced models to allow scientists to rapidly test and predict neuropharmacological drug effects at a systems level.

  15. Thyroxine Induced Resorption of Xenopus Laevis Tail Tissue in Vitro.

    Scadding, Steven R.


    A simple method of studying thyroxine-induced resorption of tadpole tails in vitro is described. This procedure demonstrates that resorption is dependent on thyroxine and requires protein synthesis. It introduces students to the use of tissue culture methods. (Author)

  16. Sequential defunctionalization followed by thyroxine supple-mentation as preoperative preparation of hyperthyroid patients undergoing thyroidectomy

    ZHU Jing-qiang; WU Xiao-ying; LI Zhi-hui; GONG Ri-xiang; WEI Tao; ZHANG Heng; ZHANG Wen-yan; YANG Xiao-yan; LUO Yan-li; GONG Shu


    Background Preparing hyperthyroid patients for thyroid surgery with a combination of antithyroid drugs and thyroxine has long been controversial because this combination usually results in only partial inhibition of thyroid function. We therefore used large doses of antithyroid drugs to completely inhibit the synthesis of thyroxine and render the thyroid gland defunctionalized. We then administered physiologic doses of thyroxine to inhibit thyroid-stimulating hormone secretion. We have named this treatment "sequential thyroid defunctionalization followed by thyroxine supplementation." Methods Four hundred and seventy-one hyperthyroid patients seen at our hospital were divided into experimental and control groups. The control group was treated preoperatively with antithyroid drugs and iodine preparation. The experimental group was further divided into four subgroups and treated with "sequential thyroid defunctionalization followed by thyroxine supplementation". Each of the four subgroups received different doses of antithyroid drugs and thyroxine for differing time periods. Thyroid function was assessed at each stage of treatment, as were operative blood loss volumes and postoperative complications.Results Compared to the control group, the four experimental groups showed less thyroid congestion and surface varices at surgery. Patients in subgroup A also had thyroid glands that were almost histologically normal. The mean operative blood loss volume of the experimental group was less than that of the control group((326±1 63)mlin the control group;(196±57)ml in subgroup A:(230±71)ml in subgroup B;(240±80)ml in subgroup C;and(31 2±97)ml in subgroup D).The postoperative complication rate of the experimental group was 8.64%(21/243)whereas that of the control group was 1 7.54%(40/228).Conclusions Sequential thyroid defunctionalization followed by thyroxine supplementation is effective in reducing the bleeding volume and postoperative complication rate in selected

  17. Changes in the before and after thyroxine treatment levels of adipose tissue, leptin, and resistin in subclinical hypothyroid patients.

    Akbaba, Gulhan; Berker, Dilek; Isık, Serhat; Tuna, Mazhar Muslum; Koparal, Suha; Vural, Murat; Yılmaz, Fatma Meric; Topcuoglu, Canan; Guler, Serdar


    Subclinical hypothyroidism (SH) occurs when serum thyroid stimulating hormone (TSH) concentrations are raised and serum thyroid hormone concentrations are normal. The effect of SH on the proinflammatory adipose cytokine releasing visceral adipose tissue (VAT) is not clear. The aim of this study is to identify the difference between the pre and posttreatment levels of VAT, leptin, and resistin in SH patients. There were 51 SH patients and 43 age- and gender-matched healthy subjects included in the study. Thyroid functions, biochemical tests, leptin, resistin, and visceral and subcutaneous fat measurements were made. The measurements were repeated in the SH group in the third month following L-thyroxin treatment. Initially, high sensitivity C-reactive protein, carotid artery intima-media thickness (mm), leptin, and resistin levels were significantly higher in the SH group compared to the controls, while the other parameters were similar. While no correlation was observed between TSH levels and adipokines, a positive correlation was detected between waist circumference and leptin levels (r = 0.549, p adipose tissue was positively correlated to age, waist circumference, and leptin levels, but negatively correlated to free thyroxin (T4) levels (r = 0.419, p = 0.009; r = 0.794, p leptin, and resistin levels of SH patients following levothyroxine treatment. Conclusion The reduced VAT volume, leptin, and resistin levels in SH patients following treatment may support the idea that TSH affects adipose tissue functions.

  18. Reduced cognitive and psychomotor impairment with extended-release oxymorphone versus controlled-release oxycodone.

    Schoedel, Kerri A; McMorn, Stephen; Chakraborty, Bijan; Zerbe, Kathleen; Sellers, Edward M


    Opioids provide effective pain control, yet have risks including adverse events (AEs) (e.g., constipation, nausea/vomiting, sedation) and cognitive/psychomotor effects. To compare cognitive and psychomotor effects of oxymorphone extended release (OM-ER) versus oxycodone controlled release (OC-CR). Randomized, double-blind, 5-way crossover Single inpatient research unit Nondependent recreational opioid users were administered single intact oral tablets of placebo, OM-ER (15 and 30 mg), and OC-CR (30 and 60 mg), separated by a 7- to 21-day washout. The divided attention (DA) test measured psychomotor impairment (e.g., manual tracking [e.g., percentage over road], target accuracy [e.g., target hits], reaction time [hit latency]). Visual analog scales measured alertness/drowsiness, agitation/relaxation, and dizziness. Sedative, stimulant, and dysphoric effects were measured using the Addiction Research Center Inventory Pentobarbital-Chlorpromazine-Alcohol (PCAG), Benzedrine Group (BG), and Lysergic Acid Diethylamide (LSD) scales, respectively. Comparisons were made between equianalgesic doses (OM-ER 15 mg vs OC-CR 30 mg; OM-ER 30 mg vs OC-CR 60 mg), within active drug doses, and between active drugs and placebo using least squares (LS) mean difference of the peak maximum (Emax) or minimum (Emin) effect using linear mixed model analysis of covariance. Thirty-five participants received all 5 treatments. Peak cognitive and psychomotor impairment (LS mean [SE]) was less with OM-ER than equianalgesic doses of OC-CR for reaction time (Emax hit latency, longer if impaired; 571.2 [13.4] vs 588.1 ms [13.4], P=0.03 for OM-ER 15 mg vs OC-CR 30 mg, respectively; 572.4 [13.4] vs 604.3 ms [13.4], P=0.03 for OM-ER 15 mg vs OC-CR 30 mg, respectively; 572.4 [13.4] vs 604.3 ms [13.4], PLSD, P<0.001 for both equianalgesic dose groups), and sedation (Emax, PCAG; P<0.001 for both equianalgesic dose groups) and less stimulation (BG, Emin; P=0.01 for OM-ER 15 mg vs OC-CR mg; P<0.001 for OM

  19. Rab3A deletion selectively reduces spontaneous neurotransmitter release at the mouse neuromuscular synapse.

    Sons, Michèle S; Plomp, Jaap J


    Rab3A is a synaptic vesicle-associated GTP-binding protein thought to be involved in modulation of presynaptic transmitter release through regulation of vesicle trafficking and membrane fusion. Electrophysiological studies at central nervous system synapses of Rab3A null-mutant mice have indicated that nerve stimulation-evoked transmitter release and its short- and long-term modulation are partly dependent on Rab3A, whereas spontaneous uniquantal release is completely independent of it. Here, we studied the acetylcholine (ACh) release at the neuromuscular junction (NMJ) of diaphragm and soleus muscles from Rab3A-deficient mice with intracellular microelectrode methods. Surprisingly, we found 20-40% reduction of spontaneous ACh release but completely intact nerve action potential-evoked release at both high- and low-rate stimulation and during recovery from intense release. The ACh release induced by hypertonic medium was also unchanged, indicating that the pool of vesicles for immediate release is unaltered at the Rab3A-deficient NMJ. These results indicate a selective role of Rab3A in spontaneous transmitter release at the NMJ which cannot or only partly be taken over by the closely related Rab3B, Rab3C, or Rab3D isoforms when Rab3A is deleted. It has been hypothesized that Rab3A mutation underlies human presynaptic myasthenic syndromes, in which severely reduced nerve action potential-evoked ACh release at the NMJ causes paralysis. Our observation that Rab3A deletion does not reduce evoked ACh release at any stimulation rate at the mouse NMJ, argues against this hypothesis.

  20. Pregabalin reduces the release of synaptic vesicles from cultured hippocampal neurons.

    Micheva, Kristina D; Taylor, Charles P; Smith, Stephen J


    Pregabalin [S-[+]-3-isobutylGABA or (S)-3-(aminomethyl)-5-methylhexanoic acid, Lyrica] is an anticonvulsant and analgesic medication that is both structurally and pharmacologically related to gabapentin (Neurontin; Pfizer Inc., New York, NY). Previous studies have shown that pregabalin reduces the release of neurotransmitters in several in vitro preparations, although the molecular details of these effects are less clear. The present study was performed using living cultured rat hippocampal neurons with the synaptic vesicle fluorescent dye probe FM4-64 to determine details of the action of pregabalin to reduce neurotransmitter release. Our results indicate that pregabalin treatment, at concentrations that are therapeutically relevant, slightly but significantly reduces the emptying of neurotransmitter vesicles from presynaptic sites in living neurons. Dye release is reduced in both glutamic acid decarboxylase (GAD)-immunoreactive and GAD-negative (presumed glutamatergic) synaptic terminals. Furthermore, both calcium-dependent release and hyperosmotic (calcium-independent) dye release are reduced by pregabalin. The effects of pregabalin on dye release are masked in the presence of l-isoleucine, consistent with the fact that both of these compounds have a high binding affinity to the calcium channel alpha(2)-delta protein. The effect of pregabalin is not apparent in the presence of an N-methyl-d-aspartate (NMDA) antagonist [D(-)-2-amino-5-phosphonopentanoic acid], suggesting that pregabalin action depends on NMDA receptor activation. Finally, the action of pregabalin on dye release is most apparent before and early during a train of electrical stimuli when vesicle release preferentially involves the readily releasable pool.

  1. Thyroxine Level of Children with Cerebral Palsy

    Zhang Jie


    Objective:To investigate the thyroxine level of Children with cerebral palsy so as to understand thd changes of their nevous endocrine. Methods:Radioimmunoassay was applied to 57 Children with cerebral palsy and 108 normal children.The serum level of tridothyronine(T3), thyroxine(T4)free tridothyronine(FT3),free thyroxin(FT4),and thyroid stimulating hormone(TSH) were measured for those children in the moming and and in condition without any food Rsults: (1)Chiidren with cerebral palsy all showed low T3 values.The difference of T3 value between CP children and norrmal children was significant (P<0.001). (2)Results from groups with difference ages:the CP toddler′s age group also showed low T4 and FT4 values The difference of T4 and FT4 values between the toddler′s age CP childrengroup and the toddler′s age normal children group tegted was significant (CP<0.01 for T4, P <0. 05 for FT4): Conclusion:The tlyroxine level of children with cerebral palsy showed lower values compared to normal children, especisly, the low T3 values were significant.

  2. Capacity estimation and preliminary strategy for reducing the release of dioxins in China

    YU Gang; ZHANG Qing; HUANG Jun; CAI Zhenxiao; SUI Qian


    As a party of the Stockholm Convention on Persistent Organic Pollutants,China must submit its national implementation plan(NIP)for this convention.The strategy and action plan for reducing the release of dioxins in China are the most important components of the NIP.Three problems are key points for developing such strategy and action plan-what are the key sources for applying the best available technology/best environmental practice(BAT/BEP)to reduce the release of dioxins?How about the capacity for reducing the dioxins release from the key sources?Where are the areas of priority for applying BAT/BEP?This paper shows the efforts towards the solution of these problems.The list of key sources covering about half of the total dioxins release was determined considering four criteria.The capacity of key sources were estimated based on the difference between the emission factor corresponding to the actual situation in 2004 and that corresponding to the scenario that all key sources have been applied BAT/BEP to reduce the dioxins release.The priority analysis using the geographical information system(GIS)tool has revealed that eastern provinces should be of high priority in the future reduction activities of dioxins release in China.

  3. Acute mania after thyroxin supplementation in hypothyroid state

    Rohit Verma


    Full Text Available The current literature variedly ascribes depressive and manic symptoms to hypo- and hyperthyroid state, respectively, reporting mania in hypothyroidism as an unusual entity. More unusual is precipitation of manic state in hypothyroid subjects after thyroxine supplementation for which studies report otherwise treating manic symptoms in hypothyroid state with thyroxine. We report a case of a patient whose acute mania appears to have been precipitated by thyroxine supplementation in hypothyroidism state. This case underscores the importance of thyroid screening in patients with mood and psychotic disorders, as well as the potency of thyroxine in producing manic symptoms.

  4. 5alpha-Reduced androgens block estradiol-BSA-stimulated release of oxytocin.

    Caldwell, Jack D; Song, Yan; Englöf, Ila; Höfle, Simone; Key, Mary; Morris, Mariana


    In this study we test the postulate that estradiol conjugated to bovine serum albumin (E-BSA) acts via receptors for the steroid-binding protein sex hormone binding globulin (SHBG) by attempting to block E-BSA-stimulated release of oxytocin with two antagonists of SHBG receptor actions: the 5alpha-reduced androgens dihydrotestosterone (DHT) and 3alpha-diol. Simultaneous superfusion with either DHT or 3alpha-diol significantly blocked E-BSA-stimulated release of oxytocin. We also found that a wide range of free 17beta-estradiol was unable to stimulate oxytocin release, suggesting that E-BSA stimulates receptors other than those for free estradiol to release oxytocin, perhaps SHBG receptors.

  5. Reduced sarcoplasmic reticulum content of releasable Ca2+ in rat soleus muscle fibres after eccentric contractions

    Nielsen, J S; Sahlin, K; Ørtenblad, N


    AIM: The purpose was to evaluate the effects of fatiguing eccentric contractions (EC) on calcium (Ca2+) handling properties in mammalian type I muscles. We hypothesized that EC reduces both endogenous sarcoplasmic reticulum (SR) content of releasable Ca2+ (eSRCa2+) and myofibrillar Ca2+ sensitivity...

  6. Measuring free thyroxine levels in neonatal heel-prick samples

    Boelen, A.; Veen, M. van; Verkerk, P.H.; Diependaal, G.; Loeber, G.; Elvers, B.; Endert, E.


    The Dutch neonatal screening scheme for Congenital Hypothyroidism (CH) is primarily based on the determination of thyroxine (T4) in filter paper blood spots. In the lowest 5% of T4 values, thyroxine binding globulin (TBG) is measured in order to be able to correct for occasional low TBG levels. Howe

  7. The metabolic consequences of thyroxine replacement in adult hypopituitary patients

    Filipsson Nyström, Helena; Feldt-Rasmussen, Ulla; Kourides, Ione;


    The metabolic consequences of thyroxine replacement in patients with central hypothyroidism (CH) need to be evaluated. The aim was to examine the outcome of thyroxine replacement in CH. Adult hypopituitary patients (n = 1595) with and without CH from KIMS (Pfizer International Metabolic Database...

  8. Role of Thyroxine in Space-Developed Jellyfish

    Spangenberg, Dorothy B.


    The Aurelia Metamorphosis Test System was previously used to determine the effects of the space environment on the development and behavior of tiny (1-2 mm) jellyfish ephyrae during the SLS-1 and IML-2 missions. Results from the SLS-1 experiment included the discovery that statolith numbers were significantly reduced in Earth-formed ephyrae flown for nine days in space as compared with ground-based controls. In addition, upon return to Earth, six times more ephyrae which had developed in space than those developed on Earth had pulsing abnormalities, indicating that either these animals did not form their neuromuscular structures normally while in space or they were unable to adapt to the Ig environment upon return to Earth. The metamorphosis process, which enables the formation of ephyrae from polyps is influenced by a hormone, Jf-T4 Oellyfish thyroxine) which is synthesized following iodine administration. Two groups of polyps in space, however, formed ephyrae without iodine administration indicating that Jf-T4 synthesis, utilization, or excretion was different in. the ephyrae. Increased synthesis or build-up in the media of the hormone may also be linked to the increased demineralization of statoliths found in space-exposed ephyrae. In previous experiments, we found that externally administered thyroxine causes increased demineralization of statoliths on Earth. Abnormal pulsina in ephyrae following return to Earth during the SLS-1 mission may also be traced to increased Jf-T4 levels. Thyroxine is known to be important to the normal development and function of the nervous system, heart, and skeletal muscles in higher animals. For this third Jellyfish-in-Space experiment, we proposed to quantitate the levels of Jf- T4 and of T4 receptors in space-developed ephyrae and media and to compare these levels with those of animals developing and at Ig in space and on Earth. We expected to be able to determine whether Jf-T4 synthesis and/or secretion is different in space

  9. Diagnostic Evaluation of Effective Thyroxine Ratio

    Lee, Myung Chul; Choi, Sang Jae; Ro, Heung Kyu; Lee, Hong Kyu; Koh, Chang Soon; Lee, Mun Ho [Seoul National University College of Medicine, Seoul (Korea, Republic of)


    The purpose of the present study is to evaluate the diagnostic value of the ETR test as compared to other thyroid function tests in normal persons, patients with thyroid disorders and patients with alterations of thyroxine-binding proteins. The ETR values were obtained from 35 cases as normal control, 63 hyperthyroid patients, 56 euthyroid patients, 23 hypothyroid patients, 10 pregnant women, 5 women taking oral contraceptive medication, 8 liver cirrhosis patients and 4 nephrotic syndrome patients. The results obtained were as follows. 1) The mean value of ETR obtained from the normal controls was 0.99+-0.06. 2) The mean ETR values of various thyroid states were 1.25+-0.16 in hyperthyroidism, 0.99+-0.08 in euthyroidism and 0.82+-0.05 in hypothyroidism and significant difference was found between these groups. 3) Seven out of 63 hyperthyroid patients (11.1%) and 2 out of 23 hypothyroid patients (8.7%) had ETR values within normal range and among the 56 euthyroid patients 6 (10.7%) had ETR values outside normal range, so the diagnostic compatibility of ETR was 89.4% in thyroid diseases. 4) Even though the ETR value was well correlated with {sup 131}I-thyroid uptake rate, serum T{sub 3} resin uptake rate and serum T{sub 4}, a high positive correlation was found (r=0.79) between ETR and T{sub 7}. 5) The mean ETR values from patients with alteration in TBG binding capacity were 0.99+-0.05 in pregnant women, 0.98+-0.04 in women with oral contraceptive medication, 1.04+-0.09 in liver cirrhosis patients and 0.94+-0.02 in nephrotic syndrome patients and most of them (85.2%) had ETR values within normal range. Our results, therefore, suggests that the ETR estimation does offer the simplest and most reliable single procedure for the screening and diagnosis of various thyroid diseases as a indirect indicator of serum-free thyroxine concentration without essential influence of changes in the thyroxine-binding proteins in serum.

  10. Reducing Runoff Loss of Applied Nutrients in Oil Palm Cultivation Using Controlled-Release Fertilizers

    A. Bah


    Full Text Available Controlled-release fertilizers are expected to minimize nutrient loss from crop fields due to their potential to supply plant-available nutrients in synchrony with crop requirements. The evaluation of the efficiency of these fertilizers in tropical oil palm agroecological conditions is not yet fully explored. In this study, a one-year field trial was conducted to determine the impact of fertilization with water soluble conventional mixture and controlled-release fertilizers on runoff loss of nutrients from an immature oil palm field. Soil and nutrient loss were monitored for one year in 2012/2013 under erosion plots of 16 m2 on 10% slope gradient. Mean sediments concentration in runoff amounted to about 6.41 t ha−1. Conventional mixture fertilizer posed the greatest risk of nutrient loss in runoff following fertilization due to elevated nitrogen (6.97%, potassium (13.37%, and magnesium (14.76% as percentage of applied nutrients. In contrast, this risk decreased with the application of controlled-release fertilizers, representing 0.75–2.44% N, 3.55–5.09% K, and 4.35–5.43% Mg loss. Meanwhile, nutrient loss via eroded sediments was minimal compared with loss through runoff. This research demonstrates that the addition of controlled-release fertilizers reduced the runoff risks of nutrient loss possibly due to their slow-release properties.

  11. Do Ca2+-adsorbing ceramics reduce the release of calcium ions from gypsum-based biomaterials?

    Belcarz, Anna; Zalewska, Justyna; Pałka, Krzysztof; Hajnos, Mieczysław; Ginalska, Grazyna


    Bone implantable materials based on calcium sulfate dihydrate dissolve quickly in tissue liquids and release calcium ions at very high levels. This phenomenon induces temporary toxicity for osteoblasts, may cause local inflammation and delay the healing process. Reduction in the calcium ion release rate by gypsum could be therefore beneficial for the healing of gypsum-filled bone defects. The aim of this study concerned the potential use of calcium phosphate ceramics of various porosities for the reduction of high Ca(2+) ion release from gypsum-based materials. Highly porous ceramics failed to reduce the level of Ca(2+) ions released to the medium in a continuous flow system. However, it succeeded to shorten the period of high calcium level. It was not the phase composition but the high porosity of ceramics that was found crucial for both the shortening of the Ca(2+) release-related toxicity period and intensification of apatite deposition on the composite. Nonporous ceramics was completely ineffective for this purpose and did not show any ability to absorb calcium ions at a significant level. Moreover, according to our observations, complex studies imitating in vivo systems, rather than standard tests, are essential for the proper evaluation of implantable biomaterials.

  12. Study on encapsulation of chlorine dioxide in gelatin microsphere for reducing release rate.

    Ci, Ying; Wang, Lin; Guo, Yanchuan; Sun, Ruixue; Wang, Xijie; Li, Jinyou


    This study aims to explore the effects of encapsulation of chlorine dioxide in a hydrophilic biodegradable polymer gelatin to reduce its release rate. An emulsification-coacervation method was adopted. The characterizations of chlorine dioxide-gelatin microspheres were described. Using UV-vis spectrophotometer the λmax of chlorine dioxide was observed at 358 nm. The particle size and distribution of chlorine oxide-gelatin microspheres was measured by a dynamic light scattering (DLS) method, the diameter was (1400~1900) nm. The entrapment of chlorine dioxide-gelatin microspheres was confirmed by IR. The surface morphology, size, and shape of chlorine dioxide-gelatin microspheres were analyzed using Scanning electron microscope (SEM). It showed that the encapsulated microspheres size was around 2000 nm with uniform distribution. The percentage entrapment of chlorine dioxide in the encapsulated samples was about 80~85%. A slow release study of chlorine dioxide from the encapsulated biopolymer (gelatin) in air was also carried out, which showed continuous release up to ten days. It can be concluded that it is possible to make a slow release formulation of ClO2 by entrapped in a hydrophilic biodegradable polymer gelatin. ClO2-gelatin microspheres can stable release low concentration ClO2 gas over an extended period.

  13. Extended-release naltrexone reduces alcohol consumption among released prisoners with HIV disease as they transition to the community.

    Springer, Sandra A; Di Paola, Angela; Azar, Marwan M; Barbour, Russell; Krishnan, Archana; Altice, Frederick L


    Alcohol use disorders (AUDs) are highly prevalent among persons living with HIV (PLH) within the criminal justice system (CJS). Extended-release naltrexone (XR-NTX) has not been previously evaluated among CJS-involved PLH with AUDs. A randomized, double-blind, placebo-controlled trial was conducted among 100 HIV+ prisoners with AUDs. Participants were randomized 2:1 to receive 6 monthly injections of XR-NTX or placebo starting one week prior to release. Using multiple imputation strategies for data missing completely at random, data were analyzed for the 6-month post-incarceration period. Main outcomes included: time to first heavy drinking day; number of standardized drinks/drinking day; percent of heavy drinking days; pre- to post-incarceration change in average drinks/day; total number of drinking days; and a composite alcohol improvement score comprised of all 5 parameters. There was no statistically significant difference overall between treatment arms for time-to-heavy-drinking day. However, participants aged 20-29 years who received XR-NTX had a longer time to first heavy drinking day compared to the placebo group (24.1 vs. 9.5days; p<0.001). There were no statistically significant differences between groups for other individual drinking outcomes. A sub-analysis, however, found participants who received ≥4 XR-NTX were more likely (p<0.005) to have improved composite alcohol scores than the placebo group. Post-hoc power analysis revealed that despite the study being powered for HIV outcomes, sufficient power (0.94) was available to distinguish the observed differences. Among CJS-involved PLH with AUDs transitioning to the community, XR-NTX lengthens the time to heavy drinking day for younger persons; reduces alcohol consumption when using a composite alcohol consumption score; and is not associated with any serious adverse events. Published by Elsevier B.V.

  14. IGF-1 alleviates ox-LDL-induced inflammation via reducing HMGB1 release in HAECs

    Xiaofeng Yu; Chunyan Xing; Yinghua Pan; Housheng Ma; Jie Zhang; Wenjun Li


    Atherosclerosis,a multifactorial chronic inflammatory response,is closely associated with oxidatively modified lowdensity lipoprotein (ox-LDL).High-mobility group box 1 (HMGB1) is a DNA-binding protein,which upon release from cells exhibits potent inflammatory action.Insulin-like growth factor 1 (IGF-1) can elicit a repertoire of cellular responses including proliferation and anti-apoptosis.However,the role of IGF-1 in inflammation is still unclear.In the present study,we aimed to investigate the role of IGF-1 in inflammation and the underlying mechanism.Human aortic endothelial cells were stimulated by ox-LDL (50 μg/ml) to induce inflammation.The expression of intercellular adhesion molecule 1 (ICAM-1) was assessed by western blot analysis and immunofluorescence.The release of HMGB1 was determined by enzyme-linked immunosorbent assay.IGF-1 receptor (IGF-1R) expression was assessed by reverse transcription-polymerase chain reaction and western blot analysis.IGF-1R phosphorylation was determined by western blot analysis.Ox-LDL stimulation reduced IGF-1R mRNA and protein expression but increased HMGB1 release.IGF-1 treatment decreased oxLDL-induced ICAM-1 expression potentially through reducing HMGB1 release,while picropodophyllin,an IGF-1R specific inhibitor,increased the inflammatory response.In conclusion,IGF-1 can alleviate ox-LDL-induced inflammation by reducing HMGB1 release,suggesting an unexpected beneficial role of IGF-1 in inflammatory disease.

  15. Study on encapsulation of chlorine dioxide in gelatin microsphere for reducing release rate

    Ci, Ying; Wang,Lin; Guo, YanChuan; Sun, Ruixue; Wang, Xijie; Li, Jinyou


    Objective: This study aims to explore the effects of encapsulation of chlorine dioxide in a hydrophilic biodegradable polymer gelatin to reduce its release rate. Methods: An emulsification-coacervation method was adopted. The characterizations of chlorine dioxide-gelatin microspheres were described. Using UV-vis spectrophotometer the λmax of chlorine dioxide was observed at 358 nm. The particle size and distribution of chlorine oxide-gelatin microspheres was measured by a dynamic light scatte...

  16. Anabolic Steroids Reduce Muscle Degeneration Associated With Rotator Cuff Tendon Release in Sheep.

    Gerber, Christian; Meyer, Dominik C; Flück, Martin; Benn, Mario C; von Rechenberg, Brigitte; Wieser, Karl


    Chronic rotator cuff tendon tearing is associated with irreversible atrophy, fatty infiltration, and interstitial fibrosis of the corresponding muscle. Anabolic steroids can prevent musculotendinous degeneration during retraction and/or can reverse these changes after operative repair of the retracted musculotendinous unit in sheep. Controlled laboratory study. The infraspinatus tendon was released in 18 alpine sheep. All sheep underwent repair of the retracted musculotendinous unit after 16 weeks and were sacrificed after 22 weeks; 6 sheep served as controls, 6 sheep were treated with weekly intramuscular injection of 150 mg of nandrolone decanoate after infraspinatus (ISP) repair (group N6W), and 6 sheep were treated with 150 mg of nandrolone decanoate immediately after tendon release (group N22W). Muscle biopsy specimens were taken before tendon release and after 16 and 22 weeks. Muscle volume and fatty infiltration (on MRI), myotendinous retraction, and muscle density (on computed tomography) were measured immediately after ISP release, after 6 weeks, and before ISP repair and sacrifice. Muscle volume on MRI decreased to a mean (±SD) of 80% ± 8% of the original volume after 6 weeks, remained stable at 78% ± 11% after 16 weeks, and decreased further to 69% ± 9% after 22 weeks in the control group. These findings were no different from those in group N22W (72% ± 9% at 6 weeks, 73% ± 6% at 16 weeks, and 67% ± 5% at 22 weeks). Conversely, the N6W group did not show a decrease in ISP volume after repair; this finding differed significantly from the response in the control and N22W groups. Fatty infiltration (on MRI) continuously increased in the control group (12% ± 4% at tendon release, 17% ± 4% after 6 weeks, 50% ± 9% after 16 weeks, and 60% ± 8% after 22 weeks) and the N6W group. However, application of anabolic steroids at the time of tendon release (N22W group) significantly reduced fatty infiltration after 16 (16% ± 5%; P < .001) and 22 weeks (22

  17. Thyroxine modifies the effects of growth hormone in Ames dwarf mice

    Do, Andrew; Menon, Vinal; Zhi, Xu; Gesing, Adam; Wiesenborn, Denise S.; Spong, Adam; Sun, Liou; Bartke, Andrzej; Masternak, Michal M.


    Ames dwarf (df/df) mice lack growth hormone (GH), thyroid stimulating hormone and prolactin. Treatment of juvenile df/df mice with GH alone stimulates somatic growth, reduces insulin sensitivity and shortens lifespan. Early‐life treatment with thyroxine (T4) alone produces modest growth stimulation but does not affect longevity. In this study, we examined the effects of treatment of juvenile Ames dwarf mice with a combination of GH + T4 and compared them to the effects of GH alone. Treatment ...

  18. Decreased hypothalamic growth hormone-releasing hormone content and pituitary responsiveness in hypothyroidism.

    Katakami, H; Downs, T. R.; Frohman, L A


    The effects of thyroidectomy (Tx) and thyroxine replacement (T4Rx) on pituitary growth hormone (GH) secretion and hypothalamic GH-releasing hormone (GRH) concentration were compared to define the mechanism of hypothyroid-associated GH deficiency. Thyroidectomized rats exhibited a complete loss of pulsatile GH secretion with extensive reduction in GRH responsiveness and pituitary GH content. Cultured pituitary cells from Tx rats exhibited reduced GRH sensitivity, maximal GH responsiveness, and...

  19. Semi-automated competitive protein binding analysis of serum thyroxine on reusable Sephadex columns and its advantages over radioimmunoassay.

    Alexander, N M


    Competitive protein-binding analysis of serum thyroxine on small, reusable, Sephadex columns has been further studied and improved. The improved, semi-automated procedure results in reduced working time and costs. It has also been established that triiodothyronine crossreacts only 1/6 to 1/9 as well as thyroxine, and can be ignored because it represents only about 1/80 of the total serum iodothyronine content. The economic and methodological advantages of the improved method over radioammunoassay and other displacement assays are discussed.

  20. Developmental Triclosan Exposure Decreases Maternal and Offspring Thyroxine in Rats*

    Epidemiological and laboratory data have demonstrated that disruption of maternal thyroid hormones during fetal developmental may result in irreversible neurological consequences in offspring. In a short-term exposure paradigm, triclosan decreased systemic thyroxine (T4) concentr...

  1. Effect of thyroxine treatment on carnitine levels in mice.

    Cederblad, G; Engström, G


    The effect in mice of 8 subcutaneous injections of 20 microgram of L-thyroxine at 12 hr-intervals on the carnitine concentration in the heart and skeletal muscle tissue was studied. In skeletal muscle tissue, the thyroxine treatment resulted in a depressed carnitine concentration. The mean values were 1.59 +/- 0.034 (S.E.M.) and 2.03 +/- 0.045 mumol/g noncollagen protein and 1.11 +/- 0.035 and 1.45 +/- 0.037 mumol/g dry weight for the thyroxine treated and the control animals, respectively. Thyroxine produced myocardial hypertrophy. The thyroxine treated animals had lower cardiac values when dry weight was used as reference base 4.17 +/- 0.10 mumol/g dry weight than the control group, 4.69 +/- 0.18 mumol/g dry weight. No statistically significant difference was found between the two groups when the cardiac carnitine concentration was expressed per g noncollagen protein or as carnitine in the entire hearts. Thus, thyroxine has been showed to influence the metabolism of carnitine in mice.

  2. L-arginine promotes gut hormone release and reduces food intake in rodents.

    Alamshah, A; McGavigan, A K; Spreckley, E; Kinsey-Jones, J S; Amin, A; Tough, I R; O'Hara, H C; Moolla, A; Banks, K; France, R; Hyberg, G; Norton, M; Cheong, W; Lehmann, A; Bloom, S R; Cox, H M; Murphy, K G


    To investigate the anorectic effect of L-arginine (L-Arg) in rodents. We investigated the effects of L-Arg on food intake, and the role of the anorectic gut hormones glucagon-like peptide-1 (GLP-1) and peptide YY (PYY), the G-protein-coupled receptor family C group 6 member A (GPRC6A) and the vagus nerve in mediating these effects in rodents. Oral gavage of L-Arg reduced food intake in rodents, and chronically reduced cumulative food intake in diet-induced obese mice. Lack of the GPRC6A in mice and subdiaphragmatic vagal deafferentation in rats did not influence these anorectic effects. L-Arg stimulated GLP-1 and PYY release in vitro and in vivo. Pharmacological blockade of GLP-1 and PYY receptors did not influence the anorectic effect of L-Arg. L-Arg-mediated PYY release modulated net ion transport across the gut mucosa. Intracerebroventricular (i.c.v.) and intraperitoneal (i.p.) administration of L-Arg suppressed food intake in rats. L-Arg reduced food intake and stimulated gut hormone release in rodents. The anorectic effect of L-Arg is unlikely to be mediated by GLP-1 and PYY, does not require GPRC6A signalling and is not mediated via the vagus. I.c.v. and i.p. administration of L-Arg suppressed food intake in rats, suggesting that L-Arg may act on the brain to influence food intake. Further work is required to determine the mechanisms by which L-Arg suppresses food intake and its utility in the treatment of obesity. © 2016 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

  3. L‐arginine promotes gut hormone release and reduces food intake in rodents

    Alamshah, A.; McGavigan, A. K.; Spreckley, E.; Kinsey‐Jones, J. S.; Amin, A.; Tough, I. R.; O'Hara, H. C.; Moolla, A.; Banks, K.; France, R.; Hyberg, G.; Norton, M.; Cheong, W.; Lehmann, A.; Bloom, S. R.; Cox, H. M.


    Aims To investigate the anorectic effect of L‐arginine (L‐Arg) in rodents. Methods We investigated the effects of L‐Arg on food intake, and the role of the anorectic gut hormones glucagon‐like peptide‐1 (GLP‐1) and peptide YY (PYY), the G‐protein‐coupled receptor family C group 6 member A (GPRC6A) and the vagus nerve in mediating these effects in rodents. Results Oral gavage of L‐Arg reduced food intake in rodents, and chronically reduced cumulative food intake in diet‐induced obese mice. Lack of the GPRC6A in mice and subdiaphragmatic vagal deafferentation in rats did not influence these anorectic effects. L‐Arg stimulated GLP‐1 and PYY release in vitro and in vivo. Pharmacological blockade of GLP‐1 and PYY receptors did not influence the anorectic effect of L‐Arg. L‐Arg‐mediated PYY release modulated net ion transport across the gut mucosa. Intracerebroventricular (i.c.v.) and intraperitoneal (i.p.) administration of L‐Arg suppressed food intake in rats. Conclusions L‐Arg reduced food intake and stimulated gut hormone release in rodents. The anorectic effect of L‐Arg is unlikely to be mediated by GLP‐1 and PYY, does not require GPRC6A signalling and is not mediated via the vagus. I.c.v. and i.p. administration of L‐Arg suppressed food intake in rats, suggesting that L‐Arg may act on the brain to influence food intake. Further work is required to determine the mechanisms by which L‐Arg suppresses food intake and its utility in the treatment of obesity. PMID:26863991

  4. Ni and Cr addition to alloy waste forms to reduce radionuclide environmental releases

    Olson, L. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL)


    Reference alloy waste forms (RAW) were fabricated and underwent hybrid corrosion/immersion testing to parameterize the ANL analytical oxidative-dissolution model to enable the calculation of fractional release rates and to determine the effectiveness of Ni and Cr trim additions in reducing release rates of radionuclide surrogates. Figure 1 shows the prototypical multiphase microstructure of the alloys with each phase type contributing about equally to the exposed surface area. The waste forms tested at SRNL were variations of the RAW-6 formulation that uses HT9 as the main alloy component, and are meant to enable evaluation of the impact of Ni and Cr trim additions on the release rates of actinides and Tc-99. The test solutions were deaerated alkaline and acidic brines, ranging in pH 3 to pH 10, representing potential repositories with those conditions. The testing approach consisted of 4 major steps; 1) bare surface corrosion measurements at pH values of 3, 5, 8, and 10, 2) hybrid potentiostatic hold/exposure measurements at pH 3, 3) measurement of radionuclide concentrations and relations to anodic current from potentiostatic holds, and 4) identification of corroding phases using SEM/EDS of electrodes.

  5. Thyroxin Is Useful to Improve Sperm Motility

    Mendeluk Gabriela Ruth


    Full Text Available Background The aim of this study was to evaluate the non-genomic action of thyroxin on sperm kinetic and its probable use to improve sperm recovery after applying an en- richment method like “swim-up” in comparison with the available one, pentoxifylline. Materials and Methods This is an experimental study. A total of 50 patients were re- cruited, followed by infertility consultation. Conventional sperm assays were performed according to World Health Organization criteria-2010 (WHO-2010. A Computer Aided Semen Analysis System was employed to assess kinetic parameters and concentrations. Number of the motile sperm recovered after preparation technique was calculated. Results Addition of T4 (0.002 µg/ml to semen samples increased hypermotility at 20 minutes (control: 14.18 ± 5.1% vs. 17.66 ± 8.88%, P<0.03, data expressed as mean ± SD and remained unchanged after 40 minutes. Significant differences were found in the motile sperm recovered after swim-up (control: 8.93×106 ± 9.52× 06vs. 17.20×106 ± 21.16×106, P<0.03, achieving all of the tested samples a desirable threshold value for artificial insemination outcome, while adding pentoxifylline increased the number of recovered sperm after swim-up in 60% of the studied cases. No synergism between two treatments could be determined. Conclusion We propose a new physiological tool to artificially improve insemination. The discussion opens windows to investigate unknown pathways involved in sperm ca- pacitation and gives innovative arguments to better understand infertility mechanisms.

  6. Apolipoprotein E4 reduces evoked hippocampal acetylcholine release in adult mice.

    Dolejší, Eva; Liraz, Ori; Rudajev, Vladimír; Zimčík, Pavel; Doležal, Vladimír; Michaelson, Daniel M


    Apolipoprotein E4 (apoE4) is the most prevalent genetic risk factor for Alzheimer's disease. We utilized apoE4-targeted replacement mice (approved by the Tel Aviv University Animal Care Committee) to investigate whether cholinergic dysfunction, which increases during aging and is a hallmark of Alzheimer's disease, is accentuated by apoE4. This revealed that levels of the pre-synaptic cholinergic marker, vesicular acetylcholine transporter in the hippocampus and the corresponding electrically evoked release of acetylcholine, are similar in 4-month-old apoE4 and apolipoprotein E3 (apoE3) mice. Both parameters decrease with age. This decrease is, however, significantly more pronounced in the apoE4 mice. The levels of cholinacetyltransferase (ChAT), acetylcholinesterase (AChE), and butyrylcholinesterase (BuChE) were similar in the hippocampus of young apoE4 and apoE3 mice and decreased during aging. For ChAT, this decrease was similar in the apoE4 and apoE3 mice, whereas it was more pronounced in the apoE4 mice, regarding their corresponding AChE and BuChE levels. The level of muscarinic receptors was higher in the apoE4 than in the apoE3 mice at 4 months and increased to similar levels with age. However, the relative representation of the M1 receptor subtype decreased during aging in apoE4 mice. These results demonstrate impairment of the evoked release of acetylcholine in hippocampus by apoE4 in 12-month-old mice but not in 4-month-old mice. The levels of ChAT and the extent of the M2 receptor-mediated autoregulation of ACh release were similar in the adult mice, suggesting that the apoE4-related inhibition of hippocampal ACh release in these mice is not driven by these parameters. Evoked ACh release from hippocampal and cortical slices is similar in 4-month-old apoE4 and apoE3 mice but is specifically and significantly reduced in hippocampus, but not cortex, of 12-month-old apoE4 mice. This effect is accompanied by decreased VAChT levels. These findings show that

  7. Thyroxine treatment for elderly patients with heart failure and sick euthyroid syndrome

    Yi ZHU; Ling GONG; Kailei SHI; Jin LI; Zhaohui QIU; Wenliang LU; Yu ZHANG; Jianying YANG


    Objectives To evaluate the effect of thyroid hormone therapy with low dose of thyroxin on cardiac function in elderly patients with heart failure and sick euthyroid syndrome. Methods Forty-seven patients (33 males and 14 females, mean age 85.9+4.6 years,ranging from 80 to 99 years) with chronic heart failure (NYHA Ⅱ-Ⅳ) and low triiodothyronine (T3) state were randomly allocated to the treatment group or control group. The treatment group patients received oral administration of levothyroxine sodium (Euthyrox) 25-50mg/d in addition to conventional therapy of heart failure, whereas patients in control group were given conventional therapy only. Serum level of total T3 (TT3), free T3 (FT3), total thyroxine (TT4), free thyroxine (FT4), and thyroid-stimulating hormone (TSH) were determined. For both groups, left ventricular ejection fraction (LVEF) and stroke volume (SV) were assessed by two-dimensional echocardiography before and at 8 weeks after treatment. The changes of these parameters after the treatment were evaluated by adjusting heart rate in the two groups. Results The reduced serum T3 level in the treatment group was corrected after thyroid hormone therapy,and these patients had a significant improvement in cardiac function after treatment. By contrast, in the control group only changes of serum TT3 and TT4 levels and SV and LVEF after treatment were statistically significant. The heart rate-adjusted mean SV and LVEF in both groups were also increased, which was significantly greater in the treatment group than in the control group. Conclusion In the elderly patients with heart failure and sick euthyroid syndrome, addition of thyroxine at a low dosage to the conventional treatment could effectively improve the low T3 state and cardiac function independent of changes of heart rate.

  8. Automated assay for screening the enzymatic release of reducing sugars from micronized biomass

    Asther Marcel


    Full Text Available Abstract Background To reduce the production cost of bioethanol obtained from fermentation of the sugars provided by degradation of lignocellulosic biomass (i.e., second generation bioethanol, it is necessary to screen for new enzymes endowed with more efficient biomass degrading properties. This demands the set-up of high-throughput screening methods. Several methods have been devised all using microplates in the industrial SBS format. Although this size reduction and standardization has greatly improved the screening process, the published methods comprise one or more manual steps that seriously decrease throughput. Therefore, we worked to devise a screening method devoid of any manual steps. Results We describe a fully automated assay for measuring the amount of reducing sugars released by biomass-degrading enzymes from wheat-straw and spruce. The method comprises two independent and automated steps. The first step is the making of "substrate plates". It consists of filling 96-well microplates with slurry suspensions of micronized substrate which are then stored frozen until use. The second step is an enzymatic activity assay. After thawing, the substrate plates are supplemented by the robot with cell-wall degrading enzymes where necessary, and the whole process from addition of enzymes to quantification of released sugars is autonomously performed by the robot. We describe how critical parameters (amount of substrate, amount of enzyme, incubation duration and temperature were selected to fit with our specific use. The ability of this automated small-scale assay to discriminate among different enzymatic activities was validated using a set of commercial enzymes. Conclusions Using an automatic microplate sealer solved three main problems generally encountered during the set-up of methods for measuring the sugar-releasing activity of plant cell wall-degrading enzymes: throughput, automation, and evaporation losses. In its present set-up, the

  9. Reduced Glutamate Release in Adult BTBR Mouse Model of Autism Spectrum Disorder.

    Wei, Hongen; Ma, Yuehong; Ding, Caiyun; Jin, Guorong; Liu, Jianrong; Chang, Qiaoqiao; Hu, Fengyun; Yu, Li


    Autism spectrum disorder (ASD) is a developmental disorder characterized by impairments in social and communication abilities, as well as by restricted and repetitive behaviors. The BTBR T (+) Itpr3 (tf) (BTBR) mice have emerged as a well characterized and widely used mouse model of a range of ASD-like phenotype, showing deficiencies in social behaviors and unusual ultrasonic vocalizations as well as increased repetitive self-grooming. However, the inherited neurobiological changes that lead to ASD-like behaviors in these mice are incompletely known and still under active investigation. The aim of this study was to further evaluate the structure and neurotransmitter release of the glutamatergic synapse in BTBR mice. C57BL/6J (B6) mice were used as a control strain because of their high level of sociability. The important results showed that the evoked glutamate release in the cerebral cortex of BTBR mice was significantly lower than in B6 mice. And the level of vesicle docking-related protein Syntaxin-1A was reduced in BTBR mice. However, no significant changes were observed in the number of glutamatergic synapse, level of synaptic proteins, density of dendritic spine and postsynaptic density between BTBR mice and B6 mice. Overall, our results suggest that abnormal vesicular glutamate activity may underlie the ASD relevant pathology in the BTBR mice.

  10. Reduced release probability prevents vesicle depletion and transmission failure at dynamin mutant synapses.

    Lou, Xuelin; Fan, Fan; Messa, Mirko; Raimondi, Andrea; Wu, Yumei; Looger, Loren L; Ferguson, Shawn M; De Camilli, Pietro


    Endocytic recycling of synaptic vesicles after exocytosis is critical for nervous system function. At synapses of cultured neurons that lack the two "neuronal" dynamins, dynamin 1 and 3, smaller excitatory postsynaptic currents are observed due to an impairment of the fission reaction of endocytosis that results in an accumulation of arrested clathrin-coated pits and a greatly reduced synaptic vesicle number. Surprisingly, despite a smaller readily releasable vesicle pool and fewer docked vesicles, a strong facilitation, which correlated with lower vesicle release probability, was observed upon action potential stimulation at such synapses. Furthermore, although network activity in mutant cultures was lower, Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) activity was unexpectedly increased, consistent with the previous report of an enhanced state of synapsin 1 phosphorylation at CaMKII-dependent sites in such neurons. These changes were partially reversed by overnight silencing of synaptic activity with tetrodotoxin, a treatment that allows progression of arrested endocytic pits to synaptic vesicles. Facilitation was also counteracted by CaMKII inhibition. These findings reveal a mechanism aimed at preventing synaptic transmission failure due to vesicle depletion when recycling vesicle traffic is backed up by a defect in dynamin-dependent endocytosis and provide new insight into the coupling between endocytosis and exocytosis.

  11. Mixture experiment techniques for reducing the number of components applied for modeling waste glass sodium release

    Piepel, G.; Redgate, T. [Pacific Northwest National Lab., Richland, WA (United States). Statistics Group


    Statistical mixture experiment techniques were applied to a waste glass data set to investigate the effects of the glass components on Product Consistency Test (PCT) sodium release (NR) and to develop a model for PCT NR as a function of the component proportions. The mixture experiment techniques indicate that the waste glass system can be reduced from nine to four components for purposes of modeling PCT NR. Empirical mixture models containing four first-order terms and one or two second-order terms fit the data quite well, and can be used to predict the NR of any glass composition in the model domain. The mixture experiment techniques produce a better model in less time than required by another approach.

  12. Reduced levels of intracellular calcium releasing in spermatozoa from asthenozoospermic patients

    García Juan F


    Full Text Available Abstract Background Asthenozoospermia is one of the most common findings present in infertile males characterized by reduced or absent sperm motility, but its aetiology remains unknown in most cases. In addition, calcium is one of the most important ions regulating sperm motility. In this study we have investigated the progesterone-evoked intracellular calcium signal in ejaculated spermatozoa from men with normospermia or asthenozoospermia. Methods Human ejaculates were obtained from healthy volunteers and asthenospermic men by masturbation after 4–5 days of abstinence. For determination of cytosolic free calcium concentration, spermatozoa were loaded with the fluorescent ratiometric calcium indicator Fura-2. Results Treatment of spermatozoa from normospermic men with 20 micromolar progesterone plus 1 micromolar thapsigargin in a calcium free medium induced a typical transient increase in cytosolic free calcium concentration due to calcium release from internal stores. Similar results were obtained when spermatozoa were stimulated with progesterone alone. Subsequent addition of calcium to the external medium evoked a sustained elevation in cytosolic free calcium concentration indicative of capacitative calcium entry. However, when progesterone plus thapsigargin were administered to spermatozoa from patients with asthenozoospermia, calcium signal and subsequent calcium entry was much smaller compared to normospermic patients. As expected, pretreatment of normospermic spermatozoa with both the anti-progesterone receptor c262 antibody and with progesterone receptor antagonist RU-38486 decreased the calcium release induced by progesterone. Treatment of spermatozoa with cytochalasin D or jasplakinolide decreased the calcium entry evoked by depletion of internal calcium stores in normospermic patients, whereas these treatments proved to be ineffective at modifying the calcium entry in patients with asthenozoospermia. Conclusion Our results suggest

  13. Evaluating High Release Rate MCH (3-Methylcyclohex-2-en-1-one) Treatments for Reducing Dendroctonus pseudotsugae (Coleoptera: Curculionidae) Infestations.

    Brookes, Harrison M; Ross, Darrell W; Strand, Tara M; Thistle, Harold W; Ragenovich, Iral R; Lowrey, Laura L


    Current recommendations for applying the antiaggregation pheromone 3-methylcyclohex-2-en-1-one (MCH) to protect live trees from Douglas-fir beetle, Dendroctonus pseudotsugae Hopkins, infestation are to space individual passive releasers (MCH bubble capsules) on a 12- by 12-m grid throughout areas to be protected. Previous field studies and a theoretical study using a puff dispersion model to predict pheromone concentrations have shown that releasers emitting higher rates of MCH spaced farther apart may be as effective as the established standard treatment. During 2012 and 2013, we tested higher release rates of MCH at correspondingly wider spacings to keep the total amount of MCH released per unit area equal in all treatments. In 2012 near Challis, ID, treatments included the established standard release rate and spacing, four and six times the standard release rate at correspondingly wider spacings, and an untreated control. In 2013 near Ketchum, ID, treatments included the established standard release rate and spacing, five and seven times the standard release rate at correspondingly wider spacings, and an untreated control. Results from both years indicated that all MCH treatments were equally effective in reducing Douglas-fir beetle infestation. Using higher release rate formulations at wider spacings will reduce labor costs of installing MCH treatments, and, in cases where it is necessary, retrieving the releasers as well. In addition to reducing labor costs, the revised treatment protocol may increase the feasibility of treating areas that currently may not be possible due to treatment costs. © The Authors 2016. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email:

  14. Potent neutralizing anti-CD1d antibody reduces lung cytokine release in primate asthma model.

    Nambiar, Jonathan; Clarke, Adam W; Shim, Doris; Mabon, David; Tian, Chen; Windloch, Karolina; Buhmann, Chris; Corazon, Beau; Lindgren, Matilda; Pollard, Matthew; Domagala, Teresa; Poulton, Lynn; Doyle, Anthony G


    CD1d is a receptor on antigen-presenting cells involved in triggering cell populations, particularly natural killer T (NKT) cells, to release high levels of cytokines. NKT cells are implicated in asthma pathology and blockade of the CD1d/NKT cell pathway may have therapeutic potential. We developed a potent anti-human CD1d antibody (NIB.2) that possesses high affinity for human and cynomolgus macaque CD1d (KD ∼100 pM) and strong neutralizing activity in human primary cell-based assays (IC50 typically <100 pM). By epitope mapping experiments, we showed that NIB.2 binds to CD1d in close proximity to the interface of CD1d and the Type 1 NKT cell receptor β-chain. Together with data showing that NIB.2 inhibited stimulation via CD1d loaded with different glycolipids, this supports a mechanism whereby NIB.2 inhibits NKT cell activation by inhibiting Type 1 NKT cell receptor β-chain interactions with CD1d, independent of the lipid antigen in the CD1d antigen-binding cleft. The strong in vitro potency of NIB.2 was reflected in vivo in an Ascaris suum cynomolgus macaque asthma model. Compared with vehicle control, NIB.2 treatment significantly reduced bronchoalveolar lavage (BAL) levels of Ascaris-induced cytokines IL-5, IL-8 and IL-1 receptor antagonist, and significantly reduced baseline levels of GM-CSF, IL-6, IL-15, IL-12/23p40, MIP-1α, MIP-1β, and VEGF. At a cellular population level NIB.2 also reduced numbers of BAL lymphocytes and macrophages, and blood eosinophils and basophils. We demonstrate that anti-CD1d antibody blockade of the CD1d/NKT pathway modulates inflammatory parameters in vivo in a primate inflammation model, with therapeutic potential for diseases where the local cytokine milieu is critical.

  15. Reducing Mortality from Terrorist Releases of Chemical and Biological Agents: I. Filtration for Ventilation Systems in Commercial Building

    Thatcher, Tracy L.; Daisey, Joan M.


    There is growing concern about potential terrorist attacks involving releases of chemical and/or biological (CB) agents, such as sarin or anthrax, in and around buildings. For an external release, the CB agent can enter the building through the air intakes of a building's mechanical ventilation system and by infiltration through the building envelope. For an interior release in a single room, the mechanical ventilation system, which often recirculates some fraction of the air within a building, may distribute the released CB agent throughout the building. For both cases, installing building systems that remove chemical and biological agents may be the most effective way to protect building occupants. Filtration systems installed in the heating, ventilating and air-conditioning (HVAC) systems of buildings can significantly reduce exposures of building occupants in the event of a release, whether the release is outdoors or indoors. Reduced exposures can reduce the number of deaths from a terrorist attack. The purpose of this report is to provide information and examples of the design of filtration systems to help building engineers retrofit HVAC systems. The report also provides background information on the physical nature of CB agents and brief overviews of the basic principles of particle and vapor filtration.

  16. Glucuronidation of thyroxine in human liver, jejunum, and kidney microsomes.

    Yamanaka, Hiroyuki; Nakajima, Miki; Katoh, Miki; Yokoi, Tsuyoshi


    Glucuronidation of thyroxine is a major metabolic pathway facilitating its excretion. In this study, we characterized the glucuronidation of thyroxine in human liver, jejunum, and kidney microsomes, and identified human UDP-glucuronosyltransferase (UGT) isoforms involved in the activity. Human jejunum microsomes showed a lower K(m) value (24.2 microM) than human liver (85.9 microM) and kidney (53.3 microM) microsomes did. Human kidney microsomes showed a lower V(max) value (22.6 pmol/min/mg) than human liver (133.4 pmol/min/mg) and jejunum (184.6 pmol/min/mg) microsomes did. By scaling-up, the in vivo clearances in liver, intestine, and kidney were estimated to be 1440, 702, and 79 microl/min/kg body weight, respectively. Recombinant human UGT1A8 (108.7 pmol/min/unit), UGT1A3 (91.6 pmol/min/unit), and UGT1A10 (47.3 pmol/min/unit) showed high, and UGT1A1 (26.0 pmol/min/unit) showed moderate thyroxine glucuronosyltransferase activity. The thyroxine glucuronosyltransferase activity in microsomes from 12 human livers was significantly correlated with bilirubin O-glucuronosyltransferase (r = 0.855, p microsomes was mainly catalyzed by UGT1A8 and UGT1A10 and to a lesser extent by UGT1A1, and the activity in human kidney microsomes was mainly catalyzed by UGT1A7, UGT1A9, and UGT1A10. The changes of activities of these UGT1A isoforms via inhibition and induction by administered drugs as well as genetic polymorphisms may be a causal factor of interindividual differences in the plasma thyroxine concentration.

  17. Sulfate-reducing bacteria release barium and radium from naturally occurring radioactive material in oil-field barite

    Phillips, E.J.P.; Landa, E.R.; Kraemer, T.; Zielinski, R.


    Scale and sludge deposits formed during oil production can contain elevated levels of Ra, often coprecipitated with barium sulfate (barite). The potential for sulfate-reducing bacteria to release 226 Ra and Ba (a Ra analog) from oil-field barite was evaluated. The concentration of dissolved Ba increased when samples containing pipe scale, tank sludge, or oil-field brine pond sediment were incubated with sulfate-reducing bacteria Desulfovibrio sp., Str LZKI, isolated from an oil-field brine pond. However, Ba release was not stoichiometric with sulfide production in oil-field samples, and material.

  18. Specific immunotherapy with mugwort pollen allergoid reduce bradykinin release into the nasal fluid

    Grzanka, Alicja; Jawor, Barbara; Czecior, Eugeniusz


    Introduction A pathomechanism of allergic rhinitis is complex. A neurogenic mechanism seems to play a significant role in this phenomenon. Aim The evaluation of influence of specific immunotherapy of mugwort pollen allergic patients on the bradykinin concentration in the nasal lavage fluid. Material and methods The study included 22 seasonal allergic rhinitis patients. Thirty persons with monovalent allergy to mugwort pollen, confirmed with skin prick tests and allergen-specific immunoglobulin E, underwent a 3-year-long allergen immunotherapy with the mugwort extract (Allergovit, Allergopharma, Germany). The control group was composed of 9 persons with polyvalent sensitivity to pollen, who were treated with pharmacotherapy. Before the allergen-specific immunotherapy (AIT) and in subsequent years before the pollen seasons, a provocation allergen test with the mugwort extract was performed, together with collection of nasal fluids, where bradykinin concentration was determined according to Proud method. Results There were similar levels of bradykinin in both groups at baseline prior to therapy (AIT group: 584.0 ±87.2 vs. controls 606.3 ±106.5 pg/ml) and changes after allergen challenge 1112.4 ±334.8 vs. 1013.3 ±305.9 pg/ml as well. The bradykinin concentration in nasal lavage fluid after mugwort challenge in 1 year was lower in the AIT group (824.1 ±184.2 pg/ml vs. 1000.4 ±411.5 pg/l; p < 005) with a further significant decrease after the 2nd and 3rd year of specific immunotherapy. Significant reduction of symptoms and medications use was observed in hyposensitized patients. Conclusions A decreased level of bradykinin as a result of AIT suggests that some of the symptomatic benefits of AIT may be related to the reduced release of bradykinin into nasal secretions. These values correlate with clinical improvement within the course of treatment. PMID:27605897

  19. Surgical capsular release reduces flexion contracture in a rabbit model of arthrofibrosis.

    Barlow, Jonathan D; Hartzler, Robert U; Abdel, Matthew P; Morrey, Mark E; An, Kai-Nan; Steinmann, Scott P; Morrey, Bernard F; Sanchez-Sotelo, Joaquin


    Animal models of joint contracture may be used to elucidate the mechanisms of arthrofibrosis. Patients with joint contracture commonly undergo surgical capsular release. Previous animal models of joint contracture do not simulate this aspect of arthrofibrosis. We hypothesize that a surgical capsular release will decrease the severity of arthrofibrosis in this rabbit model. A capsular contracture was surgically created in 20 skeletally mature rabbits. Eight weeks later, ten rabbits underwent capsular release, which consisted of elevation of the posterior capsule through a lateral incision and manipulation under anesthesia. Ten rabbits had a sham incision, without release (control group). Immediately after release or sham surgery, extension loss (calculated by subtracting the knee extension angle (degrees) of the operative limb from the nonoperative, contralateral limb) was measured using fluoroscopy. All animals were sacrificed following 16 weeks of postoperative free cage activity. At sacrifice, joint contracture was measured using a custom, calibrated device. The histology of the posterior joint capsule was assessed at sacrifice. All animals survived both operations without complications. Immediately after surgical release or sham surgery, the average extension loss was 129.2 ± 10.7° in the control group versus 29.6 ± 8.2° in the capsular release group (p = 0.0002). Following 16 weeks of remobilization, the average extension loss of the control and capsular release animals were 49.0 ± 12.7° and 36.5 ± 14.2°, respectively (p = 0.035). There were no histological differences between the two groups. In this animal model, a surgical capsular release decreased the extension loss (flexion contracture) immediately after surgery, as well as following sixteen weeks of remobilization. There were no histological changes detected in the posterior joint capsule. Copyright © 2013 Orthopaedic Research Society.

  20. Effectiveness of a personalized ventilation system in reducing personal exposure against directly released simulated cough droplets

    Pantelic, J.; Tham, K. W.; Licina, Dusan


    The inhalation intake fraction was used as an indicator to compare effects of desktop personalized ventilation and mixing ventilation on personal exposure to directly released simulated cough droplets. A cough machine was used to simulate cough release from the front, back, and side of a thermal...... the inhalation intake fraction compared to mixing ventilation for all investigated distances and orientations of the cough release. The results point out that the orientation between the cough source and the breathing zone of the exposed occupant is an important factor that substantially influences exposure...

  1. Treating Hypothyroidism with Thyroxine/Triiodothyronine Combination Therapy in Denmark

    Michaelsson, Luba Freja; Medici, Bjarke Borregaard; la Cour, Jeppe Lerche


    BACKGROUND: Five to ten percent of patients with hypothyroidism describe persistent symptoms despite being biochemically well regulated on levothyroxine (L-T4). Thyroxine (T4)/triiodothyronine (T3) combination therapy [L-T4/liothyronine (L-T3) or desiccated thyroid] are still regarded as experime......BACKGROUND: Five to ten percent of patients with hypothyroidism describe persistent symptoms despite being biochemically well regulated on levothyroxine (L-T4). Thyroxine (T4)/triiodothyronine (T3) combination therapy [L-T4/liothyronine (L-T3) or desiccated thyroid] are still regarded...... after a patient published a book describing her experiences with hypothyroidism and treatment. OBJECTIVE: To investigate current Danish trends in the use of T4/T3 combination therapy. METHODS: We used an Internet-based questionnaire, distributed as a link via two Danish patient fora. Further...

  2. Dopamine release from serotonergic nerve fibers is reduced in L-DOPA-induced dyskinesia

    Nevalainen, Nina; af Bjerkén, Sara; Lundblad, Martin; Gerhardt, Greg A.; Strömberg, Ingrid


    L-DOPA (3,4-dihydroxyphenyl-L-alanine) is the most commonly used treatment for symptomatic control in patients with Parkinson’s disease. Unfortunately, most patients develop severe side effects, such as dyskinesia, upon chronic L-DOPA treatment. The patophysiology of dyskinesia is unclear, however, involvement of serotonergic nerve fibers in converting L-DOPA to dopamine has been suggested. Therefore, potassium-evoked dopamine release was studied after local application of L-DOPA in the striata of normal, dopamine- and dopamine/serotonin-lesioned L-DOPA naïve, and dopamine-denervated chronically L-DOPA-treated dyskinetic rats using in vivo chronoamperometry. The results revealed that local L-DOPA administration into normal and intact hemisphere of dopamine-lesioned L-DOPA naïve animals significantly increased the potassium-evoked dopamine release. L-DOPA application also increased the dopamine peak amplitude in the dopamine-depleted L-DOPA naïve striatum, although these dopamine levels were several-folds lower than in the normal striatum, while no increased dopamine release was found in the dopamine/serotonin-denervated striatum. In dyskinetic animals, local L-DOPA application did not affect the dopamine release, resulting in significantly attenuated dopamine levels compared to those measured in L-DOPA naïve dopamine-denervated striatum. To conclude, L-DOPA is most likely converted to dopamine in serotonergic nerve fibers in the dopamine-depleted striatum, but the dopamine release is several-fold lower than in normal striatum. Furthermore, L-DOPA loading does not increase the dopamine release in dyskinetic animals as found in L-DOPA naïve animals, despite similar density of serotonergic innervation. Thus, the dopamine overflow produced from the serotonergic nerve fibers appears not to be the major cause of dyskinetic behavior. PMID:21534956

  3. Thyroxine lipophilicity is dominated by its zwitterionic microspecies.

    Mazák, Károly; Tóth, Gergő; Kökösi, József; Noszál, Béla


    Species-specific partition coefficients were determined for a triprotic molecule for the first time. Thyroxine, the vitally important thyroid hormone which exists in solution in the forms of eight microspecies due to its phenolate, amino and carboxylate basic sites, was studied by combined methods of microspeciation and lipophilicity. Partition of the individual microspecies was mimicked by model compounds of the closest possible similarity, then correction factors were determined and introduced. The non-charged microspecies is only 2.40 times as lipophilic as its zwitterionic protonation isomer, showing that for thyroxine the iodinated aromatic rings are the structural elements that determine the lipophilicity of this molecule, and the protonation state of the other substituents plays only a minor role. The overwhelming dominance of the zwitterionic form, however, ensures that its contribution to the overall lipophilicity exceeds 14,500 times that of the non-charged one. This fact is so far the sharpest counter-example of the widespread belief that passive diffusion into lipophilic media is predominated by the non-charged species. The lipophilicity profile of thyroxine is expressed, calculated and depicted in terms of species-specific lipophilicities over the entire pH range. Copyright © 2012 Elsevier B.V. All rights reserved.

  4. Luteinizing hormone-releasing hormone receptor antagonist may reduce postmenopausal flushing

    Gastel, P. van; Zanden, M. van der; Telting, D.; Filius, M.; Bancsi, L.; Boer, H. de


    OBJECTIVE: Hormone therapy (HT) is the most effective treatment of postmenopausal (PMP) flushing; however, its use is often contraindicated. As an alternative option, we explored the efficacy of the luteinizing hormone-releasing hormone (LHRH) receptor antagonist cetrorelix in women with severe PMP

  5. [Thyroxine treatment in acute renal failure (author's transl)].

    Straub, E


    8 patients suffering from acute renal failure (shock kidney) with anuria extending over 3 to 5 days, were treated with L-thyroxine for 5 to 9 days (5-6 mug per kg body weight per day orally). Diuresis was restored within 34 to 46 hrs. Plasma levels of urea and creatinine decreased earlier and much more rapidly to normal than was to be expected from the natural history of the disease, indicating the prompt and extensive increase of glomerular filtration rate. Polyuria seemed less pronounced and also shortened as compared with the ordinary course of that form of sudden renal insufficiency. Obviously, the well-known diuretic response in the normal individual to high doses of thyroid hormones in not a factor in the induction of diuresis in acute renal failure. The tendency with L-thyroxine treatment to dilate the preglomerular arterial vessel is considered a consequence of the stimulation of sodium reabsorption in the upper nephron. High values of RPF and GFR, regularly observed in hyperthyroidism or after L-thyroxine administration, do not depend on any augmentation of cardiac output or on arterial hypertension, since such symptoms were missed in our patients and, in our view, such an interpretation is excluded by the very existence of the so-called autoregulation of the kidney which leaves RPF (and therefore GFR) independent of systemic blood pressure. The same intrarenal feed-back mechanism, normally adapting the glomerular blood supply to the resorptive capacity of the proximal-tubular epithelium (mediation via the juxta-glomerular apparatus), is responsible for the GFR- and RPF-raising effect of exogenous L-thyroxine in the intact kidney as well as in acute renal failure: both sodium reabsorption and sodium filtration are accelerated.--The special conditions under which L-thyroxine interferes with the pathogenetic process of acute renal failure, the latter being characterised by the critical insufficiency of tubular sodium reabsorption and therefore by

  6. The mast cell stabilizer sodium cromoglycate reduces histamine release and status epilepticus-induced neuronal damage in the rat hippocampus.

    Valle-Dorado, María Guadalupe; Santana-Gómez, César Emmanuel; Orozco-Suárez, Sandra Adela; Rocha, Luisa


    Experiments were designed to evaluate changes in the histamine release, mast cell number and neuronal damage in hippocampus induced by status epilepticus. We also evaluated if sodium cromoglycate, a stabilizer of mast cells with a possible stabilizing effect on the membrane of neurons, was able to prevent the release of histamine, γ-aminobutyric acid (GABA) and glutamate during the status epilepticus. During microdialysis experiments, rats were treated with saline (SS-SE) or sodium cromoglycate (CG-SE) and 30 min later received the administration of pilocarpine to induce status epilepticus. Twenty-four hours after the status epilepticus, the brains were used to determine the neuronal damage and the number of mast cells in hippocampus. During the status epilepticus, SS-SE group showed an enhanced release of histamine (138.5%, p = 0.005), GABA (331 ± 91%, p ≤ 0.001) and glutamate (467%, p ≤ 0.001), even after diazepam administration. One day after the status epilepticus, SS-SE group demonstrated increased number of mast cells in Stratum pyramidale of CA1 (88%, p histamine (but not GABA and glutamate) release, lower number of mast cells (p = 0.008) and reduced neuronal damage in hippocampus. Our data revealed that histamine, possibly from mast cells, is released in hippocampus during the status epilepticus. This effect may be involved in the subsequent neuronal damage and is diminished with sodium cromoglycate pretreatment.

  7. Reduced Burst Release and Enhanced Oral Bioavailability in Shikimic Acid-Loaded Polylactic Acid Submicron Particles by Coaxial Electrospray.

    Wang, Miaomiao; Wang, Yuanwen; Omari-Siaw, Emmanuel; Wang, Shengli; Zhu, Yuan; Xu, Ximing


    In this study, using the coaxial electrospray method, we prepared submicron particles of the water-soluble drug shikimic acid (SA) with polylactic acid (PLA) as a polymer, to reduce the burst release and enhance the oral bioavailability. In vitro release study performed in HCl solution (pH 1.2) showed that the coaxial electrospray submicron particles could reduce burst release effect and presented a sustained release profile, compared with free SA and the particles prepared by electrospray method. The absorption of SA in the intestinal tract, studied using an in situ perfusion method in rats, also revealed jejunum as the main absorptive segment followed by duodenum and ileum. Moreover, the SA-loaded particles greatly enhanced the absorption of SA in the tested intestinal segments. The intestinal absorption rate was not enhanced with increasing drug concentration (5-15 μg/mL) which suggested that active transport or facilitated diffusion could play vital role in SA absorption. In addition, the SA-loaded PLA coaxial electrospray particle exhibited a prolonged plasma circulation with enhanced bioavailability after oral administration. In all, the coaxial electrospray technique could provide notable advantages for the oral delivery of SA, thereby enhancing its clinical application.

  8. Release of Extracellular Polymeric Substance and Disintegration of Anaerobic Granular Sludge under Reduced Sulfur Compounds-Rich Conditions

    Takuro Kobayashi


    Full Text Available The effect of reduced form of sulfur compounds on granular sludge was investigated. Significant release of extracellular polymeric substance (EPS from the granular sludge occurred in the presence of sulfide and methanethiol according to various concentrations. Granular sludge also showed a rapid increase in turbidity and decrease in diameter in accordance with sulfide concentration during the long-term shaking, suggesting that the strength of the granules was reduced with high-concentration sulfide. A continuous experiment of up-flow anaerobic sludge blanket reactors with different concentrations of sulfide (10, 200, 500 mg-S/L influence demonstrated that the reactor fed with higher concentration of sulfide allowed more washout of small particle-suspended solid (SS content and soluble carbohydrate and protein, which were considered as EPS released from biofilm. Finally, the presence of sulfide negatively affected methane production, chemical oxygen demand removal and sludge retention in operational performance.

  9. Risk of Depression, Chronic Morbidities, and l-Thyroxine Treatment in Hashimoto Thyroiditis in Taiwan: A Nationwide Cohort Study.

    Lin, I-Ching; Chen, Hsin-Hung; Yeh, Su-Yin; Lin, Cheng-Li; Kao, Chia-Hung


    The aim of this study was to evaluate the risk of depression in and effect of L-thyroxine therapy on patients with Hashimoto thyroiditis (HT) in Taiwan.In this retrospective, nationwide cohort study, we retrieved data from the Longitudinal Health Insurance Database 2000. We collected data of 1220 patients with HT and 4880 patients without HT for the period 2000 to 2011. The mean follow-up period for the HT cohort was 5.77 years. Univariate and multivariate Cox proportional hazards regression models were used to estimate the risk of depression in the HT cohort.In the HT cohort, 89.6% of the patients were women. Compared with the non-HT cohort, the HT cohort exhibited a higher prevalence of diabetes mellitus, hyperlipidemia, and coronary artery disease. Furthermore, the HT cohort showed a higher overall incidence of depression compared with the non-HT cohort (8.67 and 5.49 per 1000 person-year; crude hazard ratio [HR] = 1.58, 95% confidence interval [CI] = 1.18-2.13). The risk of depression decreased after administration of L-thyroxine treatment for more than 1 year (adjusted HR = 1.02; 95% CI = 0.66-1.59).In Taiwan, the overall incidence of depression was greater in the young HT cohort. L-thyroxine treatment reduced the risk of depression.

  10. Large methane releases lead to strong aerosol forcing and reduced cloudiness

    Kurten, T.; Zhou, L.; Makkonen, R.;


    The release of vast quantities of methane into the atmosphere as a result of clathrate destabilization is a potential mechanism for rapid amplification of global warming. Previous studies have calculated the enhanced warming based mainly on the radiative effect of the methane itself, with smaller...... contributions from the associated carbon dioxide or ozone increases. Here, we study the effect of strongly elevated methane (CH4) levels on oxidant and aerosol particle concentrations using a combination of chemistry-transport and general circulation models. A 10-fold increase in methane concentrations...

  11. Management Options For Reducing The Release Of Antibiotics And Antibiotic Resistance Genes To The Environment

    Background: There is growing concern worldwide about the role of polluted soil and water - 77 environments in the development and dissemination of antibiotic resistance. 78 Objective: To identify management options for reducing the spread of antibiotics and 79 antibiotic resist...

  12. Management Options For Reducing The Release Of Antibiotics And Antibiotic Resistance Genes To The Environment

    Background: There is growing concern worldwide about the role of polluted soil and water - 77 environments in the development and dissemination of antibiotic resistance. 78 Objective: To identify management options for reducing the spread of antibiotics and 79 antibiotic resist...

  13. Loss of hypothalamic corticotropin-releasing hormone markedly reduces anxiety behaviors in mice

    Zhang, Rong; Asai, Masato; Mahoney, Carrie E; Joachim, Maria; Shen, Yuan; Gunner, Georgia; Majzoub, Joseph A


    A long-standing paradigm posits that hypothalamic corticotropin-releasing hormone (CRH) regulates neuroendocrine functions such as adrenal glucocorticoid release, while extra-hypothalamic CRH plays a key role in stressor-triggered behaviors. Here we report that hypothalamus-specific Crh knockout mice (Sim1CrhKO mice, created by crossing Crhflox with Sim1Cre mice) have absent Crh mRNA and peptide mainly in the paraventricular nucleus of the hypothalamus (PVH) but preserved Crh expression in other brain regions including amygdala and cerebral cortex. As expected, Sim1CrhKO mice exhibit adrenal atrophy as well as decreased basal, diurnal and stressor-stimulated plasma corticosterone secretion and basal plasma ACTH, but surprisingly, have a profound anxiolytic phenotype when evaluated using multiple stressors including open field, elevated plus maze, holeboard, light-dark box, and novel object recognition task. Restoring plasma corticosterone did not reverse the anxiolytic phenotype of Sim1CrhKO mice. Crh-Cre driver mice revealed that PVHCrh fibers project abundantly to cingulate cortex and the nucleus accumbens shell, and moderately to medial amygdala, locus coeruleus, and solitary tract, consistent with the existence of PVHCrh-dependent behavioral pathways. Although previous, nonselective attenuation of CRH production or action, genetically in mice and pharmacologically in humans, respectively, has not produced the anticipated anxiolytic effects, our data show that targeted interference specifically with hypothalamic Crh expression results in anxiolysis. Our data identify neurons that express both Sim1 and Crh as a cellular entry point into the study of CRH-mediated, anxiety-like behaviors and their therapeutic attenuation. PMID:27595593

  14. Telmisartan Ameliorates Nephropathy in Metabolic Syndrome by Reducing Leptin Release From Perirenal Adipose Tissue.

    Li, Hao; Li, Min; Liu, Ping; Wang, YaPing; Zhang, Heng; Li, HongBin; Yang, ShiFeng; Song, Yan; Yin, YanRong; Gao, Lan; Cheng, Si; Cai, Jun; Tian, Gang


    Metabolic syndrome (MetS) is associated with nephropathy. Along with common risk factors such as hypertension and hyperglycemia, adipocytokines released from perirenal adipose tissue (PRAT) are implicated in the pathogenesis of MetS nephropathy. The study was designed to elucidate the adverse effects of PRAT-derived leptin on nephropathy and to determine whether the angiotensin II type 1 receptor antagonist telmisartan exerts a renoprotective effect by decreasing the PRAT-derived leptin level in the high-fat diet-induced MetS rat. In MetS rats, PRAT-derived leptin expression increased concomitant with dysfunction of adipogenesis, and the activities of the angiotensin II-angiotensin II type 1 receptor and the angiotensin-converting enzyme 2-angiotensin (1-7)-Mas receptor axes were imbalanced in PRAT. PRAT-derived leptin from MetS rats promoted proliferation of rat glomerular endothelial cells (GERs) by activating the p38 MAPK (mitogen-activated protein kinase) pathway, thereby contributing to the development of nephropathy. Long-term telmisartan treatment improved metabolic parameters and renal function, decreased the amount of PRAT, promoted adipogenesis, increased the expression of angiotensin-converting enzyme 2, restored balanced activities of the angiotensin II-AT1R and angiotensin-converting enzyme 2-angiotensin (1-7)-Mas axes, and exerted an indirect renoprotective effect on MetS rats by decreasing PRAT-derived leptin release. Our results demonstrate a novel link between nephropathy and PRAT in MetS and show that telmisartan confers an underlying protective effect on visceral adipose tissue and the kidney, suggesting that it has potential as a therapeutic agent for the treatment of MetS-associated nephropathy. © 2016 American Heart Association, Inc.

  15. How to (really) reduce the greenhouse gases releases; Comment (vraiment) reduire les emissions de gaz a effet de serre

    Masurel, J.; Frot, J. [Sauvons le Climat (France)


    Based on the last 2008 GIEC report, 'Sauvons le Climat' presupposes the character essentially anthropic of the climatic change and concludes to the requirement to divide by four, between now and 2050, the releases of greenhouse gases of the OECD countries. The world energetic balance is composed, for 80% of carbonaceous energies: petroleum, coal and natural gas. At the world-wide level, the preoccupations of the energetic resources and those of climate protection go therefore hand in hand. It is the same thing for the European Union but not for France whose carbonaceous energies part is only of 50%. That is to say, in France, an energy savings has only one chance of two to improve its energetic independence and to protect the climate. Especially for France, 'Sauvons le Climat' gives then here some advices to really reduce the greenhouse gases releases. (O.M.)

  16. Considerations for conducting incubations to study the mechanisms of As release in reducing groundwater aquifers

    Radloff, Kathleen A. [Department of Earth and Environmental Engineering, Columbia University, New York, NY 10027 (United States)], E-mail:; Manning, Anya R.; Mailloux, Brian [Barnard College, Columbia University, New York, NY 10027 (United States); Zheng Yan [Queens College, City University of New York, Flushing, NY 11367 (United States); Lamont-Doherty Earth Observatory of Columbia University, Palisades, NY 10964 (United States); Moshiur Rahman, M.; Rezaul Huq, M.; Ahmed, Kazi M. [Department of Geology, University of Dhaka, Dhaka (Bangladesh); Geen, Alexander van [Lamont-Doherty Earth Observatory of Columbia University, Palisades, NY 10964 (United States)


    Microbial Fe reduction is widely believed to be the primary mechanism of As release from aquifer sands in Bangladesh, but alternative explanations have been proposed. Long-term incubation studies using natural aquifer material are one way to address such divergent views. This study addresses two issues related to this approach: (1) the need for suitable abiotic controls and (2) the spatial variability of the composition of aquifer sands. Four sterilization techniques were examined using orange-colored Pleistocene sediment from Bangladesh and artificial groundwater over 8 months. Acetate (10 mM) was added to sacrificial vials before sterilization using either (1) 25 kGy of gamma irradiation, (2) three 1-h autoclave cycles, (3) a single addition of an antibiotic mixture at 1x or (4) 10x the typical dose, and (5) a 10 mM addition of azide. The effectiveness of sterilization was evaluated using two indicators of microbial Fe reduction, changes in diffuse spectral reflectance and leachable Fe(II)/Fe ratios, as well as changes in P-extractable As concentrations in the solid phase. A low dose of antibiotics was ineffective after 70 days, whereas autoclaving significantly altered groundwater composition. Gamma irradiation, a high dose of antibiotics, and azide were effective for the duration of the experiment. Using gamma irradiation as an abiotic control, shallow grey sediment and groundwater from 3 closely spaced locations along a gradient of dissolved As concentrations (60-130-210 {mu}g/L) in Bangladesh were incubated for 8 months with and without organic C addition (0.9 and 0.6 mM of acetate and lactate). Unexpectedly, levels of dissolved As (64 {+-} 68, 92 {+-} 70, 217 {+-} 68 {mu}g/L) and P-extractable As (0.7 {+-} 0.2, 2.1 {+-} 0.5 and 2.0 {+-} 0.3 mg/kg) at each location were highly variable over the duration of the experiment and prevented the detection of the relatively small levels of As release that were anticipated. Maintenance of an adsorptive equilibrium

  17. Thylakoids promote release of the satiety hormone cholecystokinin while reducing insulin in healthy humans

    Köhnke, Rickard; Lindbo, Agnes; Larsson, Therese


    (CCK, leptin and ghrelin), insulin and blood metabolites (glucose and free fatty acids). RESULTS: The CCK level increased, in particular between the 120 min time-point and onwards, the ghrelin level was reduced at 120 min and leptin level increased at 360 min after intake of the thylakoid-enriched meal...

  18. Interplay between thyroxin, BDNF and GABA in injured neurons.

    Shulga, A; Rivera, C


    Accumulating experimental evidence suggests that groups of neurons in the CNS might react to pathological insults by activating developmental-like programs for survival, regeneration and re-establishment of lost connections. For instance, in cell and animal models it was shown that after trauma mature central neurons become dependent on brain-derived neurotrophic factor (BDNF) trophic support for survival. This event is preceded by a shift of postsynaptic GABAA receptor-mediated responses from hyperpolarization to developmental-like depolarization. These profound functional changes in GABAA receptor-mediated transmission and the requirement of injured neurons for BDNF trophic support are interdependent. Thyroid hormones (THs) play a crucial role in the development of the nervous system, having significant effects on dendritic branching, synaptogenesis and axonal growth to name a few. In the adult nervous system TH thyroxin has been shown to have a neuroprotective effect and to promote regeneration in experimental trauma models. Interestingly, after trauma there is a qualitative change in the regulatory effect of thyroxin on BDNF expression as well as on GABAergic transmission. In this review we provide an overview of the post-traumatic changes in these signaling systems and discuss the potential significance of their interactions for the development of novel therapeutic strategies.

  19. Effect of short-term thyroxine administration on energy metabolism and mitochondrial efficiency in humans.

    Darcy L Johannsen

    Full Text Available The physiologic effects of triiodothyronine (T3 on metabolic rate are well-documented; however, the effects of thyroxine (T4 are less clear despite its wide-spread use to treat thyroid-related disorders and other non-thyroidal conditions. Here, we investigated the effects of acute (3-day T4 supplementation on energy expenditure at rest and during incremental exercise. Furthermore, we used a combination of in situ and in vitro approaches to measure skeletal muscle metabolism before and after T4 treatment. Ten healthy, euthyroid males were given 200 µg T4 (levothyroxine per day for 3 days. Energy expenditure was measured at rest and during exercise by indirect calorimetry, and skeletal muscle mitochondrial function was assessed by in situ ATP flux ((31P MRS and in vitro respiratory control ratio (RCR, state 3/state 4 rate of oxygen uptake using a Clark-type electrode before and after acute T4 treatment. Thyroxine had a subtle effect on resting metabolic rate, increasing it by 4% (p = 0.059 without a change in resting ATP demand (i.e., ATP flux of the vastus lateralis. Exercise efficiency did not change with T4 treatment. The maximal capacity to produce ATP (state 3 respiration and the coupled state of the mitochondria (RCR were reduced by approximately 30% with T4 (p = 0.057 and p = 0.04, respectively. Together, the results suggest that T4, although less metabolically active than T3, reduces skeletal muscle efficiency and modestly increases resting metabolism even after short-term supplementation. Our findings may be clinically relevant given the expanding application of T4 to treat non-thyroidal conditions such as obesity and weight loss.

  20. Early outgrowth cells release soluble endocrine antifibrotic factors that reduce progressive organ fibrosis.

    Yuen, Darren A; Connelly, Kim A; Zhang, Yanling; Advani, Suzanne L; Thai, Kerri; Kabir, Golam; Kepecs, David; Spring, Christopher; Smith, Christopher; Batruch, Ihor; Kosanam, Hari; Advani, Andrew; Diamandis, Eleftherios; Marsden, Philip A; Gilbert, Richard E


    Adult bone marrow-derived cells can improve organ function in chronic disease models, ostensibly by the release of paracrine factors. It has, however, been difficult to reconcile this prevailing paradigm with the lack of cell retention within injured organs and their rapid migration to the reticuloendothelial system. Here, we provide evidence that the salutary antifibrotic effects of bone marrow-derived early outgrowth cells (EOCs) are more consistent with an endocrine mode of action, demonstrating not only the presence of antifibrotic factors in the plasma of EOC-treated rats but also that EOC conditioned medium (EOC-CM) potently attenuates both TGF-β- and angiotensin II-induced fibroblast collagen production in vitro. To examine the therapeutic relevance of these findings in vivo, 5/6 subtotally nephrectomized rats, a model of chronic kidney and heart failure characterized by progressive fibrosis of both organs, were randomized to receive i.v. injections of EOC-CM, unconditioned medium, or 10(6) EOCs. Rats that received unconditioned medium developed severe kidney injury with cardiac diastolic dysfunction. In comparison, EOC-CM-treated rats demonstrated substantially improved renal and cardiac function and structure, mimicking the changes found in EOC-treated animals. Mass spectrometric analysis of EOC-CM identified proteins that regulate cellular functions implicated in fibrosis. These results indicate that EOCs secrete soluble factor(s) with highly potent antifibrotic activity, that when injected intravenously replicate the salutary effects of the cells themselves. Together, these findings suggest that an endocrine mode of action may underlie the effectiveness of cell therapy in certain settings and portend the possibility for systemic delivery of cell-free therapy.

  1. Influence of adsorption and deproteination on potential free thyroxine reference methods

    Holm, Steen S; Andreasen, Lisbeth; Hansen, Palle Steen;


    There is a need for consensus concerning reference methods to be used for calibration of commercial free-thyroxine (FT(4)) assays.......There is a need for consensus concerning reference methods to be used for calibration of commercial free-thyroxine (FT(4)) assays....

  2. 21 CFR 862.1685 - Thyroxine-binding globulin test system.


    ... protein which binds thyroxine, in serum and plasma. Measurements obtained by this device are used in the... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Thyroxine-binding globulin test system. 862.1685 Section 862.1685 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN...

  3. Effectiveness of rosiglitazone in reducing flexion contracture in a rabbit model of arthrofibrosis with surgical capsular release

    Barlow, J. D.; Morrey, M. E.; Hartzler, R. U.; Arsoy, D.; Riester, S.; van Wijnen, A. J.; Morrey, B. F.; Sanchez-Sotelo, J.


    Aims Animal models have been developed that allow simulation of post-traumatic joint contracture. One such model involves contracture-forming surgery followed by surgical capsular release. This model allows testing of antifibrotic agents, such as rosiglitazone. Methods A total of 20 rabbits underwent contracture-forming surgery. Eight weeks later, the animals underwent a surgical capsular release. Ten animals received rosiglitazone (intramuscular initially, then orally). The animals were sacrificed following 16 weeks of free cage mobilisation. The joints were tested biomechanically, and the posterior capsule was assessed histologically and via genetic microarray analysis. Results There was no significant difference in post-traumatic contracture between the rosiglitazone and control groups (33° (standard deviation (sd) 11) vs 37° (sd14), respectively; p = 0.4). There was no difference in number or percentage of myofibroblasts. Importantly, there were ten genes and 17 pathways that were significantly modulated by rosiglitazone in the posterior capsule. Discussion Rosiglitazone significantly altered the genetic expression of the posterior capsular tissue in a rabbit model, with ten genes and 17 pathways demonstrating significant modulation. However, there was no significant effect on biomechanical or histological properties. Cite this article: M. P. Abdel. Effectiveness of rosiglitazone in reducing flexion contracture in a rabbit model of arthrofibrosis with surgical capsular release: A biomechanical, histological, and genetic analysis. Bone Joint Res 2016;5:11–17. DOI: 10.1302/2046-3758.51.2000593 PMID:26813567

  4. Longevity and effectiveness of aluminum addition to reduce sediment phosphorus release and restore lake water quality

    Huser, Brian J; Egemose, Sara; Harper, Harvey;


    114 lakes treated with aluminum (Al) salts to reduce internal phosphorus (P) loading were analyzed to identify factors driving longevity of post-treatment water quality improvements. Lakes varied greatly in morphology, applied Al dose, and other factors that may have affected overall treatment...... (OI, a morphological index), and watershed to lake area ratio (related to hydraulic residence time, WA:LA) were the most important variables determining treatment longevity. Multiple linear regression showed that Al dose, WA:LA, and OI explained 47, 32 and 3% respectively of the variation in treatment...

  5. Increased release of brain serotonin reduces vulnerability to ventricular fibrillation in the cat

    Lehnert, Hendrik; Lombardi, Federico; Raeder, Ernst A.; Lorenzo, Antonio V.; Verrier, Richard L.; Lown, Bernard; Wurtman, Richard J.


    The effect of administering the serotonin precursor 5-l-hydroxytryptophan, in conjunction with a monamine oxidase inhibitor phenelzine and a l-amino acid decarboxylase inhibitor carbidopa, on neurochemical changes in the concentrations of serotonin and 5-hydroxyindoleacetic acid (5-HIAA) in the cerebrospinal fluid of the cat were investigated. Results showed that this drug regimen led to increases of serotonin and 5-hydroxyindoleacetic acid (5-HIAA) concentrations in the cerebrospinal fluid by 330 and 830 percent, respectively. Concomitantly, the threshold of ventricular fibrillation was found to be elevated by 42 percent and the effective refractory period was prolonged by 7 percent; the efferent sympathetic neural activity was suppressed in the normal heart. The results indicate that the enhancement of central serotoninergic neurotransmission can reduce the susceptibility of the heart to ventricular fibrillation mediated through a decline in sympathetic neural traffic to the heart.

  6. Management options for reducing the release of antibiotics and antibiotic resistance genes to the environment

    Pruden, Amy; Larsson, D.G. Joakim; Amézquita, Alejandro


    determinants via environmental pathways, with the ultimate goal of extending the useful life span of antibiotics. We also examined incentives and disincentives for action. Methods: We focused on management options with respect to limiting agricultural sources; treatment of domestic, hospital, and industrial......Background: There is growing concern worldwide about the role of polluted soil and water environments in the development and dissemination of antibiotic resistance. Objective: Our aim in this study was to identify management options for reducing the spread of antibiotics and antibiotic resistance...... wastewater; and aquaculture. Discussion: We identified several options, such as nutrient management, runoff control, and infrastructure upgrades. Where appropriate, a cross-section of examples from various regions of the world is provided. The importance of monitoring and validating effectiveness...

  7. Statins potently reduce the cytokine-mediated IL-6 release in SMC/MNC cocultures.

    Loppnow, Harald; Zhang, Li; Buerke, Michael; Lautenschläger, Michael; Chen, Li; Frister, Adrian; Schlitt, Axel; Luther, Tanja; Song, Nan; Hofmann, Britt; Rose-John, Stefan; Silber, Rolf-Edgar; Müller-Werdan, Ursula; Werdan, Karl


    Inflammatory pathways are involved in the development of atherosclerosis. Interaction of vessel wall cells and invading monocytes by cytokines may trigger local inflammatory processes. 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) are standard medications used in cardiovascular diseases. They are thought to have anti-inflammatory capacities, in addition to their lipid-lowering effects. We investigated the anti-inflammatory effect of statins in the cytokine-mediated-interaction-model of human vascular smooth muscle cells (SMC) and human mononuclear cells (MNC). In this atherosclerosis-related inflammatory model LPS (lipopolysaccharide, endotoxin), as well as high mobility group box 1 stimulation resulted in synergistic (i.e. over-additive) IL-6 (interleukin-6) production as measured in ELISA. Recombinant IL-1, tumour necrosis factor-α and IL-6 mediated the synergistic IL-6 production. The standard anti-inflammatory drugs aspirin and indomethacin (Indo) reduced the synergistic IL-6 production by 60%. Simvastatin, atorvastatin, fluvastatin or pravastatin reduced the IL-6 production by 53%, 50%, 64% and 60%, respectively. The inhibition by the statins was dose dependent. Combination of statins with aspirin and/or Indo resulted in complete inhibition of the synergistic IL-6 production. The same inhibitors blocked STAT3 phosphorylation, providing evidence for an autocrine role of IL-6 in the synergism. MNC from volunteers after 5 day aspirin or simvastatin administration showed no decreased IL-6 production, probably due to drug removal during MNC isolation. Taken together, the data show that anti-inflammatory functions (here shown for statins) can be sensitively and reproducibly determined in this novel SMC/MNC coculture model. These data implicate that statins have the capacity to affect atherosclerosis by regulating cytokine-mediated innate inflammatory pathways in the vessel wall.

  8. Controlled-release urea commingled with rice seeds reduced emission of ammonia and nitrous oxide in rice paddy soil.

    Yang, Yuechao; Zhang, Min; Li, Yuncong; Fan, Xiaohui; Geng, Yuqing


    Reduction of ammonia (NH) and nitrous oxide (NO) emission and enhanced nitrogen (N) fertilizer use efficiency have been investigated with different N fertilizer management and application methods for irrigated rice production. Few studies have examined NH and NO emissions from rice paddy soil when commingling controlled release urea with rice seeds. The objective of this study was to assess NH volatilization and NO emission from a novel controlled-release urea formulation (CRU-180) when commingled at the full application rate with seeds in a single application during the preparation of plant plugs at the nursery stage. The experiment was conducted as a factorial design with two fertilizer sources (conventional urea and CRU-180), four rates (0, 100, 200, and 300 kg N ha), and three replicates. The entire amount of CRU-180 was incorporated into each plug with germinated seed. The conventional urea was split into four applications based on the standard practice for fertilizer application. The CRU-180 treatments reduced the NH and NO concentration in the paddy flood water and paddy soil solution as compared with the conventional urea treatments. The percentage of applied N fertilizer emitted as NH volatilization and NO emission in the CRU-180 treatments was only about 10% of that from the conventional urea treatments at the same N application rate. The application of CRU-180 with seeds offers a novel N fertilizer management technique, a method to reduce environmental impacts associated with rice production and the cost of rice production.

  9. Oophorectomy did not show any additional effect on bone density and mineral content in thyroxine treated mice.

    Broulik, P D; Pacovský, V; Límanová, Z


    Experimental hyperthyroidism (thyroxine administration for 21 days) caused a significant decrease in ash mass, bone density and mineral content in the femora of mice, the same degree of reduction in individual measures of bone mass being found in oophorectomized and intact mice treated with thyroxine. It may be suggested that estrogens did not protect the skeleton against the resorbing action of thyroxine or triiodothyronine.

  10. Effect of magnesium sulfate and thyroxine on inflammatory markers in a rat model of hypothyroidism.

    Abbas, Amr M; Sakr, Hussein F


    Inflammation is a major risk factor for cardiovascular complications. Magnesium sulfate (MgSO4) has anti-inflammatory actions. Therefore we investigated the effects of levothyroxine and MgSO4 on inflammatory markers as C-reactive protein (CRP), interleukin-6, tumor necrosis factor-α (TNF-α), intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) in hypothyroid rats. Sixty male rats were divided into 6 groups; normal, normal + MgSO4, hypothyroidism, hypothyroidism + levothyroxine, hypothyroidism + MgSO4, and hypothyroidism + levothyroxine + MgSO4. Thyroxine, triiodothyronine, and thyroid-stimulating hormone (TSH), CRP, interleukin-6, TNF-α, ICAM-1, and VCAM-1 were measured in all rats. Hypothyroidism significantly increased TSH, CRP, interleukin-6, TNF-α, ICAM-1, and VCAM-1 and decreased triiodothronine and thyroxine. Treatment of hypothyroid rats with levothyroxine or MgSO4 significantly decreased CRP, interleukin-6, TNF-α, ICAM-1, and VCAM-1. Combined therapy of hypothyroid rats with levothyroxine and MgSO4 significantly decreased CRP, interleukin-6, TNF-α, ICAM-1, and VCAM-1 compared with hypothyroid rats either untreated or treated with levothyroxine or MgSO4. This study demonstrates that hypothyroid rats have chronic low grade inflammation, which may account for increased risk of cardiovascular diseases. Combined levothyroxine and MgSO4 is better than levothyroxine or MgSO4 alone in alleviating the chronic low grade inflammatory status and therefore reducing the risk of cardiovascular diseases in hypothyroid animals.

  11. Higher free thyroxine levels are associated with frailty in older men: the Health In Men Study.

    Yeap, Bu B; Alfonso, Helman; Chubb, Stephen A Paul; Walsh, John P; Hankey, Graeme J; Almeida, Osvaldo P; Flicker, Leon


    Frailty is common in the elderly and predisposes to ill-health. Some symptoms of frailty overlap those of thyroid dysfunction, but it is unclear whether differences in thyroid status influence risk of frailty. We evaluated associations between thyroid status and frailty in older men. Cross-sectional epidemiological study. Community-dwelling men aged 70-89 years. Circulating thyrotropin (TSH) and free thyroxine (FT(4) ) were assayed. Frailty was assessed as ≥3 of the Fatigue, Resistance, Ambulation, Illnesses and Loss (FRAIL) scale's 5 domains: fatigue; resistance (difficulty climbing flight of stairs); ambulation (difficulty walking 100 m); illness (>5); or weight loss (>5%), blinded to hormone results. Of 3943 men, 27 had subclinical hyperthyroidism, 431 subclinical hypothyroidism and 608 were classified as being frail (15·4%). There was an inverse log-linear association of TSH with FT(4). There was no association between TSH and frailty. After adjusting for covariates, men with FT(4) in the highest two quartiles had increased odds of being frail (Q3:Q1, odds ratio [OR] = 1·32, 95% confidence interval [CI] = 1·01-1·73 and Q4:Q1, OR = 1·36, 95% CI = 1·04-1·79, P = 0·010 for trend). Higher FT(4) was associated with fatigue (P = 0·038) and weight loss (P < 0·001). The association between FT(4) and frailty remained significant when the analysis was restricted to euthyroid men. High-normal FT(4) level is an independent predictor of frailty among ageing men. This suggests that even within the euthyroid range, circulating thyroxine may contribute to reduced physical capability. Further studies are needed to clarify the utility of thyroid function testing and the feasibility of preventing or reversing frailty in older men. © 2012 Blackwell Publishing Ltd.

  12. Alpha-defensins 1-3 release by dendritic cells is reduced by estrogen

    Sperling Rhoda


    Full Text Available Abstract Background During pregnancy the immune system of the mother must protect any activation that may negatively affect the fetus. Changes in susceptibility to infection as well as resolution of some autoimmune disorders represent empirical evidence for pregnancy related alterations in immunity. Sex hormones reach extremely high levels during pregnancy and have been shown to have direct effects on many immune functions including the antiviral response of dendritic cells. Among the immunologically active proteins secreted by monocyte derived DCs (MDDC are the alpha-defensins 1-3. This family of cationic antimicrobial peptides has a broad spectrum of microbicidal activity and has also been shown to link innate to adaptive immunity by attracting T cells and immature DCs, which are essential for initiating and polarizing the immune response. Methods We compare culture-generated monocyte derived DCs (MDDCs with directly isolated myeloid dendritic cells (mDCs and plasmacytoid dendritic cells (pDCs and measure their alpha-defensins 1-3 secretion by ELISA both, in basal situations and after hormone (E2 or PG treatments. Moreover, using a cohort of pregnant women we isolated mDCs from blood and also measure the levels of these anti-microbial peptides along pregnancy. Results We show that mDCs and pDCs constitutively produce alpha-defensins 1-3 and at much higher levels than MDDCs. Alpha-defensins 1-3 production from mDCs and MDDCs but not pDCs is inhibited by E2. PG does not affect alpha-defensins 1-3 in any of the populations. Moreover, alpha-defensins 1-3 production by mDCs was reduced in the later stages of pregnancy in 40% of the patients. Conclusions Here, we demonstrate that mDCs and pDCs secrete alpha-defensins 1-3 and present a novel effect of E2 on the secretion of alpha-defensins 1-3 by dendritic cells.

  13. Pituitary hyperplasia: a complication of the pseudomalabsorption of thyroxine

    Doyle MA


    Full Text Available Mary-Anne Doyle, Heather A Lochnan Division of Endocrinology, University of Ottawa, Ottawa, ON, Canada Objective: “The pseudomalabsorption of thyroxine” has been used to describe patients with hypothyroidism who fail to comply with their treatment. We describe a unique case of a 32-year-old with hypothyroidism who developed pituitary hyperplasia and hyperprolactinemia secondary to the pseudomalabsorption of thyroxine. Investigations and treatment: After baseline thyroid-function tests were performed, the patient was administered levothyroxine 0.5 mg under the supervision of a registered nurse. Thyroid function testing was repeated at 30, 60, 120, and 180 minutes. Arrangements were made for further daily supervised loading of levothyroxine 0.1 mg. Results: With the administration of 0.5 mg levothyroxine, free thyroxine levels increased by 120 minutes, and with daily supervised dosing of 0.1 mg there was normalization of the thyroid hormone levels and a reduction of thyroid-stimulating hormone levels. Maintenance of thyroid-stimulating hormone < 15 mU/L for 2 weeks led to a reduction in prolactin levels and regression in the size of the pituitary on magnetic resonance imaging. Conclusion: If left untreated, these patients face significant morbidity and are at risk of developing pituitary hyperplasia, complications from an increase in pituitary size, hyperprolactinemia, and potentially myxedema coma. Recognizing pituitary hyperplasia and hyperprolactinemia as a complication from the pseudomalabsorption of levothyroxine may prevent the potential of a misdiagnosis of a prolactinoma leading to unnecessary investigations and inappropriate treatment. Patient awareness of this serious complication and the rapid, demonstrable resolution with adequate thyroid hormone replacement may provide motivation to comply with supervised dosing of levothyroxine. It has also been suggested that supervised treatment enables the individual to maintain their patient

  14. Recovery following Thyroxine Treatment Withdrawal, but Not Propylthiouracil, Averts In Vivo and Ex Vivo Thyroxine-Provoked Cardiac Complications in Adult FVB/N Mice

    Nancy S. Saad


    Full Text Available Persistent cardiovascular pathology has been described in hyperthyroid patients even with effective antithyroid treatment. Here, we studied the effect of a well-known antithyroid drug, propylthiouracil (PTU; 20 mg/kg/day, on thyroxine (T4; 500 µg/kg/day-induced increase in blood pressure (BP, cardiac hypertrophy, and altered responses of the contractile myocardium both in vivo and ex vivo after 2 weeks of treatment. Furthermore, the potential recovery through 2 weeks of T4 treatment discontinuation was also investigated. PTU and T4 recovery partially reduced the T4-prompted increase in BP. Alternatively, PTU significantly improved the in vivo left ventricular (LV function with no considerable effects on cardiac hypertrophy or ex vivo right ventricular (RV contractile alterations subsequent to T4 treatment. Conversely, T4 recovery considerably enhanced the T4-provoked cardiac changes both in vivo and ex vivo. Altogether, our data is in agreement with the proposal that hyperthyroidism-induced cardiovascular pathology could persevere even with antithyroid treatments, such as PTU. However, this cannot be generalized and further investigation with different antithyroid treatments should be executed. Moreover, we reveal that recovery following experimental hyperthyroidism could potentially ameliorate cardiac function and decrease the risk for additional cardiac complications, yet, this appears to be model-dependent and should be cautiously construed.

  15. [Once weekly L-thyroxine treatment in non-compliance: A case report].

    Oliver, C; Grino, M; Moatti Vacher-Coponat, P; Morange, I; Retornaz, F


    The non-adherence to substitutive treatment by L-thyroxine is the main cause of the discordance between high thyrotropin values and high doses of the drug. In a 36-year-old patient with post-surgery hypothyroidism, thyrotropin values ranged between 100 and 400 mUI/L, although daily replacement therapy included 300 μg of L-thyroxine and 75 μg of L-triiodothyronine. The oral loading test with L-thyroxine was normal and thyrotropin serum level returned to normal values under weekly oral administration of 1000 μg L-thyroxine. The strategy of non-adherence treatment in hypothyroidism is well defined with oral testing of L-thyroxine, followed by oral or parenteral weekly administration of the drug. The L-thyroxine oral test is the gold standard for diagnosis after eliminating of the other conventional causes: drug interactions or digestive malabsorption. L-thyroxine treatment should be discussed on a case-by-case basis, either daily under surveillance or once weekly oral or parenteral high dose. Copyright © 2017 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  16. The Relationship Between Thyroxine Level and Short Term Clinical Outcome Among Sick Newborn Infants

    Maliheh Kadivar


    Full Text Available Premature and critically sick infants frequently experience several interventions, including blood transfusions, parentral nutrition, and prescriptions during hospitalization that could affect the result of thyroid function test. This study aims to investigate the correlation between thyroxine level and clinical short term outcome among the newborn infants in the neonatal intensive care unit (NICU. We assessed serum levels of thyroxine and thyroid stimulating hormone of 99 neonates who were admitted in the NICU from September 1st 2004 to March 30th 2005. Number of patients with low thyroxin level (less than 6.5 µg/dl was determined and the relation between serum total thyroxine level and birth weight, gestational age, duration of hospitalization, clinical diagnosis, and final outcome was investigated. Short term outcome was considered as duration of hospitalization and discharge alive from hospital. Prevalence of hypothyroxinemia was 26 percent. Later assessment of thyroxine level within 3 weeks revealed normal level of this parameter (8.12 µg/dl ±1.36. Patients with lower gestational age and lower birth weight had lower thyroxine level (7.15 µg/dl ±2.56, and P=0.03, 6.72 µg/dl ±3.03, and P=0.08. Low thyroxine level was not associated with adverse short-term clinical outcome (mortality rates; 3(11% and 9(12%, and duration of hospitalization among 17.7±9.8 vs 16.7± 13.0 in patients with hypothyroxinemia and low thyroxine level respectively. Hypothyroxinemia has considerable prevalence in neonatal intensive care setting and is related with lower birth weight and gestational age. Whether thyroxin levels are a marker or mediator of short term clinical outcome remains to be determined by further studies.

  17. Winter warming delays dormancy release, advances budburst, alters carbohydrate metabolism and reduces yield in a temperate shrub

    Pagter, Majken; Andersen, Uffe Brandt; Andersen, Lillie


    winter warming modifies phenological traits in a woody perennial known to have a large chilling requirement and to be sensitive to spring frost. Warming delayed dormancy release more in the cultivar ‘Narve Viking’ than in the cultivar ‘Titania’, but advanced budburst and flowering predominantly...... in ‘Titania’. Since ‘Narve Viking’ has a higher chilling requirement than ‘Titania’, this indicates that, in high-chillingrequiring genotypes, dormancy responses may temper the effect of warming on spring phenology. Winter Warming significantly reduced fruit yield the following summer in both cultivars...... at elevated temperature showed decreased levels of sucrose in stems of both cultivars and flower buds of ‘Narve Viking’, which, in buds, was associated with increased concentrations of glucose and fructose. Hence, winter warming influences carbohydrate metabolism, but it remains to be elucidated whether...


    Kuznetsova, L A; Derkach, K V; Sharova, T S; Bondareva, V M; Shpakov, A O


    Under obesity, a component of metabolic syndrome (MS), macro- and microcirculation are attenuated, which is associated with abnormalities of NO-dependent cascades and leads to pathology of the cardiovascular system. Among the activators of NO-synthases (NOS), the enzymes catalyzing NO synthesis, are thyroid hormones. Since obesity and MS are characterized by reduced functions, of the thyroid gland, the replacement therapy with thyroid hormones, possessing the properties of vasodilators, is one of approached to restore functioning of the cardiovascular system. However, data on influence of thyroid hormones on NOS activity in obesity are not currently available. The aim of this work was to study the effect of four-week treatment of rats with obesity induced by high-fat diet with L-thyroxine (at a daily dose of 20 mg-kg) on functional activity of total NOS, as well as one endothelial (eNOS) and neuronal (nNOS) isoforms of the enzyme in the brain, myocardium and skeletal muscles of animals. In obese rats the decrease of thyroid hormones level, impaired glucose toleranse, and dyslipidemia were detected. In the myocardium and skeletal muscles of obese rats the activity of total NOS and eNOS was strongly decreased, whereas in the brain the activity of these enzymes was not significantly changed. Long-term treatment of obese rats with thyroxine led to a significant increase in activity of total NOS and eNOS in the myocardium and skeletal muscles and to an increase in activity of total NOS and nNOS in the brain, with the enzyme activity exceeding that in control. In healthy animals treated with thyroxine a significant increase in activity of total NOS and eNOS in the myocardium and skeletal muscles and in activity of total NOS in the brain was also eNOS in the myocardium and skeletal muscles and in activity of total NOS in the brain was also found. A significant contribution to the increasing activity of total NOS in obese rats and healthy animals treated with thyroxine

  19. Hypothalamic corticotropin-releasing factor immunoreactivity is reduced during induction of pituitary tumors by chronic estrogen treatment

    Haas, D.A.; Borgundvaag, B.; Sturtridge, W.C.; George, S.R.


    The role that estrogen plays in the regulation of corticotropin-releasing factor (CRF) is not known. A radioimmunoassay specific for rat CRF was utilized to measure the CRF-like immunoreactivity (CRF-ir) in the hypothalamus of ovariectomized rats treated with estradiol for periods up to 12 weeks. Compared to ovariectomized controls, estradiol treatment resulted in significantly reduced CRF-ir after 3 and 12 weeks, although no significant change was seen after 8 weeks. Anterior pituitary (AP) weight was greatly increased by estradiol treatment at all time points studied. Bromocriptine treatment for the last 3 weeks of the 12-week period, or removal of estradiol for 3 weeks after 9 weeks of treatment did not reverse the changes in CRF-ir even though significant regressions of tumor size was achieved. There was no correlation between AP weight and CRF-ir in individual animals. These data show that chronic treatment with estrogen reduced hypothalamic CRF-ir content. Neither a direct estrogenic effect or an indirect effect mediated through alterations in the adenohypophysis could be ruled out. 21 references, 3 figures.

  20. Thyroxine signal transduction in liver cells involves phospholipase C and phospholipase D activation. Genomic independent action of thyroid hormone

    Krasilnikova Oksana A


    Full Text Available Abstract Background Numerous investigations demonstrate a novel role of thyroid hormone as a modulator of signal transduction. Protein kinase C (PKC is critical to the mechanism by which thyroid hormones potentiate both the antiviral and immunomodulatory actions of IFNγ in different cells and regulate the exchange of signalling phospholipids in hepatocytes. Because nothing is known about accumulation of PKC modulator - diacylglycerol in cells treated with T4, we examined the nongenomic effect of thyroid hormones on DAG formation and phospholipase activation in liver cells. Results The results obtained provide the first demonstration of phospholipase C, phospholipase D and protein kinase C nongenomic activation and diacylglycerol (DAG accumulation by L-T4 in liver cells. The experiments were performed in either the [14C]CH3COOH-labeled rat liver slices or isolated hepatocytes pre-labeled by [14C]oleic acid. L-T4 activates the DAG production in a concentration- and time-dependent manner. DAG formation in stimulated cells is biphasic and short-lived event: there is an initial, rapid rise in DAG concentration and then a slower accumulation that can be sustained for a few minutes. The early phase of L-T4 generated DAG only is accompanied by phosphatidylinositol 4,5-bisphosphate level decrease and inositol 1,4,5-trisphosphate formation while the second phase is abolished by PKC inhibitor l,(5-isoquinolinesulphonyl2methylpiperasine dihydrochloride (H7 and propranolol. The second phase of DAG production is accompanied by free choline release, phosphatidylcholine content drop and phosphatidylethanol (Peth formation. Inhibitor of phospholipase-C-dependent phosphoinositide hydrolysis, neomycin sulfate, reduced the Peth as well as the DAG response to L-T4. Conclusions The present data have indicated the DAG signaling in thyroid hormone-stimulated liver cells. L-thyroxine activates a dual phospholipase pathway in a sequential and synchronized manner

  1. Caveolar disruption causes contraction of rat femoral arteries via reduced basal NO release and subsequent closure of BKCa channels

    AY Al-Brakati


    Full Text Available Background and Purpose. Caveolae act as signalling hubs in endothelial and smooth muscle cells. Caveolar disruption by the membrane cholesterol depleting agent methyl-β-cyclodextrin (M-β-CD has various functional effects on arteries including (i impairment of endothelium-dependent relaxation, and (ii alteration of smooth muscle cell (SMC contraction independently of the endothelium. The aim of this study was to explore the effects of M-β-CD on rat femoral arteries.Methods. Isometric force was measured in rat femoral arteries stimulated to contract with a solution containing 20 mM K+ and 200 nM Bay K 8644 (20 K/Bay K or with one containing 80 mM K+(80 K.Results. Incubation of arteries with M-β-CD (5 mM, 60 min increased force in response to 20 K/Bay K but not that induced by 80 K. Application of cholesterol saturated M-β-CD (Ch-MCD, 5 mM, 50 min reversed the effects of M-β-CD. After mechanical removal of endothelial cells M-β-CD caused only a small enhancement of contractions to 20 K/Bay K. This result suggests M-β-CD acts via altering release of an endothelial-derived vasodilator or vasoconstrictor. When nitric oxide synthase was blocked by pre-incubation of arteries with L-NAME (250 µM the contraction of arteries to 20 K/Bay K was enhanced, and this effect was abolished by pre-treatment with M-β-CD. This suggests M-β-CD is inhibiting endothelial NO release. Inhibition of large conductance voltage- and Ca2+-activated (BKCa channels with 2 mM TEA+ or 100 nM Iberiotoxin (IbTX enhanced 20 K/Bay K contractions. L-NAME attenuated the contractile effect of IbTX, as did endothelial removal.Conclusions. Our results suggest caveolar disruption results in decreased release of endothelial-derived nitric oxide in rat femoral artery, resulting in a reduced contribution of BKCa channels to the smooth muscle cell membrane potential, causing depolarisation and contraction.

  2. Effect on pathogenesis of Keshan disease by change of thyroxine 5’—monodeiodinase activity.


    In this paper, writers investigate the activities of myocardial hepatic and renal thyroxine 5’—monodeiodinase of rats fed with grains from a KD endemic area. The results showed that myocardial ,hepatic and renal

  3. First experience with a new principle for measurement of free serum thyroxine

    Klingler, W.; Ball, P.; Knuppen, R.


    A new test principle for direct measurement of free thyroxine in serum was investigated the technical handling being remarkably simple. In 257 patients (169 euthyroid, 34 hypothyroid, 20 hyperthyroid, 11 pregnant women, 23 newborns) free thyroxine was measured resulting in a normal range of 6.9-18.5 pg/ml. The correlation between fT/sub 4/ and T/sub 4//TBG-ratio was 0.8207.

  4. Effects of growth hormone and thyroxine replacement therapy on insulin signaling in Ames dwarf mice.

    Louis, Audreen; Bartke, Andrzej; Masternak, Michal M


    Ames dwarf (Prop1(df), df/df) mice lack growth hormone (GH), prolactin, and thyrotropin and live remarkably longer than their normal siblings. Significance of reduced activity of the somatotropic and thyroid axes during development and adulthood on longevity are unknown. Because enhanced insulin sensitivity and reduced insulin levels are among likely mechanisms responsible for increased longevity in these mutants, we compared the effects of GH and thyroxine (T4) replacement on various parameters related to insulin signaling in young and old male df/df mice. The results suggest that altered plasma adiponectin and insulin-like growth factor-1 (IGF-1) and hepatic IGF-1, insulin receptor (IR), IR substrate-1, peroxisome proliferator-activated receptor (PPAR) gamma, and PPARgamma coactivator-1 alpha may contribute to increased insulin sensitivity in Ames dwarfs. The stimulatory effect of GH and T4 treatment on plasma insulin and inhibitory effect on expression of hepatic glucose transporter-2 were greater in old than in young dwarfs. These results indicate that GH and T4 treatment has differential impact on insulin signaling during development and adulthood.

  5. Thyroxine modifies the effects of growth hormone in Ames dwarf mice

    Do, Andrew; Menon, Vinal; Zhi, Xu; Gesing, Adam; Wiesenborn, Denise S.; Spong, Adam; Sun, Liou; Bartke, Andrzej; Masternak, Michal M.


    Ames dwarf (df/df) mice lack growth hormone (GH), thyroid stimulating hormone and prolactin. Treatment of juvenile df/df mice with GH alone stimulates somatic growth, reduces insulin sensitivity and shortens lifespan. Early‐life treatment with thyroxine (T4) alone produces modest growth stimulation but does not affect longevity. In this study, we examined the effects of treatment of juvenile Ames dwarf mice with a combination of GH + T4 and compared them to the effects of GH alone. Treatment of female and male dwarfs with GH + T4 between the ages of 2 and 8 weeks rescued somatic growth yet did not reduce lifespan to match normal controls, thus contrasting with the previously reported effects of GH alone. While the male dwarf GH + T4 treatment group had no significant effect on lifespan, the female dwarfs undergoing treatment showed a decrease in maximal longevity. Expression of genes related to GH and insulin signaling in the skeletal muscle and white adipose tissue (WAT) of female dwarfs was differentially affected by treatment with GH + T4 vs. GH alone. Differences in the effects of GH + T4 vs. GH alone on insulin target tissues may contribute to the differential effects of these treatments on longevity. PMID:25935838

  6. Controlled lecithin release from a hierarchical architecture on blood-contacting surface to reduce hemolysis of stored red blood cells.

    Shi, Qiang; Fan, Qunfu; Ye, Wei; Hou, Jianwen; Wong, Shing-Chung; Xu, Xiaodong; Yin, Jinghua


    Hemolysis of red blood cells (RBCs) caused by implant devices in vivo and nonpolyvinyl chloride containers for RBC preservation in vitro has recently gained much attention. To develop blood-contacting biomaterials with long-term antihemolysis capability, we present a facile method to construct a hydrophilic, 3D hierarchical architecture on the surface of styrene-b-(ethylene-co-butylene)-b-styrene elastomer (SEBS) with poly(ethylene oxide) (PEO)/lecithin nano/microfibers. The strategy is based on electrospinning of PEO/lecithin fibers onto the surface of poly [poly(ethylene glycol) methyl ether methacrylate] [P(PEGMEMA)]-modified SEBS, which renders SEBS suitable for RBC storage in vitro. We demonstrate that the constructed 3D architecture is composed of hydrophilic micro- and nanofibers, which transforms to hydrogel networks immediately in blood; the controlled release of lecithin is achieved by gradual dissolution of PEO/lecithin hydrogels, and the interaction of lecithin with RBCs maintains the membrane flexibility and normal RBC shape. Thus, the blood-contacting surface reduces both mechanical and oxidative damage to RBC membranes, resulting in low hemolysis of preserved RBCs. This work not only paves new way to fabricate high hemocompatible biomaterials for RBC storage in vitro, but provides basic principles to design and develop antihemolysis biomaterials for implantation in vivo.

  7. Geniposide ameliorates TNBS-induced experimental colitis in rats via reducing inflammatory cytokine release and restoring impaired intestinal barrier function.

    Xu, Bin; Li, Yan-Li; Xu, Ming; Yu, Chang-Chun; Lian, Meng-Qiao; Tang, Ze-Yao; Li, Chuan-Xun; Lin, Yuan


    Geniposide is an iridoid glycosides purified from the fruit of Gardenia jasminoides Ellis, which is known to have antiinflammatory, anti-oxidative and anti-tumor activities. The present study aimed to investigate the effects of geniposide on experimental rat colitis and to reveal the related mechanisms. Experimental rat colitis was induced by rectal administration of a TNBS solution. The rats were treated with geniposide (25, 50 mg·kg(-1)·d(-1), ig) or with sulfasalazine (SASP, 100 mg·kg(-1)·d(-1), ig) as positive control for 14 consecutive days. A Caco-2 cell monolayer exposed to lipopolysaccharides (LPS) was used as an epithelial barrier dysfunction model. Transepithelial electrical resistance (TER) was measured to evaluate intestinal barrier function. In rats with TNBS-induced colitis, administration of geniposide or SASP significantly increased the TNBS-decreased body weight and ameliorated TNBS-induced experimental colitis and related symptoms. Geniposide or SASP suppressed inflammatory cytokine (TNF-α, IL-1β, and IL-6) release and neutrophil infiltration (myeloperoxidase activity) in the colon. In Caco-2 cells, geniposide (25-100 μmol/L) ameliorated LPS-induced endothelial barrier dysfunction via dose-dependently increasing transepithelial electrical resistance (TER). The results from both in vivo and in vitro studies revealed that geniposide down-regulated NF-κB, COX-2, iNOS and MLCK protein expression, up-regulated the expression of tight junction proteins (occludin and ZO-1), and facilitated AMPK phosphorylation. Both AMPK siRNA transfection and AMPK overexpression abrogated the geniposide-reduced MLCK protein expression, suggesting that geniposide ameliorated barrier dysfunction via AMPK-mediated inhibition of the MLCK pathway. In conclusion, geniposide ameliorated TNBS-induced experimental rat colitis by both reducing inflammation and modulating the disrupted epithelial barrier function via activating the AMPK signaling pathway..

  8. Pregnant women on thyroxine substitution are often dysregulated in early pregnancy.

    Hallengren, Bengt; Lantz, Mikael; Andreasson, Bengt; Grennert, Lars


    Thyroid hormones are important for normal fetal development. Maternal hypothyroidism during early pregnancy is associated with impaired neuropsychological development of children and other adverse outcomes. The primary aim of this prospective study was to determine whether thyroxine-treated pregnant women with hypothyroidism are adequately thyroxine substituted in early pregnancy. A secondary aim was to determine if fetal loss differed between females with thyrotropin (TSH) values within and outside the reference range at their first TSH test, scheduled for 1-2 weeks after verification of pregnancy. This was a prospective open-labeled study. During the years 1997-2002, 119 consecutive pregnancies in 101 females with thyroid diseases were followed at the Department of Endocrinology, Malmö University Hospital. At the first visit, 63 patients, median age 30 years (range 17-45 years), were on thyroxine substitution therapy for hypothyroidism. In these patients 83% were in their first trimester at the time of the initial test. Of the 63 patients on thyroxine substitution for hypothyroidism 32 (51%; Group A) patients had serum TSH values within the reference range at their initial test and 31 (49%; Group B) had serum TSH values outside the reference range. Twelve (19%) had TSH values of 4.0 mIU=l. The fetal loss was 2 of 32 (6%) in Group A compared to 9 of 31 (29%) in Group B ( p pregnant women on thyroxine substitution, serum TSH values were outside the reference range when first tested, generally in the first trimester. Fetal loss was significantly greater in pregnant women with abnormal TSH values compared to those with normal TSH values. Thyroid function in pregnant women on thyroxine substitution should be monitored early in pregnancy and carefully followed during pregnancy. The thyroxine dose should be increased as needed early in pregnancy to avoid hypothyroidism.

  9. Treatment of subclinical hypothyroidism in pregnancy using fixed thyroxine daily doses of 75 μg.

    Penin, Manuel; Trigo, Cristina; López, Yolanda; Barragáns, María


    Treatment of hypothyroid pregnant women is usually calculated based on weight (1 μg/kg/day) and TSH levels. This study assessed the usefulness of treating these women with a fixed dose of 75 μg/day. All women with pregnancy diagnosed from January to August 2012 in the Vigo Health Area (Spain) without previous diagnosis of thyroid disease or thyroxine treatment and with TSH levels over 4,5 mUI/ml were enrolled by consecutive sampling. All 116 women in the sample were treated with a fixed daily dose of thyroxine 75 μg-thyroxine levels were measured at two, four, and six months, and thyroxine dose was modified if TSH level was lower than 0.3 or higher than 4.5 mUI/ml. A woman had a TSH level less than 0.3 mUI/ml in a test; reduction of thyroxine dose to 50 μg/day allowed for maintaining TSH level within the desired range until delivery. Six women had TSH levels over 4.5 mUI/ml in one test; in all of them, increase in thyroxine dose to 100 μg/day allowed for maintaining the level within the desired range until delivery. Fixed daily doses of thyroxine 75 μg allowed for achieving goal TSH levels in most of our pregnant women with subclinical hypothyroidism, irrespective of their weight and baseline TSH level. Copyright © 2013 SEEN. Published by Elsevier Espana. All rights reserved.

  10. Effect of vitamin C in pineapple rind (Ananas comosus L. Merr on thyroxine hormone and anti stress on broilers in tropical region

    Syahruddin E


    Full Text Available This study was aimed to determine the right level of vitamin C in extracted pineapple rind to prevent heat stress effects so it does not interfere with the performance of broiler chickens. This study was done in a series of field experiments. Experiments in the field/cage was biological test of the effect of vitamin C from pineapple rind on production responses (percentage of body weight gain and carcass and physiological responses (thyroxine hormone levels in broiler chicken aged 3 weeks as many as 360 of Strain Arbor acress. The basic design used was CRD 3 x 4 factorial models and 3 replications with 10 chickens for each box, as factor 1: Room temperature (21 : 27 and 33ºC, and factor II: level of vitamin C in the pineapple rind (0:500:1000 and 1500 ppm. The data obtained were statistically analyzed using SAS program package, and if it showed any significant effect then followed by Duncans test/DMRT. Variables measured were body weight gain, carcass percentage and levels of thyroxine hormone of broiler. Results showed that addition of pineapple rind containing 500 ppm vitamin C in the drinking water reduced heat stress in chicken that were kept at temperature of 27ºC, while at 33ºC needed 1000 ppm vitamin C. Both treatments increase level of thyroxine hormone, produce weight gain equal to control, more over, there was no effect on the percentage of carcasses.

  11. Propranolol and verapamil inhibit mRNA expression of RyR2 and SERCA in L-thyroxin-induced rat ventricular hypertrophy

    Xiao-dong WU; De-zai DAI; Qiu-pin ZHANG; Feng GAO


    AIM: To study the alteration in the mRNA level of cardiac ryanodine receptor 2 (RyR2) and sarco-endoplasmic reticulum Ca2+-ATPase (SERCA) in L-thyroxin-induced hypertrophy. METHODS: L-thyroxin (500 g/kg) daily was injected for 10 d. RT-PCR was used to determine mRNA expression. RESULTS: An increase in the relative amount of RyR2 (111%) and SERCA mRNA (65 %) expression was observed in the hypertrophied rats (RyR2:77± 11; SERCA: 87± 10, n=9) compared with the normal rats (RyR2: 36± 10; SERCA: 53± 10, n=9). Propranolol was effective to inhibit the increase in RyR2 (51±7) and SERCA (63±13) mRNA expression in hypertrophied rats,respectively. Verapamil also reduced RyR2 (62±5) and SERCA (75±8) mRNA expression. CONCLUSION: Both RyR2 and SERCA mRNA level in L-thyroxin-induced cardiac hypertrophy was over-expressed and propranolol or verapamil inhibited the alteration.

  12. Serum 25-Hydroxyvitamin D and Parathyroid Hormone Levels in Non-Lactating Women with Post-Partum Thyroiditis: The Effect of L-Thyroxine Treatment.

    Krysiak, Robert; Kowalska, Beata; Okopien, Bogusław


    Vitamin D deficiency seems to be implicated in the onset and progression of some autoimmune disorders. No previous study has investigated vitamin D homeostasis in post-partum thyroiditis. We compared 25-hydroxyvitamin D and parathyroid hormone (PTH) levels between four groups of non-lactating women who gave birth within 12 months before the beginning of the study: hypothyroid women with post-partum thyroiditis (group A; n = 14), euthyroid females with post-partum thyroiditis (group B; n = 14), women with non-autoimmune hypothyroidism (group C; n = 16) and healthy euthyroid females without thyroid autoimmunity (group D; n = 15). In the second part of the study, groups A and C were treated for 6 months with L-thyroxine. Serum levels of 25-hydroxyvitamin D were lower, while PTH higher in patients with post-partum thyroiditis than in patients without thyroid autoimmunity. They were also lower (25-hydroxyvitamin D) or higher (PTH) in group A than in group B, as well as in group C in comparison with group D. L-thyroxine treatment increased 25-hydroxyvitamin D and reduced PTH levels only in hypothyroid women with post-partum thyroiditis. Baseline levels of 25-hydroxyvitamin D correlated with thyroid antibody titres, thyroid function and circulating PTH levels, while the effect of L-thyroxine on serum levels of this vitamin correlated with the changes in thyroid antibody titres and PTH levels. The results of our study suggest the association of vitamin D status with post-partum thyroiditis and L-thyroxine treatment of this disorder.

  13. Distribution of /sup 125/I-thyroxine in different organs and tissues of dietically obese rats

    Hartmann, K.; Voss, C.; Huebner, G. (Ernst-Moritz-Arndt-Universitaet, Greifswald (German Democratic Republic)); Weber, A. (Ernst-Moritz-Arndt-Universitaet, Greifswald (German Democratic Republic). Radiologische Klinik)


    The distribution of /sup 125/I-thyroxine (% dose/g tissue; tissue/plasma radioactivity ratio) was investigated in different tissues of 28-week-old obese Wistar rats. Obesity was induced by high-fat diet (HFD) and confirmed by carcass analysis; in heavy obese animals the relative and absolute fat content is increased twofold and threefold, respectively, compared to control rats fed on a low-fat diet (LFD). Heavy HFD rats exhibit diminished /sup 125/I-T/sub 4/ distribution in the 'slow pool' (fat tissue, muscle) and unchanged values in the 'fast pool' (liver, kidneys) in comparison with LFD rats with low body weight. The differences in distribution presented here are not caused by the diet per se, but they are the consequence of the obesity of the animal, because no differences in the /sup 125/I-T/sub 4/ distribution were found in the /sup 125/I-T/sub 4/ between HFD and LFD rats with relatively equal body weight and body composition. The reduced T/sub 4/ distribution in the fat tissue of obese rats is discussed in connection with possibly decreased lipolysis in this tissue and possible causal participation in the beginning of obesity.

  14. Maternal behavior in transgenic mice with reduced fibroblast growth factor receptor function in gonadotropin-releasing hormone neurons

    Brooks Leah R


    Full Text Available Abstract Background Fibroblast growth factors (FGFs and their receptors (FGFRs are necessary for the proper development of gonadotropin-releasing hormone (GnRH neurons, which are key activators of the hypothalamo-pituitary-gonadal axis. Transgenic mice that have the targeted expression of a dominant negative FGFR (dnFGFR in GnRH neurons (dnFGFR mice have a 30% decrease of GnRH neurons. Additionally, only 30–40% of the pups born to the transgenic dams survive to weaning age. These data raised the possibility that FGFR defects in GnRH neurons could adversely affect maternal behavior via novel mechanisms. Methods We first determined if defective maternal behavior in dnFGFR mothers may contribute to poor pup survival by measuring pup retrieval and a battery of maternal behaviors in primiparous control (n = 10–12 and dnFGFR (n = 13–14 mothers. Other endocrine correlates of maternal behaviors, including plasma estradiol levels and hypothalamic pro-oxyphysin and GnRH transcript levels were also determined using enzyme-linked immunoassay and quantitative reverse transcription polymerase chain reaction, respectively. Results Maternal behaviors (% time crouching with pups, time off pups but not feeding, time feeding, and total number of nesting bouts were not significantly different in dnFGFR mice. However, dnFGFR dams were more likely to leave their pups scattered and took significantly longer to retrieve each pup compared to control dams. Further, dnFGFR mothers had significantly lower GnRH transcripts and circulating E2, but normal pro-oxyphysin transcript levels. Conclusions Overall, this study suggests a complex scenario in which a GnRH system compromised by reduced FGF signaling leads to not only suboptimal reproductive physiology, but also suboptimal maternal behavior.

  15. NIR Light-, Temperature-, pH-, and Redox-Responsive Polymer-Modified Reduced Graphene Oxide/Mesoporous Silica Sandwich-Like Nanocomposites for Controlled Release.

    Wang, Panjun; Chen, Shuo; Cao, Ziquan; Wang, Guojie


    Here a novel quadruple-responsive nanocarrier based on reduced graphene oxide/mesoporous silica sandwich-like nanocomposites (rGO@MS) modified by pH- and temperature-responsive poly(N,N-dimethylaminoethyl methacrylate) (PDMAEMA) with a linker of disulfide was constructed via surface-initiated atom transfer radical polymerization. The polymer chains would be used as gatekeepers to control the release of the loaded cargo molecules under pH, temperature, NIR light and redox stimuli. The cargo molecules (rhodamine B) were demonstrated to release from the polymer-modified nanocomposites triggered by the quadruple-stimuli. It is noted that the release of the loaded rhodamine B from the nanocarriers could be enhanced greatly under the synergistic effect of multiple stimuli. The prepared quadruple-responsive polymer-modified nanocomposites show a bright prospect in the field of smart nanocarriers for controlled release.

  16. Monocarboxylate transporter 8 deficiency: altered thyroid morphology and persistent high triiodothyronine/thyroxine ratio after thyroidectomy.

    Wirth, Eva K; Sheu, Sien-Yi; Chiu-Ugalde, Jazmin; Sapin, Remy; Klein, Marc O; Mossbrugger, Ilona; Quintanilla-Martinez, Leticia; de Angelis, Martin Hrabĕ; Krude, Heiko; Riebel, Thomas; Rothe, Karin; Köhrle, Josef; Schmid, Kurt W; Schweizer, Ulrich; Grüters, Annette


    Thyroid hormone transport across the plasma membrane depends on transmembrane transport proteins, including monocarboxylate transporter 8 (MCT8). Mutations in MCT8 (or SLC16A2) lead to a severe form of X-linked psychomotor retardation, which is characterised by elevated plasma triiodothyronine (T(3)) and low/normal thyroxine (T(4)). MCT8 contributes to hormone release from the thyroid gland. To characterise the potential impact of MCT8-deficiency on thyroid morphology in a patient and in Mct8-deficient mice. Thyroid morphology in a patient carrying the A224V mutation was followed by ultrasound imaging for over 10 years. After thyroidectomy, a histopathological analysis was carried out. The findings were compared with histological analyses of mouse thyroids from the Mct8(-/y) model. We show that an inactivating mutation in MCT8 leads to a unique, progressive thyroid follicular pathology in a patient. After thyroidectomy, histological analysis revealed gross morphological changes, including several hyperplastic nodules, microfollicular areas with stromal fibrosis and a small focus of microfollicular structures with nuclear features reminiscent of papillary thyroid carcinoma (PTC). These findings are supported by an Mct8-null mouse model in which we found massive papillary hyperplasia in 6- to 12-month-old mice and nuclear features consistent with PTC in almost 2-year-old animals. After complete thyroidectomy and substitution with levothyroxine (l-T(4)), the preoperative, inadequately low T(4) and free T(4) remained, while increasing the l-T(4) dosage led to T(3) serum concentrations above the normal range. Our results implicate peripheral deiodination in the peculiar hormonal constellation of MCT8-deficient patients. Other MCT8-deficient patients should be closely monitored for potential thyroid abnormalities.

  17. Potential of l-thyroxine to differentiate osteoblast-like cells via Angiopoietin1.

    Park, See-Hyoung; Lee, Jongsung; Kang, Mi-Ae; Moon, Young Jae; Wang, Sung Il; Kim, Kyoung Min; Park, Byung-Hyun; Jang, Kyu Yun; Kim, Jung Ryul


    Angiogenesis is closely associated with osteoblast differentiation. Previously, we demonstrated that bone formation can be accelerated by treatment with COMP-Angiopoietin1, a known angiogenic factor. Angiopoietin1 (Ang1) is a specific growth factor that generates stable and mature vasculature through the Tie2 receptor. In this study, we aimed to identify a novel drug that can activate endogenous Ang1 expression as a pharmacological treatment for bone formation. Therefore, Ang1 expression was examined in U2OS osteoblast-like cells treated with 770 drugs from a library of Food and Drug Administration (FDA)-approved drugs by using ELISA for Ang1. l-thyroxine was selected as a novel drug candidate. l-Thyroxine is a synthetic form of the hormone thyroxine, which is used to treat patients with hypothyroidism. Enzyme-linked immunosorbent assays (ELISAs) were performed to test whether Ang1 is induced in a dose-dependent manner in human osteoblast-like cell lines, U2OS and MG63. The effects of l-thyroxine on osteoblast differentiation and mineralization were evaluated by alkaline phosphatase (ALP) activity and Alizarin red s staining. To determine the molecular mechanism, the expression of proteins related to bone formation and differentiation, such as type I collagen (COL1A1), osteocalcin (OC), bone sialoprotein (BSP), distal-less homeobox 5 (Dlx5), Runt-related transcription factor 2 (Runx2), osterix (OSX), and ALP, was tested by Western blotting analysis. Consequently, l-thyroxine induced Ang1 expression in a dose-dependent manner in both U2OS and M63 cells, which was confirmed by ELISA and Western blotting. Also, l-thyroxine activated ALP activity in U2OS and MG63 cells as well as ALP expression. Furthermore, l-thyroxine enhanced the expression of COL1A1, Runx2, OC, BSP, Dlx5, and OSX mRNA and proteins. Taken together, we demonstrated that l-thyroxine increased Ang1 expression and induces bone formation, differentiation, and mineralization in U2OS and MG63 cell lines

  18. The effect of thyroxin on hepatic redox equilibrium and lipid metabolism in rats treated with doxorubicin

    Czuba Bartosz


    Full Text Available The main side effects of the administration of doxorubicin, a widely used anticancer drug, is the generation of a reactive oxygen species (ROS in normal cells. As a result, redox disorders and secondary oxidative stress are developed. Doxorubicin ROS generation is attributed to enzymes that are produced abundantly in hepatocytes. Oxidative stress has been a well-known risk factor of doxorubicin-related toxicity. However, in addition, according to the data collected in the last decade, changes in thyroxin status can propagate ROS generation, and, thus, initiate the doxorubicin hepatic effect. Moreover, both compounds have an impact on the cell metabolism. The aim of the study was to verify the thesis that thyroxin can modulate the effect of doxorubicin with regard to redox status and lipid metabolism disorders. In our work, we determined the ratio of NADP+/ NADPH and NAD+/NADH in liver homogenates, blood ketone bodies and triglycerides in the liver and blood in rats treated with doxorubicin and thyroxin. Our results indicate that thyroxin has an insignificant effect on NAD+/NADH, NADP+/NADPH ratios and on hepatic and blood triglycerides. Moreover, thyroxin administration normalized the level of blood ketone bodies that was disturbed by doxorubicin.

  19. Thyroxine reversibly inhibits the uncoupling action of protonophores on energy production in rat thymus lymphocytes.

    Palamarchuk, L A; Mansurova, S E; Starkov, A A


    Earlier we reported that some thyroid and steroid hormones and also 6-ketocholestanol used in micromolar concentrations modulated the effects of protonophoric uncouplers on isolated mitochondria (Starkov et al. (1997) Biochim. Biophys. Acta, 1318, 173-183). In the present study we investigated the effects of a thyroid hormone, thyroxine, on energy coupling of intact rat thymus lymphocytes and mitochondria isolated from these cells. The resting (oligomycin-inhibited) respiration of the isolated intact lymphocytes was stimulated by the addition of protonophoric uncouplers 2,4-DNP, FCCP, or SF6847. Subsequent addition of micromolar concentrations of thyroxin decreased the rate of uncoupler-stimulated respiration and partially reversed uncoupler-induced decrease of membrane potential (DeltaPsi). In experiments with mitochondria isolated from thymus lymphocytes the re-coupling effect of thyroxine was not observed. In this case thyroxine did not influence mitochondrial respiration stimulated with 2,4-DNP, but did potentiate the stimulation of respiration and DeltaPsi decrease induced with another uncoupler, SF6847. The data are discussed in terms of a hypothesis that aromatic uncouplers are transported into the cell by the thyroxine carrier of the plasma membrane.

  20. Free Thyroxine During Early Pregnancy and Risk for Gestational Diabetes.

    James E Haddow

    Full Text Available Several studies have now reported associations between gestational diabetes mellitus (GDM and low free thyroxine (fT4 during the second and third trimesters, but not in the first trimester. The present study further examines relationships between low fT4, maternal weight, and GDM among women in the FaSTER (First and Second Trimester Evaluation of Risk trial, in an effort to determine the extent to which thyroid hormones might contribute to causality. The FaSTER cohort includes 9351 singleton, euthyroid women; 272 of these women were subsequently classified as having GDM. Thyrotropin (TSH, fT4, and thyroid antibodies were measured at 11-14 weeks' gestation (first trimester and 15-18.9 weeks' gestation (second trimester. An earlier report of this cohort documented an inverse relationship between fT4 in the second trimester and maternal weight. In the current analysis, women with GDM were significantly older (32 vs. 28 years and weighed more (75 vs. 64.5 kg. Maternal weight and age (but not TSH were significantly associated univariately with fT4 (dependent variable, in the order listed. Second trimester fT4 odds ratios (OR for GDM were 2.06 [95% CI 1.37-3.09] (unadjusted; and 1.89 [95% CI 1.26-2.84] (adjusted. First trimester odds ratios were not significant: OR 1.45 [95%CI 0.97-2.16] (unadjusted and 1.11 [95% CI 0.74-1.62] (adjusted. The second trimester fT4/GDM relationship thus appeared to strengthen as gestation progressed. In FaSTER, high maternal weight was associated with both low fT4 and a higher GDM rate in the second trimester. Peripheral deiodinase activity is known to increase with high caloric intake (represented by high weight. We speculate that weight-related low fT4 (the metabolically inactive prohormone is a marker for deiodinase activity, serving as a substrate for conversion of fT4 to free triiodothyronine (fT3, the active hormone responsible for glucose-related metabolic activity.

  1. Bentonite and anthracite in alginate-based controlled release formulations to reduce leaching of chloridazon and metribuzin in a calcareous soil.

    Flores Céspedes, F; Pérez García, S; Villafranca Sánchez, M; Fernández Pérez, M


    The leaching of herbicides through soil can be minimized using controlled release formulations (CRFs). In this research, bentonite and anthracite have been used as modifying agents in alginate-based CRFs prepared with chloridazon and metribuzin. These CRFs have been evaluated in a calcareous soil. The Kf and Koc values obtained from sorption experiments in soil have demonstrated a high leaching potential for both herbicides, mainly for metribuzin. Release kinetics in soil have showed that the control of release rate of chloridazon and metribuzin was possible by using bentonite and anthracite in CRFs, being this effect greater when we use anthracite as modifying sorbent. Using an empirical equation, the time taken for 50% of the active ingredient to be released (T50(soil)) was calculated. T50 values ranged between 2.88 d for metribuzin-bentonite alginate-based granules and 14.37 d for chloridazon-anthracite alginate-based granules, being the release rate higher in metribuzin CRFs than in those prepared with chloridazon, which has lower water solubility. Besides, a linear correlation between T50 values in water and soil was obtained. Mobility experiments carried out in a calcareous soil have shown that the use of CRFs reduces the presence of herbicides in the leachate compared to technical products, mainly for chloridazon. We found that one could design a right profile in the release rate of active ingredients from CRFs in each agro-environmental situation, and thus prevent the environmental pollution derived from the use of chloridazon and metribuzin.

  2. Dyslipidemia in subclinical hypothyroidism and the effect of thyroxine on lipid profile

    Ajay Asranna


    Full Text Available Introduction: Subclinical hypothyroidism (SH has a prevalence between 4% and 10.5% in various studies. The burden of SH in India is expected to increase with increasing iodine sufficiency. Studies have shown conflicting results concerning not only the degree of lipid changes in SH but also the effect of thyroxine substitution therapy. Indian studies on dyslipidemia in SH and the effect of thyroxine on lipid profile are currently lacking. Aims and Objectives: (1 To assess the association of SH and lipid profile. (2 To quantify the effect of thyroxine treatment on lipid profile. Materials and Methods: About 54 patients who were detected to have SH were compared with 56 healthy controls. Thyroid stimulating hormone (TSH, free T3, free T4, anti thyroperoxidase (TPO antibodies, total cholesterol, high density lipoprotein (HDL cholesterol, low density lipoprotein (LDL cholesterol, Very low density lipoprotein (VLDL cholesterol, serum triglycerides were measured in all the patients after an overnight fast. Selected patients were started on thyroxine replacement. Twenty-one patients were followed up after 3 months with a repeat lipid profile. Results: Mean total cholesterol and mean LDL levels were significantly higher in SH compared to controls, but there was no statistically significant difference in the mean HDL, VLDL, and triglyceride levels. There was a significant reduction in mean T. cholesterol, mean LDL, mean VLDL, and mean triglyceride levels after treatment with thyroxine, while there was no significant difference among the mean HDL levels. Conclusion: Dyslipidemia is more common in SH compared to controls. There is a TSH dependent increase in cholesterol, LDL, VLDL, and triglyceride levels. Achieving euthyroid status with thyroxine has a favourable effect on lipid profile.

  3. Use of dietary thyroxine as an alternate molting procedure in spent turkey breeder hens.

    Gulde, V A L; Renema, R; Bédécarrats, G Y


    In the turkey industry, molting is traditionally achieved by reducing photoperiod and withdrawing feed and water for several days. Although it is the most effective method, this practice is discouraged in Canada and alternative strategies need to be established. Thyroid hormone levels naturally change during molt, and dietary thyroxine (T4) supplementation was previously shown to induce molt in chickens. This study aimed at evaluating the effectiveness of supplemental dietary T4 in inducing molt in spent turkey breeder hens. One hundred twenty 75-wk-old hens were randomly divided into 4 groups (5 floor pens/replicates, 5 hens each) with the control group kept under a 14-h photoperiod and fed a breeder's diet throughout, whereas hens from the 3 other groups were supplemented with 40 ppm (45.76 mg/kg) T4 for 10 d. One treatment group was maintained under 14 h of light and fed a breeder's diet, whereas the 2 others were subjected to a drop in photoperiod to 6 h during or after supplementation and then were fed a maintenance diet. Egg production, feed intake, BW, molt, and plasma levels of T4, prolactin, and luteinizing hormone were measured. All treated hens ceased laying by d 20; however, several individuals spontaneously returned to lay when left on 14 h of light, suggesting incomplete involution of the reproductive tract. Supplementation significantly reduced feed consumption and induced rapid BW loss. All hens returned to their initial weight by the end of the experiment. Most treated hens initiated molt by d 8 of supplementation and all completed molt by d 37. Plasma T4 in treated hens increased significantly by d 3 (P dropping the photoperiod was necessary to completely reset the reproductive system.

  4. Study on carbon-fixing,oxygen-releasing,temperature-reducing and humidity-increasing effects of evergreen plants in south highway

    LIU Minmin


    Full Text Available Li-6400 portable photosynthesis system,was used to test the diurnal variations of photosynthetic rate and stomatal conductance of evergreen plants in Southern Highway,and to calculate their ability of absorbing carbon dioxide and releasing oxygen and to calculate the transpiring water volume and absorbing heat quantity of plants.Results showed that Euonymus fortunei Hand-Mazz,Hedera helix.Aucuba eriobotryaefolia had better carbon-fixing and oxygen-releasing effects,while Photinia serrulata,Trachycarpus fortunei,Radix Ophiopogonis had worse carbon-fixing and oxygen-releasing effects.Radix Ophiopogonis,Photinia glabra,Euonymus fortunei Hand.-Mazz had higher cooling and humidification ability,while Photinia serrulata,Trachycarpus fortunei did not act as well as them.Euonymus fortunei Hand.-Mazz and Hedera helix had higher leaf chlorophyll in per unit mass,values are 12.91、10.34、9.93 mg·g-1.Radix Ophiopogonis、Cinnamomum camphora(Linn. Presl and Trachycarpus fortunei had lower leaf chlorophyll in per unit mass,value is 3.55、2.67、2.06 mg·g-1.Releasing oxygen,fixing carbon,net assimilation and chlorophyll content has good correlation(P<0.05.

  5. Reduced axonal localization of a Caps2 splice variant impairs axonal release of BDNF and causes autistic-like behavior in mice.

    Sadakata, Tetsushi; Shinoda, Yo; Oka, Megumi; Sekine, Yukiko; Sato, Yumi; Saruta, Chihiro; Miwa, Hideki; Tanaka, Mika; Itohara, Shigeyoshi; Furuichi, Teiichi


    Ca(2)(+)-dependent activator protein for secretion 2 (CAPS2 or CADPS2) potently promotes the release of brain-derived neurotrophic factor (BDNF). A rare splicing form of CAPS2 with deletion of exon3 (dex3) was identified to be overrepresented in some patients with autism. Here, we generated Caps2-dex3 mice and verified a severe impairment in axonal Caps2-dex3 localization, contributing to a reduction in BDNF release from axons. In addition, circuit connectivity, measured by spine and interneuron density, was diminished globally. The collective effect of reduced axonal BDNF release during development was a striking and selective repertoire of deficits in social- and anxiety-related behaviors. Together, these findings represent a unique mouse model of a molecular mechanism linking BDNF-mediated coordination of brain development to autism-related behaviors and patient genotype.

  6. The α7 nicotinic acetylcholine receptor ligands methyllycaconitine, NS6740 and GTS-21 reduce lipopolysaccharide-induced TNF-α release from microglia

    Thomsen, Morten S; Mikkelsen, Jens D


    The anti-inflammatory properties of, particularly the α7, nicotinic acetylcholine receptors (nAChRs) in the peripheral immune system are well documented. There are also reports of anti-inflammatory actions of nicotine in the CNS, but it is unclear, whether this is due to activation or inhibition...... of nAChRs. Here we investigate the mechanisms behind α7 nAChR-mediated modulation of TNF-α release. We show that α7 nAChR agonists or positive allosteric modulators do not affect LPS-induced release of the pro-inflammatory cytokine TNF-α from cultured microglia. This suggests that classical activation...... of, i.e. ion-flux through, the α7 nAChR does not reduce TNF-α release from activated microglia. Contrarily, the α7 nAChR antagonist methyllycaconitine and the weak (...

  7. Different effects of reducing agents on ω-conotoxin GVIA inhibition of [3H]-acetylcholine release from rat cortical slices and guinea-pig myenteric plexus

    Casali, T A A; Gomez, R S; Moraes-Santos, T; Romano-Silva, M A; Prado, M A M; Gomez, M V


    The effect of reducing reagents on ω-conotoxin GVIA (ω-CgTX) inhibition of the release of [3H]-acetylcholine ([3H]-ACh) induced by tityustoxin, K+ 50 mM and electrical stimulation was investigated in rat brain cortical slices.In cortical slices the inhibition of tityustoxin or electrically-stimulated [3H]-ACh release by ω-CgTX was dramatically increased by reducing reagents ascorbate or β-mercaptoethanol. Dehydroascorbic acid did not substitute for ascorbateDepolarization induced by K+ 50 mM caused [3H]-ACh release from cortical slices which was not inhibited by ω-CgTX, even in the presence of ascorbate.In the guinea-pig myenteric plexus, ω-CgTX inhibition of the tityustoxin induced release of [3H]-ACh was independent of ascorbate.It is suggested that N-type-like calcium channels in guinea-pig myenteric plexus may have pharmacological/biochemical diversity from similar channels of rat cerebral cortex. PMID:9117104

  8. Procalcitonin neutralizes bacterial LPS and reduces LPS-induced cytokine release in human peripheral blood mononuclear cells

    Matera Giovanni


    Full Text Available Abstract Background Procalcitonin (PCT is a polypeptide with several cationic aminoacids in its chemical structure and it is a well known marker of sepsis. It is now emerging that PCT might exhibit some anti-inflammatory effects. The present study, based on the evaluation of the in vitro interaction between PCT and bacterial lipopolisaccharide (LPS, reports new data supporting the interesting and potentially useful anti-inflammatory activity of PCT. Results PCT significantly decreased (p Salmonella typhimurium (rough chemotype and Escherichia coli (smooth chemotype. Subsequently, the in vitro effects of PCT on LPS-induced cytokine release were studied in human peripheral blood mononuclear cells (PBMC. When LPS was pre-incubated for 30 minutes with different concentrations of PCT, the release of interleukin-10 (IL-10 and tumor necrosis factor alpha (TNFα by PBMC decreased in a concentration-dependent manner after 24 hours for IL-10 and 4 hours for TNFα. The release of monocyte chemotactic protein-1 (MCP-1 exhibited a drastic reduction at 4 hours for all the PCT concentrations assessed, whereas such decrease was concentration-dependent after 24 hours. Conclusions This study provides the first evidence of the capability of PCT to directly neutralize bacterial LPS, thus leading to a reduction of its major inflammatory mediators.

  9. Impact of selected coagulants and starters on primary proteolysis and amino acid release related to bitterness and structure of reduced-fat Cheddar cheese

    Børsting, Mette Winther; Qvist, Karsten Bruun; Rasmussen, Morten;


    Despite substantial research, it is still difficult to produce high quality reduced-fat Cheddar cheese. The objective of this study was to investigate how two coagulants, bovine chymosin (BC) and camel chymosin (CC) having different proteolytic activities and two starter cultures, an O-culture (O......) and a thermophilic strain of Lactobacillus plus O-culture (OLb) having different abilities to release amino acids, contribute to the structure and flavour development in reduced-fat Cheddar cheese. Cheeses manufactured using the four combinations of coagulants and cultures were analysed during a 28-week ripening...... cheeses with BC had a higher amount of peptides released by chymosin, e. g. the bitter peptide beta-casein (f193-209) or by starter proteases from the chymosin-produced peptide alpha(s1)-CN (f1-23). BC cheeses were also judged to be softer by the sensory panel. Cheeses containing the OLb-culture had...

  10. Thyroxine softgel capsule in patients with gastric-related T4 malabsorption.

    Santaguida, Maria Giulia; Virili, Camilla; Del Duca, Susanna Carlotta; Cellini, Miriam; Gatto, Ilenia; Brusca, Nunzia; De Vito, Corrado; Gargano, Lucilla; Centanni, Marco


    The key role of an intact gastric acid secretion for subsequent intestinal T4 absorption is supported by an increased requirement of thyroxine in patients with gastric disorders. A better pH-related dissolution profile has been described in vitro for softgel T4 preparation than for T4 tablets. Our study was aimed at comparing softgel and tablet T4 requirements in patients with gastric disorders. A total of 37 patients with gastric-related T4 malabsorption were enrolled, but only 31 (28F/3M; median age = 50 years; median T4 dose = 2.04 μg/kg/day) completed the study. All patients were in long-lasting treatment (>2 years) with the same dose of T4 tablets when treatment was switched to a lower dose of softgel T4 capsules (-17 %; p = 0.0002). Assessment of serum FT4 and TSH was carried out at baseline and after 3, 6, 12, and 18 months after the treatment switch. In more than 2/3 of patients (good-responders n = 21), despite the reduced dose of T4, median TSH values were similar at each time point (p = 0.3934) with no change in FT4 levels. In the remaining patients (poor-responders n = 10), TSH levels were significantly higher at each time point than at baseline (p < 0.0001). To note, in five of them intestinal comorbidity was subsequently detected. Comorbidity associated with poor-responders status was the only significant predictor in multivariate analysis (OR = 11.333). Doses of softgel T4 capsules lower than T4 tablet preparation are required to maintain the therapeutic goal in 2/3 of patients with impaired gastric acid secretion.

  11. Treatment with fixed thyroxine doses in pregnant women with subclinical hypothyroidism.

    Seoane Cruz, Inés; Penín Álvarez, Manuel; Luna Cano, Reyes; García-Mayor, Ricardo Víctor


    Hypothyroidism is usually treated with thyroxine doses on patient weight. In some cases, however, fixed doses have proved to useful to normalize TSH levels, which is especially important during pregnancy. Sixty-eight women diagnosed with subclinical hypothyroidism, autoimmune or not, during pregnancy were given a fixed dose of thyroxine 50 mcg/day. TSH measurements were performed to assess the need to change the dose, which was increased or decreased by 25 mcg/day when necessary. With a dose of 50 mcg/day of thyroxine, 42% of patients reached a TSH level less than 3 μU/mL, 79.4% reached a TSH level less than 4.5 μU/mL, and 20.6% had TSH levels higher than 4.5 μU/mL. Our data suggest that a fixed dose of thyroxine 50 mcg/day is inadequate in a significant proportion of pregnancy-diagnosed hypothyroidism regardless of whether the reference of TSH level used is 4.5 or 3 μU/mL. S starting dose of 75 mcg/day is probably more adequate, but studies are needed to evaluate the possibility of overtreatment with such dose. Copyright © 2011 SEEN. Published by Elsevier Espana. All rights reserved.

  12. Preparation of standards of triiodothyronine, thyroxine and thyrotropin; Prepracion de estandares de triyodotironina, tiroxina y tirotrofina

    Lavalley E, C.; Delgado S, B.; Ruiz J, A.; Zambrano A, F


    The standards preparation requires of certain basic principles, some of which are described in this work, which was made with the purpose of establishing the most appropriate conditions for the preparation of standards of triiodothyronine, thyroxine and thyrotropin to be used in radioimmunoanalysis essays. The diverse standards show a balanced displacement, that which is observed in the graphs presented in this work. (Author)


    Nuclear receptor agonists phenobarbital (PB), 3-methylcholanthrene (3MC), pregnenolone-16a-carbonitrile (PCN), 2,2',4,4',5,5'-hexachlorobiphenyl (PCB 153), and 2,2' ,4,4'-tetrabromodiphenyl ether (BDE 47) decrease serum thyroxine (T4) in rats. This decrease is thought to occur th...


    Previous studies demonstrate that in vivo exposure to 2,2',4,4',5,5'-hexachlorobiphenyl (PCB-153) and 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) decrease serum thyroxine (T4) levels in rats. This decrease is thought to occur through the induction of hepatic metabolizing enzymes ...

  15. Effects of hepatic enzyme inducers on thyroxine (T4) catabolism in primary rat hepatocytes

    Nuclear receptor agonists such as phenobarbital (PB), 2,2',4,4',5,5'-hexachlorobiphenyl (PCB 153), and 3-methylcholantrene (3-MC) decrease circulating thyroxine (T4) concentrations in rats. It is suspected that this decrease occurs through the induction of hepatic metabolizing en...


    Nuclear receptor agonists such as 3-methylcholantrene (3-MC), phenobarbital (PB), 2,2',4,4',5,5'-hexachlorobiphenyl (PCB 153), and, pregnenolone-16a-carbonitrile (PCN) decrease serum thyroxine (T4) concentrations in rats. It appears that this decrease occurs through the induction...

  17. Maternal Thyroxine Levels During Pregnancy and Outcomes of Cognitive Development in Children.

    Wang, Pingping; Gao, Jian; Zhao, Shihua; Guo, Yong; Wang, Zengfang; Qi, Feng


    Though there were many studies assessing the relationship between maternal thyroxine levels during pregnancy and cognitive development in children, there was still lack of evidence for the association from a comprehensive assessment of published data. To get a more comprehensive estimate of the influence of low maternal thyroxine levels on cognitive function, a meta-analysis of prospective cohort studies was performed. Two electronic databases, MEDLINE and EMBASE, were searched for relevant prospective cohort studies. Relative risks (RR) with 95% confidence intervals (95% CI) were pooled using random-effect model of meta-analysis to assess the risk of delayed cognitive development in children. Seven prospective cohort studies with a total of 8273 mother-child pairs were included into the meta-analysis. There was obvious between-study heterogeneity in the meta-analysis (I(2) = 69.6%). Meta-analysis of using random-effect model showed that low maternal thyroxine level was significantly associated with a threefold risk of delayed cognitive development in children (random RR = 3.08, 95% CI 1.83-5.18, P cognitive development in children (random RR = 3.76, 95% CI 2.14-6.58, P cognitive development in children. Low maternal thyroxine level is significantly associated with a threefold risk of delayed cognitive development in children.

  18. Proposal of a candidate international conventional reference measurement procedure for free thyroxine in serum.

    Thienpont, L.M.; Beastall, G.H.; Christofides, N.D.; Faix, J.D.; Ieiri, T.; Jarrige, V.; Miller, W.G.; Miller, R.; Nelson, J.C.; Ronin, C.; Ross, H.A.; Rottmann, M.; Thijssen, J.H.; Toussaint, B.


    In the present paper the IFCC WG-STFT recommends and provides the rationale to establish metrological traceability of serum free thyroxine (FT4) measurements to a candidate international conventional reference measurement procedure. It is proposed that this procedure be based on equilibrium dialysis

  19. Establishment of an Enzyme Linked Immunosorbent Assay for Total Thyroxine (T4)


    A sensitive and specific ELISA for total thyroxine (T4) is established. The anti-T4 antibody is coatedon the microtiter plate, the T4 antigen is conjugated to the biotin. The label is horseradish peroxidase(HRP)

  20. Triclosan Decreases Rat Thyroxine: Mode-of-Action, Developmental Susceptibility and Human Relevance

    Triclosan (TCS) decreases serum thyroxine (T4) in the rat. In vivo and in vitro approaches were used to address three uncertainties: by what mode-of-action (MOA) does TCS decrease T4; does TCS decrease T4 developmentally; and, are effects observed in rats relevant to humans? To t...

  1. Impact of adjusting for the reciprocal relationship between maternal weight and free thyroxine during early pregnancy.

    Haddow, James E


    Among euthyroid pregnant women in a large clinical trial, free thyroxine (FT4) measurements below the 2.5th centile were associated with a 17 lb higher weight (2.9 kg\\/m(2)) than in the overall study population. We explore this relationship further.

  2. Long-term sustained release of salicylic acid from cross-linked biodegradable polyester induces a reduced foreign body response in mice.

    Chandorkar, Yashoda; Bhaskar, Nitu; Madras, Giridhar; Basu, Bikramjit


    There has been a continuous surge toward developing new biopolymers that exhibit better in vivo biocompatibility properties in terms of demonstrating a reduced foreign body response (FBR). One approach to mitigate the undesired FBR is to develop an implant capable of releasing anti-inflammatory molecules in a sustained manner over a long time period. Implants causing inflammation are also more susceptible to infection. In this article, the in vivo biocompatibility of a novel, biodegradable salicylic acid releasing polyester (SAP) has been investigated by subcutaneous implantation in a mouse model. The tissue response to SAP was compared with that of a widely used biodegradable polymer, poly(lactic acid-co-glycolic acid) (PLGA), as a control over three time points: 2, 4, and 16 weeks postimplantation. A long-term in vitro study illustrates a continuous, linear (zero order) release of salicylic acid with a cumulative mass percent release rate of 7.34 × 10(-4) h(-1) over ∼1.5-17 months. On the basis of physicochemical analysis, surface erosion for SAP and bulk erosion for PLGA have been confirmed as their dominant degradation modes in vivo. On the basis of the histomorphometrical analysis of inflammatory cell densities and collagen distribution as well as quantification of proinflammatory cytokine levels (TNF-α and IL-1β), a reduced foreign body response toward SAP with respect to that generated by PLGA has been unambiguously established. The favorable in vivo tissue response to SAP, as manifest from the uniform and well-vascularized encapsulation around the implant, is consistent with the decrease in inflammatory cell density and increase in angiogenesis with time. The above observations, together with the demonstration of long-term and sustained release of salicylic acid, establish the potential use of SAP for applications in improved matrices for tissue engineering and chronic wound healing.

  3. Initial catch-up growth in children with hypothyroidism on thyroxine replacement therapy

    Rajitha D


    Full Text Available Background: There is a paucity of observational data from India on initial catch up growth in hypothyroid children started on thyroxine replacement therapy. Methods: We retrospectively studied 44 children and adolescents (32 girls with a diagnosis of primary hypothyroidism i.e., (thyrotropin > 15 µIU/mL and thyroxine < 55ng/mL. All were started on treatment with oral thyroxine. The dose was adjusted to maintain thyrotropin between 0.5-5 µIU/mL. Height was measured at baseline and at each follow-up visit and height standard deviation scores (HtSDS were calculated. We studied the therapeutic benefit of thyroxine replacement therapy on growth in the initial couple of years of treatment. Results: Dose of thyroxine required to restore euthyroidism was 4.1±2.5 µg/kg body weight. The dose fell from 9.7±2.4 µg/kg body weight in infants to 3.0±1.5 µg/kg body weight in adolescence (p<0.001. Likewise, the dose per unit body surface area also fell consistently from 207 ± 70.3 µg/m2 in infants to only 89.3±17.9 µg/m2 in adolescents (p<0.001. The initial HtSDS was 2.0±1.5 and this improved by 0.4 to final value of 1.6±1.3 (p < 0.001 after an average follow up of 14.1±2.5 months. The mean catch-up growth velocity, weighted for the duration of follow-up was 7.7 cm/year. Conclusions: The HtSDS deficit because of hypothyroidism is partially regained in the first few years after treatment.

  4. Thyroid function in children and adolescents with Hashimoto's thyroiditis after l-thyroxine discontinuation.

    Radetti, Giorgio; Salerno, Mariacarolina; Guzzetti, Chiara; Cappa, Marco; Corrias, Andrea; Cassio, Alessandra; Cesaretti, Graziano; Gastaldi, Roberto; Rotondi, Mario; Lupi, Fiorenzo; Fanolla, Antonio; Weber, Giovanna; Loche, Sandro


    Thyroid function may recover in patients with Hashimoto's thyroiditis (HT). To investigate thyroid function and the need to resume l-thyroxine treatment after its discontinuation. Nine Italian pediatric endocrinology centers. 148 children and adolescents (25 m and 123 f) with HT on treatment with l-thyroxine for at least one year. Treatment was discontinued in all patients, and serum TSH and fT4 concentrations were measured at the time of treatment discontinuation and then after 2, 6, 12 and 24 months. Therapy with l-thyroxine was re-instituted when TSH rose >10 U/L and/or fT4 was below the normal range. The patients were followed up when TSH concentrations were between 5 and 10 U/L and fT4 was in the normal range. At baseline, TSH was in the normal range in 139 patients, and was between 5 and 10 U/L in 9 patients. Treatment was re-instituted after 2 months in 37 (25.5%) patients, after 6 months in 13 patients (6.99%), after 12 months in 12 patients (8.6%), and after 24 months in an additional 3 patients (3.1%). At 24 months, 34 patients (34.3%) still required no treatment. TSH concentration >10 U/L at the time of diagnosis was the only predictive factor for the deterioration of thyroid function after l-thyroxine discontinuation. This study confirms that not all children with HT need life-long therapy with l-thyroxine, and the discontinuation of treatment in patients with a TSH level L at the time of diagnosis should be considered. © 2017 The authors.

  5. The effect of phenobarbital on the metabolism and excretion of thyroxine in rats

    McClain, R.M.; Levin, A.A.; Posch, R.; Downing, J.C.


    The effect of phenobarbital on thyroid function and the metabolism and biliary excretion of thyroxine in rats was determined. Phenobarbital, administered for 2 weeks at a dose of 100 mg/kg/day, resulted in an increase in hepatic and thyroid gland weights, decreased circulating levels of T4, T3 and rT3, and increased TSH levels in male and female rats. After 3 months of treatment liver and thyroid weights were still increased; however, hormone values were not as markedly affected indicating that the rats had partially compensated for the effect on thyroid function. In thyroidectomized rats the plasma clearance of thyroxine was increased with phenobarbital. In bile duct cannulated phenobarbital-treated male rats the hepatic uptake at 4 hr was markedly increased. Bile flow was increased and the 4-hr cumulative biliary excretion of administered radioactivity was increased by 42%. Most of the increase in the excretion (76%) was accounted for by an increase in the excretion of thyroxine-glucuronide in phenobarbital-treated rats. Hepatic thyroxine-glucuronyltransferase activity in phenobarbital-treated rats expressed as picomoles per milligram of protein was increased by 40%; enzyme activity per gram of liver was increased by about twofold which, coupled with increased hepatic weight, resulted in about a threefold increase in total hepatic thyroxine-glucuronyltransferase activity in phenobarbital-treated rats as compared to that of controls. Qualitatively similar effects on metabolism, excretion, and enzyme induction were noted in female rats; however, the magnitude of increase was less than that observed in male rats. It is concluded that the effect of phenobarbital on thyroid function in rats is primarily a result of its effects on the hepatic disposition of thyroid hormone.

  6. Thyroid function in children and adolescents with Hashimoto’s thyroiditis after l-thyroxine discontinuation

    Giorgio Radetti


    Full Text Available Objective: Thyroid function may recover in patients with Hashimoto’s thyroiditis (HT. Design: To investigate thyroid function and the need to resume l-thyroxine treatment after its discontinuation. Setting: Nine Italian pediatric endocrinology centers. Patients: 148 children and adolescents (25 m and 123 f with HT on treatment with l-thyroxine for at least one year. Intervention and main outcome measure: Treatment was discontinued in all patients, and serum TSH and fT4 concentrations were measured at the time of treatment discontinuation and then after 2, 6, 12 and 24 months. Therapy with l-thyroxine was re-instituted when TSH rose >10 U/L and/or fT4 was below the normal range. The patients were followed up when TSH concentrations were between 5 and 10 U/L and fT4 was in the normal range. Results: At baseline, TSH was in the normal range in 139 patients, and was between 5 and 10 U/L in 9 patients. Treatment was re-instituted after 2 months in 37 (25.5% patients, after 6 months in 13 patients (6.99%, after 12 months in 12 patients (8.6%, and after 24 months in an additional 3 patients (3.1%. At 24 months, 34 patients (34.3% still required no treatment. TSH concentration >10 U/L at the time of diagnosis was the only predictive factor for the deterioration of thyroid function after l-thyroxine discontinuation. Conclusions: This study confirms that not all children with HT need life-long therapy with l-thyroxine, and the discontinuation of treatment in patients with a TSH level <10 U/L at the time of diagnosis should be considered.

  7. Controlling Heat Release from a Close-Packed Bisazobenzene-Reduced-Graphene-Oxide Assembly Film for High-Energy Solid-State Photothermal Fuels.

    Zhao, Xiaoze; Feng, Yiyu; Qin, Chengqun; Yang, Weixiang; Si, Qianyu; Feng, Wei


    A closed-cycle system for light-harvesting, storage, and heat release is important for utilizing and managing renewable energy. However, combining a high-energy, stable photochromic material with a controllable trigger for solid-state heat release remains a great challenge for developing photothermal fuels (PTFs). This paper presents a uniform PTF film fabricated by the assembly of close-packed bisazobenzene (bisAzo) grafted onto reduced graphene oxide (rGO). The assembled rGO-bisAzo template exhibited a high energy density of 131 Wh kg(-1) and a long half-life of 37 days owing to inter- or intramolecular H-bonding and steric hindrance. The rGO-bisAzo PTF film released and accumulated heat to realize a maximum temperature difference (DT) of 15 °C and a DT of over 10 °C for 30 min when the temperature difference of the environment was greater than100 °C. Controlling heat release in the solid-state assembly paves the way to develop highly efficient and high-energy PTFs for a multitude of applications.

  8. The type 2 diabetes associated minor allele of rs2237895 KCNQ1 associates with reduced insulin release following an oral glucose load.

    Johan Holmkvist

    Full Text Available BACKGROUND: Polymorphisms in the potassium channel, voltage-gated, KQT-like subfamily, member 1 (KCNQ1 have recently been reported to associate with type 2 diabetes. The primary aim of the present study was to investigate the putative impact of these KCNQ1 polymorphisms (rs2283228, rs2237892, rs2237895, and rs2237897 on estimates of glucose stimulated insulin release. METHODOLOGY/PRINCIPAL FINDINGS: Genotypes were examined for associations with serum insulin levels following an oral glucose tolerance test (OGTT in a population-based sample of 6,039 middle-aged and treatment-naïve individuals. Insulin release indices estimated from the OGTT and the interplay between insulin sensitivity and insulin release were investigated using linear regression and Hotelling T2 analyses. Applying an additive genetic model the minor C-allele of rs2237895 was associated with reduced serum insulin levels 30 min (mean+/-SD: (CC 277+/-160 vs. (AC 280+/-164 vs. (AA 299+/-200 pmol/l, p = 0.008 after an oral glucose load, insulinogenic index (29.6+/-17.4 vs. 30.2+/-18.7vs. 32.2+/-22.1, p = 0.007, incremental area under the insulin curve (20,477+/-12,491 vs. 20,503+/-12,386 vs. 21,810+/-14,685, p = 0.02 among the 4,568 individuals who were glucose tolerant. Adjustment for the degree of insulin sensitivity had no effect on the measures of reduced insulin release. The rs2237895 genotype had a similar impact in the total sample of treatment-naïve individuals. No association with measures of insulin release were identified for the less common diabetes risk alleles of rs2237892, rs2237897, or rs2283228. CONCLUSION: The minor C-allele of rs2237895 of KCNQ1, which has a prevalence of about 42% among Caucasians was associated with reduced measures of insulin release following an oral glucose load suggesting that the increased risk of type 2 diabetes, previously reported for this variant, likely is mediated through an impaired beta cell function.

  9. The minor C-allele of rs2014355 in ACADS is associated with reduced insulin release following an oral glucose load

    Pisinger Charlotta


    Full Text Available Abstract Background A genome-wide association study (GWAS using metabolite concentrations as proxies for enzymatic activity, suggested that two variants: rs2014355 in the gene encoding short-chain acyl-coenzyme A dehydrogenase (ACADS and rs11161510 in the gene encoding medium-chain acyl-coenzyme A dehydrogenase (ACADM impair fatty acid β-oxidation. Chronic exposure to fatty acids due to an impaired β-oxidation may down-regulate the glucose-stimulated insulin release and result in an increased risk of type 2 diabetes (T2D. We aimed to investigate whether the two variants associate with altered insulin release following an oral glucose load or with T2D. Methods The variants were genotyped using KASPar® PCR SNP genotyping system and investigated for associations with estimates of insulin release and insulin sensitivity following an oral glucose tolerance test (OGTT in a random sample of middle-aged Danish individuals (nACADS = 4,324; nACADM = 4,337. The T2D-case-control study involved a total of ~8,300 Danish individuals (nACADS = 8,313; nACADM = 8,344. Results In glucose-tolerant individuals the minor C-allele of rs2014355 of ACADS associated with reduced measures of serum insulin at 30 min following an oral glucose load (per allele effect (β = -3.8% (-6.3%;-1.3%, P = 0.003, reduced incremental area under the insulin curve (β = -3.6% (-6.3%;-0.9%, P = 0.009, reduced acute insulin response (β = -2.2% (-4.2%;0.2%, P = 0.03, and with increased insulin sensitivity ISIMatsuda (β = 2.9% (0.5%;5.2%, P = 0.02. The C-allele did not associate with two other measures of insulin sensitivity or with a derived disposition index. The C-allele was not associated with T2D in the case-control analysis (OR 1.07, 95% CI 0.96-1.18, P = 0.21. rs11161510 of ACADM did not associate with any indices of glucose-stimulated insulin release or with T2D. Conclusions In glucose-tolerant individuals the minor C-allele of rs2014355 of ACADS was associated with reduced

  10. Nicotine-stimulated release of [3H]norepinephrine is reduced in the hippocampus of an animal model of attention-deficit/hyperactivity disorder, the spontaneously hypertensive rat.

    Sterley, Toni-Lee; Howells, Fleur M; Russell, Vivienne A


    Attention-deficit/hyperactivity disorder (ADHD) is a heterogeneous, developmental disorder, and is one of the most common child-psychiatric disorders. It is also a risk factor for early smoking and adult nicotine dependence. Nicotine has been shown to improve symptoms associated with ADHD, including problems with attention, working memory and response inhibition. Norepinephrine, a neurotransmitter involved in attention, is highly implicated in ADHD, and often targeted in the treatment thereof. In the present study we investigated nicotine׳s effect on release of norepinephrine in the hippocampus of a validated rat model of ADHD, the spontaneously hypertensive rat (SHR), as well as in two control strains: Wistar-Kyoto rats (WKY) and Sprague-Dawley rats (SD). Hippocampal slices obtained from male SHR, WKY and SD (postnatal day 31-33) were pre-incubated with radioactively labelled norepinephrine ([3H]NE) and perfused with buffer. The slices were stimulated by exposure to different concentrations of nicotine (1, 10, 100 or 1000 µM) for 1 min at 2 intervals (S1 and S2, separated by 20 min). Following a 10 min wash, slices were stimulated with 25 mM potassium. Since glutamate and GABA receptor function differ in SHR and WKY, we investigated the possible involvement of AMPA and GABA(A) receptors in nicotine (100 µM)-stimulated release of hippocampal [3H]NE in each of the strains by blocking these receptors with CNQX (AMPA receptor antagonist, 10 µM) or bicuculline (GABAA receptor antagonist, 30 µM) respectively. Nicotine-stimulated release (S1) of [3H]NE from SHR hippocampal slices was less than that of WKY and SD, at 100 µM and 1000 µM nicotine, suggesting reduced density and/or function of nicotinic receptors in SHR hippocampus. Nicotine-stimulated release of [3H]NE in response to S2 was reduced compared to S1 in all strains, indicating desensitization of receptors involved in stimulation of [3H]NE by nicotine. Potassium-stimulated release of [3H]NE following the

  11. Roles of MgO release from polyethylene glycol 6000-based solid dispersions on microenvironmental pH, enhanced dissolution and reduced gastrointestinal damage of telmisartan.

    Tran, Phuong Ha-Lien; Tran, Thao Truong-Dinh; Lee, Seung Aeon; Nho, Vo Hong; Chi, Sang-Cheol; Lee, Beom-Jin


    The roles of magnesium oxide (MgO) release from solid dispersions (SDs) in simulated gastric fluid (SGF), simulated intestinal fluid (SIF) and water were investigated to elucidate the enhanced dissolution and reduced intestinal damages of telmisartan as a model drug. The polyethylene glycol 6000 (PEG 6000) was used to prepare the SDs. Three SDs were prepared: SD1 (PEG, MgO, TEL), SD2 (PEG 6000, TEL), SD3 (MgO, TEL). The physical mixture (PM) consisting of SD2 and MgO was also prepared. A binary SD without MgO (SD2) was also prepared for comparison in microenvironmental pH (pH(M)) modulation. The faster MgO released, the less control of pH(M) and the less enhanced dissolution of TEL were in consequences. SD3 increased dissolution in SIF and water (about 67%). Interestingly, ternary SD1 showed almost complete dissolution in all three media but dissolution of PM was the lowest due to the fast release of MgO and poor modulation of pH(M). MgO did not change the drug crystallinity but did have a strong molecular interaction with the drug. Additionally, the SD3-bearing tablet quickly increased pH(M) but then gradually decreased due to faster release of MgO while the SD1-bearing tablet gradually increased pH(M) at all fractional dimensions of the tablet by the MgO slowly released. The pH(M) of PM-bearing tablets was not varied as a function of time. Thus, the MgO-bearing SD1 also minimized gastrointestinal tissue damage caused by the model drug.

  12. Protolichesterinic acid, isolated from the lichen Cetraria islandica, reduces LRRC8A expression and volume-sensitive release of organic osmolytes in human lung epithelial cancer cells

    Thorsteinsdottir, Unnur Arna; Thorsteinsdottir, Margret; Lambert, Ian Henry


    We have tested the effect of protolichesterinic acid (PA) on the activity of the volume-sensitive release pathway for the organic osmolyte taurine (VSOAC) and the expression of the leucine-rich-repeat-channel 8A (LRRC8A) protein, which constitutes an essential VSOAC component. Exposing human lung...... of apoptosis) and p21 (regulator of cell cycle progression), respectively. PA reduces cell viability by 30% but has no effect on p21/Bax expression. This excludes PA as a pro-apoptotic drug in A549 cells....... cancer cells (A549) to PA (20 μg/mL, 24 h) reduces LRRC8A protein expression by 25% and taurine release following osmotic cell swelling (320 → 200 mOsm) by 60%. C75 (20 μg/mL, 24 h), a γ-lactone with a C8 carbon fatty acid chain, reduces VSOAC activity by 30%, i.e. less than PA. Stearic acid (20 μg......, excluding that PA mediated inhibition of VSOAC involves 5-LO inhibition. A549 cells exposed to the chemotherapeutic drug cisplatin (10 μM, 24 h) reveal signs of apoptosis, i.e. 25% reduction in cell viability as well as 1.3-, 1.5- and 3.3-fold increase in the expression of LRRC8A, Bax (regulator...

  13. Effectiveness of rosiglitazone in reducing flexion contracture in a rabbit model of arthrofibrosis with surgical capsular release: A biomechanical, histological, and genetic analysis.

    Barlow, J D; Morrey, M E; Hartzler, R U; Arsoy, D; Riester, S; van Wijnen, A J; Morrey, B F; Sanchez-Sotelo, J; Abdel, M P


    Animal models have been developed that allow simulation of post-traumatic joint contracture. One such model involves contracture-forming surgery followed by surgical capsular release. This model allows testing of antifibrotic agents, such as rosiglitazone. A total of 20 rabbits underwent contracture-forming surgery. Eight weeks later, the animals underwent a surgical capsular release. Ten animals received rosiglitazone (intramuscular initially, then orally). The animals were sacrificed following 16 weeks of free cage mobilisation. The joints were tested biomechanically, and the posterior capsule was assessed histologically and via genetic microarray analysis. There was no significant difference in post-traumatic contracture between the rosiglitazone and control groups (33° (standard deviation (sd) 11) vs 37° (sd14), respectively; p = 0.4). There was no difference in number or percentage of myofibroblasts. Importantly, there were ten genes and 17 pathways that were significantly modulated by rosiglitazone in the posterior capsule. Rosiglitazone significantly altered the genetic expression of the posterior capsular tissue in a rabbit model, with ten genes and 17 pathways demonstrating significant modulation. However, there was no significant effect on biomechanical or histological properties.Cite this article: M. P. Abdel. Effectiveness of rosiglitazone in reducing flexion contracture in a rabbit model of arthrofibrosis with surgical capsular release: A biomechanical, histological, and genetic analysis. Bone Joint Res 2016;5:11-17. doi: 10.1302/2046-3758.51.2000593. © 2016 Abdel et al.

  14. The Type 2 Diabetes Associated Minor Allele of rs2237895 KCNQ1 Associates with Reduced Insulin Release Following an Oral Glucose Load

    Brunak, Søren; Holmkvist, J; Banasik, K


    , and rs2237897) on estimates of glucose stimulated insulin release. METHODOLOGY/PRINCIPAL FINDINGS: Genotypes were examined for associations with serum insulin levels following an oral glucose tolerance test (OGTT) in a population-based sample of 6,039 middle-aged and treatment-naïve individuals. Insulin......+/-SD: (CC) 277+/-160 vs. (AC) 280+/-164 vs. (AA) 299+/-200 pmol/l, p = 0.008) after an oral glucose load, insulinogenic index (29.6+/-17.4 vs. 30.2+/-18.7vs. 32.2+/-22.1, p = 0.007), incremental area under the insulin curve (20,477+/-12,491 vs. 20,503+/-12,386 vs. 21,810+/-14,685, p = 0.02) among the 4......,568 individuals who were glucose tolerant. Adjustment for the degree of insulin sensitivity had no effect on the measures of reduced insulin release. The rs2237895 genotype had a similar impact in the total sample of treatment-naïve individuals. No association with measures of insulin release were identified...

  15. Thyrotoxic periodic paralysis due to excessive L-thyroxine replacement in a Caucasian man.

    Hannon, M J


    Thyrotoxic periodic paralysis is a potentially fatal complication of hyperthyroidism, more common in Asian races, which is defined by a massive intracellular flux of potassium. This leads to profound hypokalaemia and muscle paralysis. Although the paralysis is temporary, it may be lethal if not diagnosed and treated rapidly, as profound hypokalaemia may induce respiratory muscle paralysis or cardiac arrest. The condition is often misdiagnosed in the west due to its comparative rarity in Caucasians; however it is now increasingly described in Caucasians and is also being seen with increasing frequency in western hospitals due to increasing immigration and population mobility. Here we describe the case of a patient with panhypopituitarism due to a craniopharyngioma, who developed thyrotoxic periodic paralysis due to excessive L-thyroxine replacement. This disorder has been described in Asian subjects but, to our knowledge, thyrotoxic periodic paralysis secondary to excessive L-thyroxine replacement has never been described in Caucasians.

  16. Retina maturation following administration of thyroxine in developing rats: effects on polyamine metabolism and glutamate decarboxylase.

    Macaione, S; Di Giorgio, R M; Nicotina, P A; Ientile, R


    The effects of subcutaneous daily treatment with thyroxine on cell proliferation, differentiation, polyamines, and gamma-aminobutyric acid metabolism in the rat retina were studied during the first 20 postnatal days. The retinal layers of the treated rats displayed an enhanced cell differentiation which reached its maximum 9-12 days from birth; but this effect stopped very quickly and was finished by the 20th postnatal day. Primarily there was an increase in ornithine decarboxylase activity which was accompanied by an increase in putrescine, spermidine, and spermine levels. S-Adenosylmethionine decarboxylase was induced later than ODC; corresponding with the enhanced synaptogenesis, glutamate decarboxylase increased 15-fold between the fourth and 15th days. Our data are consistent with the hypothesis that thyroxine may exert some of its effects by inducing the enzymes which regulate polyamine metabolism and synaptogenesis.

  17. Antidotes to coumarins, isoniazid, methotrexate and thyroxine, toxins that work via metabolic processes.

    Bateman, D Nicholas; Page, Colin B


    Some toxins cause their effects by affecting physiological processes that are fundamental to cell function or cause systemic effects as a result of cellular interaction. This review focuses on four examples, coumarin anticoagulants, isoniazid, methotrexate and thyroxine from the context of management of overdose as seen in acute general hospitals. The current basic clinical pharmacology of the toxin, the clinical features in overdose and evidence base for specific antidotes are discussed. The treatment for this group is based on an understanding of the toxic mechanism, but studies to determine the optimum dose of antidote are still required in all these toxins except thyroxine, where treatment dose is based on symptoms resulting from the overdose.

  18. Low serum free thyroxine level in a girl with McCune-Albright syndrome.

    Roosimaa, Mart; Pajuväli, Anett; Peet, Aleksandr; Tillmann, Vallo


    A 17-year-old girl with McCune-Albright syndrome (MAS) was suspected of having central hypothyroidism based on an inappropriately normal thyroid-stimulating hormone (TSH) and low free thyroxine (fT4). She was clinically euthyroid and her pituitary appeared normal on MRI. Treatment of hypothyroidism with levothyroxine resulted in suppression of TSH with a low fT4 and high free triiodothyronine (fT3) concentration and hence iatrogenic hyperthyroidism was diagnosed. After discontinuation of levothyroxine, the TSH and fT3 normalised while fT4 remained low. Increased conversion of thyroxine (T4) to triiodothyronine (T3) can be part of MAS. Therefore, fT3 and fT4 should both be measured when evaluating thyroid function in patients with MAS.

  19. Prevalence of hematological abnormalities in patients with Sheehan's syndrome: response to replacement of glucocorticoids and thyroxine.

    Laway, Bashir Ahmad; Mir, Shahnaz Ahmad; Bashir, Mir Iftikhar; Bhat, Javid Rasool; Samoon, Jeelani; Zargar, Abdul Hamid


    Anemia and other hematological abnormalities are common in patients with Sheehan's syndrome. The response of these abnormalities to replacement of thyroxine and glucocorticoids is not clear. The aim of the present study was to document the profile of hematological abnormalities and response to treatment in patients with Sheehan's syndrome. Forty patients of Sheehan's syndrome and an equal number of age and parity matched healthy controls were studied for prevalence of hematological abnormalities. Hemoglobin concentration, hematocrit, red cell, white cell and platelet count were significantly decreased in patients with Sheehan's syndrome compared to controls. Frequency of anemia, leucopenia, thrombocytopenia and pancytopenia was significantly higher in these patients compared to controls. After achieving euthyroid and eucortisol state, there was a complete recovery of these hematological abnormalities. We conclude that anemia and other cytopenias are common in patients with Sheehan's syndrome and replacement with thyroxine and glucocorticoids results in complete recovery of these abnormalities.

  20. Effects of thyroxin therapy on different analytes related to obesity and inflammation in dogs with hypothyroidism.

    Tvarijonaviciute, A; Jaillardon, L; Cerón, J J; Siliart, B


    Hypothyroidism in dogs is accompanied by changes in intermediary metabolism including alterations in bodyweight (BW), insulin resistance, and lipid profile. In this study, changes in selected adipokines (adiponectin, leptin), butyrylcholinesterase (BChE), and acute phase proteins, including C-reactive protein, haptoglobin (Hp) and serum amyloid A (SAA), were studied in dogs with hypothyroidism under thyroxin therapy. Blood samples were collected when hypothyroidism was diagnosed (before treatment) and after treatment with thyroxin. Twenty-eight of 39 dogs exhibited a good therapeutic response (group A), whereas the remainder were considered to have been insufficiently treated (group B). Following treatment, group A dogs demonstrated a statistically significant decrease in canine thyroid stimulating hormone (c-TSH) (Pdogs showed no statistically significant changes in c-TSH, but had a significant increase in fT4 (Pdogs. The mean increase in Hp values and decrease in SAA for some of the dogs after treatment warrants further investigation.

  1. Yucca schidigera can promote rabbit growth, fecundity, affect the release of hormones in vivo and in vitro, induce pathological changes in liver, and reduce ovarian resistance to benzene.

    Földešiová, Martina; Baláži, Andrej; Chrastinová, Ľubica; Pivko, Juraj; Kotwica, Jan; Harrath, Abdel Halim; Chrenek, Peter; Sirotkin, Alexander V


    fecundity), which may be due to the promotion of P4, OT, and PGF release. It could, however, induce some pathological changes in the liver and reduce resistance of ovaries to the environmental contaminant benzene. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Interleukin-12 plasmid DNA delivery using l-thyroxine-conjugated polyethylenimine nanocarriers

    Dehshahri, Ali; Sadeghpour, Hossein; Kazemi Oskuee, Reza; Fadaei, Mahin; Sabahi, Zahra; Alhashemi, Samira Hossaini; Mohazabieh, Erfaneh


    In this study, l-thyroxine was covalently grafted on 25 kDa branched polyethylenimine (PEI), and the ability of the nano-sized polyplexes for transferring plasmid encoding interleukin-12 (IL-12) gene was evaluated. As there are several problems in systemic administration of recombinant IL-12 protein, local expression of the plasmid encoding IL-12 gene inside the tumor tissue has been considered as an effective alternative approach. The l-thyroxine-conjugated PEI polyplexes were prepared using pUMVC3-hIL12 plasmid, and their transfection activity was determined in HepG2 human liver carcinoma and Neuro2A neuroblastoma cell lines. The polyplexes characterized in terms of DNA condensation ability, particle size, zeta potential, and buffering capacity as well as cytotoxicity and resistance to enzyme digestion. The results revealed that l-thyroxine conjugation of PEI increased gene transfer ability by up to two fold relative to unmodified 25 kDa PEI, the gold standard for non-viral gene delivery, with the highest increase occurring at degrees of conjugation around 10 %. pDNA condensation tests and dynamic light scattering measurements exhibited the ability of PEI conjugates to optimally condense the plasmid DNA into polyplexes in the size range around 200 nm. The modified polymers showed remarkable buffering capacity and protection against enzymatic degradation comparable to that of unmodified PEI. These results suggest that l-thyroxine conjugation of PEI is a simple modification strategy for future investigations aimed at developing a targeting gene vehicle.

  3. The Glycoside Hydrolase Family 8 Reducing-End Xylose-Releasing Exo-oligoxylanase Rex8A from Paenibacillus barcinonensis BP-23 Is Active on Branched Xylooligosaccharides.

    Valenzuela, Susana V; Lopez, Sergi; Biely, Peter; Sanz-Aparicio, Julia; Pastor, F I Javier


    A GH8 family enzyme involved in xylan depolymerization has been characterized. The enzyme, Rex8A, is a reducing-end xylose-releasing exo-oligoxylanase (Rex) that efficiently hydrolyzes xylooligosaccharides and shows minor activity on polymeric xylan. Rex8A hydrolyzes xylooligomers of 3 to 6 xylose units to xylose and xylobiose in long-term incubations. Kinetic constants of Rex8A were determined on xylotriose, showing a Km of 1.64 ± 0.03 mM and a kcat value of 118.8 s(-1) Besides linear xylooligosaccharides, the enzyme hydrolyzed decorated xylooligomers. The catalytic activity on branched xylooligosaccharides, i.e., the release of xylose from the reducing end, is a newly described trait of xylose-releasing exo-oligoxylanases, as the exo-activity on these substrates has not been reported for the few of these enzymes characterized to date. Modeling of the three-dimensional (3D) structure of Rex8A shows an (α/α)6 barrel fold where the loops connecting the α-helices contour the active site. These loops, which show high sequence diversity among GH8 enzymes, shape a catalytic cleft with a -2 subsite that can accommodate methyl-glucuronic acid decorations. The hydrolytic ability of Rex8A on branched oligomers can be crucial for the complete depolymerization of highly substituted xylans, which is indispensable to accomplish biomass deconstruction and to generate efficient catalysts. A GH8 family enzyme involved in xylan depolymerization has been characterized. The Rex8A enzyme from Paenibacillus barcinonensis is involved in depolymerization of glucuronoxylan, a major component of the lignocellulosic substrates. The study shows that Rex8A is a reducing-end xylose-releasing exo-oligoxylanase that efficiently hydrolyzes xylose from neutral and acidic xylooligosaccharides generated by the action of other xylanases also secreted by the strain. The activity of a Rex enzyme on branched xylooligosaccharides has not been described to date. This report provides original and

  4. An Inverse Relationship Between Weight and Free Thyroxine During Early Gestation Among Women Treated for Hypothyroidism.

    Haddow, James E; Neveux, Louis M; Palomaki, Glenn E; Lambert-Messerlian, Geralyn; Malone, Fergal D; D'Alton, Mary E


    Following treatment sufficient to normalize thyrotropin (TSH), nonpregnant hypothyroid adults display higher free thyroxine (FT(4)) concentrations than a reference population. Our aim is to determine whether FT(4) concentrations are higher during pregnancy among women treated for hypothyroidism and whether their weight is associated with FT(4) levels. Weight/FT(4) relationships have not previously been reported in treated hypothyroid adults (either pregnant or nonpregnant). Thyroid-related measurements were available from over 10,000 women at two early pregnancy time periods from the FaSTER (First and Second Trimester Evaluation of Risk for Fetal aneuploidy) trial (1999-2002). All women were receiving routine prenatal care. Present analyses were restricted to 9267 reference women and 306 treated, hypothyroid women with TSH between the 2nd and 98th reference percentiles. We compared FT(4) values between those groups at 11-14 and 15-18 weeks' gestation, using linear regression to estimate FT(4)/maternal weight relationships, after accounting for treatment and other potential covariates. In comparison to reference women, median FT(4) values and percent of FT(4) values ≥95th reference percentile were significantly higher in treated women at both 11-14 and 15-18 weeks' gestation (pwomen, median FT(4) decreased monotonically with increasing weight, regardless of anti-thyroperoxidase antibody status. Maternal age, maternal weight, and treatment status were important predictors of FT(4) levels (pwomen, independent of other factors. Maternal age and weight reduced FT(4) levels by 0.0694 pmol/L/y and 0.0208 pmol/L/kg, respectively. FT(4) concentrations are higher among treated hypothyroid pregnant women than among reference women, and higher maternal weight is associated with lower FT(4) levels, regardless of treatment status. This inverse relationship is not associated with higher TSH levels. While no immediate clinical implications are attached to the current

  5. Effects of thyroxine and 1-methyl, 2-mercaptoimidazol on phosphoinositides synthesis in rat liver

    Krasilnikova Oksana A


    Full Text Available Abstract Background Phosphoinositides mediate one of the intracellular signal transduction pathways and produce a class of second messengers that are involved in the action of hormones and neurotransmitters on target cells. Thyroid hormones are well known regulators of lipid metabolism and modulators of signal transduction in cells. However, little is known about phosphoinositides cycle regulation by thyroid hormones. The present paper deals with phosphoinositides synthesis de novo and acylation in liver at different thyroid status of rats. Results The experiments were performed in either the rat liver or hepatocytes of 90- and 720-day-old rats. Myo-[3H]inositol, [14C]CH3COONa, [14C]oleic and [3H]arachidonic acids were used to investigate the phosphatidylinositol (PtdIns, phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate (PtdInsP2 synthesis. 1-methyl, 2-mercaptoimidazol-induced hypothyroidism was associated with the decrease of myo-[3H]inositol and [3H]arachidonic acids incorporation into liver phosphoinositides and total phospholipids, respectively. The thyroxine (L-T4 injection to hypothyroid animals increased the hormones contents in blood serum and PtdInsP2 synthesis de novo as well as [3H]arachidonic acids incorporation into the PtdIns and PtdInsP2. Under the hormone action, the [14C]oleic acid incorporation into PtdIns reduced in the liver of hypothyroid animals. A single injection of L-T4 to the euthyroid [14C]CH3COONa-pre-treated animals or addition of the hormone to a culture medium of hepatocytes was accompanied by the rapid prominent increase in the levels of the newly synthesized PtdIns and PtdInsP2 and in the mass of phosphatidic acid in the liver or the cells. Conclusions The data obtained have demonstrated that thyroid hormones are of vital importance in the regulation of arachidonate-containing phosphoinositides metabolism in the liver. The drug-induced malfunction of thyroid gland noticeably changed the

  6. The minor C-allele of rs2014355 in ACADS is associated with reduced insulin release following an oral glucose load

    Hornbak, Malene; Banasik, Karina; Justesen, Johanne Marie;


    insulin release following an oral glucose load or with T2D. Methods The variants were genotyped using KASPar(R) PCR SNP genotyping system and investigated for associations with estimates of insulin release and insulin sensitivity following an oral glucose tolerance test (OGTT) in a random sample of middle...... an oral glucose load (per allele effect (beta)=-3.8% (-6.3%;-1.3%), P=0.003), reduced incremental area under the insulin curve (beta=-3.6% (-6.3%;-0.9%), P=0.009), reduced acute insulin response (beta=-2.2% (-4.2%;0.2%), P=0.03), and with increased insulin sensitivity ISIMatsuda (beta= 2.9% (0.5%;5.2%), P......=0.02). The C-allele did not associate with two other measures of insulin sensitivity or with a derived disposition index. The C-allele was not associated with T2D in the case-control analysis (OR 1.07, 95% CI 0.96-1.18, P=0.21). rs11161510 of ACADM did not associate with any indices of glucose...

  7. Thyroxine 5'-deiodinase in human anterior pituitary tumors.

    Itagaki, Y; Yoshida, K; Ikeda, H; Kaise, K; Kaise, N; Yamamoto, M; Sakurada, T; Yoshinaga, K


    The activity of T4 5'-monodeiodinase (5'D) in the pituitary was measured in 12 patients with pituitary adenoma (3 patients with acromegaly, 2 with prolactinoma, 1 with Cushing's disease, 1 with TSH-producing tumor, and 5 with nonfunctioning tumor) and, as a control, in a patient who died of parotid cancer. The pituitaries, obtained at operation or autopsy, were homogenized in 0.1 mol/L potassium phosphate buffer, pH 7.0, and centrifuged at 800 x g. Supernatants were incubated with [125I]T4 and 20 mmol/L dithiothreitol (DTT) at 37C for 90 min. T4 5'-D was measured by the release of 125I- with the ion exchange method. The activity of T4 5'-D in the pituitaries from patients with prolactinoma and parotid cancer was dependent on protein concentration, incubation time, incubation temperature, and T4 concentration, and was labile to prior heating at 70 C for 30 min. T4 5'-D was not inhibited by 1 mmol/L propylthiouracil, but was inhibited 95% by 0.1 mmol/L iopanoic acid. The apparent Km and maximum velocity for T4 5'-D in homogenates of prolactinoma at 20 mmol/L DTT were 11 nmol/L and 1.54 pmol/mg protein.h, respectively. This reaction followed sequential-type reaction kinetics when the DTT concentration was varied. All other homogenates of pituitary tumors, except two nonfunctioning tumors, also demonstrated T4 5'-D activity. These results indicate that 1) the human pituitary express a low Km and PTU-insensitive T4 5'-D activity which is very similar to the type II enzyme activity in the rat pituitary; and 2) various types of pituitary tumor cells contain T4 5'-D activity.

  8. Grape polyphenols and propolis mixture inhibits inflammatory mediator release from human leukocytes and reduces clinical scores in experimental arthritis.

    Mossalayi, M D; Rambert, J; Renouf, E; Micouleau, M; Mérillon, J M


    Polyphenols from red fruits and bee-derived propolis (PR) are bioactive natural products in various in vitro and in vivo models. The present study shows that hematotoxicity-free doses of grape polyphenols (GPE) and PR differentially decreased the secretion of pro-inflammatory cytokines from activated human peripheral blood leucocytes. While GPE inhibited the monocytes/macrophage response, propolis decreased both monokines and interferon γ (IFNγ) production. When used together, their distinct effects lead to the attenuation of all inflammatory mediators, as supported by a significant modulation of the transcriptomic profile of pro-inflammatory genes in human leukocytes. To enforce in vitro data, GPE+PR were tested for their ability to improve clinical scores and cachexia in chronic rat adjuvant-induced arthritis (AA). Extracts significantly reduced arthritis scores and cachexia, and this effect was more significant in animals receiving continuous low doses compared to those receiving five different high doses. Animals treated daily had significantly better clinical scores than corticoid-treated rats. Together, these findings indicate that the GPE+PR combination induces potent anti-inflammatory activity due to their complementary immune cell modulation. Copyright © 2013 Elsevier GmbH. All rights reserved.

  9. Pathological gamma oscillations, impaired dopamine release, synapse loss and reduced dynamic range of unitary glutamatergic synaptic transmission in the striatum of hypokinetic Q175 Huntington mice.

    Rothe, T; Deliano, M; Wójtowicz, A M; Dvorzhak, A; Harnack, D; Paul, S; Vagner, T; Melnick, I; Stark, H; Grantyn, R


    Huntington's disease (HD) is a severe genetically inherited neurodegenerative disorder. Patients present with three principal phenotypes of motor symptoms: choreatic, hypokinetic-rigid and mixed. The Q175 mouse model of disease offers an opportunity to investigate the cellular basis of the hypokinetic-rigid form of HD. At the age of 1 year homozygote Q175 mice exhibited the following signs of hypokinesia: Reduced frequency of spontaneous movements on a precision balance at daytime (-55%), increased total time spent without movement in an open field (+42%), failures in the execution of unconditioned avoidance reactions (+32%), reduced ability for conditioned avoidance (-96%) and increased reaction times (+65%) in a shuttle box. Local field potential recordings revealed low-frequency gamma oscillations in the striatum as a characteristic feature of HD mice at rest. There was no significant loss of DARPP-32 immunolabeled striatal projection neurons (SPNs) although the level of DARPP-32 immunoreactivity was lower in HD. As a potential cause of hypokinesia, HD mice revealed a strong reduction in striatal KCl-induced dopamine release, accompanied by a decrease in the number of tyrosine hydroxylase-(TH)- and VMAT2-positive synaptic varicosities. The presynaptic TH fluorescence level was also reduced. Patch-clamp experiments were performed in slices from 1-year-old mice to record unitary EPSCs (uEPSCs) of presumed cortical origin in the absence of G-protein-mediated modulation. In HD mice, the maximal amplitudes of uEPSCs amounted to 69% of the WT level which matches the loss of VGluT1+/SYP+ synaptic terminals in immunostained sections. These results identify impairment of cortico-striatal synaptic transmission and dopamine release as a potential basis of hypokinesia in HD.

  10. Binary release of ascorbic acid and lecithin from core-shell nanofibers on blood-contacting surface for reducing long-term hemolysis of erythrocyte.

    Shi, Qiang; Fan, Qunfu; Ye, Wei; Hou, Jianwen; Wong, Shing-Chung; Xu, Xiaodong; Yin, Jinghua


    There is an urgent need to develop blood-contacting biomaterials with long-term anti-hemolytic capability. To obtain such biomaterials, we coaxially electrospin [ascorbic acid (AA) and lecithin]/poly (ethylene oxide) (PEO) core-shell nanofibers onto the surface of styrene-b-(ethylene-co-butylene)-b-styrene elastomer (SEBS) that has been grafted with poly (ethylene glycol) (PEG) chains. Our strategy is based on that the grafted layers of PEG render the surface hydrophilic to reduce the mechanical injure to red blood cells (RBCs) while the AA and lecithin released from nanofibers on blood-contacting surface can actively interact with RBCs to decrease the oxidative damage to RBCs. We demonstrate that (AA and lecithin)/PEO core-shell structured nanofibers have been fabricated on the PEG grafted surface. The binary release of AA and lecithin in the distilled water is in a controlled manner and lasts for almost 5 days; during RBCs preservation, AA acts as an antioxidant and lecithin as a lipid supplier to the membrane of erythrocytes, resulting in low mechanical fragility and hemolysis of RBCs, as well as high deformability of stored RBCs. Our work thus makes a new approach to fabricate blood-contacting biomaterials with the capability of long-term anti-hemolysis. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. Gold ions bio-released from metallic gold particles reduce inflammation and apoptosis and increase the regenerative responses in focal brain injury

    Larsen, Agnete; Kolind, Kristian; Pedersen, Dan Sonne


    neural stem cell response. We conclude that bio-liberated gold ions possess pronounced anti-inflammatory and neuron-protective capacities in the brain and suggest that metallic gold has clinical potentials. Intra-cerebral application of metallic gold as a pharmaceutical source of gold ions represents......Traumatic brain injury results in loss of neurons caused as much by the resulting neuroinflammation as by the injury. Gold salts are known to be immunosuppressive, but their use are limited by nephrotoxicity. However, as we have proven that implants of pure metallic gold release gold ions which do...... not spread in the body, but are taken up by cells near the implant, we hypothesize that metallic gold could reduce local neuroinflammation in a safe way. Bio-liberation, or dissolucytosis, of gold ions from metallic gold surfaces requires the presence of disolycytes i.e. macrophages and the process...

  12. Promoting endothelial recovery and reducing neointimal hyperplasia using sequential-like release of acetylsalicylic acid and paclitaxel-loaded biodegradable stents

    Lee CH


    Full Text Available Cheng-Hung Lee,1,2 Chia-Ying Yu,2 Shang-Hung Chang,1 Kuo-Chun Hung,1 Shih-Jung Liu,2 Chao-Jan Wang,3 Ming-Yi Hsu,3 I-Chang Hsieh,1 Wei-Jan Chen,1 Yu-Shien Ko,1 Ming-Shien Wen1 1Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital-Linkou, Tao-Yuan, Taiwan; 2Department of Mechanical Engineering, Chang Gung University, Tao-Yuan, Taiwan; 3Department of Medical Imaging and Intervention, Chang Gung Memorial Hospital, Linkou, Tao-Yuan, Taiwan Introduction: This work reports on the development of a biodegradable dual-drug-eluting stent with sequential-like and sustainable drug-release of anti-platelet acetylsalicylic acid and anti-smooth muscle cell (SMC proliferative paclitaxel.Methods: To fabricate the biodegradable stents, poly-L-lactide strips are first cut from a solvent-casted film. They are rolled onto the surface of a metal pin to form spiral stents. The stents are then consecutively covered by acetylsalicylic acid and paclitaxel-loaded polylactide-polyglycolide nanofibers via electrospinning.Results: Biodegradable stents exhibit mechanical properties that are superior to those of metallic stents. Biodegradable stents sequentially release high concentrations of acetylsalicylic acid and paclitaxel for more than 30 and 60 days, respectively. In vitro, the eluted drugs promote endothelial cell numbers on days 3 and 7, and reduce the proliferation of SMCs in weeks 2, 4, and 8. The stents markedly inhibit the adhesion of platelets on days 3, 7, and 14 relative to a non-drug-eluting stent. In vivo, the implanted stent is intact, and no stent thrombosis is observed in the stent-implanted vessels without the administration of daily oral acetylsalicylic acid. Promotion of endothelial recovery and inhibition of neointimal hyperplasia are also observed on the stented vessels.Conclusion: The work demonstrates the efficiency and safety of the biodegradable dual-drug-eluting stents with sequential and sustainable drug release

  13. Technical note: Reduced pulsation chamber vacuum at normal pulsation rate and ratio provides adequate prestimulation to induce oxytocin release and milk ejection while simultaneous milk flow is prevented.

    Neuheuser, Anna-Lena; Belo, Claire; Bruckmaier, Rupert M


    In the present study we investigated the milking characteristics and the oxytocin release in dairy cows milked after either manual prestimulation or a premilking period with pulsating liners at normal pulsation rate (60) and ratio (60:40) while the pulsation chamber vacuum (PCV) was reduced to 20 kPa to prevent the opening of the liners. During the milking trial with 8 cows the PCV reduction was started either before attachment (PCV-1) or immediately after attachment (PCV-2) of the teat cups. Milk yields, total milking times, average milk flows, peak flow rates, the duration of milk flow plateaus, and the duration of milk flow declines did not differ among the 3 treatments. Only the time to reach peak milk flow was prolonged when the vacuum reduction was started after teat cup attachment (PCV-2). In this treatment, milk flow >200 g/min already occurred during the premilking period, resulting in bimodal milk flow curves. In 5 of the 8 cows, plasma oxytocin (OT) concentrations were measured from -2 min before the start of milking until 3 min of milking to compare the OT release in response to manual prestimulation and during PCV-1. In both treatments, OT increased similarly and remained elevated until the end of measurements. Consequently, the areas under the curve of OT concentrations did not differ between treatments. In conclusion, milking performance is similar if milking is performed after manual prestimulation or after normal pulsation at reduced PCV. To prevent milk flow during the prestimulation period, it is of crucial importance to start the reduction of the PCV before cluster attachment. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  14. Reducing nitrogen losses through ammonia volatilization and surface runoff to improve apparent nitrogen recovery of double cropping of late rice using controlled release urea.

    Li, Pengfei; Lu, Jianwei; Hou, Wenfeng; Pan, Yonghui; Wang, Yang; Khan, Muhammad Rizwan; Ren, Tao; Cong, Rihuan; Li, Xiaokun


    Controlled release fertilizer can reduce nitrogen losses to the environment while increasing grain yield and improving apparent nitrogen recovery (ANR) of rice. However, few studies have evaluated the comparative efficacy of different polymer-coated urea products on nitrogen (N) losses, ANR, and N uptake of rice. A 2-year field experiment was conducted to compare the effects of three different types of polymer-coated urea fertilizer on nitrogen losses through NH3 volatilization and surface runoff to the environment, ANR, grain yield, and N uptake as compared to conventional urea of rice. Six treatments including (1) control with 0 kg N ha(-1) (CK), (2) basal application of urea (Ub), (3) split application (Us) of urea (50% at transplanting, 25% at tillering, and 25% at panicle stages), (4) CRU-1 (polyurethane-coated urea), (5) CRU-2 (degradable polymer-coated urea), and (6) CRU-3 (water-based polymer-coated urea) all applied at 165 kg N ha(-1). It was found that CRU-2 resulted in the highest grain yield and panicle numbers among the N fertilization treatments in 2013 and 2014. Applying CRU could help increase N uptake in rice, reduce N losses through NH3 volatilization and surface runoff, and hence improve ANR. Its single dose can meet the nutrient demand of the rice plant. Controlled release urea could be adopted as an effective mitigation alternative to retard N losses through NH3 volatilization and surface runoff while improving ANR of double cropping of late rice.

  15. Effects of hydrocolloids addition on the retention and release profile of diacetyl and (--α-pinene in model reduced fat salad dressings

    Grażyna Bortnowska


    Full Text Available Background. Salad dressings due to their gustatory and nutritious advantages have been very often used in many food products. Traditional dressings usually contain large amount of fat (20-65%. Reduction of its content in such systems in most cases leads to their physical destabilization and causes worsening of sensory properties particularly because of increase in volatility of lipophilic aroma compounds which have been mostly found in food products. The objective of this study was to investigate the influence of hydrocolloid type and concentration on the retention and release profile of diacetyl and (--α-pinene in model reduced fat salad dressings formed with sodium caseinate. Material and methods. Model reduced fat salad dressings containing 10 wt% vegetable fat and stabilized by both 1 wt% sodium caseinate and 0.01-0.2 wt% hydrocolloids (xanthan gum, guar gum, gum arabic, native pregelatinised rice starch – Remyline XS-DR-P and acetylated distarch phosphate – Microlys CA – produced from potato starch were investigated. The samples were flavoured with diacetyl or (--α-pinene at concentration of 0.1 wt% for each flavour compound. Following measurements were done: dressings characteristics (oil droplet size and distribution, apparent viscosity, thermodynamic and kinetic stability, stability of the odorants (relative retention and release profile and odour intensity by method using scale. Results. The studies showed significant dependence (α £ 0.001 between relative retention of the investigated odorants and hydrocolloid type as well as concentration. Moreover, it was detected that the values of persistence index of flavour compounds (related to the release profile were in majority significantly correlated (α £ 0.05 with viscosity and creaming stability of the dressings, whereas relatively low and mostly statistically insignificantly with mean droplet size (D[3,2]. Furthermore, significant correlation values (α £ 0.05 were


    Ahmad Muzaki


    Full Text Available Thyroxin administration in tiger grouper larval rearing was conducted to determine its effect on development of digestive tract of the larvae. Newly hatched larvae were treated with 0 mg/L (control, 0.1 mg/L, and 0.2 mg/L of thyroxin for 2 hours in a 30 L tank before were transferred into a 1 m3 rearing tank. Samples were collected daily until 10 DAH and every 3 days until 40 DAH. Development of digestive tract was observed using histological method. For all treatments, the digestive tract was the same on 1 DAH and 2 DAH. The digestive tract of 1 DAH larvae was still closed and still in the form of a simple tube. The mouth, buccopharynx, liver, pancreas, and rectum were found on 2 DAH. On 3 DAH, the esophagus, stomach, intestines, and anus started to develop. At this stage, the digestive tract of larvae treated with and without thyroxin started to become distinguishable. Several goblet cells were noticed in the rectum of the treated larvae but not in the control. Digestive tract developed earlier in treated larvae compared to the control group, such as appearance of tongue, gill raker, fundic, and cardiac stomach development, formation of pharyngeal tooth, and gastric gland. Metamorphosis of larvae into juvenile on treated larvae occurred than that the control larvae earlier.

  17. Reducing the dose of gonadotrophin-releasing hormone agonist on starting ovarian stimulation: effect on ovarian response and in-vitro fertilization outcome.

    Elgendy, M; Afnan, M; Holder, R; Lashen, H; Afifi, Y; Lenton, W; Sharif, K


    The aim of this study was to examine if lowering the dose of gonadotrophin-releasing hormone agonist (GnRHa) on starting ovarian stimulation could be beneficial in in-vitro fertilization (IVF) programmes. A total of 64 normally ovulating patients entering an IVF programme were randomized to receive GnRHa (nafarelin acetate/Synarel) as an intranasal spray commencing in the midluteal phase, either at a dosage of 200 microg three times daily until the day of human chorionic gonadotrophin (HCG) administration, or to be reduced to 200 microg twice daily as ovarian stimulation was initiated. Patients in both groups were below 35 years with a body mass index below 30. All patients received three ampoules of Metrodin HP per day. Blood samples were taken on the day of HCG administration to measure luteinizing hormone (LH), oestradiol, and progesterone. LH and oestradiol were found to be significantly higher in the lower Synarel dose group. Our results show that reducing the GnRHa dose during ovarian stimulation in IVF might be beneficial in terms of significantly more oocytes recovered, and significantly greater number of embryos available for transfer and freezing, with no incidence of premature luteinization.

  18. Brown dog tick, Rhipicephalus sanguineus sensu lato, infestation of susceptible dog hosts is reduced by slow release of semiochemicals from a less susceptible host.

    de Oliveira Filho, Jaires Gomes; Ferreira, Lorena Lopes; Sarria, André Lucio Franceschini; Pickett, John A; Birkett, Michael A; Mascarin, Gabriel Moura; de León, Adalberto A Pérez; Borges, Lígia Miranda Ferreira


    Domestic dog breeds are hosts for the brown dog tick, Rhipicephalus sanguineus sensu lato, but infestation levels vary among breeds. Beagles are less susceptible to tick infestations than English cocker spaniels due to enhanced production of 2-hexanone and benzaldehyde that act as volatile tick repellents. We report the use of prototype slow-release formulations of these compounds to reduce the burden of R. sanguineus s. l. on English cocker spaniel dogs. Twelve dogs were randomly assigned to two groups with six dogs each. The treated group received collars with slow-release formulations of the compounds attached, while the control group received collars with clean formulations attached. Five environmental infestations were performed, with the number of ticks (at all stages) on the dogs being counted twice a day for 45days. The counts on the number of tick stages found per dog were individually fitted to linear mixed effects models with repeated measures and normal distribution for errors. The mean tick infestation in the treated group was significantly lower than in the control group. For larvae and nymphs, a decrease in tick infestation was observed at the fifth count, and for adults, lower average counts were observed in all counts. The compounds did not interfere with the distribution of the ticks on the body of the dogs, as a similar percentage of ticks was found on the anterior half of the dogs (54.5% for the control group and 56.2% for the treated group). The biological and reproductive parameters of the ticks were not affected by the repellents. This study highlights for the first time the potential use of a novel allomone (repellent)-based formulation for reduction of tick infestation on susceptible dogs. Copyright © 2016 Elsevier GmbH. All rights reserved.

  19. Prostaglandin E2 reduces the release and infectivity of new cell-free virions and cell-to-cell HIV-1 transfer.

    María Isabel Clemente

    Full Text Available BACKGROUND: The course of human immunodeficiency virus type-1 (HIV-1 infection is influenced by a complex interplay between viral and host factors. HIV infection stimulates several proinflammatory genes, such as cyclooxigense-2 (COX-2, which leads to an increase in prostaglandin (PG levels in the plasma of HIV-1-infected patients. These genes play an indeterminate role in HIV replication and pathogenesis. The effect of prostaglandin E2 (PGE2 on HIV infection is quite controversial and even contradictory, so we sought to determine the role of PGE2 and the signal transduction pathways involved in HIV infection to elucidate possible new targets for antiretrovirals. RESULTS: Our results suggest that PGE2 post-infection treatment acts in the late stages of the viral cycle to reduce HIV replication. Interestingly, viral protein synthesis was not affected, but a loss of progeny virus production was observed. No modulation of CD4 CXCR4 and CCR5 receptor expression, cell proliferation, or activation after PGE2 treatment was detected. Moreover, PGE2 induced an increase in intracellular cAMP (cyclic AMP levels through the EP2/EP4 receptors. PGE2 effects were mimicked by dbcAMP and by a specific Epac (exchange protein directly activated by cyclic AMP agonist, 8-Cpt-cAMP. Treatment with PGE2 increased Rap1 activity, decreased RhoA activity and subsequently reduced the polymerization of actin by approximately 30% compared with untreated cells. In connection with this finding, polarized viral assembly platforms enriched in Gag were disrupted, altering HIV cell-to-cell transfer and the infectivity of new virions. CONCLUSIONS: Our results demonstrate that PGE2, through Epac and Rap activation, alters the transport of newly synthesized HIV-1 components to the assembly site, reducing the release and infectivity of new cell-free virions and cell-to-cell HIV-1 transfer.

  20. Body weight loss, reduced urge for palatable food and increased release of GLP-1 through daily supplementation with green-plant membranes for three months in overweight women.

    Montelius, Caroline; Erlandsson, Daniel; Vitija, Egzona; Stenblom, Eva-Lena; Egecioglu, Emil; Erlanson-Albertsson, Charlotte


    The frequency of obesity has risen dramatically in recent years but only few effective and safe drugs are available. We investigated if green-plant membranes, previously shown to reduce subjective hunger and promote satiety signals, could affect body weight when given long-term. 38 women (40-65 years of age, body mass index 25-33 kg/m(2)) were randomized to dietary supplementation with either green-plant membranes (5 g) or placebo, consumed once daily before breakfast for 12 weeks. All individuals were instructed to follow a three-meal paradigm without any snacking between the meals and to increase their physical activity. Body weight change was analysed every third week as was blood glucose and various lipid parameters. On days 1 and 90, following intake of a standardized breakfast, glucose, insulin and glucagon-like peptide 1 (GLP-1) in plasma were measured, as well as subjective ratings of hunger, satiety and urge for different palatable foods, using visual analogue scales. Subjects receiving green-plant membranes lost significantly more body weight than did those on placebo (p weight loss with green-plant extract was 5.0 ± 2.3 kg compared to 3.5 ± 2.3 kg in the control group. Consumption of green-plant membranes also reduced total and LDL-cholesterol (p weight loss, improves obesity-related risk-factors, and reduces the urge for palatable food. The mechanism may reside in the observed increased release of GLP-1.

  1. Pyrroloquinoline quinone ameliorates l-thyroxine-induced hyperthyroidism and associated problems in rats.

    Kumar, Narendra; Kar, Anand; Panda, Sunanda


    Pyrroloquinoline quinone (PQQ) is believed to be a strong antioxidant. In this study, we have evaluated its hitherto unknown role in l-thyroxin (L-T4 )-induced hyperthyroidism considering laboratory rat as a model. Alterations in the serum concentration of thyroxin (T4 ) and triiodothyronine (T3 ); lipid peroxidation (LPO) of liver, kidney, heart, muscles and brain; in the endogenous antioxidants such as superoxide dismutase, catalase and glutathione and in serum total cholesterol, high-density lipoprotien, triglycerides, serum glutamate pyruvate transaminase (SGPT), serum glutamate oxaloacetate transaminase (SGOT) and urea were evaluated. Administration of l-T4 (500-µg kg(-1) body weight) enhanced not only the serum T3 and T4 levels but also the tissue LPO, serum SGOT, SGPT and urea with a parallel decrease in the levels of antioxidants and serum lipids. However, on simultaneous administration of PQQ (5 mg kg(-1) for 6 days), all these adverse effects were ameliorated, indicating the potential of PQQ in the amelioration of hyperthyroidism and associated problems. Possibly, the curative effects were mediated through inhibition of oxidative stress. We suggest that PQQ may be considered for therapeutic use for hyperthyroidism after dose standardization.

  2. Free serum thyroxine. Analysis of its clinical value through ''ROC'' curves

    Degrossi, O.J.; Altschuler, N.; de Cabrejas, M.L. (Comision Nacional de Energia Nuclear Atomica, Buenos Aires (Argentina). Dept. Aplicaciones Biologicas); Pinkas, M.; Garcia del Rio, H. (Hospital Aleman, Buenos Aires (Argentina). Servicio de Medicina Nuclear)


    The use of radiommunoassay (RIA) tehcniques has increased the diagnosis of thyroid functional alterations. A solid phase RIA method for free thyroxine (FT4) measurement was tested. Serum FT4, Total T4, T3 and TSH were determined by radioimmunoassay in 179 subjects. One hundred twenty two patients were normal (8 to 75 years old); FT4 was 1.42 +- 0.03 ng/100 ml (avg. value and std. error). In 27 cases of thyrotoxicosis the values were 4.66 +- 0.48 ng/100 ml and in 15 cases of hypothyroidism 0.50 +- 0.06 ng/100 ml (statistics probability <0,01). Four euthyroid patients under estrogen treatment, 9 hypothyroid patients under l-thyroxine treatment, one hyperthyroid patient under antithyroid drugs and one hyperthyroid patient under estrogen treatment, were studied. Total T4 and T3 values were in agreement with the variations of the serum protein transport capacity, and for that reason did not show the real thyroid function state. Clinical decision making analysis (with Receiver Operating Characteristic (ROC) curves) indicate that FT4 is the best choice for hyperthyroidism diagnosis and T4 for hypothyroidism. Cost/benefit analysis indicates also that FT4 has the best ratio.

  3. Role of cytosol receptor in regulation of deiodination of thyroxine to triiodothyronine in rat liver microsomal fraction

    Nauman, A.; Vogtt, E.; Bardowska, U. (Centrum Medyczne Ksztalcenia Podyplomowego, Warsaw (Poland))


    It was shown that partially purified and concentrated thyroid hormones binding cytosol proteins inhibit in vitro deiodination of thyroxine to triiodothyronine. The similar effect was evoked by equivalent concentration of bovine albumine. These results show that cytosol binding proteins may indirectly, by acting on concentration of free thyroxine, regulate the rate of conversion reaction. Results of studies with dithiotreitol-SH group protecting compound - suggest the possibility of indirect interaction between the cytosol binding proteins and converting system. These interactions were also observed in the presence of albumine which suggest that such a mechanism is not specific for cytosol receptor only.

  4. Median nerve conduction velocity and central conduction time measured with somatosensory evoked potentials in thyroxine-treated infants with Down syndrome

    van Trotsenburg, A. S. Paul; Smit, Bert J.; Koelman, Johannes H. T. M.; Sloot, Marijke Dekker-van der; Ridder, Jeannette C. D.; Tijssen, Jan G. P.; de Vijlder, Jan J. M.; Vulsma, Thomas


    OBJECTIVE. The aim of this study was to determine whether thyroxine treatment would improve nerve conduction in infants with Down syndrome. METHODS. A single-center, nationwide, randomized, double-blind, clinical trial was performed. Neonates with Down syndrome were assigned randomly to thyroxine (N

  5. High Sensitive and Selective Sensing of Hydrogen Peroxide Released from Pheochromocytoma Cells Based on Pt-Au Bimetallic Nanoparticles Electrodeposited on Reduced Graphene Sheets

    Guangxia Yu


    Full Text Available In this study, a high sensitive and selective hydrogen peroxide (H2O2 sensor was successfully constructed with Pt-Au bimetallic nanoparticles (Pt-Au NPs/reduced graphene sheets (rGSs hybrid films. Various molar ratios of Au to Pt and different electrodeposition conditions were evaluated to control the morphology and electrocatalytic activity of the Pt-Au bimetallic nanoparticles. Upon optimal conditions, wide linear ranges from 1 µM to 1.78 mM and 1.78 mM to 16.8 mM were obtained, with a detection limit as low as 0.31 µM. Besides, due to the synergetic effects of the bimetallic NPs and rGSs, the amperometric H2O2 sensor could operate at a low potential of 0 V. Under this potential, not only common anodic interferences induced from ascorbic acid, uric acid and dopamine, but also the cathodic interference induced from endogenous O2 could be effectively avoided. Furthermore, with rat pheochromocytoma cells (PC 12 as model, the proposed sensor had been successfully used in the detection of H2O2 released from the cancer cells. This method with wide linear ranges and excellent selectivity can provide a promising alternative for H2O2 monitoring in vivo in the fields of physiology, pathology and diagnosis.

  6. Vernonia cinerea Less. supplementation and strenuous exercise reduce smoking rate: relation to oxidative stress status and beta-endorphin release in active smokers

    Yankai Araya


    Full Text Available Abstract Purpose The aim of this study was to evaluate the effects of Vernonia cinerea Less. (VC supplementation and exercise on oxidative stress biomarkers, beta-endorphin release, and the rate of cigarette smoking. Methods Volunteer smokers were randomly divided into four groups: group 1: VC supplement; group 2: exercise with VC supplement; group 3: exercise; and group 4: control. VC was prepared by wash and dry techniques and taken orally before smoking, matching the frequency of strenuous exercise (three times weekly. Before and after a two month period, exhaled carbon monoxide (CO, blood oxidative stress (malondialdehyde [MDA], nitric oxide [NOx], protein hydroperoxide [PrOOH] and total antioxidant capacity [TAC], beta-endorphin and smoking rate were measured, and statistically analyzed. Results In Group 1, MDA, PrOOH, and NOx significantly decreased, whereas TAC increased (p 0.05. In Group 3, MDA, PrOOH, NOx, TAC, and beta-endorphin levels increased significantly (p 0.05. All groups had lower levels of CO after the intervention. The smoking rate for light cigarette decreased in group 2(62.7%, 1(59.52%, 3 (53.57% and 4(14.04%, whereas in self-rolled cigarettes it decreased in group 1 (54.47%, 3 (42.30%, 2 (40% and 4 (9.2%. Conclusion Supplementation with Vernonia cinerea Less and exercise provided benefit related to reduced smoking rate, which may be related to oxidaive stress and beta-endorphine levels.

  7. High sensitive and selective sensing of hydrogen peroxide released from pheochromocytoma cells based on Pt-Au bimetallic nanoparticles electrodeposited on reduced graphene sheets.

    Yu, Guangxia; Wu, Weixiang; Pan, Xiaoqi; Zhao, Qiang; Wei, Xiaoyun; Lu, Qing


    In this study, a high sensitive and selective hydrogen peroxide (H2O2) sensor was successfully constructed with Pt-Au bimetallic nanoparticles (Pt-Au NPs)/reduced graphene sheets (rGSs) hybrid films. Various molar ratios of Au to Pt and different electrodeposition conditions were evaluated to control the morphology and electrocatalytic activity of the Pt-Au bimetallic nanoparticles. Upon optimal conditions, wide linear ranges from 1 µM to 1.78 mM and 1.78 mM to 16.8 mM were obtained, with a detection limit as low as 0.31 µM. Besides, due to the synergetic effects of the bimetallic NPs and rGSs, the amperometric H2O2 sensor could operate at a low potential of 0 V. Under this potential, not only common anodic interferences induced from ascorbic acid, uric acid and dopamine, but also the cathodic interference induced from endogenous O2 could be effectively avoided. Furthermore, with rat pheochromocytoma cells (PC 12) as model, the proposed sensor had been successfully used in the detection of H2O2 released from the cancer cells. This method with wide linear ranges and excellent selectivity can provide a promising alternative for H2O2 monitoring in vivo in the fields of physiology, pathology and diagnosis.

  8. Reduced Cytokine Release in Ex Vivo Response to Cilengitide and Cetuximab Is a Marker for Improved Survival of Head and Neck Cancer Patients.

    Cedra, Susan; Wiegand, Susanne; Kolb, Marlen; Dietz, Andreas; Wichmann, Gunnar


    Targeting of αVβ3 and αVβ5 integrins by cilengitide may reduce growth of solid tumors including head and neck squamous cell carcinoma (HNSCC). Preclinical investigations suggest increased activity of cilengitide in combination with other treatment modalities. The only published trial in HNSCC (ADVANTAGE) investigated cisplatin, 5-fluorouracil, and cetuximab (PFE) without or with once (PFE+CIL1W) or twice weekly cilengitide (PFE+CIL2W) in recurrent/metastatic HNSCC. ADVANTAGE showed good tolerability of the cilengitide arms and even lower adverse events (AEs) compared to PFE but not the benefit in overall survival expected based on preclinical data. As we found in the FLAVINO assay, a short-time ex vivo assay for prediction of chemosensitivity, only a subgroup of HNSCC had an increased suppressive effect of cilengitide containing combination therapies on colony formation of epithelial cells (CFec) and release of pro-angiogenetic and pro-inflammatory cytokines, whereas other HNSCC failed to respond. Response to αVβ3 and αVβ5 integrin targeting by cilengitide classifies HNSCC regarding outcome. We present FLAVINO data arguing for further development of cilengitide plus cetuximab in treatment of a subgroup of HNSCC potentially identified by the FLAVINO assay using a set of biomarkers for response evaluation.

  9. Central nesfatin-1 reduces dark-phase food intake and gastric emptying in rats: differential role of corticotropin-releasing factor2 receptor.

    Stengel, Andreas; Goebel, Miriam; Wang, Lixin; Rivier, Jean; Kobelt, Peter; Mönnikes, Hubert; Lambrecht, Nils W G; Taché, Yvette


    Nesfatin-1, derived from nucleobindin2, is expressed in the hypothalamus and reported in one study to reduce food intake (FI) in rats. To characterize the central anorexigenic action of nesfatin-1 and whether gastric emptying (GE) is altered, we injected nesfatin-1 into the lateral brain ventricle (intracerebroventricular, icv) or fourth ventricle (4v) in chronically cannulated rats or into the cisterna magna (intracisternal, ic) under short anesthesia and compared with ip injection. Nesfatin-1 (0.05 microg/rat, icv) decreased 2-3 h and 3-6 h dark-phase FI by 87 and 45%, respectively, whereas ip administration (2 microg/rat) had no effect. The corticotropin-releasing factor (CRF)(1)/CRF(2) antagonist astressin-B or the CRF(2) antagonist astressin(2)-B abolished icv nesfatin-1's anorexigenic action, whereas an astressin(2)-B analog, devoid of CRF-receptor binding affinity, did not. Nesfatin-1 icv induced a dose-dependent reduction of GE by 26 and 43% that was not modified by icv astressin(2)-B. Nesfatin-1 into the 4v (0.05 microg/rat) or ic (0.5 microg/rat) decreased cumulative dark-phase FI by 29 and 60% at 1 h and by 41 and 37% between 3 and 5 h, respectively. This effect was neither altered by ic astressin(2)-B nor associated with changes in GE. Cholecystokinin (ip) induced Fos expression in 43% of nesfatin-1 neurons in the paraventricular hypothalamic nucleus and 24% of those in the nucleus tractus solitarius. These data indicate that nesfatin-1 acts centrally to reduce dark phase FI through CRF(2)-receptor-dependent pathways after forebrain injection and CRF(2)-receptor-independent pathways after hindbrain injection. Activation of nesfatin-1 neurons by cholecystokinin at sites regulating food intake may suggest a role in gut peptide satiation effect.

  10. Separating semiconductor devices from substrate by etching graded composition release layer disposed between semiconductor devices and substrate including forming protuberances that reduce stiction

    Tauke-Pedretti, Anna; Nielson, Gregory N; Cederberg, Jeffrey G; Cruz-Campa, Jose Luis


    A method includes etching a release layer that is coupled between a plurality of semiconductor devices and a substrate with an etch. The etching includes etching the release layer between the semiconductor devices and the substrate until the semiconductor devices are at least substantially released from the substrate. The etching also includes etching a protuberance in the release layer between each of the semiconductor devices and the substrate. The etch is stopped while the protuberances remain between each of the semiconductor devices and the substrate. The method also includes separating the semiconductor devices from the substrate. Other methods and apparatus are also disclosed.

  11. Mass release of Trichogramma evanescens and T. cacoeciae can reduce damage by the apple codling moth Cydia pomonella in organic orchards under pheromone disruption

    Sigsgaard, Lene; Herz, Annette; Korsgaard, Maren


    of the two species were evaluated for mass-release to control C. pomonella in two commercial organic apple orchards, one in 2012 and one in 2013, using a complete randomized block design. Pheromone disruption was used in both orchards, making the study one of the first to evaluate Trichogramma release under...


    Nuclear receptor agonists such as phenobarbital (PB), 3-methylcholantrene (3MC), 2,2',4,4',5,5'-hexachlorobiphenyl (PCB 153), and, pregnenolone-16a-carbonitrile (PCN) decrease serum thyroxine (T4) concentrations in rats. This decrease is thought to occur through the induction of ...

  13. Combinatorial release of dexamethasone and amiodarone from a nano-structured parylene-C film to reduce perioperative inflammation and atrial fibrillation

    Robinson, Erik; Kaushal, Sunjay; Alaboson, Justice; Sharma, Sudhish; Belagodu, Amogh; Watkins, Claire; Walker, Brandon; Webster, Gregory; McCarthy, Patrick; Ho, Dean


    Suppressing perioperative inflammation and post-operative atrial fibrillation requires effective drug delivery platforms (DDP). Localized anti-inflammatory and anti-arrhythmic agent release may be more effective than intravenous treatment to improve patient outcomes. This study utilized a dexamethasone (DEX) and amiodarone (AMIO)-loaded Parylene-C (PPX) nano-structured film to inhibit inflammation and atrial fibrillation. The PPX film was tested in an established pericardial adhesion rabbit model. Following sternotomy, the anterior pericardium was resected and the epicardium was abraded. Rabbits were randomly assigned to five treatment groups: control, oxidized PPX (PPX-Oxd), PPX-Oxd infused with DEX (PPX-Oxd[DEX]), native PPX (PPX), and PPX infused with DEX and AMIO (PPX[AMIO, DEX]). 4 weeks post-sternotomy, pericardial adhesions were evaluated for gross adhesions using a 4-point grading system and histological evaluation for epicardial neotissue fibrosis (NTF). Atrial fibrillation duration and time per induction were measured. The PPX[AMIO, DEX] group had a significant reduction in mean adhesion score compared with the control group (control 2.75 +/- 0.42 vs. PPX[AMIO, DEX] 0.25 +/- 0.42, P films compared to control (9.5 +/- 6.8 s vs. 187.6 +/- 174.7 s, p = 0.003). Time of atrial fibrillation per successful induction decreased among PPX[AMIO, DEX] films compared to control (2.8 +/- 1.2 s vs. 103.2 +/- 178 s, p = 0.004). DEX/AMIO-loaded PPX films are associated with reduced perioperative inflammation and a diminished atrial fibrillation duration. Epicardial application of AMIO, DEX films is a promising strategy to prevent post-operative cardiac complications.Suppressing perioperative inflammation and post-operative atrial fibrillation requires effective drug delivery platforms (DDP). Localized anti-inflammatory and anti-arrhythmic agent release may be more effective than intravenous treatment to improve patient outcomes. This study utilized a dexamethasone (DEX

  14. [Role of ultrasensitive TSH assay and ultrarapid total thyroxine assay in the thyroid studies].

    Fragu, P; Comoy, E; Noël, M; Lounis, M; Patois, E; Parmentier, C


    The diagnostic value of high sensitivity thyrotrophin assay (HS-TSH) and that of ultra-short determination of total thyroxine (T4) by fluorescence polarization (T4-TDX) were evaluated in 284 patients (29 hyperthyroid, 137 euthyroid without treatment and 118 under substitutive therapy). After comparing the clinician's first impression with the results of these laboratory tests the proportion of correctly classified untreated euthyroid patients was the same with T4-TDX as with HS-TSH (90%). In contrast, this proportion in hyperthyroid patients was about twice as low with HS-TSH (23%) as with T4-TDX (42%). While HS-TSH gives a better diagnostic evaluation, T4-TDX is an excellent indicator of the degree of hyperthyroidism. In patients under suppressive therapy HS-TSH and T4-TDX provide a better evaluation of therapeutic effectiveness.

  15. Changes in brain gangliosides of the neotene and metamorphic (thyroxine-induced) newt axolotl (Ambystoma mexicanum).

    Hilbig, R; Schmitt, M; Rahmann, H


    Qualitative and quantitative changes in the concentration of proteins, sialoglycoproteins and gangliosides and in the composition of gangliosides in the brains of the neotene and the thyroxine-induced metamorphic newt axolotl (Ambystoma mexicanum) were investigated. During metamorphosis two polar gangliosides (GT1b and GQ1b) decreased by about 5% each. On the contrary GD1a increased to 10%. Another developmental trend was a slight increase of two other disialogangliosides (GD1b, GD2). Additionally, incorporation profiles (2-8 days) of 14C-N-Ac-mannosamine, the specific precursor for gangliosides, in the brain of neotene and metamorphic axolotls were followed giving evidence of significant changes in the sialoglycoconjugate metabolism of the central nervous system during metamorphosis of this newt.

  16. Free thyroxine in needle washout after fine needle aspiration biopsy of toxic thyroid nodules.

    Raikov, Nikolai; Nonchev, Boyan; Chaushev, Borislav; Vjagova, Diyana; Todorov, Svetoslav; Bocheva, Yana; Malceva, Daniela; Vicheva, Snejinka; Raikova, Asyia; Argatska, Antoaneta; Raikov, Miroslav


    The main diagnostic tool for toxic adenomas (TA) is radionuclide imaging indicated in patients with evidence of thyroid nodules in combination with thyrotoxic syndrome. Thyroid ultrasound and fine-needle aspiration biopsy (FNAB) are widely used for the valuation of thyroid masses. There is no literature data concerning the utility of FNAB and related tests for the diagnosis of hyperfunctioning thyroid nodules. The purpose of this study is to determine the levels of free thyroxine (FT4) in the needle washout after FNAB of hot thyroid nodules. The results of our study show that the FT4 levels in needle washout from TA were significantly higher than the surrounding parenchyma and correlated with the hormonal changes in patients with thyroid hyperfunctioning nodules. Further studies on a large number of patients are needed to refine the diagnostic value of this method and evaluate its importance in quantitative risk assessment of thyroid autonomy.

  17. Corticotropin-releasing factor-overexpressing mice exhibit reduced neuronal activation in the arcuate nucleus and food intake in response to fasting.

    Stengel, Andreas; Goebel, Miriam; Million, Mulugeta; Stenzel-Poore, Mary P; Kobelt, Peter; Mönnikes, Hubert; Taché, Yvette; Wang, Lixin


    Corticotropin-releasing factor (CRF) overexpressing (OE) mice are a genetic model that exhibits features of chronic stress. We investigated whether the adaptive feeding response to a hypocaloric challenge induced by food deprivation is impaired under conditions of chronic CRF overproduction. Food intake response to a 16-h overnight fast and ip injection of gut hormones regulating food intake were compared in CRF-OE and wild type (WT) littermate mice along with brain Fos expression, circulating ghrelin levels, and gastric emptying of a nonnutrient meal. CRF-OE mice injected ip with saline showed a 47 and 44% reduction of 30-min and 4-h cumulative food intake response to an overnight fast, respectively, compared with WT. However, the 30-min food intake decrease induced by ip cholecystokinin (3 microg/kg) and increase by ghrelin (300 microg/kg) were similar in CRF-OE and WT mice. Overnight fasting increased the plasma total ghrelin to similar levels in CRF-OE and WT mice, although CRF-OE mice had a 2-fold reduction of nonfasting ghrelin levels. The number of Fos-immunoreactive cells induced by fasting in the arcuate nucleus was reduced by 5.9-fold in CRF-OE compared with WT mice whereas no significant changes were observed in other hypothalamic nuclei. In contrast, fasted CRF-OE mice displayed a 5.6-fold increase in Fos-immunoreactive cell number in the dorsal motor nucleus of the vagus nerve and a 34% increase in 20-min gastric emptying. These findings indicate that sustained overproduction of hypothalamic CRF in mice interferes with fasting-induced activation of arcuate nucleus neurons and the related hyperphagic response.

  18. Membrane Vesicles Released by a hypervesiculating Escherichia coli Nissle 1917 tolR Mutant Are Highly Heterogeneous and Show Reduced Capacity for Epithelial Cell Interaction and Entry

    Pérez-Cruz, Carla; Cañas, María-Alexandra; Giménez, Rosa; Badia, Josefa; Mercade, Elena; Aguilera, Laura


    Membrane vesicles (MVs) produced by Gram-negative bacteria are being explored for novel clinical applications due to their ability to deliver active molecules to distant host cells, where they can exert immunomodulatory properties. MVs released by the probiotic Escherichia coli Nissle 1917 (EcN) are good candidates for testing such applications. However, a drawback for such studies is the low level of MV isolation from in vitro culture supernatants, which may be overcome by the use of mutants in cell envelope proteins that yield a hypervesiculation phenotype. Here, we confirm that a tolR mutation in EcN increases MV production, as determined by protein, LPS and fluorescent lipid measurements. Transmission electron microscopy (TEM) of negatively stained MVs did not reveal significant differences with wild type EcN MVs. Conversely, TEM observation after high-pressure freezing followed by freeze substitution of bacterial samples, together with cryo-TEM observation of plunge-frozen hydrated isolated MVs showed considerable structural heterogeneity in the EcN tolR samples. In addition to common one-bilayer vesicles (OMVs) and the recently described double-bilayer vesicles (O-IMVs), other types of MVs were observed. Time-course experiments of MV uptake in Caco-2 cells using rhodamine- and DiO-labelled MVs evidenced that EcN tolR MVs displayed reduced internalization levels compared to the wild-type MVs. The low number of intracellular MVs was due to a lower cell binding capacity of the tolR-derived MVs, rather than a different entry pathway or mechanism. These findings indicate that heterogeneity of MVs from tolR mutants may have a major impact on vesicle functionality, and point to the need for conducting a detailed structural analysis when MVs from hypervesiculating mutants are to be used for biotechnological applications. PMID:28036403

  19. Slow-release nitrogen fertilizers can improve yield and reduce Cd concentration in pakchoi (Brassica chinensis L.) grown in Cd-contaminated soil.

    Zhang, Ran-Ran; Liu, Yue; Xue, Wan-Lei; Chen, Rong-Xin; Du, Shao-Ting; Jin, Chong-Wei


    Cadmium (Cd) pollution in vegetable crops has become a serious problem in recent years. Owing to the limited availability of arable land resources, large areas of Cd-contaminated lands are inevitably being used for the production of vegetables, posing great risks to human health via the food chain. However, strategies to improve yield and reduce Cd concentration in crops grown in contaminated soils are being developed. In the present study, using pot experiments, we investigated the effects of two slow-release nitrogen fertilizers (SRNFs), resin-coated ammonium nitrate (Osmocote313s), and resin-coated urea (urea620), on the growth and Cd concentration of the Cd-contaminated pakchoi. The results showed that pakchoi grown in soil containing 5 mg kg(-1) of Cd-induced oxidative stress (indicated by malondialdehyde (MDA), H2O2, and O2(·-)) and photosynthesis inhibition, which in turn was restored with the application of SRNFs. However, pakchoi grown in Cd-contaminated soil supplied with Osmocote313s and urea620 showed 103 and 203 % increase in fresh weight and 51-55 % and 44-56 % decrease in Cd concentration, respectively, as compared with their controls (pakchoi treated with instant soluble nitrogen fertilizers). On the basis of an increase in their tolerance index (47-238 %) and a decrease in their translocation factor (7.5-21.6 %), we inferred that the plants treated with SRNFs have a stronger tolerance to Cd and a lower efficiency of Cd translocation to edible parts than those treated with instant soluble nitrogen fertilizers. Therefore, in terms of both crop production and food safety, application of SRNFs could be an effective strategy for improving both biomass production and quality in pakchoi grown under Cd stress.

  20. Antimicrobial packaging to retard the growth of spoilage bacteria and to reduce the release of volatile metabolites in meat stored under vacuum at 1°C.

    Ferrocino, Ilario; La Storia, Antonietta; Torrieri, Elena; Musso, Salvatore Spagna; Mauriello, Gianluigi; Villani, Francesco; Ercolini, Danilo


    A nisin-EDTA solution was used for activation of the internal surface of plastic bags that were used to store beef chops at 1°C after vacuum packaging. The aim of the work was to evaluate the effect of the antimicrobial packaging on beef during storage. Volatile compounds and microbial populations were monitored after 0, 9, 20, 36, and 46 days of storage. The active packaging retarded the growth of lactic acid bacteria. Brochothrix thermosphacta was unable to grow for the whole storage time in treated samples, while the levels of Carnobacterium spp. in treated samples were below the detection limit for the first 9 days and reached loads below 5 Log CFU/cm(2) after 46 days. On the other hand, Enterobacteriaceae and Pseudomonas spp. were not affected by the use of the antimicrobial packaging and grew in all of the samples, with final populations of about 4 Log CFU/cm(2). Carnobacterium divergens was identified by PCR-denaturing gradient gel electrophoresis analysis of DNA extracted from beef after 36 days of storage. During beef storage, alcohols, aldehydes, ketones, and carboxylic acids were detected in the headspace of beef samples by solid-phase microextraction-gas chromatography-mass spectrometry analysis. The microbial metabolic activity was affected by the use of the antimicrobial film from the beginning up to 36 days with a maximum in the differences of volatile metabolites in samples analyzed at 20 days. The volatiles were also determined by electronic nose, allowing differentiation based on the time of storage and not on the type of packaging. The active packaging reduces the loads of spoilage microbial populations and the release of metabolites in the headspace of beef with a probable positive impact on meat quality.

  1. Measurement of free thyroxine and free triiodothyronine concentrations by DPC RIA kits

    Kasagi, Kanji; Kousaka, Tadako; Hatabu, Hiroto; Tokuda, Yasutaka; Iida, Yasuhiro; Konishi, Junji


    'DPC RIA' kits for measuring free triiodothyronine (T3) and free thyroxine (T4) were fundamentally and clinically studied. Standard curves for incubation temperature and time were favorable. The present kits yielded satisfactory precision and reproducibility. The upper and lower limits of the normal range for T4 were 0.88 ng/dl and 2.08 ng/dl, respectively. The serum concentration of T4 was 3.91 ng/dl or more for hyperthyroidism and 0.57 ng/dl or less for hypothyroidism, allowing discrimination between the two diseases. For T3, the upper and lower limits of the normal range were 1.45 ng/dl and 3.45 ng/dl, respectively. In pregnant women and patients with decreased or increased levels of thyroxine binding globulin (TBG), the serum T3 concentration lay within the normal range. Low free T4 and T3 levels were found in 22 % and 67 %, respectively, of patients with serious non-thyroidal illness (NTI). There was a good correlation between the present kits and the other commercially available kits. Measurements of free T3 and T4 obtained by ''Amerlex RIA'' kits tended to be lower than those by the present kits in pregnant women and NTI patients with hypoalbuminemia. In view of the simplified procedure, satisfactory precision and reproducibility, and the lack of influences of serum albumin and TBG, the present kits have a potential in routine use. (Namekawa, K.).

  2. In vitro fluorescence displacement investigation of thyroxine transport disruption by bisphenol A

    Jie Cao; Liang-Hong Guo; Bin Wan; Yin Wei


    Bisphenol A (BPA) is a chemical with high production volume and wide applications in many industries.Although BPA is known as an endocrine disruptor, its toxic mechanisms have not been fully characterized.Due to its structural similarity to thyroid hormones thyroxine (T4) and triiodothyronine (T3), one possible mechanism of BPA toxicity is disruption of hormone transport by competitive binding with the transport proteins.In this study, the binding interactions of BPA, T4, and T3 with three thyroid hormone transport proteins, human serum albumin (HSA), transthyretin (TTR), and thyroxine-binding globulin (TBG) were investigated by fluorescence measurement.Using two site-specific fluorescence probes dansylamide and dansyl-L-proline, the binding constants of BPA with HSA at drug site I and site Ⅱ were determined as 2.90 × 104 and 3.14 × 104 L/mol, respectively.By monitoring the intrinsic fluorescence of tryptophan, a binding constant of 4.70 × 103 L/mol was obtained.Similarly, by employing 8-anilino-1-naphthalenesulfonic acid as fluorescence probe, the binding affinity of BPA with TTR and TBG was measured to be 3.10 × 105 and 5.90 × 105 L/mol, respectively.In general, BPA showed lower binding affinity with the proteins than T3 did, and even lower affinity than T4.Using these binding constants, the amount of BPA which would bind to the transport proteins in human plasma was estimated.These results suggest that the concentrations of BPA commonly found in human plasma are probably not high enough to interfere with T4 transport.

  3. An intracellular adrenomedullin system reduces IL-6 release via a NF-kB-mediated, cAMP-independent transcriptional mechanism in rat thymic epithelial cells.

    Castellani, Giulia; Paliuri, Giovanna; Orso, Genny; Paccagnella, Nicola; D'Amore, Claudio; Facci, Laura; Cima, Francesca; Caicci, Federico; Palatini, Pietro; Bova, Sergio; De Martin, Sara


    Thymic epithelial cells (TECs) play a key role in the regulation of central immune tolerance by expressing autoantigens and eliminating self-reactive T cells. In a previous paper we reported that adrenomedullin (ADM) and its co-receptor protein RAMP2 are located intracellularly in newborn human thymic epithelial cells (TECs). This work has two main aims: (1) to examine the cellular localization of ADM and its receptor in TECs of adult Wistar rats to validate this animal model for the study of the ADM system and its function(s) in thymus; (2) to investigate the potential modulating effect of ADM on the NF-kB pathway, which is involved through the production of cytokines such as IL-6, in the maturation of T-lymphocytes and immunological tolerance. Our results show that, similarly to human newborn TECs, ADM is localized to the cytoplasm of adult rat TECs, and RAMP2 is expressed in the nucleus but not in the plasma membrane. Pretreatment of TECs for 4h with ADM significantly reduced lipopolysaccharide (LPS)-induced release of IL-6 (P<0.001) and expression of the p65 subunit of NF-kB, while doubled the expression of IkBα (P<0.001), the physiological inhibitor of NF-kB nuclear translocation. These effects were not mediated by activation of the cAMP pathway, a signalling cascade that is rapidly activated by ADM in cells that express plasma membrane RAMP2, but were the consequence of a reduction in the transcription of p65 (P<0.001) and an increase in the transcription of IkBα (P<0.05). On the basis of these findings we propose that in rat TECs ADM reduces IL-6 secretion by modulating NF-kB genes transcription through an interaction with a receptor localized to the nucleus. This may partly explain the protective effects of ADM in autoimmune diseases and points to the ADM system of TECs as a novel potential target for immunomodulating drugs. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Improvement of left ventricular remodeling after myocardial infarction with eight weeks L-thyroxine treatment in rats

    Chen Yue-Feng


    Full Text Available Abstract Background Left ventricular (LV remodeling following large transmural myocardial infarction (MI remains a pivotal clinical issue despite the advance of medical treatment over the past few decades. Identification of new medications to improve the remodeling process and prevent progression to heart failure after MI is critical. Thyroid hormones (THs have been shown to improve LV function and remodeling in animals post-MI and in the human setting. However, changes in underlying cellular remodeling resulting from TH treatment are not clear. Methods MI was produced in adult female Sprague–Dawley rats by ligation of the left descending coronary artery. L-thyroxine (T4 pellet (3.3 mg, 60 days sustained release was used to treat MI rats for 8 weeks. Isolated myocyte shape, arterioles, and collagen deposition in the non-infarcted area were measured at terminal study. Results T4 treatment improved LV ±dp/dt, normalized TAU, and increased myocyte cross-sectional area without further increasing myocyte length in MI rats. T4 treatment increased the total LV tissue area by 34%, increased the non-infarcted tissue area by 41%, and increased the thickness of non-infarcted area by 36% in MI rats. However, myocyte volume accounted for only ~1/3 of the increase in myocyte mass in the non-infarct area, indicating the presence of more myocytes with treatment. T4 treatment tended to increase the total length of smaller arterioles (5 to 15 μm proportional to LV weight increase and also decreased collagen deposition in the LV non-infarcted area. A tendency for increased metalloproteinase-2 (MMP-2 expression and tissue inhibitor of metalloproteinases (TIMPs -1 to −4 expression was also observed in T4 treated MI rats. Conclusions These results suggest that long-term T4 treatment after MI has beneficial effects on myocyte, arteriolar, and collagen matrix remodeling in the non-infarcted area. Most importantly, results suggest improved survival of myocytes in

  5. Omnigen-AF reduces basal plasma cortisol, AWA cortisol release to adrencocorticotropic hormone or corticotrophin releasing hormone & vasopressin in lactating dairy cows under thermoneutral or acute heat stress conditions.

    Differences in the adrenal cortisol response of OmniGen-AF (OG) supplemented dairy cows to a corticotrophin releasing hormone (CRH) and vasopressin (VP) or an adrenocorticotropic hormone (ACTH) challenge when housed at different temperature-humidity indices (THI) were studied. Holstein cows (n=12; 1...

  6. Quantification of thyroxine by the selective photoluminescence quenching of L-cysteine–ZnS quantum dots in aqueous solution containing hexadecyltrimethylammonium bromide

    Khan, Sarzamin; Carneiro, Leonardo S.A. [Chemistry Department, Pontifícia Universidade Católica do Rio de Janeiro, 22451-900 Rio de Janeiro-RJ (Brazil); Romani, Eric C.; Larrudé, Dunieskys G. [Physics Department, Pontifícia Universidade Católica do Rio de Janeiro, 22451-900, Rio de Janeiro-RJ (Brazil); Aucelio, Ricardo Q., E-mail: [Chemistry Department, Pontifícia Universidade Católica do Rio de Janeiro, 22451-900 Rio de Janeiro-RJ (Brazil)


    The determination of L-thyroxine is proposed based on the photoluminescence quenching effect caused on the L-cysteine modified ZnS quantum dots (L-cysteine ZnS QDs) aqueous dispersion. Under optimum conditions, the analytical response followed a Stern–Volmer model and the experimental conditions were adjusted to enable a robust and reproducible photoluminescence signal. The linear response observed in the quantum dots aqueous dispersion covered the L-thyroxine concentration from the LOQ (2.0×10{sup −8} mol L{sup −1}) to 4.0×10{sup −6} mol L{sup −1}. The approach was tested in the determination of L-thyroxine in pharmaceutical formulations used to treat patients with thyroid gland disorder. The percent recoveries in controlled samples were between 93.3 and 103%. Analyte fortified saliva was also evaluated as a possible sample for L-thyroxine monitoring of a patient under treatment. It was identified a static type of photoluminescence quenching caused by L-thyroxine. - Highlights: • L-cysteine ZnS QDs were used as a photoluminescent probe to detect L-thyroxine. • Intensity of probe decreases following a Stern–Volmer model. • The method can detect down ng L{sup −1} levels of L-thyroxine in the probe dispersion. • Method was used to determinate of L-thyroxine in saliva and in pharmaceuticals. • Mechanism of interaction between L-thyroxine and quantum dots was studied.

  7. Plasma membrane ordering agent pluronic F-68 (PF-68) reduces neurotransmitter uptake and release and produces learning and memory deficits in rats

    Clarke, M. S.; Prendergast, M. A.; Terry, A. V. Jr


    A substantial body of evidence indicates that aged-related changes in the fluidity and lipid composition of the plasma membrane contribute to cellular dysfunction in humans and other mammalian species. In the CNS, reductions in neuronal plasma membrane order (PMO) (i.e., increased plasma membrane fluidity) have been attributed to age as well as the presence of the beta-amyloid peptide-25-35, known to play an important role in the neuropathology of Alzheimer's disease (AD). These PMO increases may influence neurotransmitter synthesis, receptor binding, and second messenger systems as well as signal transduction pathways. The effects of neuronal PMO on learning and memory processes have not been adequately investigated, however. Based on the hypothesis that an increase in PMO may alter a number of aspects of synaptic transmission, we investigated several neurochemical and behavioral effects of the membrane ordering agent, PF-68. In cell culture, PF-68 (nmoles/mg SDS extractable protein) reduced [3H]norepinephrine (NE) uptake into differentiated PC-12 cells as well as reduced nicotine stimulated [3H]NE release. The compound (800-2400 microg/kg, i.p., resulting in nmoles/mg SDS extractable protein in the brain) decreased step-through latencies and increased the frequencies of crossing into the unsafe side of the chamber in inhibitory avoidance training. In the Morris water maze, PF-68 increased the latencies and swim distances required to locate a hidden platform and reduced the time spent and distance swam in the previous target quadrant during transfer (probe) trials. PF-68 did not impair performance of a well-learned working memory task, the rat delayed stimulus discrimination task (DSDT), however. Studies with 14C-labeled PF-68 indicated that significant (pmoles/mg wet tissue) levels of the compound entered the brain from peripheral (i.p.) injection. No PF-68 related changes were observed in swim speeds or in visual acuity tests in water maze experiments, rotorod

  8. Induction of mitochondrial uncoupling enhances VEGF₁₂₀ but reduces MCP-1 release in mature 3T3-L1 adipocytes: possible regulatory mechanism through endogenous ER stress and AMPK-related pathways.

    Miyokawa-Gorin, Kaoru; Takahashi, Kazuto; Handa, Keiko; Kitahara, Atsuko; Sumitani, Yoshikazu; Katsuta, Hidenori; Tanaka, Toshiaki; Nishida, Susumu; Yoshimoto, Katsuhiko; Ohno, Hideki; Ishida, Hitoshi


    Although white adipocytes contain a larger number of mitochondria per cytoplasmic volume, adipocyte mitochondrial uncoupling to reduce the efficiency of ATP production on cellular function including secretory regulation of bioactive molecules such as VEGF and MCP-1 remains to be elucidated. Here we induce mitochondrial uncoupling under hypoxia-independent conditions in mature 3T3-L1 adipocytes using a metabolic uncoupler, dinitrophenol (DNP). MCP-1 release was significantly decreased by 26% (poxidative stress was observed. Treatment with thapsigargin, which can induce exogenous endoplasmic reticulum (ER) stress, clearly attenuated MCP-1 release (pmetabolic syndrome and type 2 diabetes.

  9. AdBlue: the solution retained by Total to reduce the nitrogen oxides releases of heavy lorries; AdBlue: la solution retenue par Total pour reduire les emissions d'oxydes d'azote des poids lourds

    Salomon, A.


    On the 15 of June 2005, Total has inaugurated, near Lyon, the first French gasoline service station delivering AdBlue to heavy-duty cars. Adblue is an aqueous solution of urea which, injected in exhaust systems, allows to reduce the nitrogen oxides releases. In this technology, called SCR (Selective Catalytic Reduction), nitrogen oxides are converted into nitrogen and steam by the mean of a catalytic converter of AdBlue pulverized in the hot exhaust gas. The releases are abated of about 85%. (O.M.)

  10. Reduced axonal localization of a Caps2 splice variant impairs axonal release of BDNF and causes autistic-like behavior in mice

    Sadakata, Tetsushi; Shinoda, Yo; Oka, Megumi; Sekine, Yukiko; Sato, Yumi; Saruta, Chihiro; Miwa, Hideki; Tanaka, Mika; Itohara, Shigeyoshi; Furuichi, Teiichi


    Ca2+-dependent activator protein for secretion 2 (CAPS2 or CADPS2) potently promotes the release of brain-derived neurotrophic factor (BDNF). A rare splicing form of CAPS2 with deletion of exon3 (dex3) was identified to be overrepresented in some patients with autism. Here, we generated Caps2-dex3 mice and verified a severe impairment in axonal Caps2-dex3 localization, contributing to a reduction in BDNF release from axons. In addition, circuit connectivity, measured by spine and interneuron ...

  11. TSG-6 released from intradermally injected mesenchymal stem cells accelerates wound healing and reduces tissue fibrosis in murine full-thickness skin wounds.

    Qi, Yu; Jiang, Dongsheng; Sindrilaru, Anca; Stegemann, Agatha; Schatz, Susanne; Treiber, Nicolai; Rojewski, Markus; Schrezenmeier, Hubert; Vander Beken, Seppe; Wlaschek, Meinhard; Böhm, Markus; Seitz, Andreas; Scholz, Natalie; Dürselen, Lutz; Brinckmann, Jürgen; Ignatius, Anita; Scharffetter-Kochanek, Karin


    Proper activation of macrophages (Mφ) in the inflammatory phase of acute wound healing is essential for physiological tissue repair. However, there is a strong indication that robust Mφ inflammatory responses may be causal for the fibrotic response always accompanying adult wound healing. Using a complementary approach of in vitro and in vivo studies, we here addressed the question of whether mesenchymal stem cells (MSCs)-due to their anti-inflammatory properties-would control Mφ activation and tissue fibrosis in a murine model of full-thickness skin wounds. We have shown that the tumor necrosis factor-α (TNF-α)-stimulated protein 6 (TSG-6) released from MSCs in co-culture with activated Mφ or following injection into wound margins suppressed the release of TNF-α from activated Mφ and concomitantly induced a switch from a high to an anti-fibrotic low transforming growth factor-β1 (TGF-β1)/TGF-β3 ratio. This study provides insight into what we believe to be a previously undescribed multifaceted role of MSC-released TSG-6 in wound healing. MSC-released TSG-6 was identified to improve wound healing by limiting Mφ activation, inflammation, and fibrosis. TSG-6 and MSC-based therapies may thus qualify as promising strategies to enhance tissue repair and to prevent excessive tissue fibrosis.

  12. Human muscle net K+ release during exercise is unaffected by elevated anaerobic metabolism, but reduced after prolonged acclimatization to 4100 m

    Nordsborg, Nikolai Baastrup; Calbet, Jose A. L.; Sander, Mikael


    It was investigated if skeletal muscle K(+) release is linked to the degree of anaerobic energy production. Six subjects performed an incremental bicycle exercise test in normoxic and hypoxic conditions prior to and after 2 and 8 weeks of acclimatization to 4100 m. The highest workload completed ...

  13. Isosorbide-5-mononitrate (5-ISMN) sustained-release pellets prepared by double layer coating for reducing 5-ISMN migration and sublimation.

    Li, Guofei; Han, Dandan; Guan, Tingting; Zhao, Xingna; He, Haibing; Tang, Xing


    The major aim of this study was to prepare isosorbide-5-mononitrate (5-ISMN) sustained-release pellets and evaluate their stability. The pellets were prepared by extrusion/spheronization, and then the core pellets were coated with ethylcellulose (EC 10cp) and Eudragit(®)NE30D. Here, EC was used as the subcoating agent while Eudragit(®)NE30D acted as the outer-coating agent. 5-ISMN sustained-release pellets as a novel drug delivery system contained the immediate-release portion in the outer-coating layer. Unexpectedly, 5-ISMN was found to migrate from the interior of the pellets to the surface forming needle crystals and exhibited the phenomenon of sublimation, which resulted in a tremendous increase in the release rate. Our research showed that the migration and sublimation of the active ingredient was related to the temperature and humidity. Polyvinylpyrrolidone (PVP K30) can affect the precipitation of 5-ISMN by forming a charge transfer complex between the drug and PVP, while hydroxypropyl methyl cellulose (HPMC E5) had no effect, and confirmed the correctness of this view through photographs and IR spectra. In the investigation of the stability, the results showed that there was no sublimation and migration while the pellets stored at 25°C/60%RH (ambient conditions) and 40°C/75% RH (stress conditions) during a 6-month period.

  14. Influences of hypertonic and hypovolemic treatments on vasopressin response in propylthiouracil (PTU) induced hypothyroid rat and effect on supplementation with L-thyroxine.

    Aydin, Leyla; Mogulkoc, R; Baltaci, A K


    This study was performed to investigate the effects of L-thyroxine treatment on plasma vasopressin (AVP) levels in rats with hypothyroidism induced by propylthiouracil (PTU). Animals were separated into three groups each having 6 rats: control, PTU, PTU+L-thyroxine groups. Then, the groups were further divided into 3 sub-groups including 6 rats (a; basal, b; hypertonic stimulated and c; hypovolemic stimulated). At the end of the experiments all rats were decapitated in order to obtain plasma samples for analysis in terms of Hct, osmolality, TT 3 , TT 4 and vasopressin. Haematocrit (Hct) levels were the highest in hypovolemic stimulated sub-group (P PTU group and the highest in the L-thyroxine treated group (P PTU group (P PTU-induced hypothyroidism. However, L-thyroxine treatment following hypothyroidism prevents this reduction.


    Michelson, C.


    An electromagnetic release mechanism is offered that may be used, for example, for supporting a safety rod for a nuclear reactor. The release mechanism is designed to have a large excess holding force and a rapid, uniform, and dependable release. The fast release is accomplished by providing the electromagnet with slotttd polts separated by an insulating potting resin, and by constructing the poles with a ferro-nickel alloy. The combination of these two features materially reduces the eddy current power density whenever the magnetic field changes during a release operation. In addition to these features, the design of the armature is such as to provide ready entrance of fluid into any void that might tend to form during release of the armature. This also improves the release time for the mechanism. The large holding force for the mechanism is accomplished by providing a small, selected, uniform air gap between the inner pole piece and the armature.

  16. Muscle weakness in Ryr1I4895T/WT knock-in mice as a result of reduced ryanodine receptor Ca2+ ion permeation and release from the sarcoplasmic reticulum.

    Loy, Ryan E; Orynbayev, Murat; Xu, Le; Andronache, Zoita; Apostol, Simona; Zvaritch, Elena; MacLennan, David H; Meissner, Gerhard; Melzer, Werner; Dirksen, Robert T


    The type 1 isoform of the ryanodine receptor (RYR1) is the Ca(2+) release channel of the sarcoplasmic reticulum (SR) that is activated during skeletal muscle excitation-contraction (EC) coupling. Mutations in the RYR1 gene cause several rare inherited skeletal muscle disorders, including malignant hyperthermia and central core disease (CCD). The human RYR1(I4898T) mutation is one of the most common CCD mutations. To elucidate the mechanism by which RYR1 function is altered by this mutation, we characterized in vivo muscle strength, EC coupling, SR Ca(2+) content, and RYR1 Ca(2+) release channel function using adult heterozygous Ryr1(I4895T/+) knock-in mice (IT/+). Compared with age-matched wild-type (WT) mice, IT/+ mice exhibited significantly reduced upper body and grip strength. In spite of normal total SR Ca(2+) content, both electrically evoked and 4-chloro-m-cresol-induced Ca(2+) release were significantly reduced and slowed in single intact flexor digitorum brevis fibers isolated from 4-6-mo-old IT/+ mice. The sensitivity of the SR Ca(2+) release mechanism to activation was not enhanced in fibers of IT/+ mice. Single-channel measurements of purified recombinant channels incorporated in planar lipid bilayers revealed that Ca(2+) permeation was abolished for homotetrameric IT channels and significantly reduced for heterotetrameric WT:IT channels. Collectively, these findings indicate that in vivo muscle weakness observed in IT/+ knock-in mice arises from a reduction in the magnitude and rate of RYR1 Ca(2+) release during EC coupling that results from the mutation producing a dominant-negative suppression of RYR1 channel Ca(2+) ion permeation.

  17. Changes in arterial stiffness, carotid intima-media thickness, and epicardial fat after L-thyroxine replacement therapy in hypothyroidism.

    del Busto-Mesa, Abdel; Cabrera-Rego, Julio Oscar; Carrero-Fernández, Lisván; Hernández-Roca, Cristina Victoria; González-Valdés, Jorge Luis; de la Rosa-Pazos, José Eduardo


    To assess the relationship between primary hypothyroidism and subclinical atherosclerosis and its potential changes with L-thyroxine replacement therapy. A prospective cohort study including 101 patients with primary hypothyroidism and 101 euthyroid patients as controls was conducted from July 2011 to December 2013. Clinical, anthropometrical, biochemical, and ultrasonographic parameters were assessed at baseline and after one year of L-thyroxine replacement therapy. At baseline, hypothyroid patients had significantly greater values of blood pressure, total cholesterol, VLDL cholesterol, left ventricular mass, epicardial fat, and carotid intima-media thickness as compared to controls. Total cholesterol, VLDL cholesterol, ventricular diastolic function, epicardial fat, carotid intima-media thickness, carotid local pulse wave velocity, pressure strain elastic modulus, and β arterial stiffness index showed a significant and positive correlation with TSH levels. After one year of replacement therapy, patients with hypothyroidism showed changes in total cholesterol, VLDL cholesterol, TSH, carotid intima-media thickness, and arterial stiffness parameters. Primary hypothyroidism is characterized by an increased cardiovascular risk. In these patients, L-thyroxine replacement therapy for one year is related to decreased dyslipidemia and improvement in markers of subclinical carotid atherosclerosis. Copyright © 2014 SEEN. Published by Elsevier España, S.L.U. All rights reserved.

  18. Erythropoietin, testosterone, and thyroxine in the erythropoietic response of the snake, Xenochrophis piscator.

    Pati, A K; Thapliyal, J P


    The erythropoietic response of snakes was examined after injecting human urinary erythropoietin (Ep), testosterone propionate (TP), and L-thyroxine (T4), separately and in combinations, into starved ophids. The effect of starvation was reflected by a decrease in the number of erythrocytes, a fall in hemoglobin concentration, and a decline in hematocrit. Statistically significant elevation of erythrocyte number, hemoglobin concentration, and hematocrit was observed at 24 hr following the administration of Ep + T4, and Ep + TP + T4 into starved ophids. The erythrocyte number was also increased by T4 treatment at 24 hr. Furthermore, while T4 and Ep individually increased the red blood cell number at 168 hr, T4, TP + T4, and Ep + TP + T4 elevated the hemoglobin concentration and Ep + T4 and Ep + TP + T4 increased the hematocrit value. It is suggested that the influence of any one of the hormones utilized in the present study on blood morphology of fasted snakes depends to a greater extent on the presence or absence of the other hormone(s).

  19. CyPPA, a Positive SK3/SK2 Modulator, Reduces Activity of Dopaminergic Neurons, Inhibits Dopamine Release, and Counteracts Hyperdopaminergic Behaviors Induced by Methylphenidate

    Herrik, Kjartan F; Redrobe, John P; Holst, Dorte


    Dopamine (DA) containing midbrain neurons play critical roles in several psychiatric and neurological diseases, including schizophrenia and attention deficit hyperactivity disorder, and the substantia nigra pars compacta neurons selectively degenerate in Parkinson's disease. Pharmacological...... modulation of DA receptors and transporters are well established approaches for treatment of DA-related disorders. Direct modulation of the DA system by influencing the discharge pattern of these autonomously firing neurons has yet to be exploited as a potential therapeutic strategy. Small conductance Ca(2...... mouse and rat midbrain slices. Using an immunocytochemically and pharmacologically validated DA release assay employing cultured DA neurons from rats, we show that CyPPA repressed DA release in a concentration-dependent manner with a maximal effect equal to the D2 receptor agonist quinpirole. In vivo...

  20. Transcranial focal electrical stimulation reduces the convulsive expression and amino acid release in the hippocampus during pilocarpine-induced status epilepticus in rats.

    Santana-Gómez, César E; Alcántara-González, David; Luna-Munguía, Hiram; Bañuelos-Cabrera, Ivette; Magdaleno-Madrigal, Víctor; Fernández-Mas, Rodrigo; Besio, Walter; Rocha, Luisa


    The aim of the present study was to evaluate the effects of transcranial focal electrical stimulation (TFS) on γ-aminobutyric acid (GABA) and glutamate release in the hippocampus under basal conditions and during pilocarpine-induced status epilepticus (SE). Animals were previously implanted with a guide cannula attached to a bipolar electrode into the right ventral hippocampus and a concentric ring electrode placed on the skull surface. The first microdialysis experiment was designed to determine, under basal conditions, the effects of TFS (300 Hz, 200 μs biphasic square pulses, for 30 min) on afterdischarge threshold (ADT) and the release of GABA and glutamate in the hippocampus. The results obtained indicate that at low current intensities (Status Epilepticus".

  1. Corticotropin-Releasing Factor-Overexpressing Mice Exhibit Reduced Neuronal Activation in the Arcuate Nucleus and Food Intake in Response to Fasting


    Corticotropin-releasing factor (CRF) overexpressing (OE) mice are a genetic model that exhibits features of chronic stress. We investigated whether the adaptive feeding response to a hypocaloric challenge induced by food deprivation is impaired under conditions of chronic CRF overproduction. Food intake response to a 16-h overnight fast and ip injection of gut hormones regulating food intake were compared in CRF-OE and wild type (WT) littermate mice along with brain Fos expression, circulatin...

  2. MDMA increases glutamate release and reduces parvalbumin-positive GABAergic cells in the dorsal hippocampus of the rat: role of cyclooxygenase.

    Anneken, John H; Cunningham, Jacobi I; Collins, Stuart A; Yamamoto, Bryan K; Gudelsky, Gary A


    3,4-Methylenedioxymethamphetamine (MDMA; Ecstasy) is a popular drug of abuse with well-documented acute effects on serotonergic, dopaminergic, and cholinergic transmitter systems, as well as evidence of long-term disruption of serotoninergic systems in the rat brain. Recently, it was demonstrated that MDMA evokes a delayed and sustained increase in glutamate release in the hippocampus. The purpose of the present study was to determine the role of inflammatory mediators in the MDMA-induced increase in glutamate release, as well as the contribution of inflammatory pathways in the persistent neurochemical toxicity associated with repeated MDMA treatment. Treatment with the non-selective cyclooxygenase (COX) inhibitor ketoprofen and the COX-2 selective inhibitor nimesulide attenuated the increase in extracellular glutamate in the hippocampus evoked by repeated MDMA exposure (10 mg/kg, i.p., every 2 h); no attenuation was observed in rats treated with the COX-1 selective inhibitor piroxicam. Reverse dialysis of a major product of COX activity, prostaglandin E2, also resulted in a significant increase in extracellular glutamate in the hippocampus . Repeated exposure to MDMA diminished the number of parvalbumin-positive GABA interneurons in the dentate gyrus of the hippocampus, an effect that was attenuated by ketoprofen treatment. However, COX inhibition with ketoprofen did not prevent the long-term depletion of 5-HT in the hippocampus evoked by MDMA treatment. These data are supportive of the view that cyclooxygenase activity contributes to the mechanism underlying both the increased release of glutamate and decreased number of GABA interneurons in the rat hippocampus produced by repeated MDMA exposure.

  3. Growth Hormone-Releasing Peptide-2 Suppresses Vascular Oxidative Stress in ApoE−/− Mice But Does Not Reduce Atherosclerosis


    GH-releasing peptide-2 (GHRP-2) is a synthetic peptide that increases circulating GH and IGF-I levels. It also binds to CD36, a scavenger receptor for oxidized low-density lipoprotein (OxLDL), and may prevent cellular uptake of this proatherogenic complex. To determine its potential antiatherogenic effects, GHRP-2 (20 μg twice daily) was administered sc to ApoE−/− mice for 12 wk. GHRP-2 increased circulating IGF-I 1.2- to 1.6-fold and decreased circulating interferon-γ by 66%. Although GHRP-2...

  4. Sustained-release protamine sulphate-impregnated microspheres may reduce the frequent administration of recombinant interferon α-2b in ovarian cancer: in-vitro characterization.

    Gulia, Monika; Rai, Shweta; Jain, Upendra Kumar; Katare, Om Prakash; Katyal, Anju; Madan, Jitender


    Parenteral administration of recombinant interferon-α-2b (rINF-α-2b) at a dose of 50×10 IU once a week for 8 weeks is recommended for ovarian cancer. However, short half-life, small therapeutic index and proteolytic degradation cause fluctuations in plasma level and pose barriers in the development of a clinically viable dosage form. Therefore, in the present investigation, fluorescein isothiocynate-tagged rINF-α-2b was loaded into stearic acid (*rINF-α-2b-SMs), pectin (*rINF-α-2b-PMs) and gelatin (*rINF-α-2b-GMs) microspheres. Parameters such as particle size, ζ potential, encapsulation efficiency and in-vitro release were studied to follow the optimization process. The formulation, *rINF-α-2b-GMs of particle size 8.3±2.1 μm with an encapsulation efficiency of 76.0±7.4%, offered 97.4% of *rINF-α-2b release at 288 h. Thus, negatively charged extended-release formulation *rINF-α-2b-GMs was then tethered with a gradient concentration (5-20 mg/ml) of a cationic arginine-rich protein stabilizer, protamine sulphate (Pt). The nanoformulation, *rINF-α-2b-Pt-GMs-15 superimposed with 15 mg/ml of Pt, released 95.0% of *rINF-α-2b at 336 h and was designated as the optimized formulation. The optimized formulation also conserved the primary and secondary structure of *rINF-α-2b as analysed by gel electrophoresis and circular dichroism. Moreover, in-vitro cytotoxicity analysis of SKOV3 cells of the optimized nanoformulation reported significantly (one-way analysis of variance test, P<0.05) lower IC50 (414.3 IU/ml) compared with *rINF-α-2b-GMs (514.3 IU/ml) and pure rINF-α-2b (628.6 IU/ml) at 72 h by offering a prolonged cytotoxic effect. Therefore, *rINF-α-2b-Pt-GMs-15, a promising nanomedicine, warrants further in-depth in-vivo study to scale up the technology for clinical translation.

  5. The minor C-allele of rs2014355 in ACADS is associated with reduced insulin release following an oral glucose load

    Pisinger Charlotta; Lauritzen Torsten; Sandbæk Annelli; Andersson Åsa; Sandholt Camilla H; Krarup Nikolaj T; Justesen Johanne M; Banasik Karina; Hornbak Malene; Witte Daniel R; Sørensen Thorkild IA; Pedersen Oluf; Hansen Torben


    Abstract Background A genome-wide association study (GWAS) using metabolite concentrations as proxies for enzymatic activity, suggested that two variants: rs2014355 in the gene encoding short-chain acyl-coenzyme A dehydrogenase (ACADS) and rs11161510 in the gene encoding medium-chain acyl-coenzyme A dehydrogenase (ACADM) impair fatty acid β-oxidation. Chronic exposure to fatty acids due to an impaired β-oxidation may down-regulate the glucose-stimulated insulin release and result in an increa...

  6. Curcumin reduces prostaglandin E2, matrix metalloproteinase-3 and proteoglycan release in the secretome of interleukin 1β-treated articular cartilage [v2; ref status: indexed,

    Abigail L Clutterbuck


    Full Text Available Objective: Curcumin (diferuloylmethane is a phytochemical with potent anti-inflammatory and anti-oxidant properties, and has therapeutic potential for the treatment of a range of inflammatory diseases, including osteoarthritis (OA. The aim of this study was to determine whether non-toxic concentrations of curcumin can reduce interleukin-1beta (IL-1β-stimulated inflammation and catabolism in an explant model of cartilage inflammation. Methods: Articular cartilage explants and primary chondrocytes were obtained from equine metacarpophalangeal joints. Curcumin was added to monolayer cultured primary chondrocytes and cartilage explants in concentrations ranging from 3μM-100μM. Prostaglandin E2 (PGE2 and matrix metalloproteinase (MMP-3 release into the secretome of IL-1β-stimulated explants was measured using a competitive ELISA and western blotting respectively. Proteoglycan (PG release in the secretome was measured using the 1,9-dimethylmethylene blue (DMMB assay. Cytotoxicity was assessed with a live/dead assay in monolayer cultures after 24 hours, 48 hours and five days, and in explants after five days. Results: Curcumin induced chondrocyte death in primary cultures (50μM p<0.001 and 100μM p<0.001 after 24 hours. After 48 hours and five days, curcumin (≥25μM significantly increased cell death (p<0.001 both time points. In explants, curcumin toxicity was not observed at concentrations up to and including 25μM after five days. Curcumin (≥3μM significantly reduced IL-1β-stimulated PG (p<0.05 and PGE2 release (p<0.001 from explants, whilst curcumin (≥12μM significantly reduced MMP-3 release (p<0.01. Conclusion: Non-cytotoxic concentrations of curcumin exert anti-catabolic and anti-inflammatory effects in cartilage explants.

  7. Curcumin reduces prostaglandin E2, matrix metalloproteinase-3 and proteoglycan release in the secretome of interleukin 1β-treated articular cartilage [v1; ref status: indexed,

    Abigail L Clutterbuck


    Full Text Available Objective: Curcumin (diferuloylmethane is a phytochemical with potent anti-inflammatory and anti-oxidant properties, and has therapeutic potential for the treatment of a range of inflammatory diseases, including osteoarthritis (OA. The aim of this study was to determine whether non-toxic concentrations of curcumin can reduce interleukin-1beta (IL-1β-stimulated inflammation and catabolism in an explant model of cartilage inflammation. Methods: Articular cartilage explants and primary chondrocytes were obtained from equine metacarpophalangeal joints. Curcumin was added to monolayer cultured primary chondrocytes and cartilage explants in concentrations ranging from 3μM-100μM. Prostaglandin E2 (PGE2 and matrix metalloproteinase (MMP-3 release into the secretome of IL-1β-stimulated explants was measured using a competitive ELISA and western blotting respectively. Proteoglycan (PG release in the secretome was measured using the 1,9-dimethylmethylene blue (DMMB assay. Cytotoxicity was assessed with a live/dead assay in monolayer cultures after 24 hours, 48 hours and five days, and in explants after five days. Results: Curcumin induced chondrocyte death in primary cultures (50μM p<0.001 and 100μM p<0.001 after 24 hours. After 48 hours and five days, curcumin (≥25μM significantly increased cell death (p<0.001 both time points. In explants, curcumin toxicity was not observed at concentrations up to and including 25μM after five days. Curcumin (≥3μM significantly reduced IL-1β-stimulated PG (p<0.05 and PGE2 release (p<0.001 from explants, whilst curcumin (≥12μM significantly reduced MMP-3 release (p<0.01. Conclusion: Non-cytotoxic concentrations of curcumin exert anti-catabolic and anti-inflammatory effects in cartilage explants.

  8. Exovascular application of epigallocatechin-3-O-gallate-releasing electrospun poly(L-lactide glycolic acid) fiber sheets to reduce intimal hyperplasia in injured abdominal aorta.

    Lee, Mi Hee; Kwon, Byeong-ju; Koo, Min-Ah; Jang, Eui Hwa; Seon, Gyeung Mi; Park, Jong-Chul


    Intimal hyperplasia is an excessive ingrowth of tissue resulting in chronic structural lesions commonly found at sites of atherosclerotic lesions, arterial angioplasty, vascular graft anastomoses, and other vascular abnormalities. Epigallocatechin-3-O-gallate (EGCG) was shown to elicit antioxidant, anti-proliferative, and anti-thrombogenic effects. In this study, we used an electrospinning technique to synthesize EGCG-eluting biodegradable poly(L-lactide glycolic acid) (PLGA) fiber sheets for local delivery of EGCG and investigated the effect of their exovascular application on intimal hyperplasia following balloon-induced abdominal aorta injury in a rabbit experimental model. The morphology of the composite sheets was characterized using scanning electron microscopy and Fourier transform-infrared spectroscopy. EGCG was loaded and dispersed into the PLGA-based electrospun fibers. The EGCG-loaded PLGA sheets exhibited sustained EGCG release following the initial 24 h of burst release in phosphate-buffered saline. In vivo studies demonstrated significant inhibition of intimal hyperplasia following the application of the EGCG-eluting electrospun PLGA fiber sheets, compared with vehicle PLGA controls. In conclusion, our results show that exovascular application of EGCG-eluting PLGA electrospun fiber sheets may provide a useful system for the effective local delivery of drugs for the prevention of intimal hyperplasia.

  9. Effect of adjuvant lithium on thyroxine (T4) concentration after radioactive iodine therapy

    Hammond, Emmanuel NiiBoye; Vangu, Mboyo-Di-Tamba Heben Willy [University of the Witwatersrand, Division of Nuclear Medicine and Molecular Imaging, Department of Radiation Sciences, Johannesburg (South Africa)


    To study the effect of adjuvant lithium on serum thyroxine (T4) concentrations in patients treated with radioactive iodine (RAI) therapy in our environment. This was a prospective simple randomized comparative, experimental cohort study of patients with hyperthyroidism referred for RAI ablation therapy in the two main academic hospitals in Johannesburg between February 2014 and September 2015. Amongst the 163 participants in the final analysis, 75 received RAI alone and 88 received RAI with lithium. The difference in mean T4 concentrations at 3 months between the RAI-only group (17.67 pmol/l) and the RAI with lithium group (11.55 pmol/l) was significant with a small effect size (U = 2328.5, Z = -2.700, p = 0.007, r = 0.01). Significant decreases in T4 concentrations were observed as early as 1 month after RAI (p = 0.0001) in the RAI with lithium group, but in the RAI-only group, significant decreases in T4 concentrations were observed only at 3 months after RAI therapy (p = 0.000). Women and patients with Graves' disease who received RAI with adjuvant lithium also showed significant decreases in T4 concentrations at 1 month (p = 0.002 and p = 0.003, respectively). Adjuvant lithium leads to an earlier and better response to RAI therapy with lower T4 concentrations that are achieved earlier. This earlier response and decrease in T4 concentrations were noted in patients with Graves' disease and nodular goitre, and in women with hyperthyroidism who received adjuvant lithium therapy. (orig.)

  10. Circulating thyroxine, thyroid-stimulating hormone, and hypothyroid status and the risk of prostate cancer.

    Alison M Mondul

    Full Text Available BACKGROUND: Thyroid hormones may influence risk of cancer through their role in cell differentiation, growth, and metabolism. One study of circulating thyroid hormones supports this hypothesis with respect to prostate cancer. We undertook a prospective analysis of thyroid hormones and prostate cancer risk in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC Study. METHODS: Within the ATBC Study, a randomized controlled trial of α-tocopherol and β-carotene supplements and cancer incidence in male smokers, 402 prostate cancer cases were sampled. Controls were matched 2:1 to cases on age and date of blood collection. Odds ratios (OR and 95% confidence intervals (CI of prostate cancer were estimated for quintiles of serum total and free thyroxine (T4, thyroid-stimulating hormone (TSH, thyroid-binding globulin (TBG, and by categories of thyroid status. RESULTS: Men with serum higher TSH had a decreased risk of prostate cancer compared to men with lower TSH (Q5 vs. Q1-4: OR = 0.70, 95% CI: 0.51-0.97, p = 0.03. When the T4 and TSH measurements were combined to define men as hypothyroid, euthyroid or hyperthyroid, hypothyroid men had a lower risk of prostate cancer compared to euthyroid men (OR = 0.48, 95% CI = 0.28-0.81, p = 0.006. We observed no association between hyperthyroid status and risk, although the number of hyperthyroid men with prostate cancer was small (n = 9. CONCLUSIONS: In this prospective study of smokers, men with elevated TSH and those classified as being in a hypothyroid state were at decreased risk of prostate cancer. Future studies should examine the association in other populations, particularly non-smokers and other racial/ethnic groups.

  11. Seasonal variations in TSH serum levels in athyreotic patients under L-thyroxine replacement monotherapy.

    Gullo, Damiano; Latina, Adele; Frasca, Francesco; Squatrito, Sebastiano; Belfiore, Antonino; Vigneri, Riccardo


    Whether serum TSH undergoes seasonal fluctuations in euthyroid and hypothyroid residents of temperate climates is controversial. Monthly TSH and thyroid hormone levels were cross-sectionally analysed in a large cohort of euthyroid subjects (n=11 806) and L-thyroxine (L-T4)-treated athyreotic patients (n=3 934). Moreover, in a small group (n=119) of athyreotic patients treated with an unchanged dosage of L-T4 monotherapy, hormones were measured both in the coldest and in the hottest seasons of the same year (longitudinal study). No seasonal hormone change was observed in the euthyroid subjects except for a small FT3 increase in winter (+2.9%, PL-T4-treated athyreotic patients had significantly higher serum TSH values in the cold season when the FT4 values were significantly lower. The differences were more notable in the longitudinal series (TSH, 0.80 vs. 0.20 mU/L and FT4, 16.3 vs. 17.8 pmol/L in December-March vs. June-September, respectively). In these patients also serum FT3 values significantly decreased in winter (in the longitudinal series, 3.80 in winter vs 4.07 pmol/L in summer). Regression analysis showed that in athyreotic subjects, a greater FT4 change is required to obtain a TSH change similar to that of euthyroid controls and that this effect is more pronounced in the summer. Athyreotic patients undergoing L-T4 monotherapy have abnormal seasonal variations in TSH. These changes are secondary to the FT4 and FT3 serum decreases in winter, which occur in spite of the constant treatment. The underlying mechanisms are unclear, but in some cases, these changes may be clinically relevant. © 2017 John Wiley & Sons Ltd.

  12. Thyroxine differentially modulates the peripheral clock: lessons from the human hair follicle.

    Jonathan A Hardman

    Full Text Available The human hair follicle (HF exhibits peripheral clock activity, with knock-down of clock genes (BMAL1 and PER1 prolonging active hair growth (anagen and increasing pigmentation. Similarly, thyroid hormones prolong anagen and stimulate pigmentation in cultured human HFs. In addition they are recognized as key regulators of the central clock that controls circadian rhythmicity. Therefore, we asked whether thyroxine (T4 also influences peripheral clock activity in the human HF. Over 24 hours we found a significant reduction in protein levels of BMAL1 and PER1, with their transcript levels also decreasing significantly. Furthermore, while all clock genes maintained their rhythmicity in both the control and T4 treated HFs, there was a significant reduction in the amplitude of BMAL1 and PER1 in T4 (100 nM treated HFs. Accompanying this, cell-cycle progression marker Cyclin D1 was also assessed appearing to show an induced circadian rhythmicity by T4 however, this was not significant. Contrary to short term cultures, after 6 days, transcript and/or protein levels of all core clock genes (BMAL1, PER1, clock, CRY1, CRY2 were up-regulated in T4 treated HFs. BMAL1 and PER1 mRNA was also up-regulated in the HF bulge, the location of HF epithelial stem cells. Together this provides the first direct evidence that T4 modulates the expression of the peripheral molecular clock. Thus, patients with thyroid dysfunction may also show a disordered peripheral clock, which raises the possibility that short term, pulsatile treatment with T4 might permit one to modulate circadian activity in peripheral tissues as a target to treat clock-related disease.

  13. Measurement of thyroid hormones (thyroxine, T4; triiodothyronine, T3) in captive nondomestic felids.

    Rodini, Débora Cattaruzzi; Felippe, Erika Cristiane Gutierrez; Oliveira, Cláudio Alvarenga


    The aim of this research was to obtain basic values for the evaluation of thyroid function in nondomestic felids. Serum thyroid hormone concentrations (thyroxine, T4; triiodothyronine, T3) were measured by radioimmunoassay in 145 cats, representing nine species of captive nondomestic felids: jaguar (Panthera onca), n = 49; puma (Puma concolor), n = 10; ocelot (Leopardus pardalis), n = 22; oncilla (Leopardus tigrinus), n = 12; geoffroy (Oncifelis geoffroyi), n = 4; jaguarundi (Herpailurus yaguarondi), n = 8; margay (Leopardus wiedii), n = 7; lion (Panthera leo), n = 26; and tiger (Panthera tigris), n = 7. For each species, mean +/- SEM of T3 and T4, respectively, were as follows: jaguar, 0.56 +/- 0.03 and 9.7 +/- 0.8 ng/ml; puma, 0.67 +/- 0.04 and 11.2 +/- 1.2 ng/ml; ocelot, 0.48 +/- 0.03 and 13.8 +/- 1.5 ng/ml; oncilla, 0.43 +/- 0.03 and 10.0 +/- 1.6 ng/ml; geoffroy, 0.44 +/- 0.04 and 8.0 +/- 0.16 ng/ml; jaguarundi, 0.7 +/- 0.03 and 5.0 +/- 1.0 ng/ml; margay, 0.48 +/- 0.04 and 12.2 +/- 2.3 ng/ml; lion, 0.43 +/- 0.02 and 5.7 +/- 2.6 ng/ml; and tiger, 0.66 +/- 0.03 and 12.6 +/- 0.9 ng/ml. Within species, T3 and T4 concentrations did not differ (P > 0.05) between males and females.

  14. Reduced radioiodine uptake at increased iodine intake and {sup 131}I-induced release of ''cold'' iodine stored in the thyroid

    Meller, B.; Haase, A.; Richter, E.; Baehre, M. [Dept. of Radiotherapy and Nuclear Medicine, Univ. of Luebeck (Germany); Seyfarth, M. [Inst. of Clinical Chemistry, Univ. of Luebeck (Germany); Wenzel, B.E. [Clinic of Internal Medicine I, Univ. of Luebeck (Germany)


    Aim: the extent of urinary iodine excretion (UIE) provides information about iodine supply and release. In the present study we investigated correlations between UIE and radioiodine uptake (RIU) as well as effects of radioiodine therapy on UIE in patients with autonomous goitre. Patients, methods: In 197 consecutive patients with thyroid autonomy, UIE was measured twice during radioiodine test (RITe) and correlated with RIU. In 98 of these patients, thyroglobulin and thyroid volume (V) were determined prior to therapy. Individual changes in urinary iodine excretion ({delta}UIE) and TG ({delta}TG) could be investigated four weeks (4W) and six months (6M) after radioiodine therapy. Additionally, {delta}V was determined 6M after therapy. {delta}UIE, {delta}TG and {delta}V were correlated with target dose and target volume. Results: patients with higher iodine excretion exhibited significantly lower thyroidal radioiodine uptake values. Twofold increased UIE prior to therapy decreased radioiodine uptake by 25%. Compared with pretherapeutic values, UIE and TG were significantly increased four weeks after radioiodine therapy (p < 0.001). Median values of both parameters were found to be doubled. The product of target dose and target volume was not only correlated with a decrease of thyroid volume 6M after therapy, but also with an increase of UIE and TG in the early phase after therapy. Conclusions: it was confirmed that UIE during RITe is a measure for iodine intake and can be used to investigate the competition between stable iodine and radioiodine. The increase of UIE and TG four weeks after therapeutic administration of radioiodine can be explained by disintegrated thyroid follicles. The therapy-induced iodine release may be one important cause for the development of hyperthyroidism in some patients during the first weeks after radioiodine therapy. It may contribute to the known decrease of radioiodine uptake after preapplications of {sup 131}I in various thyroid

  15. CyPPA, a positive SK3/SK2 modulator, reduces activity of dopaminergic neurons, inhibits dopamine release, and counteracts hyperdopaminergic behaviors induced by methylphenidate

    Kjartan F. Herrik


    Full Text Available Dopamine (DA containing midbrain neurons play critical roles in several psychiatric and neurological diseases, including schizophrenia and attention deficit hyperactivity disorder (ADHD, and the substantia nigra pars compacta neurons selectively degenerate in Parkinson’s disease. Pharmacological modulation of DA receptors and transporters are well established approaches for treatment of DA-related disorders. Direct modulation of the DA system by influencing the discharge pattern of these autonomously firing neurons has yet to be exploited as a potential therapeutic strategy. Small conductance Ca2+-activated K+ channels (SK channels, in particular the SK3 subtype, are important in the physiology of DA neurons, and agents modifying SK channel activity could potentially affect DA-signaling and DA-related behaviors. Here we show that CyPPA (cyclohexyl-[2-(3,5-dimethyl-pyrazol-1-yl-6-methyl-pyrimidin-4-yl]-amine, a subtype-selective positive modulator of SK channels (SK3 > SK2 >>> SK1, IK, decreased spontaneous firing rate, increased the duration of the apamin-sensitive, medium duration afterhyperpolarization (mAHP, and caused an activity-dependent inhibition of current-evoked action potentials in DA neurons from both mouse and rat midbrain slices. Using a immunohistochemically and pharmacologically validated DA release assay employing cultured DA neurons from rats, we show that CyPPA repressed DA release in a concentration-dependent manner with a maximal effect equal to the D2 receptor agonist quinpirole. In vivo studies revealed that systemic administration of CyPPA attenuated methylphenidate-induced hyperactivity and stereotypic behaviors in mice. Taken together, the data accentuate the important role played by SK3 channels in the physiology of DA neurons, and indicate that their facilitation by CyPPA profoundly influences physiological as well as pharmacologically induced hyperdopaminergic behavior.

  16. Recalculation of data from 1990 to 2010 on the effects of highly diluted thyroxine on the metamorphosis of highland amphibians

    Peter Christian Endler


    Full Text Available Experiments on amphibian metamorphosis can vary considerably in duration. The authors had set themselves the task of defining a generally applicable pooling method for metamorphosis experiments [1]. Normalization with respect to time was done on the assumption that differences in speed of metamorphosis attributable to treatment would override differences in duration between experiments. The problem of artificial differences in variability when comparing and pooling data from several experiments was approached by normalization with respect to time based on the development of both the test and the control animals. The range from 0% to 100% over which the fraction of four-legged animals progresses in the course of an experiment is divided into 10%-intervals and mapped onto a corresponding relative scale. Each measurement is then assigned to the point on the 10%-scale to which it is closest. In this way each reference point is assigned a value giving the number or percentage of four-legged animals at that point. These values are aggregated over all experiments within the test- and control-group. The results of experiments performed over the course of two decades (1990 - 2010 on highland Rana temporaria treated with a homeopathically prepared high dilution of thyroxine (“30x” are presented in full detail based on this normalization method[1]. It was found that differences between treatment groups thus calculated were in line with those obtained with other pooling methods [2]. Thyroxine 30x does slow down metamorphosis in inert highland amphibians. This was observed by 5 researchers in 20 sub-experiments, and it seems to be the most reliable bio-assay found in amphibian research on homeopathy so far2. When experiments were performed with highland animals pretreated by hyperstimulation with molecular thyroxine, slowing down of metamorphosis was again observed (by 3 of 4 researchers in most of 10 sub-experiments.

  17. Intracellular Conversion of Thyroxine to Triidothyronine Is Required for the Optimal Thermogenic Function of Brown Adipose Tissue


    The effect of thyroxine (T4) and triiodothyronine (T3) on the expression of uncoupling protein (UCP) in rat brown adipose tissue (BAT) has been examined. Thyroidectomized rats have a threefold reduction in basal UCP levels. When exposed to cold, they become hypothermic and show a fivefold lower response of UCP than euthyroid controls. T3 augments the basal levels and the response of UCP and its mRNA to cold in a dose-dependent manner. However, to normalize the response of UCP, T3 has to be gi...

  18. D-propranolol and DL-propranolol both decrease conversion of L-thyroxine to L-triiodothyronine.

    Heyma, P; Larkins, R G; Higginbotham, L; Ng, K. W.


    The effects of propranolol (DL-propranolol) and D-propranolol on thyroid hormone metabolism were studied in six euthyroid volunteers receiving L-thyroxine (T4) and six hypothyroid patients receiving T4 replacement. D-propranolol as well as propranolol decreased L-triiodothyronine (T3) concentrations and the ratio of T3 to T4 in the euthyroid subjects, and D-propranolol decreased these variables in the subjects with hypothyroidism (propranolol was not given to this group). It is concluded from...

  19. Thyroid Function Test in Thyroid Diseases and Pregnancy - The diagnostic value of free thyroxine by RIA -

    Yoo, M. H.; Yoon, H. J.; Shin, Y. T.; Lee, J. C.; Chung, S. I.; Cho, B. Y.; Lee, M. H. [Seoul National University College of Medicine, Seoul (Korea, Republic of); Lee, M. C. [Capotal Armed Forces General Hospital, Seoul (Korea, Republic of)


    To evaluate the diagnostic accuracy of the measurement of free thyroxine(FT4) by radioimmunoassay, we measured free T{sub 4} and T{sub 4}, T{sub 3}, T{sub 3}RU, TSH and TBG serum levels by radioimmunoassay in 18 healthy persons and 52 patients with various thyroid diseases and 11 normal pregnant women. The results are as follows. 1) In 19 cases of overt hyperthyroidism, T{sub 3}, free T{sub 4} and FTI, T{sub 4}/TBG ratio reflect hyperfunction in all cases. T{sub 4} is increased in 94%(18/19) and TBG and TSH are decreased in 79%(15/19). 2) In 8 patients with overt hypothyroidism, TSH is increased in all cases and free T{sub 4} and FTI is decreased in all cases. T{sub 4} is decreased in 87.5%(7/8), T{sub 3} is decreased in 75%(6/8) and T{sub 4}/TBG ratio is decreased in 62.5%(5/8). 3) In 5 patients who are clinically in euthyroid state after treatment of hyperthyroidism, T{sub ,}4 free T{sub 4}, FTI and TSH are in the normal range in all cases and T{sub 3} is normal in 60%(3/5) and slightly increased in 40%(2/5). 4) In 10 patients who showed clinically borderline hypothyroidism after treatment of hyperthyroidism, TSH is increased in all cases and free T{sub 4} and FTI are decreased in all cases, but T{sub 4} and T{sub 3}, T{sub 4}/TBG ratio are in the normal limit in all cases. So after treatment of hyperthyroidism, TSH, free T{sub 4} or FTI are recommended as optimal function test. 5) In normal pregnancy, free T{sub 4}, FTI and T{sub 4}/TBG ratio reflect normal function, but the other parameters unreliable due to the influence of increased TBG. Also TBG and TSH level in pregnancy is increased significantly compared with normal healthy control group. 6) The coefficients of correlation between T{sub 4} and FTI were 0.862(p<0.001) and 0.685(p<0.001) between free T{sub 4} and T{sub 4}/TBG ratio. In most patients, diagnostic value of free T{sub 4} was comparable and even superior to FTI, so free T{sub 4} measurement can be used routinely with thyrotropin assay in the

  20. Individually-tailored thyroxine requirement in the same patients before and after thyroidectomy: a longitudinal study.

    Del Duca, S C; Santaguida, M G; Brusca, N; Gatto, I; Cellini, M; Gargano, L; Verga Falzacappa, C; Frattaroli, F M; Virili, C; Centanni, M


    Thyroxine (T4) requirement after total thyroidectomy for differentiated thyroid carcinoma (DTC) is a debated issue. As most of the studies in the area have been retrospective and/or performed with heterogeneous therapeutic approaches, we designed our study to determine T4 requirement in the same patients and treatment settings, before and after total thyroidectomy. This was a longitudinal study including 23 goitrous patients treated with T4 in an individually tailored fashion. All patients exhibited a stable TSH (median TSH = 0.28 mU/l) at a stable T4 dose for at least 1 year before surgery (median T4 dose = 1.50 μg/kg per day). The patients underwent total thyroidectomy based on cancer suspicion or compressive symptoms. Eventually diagnosed as having DTC (pT1b-pT2N0) and following surgical and radiometabolic treatment, they were treated with the same pre-surgical doses of T4. Three months after surgery,using the same pre-surgical dose, median TSH increased up to 5.38 mU/l (P<0.0001) and so the T4 dose had to be increased (median T4 dose = 1.95 μg/kg per day; +30%; P < 0.0001). Once divided by patients' age, we observed that, after thyroidectomy and maintaining the same pre-surgical dose, serum TSH significantly increased both in younger and in older patients (median TSH = 4.57 and 6.11 mU/l respectively). Serum TSH was restored to the pre-surgical level by increasing the dose up to 1.95 and 1.77 μg/kg per day (+25 and +21%) respectively. Following the same treatment regimen, a thyroidectomized patient requires one-third higher therapeutic T4 dose than before surgery. Despite this increase, the dose of T4 needed in our patients remains significantly lower than that previously described in athyreotic patients. © 2015 European Society of Endocrinology.

  1. Thyroxine inner ring monodeiodinating activity in fetal tissues of the rat

    Huang, T.S.; Chopra, I.J.; Boado, R.; Soloman, D.H.; Chua Teco, G.N.


    We studied thyroxine (T4) inner ring monodeiodinating activity (5-MA) in various tissues of fetal, maternal, and adult male rats. Tissue homogenates were incubated with 0.26 microM T4 in 0.1 M phosphate buffer (pH 7.4) containing 10 mM EDTA and 400 mM dithiothreitol (final volume 0.7 ml) for 10 min at 37 degrees C; the 3,3',5'-triiodothyronine (rT3) generated was measured by radioimmunoassay of ethanol extracts of incubation mixture and the result was corrected for rT3 degradation during incubation. Compared to maternal tissues, T4 to rT3 5-MA in the 14-day-old fetus was increased about 70 times in skeletal muscle (mean +/- SEM, velocity, 5.4 +/- 0.9 versus 0.08 +/- 0.01, pmol rT3/h/mg protein); approximately 8 times in intestine (0.72 +/- 0.17 versus 0.09 +/- 0.03);and approximately 4 times in cerebral cortex (19 +/- 0.5 versus 4.5 +/- 0.9), while it was similar in skin (3.2 +/- 0.48 versus 2.6 +/- 0.52). Hepatic T4 5-MA approximated 1.1 +/- 0.63 in the 14-day-old fetus; it could not be measured reliably in maternal or 19-day fetal tissue because of extensive (greater than 90%) degradation of rT3 during incubation. Relative to mother, T4 5-MA in 19-day fetal tissues was increased approximately 30-fold intestine, approximately 20-fold in skeletal muscle, and approximately 6-fold in cerebral cortex while it was similar in skin. The T4 5-MA in maternal rat tissues did not differ significantly from corresponding values in adult male rat, except skin, where it was lower in the mother rat (2.6 +/- 0.52 versus 4.6 +/- 0.61, p less than 0.05). In summary, relative to adult tissues T4 5-MA is exceedingly active in several fetal tissues, most notably in skeletal muscle followed by intestine and cerebral cortex.

  2. [Olpadronate prevents cortical and trabecular bone loss induced by supraphysiological dosis of thyroxine in ovariectomized rats].

    Zeni, S N; Gómez Acotto, C; Di Gregorio, S


    The aim of the present report was to clarify the effect of excess T4 on axial and peripheral bone mineral density (BMD) in estrogen-depleted rats. The protective effect of olpadronate (Olpa) on axial and peripheral bone mass in thyroxine-treated rats was also investigated. Female Sprague-Dawley rats were used: SHAM, OVX + Vh, OVX + Olpa (0.3 mg/kg/week), OVX + T4 (250 micrograms/kg/day) and OVX + T4 + Olpa rats. OVX + Vh group presented a BMD lower than SHAM in the tibia (p < 0.01) but not in femur or lumbar spine; the middle tibia BMD did not change but it was lower at the distal (pns.) and proximal levels (p < 0.003) in OVX + Vh. OVX + T4 rats presented a BMD significantly lower than OVX + Vh rats in total tibia (p < 0.02), femur (p < 0.006) and lumbar spine (p < 0.006). Moreover the BMD was lower in all studied areas of the tibia, but it was statistically significant only at the middle level (p < 0.004). OVX + Olpa rats had a BMD higher than OVX + Vh rats in femur (p < 0.002), lumbar spine (p < 0.0001), total (p < 0.001) and proximal tibia (p < 0.001). Surprisingly, total and proximal tibia BMD values in OVX + Olpa rats presented a BMD significantly higher than OVX + T4 rats in femur (p < 0.001), lumbar spine (p < 0.001), tibia (p < 0.001) and proximal tibia (p < 0.0001). It is important to point out that OVX + T4 + Olpa BMD was significantly higher than in SHAM rats at the lumbar spine, total and proximal tibia (p < 0.01). The present study suggests that although supraphysiological thyroid hormone affected both cortical and trabecular bone, under estrogen-depleted conditions, the cortical bone appears to be more sensitive than the trabecular bone to T4 treatment. We also found that Olpa could prevent the peripheral and axial bone loss induced by thyroid hormone excess.

  3. Reducing scar formation by regulation of IL-1 and MMP-9 expression by using sustained release of prednisolone-loaded PDLL microspheres in a murine wound model.

    Wu, Tsui-Hsun; Hsu, Sung-Hao; Chang, Mei-Hwei; Huang, Yi-You


    In this study, we provide a new pharmacological treatment, which may prevent scar formation on wound healing and/or plastic surgery wounds. We used prednisolone to reduce scar formation in wound excision. To prolong the drug effect, prednisolone of different amounts were encapsulated in biodegradable poly(D,L-lactide) (PDLL) microspheres. In the in vitro cell healing study, prednisolone was markedly effective in reducing the growth rate of fibroblast cells according to electric cell-substrate impedance sensing results. At a higher density of prednisolone, a slower growth rate was observed (ANOVA, p increase MMP-9 expression levels as compared with the control groups (ANOVA, p scar tissue during wound regeneration by inhibiting the degree of inflammation.

  4. Poligalen, a new coumarin from Polygala boliviensis, reduces the release of TNF and IL-6 independent of NF-kB downregulation.

    Silva, Danielle F; Alves, Clayton Q; Brandão, Hugo N; David, Jorge M; David, Juceni P; Silva, Rangel L; Franchin, Marcelo; Cunha, Thiago M; Martins, Felipe T; Oliveira, Cecilia M A


    An unusually substituted coumarin, named poligalen, was isolated from a chloroform extract of the aerial parts of Polygala boliviensis. This coumarin was identified by one- and two-dimensional NMR techniques, and the structure of the compound was confirmed by X-ray diffraction. Poligalen exhibits immunomodulatory effects, reducing the levels of IL-6 and TNF after LPS stimulation in peritoneal macrophages. However, poligalen potentiates NF-kB activation.

  5. Reduced insulin-receptor mediated modulation of striatal dopamine release by basal insulin as a possible contributing factor to hyperdopaminergia in schizophrenia.

    Caravaggio, Fernando; Hahn, Margaret; Nakajima, Shinichiro; Gerretsen, Philip; Remington, Gary; Graff-Guerrero, Ariel


    Schizophrenia is a severe and chronic neuropsychiatric disorder which affects 1% of the world population. Using the brain imaging technique positron emission tomography (PET) it has been demonstrated that persons with schizophrenia have greater dopamine transmission in the striatum compared to healthy controls. However, little progress has been made as to elucidating other biological mechanisms which may account for this hyperdopaminergic state in this disease. Studies in animals have demonstrated that insulin receptors are expressed on midbrain dopamine neurons, and that insulin from the periphery acts on these receptors to modify dopamine transmission in the striatum. This is pertinent given that several lines of evidence suggest that insulin receptor functioning may be abnormal in the brains of persons with schizophrenia. Post-mortem studies have shown that persons with schizophrenia have less than half the number of cortical insulin receptors compared to healthy persons. Moreover, these post-mortem findings are unlikely due to the effects of antipsychotic treatment; studies in cell lines and animals suggest antipsychotics enhance insulin receptor functioning. Further, hyperinsulinemia - even prior to antipsychotic use - seems to be related to less psychotic symptoms in patients with schizophrenia. Collectively, these data suggest that midbrain insulin receptor functioning may be abnormal in persons with schizophrenia, resulting in reduced insulin-mediated regulation of dopamine transmission in the striatum. Such a deficit may account for the hyperdopaminergic state observed in these patients and would help guide the development of novel treatment strategies. We hypothesize that, (i) insulin receptor expression and/or function is reduced in midbrain dopamine neurons in persons with schizophrenia, (ii) basal insulin should reduce dopaminergic transmission in the striatum via these receptors, and (iii) this modulation of dopaminergic transmission by basal insulin

  6. Free Thyroxine, Anti-Thyroid Stimulating Hormone Receptor Antibody Titers, and Absence of Goiter Were Associated with Responsiveness to Methimazole in Patients with New Onset Graves' Disease.

    Choi, Hoon Sung; Yoo, Won Sang


    Anti-thyroid drug therapy is considered a treatment of choice for Graves' disease; however, treatment response varies among individuals. Although several studies have reported risk factors for relapse after initial treatment, few have assessed responsiveness during the early treatment period. Our study aimed to identify the clinical characteristics for responsiveness to methimazole. We included 99 patients diagnosed with Graves' disease for the first time. Drug responsiveness was defined as the correlation coefficients between decreasing rates of free thyroxine level per month and methimazole exposure dose. According to their responsiveness to treatment, the patients were classified into rapid or slow responder groups, and age, sex, free thyroxine level, and thyrotropin binding inhibiting immunoglobulin (TBII) titers were compared between groups. The mean patient age was 44.0±13.5 years and 40 patients were male (40%). The mean TBII titer was 36.6±74.4 IU/L, and the mean free thyroxine concentration was 48.9±21.9 pmol/L. The rapid responder group showed higher TBII titer and free thyroxine level at diagnosis, while age, sex, smoking, and presence of goiter did not differ between the two groups. Logistic regression analyses revealed that high level of serum thyroxine, high titer of TBII, and absence of goiter were significantly associated with a rapid response, while age, sex, and smoking were not significant factors for the prediction of responsiveness. In patients with new onset Graves' disease, high level of free thyroxine, high titer of TBII, and absence of goiter were associated with rapid responsiveness to methimazole treatment.

  7. Altered thyroxin and retinoid metabolic response to 2,3,7,8-tetrachlorodibenzo-p-dioxin in aryl hydrocarbon receptor-null mice

    Nishimura, Noriko; Yonemoto, Junzo [National Institute for Environmental Studies, Endocrine Disruptors and Dioxin Research Project, Tsukuba (Japan); Miyabara, Yuichi [Shinshu University, Research and Education Center for Inlandwater Environment, Nagano (Japan); Fujii-Kuriyama, Yoshiaki [University of Tsukuba, Center for Tsukuba Advanced Research Alliance, Tsukuba (Japan); Tohyama, Chiharu [National Institute for Environmental Studies, Environmental Health Sciences Division, Tsukuba (Japan)


    To determine whether the disruption of thyroid hormone and retinoid homeostasis that occurs after exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) can be mediated by the arylhydrocarbon receptor (AhR), pregnant AhR-heterozygous (AhR+/-) mice were administered a single oral dose of 10 {mu}g kg{sup -1} TCDD at gestation day 12.5. Serum and liver were collected on postnatal day 21 from vehicle-treated control or TCDD-treated AhR+/- and AhR-null (AhR-/-) mouse pups. Whereas TCDD exposure resulted in a marked reduction of total thyroxin (TT4) and free T4 (FT4) levels in the serum of AhR+/- mice, TCDD had no effects on AhR-/- mice. Gene expression of UDP-glucuronosyltransferase (UGT)1A6, cytochrome P450 (CYP)1A1, and CYP1A2 in the liver was induced markedly by TCDD in AhR+/- but not AhR-/- mice. Induction of CYP1A1 in response to TCDD was confirmed by immunohistochemical evidence in that CYP1A1 protein was conspicuously localized in the cytoplasm of hepatocytes in the centrilobular region. Levels of retinyl palmitate were greatly reduced in the liver of TCDD-exposed AhR+/- mice, but not in vehicle-treated AhR+/- mice. No effects of TCDD on retinoid levels in the liver were found in AhR-/- mice. We conclude that disruption of thyroid hormone and retinoid homeostasis is mediated entirely via AhR. Induction of UGT1A6 is thought to be responsible at least partly for reduced serum thyroid hormone levels in TCDD-exposed mice. (orig.)

  8. Normal cortisol response to cold pressor test, but lower free thyroxine, after recovery from undernutrition.

    Martins, Vinicius J B; Neves, Andrea P O; Garcia, Márcia C; Spadari, Regina C; Clemente, Ana Paula G; de Albuquerque, Maria P; Hoffman, Daniel J; Sawaya, Ana L


    Undernutrition is a stressor with long-term consequences, and the effect of nutritional recovery on cortisol and thyroid hormone status is unknown. To investigate basal thyroid hormones and the cortisol response to a cold pressor test in children recovered from undernutrition, a cross-sectional study was undertaken on children (6-16 years) separated into four groups: control (n 41), stunted (n 31), underweight (n 27) and recovered (n 31). Salivary cortisol was collected over the course of 10 h: upon awakening, before and after an unpleasant and a pleasant stimulus. Cortisol upon awakening was highest in the stunted and lowest in the underweight groups: control=5·05 (95% CI 3·71, 6·89) nmol/l, stunted=6·62 (95% CI 3·97, 11·02) nmol/l, underweight=2·51 (95% CI 1·75, 3·63) nmol/l and recovered=3·46 (95% CI 2·46, 4·90) nmol/l (P=0·005). Girls had higher cortisol concentrations upon awakening compared with boys (P=0·021). The undernourished groups showed an elevated cortisol response both to the unpleasant stimulus and at the last measurement (16.00 hours) compared with that of the recovered group: AUC, control=2·07 (95% CI 1·69, 2·45) nmol/l×30 min, stunted=2·48 (95% CI 1·91, 3·06) nmol/l×30 min, underweight=2·52 (95% CI 2·07, 2·97) nmol/l×30 min, recovered=1·68 (95% CI 1·26, 2·11) nmol/l×30 min (P=0·042); and control=2·03 (95% CI 1·75, 2·39) nmol/l×30 min, stunted=2·51 (95% CI 1·97, 3·19) nmol/l×30 min, underweight=2·61 (95% CI 2·16, 3·16) nmol/l×30 min, recovered=1·70 (95% CI 1·42, 2·03) nmol/l×30 min (P=0·009). Lower free thyroxine (T4) was found in the recovered and stunted groups: control=1·28 (95% CI 1·18, 1·39) pmol/l, stunted=0·98 (95% CI 0·87, 1·10) pmol/l, underweight=1·10 (95% CI 1·01, 1·21) pmol/l and recovered=0·90 (95% CI 0·83, 0·99) pmol/l (Pcortisol concentration along 10 h (06.00-16.00 hours) in the recovered compared with the other groups (P=0·017), and similar concentrations between the

  9. The Wobbler mouse model of amyotrophic lateral sclerosis (ALS displays hippocampal hyperexcitability, and reduced number of interneurons, but no presynaptic vesicle release impairments.

    Karina D Thielsen

    Full Text Available Amyotrophic lateral sclerosis (ALS is the most common adult-onset motor neuron disease. It is a fatal degenerative disease, best recognized for its debilitating neuromuscular effects. ALS however also induces cognitive impairments in as many as 50% of affected individuals. Moreover, many ALS patients demonstrate cortical hyperexcitability, which has been shown to precede the onset of clinical symptoms. The wobbler mouse is a model of ALS, and like ALS patients the wobbler mouse displays cortical hyperexcitability. Here we investigated if the neocortical aberrations of the wobbler mouse also occur in the hippocampus. Consequently, we performed extracellular field excitatory postsynaptic potential recordings in the CA1 region of the hippocampus on acute brain slices from symptomatic (P45-P60 and presymptomatic (P17-P21 wobbler mice. Significant increased excitation of hippocampal synapses was revealed by leftward shifted input/output-curves in both symptomatic and presymptomatic wobbler mice, and substantiated by population spike occurrence analyses, demonstrating that the increased synaptic excitation precedes the onset of visible phenotypic symptoms in the mouse. Synaptic facilitation tested by paired-pulse facilitation and trains in wobbler and control mice showed no differences, suggesting the absence of presynaptic defects. Immunohistochemical staining revealed that symptomatic wobbler mice have a lower number of parvalbumin positive interneurons when compared to controls and presymptomatic mice. This study reveals that the wobbler mouse model of ALS exhibits hippocampal hyperexcitability. We suggest that the hyperexcitability could be caused by increased excitatory synaptic transmission and a concomitant reduced inhibition due to a decreased number of parvalbumin positive interneurons. Thus we substantiate that wobbler brain impairments are not confined to the motor cortex, but extend to the hippocampus. Importantly, we have revealed more


    Studies demonstrate that exposure to 2,2',4,4'-tetrabromodiphenyl ether (BDE 47) and 2,2',4,4',5,5'· hexachlorobiphenyl (PCB 153) decrease serum thyroxine (T4)levels in laboratory animals 1,2,3. The T4 decrease in rodents is thought to occur through the induction of UDP-glucurono...

  11. Kinetic method for the determination of traces of thyroxine by its catalytic effect on the Mn(III) metaphosphate-As(III) reaction.

    Pastor, Ferenc T; Milovanović, Gordana A; Todorović, Marija


    A new, highly sensitive and simple kinetic method for the determination of thyroxine was proposed. The method was based on the catalytic effect of thyroxine on the oxidation of As(III) by Mn(III) metaphosphate. The kinetics of the reaction was studied in the presence of orthophosphoric acid. The reaction rate was followed spectrophotometrically at 516 nm. It was established that orthophosphoric acid increased the reaction rate and that the extent of the non-catalytic reaction was extremely small. A kinetic equation was postulated and the apparent rate constant was calculated. The dependence of the reaction rate on temperature was investigated and the energy of activation and other kinetic parameters were determined. Thyroxine was determined under the optimal experimental conditions in the range 7.0 x 10(-9) to 3.0 x 10(-8) mol L(-1) with a relative standard deviation up to 6.7% and a detection limit of 2.7 x 10(-9) molL(-1). In the presence of 0.08 mol L(-1) chloride, the detection limit decreased to 6.6 x 10(-10) mol L(-1). The proposed method was applied for the determination of thyroxine in tablets. The accuracy of the method was evaluated by comparison with the HPLC method.

  12. Developmental Triclosan Exposure Decreases Maternal,Fetal, and Early Neonatal Thyroxine: Dynamic and Kinetic Data Support for a Mode-of-Action

    This work tests the mode-of-action (MOA) hypothesis that perinatal triclosan (TCS) exposure decreases circulating thyroxine (T4) concentrations via activation of pregnane X and/or constitutive androstane receptors (PXR, CAR), resulting in up-regulation of hepatic catabolism and e...

  13. Composite reference interval for thyroid-stimulating hormone and free thyroxine, comparison with common cutoff values, and reconsideration of subclinical thyroid disease.

    Ross, H.A.; Heijer, M. den; Hermus, A.R.M.M.; Sweep, C.G.J.


    BACKGROUND: Examination of the 2-dimensional probability distribution of thyroid-stimulating hormone (TSH) and free thyroxine (FT(4)) shows that the widths of the TSH and FT(4) reference intervals derived from this bivariate distribution are mutually interdependent, an aspect commonly ignored when i

  14. Effect of thyroxine on cellular oxygen-consumption and glucose uptake: evidence of an effect of total T4 and not "free T4"

    Kvetny, J; Matzen, L E


    in human mononuclear blood cells. Cells were incubated in protein free medium and in human serum totally depleted of thyroid hormones by resin treatment and fixed amounts of T4 (total T4 = 0-50-100-5000 nmol/l; free T4 = 0-5-11-5600 pmol/l) were added. Thyroxine stimulated glucose uptake and oxygen...

  15. Evaluation of testosterone serum levels in testicular interstitial fluid under thyroxine influence; Avaliacao da testosterona no fluido intersticial testicular sob influencia da tiroxina

    Silva, Isvania Maria S. da; Pereira, Simey de L.S.; Souza, Grace Mary L.; Carvalho, Elaine F.M.B.; Catanho, Maria Teresa J. de A. [Pernambuco Univ., Recife, PE (Brazil). Dept. de Biofisica e Radiobiologia; Silveira, Maria de Fatima G. da [Pernambuco Univ., Recife, PE (Brazil). Dept. de Anatomia; Lima Filho, Guilherme L. [Universidade de Pernambuco (UPE), Nazare da Mata, PE (Brazil). Faculdade de Formacao de Professores


    The thyroid hormones possibly exert a reciprocal action between testicular steroids and Sertoli's cells during the premature period. This work aims to evaluate thyroxine effect on testosterone serum levels and in the testicular interstitial fluid (TIF) in rats. Wistar males rats, 22 days old, 80g of body weight, were induced to hyperthyroidism with thyroxine (20{mu}g/kg) in periods of 5, 10, 15 and 20 consecutive days. After the treatment the animals were weighed and sacrificed for blood and testis collection. From the blood serum and from the TIF drained from the testis were performed testes in order to obtain testosterone attached to {sup 125} I with a specific activity of 36,86 MBq/ig. The results have shown a testosterone significant lineal increase in both - serum and TIF - in the group treated with thyroxine as a time function. In the control group, testosterone levels remained low in both serum and TIF dosages. As a result, we were able to verify that the testosterone levels could be modified by thyroxine in serum and TIF. And so, it could affect luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels in hypophysis. (author)

  16. Maternal thyroid function at 11-13 weeks of gestation in women with hypothyroidism treated by thyroxine.

    Ashoor, Ghalia; Rotas, Michael; Maiz, Nerea; Kametas, Nikos A; Nicolaides, Kypros H


    The aim of this study in pregnant women with hypothyroidism treated by levothyroxine is to examine the interrelations between thyroid-stimulating hormone (TSH), free thyroxine (FT(4)) and free tri-iodothyronine (FT(3)), and examine whether in such patients the treatment is adequate. This was a retrospective cross-sectional study. Maternal serum concentrations of FT(3), FT(4) and TSH were measured at 11-13 weeks in 164 singleton pregnancies from women with hypothyroidism before pregnancy receiving treatment with thyroxine. The values were compared to the results in 4,318 normal singleton pregnancies. In the hypothyroid group, compared to the normal group, there was an increase in median TSH (1.990 vs. 1.007 MoM) and FT(4) (1.052 vs. 0.992 MoM) and decrease in FT(3) (0.901 vs. 0.991 MoM). Serum FT(4) was at or above the 2.5th centile in 158 (96.3%) cases but TSH was above the 97.5th centile in 48 (29.3%) and FT(3) was below the 2.5th centile in 49 (29.9%) cases. In both the hypothyroid and unaffected groups there were significant associations between TSH and FT(4), TSH and FT(3) and between FT(3) and FT(4). In a high proportion of pregnant women with hypothyroidism treated with levothyroxine there is evidence of persistent hypothyroidism because the treatment is inadequate in correcting the levels of FT(3). Copyright 2010 S. Karger AG, Basel.

  17. Potential Influence of Selenium, Copper, Zinc and Cadmium on L-Thyroxine Substitution in Patients with Hashimoto Thyroiditis and Hypothyroidism.

    Rasic-Milutinovic, Z; Jovanovic, D; Bogdanovic, G; Trifunovic, J; Mutic, J


    Background: Besides genetic factors, it is known that some trace elements, as Selenium, Copper, and Zinc are essential for thyroid gland fuction and thyroid hormone metabolism. Moreover, there were some metals effect that suggested patterns associated with overt thyroid disease. Aim of study: Hashimoto thyroiditis (HT), chronic autoimune inflamation of thyroid gland with cosequtive hipothyroidism, is common disease in Serbia, and we thought it is worthwile to explore potential effects of essential and toxic metals and metalloides on thyroid function and ability to restore euthyroid status of them. Results: This cross-sectional, case-control, study investigated the status of essential elements (Selenium,Copper,and Zinc) and toxic metals and metalloides (Al, Cr, Mn, Co, As, Cd, Sb, Ba, Be, Pb and Ni) from the blood of 22 female, patients with Hashimoto thyroiditis and overt hypothyroidism, and compared it with those of 55 female healthy persons. We tried to establish the presence of any correlation between previous mentioned elements and thyroid function in hypothyroid patients and healthy participants. Conclusions: The results of our study suggested that the blood concentration of essential trace elements, especially the ratio of Copper, and Selenium may influence directly thyroid function in patients with HT and overt hypothyroidism.Thus, our findings may have implication to life-long substitution therapy in terms of l-thyroxine dose reduction. Furthermore, for the first time, our study shown potential toxic effect of Cadmium on thyroid function in HT patients, which may implicate the dose of l-thyroxine substitution. © Georg Thieme Verlag KG Stuttgart · New York.

  18. [Thyroxine (T4) and tri-iodothyronine (T3) determinations: techniques and value in the assessment of thyroid function].

    Sapin, R; Schlienger, J-L


    Hormonal production of the thyroid gland is constituted of thyroxine or T4 (80%) and triiodothyronine or T3 (20%). In the circulation, whole T4 originates from thyroid secretion but most of T3 (80%) is produced extrathyroidally from T4 deiodination. Conversion of T4 to T3 may be influenced by various conditions and circulating T3 is a less reliable reflection of thyroid hormone production than T4. In serum most of T4 and T3 is bound to binding proteins and only 0.02% of T4 and 0.3% of T3 is free. Because of their higher diagnostic performance, free T4 (FT4) and free T3 (FT3) measurements have superseded total (free + bound) hormone determination. Total hormone measurements remain useful for research studies or in case of severe hyperthyroidism. Equilibrium dialysis/RIA is considered as the reference method for free hormone measurements. Routine clinical laboratories use automated direct two-step or one-step immunoassays with a high molecular weight ligand or labelled antibody. Free hormone measurement remains technically demanding, especially in sera from severe non-thyroid ill patients with low serum thyroxine binding capacity. Interference from anti-thyroid hormone antibodies and familial dysalbuminemic hyperthyroxinemia depends on the assay method, but is now less marked and less frequently detected. To be able to correctly interpret the results of an assay, it is necessary to assess its performance in biologically and clinically well-characterised serum samples. FT4, and FT3 measurements, if FT4 is normal and hyperthyroidism suspected, are used to confirm and assess the level of hypo and hyperthyroidism (overt or subclinical). When the thyroidal status is unstable (first months of a thyroid treatment, altered L-T4 dose, subacute thyroiditis) or when the hypothalamic-pituitary function is disturbed (central hypothyroidism), TSH determination is diagnostically misleading and only free hormone measurements are reliable for thyroid function assessment.

  19. Adding Thyroxin in Treatment of 96 Cases of Hyperthyroidism%加用甲状腺素片治疗甲亢患者96例的临床观察



    Objective:To explore the efficacy of extra small dose of thyroxin in treating hyper-thyroidism. Methods:96 patients with hyperthyroidism were randomly divided into treatment group (50 cases) and control group (46 cases). Treatment group was added small dose of thyroxin after thyroid function becoming normal or being close to normal on the basis of conventional medicine treatment. Control group were treated by anti-thyroid drug. The efficacy of two groups was ob-served. Results:In treatment group, the symptoms of thyroid enlargement and exophthalmos all fad-ed away faster. The occurrence rate of fat and drug resistance secondary hypothyroidism were lower (P<0.05), and the untoward effect was less. Conclusion:Both small dose of thyroxin and anti-thy-roid drug can effective relieve the high metabolic symptoms of hyperthyroidism, and make TSH, TT3, TT4, FT3 and FT4 return to normal. But adding small dose of thyroxin can not only effective alleviate the thyroid enlargement, exophthalmos and avoid drug resistance secondary hypothyroid-ism, but also reduce the recrudescence of hyperthyroidism. The efficacy of it is remarkable and safe.%  目的:探讨加用小剂量甲状腺素治疗甲亢患者的临床疗效.方法:对收治的甲亢患者96例,随机分为治疗组50例(常规给予抗甲亢药物治疗,甲功正常或接近正常时开始加用小剂量甲状腺素治疗),和对照组46例(给予抗甲亢药物治疗),观察统计两组患者的临床疗效.结果:治疗组50例患者中,甲状腺肿大、突眼症状消退均较快,肥胖和药物性继发性甲状腺功能减退症的发生率较对照组低(P<0.05),不良反应发生较少.结论:两组治疗均能有效缓解甲亢患者甲状腺功能亢进的高代谢症状,使TSH、TT3、TT4、FT3、FT4恢复正常,但治疗组加用小剂量甲状腺素治疗,能有效地减轻甲状腺肿大、突眼及避免发生药物性继发性甲减,并能减少甲亢的复发,疗效显著,安全.

  20. Mycoprotein reduces energy intake and postprandial insulin release without altering glucagon-like peptide-1 and peptide tyrosine-tyrosine concentrations in healthy overweight and obese adults: a randomised-controlled trial.

    Bottin, Jeanne H; Swann, Jonathan R; Cropp, Eleanor; Chambers, Edward S; Ford, Heather E; Ghatei, Mohammed A; Frost, Gary S


    Dietary mycoprotein decreases energy intake in lean individuals. The effects in overweight individuals are unclear, and the mechanisms remain to be elucidated. This study aimed to investigate the effect of mycoprotein on energy intake, appetite regulation, and the metabolic phenotype in overweight and obese volunteers. In two randomised-controlled trials, fifty-five volunteers (age: 31 (95 % CI 27, 35) years), BMI: 28·0 (95 % CI 27·3, 28·7) kg/m2) consumed a test meal containing low (44 g), medium (88 g) or high (132 g) mycoprotein or isoenergetic chicken meals. Visual analogue scales and blood samples were collected to measure appetite, glucose, insulin, peptide tyrosine-tyrosine (PYY) and glucagon-like peptide-1 (GLP-1). Ad libitum energy intake was assessed after 3 h in part A (n 36). Gastric emptying by the paracetamol method, resting energy expenditure and substrate oxidation were recorded in part B (n 14). Metabonomics was used to compare plasma and urine samples in response to the test meals. Mycoprotein reduced energy intake by 10 % (280 kJ (67 kcal)) compared with chicken at the high content (P=0·009). All mycoprotein meals reduced insulin concentrations compared with chicken (incremental AUClow (IAUClow): -8 %, IAUCmedium: -12 %, IAUChigh: -21 %, P=0·004). There was no significant difference in glucose, PYY, GLP-1, gastric emptying rate and energy expenditure. Following chicken intake, paracetamol-glucuronide was positively associated with fullness. After mycoprotein, creatinine and the deamination product of isoleucine, α-keto-β-methyl-N-valerate, were inversely related to fullness, whereas the ketone body, β-hydroxybutyrate, was positively associated. In conclusion, mycoprotein reduces energy intake and insulin release in overweight volunteers. The mechanism does not involve changes in PYY and GLP-1. The metabonomics analysis may bring new understanding to the appetite regulatory properties of food.

  1. Renin release

    Schweda, Frank; Friis, Ulla; Wagner, Charlotte;


    The aspartyl-protease renin is the key regulator of the renin-angiotensin-aldosterone system, which is critically involved in salt, volume, and blood pressure homeostasis of the body. Renin is mainly produced and released into circulation by the so-called juxtaglomerular epithelioid cells, located......, salt, and volume overload. In contrast, the events controlling the function of renin-secreting cells at the organ and cellular level are markedly less clear and remain mysterious in certain aspects. The unravelling of these mysteries has led to new and interesting insights into the process of renin...

  2. Effects of Long-Term Low-Level Radiofrequency Radiation Exposure on Rats. Volume 6. Hematological, Serum Chemistry, Thyroxine, and Protein Electrophoresis Evaluations.


    111I. 11 MICROCOPY RESOLUTION TESI CHART i ~ ~ ~ ~ ~ ~ ~ ~ ~ A N... DS................. ...".... , II I - I Reort USAFSAM-TR-84-2 EFFECTS OF LONG-TERM...obstruction, and resolving internal hemorrhage. The total levels are decreased in cases of bone-marrow-depression anemia . The direct and indirect...VIR" 4 THYROXINE Elevated contents of serum cholestrol and triglycerides and a mild normochromic, norioocytic anemia are nonspecific traits suggestive

  3. Pattern of thyroid function during early pregnancy in women diagnosed with subclinical hypothyroidism and treated with l-thyroxine is similar to that in euthyroid controls.

    De Geyter, Christian; Steimann, Sabine; Müller, Beat; Kränzlin, Marius E; Meier, Christian


    Subclinical hypothyroidism (SCH) is associated with a higher miscarriage rate. It is unclear how the thyroid function in SCH differs from that in euthyroidism during early pregnancy. We intended to determine the regulation of thyroid function in women with SCH receiving constant l-thyroxine (T4) replacement during early pregnancy as compared to euthyroid controls. This was a prospective cohort study with weekly serum sampling in eight women in early pregnancy with SCH and eight euthyroid women from week 5 to week 12 of pregnancy. Thyroid function was assessed before pregnancy. Women with SCH were treated with T4 (50 microg daily) and continued on an unchanged dose until week 12. The following parameters were measured weekly: thyrotropin (TSH), thyroglobulin, thyroxine, triiodothyronine, free thyroxine (FT4), free triiodothyronine (FT3), estradiol, progesterone, human chorionic gonadotropin, and prolactin. Although the pregestational levels of TSH were significantly higher among women with SCH as compared to euthyroid controls, the self-limited estrogen-induced increment of TSH during early pregnancy was similar in both groups. Although both SCH and ovarian hyperstimulation were associated with an intermediate rise in TSH, the pattern of thyroid function followed similar changes as in euthyroid controls and is unlikely to cause the higher miscarriage rate observed in SCH.

  4. New test principle for measurement of free thyroxine (fT/sub 4/) in serum. Results of a multicenter trial

    Mahlstedt, J.


    A new principle for measurement of free serum thyroxine was investigated being a nearly classical radioimmunoassay by use of an analogue of /sup 125/I-T/sub 4/, which does not bind to serum proteins but binds as well as T/sub 4/ to the T/sub 4/-antiserum. The distribution of 438 test-results of euthyroid patients with and without goitre is normal, anti x being 1.34 ng/dl with 2s-range between 0.73-1.95 ng/dl. This normal range was derived from areas in FRG known for more or less iodine deficiency. Thus fT/sub 4/ seems not to be strongly dependent on iodine intake. fT/sub 4/ in sera from pregnant women of the third trimester was clearly decreased, one half of the values being in the lower normal range, the other half being in the hypothyroid range. Patients on contraceptive therapy showed values within the normal range. Patients on T/sub 4/-supplementation in part revealed more or less increased values. Quality control was performed using 44 assays. The mean interassay variation coefficient was clearly less than 10% using three control sera in the euthyroid, hyperthyroid and extremely hypothyroid range. The technical handling of the assay is very convenient. The assay is to be performed within 2 hours.

  5. Higher Thyroid-Stimulating Hormone, Triiodothyronine and Thyroxine Values Are Associated with Better Outcome in Acute Liver Failure.

    Olympia Anastasiou

    Full Text Available Changes in thyroid hormone levels, mostly as non-thyroidal illness syndrome (NTIS, have been described in many diseases. However, the relationship between acute liver failure (ALF and thyroid hormone levels has not yet been clarified. The present study evaluates potential correlations of select thyroid functional parameters with ALF.84 consecutively recruited ALF patients were grouped according to the outcome of ALF (spontaneous recovery: SR; transplantation or death: NSR. TSH, free thyroxine (fT4, free triiodothyronine (fT3, T4, and T3 were determined.More than 50% of patients with ALF presented with abnormal thyroid parameters. These patients had greater risk for an adverse outcome than euthyroid patients. SR patients had significantly higher TSH, T4, and T3 concentrations than NSR patients. Albumin concentrations were significantly higher in SR than in NSR. In vitro T3 treatment was not able to rescue primary human hepatocytes from acetaminophen induced changes in mRNA expression.In patients with ALF, TSH and total thyroid hormone levels differed significantly between SR patients and NSR patients. This might be related to diminished liver-derived transport proteins, such as albumin, in more severe forms of ALF. Thyroid parameters may serve as additional indicators of ALF severity.

  6. Beneficial role of ascorbic and folic acids antioxidants against thyroxin-induced testicular dysfunction in hyperthyroid rats.

    Beltagy, Doha M; Mohamed, Tarek M; El Said, Ahmed S; Tousson, Ehab


    Thyroid hormones play a fundamental role in the regulation of metabolism of almost all mammalian tissue including the reproductive system. Hyperthyroidism in early life may cause delayed sexual maturation, although physical development is normal and skeletal growth may be accelerated. Hyperthyroidism after puberty influences reproductive functions and increases testosterone level. The aim of this work is to study the effect of induced hyperthyroidism by L-thyroxine sodium administration on the testis of rats and to evaluate the ameliorating role of different antioxidants as ascorbic acid and folic acid on the hyperthyroid state via the assessment of different biochemical markers, histopathological and immunochemical sections. DNA analysis of the D1 deiodinase was performed to determine genetic mutation due to hyperthyroidism. The results showed partially disrupted in the measured biochemical parameters and spermatogenesis in hyperthyroid rats. Post-administration of both folic and ascorbic acids together in hyperthyroid rats showed the best ameliorating effects on the thyroid hormones, testosterone, testicular GGT and ALP, and all oxidative stress markers. There is no genetic mutations that occurred in D1 deiodinase due to hyperthyroidism. These findings were indicated by the proliferating cell nuclear antigen (PCNA) studies of testes.

  7. Evaluation of routine hematology profile results and fructosamine, thyroxine, insulin, and proinsulin concentrations in lean, overweight, obese, and diabetic cats.

    Hoenig, Margarethe; Traas, Anne M; Schaeffer, David J


    To compare results of hematologic testing in nondiabetic and diabetic cats to identify possible indicators of alterations in long-term glucose control. Cross-sectional study. 117 client-owned cats (76 nondiabetic cats [25 with normal body condition, 27 overweight, and 24 obese] and 41 naïve [n = 21] and treated [20] diabetic cats). Signalment and medical history, including data on feeding practices, were collected. A body condition score was assigned, and feline body mass index was calculated. Complete blood counts and serum biochemical analyses, including determination of fructosamine, thyroxine, insulin, and proinsulin concentrations, were performed. Urine samples were obtained and analyzed. Glucose and fructosamine concentrations were significantly higher in the naïve and treated diabetic cats than in the nondiabetic cats. Insulin and proinsulin concentrations were highest in the obese cats but had great individual variation. Few other variables were significantly different among cat groups. Most cats, even when obese or diabetic, had unlimited access to food. Results suggested that cats at risk of developing diabetes (ie, overweight and obese cats) could not be distinguished from cats with a normal body condition on the basis of results of isolated hematologic testing. A longitudinal study is indicated to follow nondiabetic cats over a period of several years to identify those that eventually develop diabetes. Findings also suggested that dietary education of cat owners might be inadequate.

  8. Self-Assembly of Pyridine-Modified Lipoic Acid Derivatives on Gold and Their Interaction with Thyroxine (T4

    Pierangelo Metrangolo


    Full Text Available Pyridyl derivatives of lipoic acid were prepared as ligands for the study of the interaction with thyroxine (T4. Thin self-assembled films of the ligands were prepared in 70% ethanol on gold and their interaction with T4 was studied by titration experiments in an aqueous buffer solution using Surface Plasmon Resonance (SPR. The thickness and refractive index of the ligand layers were calculated from SPR spectra recorded in two media, also allowing for surface coverage and the density of the layers to be estimated. Two ligands, a 4-pyridyl and a bis(2-hydroxyethyl derivative of lipoic acid, were selected to investigate the feasibility for producing molecularly imprinted self-assembled layers on gold for T4. The methodology was to co-assemble T4 and the ligand onto the gold surface, elute the T4 from the layer under alkaline conditions, and study the rebinding of T4 to the layer. Multiple elution/rebinding cycles were conducted in different buffer solutions, and rebinding of T4 could be observed, with a moderate binding affinity that depended greatly on the solvent used. More optimal binding was observed in HBS buffer, and the affinity of the interaction could be slightly increased when the 4-pyridyl and bis(2-hydroxy-ethyl derivatives of lipoic acid were combined in the imprinted layer.

  9. Inner ring deiodination of thyroxine and 3,5,3'-triiodothyronine by human fetal membranes

    Roti, E.; Fang, S.L.; Green, K.; Braverman, L.E.; Emerson, C.H.


    Indirect evidence, based on injection of thyroxine (T4) into the amniotic cavity of humans, and maternal thyroidectomy in the rat, suggests that fetal membranes might be capable of converting T4 to 3,3',5'-triiodothyronine (rT3) by virtue of inner ring iodothyronine deiodinase activity. The present study was undertaken to provide direct evidence that human fetal membranes contain inner ring iodothyronine deiodinase activity directed toward T4 and 3,5,3'-triiodothyronine (T3). Homogenates of human fetal membranes were incubated with 125I-labeled T4, rT3, and T3, and with stable T4. Conversion of 125(I)-T4 to 125(I)-rT3 was noted in chorion and amnion. 125I-T3 was converted to 125(I)-3,3'-diiodothyronine (T2) in chorion and amnion. 125(I)-rT3 was stable in fetal membranes under the incubation conditions employed. Time-, temperature-, pH-, and protein content-dependent conversion of stable T4 to rT3 was found in fetal membranes. Iodothyronine metabolism did not occur in the absence of dithiothreitol. These studies indicate that human fetal membranes contain an inner ring deiodinase enzyme. Because of its intimate contact with the amniotic cavity, this enzyme may generate a portion of the rT3 found in amniotic fluid.

  10. Conversion of L-thyroxine to L-triiodothyronine in the rat liver under in vitro conditions

    Nauman, A.; Kaminski, T.; Pastuszko, D. (Centrum Medyczne Ksztalcenia Podyplomowego, Warsaw (Poland))


    Conversion of thyroxine (T/sub 4/) to triiodothyronine (T/sub 3/) has been studied in liver homogenates obtained from normal and hypothyroid rats. Liver homogenates were incubated for 0-60 minutes at 37/sup 0/C in Tris buffer containing sucrose and T/sub 4/, pH 7.4. T/sub 3/ generated during incubation was measured by a specific radioimmunoassay of an ethanol extract of the incubates. Conversion rate of T/sub 4/ to T/sub 3/ by liver homogenates from intact rats was found to be time, protein concentration and substrate concentration (T/sub 4/) dependent. Heating of homogenate above 60/sup 0/C abolished while cooling significantly decreased the monodeiodination. In homogenates from hypothyroid rats the conversion and its rate were significantly decreased. The results of present study confirmed enzymatic character of monodeiodination reaction. Decreased conversion of T/sub 4/ to T/sub 3/ in hypothyroidism suggests that biosynthesis of converting enzyme may be regulated by thyroid hormones.

  11. Self-Assembly of Pyridine-Modified Lipoic Acid Derivatives on Gold and Their Interaction with Thyroxine (T4)

    Albers, Willem M.; Milani, Roberto; Tappura, Kirsi; Munter, Tony; Resnati, Giuseppe; Metrangolo, Pierangelo


    Pyridyl derivatives of lipoic acid were prepared as ligands for the study of the interaction with thyroxine (T4). Thin self-assembled films of the ligands were prepared in 70% ethanol on gold and their interaction with T4 was studied by titration experiments in an aqueous buffer solution using Surface Plasmon Resonance (SPR). The thickness and refractive index of the ligand layers were calculated from SPR spectra recorded in two media, also allowing for surface coverage and the density of the layers to be estimated. Two ligands, a 4-pyridyl and a bis(2-hydroxyethyl) derivative of lipoic acid, were selected to investigate the feasibility for producing molecularly imprinted self-assembled layers on gold for T4. The methodology was to co-assemble T4 and the ligand onto the gold surface, elute the T4 from the layer under alkaline conditions, and study the rebinding of T4 to the layer. Multiple elution/rebinding cycles were conducted in different buffer solutions, and rebinding of T4 could be observed, with a moderate binding affinity that depended greatly on the solvent used. More optimal binding was observed in HBS buffer, and the affinity of the interaction could be slightly increased when the 4-pyridyl and bis(2-hydroxy-ethyl) derivatives of lipoic acid were combined in the imprinted layer. PMID:23389045

  12. 以社区矫正降低青年刑满释放人员再犯罪率初探%Primary Research on the Community Correction to Reduce Crime Rate of Youth Personnel Released after Serving His Sentence



    刑满释放人员一直是我国社会需要:关注的群体,因为这些人员长时间脱离社会而无法跟上社会发展的脚步,并由此导致了一些人走上重新犯罪的道路。社区矫正作为一种监外刑罚执行方法可以避免犯罪人员与社会的脱节,不无遗憾的是社区矫正的实施存在许多不足,我们旨在以对社区矫正试点的实施情况为立足点,提出完善社区矫正制度的方向,同时通过对青年再犯罪特点的分析,提出降低青年再犯罪率的措施。%The personnel released after serving his sentence has been the groups needed to concern in our society. Because of long time away from society they couldn't keep up with the steps of social development, and this has resulted in some of them to go to the road of crime again. Community correction as a kind of penalty execution method outside of prison can prevent criminals and social disconnection. But the implementation of community correction has many shortcomings. This paper puts forward to perfect the system of community correction direction, and the measures to reduce youth crime rate.


    S.O. Bader


    The purpose of this design analysis is to specify and document the total and respirable fractions for radioactive materials that are released from an accident event at the Monitored Geologic Repository (MGR) involving commercial spent nuclear fuel (CSNF) in a dry environment. The total and respirable release fractions will be used to support the preclosure licensing basis for the MGR. The total release fraction is defined as the fraction of total CSNF assembly inventory, typically expressed as an activity inventory (e.g., curies), of a given radionuclide that is released to the environment from a waste form. The radionuclides are released from the inside of breached fuel rods (or pins) and from the detachment of radioactive material (crud) from the outside surfaces of fuel rods and other components of fuel assemblies. The total release fraction accounts for several mechanisms that tend to retain, retard, or diminish the amount of radionuclides that are available for transport to dose receptors or otherwise can be shown to reduce exposure of receptors to radiological releases. The total release fraction includes a fraction of airborne material that is respirable and could result in inhalation doses. This subset of the total release fraction is referred to as the respirable release fraction. Potential accidents may involve waste forms that are characterized as either bare (unconfined) fuel assemblies or confined fuel assemblies. The confined CSNF assemblies at the MGR are contained in shipping casks, canisters, or disposal containers (waste packages). In contrast to the bare fuel assemblies, the container that confines the fuel assemblies has the potential of providing an additional barrier for diminishing the total release fraction should the fuel rod cladding breach during an accident. However, this analysis will not take credit for this additional bamer and will establish only the total release fractions for bare unconfined CSNF assemblies, which may however be

  14. Non-inferiority of nitric oxide releasing intranasal spray compared to sub-therapeutic antibiotics to reduce incidence of undifferentiated fever and bovine respiratory disease complex in low to moderate risk beef cattle arriving at a commercial feedlot.

    Regev-Shoshani, G; McMullin, B; Nation, N; Church, J S; Dorin, C; Miller, C


    Undifferentiated fever, or bovine respiratory disease complex (BRDc), is a challenging multi-factorial health issue caused by viral/bacterial pathogens and stressors linked to the transport and mixing of cattle, negatively impacting the cattle feedlot industry. Common practice during processing at feedlots is administration of antibiotic metaphylaxis to reduce the incidence of BRDc. Nitric oxide (NO) is a naturally occurring nano-molecule with a wide range of physiological attributes. This study evaluated the metaphylactic use of intranasal NO releasing spray (NORS) to control BRDc incidence in calves at low-moderate risk of developing BRDc, arriving at a commercial feedlot as compared to conventional antibiotic metaphylaxis. One thousand and eighty crossbred, multiple-sourced, commingled, commercial, weaned beef calves were screened, enrolled, randomized and treated upon arrival. Animals appearing sick were pulled (from their pen) by blinded pen keepers then assessed for BRDc symptoms; blood samples were taken for haptoglobin quantification and the animals were rescued with an antibiotic. After 35 days both groups showed no significant difference in BRDc incidence (5.2% of animals from NORS group and 3.2% from antibiotic group). Average daily weight gain of animals at day 150 for the NORS cohort was 1.17kg compared to 1.18kg for the antibiotic group (p>0.05). There was no significant difference in mortality in the first 35 days (p=0.7552), however, general mortality over 150 days trended higher in the antibiotic cohort. NORS treatment was shown to be safe, causing neither distress nor adverse effects on the animals. This large randomized controlled study in low-moderate BRDc incidence risk calves demonstrates that NORS treatment, as compared to conventional metaphylactic antibiotics, is non-inferior based on BRDc incidence and other metrics like weight and mortality. These data justify further studies in higher BRDc incidence risk populations to evaluate NORS as

  15. Effects of larval-juvenile treatment with perchlorate and co-treatment with thyroxine on zebrafish sex ratios

    Mukhi, S.; Torres, L.; Patino, R.


    The objective of this study was to determine the effect of larval-juvenile exposure to perchlorate, a thyroid hormone synthesis inhibitor, on the establishment of gonadal sex ratios in zebrafish. Zebrafish were exposed to untreated water or water containing perchlorate at 100 or 250 ppm for a period of 30 days starting at 3 days postfertilization (dpf). Recovery treatments consisted of a combination of perchlorate and exogenous thyroxine (T4; 10 nM). Thyroid histology was assessed at the end of the treatment period (33 dpf), and gonadal histology and sex ratios were determined in fish that were allowed an additional 10-day period of growth in untreated water. As expected, exposure to perchlorate caused changes in thyroid histology consistent with hypothyroidism and these effects were reversed by co-treatment with exogenous T4. Perchlorate did not affect fish survival but co-treatment with T4 induced higher mortality. However, relative to the corresponding perchlorate concentration, co-treatment with T4 caused increased mortality only at a perchlorate concentration of 100 ppm. Perchlorate alone or in the presence of T4 suppressed body length at 43 dpf relative to control values. Perchlorate exposure skewed the sex ratio toward female in a concentration-dependent manner, and co-treatment with T4 not only blocked the feminizing effect of perchlorate but also overcompensated by skewing the sex ratio towards male. Moreover, co-treatment with T4 advanced the onset of spermatogenesis in males. There was no clear association between sex ratios and larval survival or growth. We conclude that endogenous thyroid hormone plays a role in the establishment of gonadal sex phenotype during early development in zebrafish. ?? 2006 Elsevier Inc. All rights reserved.

  16. Pediatric Reference Intervals for Free Thyroxine and Free Triiodothyronine by Equilibrium Dialysis-Liquid Chromatography-Tandem Mass Spectrometry

    La’ulu, Sonia L.; Rasmussen, Kyle J.; Straseski, Joely A.


    Objective: Thyroid hormone concentrations fluctuate during growth and development. To accurately diagnose thyroid disease in pediatric patients, reference intervals (RIs) should be established with appropriate age groups from an adequate number of healthy subjects using the most exact methods possible. Obtaining statistically useful numbers of healthy patients is particularly challenging for pediatric populations. The objective of this study was to determine non-parametric RIs for free thyroxine (fT4) and free triiodothyronine (fT3) using equilibrium dialysis-high performance liquid chromatography-tandem mass spectrometry with over 2200 healthy children 6 months-17 years of age. Methods: Subjects were negative for both thyroglobulin and thyroid peroxidase autoantibodies and had normal thyrotropin concentrations. The study included 2213 children (1129 boys and 1084 girls), with at least 120 subjects (average of 125) from each year of life, except for the 6 month to 1 year age group (n=96). Results: Non-parametric RIs (95th percentile) for fT4 were: 18.0-34.7 pmol/L (boys and girls, 6 months-6 years) and 14.2-25.7 pmol/L (boys and girls, 7-17 years). RIs for fT3 were: 5.8-13.1 pmol/L (girls, 6 months-6 years); 5.7-11.8 pmol/L (boys, 6 months-6 years); 5.7-10.0 pmol/L (boys and girls, 7-12 years); 4.5-8.6 pmol/L (girls, 13-17 years); and 5.2-9.4 pmol/L (boys, 13-17 years). Conclusion: Numerous significant differences were observed between pediatric age groups and previously established adult ranges. This emphasizes the need for well-characterized RIs for thyroid hormones in the pediatric population. PMID:26758817

  17. The effect of severe starvation and captivity stress on plasma thyroxine and triiodothyronine concentrations in an antarctic bird (emperor penguin).

    Groscolas, R; Leloup, J


    The effect of confinement and severe starvation on the plasma thyroxine (T4) and triiodothyronine (T3) concentrations was determined in emperor penguins (Aptenodytes forsteri). During their annual cycle, emperor penguins fast freely for periods of up to 4 months and may thus represent a unique subject to study endocrine adaptations to fasting. Plasma T4 concentrations progressively decreased following capture and confinement of naturally fasting penguins, and within 15-20 days stabilized at levels three times lower than in free-living penguins. A transient fourfold increase in plasma T3 concentration developed within the day following confinement in parallel with a rise in daily body mass loss. Both plasma T3 concentration and mass loss subsided to normal levels within 15 days. The decrease in plasma T4 concentration is in accordance with the well-known inhibitory effect of stress on thyroid function in birds and mammals, whereas the transient increase in plasma T3 concentration seems related to enhancement of energy expenditure as a consequence of restlessness. Starvation severe enough to exhaust fat stores and to activate protein catabolism induced a 6- and 5 to 10-fold fall in plasma T4 and T3, respectively. This is in marked contrast with maintenance of plasma thyroid levels during long-term natural fasting associated with protein sparing (R. Groscolas and J. Leloup (1986) Gen. Comp. Endocrinol. 63, 264-274). Surprisingly, there was a final reincrease in plasma T4 concentration in very lean penguins. These results suggest that the effect of starvation on plasma thyroid hormones seems to depend on how much protein catabolism is activated and demonstrate the acute sensitivity of thyroid hormone balance to stress in penguins.

  18. Effects of thyroxine on cardiac function and lymphocyte β-adrenoceptors in patients with chronic congestive heart failure

    卢新政; 黄峻; 张晓文; 李新华; 王赤京; 张佩生; 陈永生


    Objective To explore the effects of thyroid hormone (TH) on cardiac function and peripheral lymphocyte β-adrenoceptors (β-Ars) of patients with chronic congestive heart failure (CHF). Methods Twenty-eight patients with class Ⅲ or Ⅳ advanced CHF due to dilated cardiomyopathy (DCM) or ischemic cardiomyopathy (ICM) were randomly divided into groups A and B. L-thyroxine (L-T50) was administered to group B. Exercise tolerance, chest X-rays, and echocardiographic parameters were obtained before and after one month of treatment, Ficoll-hypaque solution was used to separate peripheral lymphocytes, and 125I-pindolol radioligand binding was used to measure β-AR levels in peripheral lymphocytes. Results L-T50 therapy improved cardiac output [CO, (2.98±0.31)L/min vs (3.24±0.28) L/min, P<0.01], left ventricular ejection fraction (LVEF, 26.21%±3.21% vs 37.93%±9.01%, P<0.01), and decreased isovolumetric relaxation time (IVRT, 0.12±0.04 vs 0.10±0.02, P<0.01). Serum TH levels and the maximal number of β-AR binding sites (βmax ) in peripheral lymphocytes were lower in patients with CHF than in normal healthy people, but L-T50 administration induced a β-AR up-regulation on peripheral lymphocyte surfaces. L-T50 was well tolerated without episodes of ischemia or arrhythmia. There was no significant change in heart rate or metabolic rate.Conclusion TH administration improves cardiac function and β-AR expression in peripheral lymphocytes of patients with CHF.

  19. Pediatric Reference Intervals for Free Thyroxine and Free Triiodothyronine by Equilibrium Dialysis-Liquid Chromatography-Tandem Mass Spectrometry.

    La'ulu, Sonia L; Rasmussen, Kyle J; Straseski, Joely A


    Thyroid hormone concentrations fluctuate during growth and development. To accurately diagnose thyroid disease in pediatric patients, reference intervals (RIs) should be established with appropriate age groups from an adequate number of healthy subjects using the most exact methods possible. Obtaining statistically useful numbers of healthy patients is particularly challenging for pediatric populations. The objective of this study was to determine non-parametric RIs for free thyroxine (fT4) and free triiodothyronine (fT3) using equilibrium dialysis-high performance liquid chromatography-tandem mass spectrometry with over 2200 healthy children 6 months-17 years of age. Subjects were negative for both thyroglobulin and thyroid peroxidase autoantibodies and had normal thyrotropin concentrations. The study included 2213 children (1129 boys and 1084 girls), with at least 120 subjects (average of 125) from each year of life, except for the 6 month to 1 year age group (n=96). Non-parametric RIs (95th percentile) for fT4 were: 18.0-34.7 pmol/L (boys and girls, 6 months-6 years) and 14.2-25.7 pmol/L (boys and girls, 7-17 years). RIs for fT3 were: 5.8-13.1 pmol/L (girls, 6 months-6 years); 5.7-11.8 pmol/L (boys, 6 months-6 years); 5.7-10.0 pmol/L (boys and girls, 7-12 years); 4.5-8.6 pmol/L (girls, 13-17 years); and 5.2-9.4 pmol/L (boys, 13-17 years). Numerous significant differences were observed between pediatric age groups and previously established adult ranges. This emphasizes the need for well-characterized RIs for thyroid hormones in the pediatric population.

  20. Hashimoto's thyroiditis, risk of coronary heart disease, and L-thyroxine treatment: a nationwide cohort study.

    Chen, Wei-Hung; Chen, Yen-Kung; Lin, Cheng-Li; Yeh, Jiann-Horng; Kao, Chia-Hung


    Our objective was to investigate the risk of coronary heart disease (CHD) in patients with Hashimoto's thyroiditis (HT). The Taiwan National Health Insurance Research Database was used to conduct a retrospective cohort analysis. The cohort study consisted of 1165 newly diagnosed HT patients and 4660 matched controls (non-HT patients) from 2000 to 2010. The median follow-up time was 5.46 years. The risk of developing CHD for HT patients was measured using the Cox proportional hazards model. The risk of developing CHD in HT patients was increased compared with the non-HT controls, with an adjusted hazard ratio (HR) of 1.44 (95% confidence interval [CI] = 1.05-1.99). The risk was significant in women but not in men, and restricted to subjects younger than 49 years. HT remained an independent risk factor after adjusting for comorbidities; however, combining with hypertension or hyperlipidemia further increased the risk of CHD (adjusted HR = 2.06, 95% CI = 1.46-2.92; and adjusted HR = 1.83, 95% CI = 1.31-2.55, respectively). Furthermore, HT without T4 treatment and HT with treatment for less than 1 year were associated with higher risk of CHD (adjusted HR = 1.55, 95% CI = 0.98-2.46; and adjusted HR = 2.42, 95% CI = 1.43-3.97, respectively). The risk of CHD decreased after treatment with T4 for more than 1 year and did not differ from the non-HT cohort (adjusted HR = 0.84, 95% CI = 0.0.47-1.52). Patients with HT, are at higher risk of developing CHD compared with the general population. Treatment with T4 reduces the risk of CHD.

  1. Multicompartmental model for iodide, thyroxine, and triiodothyronine metabolism in normal and spontaneously hyperthyroid cats

    Hays, M.T.; Broome, M.R.; Turrel, J.M.


    A comprehensive multicompartmental kinetic model was developed to account for the distribution and metabolism of simultaneously injected radioactive iodide (iodide*), T3 (T3*), and T4 (T4*) in six normal and seven spontaneously hyperthyroid cats. Data from plasma samples (analyzed by HPLC), urine, feces, and thyroid accumulation were incorporated into the model. The submodels for iodide*, T3*, and T4* all included both a fast and a slow exchange compartment connecting with the plasma compartment. The best-fit iodide* model also included a delay compartment, presumed to be pooling of gastrosalivary secretions. This delay was 62% longer in the hyperthyroid cats than in the euthyroid cats. Unexpectedly, all of the exchange parameters for both T4 and T3 were significantly slowed in hyperthyroidism, possibly because the hyperthyroid cats were older. None of the plasma equivalent volumes of the exchange compartments of iodide*, T3*, or T4* was significantly different in the hyperthyroid cats, although the plasma equivalent volume of the fast T4 exchange compartments were reduced. Secretion of recycled T4* from the thyroid into the plasma T4* compartment was essential to model fit, but its quantity could not be uniquely identified in the absence of multiple thyroid data points. Thyroid secretion of T3* was not detectable. Comparing the fast and slow compartments, there was a shift of T4* deiodination into the fast exchange compartment in hyperthyroidism. Total body mean residence times (MRTs) of iodide* and T3* were not affected by hyperthyroidism, but mean T4* MRT was decreased 23%. Total fractional T4 to T3 conversion was unchanged in hyperthyroidism, although the amount of T3 produced by this route was increased nearly 5-fold because of higher concentrations of donor stable T4.

  2. Press release

    Association du personnel


    Geneva, 26 April 2006 – In the framework of the current five-yearly review, the CERN Staff Association denounces a serious attack on employment conditions. Indeed, the Management of the Organization has announced that it will not raise salary levels, even though after-tax salaries in the reference sector (high-tech industry, following a decision by the Member States) in Switzerland are today on average 20% higher than those at CERN. With this decision, the ever-increasing gap between CERN and this comparator as well as other international organizations will not be reduced. In view of the apathy and deceit of the Management which reveals an obvious contempt for the efforts agreed to by the staff, a notice of strike action has been given for Friday 28 April 2006.

  3. Circadian rhythm disturbance after radiotherapy for brain tumor in infantile period; Clinical effect of L-thyroxine and vitamin B[sub 12

    Kubota, Masaya; Shinozaki, Masako (Metropolitan Medical Center for the Severely Handicapped, Fuchu, Tokyo (Japan)); Sasaki, Hideo


    We report a 19-year-old man suffering from circadian sleep-wake (S-W) rhythm disturbance after total tumor resection and whole brain irradiation. The patient was diagnosed as having astrocytoma in the right temporal lobe by CT scan and angiography at the age of 6 months. After total tumor resection and whole brain irradiation ([sup 60]Co 60 Gy), he showed profound psychomotor retardation, endoclinologic dysfunction including hypothyroidism and growth hormone deficiency, and S-W rhythm disturbance. At age 19, brain MRI revealed asymmetrical low intensity in the hypothalamic region. On endoclinological examination panhypopituitarism due to primary hypothalamic lesion was evident. His S-W rhythm was disturbed; i.e., sleep periods were dispersedly distributed throughout 24 hours. He showed a lethargic tendency in the daytime. All-day polysomnography revealed abnormal sleep structure such as the absence of sleep spindle and hump, peripheral apnea, snoring and low oxygen saturation. After L-thyroxine supplementation his daily activity improved gradually. The decrease in short time sleep and tendency of a free-running rhythm were observed and oxygen saturation improved remarkably. Peripheral apnea and snoring disappeared. This wakening effect of L-thyroxine administration may be due to improvement of hypothyroidism symptom such as myxoedematous pharynx. It also seems related to the alteration of the central S-W rhythm regulation, because free-running rhythm appeared after L-thyroxine administration. Vitamin B[sub 12] (VB[sub 12]), which has been reported to be effective for S-W rhythm disorders, was not effective for our patient's free-running rhythm. Compared with the patients responding to VB[sub 12], our patient's organic brain damage was more evident radiologically and endoclinologically. Following the hypothesis that VB[sub 12] has a potential to reinforce the entrainment of circadian rhythm, our patient's organic brain damage may include entrainment

  4. Effects of rifampicin, dexamethasone, St. John's Wort and Thyroxine on maternal and foetal expression of Abcb1 and organ distribution of talinolol in pregnant rats.

    Saljé, Karen; Lederer, Kirstin; Oswald, Stefan; Dazert, Eike; Warzok, Rolf; Siegmund, Werner


    It is well accepted that ABCB1 plays a critical role in absorption, distribution and elimination of many xenobiotics and drugs. Only little is known about the regulation and function of ABCB1 during pregnancy. Thus, the aim of this study is to investigate maternal, placental and foetal Abcb1 expression and function in pregnant rats after induction with rifampicin, dexamethasone, St. John's wort (SJW) or thyroxine. Wistar rats were orally treated with rifampicin (250 mg/kg), SJW (1.0 g/kg), thyroxine (9 μg/kg), dexamethasone (1 mg/kg) or 0.5% methylcellulose suspension (control) for 9 days during late pregnancy (each N = 5). Afterwards, organ mRNA expression and protein content of Abcb1a were determined. Tissue concentrations of the ABCB1 probe drug talinolol were measured after repeated administration of the drug (100 mg/kg, 9 days) and after induction with oral rifampicin (250 mg/kg, 9 days, N = 5). Abcb1 expression was substantially lower in foetal than in maternal organs. Abcb1 was significantly induced by SJW in the maternal jejunum and placenta, by dexamethasone in foetal brain and liver and by thyroxine in the placenta and maternal and foetal brain. Rifampicin induced Abcb1 in all maternal and foetal organs. However, organ distribution of talinolol was not influenced by comedication of rifampicin. In conclusion, maternal and foetal Abcb1 organ expression in pregnant rats is inducible by nuclear receptor agonists. Although rifampicin regulates maternal and foetal Abcb1 expression, organ distribution of talinolol remains unchanged most likely caused by the known inhibitory effect of rifampicin on Abcb1 function.

  5. Association of Hypothyroidism with Body Mass Index, Systolic Blood Pressure and Proteinuria in Diabetic Patients: Does treated Hypothyroidism with Thyroxine Replacement Therapy Prevent Nephropathy/Chronic Renal Disease?

    Aziz, Kamran M A


    Untreated or sub-clinical hypothyroidism is associated with insulin resistance, obesity, adverse effects on cardiovascular system, hypertension and in turn risk of nephropathy. However, these changes are reversible with thyroxine replacement therapy (TRT). Current research studied 4235 diabetic patients, divided into two groups, those with clinical hypothyroidism /on TRT, compared to those without thyroid disease or undiagnosed. BMI, blood pressure, creatinine, urine microalbumin and spot urine protein levels were compared between these two groups. Study finding demonstrated that for hypothyroid cases, BMI was higher (32.2 ± 7.44 versus 29.4 ± 5.7; p hypothyroidism (on TRT) was strongly associated with obesity (p hypothyroidism.

  6. Radioimmunoassay detection of levels of triiodothyronine and thyroxine in Mangalarga Marchador equine; Niveis sericos de triiodotinonina e tiroxina, atraves de radioimunoensaio, em equinos Mangalarga Marchador

    Viana, F.A.B.; Pessoa, J.M.; Biondini, J. [Minas Gerais Univ., Belo Horizonte, MG (Brazil). Escola de Veterinaria


    Serum levels of triiodothyronine (T{sub 3}) and thyroxine (T{sub 4}) were determined in equine of Mangalarga Marchador breed through radioimmunoassay. Forty-two animals (17 males and 25 females), with age ranging from two to eighteen years, were utilized. The values recorded for males and females were, respectively: 101.68 {+-} 23.44 and 71.14 {+-} 18.82 ng/d l of T{sub 3} (P<0.05); 1.89 {+-} 0.58 and 2.94 {+-} 0.87 mc g/d l of T{sub 4} (P<0.05). (author). 10 refs, 1 tab.

  7. A genome-wide association study of thyroid stimulating hormone and free thyroxine in Danish children and adolescents

    Svendstrup, Mathilde; Ohrt, Johanne Dam; Dahl, Maria; Fonvig, Cilius Esmann; Hollensted, Mette; Have, Christian Theil; Kadarmideen, Haja N.; Pedersen, Oluf; Hansen, Torben; Holm, Jens-Christian; Grarup, Niels


    Background Hypothyroidism is associated with obesity, and thyroid hormones are involved in the regulation of body composition, including fat mass. Genome-wide association studies (GWAS) in adults have identified 19 and 6 loci associated with plasma concentrations of thyroid stimulating hormone (TSH) and free thyroxine (fT4), respectively. Objective This study aimed to identify and characterize genetic variants associated with circulating TSH and fT4 in Danish children and adolescents and to examine whether these variants associate with obesity. Methods Genome-wide association analyses of imputed genotype data with fasting plasma concentrations of TSH and fT4 from a population-based sample of Danish children, adolescents, and young adults, and a group of children, adolescents, and young adults with overweight and obesity were performed (N = 1,764, mean age = 12.0 years [range 2.5−24.7]). Replication was performed in additional comparable samples (N = 2,097, mean age = 11.8 years [1.2−22.8]). Meta-analyses, using linear additive fixed-effect models, were performed on the results of the discovery and replication analyses. Results No novel loci associated with TSH or fT4 were identified. Four loci previously associated with TSH in adults were confirmed in this study population (PDE10A (rs2983511: β = 0.112SD, p = 4.8 ∙ 10−16), FOXE1 (rs7847663: β = 0.223SD, p = 1.5 ∙ 10−20), NR3C2 (rs9968300: β = 0.194SD), p = 2.4 ∙ 10−11), VEGFA (rs2396083: β = 0.088SD, p = 2.2 ∙ 10−10)). Effect sizes of variants known to associate with TSH or fT4 in adults showed a similar direction of effect in our cohort of children and adolescents, 11 of which were associated with TSH or fT4 in our study (padolescents, four loci previously associated with plasma TSH concentrations in adults, were associated with plasma TSH concentrations in children, suggesting comparable genetic determinants of thyroid function in adults and children. PMID:28333968

  8. Differential binding of thyroxine and triiodothyronine to acidic isoforms of thyroid hormone binding globulin in human serum

    Terasaki, T.; Pardridge, W.M.


    The differential availability of thyroxine (T/sub 4/) and 3,5,3'-triiodothyronine (T/sub 3/) to liver from the circulating thyroid hormone binding globulin (TBG)-bound pool suggests that the two thyroid hormones may bind to different TBG isoforms in human serum. In the present study, the binding of (/sup 125/I)T/sub 4/ and (/sup 125/I)T/sub 3/ to human serum proteins was investigated by using slab gel isoelectric focusing and chromatofocusing. In normal human male serum, (/sup 125/I)T/sub 4/ was localized to four isoforms of TBG called TBG-I, -II, -III, and -IV, with isoelectric points (pI's) of 4.30, 4.35, 4.45, and 4.55, respectively. (/sup 125/I)T/sub 3/ was localized to only two isoforms of TBG, TBG-III, and -IV, with pI's that were identical with those for (/sup 125/I)T/sub 4/. In normal female serum, (/sup 125/I)T/sub 4/ was localized to the same four isoforms of TBG as those of normal male serum, while (/sup 125/I)T/sub 3/ was localized to TBG-II, -III, -IV, and -V (pI = 4.65). In pregnant female serum, (/sup 125/I)T/sub 4/ was localized to five isoforms, whereas (/sup 125/I)T/sub 3/ was localized to four. IEF was also performed with male serum loaded with various concentrations of unlabeled T/sub 3/. The K/sub i/ values of T/sub 3/ binding to TBG-I, -II, -III, and -IV were 5.0, 2.4, 0.86, and 0.46 nM, respectively. The TBG isoforms in normal male serum were also separated by sequential concanavalin A-Sepharose affinity chromatography and the chromatofocusing (pH range of 3.5-5.0). T/sub 4/ preferentially bound to the most acidic isoforms of TBG in the pI range of 3.8-4.0, whereas the less acidic fractions (pH 4.0-4.2) bound both T/sub 4/ and T/sub 3/. In conclusion, this study shows that T/sub 4/ and T/sub 3/ do not bind to a single competitive binding site on TBG. Instead, T/sub 4/ is preferentially bound by the most acidic TBG isoforms owing to a 10-fold lower affinity of T/sub 3/ for these proteins.

  9. News/Press Releases

    Office of Personnel Management — A press release, news release, media release, press statement is written communication directed at members of the news media for the purpose of announcing programs...

  10. Short-term overt hypothyroidism affect on lipids after thyroxine-withdrawal in patients with differentiated thyroid carcinoma%骨巨细胞瘤软组织内复发两例报道及文献复习

    Hongyu Wu; Shuyao Zuo; Chao Ma; Bin Liu; Fengyu Wu; Simin Liu; Qin Zhang; Xifu Lan


    Objective: The aim of the study was to investigate the effects of short-term overt hypothyroidism on lipids after thyroxine-withdrawal in patients with iatrogenically induced hypothyroidism before radioiodine treatment for differentiated thyroid carcinoma (DTC). Methods: Thirty patients with a history of differentiated thyroid carcinoma on thyroid-stimulating hormone (TSH)-suppressive thyroxine replacement therapy were studied. Blood sample were taken before and 4 weeks after withdrawal of thyroxine substitution. Venous blood was drawn after an overnight fast and analyzed for serum free T4 (FT4), free T3 (FT3), thyroid-stimulating hormone (TSH), total cholesterol (TC), triglyceddes (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB). Fifty healthy people matched for age and gender were controls. Their blood samples were taken only once. Results: After thyroxine-withdrawal, the patients presented with increased serum TSH and low serum FT4 and FT3 levels compared with controls. Serum TG, TC, LDL, HDL, APOB and Lp(a) increased after thyroxine withdrawal, reaching statistical significant dif-ferences with previous evaluation. However, when compared to euthyroid controls, only TC, LDL and ApoB were increased when patients were hypothyroidism. No changes were observed in ApoA1 in patients dudng thyroxine withdrawal, or when comparing the values observed in patients to those of euthyroid controls. Conclusion: TG, TC, LDL, HDL, APO8 and Lp(a) were increased during short-term overt hypothyroidism.

  11. Electrochemical immunoassay for thyroxine detection using cascade catalysis as signal amplified enhancer and multi-functionalized magnetic graphene sphere as signal tag.

    Han, Jing; Zhuo, Ying; Chai, Yaqin; Yu, Yanqing; Liao, Ni; Yuan, Ruo


    This paper constructed a reusable electrochemical immunosensor for the detection of thyroxine at an ultralow concentration using cascade catalysis of cytochrome c (Cyt c) and glucose oxidase (GOx) as signal amplified enhancer. It is worth pointing out that numerous Cyt c and GOx were firstly carried onto the double-stranded DNA polymers based on hybridization chain reaction (HCR), and then the amplified responses could be achieved by cascade catalysis of Cyt c and GOx recycling with the help of glucose. Moreover, multi-functionalized magnetic graphene sphere was synthesized and used as signal tag, which not only exhibited good mechanical properties, large surface area and an excellent electron transfer rate of graphene, but also possessed excellent redox activity and desirable magnetic property. With a sandwich-type immunoreaction, the proposed cascade catalysis amplification strategy could greatly enhance the sensitivity for the detection of thyroxine. Under the optimal conditions, the immunosensor showed a wide linear ranged from 0.05pg mL(-1) to 5ng mL(-1) and a low detection limit down to 15fg mL(-1). Importantly, the proposed method offers promise for reproducible and cost-effective analysis of biological samples.

  12. The two triiodothyronines (T3 and rT3). Thyroid biosynthesis of T3 and rT3 and peripheral metabolism of thyroxine (author's transl).

    Roche, J; Michel, R


    Thirty per cent of the iodine in thyroglobulin is present as iodothyronines. L-thyroxine (T4) represents 90-95% of hormonal iodine, 3,5,3'-triodo-L-thyronine (T3) contains at the most two per cent of it, 3,3'5'-triodo-L-thyronine (rT3) even less, as well as traces of 3,3'-diodo-L-thyronine. The plasma concentration of T4 is about 8 microgram per 100 ml, in the case of T3 it is 120 ng and 25 ng for rT3. The cell nucleus preferentially binds T3 and rT3 and there are also some specific mitochondrial proteins which possess a high affinity for T3. L-thyroxine is dehalogenated peripherically to T3, to take care of most of the requirements in T3. The enrichment of the plasma in rT3 has been shown to occur under various experimental and pathological conditoins. The blood level of T3 varies in inverse ratio to the level of rT3 and it shows that the peripheral formation of one is compensated for by the other. The excess of the prehormone T4 is metabolised as 3,5,3',5'-tetraiodothyroacetic acid (TetrAc); its level in the blood varies in the same way as the level of T3, in particular it decreases during starvation.

  13. Simple synthesis of (3,5-/sup 125/I)diiodo-L-thyronine and of (3,5-/sup 125/I)L-thyroxine of high specific activity

    Sorimachi, K.; Cahnmann, H.J.


    The customary methods for labeling T/sub 4/ and its analogs, iodination or exchange-labeling, are not applicable to those iodothyronines whose iodine atoms are exclusively in the nonphenolic ring. Therefore, (3,5-/sup 125/I)diiodo-L-thyronine had to be synthesized by a different method. This synthesis involves the coupling of (/sup 125/I)diiodo-L-tyrosine with 4-hydroxy-3,5-diiodophenylpyruvic acid to form L-thyroxine labeled in the nonphenolic ring, followed by removal of the two unlabeled iodine atoms in the phenolic ring. High specific activity, limited only by that of the (/sup 125/I)diiodo-L-tyrosine used as starting material, can be achieved. Radioactivity yields are approximately 36% in the coupling reaction and approximately 86% in the deiodination reaction, amounting to an overall yield of greater than 30%. L-Thyroxine and 3,5-diiodo-L-thyronine were purified by ion-exchange chromatography. Their radiochemical purity was checked by radiochromatography.

  14. Clinical significance of the measurements of serum free thyroxine and free triiodothyronine concentrations. Evaluation using DPC free T/sub 4/ and free T/sub 3/ kits

    Kubota, Ken; Sasaki, Norio; Takaku, Fumimaro; Uchimura, Hidemasa


    A commercially available ''DPC'' radioimmunoassay kit was used to study the serum concentrations of free triiodothyronine (FT3) and free thyroxine (FT4) in a series of 189 patients with various thyroid diseases and 120 healthy controls. The basal serum concentrations of FT3 and FT4 in normal controls ranged from 0.98 to 2.04 ng/dl and from 1.43 to 3.66 pg/ml, respectively. All untreated patients with Graves' disease had abnormally high FT3 and FT4 values, indicating the discrimination between hyperthyroid and normal subjects. A decreased ratio of FT4 to FT3 was observed in patients managed with antithyroid drugs. In diagnosing hypothyroidism, ''DPC'' FT4 kits were more sensitive than ''DPC'' TT4 and ''Amerlex'' FT4 kits. In the case of non-thyroid diseases, FT4 and FT3 values, as well as total T4 and total T3, were normal or decreased, with the exception of occasionally unknown high values. The interference of thyroxine binding globulin abnormablity was successfully eliminated by using new versions of ''DPC'' kits. (Namekawa, K.).

  15. Lake Roosevelt Fisheries Monitoring Program; Measurement of Thyroxin Concentration as an Indicator of the Critical Period for Imprinting in the Kokanee Salmon (Orcorhynchus Nerka) Implications for Operating Lake Roosevelt Kokanee Hatcheries; 1991 Supplement Report.

    Scholz, Allan T.; White, Ronald J.; Koehler, Valerie A. (Eastern Washington University, Upper Columbia United Tribes Fisheries Research Center, Cheney, WA)


    Previous investigations have determined that thyroid hormone surges activate olfactory imprinting in anadromous salmonid smolts. The mechanism of action appears to require binding of thyroid hormones to receptors in brain cell nuclei, which stimulates neuron differentiation and wires a pattern of neuron circuitry that allows for the permanent storage of the imprinted olfactory memory. In this study, thyroxine concentrations [T{sub 4}] were measured in 487 Lake Whatcom stock and 70 Lake Roosevelt stock Kokanee salmon to indicate the critical period for imprinting. Eggs, alevins and fry, reared at the Spokane Indian Kokanee Hatchery, were collected from January through August 1991. Sampled fish were flash frozen on dry ice and stored at {minus}80{degrees}C until T{sub 4} was extracted and concentrations determined by radioimmunassay. Mean concentration {+-} SEM of 10--20 individual fish (assayed in duplicate) were determined for each time period. T{sub 4} concentration peaked on the day of hatch at 16.8 ng/g body weight and again at swim-up at 16.0 {+-} 4.7 ng/g body weight. T{sub 4} concentration was 12.5 to 12.9 ng/g body weight in eggs, 7.1 to 15.2 ng/g body weight in. alevins, 4.5 to 11.4 ng/g body weight in 42 to 105 day old fry and 0.1 to 2.9 ng/g body weight in 112 to 185 day old fry. T{sub 4} concentrations were highest in eggs at 13.3 {+-} 2.8 ng/g body weight, then steadily decreased to 0.1 {+-} 0.1 ng/g body weight in older fry. Fry were released in Lake Roosevelt tributaries in July and August 1991, at about 170--180 days post hatching, in order to imprint them to those sites. The results of this study indicate that the time of release was not appropriate for imprinting. If T{sub 4} levels are an accurate guide for imprinting in kokanee, our results suggest that the critical period for imprinting in kokanee is at hatching or swim-up stages.

  16. Commercial SNF Accident Release Fractions

    J. Schulz


    The purpose of this analysis is to specify and document the total and respirable fractions for radioactive materials that could be potentially released from an accident at the repository involving commercial spent nuclear fuel (SNF) in a dry environment. The total and respirable release fractions are used to support the preclosure licensing basis for the repository. The total release fraction is defined as the fraction of total commercial SNF assembly inventory, typically expressed as an activity inventory (e.g., curies), of a given radionuclide that is released to the environment from a waste form. Radionuclides are released from the inside of breached fuel rods (or pins) and from the detachment of radioactive material (crud) from the outside surfaces of fuel rods and other components of fuel assemblies. The total release fraction accounts for several mechanisms that tend to retain, retard, or diminish the amount of radionuclides that are available for transport to dose receptors or otherwise can be shown to reduce exposure of receptors to radiological releases. The total release fraction includes a fraction of airborne material that is respirable and could result in inhalation doses; this subset of the total release fraction is referred to as the respirable release fraction. Accidents may involve waste forms characterized as: (1) bare unconfined intact fuel assemblies, (2) confined intact fuel assemblies, or (3) canistered failed commercial SNF. Confined intact commercial SNF assemblies at the repository are contained in shipping casks, canisters, or waste packages. Four categories of failed commercial SNF are identified: (1) mechanically and cladding-penetration damaged commercial SNF, (2) consolidated/reconstituted assemblies, (3) fuel rods, pieces, and debris, and (4) nonfuel components. It is assumed that failed commercial SNF is placed into waste packages with a mesh screen at each end (CRWMS M&O 1999). In contrast to bare unconfined fuel assemblies, the

  17. Effect of different polymers on release of ranolazine from extended release tablets

    Murthy, T. E. G. K.; Bhukya Swapna


    An extended release tablet provides prolonged release of drug, maintains the desired concentration of drug in plasma and thereby reduce dosing frequency, improve patient compliance and reduce the dose-related side-effects. Ranolazine is indicated for the chronic treatment of angina in patients who have not achieved an adequate response with other anti-anginal agent. The present investigation was undertaken to design the extended release tablets of ranolazine employing different polymers as ma...

  18. Is bioexsiccation releasing dioxins?

    Benfenati, E.; Mariani, G.; Lodi, M.; Reitano, G.; Fanelli, R. [' ' Mario Negri' ' Institute for Pharmacological Research, Milan (Italy)


    Bioexsiccation is a relatively new process to treat urban solid wastes. We studied the possible release of dioxins from this process, measuring dioxin concentration in the emissions from a bioexsiccation plant. As a comparison, we measured atmospheric levels nearby the plant. The biofilter treating gaseous emissions was also evaluated to assess its efficiency. Dioxin concentrations in the biofilter effluent were lower than both those before the biofilter and the nearby atmosphere. In the last years the management and treatment of solid urban wastes produced some improved processes, in a general attempt to cope with the problem of the huge amount of wastes produced by the modern society. Bio-exsiccation of waste aims at affording a much more biologically inert and manageable material compared to the original waste. In this process the urban solid waste is kept under an air stream for about two weeks. The waste undergoes biological transformation, due to fermentation, which produces an increase of the temperature up to 60-70 C. At the end of the process the weight waste is typically reduced by one third, due to the loss of water and to the degradation of putrescible compounds. Since this is a relatively new industrial process, we studied the possible release of dioxins in the atmospheric emissions of the bioexsiccation plant.

  19. PCDD/PCDF release inventories

    Fiedler, H. [UNEP Chemicals, Chatelaine (Switzerland)


    The Stockholm Convention on Persistent Organic Pollutants (POPs) entered into force on 17 May 2004 with 50 Parties. In May 2004, 59 countries had ratified or acceded the Convention. The objective of the Convention is ''to protect human health and the environment from persistent organic pollutants''. For intentionally produced POPs, e.g., pesticides and industrial chemicals such as hexachlorobenzene and polychlorinated biphenyls, this will be achieved by stop of production and use. For unintentionally generated POPs, such as polychlorinated dibenzo-pdioxins (PCDD) and polychlorinated dibenzofurans (PCDF), measures have to be taken to ''reduce the total releases derived from anthropogenic sources''; the final goal is ultimate elimination, where feasible. Under the Convention, Parties have to establish and maintain release inventories to prove the continuous release reduction. Since many countries do not have the technical and financial capacity to measure all releases from all potential PCDD/PCDF sources, UNEP Chemicals has developed the ''Standardized Toolkit for the Identification of Quantification of Dioxin and Furan Releases'' (''Toolkit'' for short), a methodology to estimate annual releases from a number of sources. With this methodology, annual releases can be estimated by multiplying process-specific default emission factors provided in the Toolkit with national activity data. At the seventh session of the Intergovernmental Negotiating Committee, the Toolkit was recommended to be used by countries when reporting national release data to the Conference of the Parties. The Toolkit is especially used by developing countries and countries with economies in transition where no measured data are available. Results from Uruguay, Thailand, Jordan, Philippines, and Brunei Darussalam have been published.

  20. Highland amphibians – Recalculation of data from 1990 to 2010 on the effects of extremely diluted thyroxine

    Gehard Lingg


    Full Text Available Experiments on amphibian metamorphosis can vary considerably in duration. The authors had set themselves the task of defining a generally applicable pooling method for metamorphosis experiments. The problem of artificial differences in variability when comparing and pooling data from several experiments was approached by normalization with respect to time based on the development of both test and the control animals. The range from 0% to 100% over which the fraction of four-legged animals progresses in the course of an experiment is divided into 10%-intervals and the 10% reference points are mapped on a corresponding scale. Each measurement is then assigned to the point on the time scale to which it is closest. In this way each reference point is assigned a value giving the number or percentage of four-legged animals at that point on the scale. Subsequent analysis was then based on the individual values for the test and control groups that corresponded to the joint 10% reference point. Normalization respect to time was done on the assumption that differences in metamorphosis speed attributable to treatment would override differences in duration between experiments. The results of experiments performed over the course of two decades (1990 - 2010 on highland Rana temporaria treated with a homeopathically prepared high dilution of thyroxine (“30x” are presented in full detail based on this normalization method. Differences found between treatment groups thus calculated were in line with those obtained with other pooling methods. Thyroxine 30x does slow down metamorphosis in inert highland amphibians. This was observed by five researchers in 20 sub-experiments, and it seems to be the most reliable bio-assay found in amphibian research on homeopathy so far. When experiments were performed with highland animals pretreated by hyperstimulation with molecular thyroxine, slowing down of metamorphosis was again observed (by

  1. Thyroxine (T 4-RIA) and triiodothyronine (T 3-RIA) serum levels in sheep fed on Leucaena Leucocephala; Niveis sericos de tiroxina (T4-RIA) e triiodotinonina (T3-RIA) em ovinos alimentados cm Leucaena Leucocephala LAM

    Pessoa, J.M.; Rodriguez, N.M. [Minas Gerais Univ., Belo Horizonte, MG (Brazil). Escola de Veterinaria; Cardoso, W.M. [Maranhao Univ., Sao Luis, MA (Brazil). Escola de Medicina Veterinaria; Velez, C.E.S.


    The aim of this work is to study the toxicity of Leucaena leucocephala on thyroxine and triiodothyronine serum concentration. Results indicate that ovine T 4 and T 3 serum levels do not decrease with Leucaena leucocephala feeding, sohen proreided for 41 days. (author). 10 refs, 1 tab.

  2. Toxics Release Inventory (TRI)

    U.S. Environmental Protection Agency — The Toxics Release Inventory (TRI) is a dataset compiled by the U.S. Environmental Protection Agency (EPA). It contains information on the release and waste...

  3. Barrier and operational risk analysis of hydrocarbon releases (BORA-Release). Part II: Results from a case study.

    Sklet, Snorre; Vinnem, Jan Erik; Aven, Terje


    This paper presents results from a case study carried out on an offshore oil and gas production platform with the purpose to apply and test BORA-Release, a method for barrier and operational risk analysis of hydrocarbon releases. A description of the BORA-Release method is given in Part I of the paper. BORA-Release is applied to express the platform specific hydrocarbon release frequencies for three release scenarios for selected systems and activities on the platform. The case study demonstrated that the BORA-Release method is a useful tool for analysing the effect on the release frequency of safety barriers introduced to prevent hydrocarbon releases, and to study the effect on the barrier performance of platform specific conditions of technical, human, operational, and organisational risk influencing factors (RIFs). BORA-Release may also be used to analyse the effect on the release frequency of risk reducing measures.

  4. Recent patents in flavor controlled release.

    Feng, Tao; Xiao, Zuobing; Tian, Huaixiang


    In recent years, considerable effort has been directed toward the preparation of flavoring materials specifically, flavor materials have been sought that provide greater flavor intensity coupled with controlled flavor release for long periods of time. Here, some recent patents related to controlled flavor release are reviewed from the angle of its application field, its mechanism and its determination method. It is found that controlled flavor release often depends not only on materials' chemical and physical properties, such as melting point, solution properties and so on, but also on flavors' chemical and physical properties, such as diffusion capacity, its stability in different media etc. Meanwhile, flavor release is also controlled by an electric reducing device according to the flavor generation condition. It might be also known that flavor release rate could be determined by using a purge-and-trap/gas chromatographic procedure. In future, it's necessary to use mathematical model to study the kinetic behavior of controlled flavor release.

  5. Cytochrome bd-I in Escherichia coli is less sensitive than cytochromes bd-II or bo'' to inhibition by the carbon monoxide-releasing molecule, CORM-3: N-acetylcysteine reduces CO-RM uptake and inhibition of respiration.

    Jesse, Helen E; Nye, Tacita L; McLean, Samantha; Green, Jeffrey; Mann, Brian E; Poole, Robert K


    CO-releasing molecules (CO-RMs) are potential therapeutic agents, able to deliver CO - a critical gasotransmitter - in biological environments. CO-RMs are also effective antimicrobial agents; although the mechanisms of action are poorly defined, haem-containing terminal oxidases are primary targets. Nevertheless, it is clear from several studies that the effects of CO-RMs on biological systems are frequently not adequately explained by the release of CO: CO-RMs are generally more potent inhibitors than is CO gas and other effects of the molecules are evident. Because sensitivity to CO-RMs cannot be predicted by sensitivity to CO gas, we assess the differential susceptibilities of strains, each expressing only one of the three terminal oxidases of E. coli - cytochrome bd-I, cytochrome bd-II and cytochrome bo', to inhibition by CORM-3. We present the first sensitive measurement of the oxygen affinity of cytochrome bd-II (Km 0.24μM) employing globin deoxygenation. Finally, we investigate the way(s) in which thiol compounds abolish the inhibitory effects of CORM-2 and CORM-3 on respiration, growth and viability, a phenomenon that is well documented, but poorly understood. We show that a strain expressing cytochrome bd-I as the sole oxidase is least susceptible to inhibition by CORM-3 in its growth and respiration of both intact cells and membranes. Growth studies show that cytochrome bd-II has similar CORM-3 sensitivity to cytochrome bo'. Cytochromes bo' and bd-II also have considerably lower affinities for oxygen than bd-I. We show that the ability of N-acetylcysteine to abrogate the toxic effects of CO-RMs is not attributable to its antioxidant effects, or prevention of CO targeting to the oxidases, but may be largely due to the inhibition of CO-RM uptake by bacterial cells. A strain expressing cytochrome bd-I as the sole terminal oxidase is least susceptible to inhibition by CORM-3. N-acetylcysteine is a potent inhibitor of CO-RM uptake by E. coli. Rational design

  6. Analytical solution of diffusion model for nutrient release from controlled release fertilizer

    Ameenuddin Irfan, Sayed; Razali, Radzuan; KuShaari, KuZilati; Mansor, Nurlidia; Azeem, Babar


    An analytical method has been developed to solve the initial value problem which arises from Fick’s diffusion equation encountered in the modelling of the Controlled Release Fertilizers. The proposed analytical solution is developed using the modified Adomian decomposition method. This method does not require the discretization method, reliability and efficiency of this method is more and it also reduces the calculation time. The model has predicted the effect of granule radius and diffusion coefficient on the nutrient release and total release time of Controlled Release Fertilizer. Model has predicted that increase in the radius of granule reduces the release and vice versa in case of diffusion coefficient. Detailed understanding of these parameters helps in improved designing of Controlled Release Fertilizer.

  7. Release the Body, Release the Mind.

    Stoner, Martha Goff


    A college English teacher describes the anxiety and resentment of students during in-class writing assignments and the successful classroom use of meditation and body movement. Movement seemed to relax the students, change their attitudes, and release their creative impulses to write. Implications related to the body-mind connection are pondered.…

  8. Serum nitric oxide levels and flow-mediated dilatation in patients with Sheehan syndrome and the effect of combination therapy consisting of L-thyroxine, prednisolone, and conjugated estrogen/medroxyprogesterone acetate.

    Bahceci, Mithat; Pasa, Semir; Akay, Hatice O; Tuzcu, Alpaslan; Tumer, Cemil; Gokalp, Deniz


    Baseline and stimulated nitric oxide (NO) levels were higher, whereas baseline arterial diameter, FMD-stimulated NO increment, and arterial dilatation ratio were lower in Sheehan syndrome (SS) patients than in control subjects. After combination therapy consisting of prednisolone, L-thyroxine, and conjugated estrogen, baseline and stimulated NO levels of SS remained as high, but FMD-stimulated NO, NO increment ratio, and arterial dilatation ratio increased with treatment.

  9. Profiles of Cortisol, Triiodothyronine, Thyroxine and Neutrophil/Lymphocyte Ratio as Stress Indicators in Swamp Buffaloes 15 Days Post-Transportation

    H. Maheshwari


    Full Text Available Transportation may cause stress that affects livestock’s health. This research was conducted to observe the effect of transportation on the profiles of blood cortisol, triiodothyronine (T3, thyroxine (T4 and neutrophil/lymphocyte (N/L ratio as stress indicators during 15 days post-transportation. Four females swamp buffaloes, 2-yr-old were used in this research. The animals were transported using an open truck, along 15 kilometers distance for 2 h. During acclimatization, the animals were fed grass twice a day and access to water ad libitum. Blood was collected at the time of arrival and everyday for 15 d post-transportation. Cortisol, T3 and T4 were analyzed using Radioimmunoassay (RIA method. Blood smears were also prepared and stained with Giemsa for leukocyte differential counts. Results showed a significant relation (P1.5 in average throughout the period of the research. It is concluded that transportation causes stress and therefore changes metabolic process.

  10. Thyroxine clearance in rats within the first month after the single whole-body {gamma} - irradiation at a dose of 10Gy

    Pryadko, Kirill A. [Institute of Radiobiology, National Academy of Sciences, Minsk (Belarus)


    The effects of acute whole-body {gamma} -irradiation at a dose of 10 Gy on thyroxine (T{sub 4}) plasma clearance rate (PCR) and thyroidal and blood T4 concentration ([T{sub 4}]) were examined within one month after exposure. The PCR values were measured using the bolus injection, single-compartmental approach. To eliminate the influence of radiation-induced anorexia animals were fasting for two days before the pharmacokinetic experiments. Hormone concentrations in blood and in thyroid tissue were measured by RIA. Throughout the observation period, PCR was elevated in irradiated rats with maximum at day 4 after exposure (0.56{+-}0.04 vs. 0.36{+-}0.03 ml/h100 gbw, P<0.001). [T{sub 4}] in blood was not significantly different from that in control animals. Thyroidal [T{sub 4}] was significantly decreased in irradiated animals 4 days after exposure (151.8{+-}21.7 vs. 258.8{+-}29.9 pmol/mg protein, P<0.01) and gradually increased after day 9. 10 Gy {gamma} -irradiation causes the intensification of T{sub 4} metabolism without the pronounced changes in concentration. Presumably, at early terms the rising local demand in O{sub 4} can not be compensated with the existing level of production. Alterations in the intensity of T{sub 4} metabolism are evident at least one month after exposure but they may not be detected without taking into account kinetic data.

  11. The thyroxine-containing thyroglobulin peptide (aa 2549-2560) is a target epitope in iodide-accelerated spontaneous autoimmune thyroiditis.

    Kolypetri, Panayota; Carayanniotis, Karen; Rahman, Shofiur; Georghiou, Paris E; Magafa, Vassiliki; Cordopatis, Paul; Carayanniotis, George


    Enhanced iodide ingestion is known to accelerate the incidence and severity of spontaneous autoimmune thyroiditis [iodide-accelerated spontaneous autoimmune thyroiditis (ISAT)] in NOD.H2(h4) mice. CD4+ cells are required for the development and maintenance of ISAT, but their target epitopes remain unknown. In this study, we show that the previously identified thyroglobulin (Tg) T cell epitope p2549-2560 containing thyroxine at position 2553 (T4p2553) induces thyroiditis as well as strong specific T and B cell responses in NOD.H2(h4) mice. In ISAT, activated CD4+ T cells specific for T4p2553 are detected before the disease onset in thyroid-draining cervical lymph nodes only in mice placed on an iodide-rich diet and not in age-matched controls. In addition, selective enrichment of CD4+ IFN-γ+ T4p2553-specific cells is observed among cervical lymph node cells and intrathyroidal lymphocytes. T4p2553 was equally detectable on dendritic cells obtained ex vivo from cervical lymph node cells of NaI-fed or control mice, suggesting that the iodide-rich diet contributes to the activation of autoreactive cells rather than the generation of the autoantigenic epitope. Furthermore, spontaneous T4p2553-specific IgG are not detectable within the strong Tg-specific autoantibody response. To our knowledge, these data identify for the first time a Tg T cell epitope as a spontaneous target in ISAT.

  12. Linear growth, growth-hormone secretion and IGF-I generation in children with neglected hypothyroidism before and after thyroxine replacement.

    Soliman, Ashraf T; Omar, Magdy; El Awwa, Ahmad; Rizk, Mostafa M; El Alaily, Rania K; Bedair, Elsaid M A


    We studied growth hormone (GH) stimulation and insulin-like growth factor -I (IGF-I) generation tests in 15 children with neglected congenital hypothyroidism (CH) (age = 6.4 +/- 4.2 years) and measured their growth parameters for >1 years after starting thyroxine (T4) replacement. One year after treatment, height SDS (HtSDS) increased from -4.3 +/- 2.5 to -2.7 +/- 2.3. Peak GH response to clonidine increased from 3.2 +/- 1.2 ng ml(-1) to 7.62 +/- 1.38 ng ml(-1) after treatments. Basal and peak IGF-I response to GH increased from (34.66 +/- 17.3 ng ml(-1) and 58.4 +/- 36.99 ng ml(-1), respectively) before treatment to (130.6 +/- 97.8 ng ml(-1) and 193.75 +/- 122.5 ng ml(-1), respectively). HtSDS increments were correlated significantly with basal free T4 concentrations (r = 0.622, P < 0.01). In summary, after long period of hypothyroidism, T4 replacement produced significant, although incomplete, catch-up growth through a partial recovery of GH- IGF-I axis.

  13. Fluoride and chlorhexidine release from filled resins.

    Shen, C; Zhang, N-Z; Anusavice, K J


    Resin-based materials that release either fluoride or chlorhexidine have been formulated for inhibiting caries activity. It is not known if the two agents, when incorporated into one material, would interact and affect their release potential. We hypothesized that the ratio of fluoride to chlorhexidine incorporated into a resin, and the pH of the storage medium, will affect their releases from the material. The material investigated contained 23 wt% of filler, and the ratios of calcium fluoride to chlorhexidine diacetate were 8/2, 5/5, and 2/8. The release was conducted in pH 4, 5, and 6 acetate buffers. The results showed that release of either agent increased as the pH of the medium decreased. The presence of fluoride salt substantially reduced the chlorhexidine release, while the presence of a specific quantity of chlorhexidine significantly increased fluoride release. This interaction can be utilized to optimize the release of either agent for therapeutic purposes.

  14. Awareness Reduces Racial Bias


    Can raising awareness of racial bias subsequently reduce that bias? We address this question by exploiting the widespread media attention highlighting racial bias among professional basketball referees that occurred in May 2007 following the release of an academic study. Using new data, we confirm that racial bias persisted in the years after the study's original sample, but prior to the media coverage. Subsequent to the media coverage though, the bias completely disappeared. We examine poten...

  15. Thyroxine and triiodothyronine in plasma and thyroids of the neotenic and metamorphosed axolotl Ambystoma mexicanum: influence of TRH injections.

    Jacobs, G F; Michielsen, R P; Kühn, E R


    Circulating levels of T3 and T4, as well as T3 and T4 content of the thyroid glands were measured by radioimmunoassay in the neotenic and metamorphosed axolotl Ambystoma mexicanum. In the two experiments which were performed plasma T4 concentrations were more elevated in metamorphosed axolotls, especially in the first experiment (2.12 +/- 0.40 ng/ml vs. 369 +/- 30 pg/ml). T3 plasma values which were only estimated in the second experiment were about five times higher in metamorphosed animals (63.2 +/- 7.4 pg/ml vs. 12.5 +/- 0.8 pg/ml). Also the thyroid hormone content of the glands was higher after metamorphosis. Nevertheless the neotenic gland still contained considerable amounts of T3 (14.7 +/- 1.8 ng and 48.3 +/- 4.8 ng/thyroid, respectively, in the first and second experiment) and T4 (530 +/- 61 ng; 2173 +/- 291 ng/thyroid). Because of the higher T3/T4 ratio found in the plasma compared to the thyroid gland, it was suggested that circulating T3 may be derived partly from peripheral T4 conversion, mainly after metamorphosis. An intravenous injection of 10 micrograms synthetic TRH was able to induce a very significant increase of the plasma T4 concentration (which was maintained during 24 hr) in the metamorphosed axolotls of the first experiment, however, not in those of the second experiment nor in the neotenic animals. Following an injection of 10 mU bovine TSH (first experiment) circulating levels of T4 were raised in both groups. The opposing TRH results could be related with the different control levels of T4 in the two experiments. However, the results indicate that TRH is capable of functioning as a possible thyrotropin-releasing factor in the metamorphosed axolotl.

  16. 利培酮致甲状腺功能改变与糖脂代谢异常的相关性分析%Correlation analysis of risperidone-induced changes on serum thyroxin with disorders of glucose and lipid metabolism

    陈晓慧; 王彦青; 赵鹏辉; 徐东; 张淑芳; 赵倩


    Objective To study the correlation of risperidone-induced changes on serum thyroxin with changes on blood glucose and lipid. Methods 35 schizophrenia patients were given risperidone 1-6mg/d for 8 weeks. Triiodothyronine (T3), thyroxin (T4), free triiodothyronine (FT3), free thyroxin (FT4), glucose (GLU) and triglyceride (TG) of all patients were measured before and after treatment. Before and after treatment, T3, T4, FT3, FT4, GLU and TG were compared respectively (t test), and the correlation of T3, T4, FT3, FT4 changs with GLU and TG changes were analyzed (Pearson test). Results After 8 weeks treatment, there was no significant difference in T3 compared with pre-treatment. T4, FT4 and GLU were significantly decreased than before treatment(P<0.05, P<0.05, P<0.01);TG were significantly increased (P<0.05). Changes between T4, FT4 and GLU were positively correlated (P<0.01, and P < 0.05). Changes between T3, FT3 and GLU were not related. And changes between T3, FT3, T4, FT4 and GLU had no correlation. Conclusion Risperidone could reduce thyroid, glucose and elevated blood lipid. There were positive correlations between the decrease of thyroid and the reduce blood glucose.%目的:研究利培酮致血清甲状腺激素水平改变与血糖、血脂水平改变之间的相关性。方法给予35例精神分裂患者利培酮8周治疗,治疗前后分别测定血清三碘甲状腺原氨酸(T3)、甲状腺素(T4)、游离三碘甲状腺原氨酸(FT3)、游离甲状腺素(FT4)、血糖(GLU)和甘油三酯(TG)水平。分别对比治疗前后各因素水平的变化情况(t检验),并对因素水平改变差值之间进行相关性分析(Pearson检验)。结果与治疗前比,治疗后血清T3水平无统计学差异,T4、FT4水平显著降低(P<0.05);GLU水平和TG水平分别有极显著性降低和升高(P<0.01)。T4、FT4变化与GLU变化呈正相关,有统计学意义(P<0.01、P<0.05);T3、FT3变化

  17. Intracellular drug release nanosystems

    Fenghua Meng


    Full Text Available In order to elicit therapeutic effects, many drugs including small molecule anticancer drugs, proteins, siRNA, and DNA have to be delivered and released into the specific cellular compartments typically the cytoplasm or nucleus of target cells. Intracellular environment-responsive nanosystems that exhibit good extracellular stability while rapidly releasing drugs inside cancer cells have been actively pursued for effective cancer therapy. Here, we highlight novel designs of smart nanosystems that release drugs in response to an intracellular biological signal of cancer cells such as acidic pH in endo/lysosomal compartments, enzymes in lysosomes, and redox potential in cytoplasm and the cell nucleus.

  18. Miniature Release Mechanism Project

    National Aeronautics and Space Administration — The objective is to design, build and functionally test a miniature release mechanism for CubeSats and other small satellites. The WFF 6U satellite structure will be...

  19. Thermoresponsive latexes for fragrance encapsulation and release.

    Popadyuk, N; Popadyuk, A; Kohut, A; Voronov, A


    To synthesize cross-linked latex particles protecting the encapsulated fragrance at ambient temperatures and facilitating the release of cargo at the temperature of the surface of the skin that varies in different regions of the body between 33.5 and 36.9°C. Poly(stearyl acrylate) (PSA), a polymer with long crystallizable alkyl side chains (undergoes order-disorder transitions at 45°C), was chosen as the main component of the polymer particles. As a result, new thermoresponsive polymer particles for fragrance encapsulation were synthesized and characterized, including assessing the performance of particles in triggered release by elevated temperature. To obtain network domains of various crystallinity, stearyl acrylate was copolymerized with dipropylene glycol acrylate caprylate (DGAC) (comonomer) in the presence of a dipropylene glycol diacrylate sebacate (cross-linker) using the miniemulsion process. Comonomers and a cross-linker were mixed directly in a fragrance during polymerization. Fragrance release was evaluated at 25, 31, 35 and 39°C to demonstrate a new material potential in personal/health care skin-related applications. Particles protect the fragrance from evaporation at 25°C. The fragrance release rate gradually increases at 31, 35 and 39°C. Two slopes were found on release plots. The first slope corresponds to a rapid fragrance release. The second slope indicates a subsequent reduction in the release rate. Crystalline-to-amorphous transition of PSA triggers the release of fragrances from cross-linked latex particles at elevated temperatures. The presence of the encapsulated fragrance, as well as the inclusion of amorphous fragments in the polymer network, reduces the particle crystallinity and enhances the release. Release profiles can be tuned by temperature and controlled by the amount of loaded fragrance and the ratio of comonomers in the feed mixture. © 2015 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

  20. Observation on short-term curative effect of low dose thyroxine for treatment of transient hypothyroxinemia in premature infants%小剂量甲状腺素治疗早产儿暂时性低甲状腺素血症近期疗效观察

    马晓红; 王彩霞; 王黎; 王秀英


    alanine transami-nase, creatinine, urea nitrogen, pre - albumin, myocardial enzyme, and blood glucose after treatment didn't change obviously ( P > 0. 05) . Conclusion: Early supplementation of low dose thyroxine is safe and effective, which can improve the quality of life of premature infmils and reduce economic burden of parents.

  1. Environmentally friendly slow-release nitrogen fertilizer.

    Ni, Boli; Liu, Mingzhu; Lü, Shaoyu; Xie, Lihua; Wang, Yanfang


    To sustain the further world population, more fertilizers are required, which may become an environmental hazard, unless adequate technical and socioeconomic impacts are addressed. In the current study, slow-release formulations of nitrogen fertilizer were developed on the basis of natural attapulgite (APT) clay, ethylcellulose (EC) film, and sodium carboxymethylcellulose/hydroxyethylcellulose (CMC/HEC) hydrogel. The structural and chemical characteristics of the product were examined. The release profiles of urea, ammonium sulfate, and ammonium chloride as nitrogen fertilizer substrates were determined in soil. To further compare the release profiles of nitrogen from different fertilizer substrates, a mathematical model for nutrient release from the coated fertilizer was applied to calculate the diffusion coefficient D. The influence of the product on water-holding and water-retention capacities of soil was determined. The experimental data indicated that the product can effectively reduce nutrient loss, improve use efficiency of water, and prolong irrigation cycles in drought-prone environments.

  2. Electromyography of arrow release in archery.

    Hennessy, M P; Parker, A W


    An electronic arrow movement detector was used to accurately locate the muscle activity associated with release of the arrow during shooting in archery. Digital computer analysis of the electromyograms from thirty shots for two archers facilitated an examination of the relationship between the measured activity of the muscles and their function during release. Changes present in the direct and integrated electromyograms of muscles acting at the wrist and elbow joints of the bow arm and the shoulder of the draw arm tended to anticipate the moment of arrow release. These changes would produce muscular force to reduce unwanted movement at this critical phase of the shot in the bow arm and initiate release of the bow string by the fingers. This study provides a detailed quantitative analysis of the muscular action of the technique and identifies possibilities for prevention of injury by improving the understanding of muscle action in shooting.

  3. Partial deficiency of thyroxine-binding globulin-Allentown is due to a mutation in the signal peptide.

    Fingerhut, Anja; Reutrakul, Sirimon; Knuedeler, Sebastian D; Moeller, Lars C; Greenlee, Carol; Refetoff, Samuel; Janssen, Onno E


    We present an unusual variant of T(4)-binding globulin (TBG) found in a family from Allentown, Pennsylvania (TBG-AT). The heterozygous proposita presented serum total T(4) and TBG levels ranging from low to normal. TBG gene sequencing revealed a C-to-T substitution in codon -2 (CAC to TAC) leading to the substitution of the normal histidine by a tyrosine within the signal peptide. No mutation within the mature peptide was found. Allele-specific PCR confirmed the H(-2)Y mutation in the propositas mother and son. T(4)-binding analysis of TBG in serum from the proposita and son showed normal affinity but reduced capacity when compared with the unaffected father. Heat stability and isoelectric focusing of TBG-AT were normal. In vitro expression of a recombinant TBG-AT in Xenopus oocytes revealed a diminished secretory efficiency and confirmed the normal binding affinity and heat stability of the small amount of secreted TBG-AT. This study has defined impaired cotranslational processing as a hitherto unrecognized cause of hereditary TBG deficiency.

  4. Development of reagents for radioimmunoassay of: triiodothyronine, thyroxine and thyrotrophin; Desarrollo de reactivos para el radioinmunoanalisis de: triyodotironina, tiroxina y tirotrofina

    Delgado S, B.; Lavalley E, C.; Ruiz J, A.; Garcia F, C.; Zamorano A, F


    The radioimmunoassay (RIA) of thyroid hormones it is the but it frequents of all the studies carried out by RIA in the laboratories of Nuclear Medicine, these essays are carried out with imported reagents. In the ININ the reagents and the necessary methodology have been developed for the triiodothyronine (T3), thyroxine (T4) and thyrotrophin (TSH). The good titles of the antibodies (Ac) primary for each hormone were of 1:4,000; 1:750 and 1:1,500. The used separation system was of double Ac with PEG to 10%, with titles of 1:10 for the second Ac of lamb. The specific activity for 125-I-T3 and 125-I-T4 oscillate between 850 at 900 {mu}Ci / {mu} g: being this of 90 {mu} Ci /{mu}g for TSH. To the first two hormones they were added 1-8 aniline naftalen sulfonic acid (ANS) to concentrations of 3 and 2 mg/ml respectively. As buffer for T3 and T4 it was used Tris-HCl pH 8.6 and PBS with normal serum of rabbit (SNC) for TSH. The standards got ready in buffer or free serum of thyroid hormones. The slope of the standard curves varied between -2.3 to -2.7 and the variation intra and inter assay among 4 to 10%. It is had at the moment in the ININ with standardized reagents for the RIA of T3, T4 and TSH, it is hoped to carry out tests in other laboratories and to establish the conditions of stability more appropriate to begin the preparation of pilot reagents. (Author)

  5. Evaluation of seasonal and daily changes of plasma thyroxine and cortisol levels in wild masu salmon Oncorhynchus masou, sampled by a Japanese fishing method.

    Munakata, A; Miura, G; Matsuda, H


    A new fish sampling method was developed using a Japanese bait fishing rod (8-9 m carbon rod and a nylon line with a small fine wire single hook), which is considered to catch wild salmonid juveniles with low sampling stress. Using this method, seasonal and daily changes of plasma thyroxine (T4 ) and cortisol levels were examined in wild parr, pre-smolts and smolts of masu salmon Oncorhynchus masou in contiguous locations in a coastal river (Kesen River; 44 km) in northern Honshu Island, Japan, overlapping the period of smoltification and seaward migration from August to March. Plasma T4 and cortisol were low in 0+ and 1+ year parr caught in August and September. In March, some yearling (1+ year) fish, which were judged as pre-smolts, and smolts appeared mainly in mid and lower reaches, while parr (0+ and 1+ year parr) continued to appear in the upper and mid reaches. In March, 1+ year pre-smolts and smolts showed high plasma T4 levels while the levels of 1+ year parr were low. During March 2008-2010, plasma T4 levels of 1+ year pre-smolts and smolts had high levels from early to mid-March, whereas plasma cortisol levels of 1+ year smolts were low in early March and increased towards mid-March. Based on these data, plasma cortisol increases probably occur following the increases of plasma T4 levels to lead the 1+ year O. masou to the completion of smoltification and initiation of seaward migration. © 2014 The Fisheries Society of the British Isles.

  6. Free thyroxine levels are associated with cognitive changes in individuals with a first episode of psychosis: A prospective 1-year follow-up study.

    Labad, J; Barbero, J D; Gutiérrez-Zotes, A; Montalvo, I; Creus, M; Cabezas, Á; Solé, M; Algora, M J; Garcia-Parés, G; Vilella, E


    The results of previous cross-sectional studies suggest that free thyroxine (FT4) levels are associated with cognitive abilities (particularly attention/vigilance) during the early stages of psychosis. We aimed to explore whether hypothalamic-pituitary-thyroid hormones predict cognitive changes in a 1-year longitudinal study following first episodes of psychosis (FEP). We studied 36 FEP patients and a control group of 50 healthy subjects (HS). Plasma levels of thyroid-stimulating hormone (TSH) and FT4 were measured. Cognitive assessment was performed with the MATRICS Cognitive Consensus Cognitive Battery (MCCB). FEP patients were assessed twice (baseline and after 1year), whereas HS were assessed only once. We compared cognitive changes at 1year between three groups based on baseline FT4 levels: 1) lowest quartile (Q1, FT41.54ng/dL). No differences in TSH or FT4 levels were found between HS and FEP patients. All participants had FT4 levels within the normal range. HS outperformed FEP patients in all cognitive tasks. In relation to the relationship between FT4 levels and cognitive changes, a U-shaped pattern was observed: FEP patients from the middle quartiles (Q2-Q3) improved in attention/vigilance, whereas both extreme quartiles (Q1 and Q4) showed a worsening in this cognitive domain over time. Patients with lower FT4 (Q1) showed poorer baseline attention; therefore, lower baseline FT4 levels predicted a poorer prognosis in terms of attention performance. Our study suggests that baseline FT4 levels are associated with changes in attention and vigilance performance over one year in FEP patients.

  7. Association of low baseline free thyroxin levels with progression of coronary artery calcification over 4 years in euthyroid subjects: the Kangbuk Samsung Health Study.

    Park, Hye-Jeong; Kim, Jihyun; Han, Eun Jin; Park, Se Eun; Park, Cheol-Young; Lee, Won-Young; Oh, Ki-Won; Park, Sung-Woo; Rhee, Eun-Jung


    Overt and subclinical hypothyroidism are risk factors for atherosclerosis and cardiovascular diseases. It is unclear whether thyroid hormone levels within the normal range are also associated with atherosclerosis measured by coronary artery calcium (CAC). This study aimed to examine the relationship between normal variations in thyroid function and changes in CAC. We conducted a 4-year retrospective study of 2173 apparently healthy men and women with normal thyroid hormone levels. Their free thyroxin (FT4), free triiodothyronin (FT3) and thyroid-stimulating hormone (TSH) levels were measured by electrochemiluminescent immunoassay. The CAC score (CACS) of each subject was measured by multidetector computed tomography in both 2010 and 2014. Progression of CAC was defined as a CACS change over 4 years > 0. The mean CACS changes over 4 years by quartiles of baseline FT4 level (lowest to highest) were 12·9, 8·43, 7·82 and 7·81 (P = 0·028). CAC progression was not significantly associated with either the baseline FT3 or TSH levels. The odds ratios (OR) for CAC progression over 4 years (highest vs lowest quartile for baseline FT4) were 0·647 (95% confidence interval (CI) 0·472-0·886) after adjustment for confounding factor, which were attenuated with further adjustment for lipid profiles, homoeostasis model assessment of insulin resistance, high-sensitivity C-reactive protein and hypertension [0·747 (95% CI 0·537-1·038)]. Quartiles of baseline FT3 or TSH level did not show any increased OR for CAC progression after adjustment for confounding factors. In this cohort of euthyroid men and women, a low baseline FT4 level was associated with a high risk of CACS progression over 4 years. © 2015 John Wiley & Sons Ltd.

  8. Effects of estrogen supplementation on PCB 126-induced effects on vertebral bone, vitamin D and thyroxin levels in serum of rats

    P. Monica Lind [Karolinska Inst., Inst. of Environmental Medicine, Stockholm (Sweden); Nyberg, I.; Oerberg, J. [Uppsala Univ., Dept. of Environmental Toxicology (Sweden)


    Own and others experimental studies in rat have demonstrated that high affinity Aryl hydrocarbon Receptor (AhR) ligands such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and the dioxin-like PCB congener, 3,3',4,4',5-pentachlorobiphenyl (PCB126), impair normal bone metabolism and result in increased bone fragility. No experimental study have, up to now, investigated effects of POCs on vertebra in bone-toxicological studies. Recently a Swedish epidemiological study showed that Swedish east-coast fishermen's wives have a significantly increased incidence for hospitalized vertebral fractures when compared with west-coast fishermen's wives7. The results give some indirect support for the notion that a high dietary intake of POCs through fatty fish might be a risk factor for vertebral fractures. The levels of POCs are much higher in the fish from the Baltic Sea compared with fish from the sea on the Swedish West coast. Vertebral bone consists to a larger extent than e.g. the long bones of trabecular bone which compared with cortical bone has a much higher metabolism and a more rapid bone turnover. It is therefore more likely to find more obvious effects of endocrine disruption in trabecular bone than in cortical bone. As an extension of our previous work, the goals of this study are therefore to (1) investigate interactive effects between PCB126 exposure, estrogen depletion (OVX) and estrogen supplementation (2) investigate the effects of PCB126 exposure of the trabecular rich vertebral bone (3) analyse serum levels 25OH- vitamin D and thyroxin as these are both important for bone tissue homeostasis and as biomarkers for organochlorines exposure.

  9. Stability of /sup 131/I--thyroxine and of /sup 131/I-tri-iodothyronine: the influence of radiolytic disintegration on certain diagnostic tests

    Reviczky, A.L.; Szanto, L.


    The blood-protein fractions responsible for the transport of thyroid hormones (TBG, TBPA, TBA) were assayed for their thyroxine-binding capacity in the serum of the same control subject over a one-year period, by a procedure based on the isotope-dilution technique. In the dilutions of /sup 131/I--T/sub 4/ (Amersham RCC) required for the procedure, the ratio /sup 131/I--T/sub 4/:/sup 131/I--T/sub 3/ was measured in every case. Parallel with the accumulation of /sup 131/I--T/sub 3/ resulting from deiodination of /sup 131/I--T/sub 4/, the binding capacity of the individual fractions was found to have shifted from TBG to TBPA. The fact that, in contrast to the principle of the isotope-dilution technique, the labelled substance and the non-radioactive T/sub 4/ were partly different, suggests that the measurements of radioactivity do not reflect the true binding conditions of T/sub 4/. Successive batches of /sup 131/I--T/sub 3/ were examined in the same manner, and the values of the Hamolsky test were determined in the same serum. The figures displayed little variations and /sup 131/I--T/sub 3/ was also found significantly more stable than /sup 131/I--T/sub 4/. Thus, the Hamolsky test was found to represent a fairly reliable indicator of thyroid function, in contrast to measurement of the T/sub 4/-binding capacity of the blood protein fractions by the isotope-dilution technique, the results of which are uncertain and therefore inconclusive in both clinical and therapeutic respects. It is suggested that the /sup 131/I--T/sub 4/ serving for the assays should be supplied as a substance and diluted before use, but not later than a few days after preparation. The advantages of doublet tagging are pointed out.

  10. Tweaking the structure to radically change the function: the evolution of transthyretin from 5-hydroxyisourate hydrolase to triiodothyronine distributor to thyroxine distributor.

    Samantha J. Richardson


    Full Text Available Often, we elucidate evolutionary processes backwards, starting with eutherian mammals and gradually climbing down the evolutionary tree to those species who have survived since long before mammals evolved. This is also true for elucidating the evolution of specific proteins, in this case the protein currently known as transthyretin. Transthyretin (TTR was first described in eutherian mammals and was known as a thyroxine (T4 binding protein. However, mammals are the exception amongst vertebrates in respect to the function of TTR, as in teleost fish, amphibians, reptiles and birds TTR preferentially binds triiodothyronine (T3, which is the active form of thyroid hormone. The TTR gene possibly arose as a duplication of the TLP (TTR-Like Protein gene, around the stage of the agnathans. Some vertebrate species have both the TTR and TLP genes, whilst others have lost the TLP gene. TLP genes have been found in all kingdoms. The TLPs analysed to date do not bind thyroid hormones or their analogues, but are enzymes involved in uric acid metabolism, specifically, they are 5-hydroxyisourate hydrolases. A Salmonella TLP knock-out strain demonstrated that TLP was essential for the bacteria’s survival in the high uric acid environment of the chicken alimentary tract. Many other TLPs are yet to be characterised for their function although several have been confirmed as 5-hydroxyisourate hydrolases. This review describes the evolution of TLP/TTR and how subtle changes in gene structure or amino acid substitution can drastically change the function of this protein, without altering its overall 3D conformation.

  11. Synthesis of a highly fluorescent beta-diketone-europium chelate and its utility in time-resolved fluoroimmunoassay of serum total thyroxine.

    Wu, Feng-Bo; Han, Shi-Quan; Zhang, Chao; He, You-Feng


    A new highly fluorescent beta-diketone-europium chelate was synthesized and employed as a tracer to develop a time-resolved fluoroimmunoassay (TRFIA) for detection of serum total thyroxine (T4). The tetradentate beta-diketone chelator, 1,10-bis(thiophene-2'-yl)-4,4,5,5,6,6,7,7-octafluorodecane-1,3,8,10-tetraone (BTOT), was structurally composed of two units of thenoyltrifluoroacetone (TTA) derivatives but expressed fluorescence that was greatly enhanced, as compared to the original TTA molecules, in the presence of excess amount of Eu3+. The luminescence properties of the europium chelate of BTOT werestudied in aqueous solution. Chlorosulfonylation of BTOT afforded 1, 10-bis(5'-chlorosulfo-thiophene-2'-yl)-4,4,5,5,6,6,7,7-octafluorodecane-1,3,8,10-tetraone (BCTOT), which could be coupled to proteins (i.e., streptavidin or the BSA-T4 conjugate) and used as a tracer for TRFIA. Although the BCTOT-Eu complex could be detected at a very low level (approximately 1.07 x 10(-12) mol/L) in buffered aqueous solution (50 mmoVLTris-HCl; pH, 8.0), the application of the chelate label in direct serum T4 TRFIA experienced a problem of matrix interference, which was probably caused by some unknown chelating components in the samples as a result of the fact that the fluorescence of the BCTOT-Eu chelate was prone to quenching or enhancement by some chelating reagents. To remove this problem, an indirect serum T4 TRFIA was proposed with the use of BCTOT-Eu-labeled streptavidin (SA) as signal generation reagent. The concentrations of T4 in 27 human serums were determined by indirect T4 TRFIA, and the assay results correlated well with those obtained by commercial Coming-CLIA (r = 0.955) and Wallac-DELFIA (r 0.965).

  12. A fluoride release-adsorption-release system applied to fluoride-releasing restorative materials.

    Suljak, J P; Hatibovic-Kofman, S


    This investigation compared the initial fluoride release and release following refluoridation of three resin-modified glass-ionomer cements (Photac-Fil Applicap, Vitremer, and Fuji II LC) and a new polyacid-modified resin composite material (Dyract). After daily flouride release was measured for 8 days, specimens were refluoridated in 1,000-ppm solutions of fluoride ion for 10 minutes and fluoride release was measured for 5 days. Two further 5-day refluoridation-release periods were carried out. All materials released fluoride initially. Photac released the most; Dyract released the least. Initial release was greatest over the first few days. All materials released significantly more fluoride for 24 to 48 hours after refluoridation. Less fluoride was released with each successive refluoridation for the three glass-ionomer cements. The release from the Dyract compomer remained at a comparatively constant and significantly lower level following each refluoridation.

  13. Phenylthiourea specifically reduces zebrafish eye size.

    Li, Zeran; Ptak, Devon; Zhang, Liyun; Walls, Elwood K; Zhong, Wenxuan; Leung, Yuk Fai


    Phenylthiourea (PTU) is commonly used for inhibiting melanization of zebrafish embryos. In this study, the standard treatment with 0.2 mM PTU was demonstrated to specifically reduce eye size in larval fish starting at three days post-fertilization. This effect is likely the result of a reduction in retinal and lens size of PTU-treated eyes and is not related to melanization inhibition. This is because the eye size of tyr, a genetic mutant of tyrosinase whose activity is inhibited in PTU treatment, was not reduced. As PTU contains a thiocarbamide group which is presented in many goitrogens, suppressing thyroid hormone production is a possible mechanism by which PTU treatment may reduce eye size. Despite the fact that thyroxine level was found to be reduced in PTU-treated larvae, thyroid hormone supplements did not rescue the eye size reduction. Instead, treating embryos with six goitrogens, including inhibitors of thyroid peroxidase (TPO) and sodium-iodide symporter (NIS), suggested an alternative possibility. Specifically, three TPO inhibitors, including those that do not possess thiocarbamide, specifically reduced eye size; whereas none of the NIS inhibitors could elicit this effect. These observations indicate that TPO inhibition rather than a general suppression of thyroid hormone synthesis is likely the underlying cause of PTU-induced eye size reduction. Furthermore, the tissue-specific effect of PTU treatment might be mediated by an eye-specific TPO expression. Compared with treatment with other tyrosinase inhibitors or bleaching to remove melanization, PTU treatment remains the most effective approach. Thus, one should use caution when interpreting results that are obtained from PTU-treated embryos.

  14. Phenylthiourea specifically reduces zebrafish eye size.

    Zeran Li

    Full Text Available Phenylthiourea (PTU is commonly used for inhibiting melanization of zebrafish embryos. In this study, the standard treatment with 0.2 mM PTU was demonstrated to specifically reduce eye size in larval fish starting at three days post-fertilization. This effect is likely the result of a reduction in retinal and lens size of PTU-treated eyes and is not related to melanization inhibition. This is because the eye size of tyr, a genetic mutant of tyrosinase whose activity is inhibited in PTU treatment, was not reduced. As PTU contains a thiocarbamide group which is presented in many goitrogens, suppressing thyroid hormone production is a possible mechanism by which PTU treatment may reduce eye size. Despite the fact that thyroxine level was found to be reduced in PTU-treated larvae, thyroid hormone supplements did not rescue the eye size reduction. Instead, treating embryos with six goitrogens, including inhibitors of thyroid peroxidase (TPO and sodium-iodide symporter (NIS, suggested an alternative possibility. Specifically, three TPO inhibitors, including those that do not possess thiocarbamide, specifically reduced eye size; whereas none of the NIS inhibitors could elicit this effect. These observations indicate that TPO inhibition rather than a general suppression of thyroid hormone synthesis is likely the underlying cause of PTU-induced eye size reduction. Furthermore, the tissue-specific effect of PTU treatment might be mediated by an eye-specific TPO expression. Compared with treatment with other tyrosinase inhibitors or bleaching to remove melanization, PTU treatment remains the most effective approach. Thus, one should use caution when interpreting results that are obtained from PTU-treated embryos.

  15. RAVEN Beta Release

    Rabiti, Cristian [Idaho National Lab. (INL), Idaho Falls, ID (United States); Alfonsi, Andrea [Idaho National Lab. (INL), Idaho Falls, ID (United States); Cogliati, Joshua Joseph [Idaho National Lab. (INL), Idaho Falls, ID (United States); Mandelli, Diego [Idaho National Lab. (INL), Idaho Falls, ID (United States); Kinoshita, Robert Arthur [Idaho National Lab. (INL), Idaho Falls, ID (United States); Wang, Congjian [Idaho National Lab. (INL), Idaho Falls, ID (United States); Maljovec, Daniel Patrick [Idaho National Lab. (INL), Idaho Falls, ID (United States); Talbot, Paul William [Idaho National Lab. (INL), Idaho Falls, ID (United States)


    This documents the release of the Risk Analysis Virtual Environment (RAVEN) code. A description of the RAVEN code is provided, and discussion of the release process for the M2LW-16IN0704045 milestone. The RAVEN code is a generic software framework to perform parametric and probabilistic analysis based on the response of complex system codes. RAVEN is capable of investigating the system response as well as the input space using Monte Carlo, Grid, or Latin Hyper Cube sampling schemes, but its strength is focused toward system feature discovery, such as limit surfaces, separating regions of the input space leading to system failure, using dynamic supervised learning techniques. RAVEN has now increased in maturity enough for the Beta 1.0 release.

  16. Controlled-release microchips.

    Sharma, Sadhana; Nijdam, A Jasper; Sinha, Piyush M; Walczak, Robbie J; Liu, Xuewu; Cheng, Mark M-C; Ferrari, Mauro


    Efficient drug delivery remains an important challenge in medicine: continuous release of therapeutic agents over extended time periods in accordance with a predetermined temporal profile; local delivery at a constant rate to the tumour microenvironment to overcome much of the systemic toxicity and to improve antitumour efficacy; improved ease of administration, and increasing patient compliance required are some of the unmet needs of the present drug delivery technology. Microfabrication technology has enabled the development of novel controlled-release microchips with capabilities not present in the current treatment modalities. In this review, the current status and future prospects of different types of controlled-release microchips are summarised and analysed with reference to microneedle-based microchips, as well as providing an in-depth focus on microreservoir-based and nanoporous microchips.

  17. Precision Departure Release Capability (PDRC) Technology Description

    Engelland, Shawn A.; Capps, Richard; Day, Kevin; Robinson, Corissia; Null, Jody R.


    Center scheduling tool. The PDRC concept also incorporates earlier NASA and FAA research into automation-assisted CFR coordination. The PDRC concept helps reduce uncertainty by automatically communicating coordinated release times with seconds-level precision enabling TMCs to work with target times rather than windows. NASA has developed a PDRC prototype system that integrates the Center's TMA system with a research prototype Tower decision support tool. A two-phase field evaluation was conducted at NASA's North Texas Research Station (NTX) in Dallas-Fort Worth. The field evaluation validated the PDRC concept and demonstrated reduced release time uncertainty while being used for tactical departure scheduling of more than 230 operational flights over 29 weeks of operations. This paper presents the Technology Description. Companion papers include the Final Report and a Concept of Operations.

  18. Precision Departure Release Capability (PDRC) Final Report

    Engelland, Shawn A.; Capps, Richard; Day, Kevin Brian; Kistler, Matthew Stephen; Gaither, Frank; Juro, Greg


    runway assignments to the Center scheduling tool. The PDRC concept also incorporates earlier NASA and FAA research into automation-assisted CFR coordination. The PDRC concept reduces uncertainty by automatically communicating coordinated release times with seconds-level precision enabling TMCs and FLMs to work with target times rather than windows. NASA has developed a PDRC prototype system that integrates the Center's TMA system with a research prototype Tower decision support tool. A two-phase field evaluation was conducted at NASA's North Texas Research Station in Dallas/Fort Worth. The field evaluation validated the PDRC concept and demonstrated reduced release time uncertainty while being used for tactical departure scheduling of more than 230 operational flights over 29 weeks of operations. This paper presents research results from the PDRC research activity. Companion papers present the Concept of Operations and a Technology Description.

  19. Effect of different polymers on release of ranolazine from extended release tablets

    T. E. G. K. Murthy


    Full Text Available An extended release tablet provides prolonged release of drug, maintains the desired concentration of drug in plasma and thereby reduce dosing frequency, improve patient compliance and reduce the dose-related side-effects. Ranolazine is indicated for the chronic treatment of angina in patients who have not achieved an adequate response with other anti-anginal agent. The present investigation was undertaken to design the extended release tablets of ranolazine employing different polymers as matrix forming agents using direct compression technique. Formulated tablets were evaluated for weight variation, hardness, friability, drug content, swelling index and in vitro release studies. The drug release followed first order kinetics and controlled by both erosion and diffusion mechanism. It is concluded that the desired drug release pattern can be obtained from the formulation containing 9.8% w/w eudragit and 39.2% w/w metallose offered relatively much slow release of ranolazine compared with other formulations. The selected formulation showed a similarity factor 76 when comparing in vitro dissolution data of the commercial formulation ranozex 500.

  20. Municipal actions to reduce mercury



    This paper presented proper management practices for products containing mercury. The measures can help reduce mercury releases, occupational exposure and mercury spills, thereby preventing impacts on human health and the environment. Despite mercury's toxic nature, many common products that contain mercury are commercially available. These include thermostats, thermometers, fluorescent lamps, pressure measuring devices, electrical switches and relays, and dental amalgam. Mercury emissions are also associated with base metal smelting, waste incineration and coal-fired power generation. Mercury in the environment is a global issue, because it can travel in the atmosphere on wind currents. The actions taken by municipalities to address the issue include reducing or eliminating mercury releases from internal municipal operations and sources within the community. This document provided guidance on how to develop a Municipal Mercury Elimination Policy and Plan that will help reduce mercury releases. It presented information and case studies that will help municipalities manage mercury-containing products found in municipal buildings and street lighting. Information on sources of mercury from within the community was presented along with case studies that can help municipalities determine where community action is needed to reduce mercury releases. The 5 modules of this document were intended to help municipalities identify priorities, timelines and budget requirements for mercury initiatives. It was emphasized that municipalities that adopt a Municipal Mercury Elimination Policy and Plan formally commit to reducing and eliminating mercury from the environment. tabs., figs.

  1. Effect of hydrophilic and hydrophobic polymers on release kinetics of metoprolol succinate extended release tablets

    Ramani Gade


    Full Text Available The purpose of the present work is to design and evaluate extended release matrix tablets of metoprolol succinate to reduce the dosing frequency and to improve patient compliance. The matrix tablets were prepared by the combination of hydrophilic and hydrophobic polymers, using methocel 10000 Cps in combination with ethyl cellulose 7 Cps, Eudragit® RS100, Eudragit® S100, and Eudragit® L100.The tablets were prepared by direct compression technique. Prepared formulations were evaluated for various parameters like weight variation, thickness, hardness, friability, and % drug content. Tablets were subjected to in vitro drug release studies. The formulations containing methocel 10000 Cps, Eudragit® L100 showed good release retardation. All the prepared formulations showed first-order release kinetics with matrix diffusion mechanism of release. The formulation containing 52.06% w/w of methocel 10000 Cps, 8.75% Eudragit® L100 offered the required release rate according to USP Pharmacopoeial guidelines. The combination of hydrophilic and hydrophobic polymers can effectively control the drug release for freely water-soluble drugs in case of extended release formulations which are the upcoming dosage forms for patient compliance in all aspects.

  2. Release of OLe peanut

    OLe is a high oleic Spanish-type peanut that has excellent yield and enhanced Sclerotinia blight and pod rot resistance when compared to other high oleic Spanish cultivars. The purpose for releasing OLe is to provide peanut producers with a true Spanish peanut that is high oleic and has enhanced yi...

  3. Border cell release

    Mravec, Jozef


    Plant border cells are specialised cells derived from the root cap with roles in the biomechanics of root growth and in forming a barrier against pathogens. The mechanism of highly localised cell separation which is essential for their release to the environment is little understood. Here I present...

  4. Release and control of hydrogen sulfide during sludge thermal drying

    Weng, Huanxin; Dai, Zhixin; Ji, Zhongqiang; Gao, Caixia; Liu, Chongxuan


    The release of hydrogen sulfide (H2S) during sludge drying is a major environmental problem because of its toxicity to human health. A series of experiments were performed to investigate the mechanisms and factors controlling the H2S release. Results of this study show that: 1) the biomass and activity of sulfate-reducing bacteria (SRB) in sludge were the major factors controlling the amount of H2S release, 2) the sludge drying temperature had an important effect on both the extent and the timing of H2S release from the sludge, and 3) decreasing sludge pH increased the H2S release. Based on the findings from this study, a new system that integrates sludge drying and H2S gas treatment was developed to reduce the amount of H2S released from sludge treatments.

  5. Superhydrophobic nitric oxide-releasing xerogels.

    Storm, Wesley L; Youn, Jonghae; Reighard, Katelyn P; Worley, Brittany V; Lodaya, Hetali M; Shin, Jae Ho; Schoenfisch, Mark H


    Superhydrophobic nitric oxide (NO)-releasing xerogels were prepared by spray-coating a fluorinated silane/silica composite onto N-diazeniumdiolate NO donor-modified xerogels. The thickness of the superhydrophobic layer was used to extend NO release durations from 59 to 105h. The resulting xerogels were stable, maintaining superhydrophobicity for up to 1month (the longest duration tested) when immersed in solution, with no leaching of silica or undesirable fragmentation detected. The combination of superhydrophobicity and NO release reduced viable Pseudomonas aeruginosa adhesion by >2-logs. The killing effect of NO was demonstrated at longer bacterial contact times, with superhydrophobic NO-releasing xerogels resulting in 3.8-log reductions in adhered viable bacteria vs. controls. With no observed toxicity to L929 murine fibroblasts, NO-releasing superhydrophobic membranes may be valuable antibacterial coatings for implants as they both reduce adhesion and kill bacteria that do adhere. Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  6. Matrix Interference in Serum Total Thyroxin (T4) Time-resolved Fluorescence Immunoassay (TRFIA) and Its Elimination With the Use of Streptavidin-biotin Separation Technique


    In development of serum total thyroxin TRFIA using the surface second-antibody (S-Ab) as separation agent, a significant bias of measurement caused by matrix interference when the surface S-Ab shows a relatively low binding capacity for primary anti-T4 monoclonal antibody (McAb) is studied. The bias ranges from 10% to 78%, depending on the matrix of individual samples and the binding capacity of the surface S-Ab prepared. So, a new separation system based on the use of a highly active surface streptavidin and biotinylated anti-T4 McAb is employed. The results indicate




    Full Text Available Oral route gets the highest priority for thedelivery of the drug as well as better patient compliance incase of self delivery dosage formulation. The aim ofpresent investigation was undertaken with the objective offormulating sustain release formulation of Itopridehydrochloride for oral drug delivery. Itopride hydrochlorideis highly water soluble prokinetic drug.Hydroxypropylmethylcellulose K4M (lower viscositygrade and K100M (higher viscosity grade were used as amatrix forming agents to control the release of drug. HPMCK4M and HPMC K100M were used individually as well asin combination with different proportion in the preparationof the Sustained release formulation. 32 factorial designswere applied to the polymer concentration that affects thedrug release profile. Reduced equation for drug release at2hr,6hr,and10hrwere22 1 2 1 Q 37.644 5.41X 3.25X 2.017X ,26 1 2 1 Q 72.367 8.05X 4.4X 3.75X ,and10 1 1 2 90.844 5.8 2.633 2.8 2 Q X X X Xrespectively. Optimized batch F019 shows good tabletproperties like hardness(7-9kg/cm2, thickness(4.48mm,friability(0.024%,assay(99.3% and nearly similar drugrelease profile to the targeted reference drug release profileand it was indicated by similarity factor (f2=86.04.

  8. Congenital hypothyroidism, as studied in rats. Crucial role of maternal thyroxine but not of 3,5,3'-triiodothyronine in the protection of the fetal brain.

    Calvo, R; Obregón, M J; Ruiz de Oña, C; Escobar del Rey, F; Morreale de Escobar, G


    To study the protective effects of maternal thyroxine (T4) and 3,5,3'-triiodothyronine (T3) in congenital hypothyroidism, we gave pregnant rats methimazole (MMI), an antithyroid drug that crosses the placenta, and infused them with three different doses of T4 or T3. The concentrations of both T4 and T3 were determined in maternal and fetal plasma and tissues (obtained near term) by specific RIAs. Several thyroid hormone-dependent biological end-points were also measured. MMI treatment resulted in marked fetal T4 and T3 deficiency. Infusion of T4 into the mothers increased both these pools in a dose-dependent fashion. There was a preferential increase of T3 in the fetal brain. Thus, with a T4 dose maintaining maternal euthyroidism, fetal brain T3 reached normal values, although fetal plasma T4 was 40% of normal and plasma TSH was high. The infusion of T3 pool into the mothers increased the total fetal extrathyroidal T3 pool in a dose-dependent fashion. The fetal T4 pools were not increased, however, and this deprived the fetal brain (and possibly the pituitary) of local generation of T3 from T4. As a consequence, fetal brain T3 deficiency was not mitigated even when dams were infused with a toxic dose of T3. The results show that (a) there is a preferential protection of the brain of the hypothyroid fetus from T3 deficiency; (b) maternal T4, but not T3, plays a crucial role in this protection, and (c) any condition which lowers maternal T4 (including treatment with T3) is potentially harmful for the brain of a hypothyroid fetus. Recent confirmation of transplacental passage of T4 in women at term suggests that present results are relevant for human fetuses with impairment of thyroid function. Finding signs of hypothyroidism at birth does not necessarily mean that the brain was unprotected in utero, provided maternal T4 is normal. It is crucial to realize that maintainance of maternal "euthyroidism" is not sufficient, as despite hypothyroxinemia, the mothers may be

  9. The effect of thyroxine on apoptosis in vascular endothelial cells%甲状腺激素对血管内皮细胞凋亡的影响

    王浩华; 向光大


    目的 探讨甲状腺激素对血管内皮细胞凋亡的影响.方法 噻唑蓝(MTT)比色法测定不同浓度的三碘甲状腺原氨酸( T3,0、0.1、1.0、10.0、50.0、100.0 nmol/L)对人脐静脉内皮细胞(HUVEC)生长的影响;Hochest 33258染色和流式细胞术检测不同浓度T3作用于HUVEC细胞48小时后的凋亡.结果 T3在0.1~ 10.0 nmol/L浓度范围时,尤其是1.0 nmol/L对HUVEC具有保护作用,而> 10.0 nmol/L或<0.1 nmol/L浓度时,HUVEC细胞凋亡增加(P<0.05).结论 生理浓度( 1.0 nmol/L)的T3对HUVEC保护作用最大.%Objective To explore the effect of thyroxine on apoptosis in vascular endothelial cells. Methods The inhibition of 3 ,3' ,5-Triiodo-L-thyronine( T_3 ) with different concentrations(0 ,0. 1 , 1.0,10.0,50.0,100.0 nraol/L) on human umbilical vein endothelial cells(HUVEC) growth was analyzed by methyl thiazoly] tetrazoliym ( MTT) assays. The cells apoptosis in different concentrations of T_3 was measured by cytometry and Hochest 33258 for 48 h. Results T_3 protected HUVEC from apoptosis at concentrations ranging from 0. 1 nmol/L to 10.0 nmol/L,especially at the concentration of 1. 0nmol/L(P <0.05) and induced HUVEC apoptosis at concentrations of more than 10. 0 nmol/L or less than 0. 1 nmol/L(P <0.05). Conclusion T_3 has the best protective effects in HUVEC at physiological concentration .

  10. Tablet and oral liquid L-thyroxine formulation in the treatment of naïve hypothyroid patients with Helicobacter pylori infection.

    Ribichini, Danilo; Fiorini, Giulia; Repaci, Andrea; Castelli, Valentina; Gatta, Luigi; Vaira, Dino; Pasquali, Renato


    To compare the clinical efficacy of tablet and oral liquid L-thyroxine (LT4) formulation in naïve hypothyroid subjects with Helicobacter pylori infection. Forty-seven adult naïve hypothyroid subjects with dyspeptic symptoms were investigated with upper endoscopy and divided into: 28 patients with Helicobacter pylori infection (Group A); 15 patients without gastric alterations (group B); 4 patients with autoimmune gastritis were excluded from the study. Subjects were randomly treated with a same dose of LT4 tablet (TAB) or oral liquid formulation (SOL), for 9 months on group A and 6 months on group B. Helicobacter pylori infection was eradicated after 3 months of LT4 treatment. On group A, after 3 months (before Helicobacter pylori eradication), subjects treated with SOL showed a greater thyroid-stimulating hormone reduction (ΔTSH3-0: TAB = -4.1 ± 4.6 mU/L; SOL = -7.7 ± 2.5 mU/L; p = 0.029) and a greater homogeneity in the thyroid-stimulating hormone values (TSH3mo: TAB = 5.7 ± 4.9 mU/L; SOL = 4.1 ± 2.0 mU/L; p = 0.025), compared to LT4 tablet. At 9 months (after 6 months of Helicobacter pylori eradication) mean thyroid-stimulating hormone values were lower in subjects treated with LT4 tablet (TSH9mo: TAB = 1.8 ± 1.2 mU/L; SOL = 3.2 ± 1.7 mU/L; p = 0.006). On group B no difference were observed, at each time point, in the mean thyroid-stimulating hormone values and thyroid-stimulating hormone variations between two LT4 formulations. LT4 liquid formulation may produce a better clinical response compared to the tablet formulation in hypothyroid subjects with Helicobacter pylori infection.

  11. Analysis of LNG import terminal release prevention systems

    Baker, E G


    The release prevention systems of liquefied natural gas (LNG) import terminal were analyzed. A series of potential release scenarios were analyzed to determine the frequency of the release events, the probability these releases are not stopped or isolated by emergency shutdown systems, the estimated release quantities, and the critical components of the system. The two plant areas identified as being most significant with respect to safety are the unloading system and the storage system. Rupture of the main transfer line and gross failure of the storage tanks are the two release scenarios of primary safety interest. Reducing the rate of failure by improved design, better maintenance and testing, or adding redundancy of the critical system components for these plant areas and release scenarios will result in improved safety. Several design alternatives which have the potential to significantly reduce the probability of a large release of LNG occurring at an import terminal are identified. These design alternatives would reduce the probability of a large release of LNG by reducing the expected number of failures which could cause a release or by reducing the magnitude of releases that do occur. All of these alternatives are technically feasible and have been used or considered for use in at least one LNG facility. A more rigorous analysis of the absolute risk of LNG import terminal operation is necessary before the benefits of these design alternatives can be determined. In addition, an economic evaluation of these alternatives must be made so the costs and benefits can be compared. It is concludd that for remotely located facilities many of these alternatives are probably not justified; however, for facilities located in highly populated areas, these alternatives deserve serious consideration.

  12. Myofascial release of carpal tunnel syndrome.

    Sucher, B M


    Current treatment for carpal tunnel syndrome may be ineffective or associated with complications or recurrence. In the case reported here, a myofascial release by the physician combined with the patient's self-stretch reduced pain and numbness and improved electromyographic results. The manipulative approach releases the transverse carpal ligament,-and "opens" or dilates the canal. The patient stretches the wrist, digits, and thumb, including myofascial components. An aggressive, conservative approach lessens the need for surgery in mild to moderate cases. Studies with magnetic resonance imaging may be helpful to document canal size before and after treatment.

  13. Free T4 (Thyroxine) Test

    Advertisement Proceeds from website advertising help sustain Lab Tests Online. AACC is a not-for-profit organization and does not endorse non-AACC products and services. Advertising & Sponsorship: Policy | Opportunities ...

  14. Carpal tunnel release

    Larsen, Morten Bo; Sørensen, A I; Crone, K L;


    A single-blind, randomized, controlled trial was done to compare the results of carpal tunnel release using classic incision, short incision, or endoscopic technique. In total, 90 consecutive cases were included. Follow-up was 24 weeks. We found a significantly shorter sick leave in the endoscopi...... incision could be found. There were no serious complications in either group. The results indicate that the endoscopic procedure is safe and has the benefit of faster rehabilitation and return to work....

  15. Cryogenic hydrogen release research.

    LaFleur, Angela Christine [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)


    The objective of this project was to devolop a plan for modifying the Turbulent Combustion Laboratory (TCL) with the necessary infrastructure to produce a cold (near liquid temperature) hydrogen jet. The necessary infrastructure has been specified and laboratory modifications are currently underway. Once complete, experiments from this platform will be used to develop and validate models that inform codes and standards which specify protection criteria for unintended releases from liquid hydrogen storage, transport, and delivery infrastructure.

  16. EIA new releases


    This report was prepared by the Energy Information Administration. It contains news releases on items of interest to the petroleum, coal, nuclear, electric and alternate fuels industries ranging from economic outlooks to environmental concerns. There is also a listing of reports by industry and an energy education resource listing containing sources for free or low-cost energy-related educational materials for educators and primary and secondary students.

  17. Contact: Releasing the news

    Pinotti, Roberto

    The problem of mass behavior after man's future contacts with other intelligences in the universe is not only a challenge for social scientists and political leaders all over the world, but also a cultural time bomb as well. In fact, since the impact of CETI (Contact with Extraterrestrial Intelligence) on human civilization, with its different cultures, might cause a serious socio-anthropological shock, a common and predetermined worldwide strategy is necessary in releasing the news after the contact, in order to keep possible manifestations of fear, panic and hysteria under control. An analysis of past studies in this field and of parallel historical situations as analogs suggests a definite "authority crisis" in the public as a direct consequence of an unexpected release of the news, involving a devastating "chain reaction" process (from both the psychological and sociological viewpoints) of anomie and maybe the collapse of today's society. The only way to prevent all this is to prepare the world's public opinion concerning contact before releasing the news, and to develop a long-term strategy through the combined efforts of scientists, political leaders, intelligence agencies and the mass media, in order to create the cultural conditions in which a confrontation with ETI won't affect mankind in a traumatic way. Definite roles and tasks in this multi-level model are suggested.

  18. Mechanisms of HSP72 release

    Alexzander Asea


    Currently two mechanisms are recognized by which heat shock proteins (HSP) are released from cells; a passive release mechanism, including necrotic cell death, severe blunt trauma, surgery and following infection with lytic viruses, and an active release mechanism which involves the non classical protein release pathway. HSPs are released both as free HSP and within exosomes. This review covers recent findings on the mechanism by which stress induces the release of HSP72 into the circulation and the biological significance of circulating HSP72 to host defense against disease.

  19. Triggered Release from Polymer Capsules

    Esser-Kahn, Aaron P. [Univ. of Illinois, Urbana, IL (United States). Beckman Inst. for Advanced Science and Technology and Dept. of Chemistry; Odom, Susan A. [Univ. of Illinois, Urbana, IL (United States). Beckman Inst. for Advanced Science and Technology and Dept. of Chemistry; Sottos, Nancy R. [Univ. of Illinois, Urbana, IL (United States). Beckman Inst. for Advanced Science and Technology and Dept. of Materials Science and Engineering; White, Scott R. [Univ. of Illinois, Urbana, IL (United States). Beckman Inst. for Advanced Science and Technology and Dept. of Aerospace Engineering; Moore, Jeffrey S. [Univ. of Illinois, Urbana, IL (United States). Beckman Inst. for Advanced Science and Technology and Dept. of Chemistry


    Stimuli-responsive capsules are of interest in drug delivery, fragrance release, food preservation, and self-healing materials. Many methods are used to trigger the release of encapsulated contents. Here we highlight mechanisms for the controlled release of encapsulated cargo that utilize chemical reactions occurring in solid polymeric shell walls. Triggering mechanisms responsible for covalent bond cleavage that result in the release of capsule contents include chemical, biological, light, thermal, magnetic, and electrical stimuli. We present methods for encapsulation and release, triggering methods, and mechanisms and conclude with our opinions on interesting obstacles for chemically induced activation with relevance for controlled release.

  20. Protecting privacy in data release

    Livraga, Giovanni


    This book presents a comprehensive approach to protecting sensitive information when large data collections are released by their owners. It addresses three key requirements of data privacy: the protection of data explicitly released, the protection of information not explicitly released but potentially vulnerable due to a release of other data, and the enforcement of owner-defined access restrictions to the released data. It is also the first book with a complete examination of how to enforce dynamic read and write access authorizations on released data, applicable to the emerging data outsou

  1. Effect of hydroxypropyl methylcellulose and hydrogenated castor oil on naproxen release from sustained-release tablets.

    Amaral, M H; Lobo, J M; Ferreira, D C


    The effect of the concentration of hydrophilic (hydroxypropyl methylcellulose [HPMC]) and hydrophobic (hydrogenated castor oil [HCO]) products, fillers (lactose and dibasic calcium phosphate), and buffers (sodium bicarbonate, calcium carbonate, and sodium citrate) on naproxen release rate was studied. Matrix tablets were prepared by double compression, and in vitro dissolution tests were performed. The dissolution results showed that an increased amount of HPMC or hydrogenated castor oil resulted in reduced drug release. The inclusion of buffers in the HPMC matrix tablets enhanced naproxen release. For HCO tablets, only sodium bicarbonate enhanced naproxen release. The presence of lactose on HPMC matrix tablets did not show a significantly different result from that obtained with the formulation containing dibasic calcium phosphate as a filler. However, for the tablets containing HCO, the presence of lactose significantly enhanced the naproxen release rate. The matrix-forming materials in this study were suitable for use in sustained-release tablets containing naproxen. The drug release can be modulated by adding suitable amounts of diluents and buffers.

  2. Environmental Release Prevention and Control Plan

    Mamatey, A.; Arnett, M.


    During the history of SRS, continual improvements in facilities, process, and operations, and changes in the site`s mission have reduced the amount of radioactive liquid releases. In the early years of SRS (1958 to 1965), the amount of tritium discharged to the Savannah River averaged approximately 61,000 curies a year. During the mid-1980`s (1983 to 1988), liquid releases of tritium averaged 27,000 curies a year. By 1996, liquid releases of tritium are projected to be just 3000 curies for the year. This large projected decrease is the result of the planned shut-down of all reactors and the anticipated significant decline in the amount of tritium migrating from the site seepage basins and the Solid Waste Disposal Facility.

  3. Encapsulated Urea-Kaolinite Nanocomposite for Controlled Release Fertilizer Formulations

    Sempeho, Siafu Ibahati; Kim, Hee Taik; Mubofu, Egid; Pogrebnoi, Alexander; Shao, Godlisten; Hilonga, Askwar


    Urea controlled release fertilizer (CRF) was prepared via kaolinite intercalation followed by gum arabic encapsulation in an attempt to reduce its severe losses associated with dissolution, hydrolysis, and diffusion...

  4. Allegheny County Toxics Release Inventory

    Allegheny County / City of Pittsburgh / Western PA Regional Data Center — The Toxics Release Inventory (TRI) data provides information about toxic substances released into the environment or managed through recycling, energy recovery, and...

  5. Changes in parasite transmission stage excretion after pheasant release


    The production of parasite transmission stages was investigated in the faeces of 77 farm-bred ring-necked pheasants (Phasianus colchicus). Coccidian oocysts (Eimeria sp.), and nematode eggs (Heterakis sp., and Capillaria-like eggs) were recovered before and after release but all birds were treated prior to release. Treatment with fenbendazole significantly reduced the abundance of trans-mission-stage excretion for all parasites, and reduced the prevalence in the case of Eimeria sp. and Hetera...

  6. Heat release mechanism of energetics

    Kubota, N. [Third Research Center, Technical Research and development Institute (Japan)


    Determination of the heat release mechanism of energetic materials is a major subject of combustion study. In order to elucidate the combustion process of various types of energetic materials a generalized combustion wave structure was proposed and the heat release process was discussed. The heat release process was significantly different between the physical structures of the materials: homogeneous and heterogeneous materials. The thermal structure of an azide polymer was evaluated to demonstrate the heat release mechanism. (author) 6 refs.

  7. Certain hormonal profiles of postpartum anestrus jersey crossbred cows treated with controlled internal drug release and ovsynch protocol

    Dayanidhi Jena


    Full Text Available Aim: The study was conducted to determine the serum levels of certain hormones in post-partum anestrus cows following treatment with controlled internal drug release (CIDR and Ovsynch protocol. Materials and Methods: A total of 30 postpartum anestrus cows were divided into three equal groups after thorough gynecoclinical examination. The Group 1 animals received an intravaginal progesterone device on day 0 and 2 ml of prostaglandin F2α (PGF2α on day of CIDR removal (7th day, Group 2 cows were treated with ovsynch protocol (gonadotropinreleasing hormone [GnRH]-PGF2α-GnRH on day 0, 7 and 9, respectively, and Group 3 cows were supplemented with mineral mixture and treated as control. The serum estrogen, progesterone, triiodothyronine, and thyroxine concentration were estimated using enzyme-linked immunosorbent assay kit and absorbance was read at 450 nm with Perkin Elmer Wallac 1420 Microplate Reader. Results: There was a significant increase in progesterone level in Group 1 after withdrawal of CIDR as compared to other two groups. However, the estrogen assay revealed a greater concentration in Group 2 against Group 1 on day 7 of sampling. However, there was no significant difference for serum triiodothyronine (T3 and thyroxine (T4 irrespective of treatment protocols and days of sampling. Conclusion: Treatment with CIDR based progesterone therapy and drug combinations may affect the reproductive hormonal balance like estrogen and progesterone, which is inevitable for successful return to cyclicity and subsequent fertilization and conception. However, as far as serum T3 and T4 concentration concerned it may not give an astounding result.

  8. Overview study of LNG release prevention and control systems

    Pelto, P.J.; Baker, E.G.; Holter, G.M.; Powers, T.B.


    The liquefied natural gas (LNG) industry employs a variety of release prevention and control techniques to reduce the likelihood and the consequences of accidental LNG releases. A study of the effectiveness of these release prevention and control systems is being performed. Reference descriptions for the basic types of LNG facilities were developed. Then an overview study was performed to identify areas that merit subsequent and more detailed analyses. The specific objectives were to characterize the LNG facilities of interest and their release prevention and control systems, identify possible weak links and research needs, and provide an analytical framework for subsequent detailed analyses. The LNG facilities analyzed include a reference export terminal, marine vessel, import terminal, peakshaving facility, truck tanker, and satellite facility. A reference description for these facilities, a preliminary hazards analysis (PHA), and a list of representative release scenarios are included. The reference facility descriptions outline basic process flows, plant layouts, and safety features. The PHA identifies the important release prevention operations. Representative release scenarios provide a format for discussing potential initiating events, effects of the release prevention and control systems, information needs, and potential design changes. These scenarios range from relatively frequent but low consequence releases to unlikely but large releases and are the principal basis for the next stage of analysis.

  9. Modifying sorbents in controlled release formulations to prevent herbicides pollution

    Cespedes, F.F.; Sanchez, M.V.; Garcia, S.P.; Perez, M.F. [University of Almeria, Almeria (Spain). Dept. of Inorganic Chemistry


    The herbicides chloridazon and metribuzin, identified as groundwater pollutants, were incorporated in alginate-based granules to obtain controlled release properties. In this research the effect of incorporation of sorbents such as bentonite, anthracite and activated carbon in alginate basic formulation were not only studied on encapsulation efficiency but also on the release rate of herbicides which was studied using water release kinetic tests. In addition, sorption studies of herbicides with bentonite, anthracite and activated carbon were made. The kinetic experiments of chloridazon and metribuzin release in water have shown that the release rate is higher in metribuzin systems than in those prepared with chloridazon, which has lower water solubility. Besides, it can be deduced that the use of sorbents reduces the release rate of the chloridazon and metribuzin in comparison to the technical product and to the alginate formulation without sorbents. The highest decrease in release rate corresponds to the formulations prepared with activated carbon as a sorbent. The water uptake, permeability, and time taken for 50% of the active ingredient to be released into water, were calculated to compare the formulations. On the basis of a parameter of an empirical equation used to fit the herbicide release data, the release of chloridazon and metribuzin from the various formulations into water is controlled by a diffusion mechanism.

  10. Hydroxypropyl methylcellulose based cephalexin extended release tablets: influence of tablet formulation, hardness and storage on in vitro release kinetics.

    Saravanan, Muniyandy; Sri Nataraj, Kalakonda; Ganesh, Kettavarampalayam Swaminath


    The object of this study was to develop hydroxypropyl methylcellulose (HPMC) based cephalexin extended release tablet, which can release the drug for six hours in predetermined rate. Twenty-one batches of cephalexin tablets were prepared by changing various physical and chemical parameters, in order to get required theoretical release profile. The influences of HPMC, microcrystalline cellulose powder (MCCP), granulation technique, wetting agent and tablet hardness on cephalexin release from HPMC based extended release tablets were studied. The formulated tablets were also characterized by physical and chemical parameters. The dissolution results showed that a higher amount of HPMC in tablet composition resulted in reduced drug release. Addition of MCCP resulted in faster drug release. Tablets prepared by dry granulation was released the drug slowly than the same prepared with a wet granulation technique. Addition of wetting agent in the tablets prepared with dry granulation technique showed slower release. An increase in tablet hardness resulted in faster drug release. Tablets prepared with a wet granulation technique and having a composition of 9.3% w/w HPMC with a hardness of 10-12 kg/cm(2) gave predicted release for 6 h. The in vitro release data was well fit in to Higuchi and Korsmeyer-Peppas model. Physical and chemical parameters of all formulated tablets were within acceptable limits. One batch among formulated twenty-one batches was successful and showed required theoretical release. The effect of storage on in vitro release and physicochemical parameters of successful batch was studied and was found to be in acceptable limits.

  11. Reducing Resistance

    Lindell, Johanna

    care may influence decisions on antibiotic use. Based on video-and audio recordings of physician-patient consultations it is investigated how treatment recommendations are presented, can be changed, are forecast and explained, and finally, how they seemingly meet resistance and how this resistance......Antibiotic resistance is a growing public health problem both nationally and internationally, and efficient strategies are needed to reduce unnecessary use. This dissertation presents four research studies, which examine how communication between general practitioners and patients in Danish primary...... is responded to.The first study in the dissertation suggests that treatment recommendations on antibiotics are often done in a way that encourages patient acceptance. In extension of this, the second study of the dissertation examines a case, where acceptance of such a recommendation is changed into a shared...

  12. Polysaccharides As Safer Release Systems For Agrochemicals

    Campos E.V.R.; de Oliveira J.L.; Fraceto L.F.; Singh B


    International audience; Agrochemicals are used to improve the production of crops. Conventional formulations of agrochemicals can contaminate the environment, in particular in the case of intensive cropping. Hence, there is a need for controlled-release formulations of agrochemicals such as polysaccharides to reduce pollution and health hazards. Natural polysaccharides are hydrophilic, biodegradable polymers. This article reviews the use of polysaccharides in the form of micro- and nanopartic...

  13. Attentional priming releases crowding.

    Kristjánsson, Arni; Heimisson, Pétur Rúnar; Róbertsson, Gunnar Freyr; Whitney, David


    Views of natural scenes unfold over time, and objects of interest that were present a moment ago tend to remain present. While visual crowding places a fundamental limit on object recognition in cluttered scenes, most studies of crowding have suffered from the limitation that they typically involved static scenes. The role of temporal continuity in crowding has therefore been unaddressed. We investigated intertrial effects upon crowding in visual scenes, showing that crowding is considerably diminished when objects remain constant on consecutive visual search trials. Repetition of both the target and distractors decreases the critical distance for crowding from flankers. More generally, our results show how object continuity through between-trial priming releases objects that would otherwise be unidentifiable due to crowding. Crowding, although it is a significant bottleneck on object recognition, can be mitigated by statistically likely temporal continuity of the objects. Crowding therefore depends not only on what is momentarily present, but also on what was previously attended.

  14. 甲状腺功能减退患者心率变异及对治疗的反应%Heart rate variability and its response to thyroxine replacement therapy in patients with hypothyroidism

    邢惠莉; 陈寒蓓; 王一尘; 沈迎; 沈卫峰


    Objective To analyze heart rate variability (HRV)and its changes with thyroxine treatment in patients with hypothyroidism. Methods HRV was analyzed using 24-hour electrocardiographic recording in 38 patients with hypothyroidism and 21 normal controls. The changes in HRV were evaluated for the 18 hypothyroid patients after 3 months of thyroxine therapy. Results The time domain measurements of HRV in hypothyroid patients were much lower than those in the control group. As to HRV frequency domain, the high frequency power was significantly higher, but the ratio of low frequency power to frequency power for hypothyroid patients was lower than in the controls. These abnormal changes of HRV measurements in hypothyroid patients were improved after treatment with thyroxine and were associated with recovery of serum concentrations of FT3 and FT4. Conclusions Patients with hypothyroidism often have autonomic neuropathies with a higher level of vagal tone. These abnormalities could be partly improved by thyoxine therapy.%目的测定甲状腺功能减退(甲减)患者心率变异(HRV)及观察甲状腺素替代治疗后的变化.方法记录38例甲减患者与21例正常者24小时动态心电图,并进行HRV分析.18例甲减患者治疗3月后重复HRV测定.结果甲减时,HRV的时阈指标较对照组明显降低;频阈指标中,高频功率(HF)较对照组明显增高,而低频(LF)与HF比值较对照组显著减低.甲减患者经甲状腺素替代治疗后,HRV时阈指标和频阈指标均明显改善,且与FT3和FT4的恢复程度相一致.结论甲减时,自主神经活动明显改变,且以迷走神经兴奋性增加占优势.这种自主神经异常在甲状腺素替代治疗后可部分改善.

  15. Sustained release choline theophyllinate in nocturnal asthma.

    Rhind, G B; Connaughton, J J; McFie, J; Douglas, N J; Flenley, D C


    Nocturnal wheeze is common in patients with asthma, and slow release theophyllines may reduce symptoms. As theophyllines are stimulants of the central nervous system the effect of 10 days' twice daily treatment with sustained release choline theophyllinate or placebo on symptoms, overnight bronchoconstriction, nocturnal oxygen saturation, and quality of sleep were studied in a double blind crossover study in nine stable patients with nocturnal asthma (five men, four women, age range 23-64 years; forced expiratory volume in one second (FEV1) 0.85-3.8 1; vital capacity 1.95-6.1 1). When treated with the active drug all patients had plasma theophylline concentrations of at least 28 mmol/l (5 micrograms/ml) (peak plasma theophylline concentrations 50-144 mmol/l (9-26 micrograms/ml]. Morning FEV1 was higher when treated with sustained release choline theophyllinate (2.7 (SEM 0.3) 1) than placebo (2.1 (0.3) 1) (p less than 0.01). Both daytime and nocturnal symptoms were reduced when the patients were treated with sustained release choline theophyllinate and subjective quality of sleep was improved (p less than 0.002). When treated with the active drug, however, quality of sleep determined by electroencephalography deteriorated with an increase in wakefulness and drowsiness (p less than 0.05) and a reduction in non-rapid eye movement sleep (p less than 0.005). Treatment with choline theophyllinate had no effect on either the occurrence or the severity of transient nocturnal hypoxaemic episodes or apnoeas or hypopnoeas. In conclusion, sustained release choline theophyllinate prevents overnight bronchoconstriction, but impairs quality of sleep defined by electroencephalography.

  16. Effect of combination therapy with thyroxine (T4) and 3,5,3'-triiodothyronine versus T4 monotherapy in patients with hypothyroidism, a double-blind, randomised cross-over study

    Nygaard, Birte; Jensen, Ebbe Winther; Kvetny, Jan


    the effect of combination therapy with thyroxine (T(4)) and T(3) versus T(4) monotherapy in patients with hypothyroidism on stable T(4) substitution. Study design Double-blind, randomised cross-over. Fifty micrograms of the usual T(4) dose was replaced with either 20 microg T(3) or 50 microg T(4) for 12...... weeks, followed by cross-over for another 12 weeks. The T(4) dose was regulated if needed, intending unaltered serum TSH levels. Evaluation Tests for quality of life (QOL) and depression (SF-36, Beck Depression Inventory, and SCL-90-R) at baseline and after both treatment periods. Inclusion criteria......, indicating a positive effect related to the combination therapy. Forty-nine percent preferred the combination and 15% monotherapy (P=0.002). Serum TSH remained unaltered between the groups as intended. CONCLUSION: In a study design, where morning TSH levels were unaltered between groups combination therapy...

  17. Optogenetic control of ATP release

    Lewis, Matthew A.; Joshi, Bipin; Gu, Ling; Feranchak, Andrew; Mohanty, Samarendra K.


    Controlled release of ATP can be used for understanding extracellular purinergic signaling. While coarse mechanical forces and hypotonic stimulation have been utilized in the past to initiate ATP release from cells, these methods are neither spatially accurate nor temporally precise. Further, these methods cannot be utilized in a highly effective cell-specific manner. To mitigate the uncertainties regarding cellular-specificity and spatio-temporal release of ATP, we herein demonstrate use of optogenetics for ATP release. ATP release in response to optogenetic stimulation was monitored by Luciferin-Luciferase assay (North American firefly, photinus pyralis) using luminometer as well as mesoscopic bioluminescence imaging. Our result demonstrates repetitive release of ATP subsequent to optogenetic stimulation. It is thus feasible that purinergic signaling can be directly detected via imaging if the stimulus can be confined to single cell or in a spatially-defined group of cells. This study opens up new avenue to interrogate the mechanisms of purinergic signaling.

  18. Cobalt release from inexpensive jewellery

    Thyssen, Jacob Pontoppidan; Jellesen, Morten Stendahl; Menné, Torkil


    Objectives: The aim was to study 354 consumer items using the cobalt spot test. Cobalt release was assessed to obtain a risk estimate of cobalt allergy and dermatitis in consumers who would wear the jewellery. Methods: The cobalt spot test was used to assess cobalt release from all items....... Microstructural characterization was made using scanning electron microscope (SEM) and energy-dispersive spectroscopy (EDS). Results: Cobalt release was found in 4 (1.1%) of 354 items. All these had a dark appearance. SEM/EDS was performed on the four dark appearing items which showed tin-cobalt plating on these....... Conclusions: This study showed that only a minority of inexpensive jewellery purchased in Denmark released cobalt when analysed with the cobalt spot test. As fashion trends fluctuate and we found cobalt release from dark appearing jewellery, cobalt release from consumer items should be monitored in the future...

  19. Determining drug release rates of hydrophobic compounds from nanocarriers.

    D'Addio, Suzanne M; Bukari, Abdallah A; Dawoud, Mohammed; Bunjes, Heike; Rinaldi, Carlos; Prud'homme, Robert K


    Obtaining meaningful drug release profiles for drug formulations is essential prior to in vivo testing and for ensuring consistent quality. The release kinetics of hydrophobic drugs from nanocarriers (NCs) are not well understood because the standard protocols for maintaining sink conditions and sampling are not valid owing to mass transfer and solubility limitations. In this work, a new in vitroassay protocol based on 'lipid sinks' and magnetic separation produces release conditions that mimic the concentrations of lipid membranes and lipoproteins in vivo, facilitates separation, and thus allows determination of intrinsic release rates of drugs from NCs. The assay protocol is validated by (i) determining the magnetic separation efficiency, (ii) demonstrating that sink condition requirements are met, and (iii) accounting for drug by completing a mass balance. NCs of itraconazole and cyclosporine A (CsA) were prepared and the drug release profiles were determined. This release protocol has been used to compare the drug release from a polymer stabilized NC of CsA to a solid drug NP of CsA alone. These data have led to the finding that stabilizing block copolymer layers have a retarding effect on drug release from NCs, reducing the rate of CsA release fourfold compared with the nanoparticle without a polymer coating.This article is part of the themed issue 'Soft interfacial materials: from fundamentals to formulation'.

  20. Assembly of bio-nanoparticles for double controlled drug release.

    Wei Huang

    Full Text Available A critical limiting factor of chemotherapy is the unacceptably high toxicity. The use of nanoparticle based drug carriers has significantly reduced the side effects and facilitated the delivery of drugs. Source of the remaining side effect includes (1 the broad final in vivo distribution of the administrated nanoparticles, and (2 strong basal drug release from nanoparticles before they could reach the tumor. Despite the advances in pH-triggered release, undesirable basal drug release has been a constant challenge under in vivo conditions. In this study, functionalized single walled carbon nanohorn supported immunoliposomes were assembled for paclitaxel delivery. The immunoliposomes were formulated with polyethylene glycol, thermal stable and pH sensitive phospholipids. Each nanohorn was found to be encapsulated within one immunoliposome. Results showed a highly pH dependent release of paclitaxel in the presence of serum at body temperature with minimal basal release under physiological conditions. Upon acidification, paclitaxel was released at a steady rate over 30 days with a cumulative release of 90% of the loaded drug. The drug release results proved our hypothesized double controlled release mechanism from the nanoparticles. Other results showed the nanoparticles have doubled loading capacity compared to that of traditional liposomes and higher affinity to breast cancer cells overexpressing Her2 receptors. Internalized nanoparticles were found in lysosomes.

  1. Meticulous Overview on the Controlled Release Fertilizers

    Siafu Ibahati Sempeho


    Full Text Available Owing to the high demand for fertilizer formulations that will exhaust the possibilities of nutrient use efficiency (NUE, regulate fertilizer consumption, and lessen agrophysicochemical properties and environmental adverse effects instigated by conventional nutrient supply to crops, this review recapitulates controlled release fertilizers (CRFs as a cutting-edge and safe way to supply crops’ nutrients over the conventional ways. Essentially, CRFs entail fertilizer particles intercalated within excipients aiming at reducing the frequency of fertilizer application thereby abating potential adverse effects linked with conventional fertilizer use. Application of nanotechnology and materials engineering in agriculture particularly in the design of CRFs, the distinctions and classification of CRFs, and the economical, agronomical, and environmental aspects of CRFs has been revised putting into account the development and synthesis of CRFs, laboratory CRFs syntheses and testing, and both linear and sigmoid release features of CRF formulations. Methodical account on the mechanism of nutrient release centring on the empirical and mechanistic approaches of predicting nutrient release is given in view of selected mathematical models. Compositions and laboratory preparations of CRFs basing on in situ and graft polymerization are provided alongside the physical methods used in CRFs encapsulation, with an emphasis on the natural polymers, modified clays, and superabsorbent nanocomposite excipients.

  2. The SAMI Galaxy Survey: Early Data Release

    Allen, J T; Konstantopoulos, I S; Bryant, J J; Sharp, R; Cecil, G N; Fogarty, L M R; Foster, C; Green, A W; Ho, I -T; Owers, M S; Schaefer, A L; Scott, N; Bauer, A E; Baldry, I; Barnes, L A; Bland-Hawthorn, J; Bloom, J V; Brough, S; Colless, M; Cortese, L; Couch, W J; Drinkwater, M J; Driver, S P; Goodwin, M; Gunawardhana, M L P; Hampton, E J; Hopkins, A M; Kewley, L J; Lawrence, J S; Leon-Saval, S G; Liske, J; López-Sánchez, Á R; Lorente, N P F; Medling, A M; Mould, J; Norberg, P; Parker, Q A; Power, C; Pracy, M B; Richards, S N; Robotham, A S G; Sweet, S M; Taylor, E N; Thomas, A D; Tonini, C; Walcher, C J


    We present the Early Data Release of the Sydney-AAO Multi-object Integral field spectrograph (SAMI) Galaxy Survey. The SAMI Galaxy Survey is an ongoing integral field spectroscopic survey of ~3400 low-redshift (z<0.12) galaxies, covering galaxies in the field and in groups within the Galaxy And Mass Assembly (GAMA) survey regions, and a sample of galaxies in clusters. In the Early Data Release, we publicly release the fully calibrated datacubes for a representative selection of 107 galaxies drawn from the GAMA regions, along with information about these galaxies from the GAMA catalogues. All datacubes for the Early Data Release galaxies can be downloaded individually or as a set from the SAMI Galaxy Survey website. In this paper we also assess the quality of the pipeline used to reduce the SAMI data, giving metrics that quantify its performance at all stages in processing the raw data into calibrated datacubes. The pipeline gives excellent results throughout, with typical sky subtraction residuals of 0.9-1...

  3. Trismus release in oral cancer patients.

    Lee, Yao-Chou; Wong, Tung-Yiu; Shieh, Shyh-Jou; Lee, Jing-Wei


    Trismus is a common problem among oral cancer patients. This report aimed to study the inciting factors of trismus and to find out the rationale of trismus release. Between 1996 and 2008, 61 oral cancer patients with retrievable records of interincisor distance (IID) were analyzed by retrospective chart review. The IID decreased from 31.4 (12.4) to 24.9 (12.0) mm in 36 patients undergoing cancer ablation only (P = 0.001). Other variables prompting trismus include buccal cancer (P = 0.017), radiotherapy (P = 0.008), and recurrence (P = 0.001). In contrast, the IID improved from 11.7 (7.1) to 22.7 (11.9) mm in 25 patients receiving cancer ablative and trismus releasing surgeries (P = 0.000). The improvement fared better in individuals with IID less than 15 mm than the others (P = 0.037). In conclusion, involvement of buccal region, ablative surgery, radiotherapy, and recurrence are provocative factors of trismus. Patients with IID less than 15 mm will benefit from releasing surgery significantly. Others may better be handled with conservative managements firstly, and enrolled as candidates of surgical release only until the patients entertained a 28-month period of disease-free interval, by which time the risk of recurrence would be markedly reduced.

  4. Delayed-release lansoprazole plus naproxen.

    Curran, Monique P; Wellington, Keri


    A combination package containing delayed-release capsules of the proton pump inhibitor lansoprazole (15 mg once daily) and tablets of the NSAID naproxen (375 or 500 mg twice daily) has been approved for reducing the risk of NSAID-associated gastric ulcers in NSAID-requiring patients with a documented history of gastric ulcer. In a large, 12-week trial in NSAID (including naproxen)-requiring patients with a documented history of gastric ulcer, significantly more recipients of delayed-release lansoprazole 15 mg once daily than placebo recipients were free from gastric ulcer (p ulcer were 80% with lansoprazole 15 mg and 51% with placebo. In a subgroup analysis of recipients of naproxen (89% received 750-1000 mg/day), the percentage of patients free from gastric ulcer after 12 weeks of treatment was significantly higher with delayed-release lansoprazole 15 mg than with placebo (89% vs 33%; p ulcer, the incidence of treatment-related adverse events in recipients of delayed-release lansoprazole 15 mg once daily was low (7%), and similar to that in recipients of placebo (10%).

  5. Ultrahigh-performance liquid chromatography-ultraviolet absorbance detection-high-resolution-mass spectrometry combined with automated data processing for studying the kinetics of oxidative thermal degradation of thyroxine in the solid state.

    Neu, Volker; Bielow, Chris; Reinert, Knut; Huber, Christian G


    Levothyroxine as active pharmaceutical ingredient of formulations used for the treatment of hypothyroidism is distributed worldwide and taken by millions of people. An important issue in terms of compound stability is its capability to react with ambient oxygen, especially in case of long term compound storage at elevated temperature. In this study we demonstrate that ultrahigh-performance liquid chromatography coupled to UV spectrometry and high-resolution mass spectrometry (UHPLC-UV-HRMS) represent very useful approaches to investigate the influence of ambient oxygen on the degradation kinetics of levothyroxine in the solid state at enhanced degradation conditions. Moreover, the impurity pattern of oxidative degradation of levothyroxine is elucidated and classified with respect to degradation kinetics at different oxygen levels. Kinetic analysis of thyroxine bulk material at 100 °C reveals bi-phasic degradation kinetics with a distinct change in degradation phases dependent on the availability of oxygen. The results clearly show that contact of the bulk material to ambient oxygen is a key factor for fast compound degradation. Furthermore, the combination of time-resolved HRMS data and automated data processing is shown to allow insights into the kinetics and mechanism of impurity formation on individual compound basis. By comparing degradation profiles, four main classes of profiles linked to reaction pathways of thyroxine degradation were identifiable. Finally, we show the capability of automated data processing for the matching of different stressing conditions, in order to extract information about mechanistic similarities. As a result, degradation kinetics is influenced by factors like availability of oxygen, stressing time, or stressing temperature, while the degradation mechanisms appear to be conserved.

  6. Modeling controlled nutrient release from a population of polymer coated fertilizers: statistically based model for diffusion release.

    Shaviv, Avi; Raban, Smadar; Zaidel, Elina


    A statistically based model for describing the release from a population of polymer coated controlled release fertilizer (CRF) granules by the diffusion mechanism was constructed. The model is based on a mathematical-mechanistic description of the release from a single granule of a coated CRF accounting for its complex and nonlinear nature. The large variation within populations of coated CRFs poses the need for a statistically based approach to integrate over the release from the individual granules within a given population for which the distribution and range of granule radii and coating thickness are known. The model was constructed and verified using experimentally determined parameters and release curves of polymer-coated CRFs. A sensitivity analysis indicated the importance of water permeability in controlling the lag period and that of solute permeability in governing the rate of linear release and the total duration of the release. Increasing the mean values of normally distributed granule radii or coating thickness, increases the lag period and the period of linear release. The variation of radii and coating thickness, within realistic ranges, affects the release only when the standard deviation is very large or when water permeability is reduced without affecting solute permeability. The model provides an effective tool for designing and improving agronomic and environmental effectiveness of polymer-coated CRFs.

  7. Trigger release liposome systems: local and remote controlled delivery?

    Bibi, Sagida; Lattmann, E; Mohammed, Afzal R; Perrie, Yvonne


    Target-specific delivery has become an integral area of research in order to increase bioavailability and reduce the toxic effects of drugs. As a drug-delivery option, trigger-release liposomes offer sophisticated targeting and greater control-release capabilities. These are broadly divided into two categories; those that utilise the local environment of the target site where there may be an upregulation in certain enzymes or a change in pH and those liposomes that are triggered by an external physical stimulus such as heat, ultrasound or light. These release mechanisms offer a greater degree of control over when and where the drug is released; furthermore, targeting of diseased tissue is enhanced by incorporation of target-specific components such as antibodies. This review aims to show the development of such trigger release liposome systems and the current research in this field.

  8. Polymer-coated echogenic lipid nanoparticles with dual release triggers.

    Nahire, Rahul; Haldar, Manas K; Paul, Shirshendu; Mergoum, Anaas; Ambre, Avinash H; Katti, Kalpana S; Gange, Kara N; Srivastava, D K; Sarkar, Kausik; Mallik, Sanku


    Although lipid nanoparticles are promising drug delivery vehicles, passive release of encapsulated contents at the target site is often slow. Herein, we report contents release from targeted, polymer-coated, echogenic lipid nanoparticles in the cell cytoplasm by redox trigger and simultaneously enhanced by diagnostic frequency ultrasound. The lipid nanoparticles were polymerized on the external leaflet using a disulfide cross-linker. In the presence of cytosolic concentrations of glutathione, the lipid nanoparticles released 76% of encapsulated contents. Plasma concentrations of glutathione failed to release the encapsulated contents. Application of 3 MHz ultrasound for 2 min simultaneously with the reducing agent enhanced the release to 96%. Folic acid conjugated, doxorubicin-loaded nanoparticles showed enhanced uptake and higher cytotoxicity in cancer cells overexpressing the folate receptor (compared to the control). With further developments, these lipid nanoparticles have the potential to be used as multimodal nanocarriers for simultaneous targeted drug delivery and ultrasound imaging.

  9. Dry release of all-polymer structures

    Haefliger, D.; Nordstrøm, M.; Rasmussen, Peter Andreas


    We present a simple dry release technique which uses a thin fluorocarbon film for efficient removal of plastic microdevices from a mould or a handling substrate by reducing the adhesion between the two. This fluorocarbon film is deposited on the substrate in an advanced Si dry etch device utilising...... the C4F8 passivation plasma. Micromachined polymer chips made of SU-8 are removed from the handling substrate by lifting them off using mechanical tweezers. Effective release of chips of several mm(2) size within a few seconds and the lift-off of fragile, 5.5-mu m-thin cantilevers at a yield of almost...... 100% were demonstrated on wafer-scale. The fluorocarbon film showed excellent compatibility with metal etch processes and polymer baking and curing steps. It further facilitates demoulding of polydimethylsiloxane stamps suitable for soft-lithography....

  10. Targeting latent TGFβ release in muscular dystrophy.

    Ceco, Ermelinda; Bogdanovich, Sasha; Gardner, Brandon; Miller, Tamari; DeJesus, Adam; Earley, Judy U; Hadhazy, Michele; Smith, Lucas R; Barton, Elisabeth R; Molkentin, Jeffery D; McNally, Elizabeth M


    Latent transforming growth factor-β (TGFβ) binding proteins (LTBPs) bind to inactive TGFβ in the extracellular matrix. In mice, muscular dystrophy symptoms are intensified by a genetic polymorphism that changes the hinge region of LTBP, leading to increased proteolytic susceptibility and TGFβ release. We have found that the hinge region of human LTBP4 was also readily proteolysed and that proteolysis could be blocked by an antibody to the hinge region. Transgenic mice were generated to carry a bacterial artificial chromosome encoding the human LTBP4 gene. These transgenic mice displayed larger myofibers, increased damage after muscle injury, and enhanced TGFβ signaling. In the mdx mouse model of Duchenne muscular dystrophy, the human LTBP4 transgene exacerbated muscular dystrophy symptoms and resulted in weaker muscles with an increased inflammatory infiltrate and greater LTBP4 cleavage in vivo. Blocking LTBP4 cleavage may be a therapeutic strategy to reduce TGFβ release and activity and decrease inflammation and muscle damage in muscular dystrophy.

  11. Workload Control with Continuous Release

    Phan, B. S. Nguyen; Land, M. J.; Gaalman, G. J. C.


    Workload Control (WLC) is a production planning and control concept which is suitable for the needs of make-to-order job shops. Release decisions based on the workload norms form the core of the concept. This paper develops continuous time WLC release variants and investigates their due date

  12. Press Oil Final Release Survey

    Whicker, Jeffrey Jay [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Ruedig, Elizabeth [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)


    There are forty-eight 55 gallon barrels filled with hydraulic oil that are candidates for release and recycle. This oil needs to be characterized prior to release. Principles of sampling as provided in MARSAME/MARSSIM approaches were used as guidance for sampling.

  13. Sucrose release from polysaccharide gels.

    Nishinari, Katsuyoshi; Fang, Yapeng


    Sucrose release from polysaccharide gels has been studied extensively because it is expected to be useful in understanding flavour release from solid foods and to find a new processing method which produces more palatable and healthier foods. We provide an overview of the release of sucrose and other sugars from gels of agar and related polysaccharides. The addition of sucrose to agar solutions leads to the increase in transparency of the resulting gels and the decrease in syneresis, which is attributed to the decrease in mesh size in gels. The syneresis occurring in the quiescent condition and fluid release induced by compression is discussed. The relationship between the sugar release and the structural, rheological and thermal properties of gels is also discussed. Finally, the future research direction is proposed.

  14. Dry release of suspended nanostructures

    Forsén, Esko Sebastian; Davis, Zachary James; Dong, M.;


    A dry release method for fabrication of suspended nanostructures is presented. The technique has been combined with an anti-stiction treatment for fabrication of nanocantilever based nanoelectromechanical systems (NEMS). The process combines a dry release method, using a supporting layer of photo......A dry release method for fabrication of suspended nanostructures is presented. The technique has been combined with an anti-stiction treatment for fabrication of nanocantilever based nanoelectromechanical systems (NEMS). The process combines a dry release method, using a supporting layer......, the technique enables long time storage and transportation of produced devices without the risk of stiction. By combining the dry release method with a plasma deposited anti-stiction coating both fabrication induced stiction, which is mainly caused by capillary forces originating from the dehydration...

  15. Potassium softens vascular endothelium and increases nitric oxide release


    In the presence of aldosterone, plasma sodium in the high physiological range stiffens endothelial cells and reduces the release of nitric oxide. We now demonstrate effects of extracellular potassium on stiffness of individual cultured bovine aortic endothelial cells by using the tip of an atomic force microscope as a mechanical nanosensor. An acute increase of potassium in the physiological range swells and softens the endothelial cell and increases the release of nitric oxide. A high physio...

  16. Acid sphingomyelinase activity triggers microparticle release from glial cells.

    Bianco, Fabio; Perrotta, Cristiana; Novellino, Luisa; Francolini, Maura; Riganti, Loredana; Menna, Elisabetta; Saglietti, Laura; Schuchman, Edward H; Furlan, Roberto; Clementi, Emilio; Matteoli, Michela; Verderio, Claudia


    We have earlier shown that microglia, the immune cells of the CNS, release microparticles from cell plasma membrane after ATP stimulation. These vesicles contain and release IL-1beta, a crucial cytokine in CNS inflammatory events. In this study, we show that microparticles are also released by astrocytes and we get insights into the mechanism of their shedding. We show that, on activation of the ATP receptor P2X7, microparticle shedding is associated with rapid activation of acid sphingomyelinase, which moves to plasma membrane outer leaflet. ATP-induced shedding and IL-1beta release are markedly reduced by the inhibition of acid sphingomyelinase, and completely blocked in glial cultures from acid sphingomyelinase knockout mice. We also show that p38 MAPK cascade is relevant for the whole process, as specific kinase inhibitors strongly reduce acid sphingomyelinase activation, microparticle shedding and IL-1beta release. Our results represent the first demonstration that activation of acid sphingomyelinase is necessary and sufficient for microparticle release from glial cells and define key molecular effectors of microparticle formation and IL-1beta release, thus, opening new strategies for the treatment of neuroinflammatory diseases.

  17. Nitrogen release during coal combustion

    Baxter, L.L.; Mitchell, R.E.; Fletcher, T.H.; Hurt, R.H.


    Experiments in entrained flow reactors at combustion temperatures are performed to resolve the rank dependence of nitrogen release on an elemental basis for a suite of 15 U.S. coals ranging from lignite to low-volatile bituminous. Data were obtained as a function of particle conversion, with overall mass loss up to 99% on a dry, ash-free basis. Nitrogen release rates are presented relative to both carbon loss and overall mass loss. During devolatilization, fractional nitrogen release from low-rank coals is much slower than fractional mass release and noticeably slower than fractional carbon release. As coal rank increases, fractional nitrogen release rate relative to that of carbon and mass increases, with fractional nitrogen release rates exceeding fractional mass and fractional carbon release rates during devolatilization for high-rank (low-volatile bituminous) coals. At the onset of combustion, nitrogen release rates increase significantly. For all coals investigated, cumulative fractional nitrogen loss rates relative to those of mass and carbon passes through a maximum during the earliest stages of oxidation. The mechanism for generating this maximum is postulated to involve nascent thermal rupture of nitrogen-containing compounds and possible preferential oxidation of nitrogen sites. During later stages of oxidation, the cumulative fractional loss of nitrogen approaches that of carbon for all coals. Changes in the relative release rates of nitrogen compared to those of both overall mass and carbon during all stages of combustion are attributed to a combination of the chemical structure of coals, temperature histories during combustion, and char chemistry.

  18. Development of gonadotropin-releasing hormone secretion and pituitary response.

    Glanowska, Katarzyna M; Burger, Laura L; Moenter, Suzanne M


    Acquisition of a mature pattern of gonadotropin-releasing hormone (GnRH) secretion from the CNS is a hallmark of the pubertal process. Little is known about GnRH release during sexual maturation, but it is assumed to be minimal before later stages of puberty. We studied spontaneous GnRH secretion in brain slices from male mice during perinatal and postnatal development using fast-scan cyclic voltammetry (FSCV) to detect directly the oxidation of secreted GnRH. There was good correspondence between the frequency of GnRH release detected by FSCV in the median eminence of slices from adults with previous reports of in vivo luteinizing hormone (LH) pulse frequency. The frequency of GnRH release in the late embryonic stage was surprisingly high, reaching a maximum in newborns and remaining elevated in 1-week-old animals despite low LH levels. Early high-frequency GnRH release was similar in wild-type and kisspeptin knock-out mice indicating that this release is independent of kisspeptin-mediated excitation. In vivo treatment with testosterone or in vitro treatment with gonadotropin-inhibitory hormone (GnIH) reduced GnRH release frequency in slices from 1-week-old mice. RF9, a putative GnIH antagonist, restored GnRH release in slices from testosterone-treated mice, suggesting that testosterone inhibition may be GnIH-dependent. At 2-3 weeks, GnRH release is suppressed before attaining adult patterns. Reduction in early life spontaneous GnRH release frequency coincides with the onset of the ability of exogenous GnRH to induce pituitary LH secretion. These findings suggest that lack of pituitary secretory response, not lack of GnRH release, initially blocks downstream activation of the reproductive system.

  19. Modifying sorbents in controlled release formulations to prevent herbicides pollution.

    Flores Céspedes, F; Villafranca Sánchez, M; Pérez García, S; Fernández Pérez, M


    The herbicides chloridazon and metribuzin, identified as groundwater pollutants, were incorporated in alginate-based granules to obtain controlled release properties. In this research the effect of incorporation of sorbents such as bentonite, anthracite and activated carbon in alginate basic formulation were not only studied on encapsulation efficiency but also on the release rate of herbicides which was studied using water release kinetic tests. In addition, sorption studies of herbicides with bentonite, anthracite and activated carbon were made. The kinetic experiments of chloridazon and metribuzin release in water have shown that the release rate is higher in metribuzin systems than in those prepared with chloridazon, which has lower water solubility. Besides, it can be deduced that the use of sorbents reduces the release rate of the chloridazon and metribuzin in comparison to the technical product and to the alginate formulation without sorbents. The highest decrease in release rate corresponds to the formulations prepared with activated carbon as a sorbent. The water uptake, permeability, and time taken for 50% of the active ingredient to be released into water, T(50), were calculated to compare the formulations. On the basis of a parameter of an empirical equation used to fit the herbicide release data, the release of chloridazon and metribuzin from the various formulations into water is controlled by a diffusion mechanism. Sorption capacity of the sorbents for chloridazon and metribuzin, ranging from 0.53mgkg(-1) for the metribuzin sorption on bentonite to 2.03x10(5)mgkg(-1) for the sorption of chloridazon on the activated carbon, was the most important factor modulating the herbicide release.

  20. Metal release from stainless steel in biological environments: A review.

    Hedberg, Yolanda S; Odnevall Wallinder, Inger


    Due to its beneficial corrosion resistance, stainless steel is widely used in, e.g., biomedical applications, as surfaces in food contact, and for products intended to come into skin contact. Low levels of metals can be released from the stainless steel surface into solution, even for these highly corrosion resistant alloys. This needs to be considered in risk assessment and management. This review aims to compile the different metal release mechanisms that are relevant for stainless steel when used in different biological settings. These mechanisms include corrosion-induced metal release, dissolution of the surface oxide, friction-induced metal release, and their combinations. The influence of important physicochemical surface properties, different organic species and proteins in solution, and of biofilm formation on corrosion-induced metal release is discussed. Chemical and electrochemical dissolution mechanisms of the surface oxides of stainless steel are presented with a focus on protonation, complexation/ligand-induced dissolution, and reductive dissolution by applying a perspective on surface adsorption of complexing or reducing ligands and proteins. The influence of alloy composition, microstructure, route of manufacture, and surface finish on the metal release process is furthermore discussed as well as the chemical speciation of released metals. Typical metal release patterns are summarized.

  1. Controlled Release of Imidacloprid from Poly Styrene-Diacetone - Nanoformulation

    Qian, Kun; Guo, Yanzhen; He, Lin


    Imidacloprid is a neonicotinoids insecticide, which is important for the cash crops such as tomato, rape and so on. The conventional formulation does not only increase the loss of pesticide but also leads to environmental pollution. Controlled-release formulations of pesticide are highly desirable not only for attaining the most effective utilization of the pesticide, but also for reducing environmental pollution. Pesticide imidacloprid was incorporated in poly (styrene-diacetone crylamide)-based formulation to obtain controlled release properties, and the imidacloprid nanocontrolled release formulation was characterized by infrared (IR) and field emission scanning electron microscope (FESEM). Factors related to loading efficiency, swelling and release behaviors of the formulation were investigated. It showed that the loading efficiency could reach about 40% (w/w). The values for the diffusion exponent "n" were in the range of 0.31-0.58, which indicated that the release of imidacloprid was diffusion-controlled. The time taken for 50% of the active ingredient to be released into water, T50, was also calculated for the comparison of formulations in different conditions. The results showed that the formulation with higher temperature and more diacetone crylamide had lower value of T50, which means a quicker release of the active ingredient. This study highlighted some pieces of evidence that improved pesticide incorporation and slower release were linked to potential interactions between the pesticide and the polymer.

  2. 同位素稀释液相色谱串联质谱法测定血清甲状腺素%Serum total thyroxine measured by isotope dilution liquid chromatography tandem mass spectrometry

    周伟燕; 张江涛; 李铭; 张天娇; 曾洁; 赵海舰; 马嵘; 王冬环; 葛梦蕾


    目的 建立同位素稀释液相色谱串联质谱法(ID-LC/MS/MS)测定血清甲状腺素的候选参考方法.方法 实验性基础研究.重量法准确地称取血清或校准溶液,稀释器加入13C6-甲状腺素,混合,除去蛋白后经过阳离子交换固相萃取柱,收集洗脱液氮气吹干,复溶后用LC/MS/MS测定甲状腺素和内标.用7种混合血清评价方法的精密度;以其中一种血清为样本,分别向样本中加入原样本浓度50%、100%和200%的标准物质评价方法的加样回收率;分别以信噪比(S/N) >3和(S/N)>10作为标准,评价方法的检测限和定量限.分析德国临床化学会参考物质CRM 21201和CRM21202,评价方法的正确度.结果 血清甲状腺素测定的批内CV和总CV分别为0.64% (0.35% ~0.89%)和0.83%(0.57% ~1.37%).加样回收率为99.6% ~ 100.7%.检测限和定量限分别为0.12和0.41nmoL/L.分析CRM 21201和CRM 21202,测定结果与认定值的平均偏差为-0.30%(范围-0.13%~0.73%).结论 建立了ID-LC/MS/MS测定血清甲状腺素的方法,方法取样量少,测定结果正确、精密,可望作为血清甲状腺素测定的参考方法.%Objective An isotope dilution liquid chromatography tandem mass spectrometric (ID-LC/MS/MS) method was developed for serum total thyroxine.Methods Serum samples were sampled by weight and the 13C6-thyroxine internal standards were added volumetrically using automated dilutors,followed by equilibration,protein precipitation,and cation exchang solid-phase extractions (SPE).After SPE,the eluates were evaporated to dryness under nitrogen and then the evaporated residues were reconstituted to prepare samples for liquid chromatography-mass spectrometry electrospray ionization (LC/MS-ESI) analysis.Seven kinds of serum pools were used to analyze the precision of the method.The analytical recovery,the limit of detection(signal to noise ratio,S/N ratio 3∶1) and the limit of quantification (S/N ratio 10∶1

  3. Protein release from electrospun nonwovens: improving the release characteristics through rational combination of polyester blend matrices with polidocanol.

    Puhl, Sebastian; Ilko, David; Li, Linhao; Holzgrabe, Ulrike; Meinel, Lorenz; Germershaus, Oliver


    Nonwoven scaffolds consisting of poly-ε-caprolactone (PCL), poly(lactic-co-glycolic acid) (PLGA) and polidocanol (PD), and loaded with lysozyme crystals were prepared by electrospinning. The composition of the matrix was varied and the effect of PD content in binary mixtures, and of PD and PLGA content in ternary mixtures regarding processability, fiber morphology, water sorption, swelling and drug release was investigated. Binary PCL/PD blend nonwovens showed a PD-dependent increase in swelling of up to 30% and of lysozyme burst release of up to 45% associated with changes of the fiber morphology. Furthermore, addition of free PD to the release medium resulted in a significant increase of lysozyme burst release from pure PCL nonwovens from approximately 2-35%. Using ternary PCL/PD/PLGA blends, matrix degradation could be significantly improved over PCL/PD blends, resulting in a biphasic release of lysozyme with constant release over 9 weeks, followed by constant release with a reduced rate over additional 4 weeks. Based on these results, protein release from PCL scaffolds is improved by blending with PD due to improved lysozyme desorption from the polymer surface and PD-dependent matrix swelling. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. Timing crisis information release via television.

    Wei, Jiuchang; Zhao, Dingtao; Yang, Feng; Du, Shaofu; Marinova, Dora


    When and how often to release information on television are important issues in crisis and emergency risk communication. There is a lot of crisis information, including warnings and news, to which people should have access, but most of it is not significantly urgent to interrupt the broadcasting of television programmes. Hence, the right timing for the release of crisis information should be selected based on the importance of the crisis and any associated communication requirements. Using recursive methods, this paper builds an audience coverage model of crisis information release. Based on 2007 Household Using TV (HUT) data for Hefei City, China, the optimal combination of broadcasting sequence (with frequencies between one and eight times) is obtained using the implicit enumeration method. The developed model is applicable to effective transmission of crisis information, with the aim of reducing interference with the normal television transmission process and decreasing the psychological effect on audiences. The same model can be employed for other purposes, such as news coverage and weather and road information.

  5. Chlorhexidine-releasing methacrylate dental composite materials.

    Leung, Danny; Spratt, David A; Pratten, Jonathan; Gulabivala, Kishor; Mordan, Nicola J; Young, Anne M


    Light curable antibacterial, dental composite restoration materials, consisting of 80 wt% of a strontium fluoroaluminosilicate glass dispersed in methacrylate monomers have been produced. The monomers contained 40-100 wt% of a 10 wt% chlorhexidine diacetate (CHXA) in hydroxyethylmethacrylate (HEMA) solution and 60-0 wt% of a 50/50 mix of urethane dimethacrylate (UDMA) and triethyleneglycol dimethacrylate (TEGDMA). On raising HEMA content, light cure polymerisation rates decreased. Conversely, water sorption induced swelling and rates of diffusion controlled CHXA release from the set materials increased. Experimental composites with 50 and 90 wt% of the CHXA in HEMA solution in the monomer were shown, within a constant depth film fermentor (CDFF), to have slower rates of biofilm growth on their surfaces between 1 and 7 days than the commercial dental composite Z250 or fluoride-releasing dental cements, Fuji II LC and Fuji IX. When an excavated bovine dentine cylinder re-filled with Z250 was placed for 10 weeks in the CDFF, both bacteria and polymers from the artificial saliva penetrated between the material and dentine. With the 50 wt% experimental HEMA/CHXA formulation, this bacterial microleakage was substantially reduced. Polymer leakage, however, still occurred. Both polymer and bacterial microleakage were prevented with a 90 wt% HEMA/CHXA restoration in the bovine dentine due to swelling compensation for polymerisation shrinkage in combination with antibacterial release.

  6. Birth control - slow release methods

    ... page: // Birth control - slow release methods To use the sharing features on this page, please enable JavaScript. Certain birth control methods contain man-made forms of hormones. These ...

  7. Turbulent lock release gravity current


    The time evolution of a turbulent lock release gravity current, formed by a finite volume ofhomogeneous fluid released instantaneously into another fluid of slightly lower density, was studied byexperimental measurements of the density structure via elaborate digital image processing and by a nu-merical simulation of the flow and mixing using a two-equation turbulence model. The essential fact thatthe gravity current passes through an initial slumping phase in which the current head advances steadilyand a second self-similar phase in which the front velocity decreases like the negative third power of thetime after release is satisfactorily presented by the laboratory observation. An overall entrainment ratioproportional to the distance from the release point is found by the numerical simulation. The renormal-ization group (RNG) k- ε model for Reynolds-stress closure is validated to characterize the gravitycurrent with transitional and localized turbulence.


    Parth Trivedi


    Full Text Available Background & Purpose: Lateral epicondylitis is the most common lesion of the elbow. Tennis elbow or lateral epicondylitis is defined as a syndrome of pain in the wrist extensor muscles at or near their lateral epicondyle origin or pain directly over the lateral epicondyle. So, the aim of this study was to compare the effectiveness of Active Release Technique (ART and Myofascial Release Technique (MFR in the treatment of Chronic Lateral Epicondylitis (CLE. Methodology: The study included thirty-six patients with Chronic Lateral Epicondylitis of age group range between 30 to 45 years. Patients were randomly divided into three groups: Control Group (A, Active Release Technique Group (B and Myofascial Release Technique Group (C. The patients were treated for 4 weeks and three outcome measures: 0-10 NPRS, Hand Dynamometer and PRTEE were taken for assessment and analysis at baseline and after 4th weeks was done. Result: In this study the result showed that Active Release Technique and Myofascial Release Technique were effective in all three outcome measures when compared to Control Group. Myofascial Release Technique was more effective in improving grip strength & reducing pain & disability when compared to Active Release Technique.(p<0.05 Conclusion: Active Release Technique and Myofascial Release Technique are effective in patients with Chronic Lateral Epicondylitis. Myofascial Release Technique demonstrated better outcomes than Active Release Technique in the management of Chronic Lateral Epicondylitis.

  9. Interleukin 1. alpha. inhibits prostaglandin E sub 2 release to suppress pulsatile release of luteinizing hormone but not follicle-stimulating hormone

    Rettori, V.; McCann, S.M. (Univ. of Texas Southwestern Medical Center, Dallas (United States)); Gimeno, M.F. (CEFYBO, Buenos Aires (Argentina)); Karara, A. (Vanderbilt Univ., Nashville, TN (United States)); Gonzalez, M.C. (Univ. de La Laguno, Tenerife (Spain))


    Interleukin 1{alpha} (IL-1{alpha}), a powerful endogenous pyrogen released from monocytes and macrophages by bacterial endotoxin, stimulates corticotropin, prolactin, and somatotropin release and inhibits thyrotropin release by hypothalamic action. The authors injected recombinant human IL-1{alpha} into the third cerebral ventricle, to study its effect on the pulsatile release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in conscious, freely moving, ovariectomized rats. Intraventricular injection of 0.25 pmol of IL-1{alpha} caused an almost immediate reduction of plasma LH concentration. To determine the mechanism of the suppression of LH release, mediobasal hypothalamic fragments were incubated in vitro with IL-1{alpha} (10 pM) and the release of LH-releasing hormone (LHRH) and prostaglandin E{sub 2} into the medium was measured by RIA in the presence or absence of nonrepinephrine. 1{alpha} reduced basal LHRH release and blocked LHRH release induced by nonrepinephrine. In conclusion, IL-1{alpha} suppresses LH but not FSH release by an almost complete cessation of pulsatile release of LH in the castrated rat. The mechanism of this effect appears to be by inhibition of prostaglandin E{sub 2}-mediated release of LHRH.

  10. Antimicrobial beeswax coated polylactide films with silver control release capacity.

    Martínez-Abad, Antonio; Lagarón, Jose Maria; Ocio, María Jose


    Although the application of silver based antimicrobial systems is a widespread technology, its implementation in areas such as food packaging is still challenging. The present paper describes the fabrication of poly(lactic acid) (PLA) coated with beeswax with controlled release properties for sustained antimicrobial performance. Release of silver ions from the polymers was monitored voltammetrically under various conditions (surface contact, immersion in various liquid media and at different pH values) throughout at least 7days. A higher release was noted with decreasing pH while surface release was much slower than the release when immersed in liquid medium. While uncoated films demonstrated a high burst release which in some instances implied surpassing some current migration restrictions (beeswax layer allowed a sustained release of the antimicrobial compound. Increasing the thickness of the beeswax layer resulted in an increase in the water barrier properties of the films while reducing the relatively constant values of sustained release. Antimicrobial performance was correlated with the release of silver ions, indicating threshold concentrations for biocide action of <6μg/L and 9-14μg/L for surface contact and in liquid media, respectively. Either by surface contact or by immersion in growth medium or vegetable soup, the coated films displayed a strong bactericidal effect against Salmonella enterica. The application of this functional barrier thus offers the possibility of tuning the release profiles of the films to suit a specific application and puts forth the possible suitability of these materials for food packaging or other migration sensitive applications.

  11. Event reconstruction for line source releases

    Zajic, Dragan [Los Alamos National Laboratory; Brown, Michael J [Los Alamos National Laboratory; Williams, Michael D [Los Alamos National Laboratory


    The goal of source inversion, also called event reconstruction, is the calculation of source parameters from information obtained by network of concentration (or dosage) and meteorological sensors. Source parameters include source location and strength, but in certain cases there could be more than one source so the inversion procedure could deal with determination of number of sources, as well. In a case of limited time period pollutant emission events, as for example during accidents or intentional releases, it is of great use to estimate starting and ending times of the event. This kind of research is very useful for estimating the source parameters of industrial pollutants since it provides important information for regulation purposes. Also it provides information to fast responders in a case of accidental pollutant releases or for homeland security needs when chemical, biological or radiological agent is deliberately released. Development of faster and more accurate algorithms is very important since it could help reduce the populace's exposure to dangerous airborne contaminants, plan evacuation routes, and help assess the magnitude of clean up. During the last decade, the large number of research papers in area of source inversion was published where many different approaches were used. Most of the source inversion work publish to date apply to point source releases. The forward dispersion models used range from fast Gaussian plume and puff codes that enable almost instantaneous calculations of concentrations and dosages to Computational Fluid Dynamics (CFD) codes that provide more detailed and precise calculation but at the same time are expensive with respect to time and computer resources. The optimization methods were often used and examples are simulated annealing and genetic algorithms.

  12. External Dentin Stimulation Induces ATP Release in Human Teeth.

    Liu, X; Wang, C; Fujita, T; Malmstrom, H S; Nedergaard, M; Ren, Y F; Dirksen, R T


    ATP is involved in neurosensory processing, including nociceptive transduction. Thus, ATP signaling may participate in dentin hypersensitivity and dental pain. In this study, we investigated whether pannexins, which can form mechanosensitive ATP-permeable channels, are present in human dental pulp. We also assessed the existence and functional activity of ecto-ATPase for extracellular ATP degradation. We further tested if ATP is released from dental pulp upon dentin mechanical or thermal stimulation that induces dentin hypersensitivity and dental pain and if pannexin or pannexin/gap junction channel blockers reduce stimulation-dependent ATP release. Using immunofluorescence staining, we demonstrated immunoreactivity of pannexin 1 and 2 in odontoblasts and their processes extending into the dentin tubules. Using enzymatic histochemistry staining, we also demonstrated functional ecto-ATPase activity within the odontoblast layer, subodontoblast layer, dental pulp nerve bundles, and blood vessels. Using an ATP bioluminescence assay, we found that mechanical or cold stimulation to the exposed dentin induced ATP release in an in vitro human tooth perfusion model. We further demonstrated that blocking pannexin/gap junction channels with probenecid or carbenoxolone significantly reduced external dentin stimulation-induced ATP release. Our results provide evidence for the existence of functional machinery required for ATP release and degradation in human dental pulp and that pannexin channels are involved in external dentin stimulation-induced ATP release. These findings support a plausible role for ATP signaling in dentin hypersensitivity and dental pain.


    Sujit Bose


    Full Text Available Sustained release matrix tablets facilitate prolonged and continuous drug release and improve the bioavailability of drugs while avoiding unwanted side effects. Ofloxacin is a broad spectrum antibacterial agent used for treating wide range of gram positive and gram negative infections. The goal in designing sustained or controlled delivery systems is to reduce frequency of dosing or to increase the effectiveness of the drug by localization at the site of action, reducing the dose required, providing uniform drug delivery. Sustained release drug administration means not only prolongation of duration of drug delivery, but the term also implies the predictability and reproducibility of drug release kinetics. The controlled release of drug substances and their effective transport to sites of action can be exploited to maximize the beneficial clinical response and to minimize the incidence of unbeneficial adverse reactions and side effects. Oral ingestion has long been the most convenient and commonly employed route of drug delivery. Indeed, for sustained release systems, oral route of administration has received most of the attention with respect to research on physiological and drug constraints as well as design and testing of products.

  14. High resolution monitoring system for IRE stack releases.

    Deconninck, B; De Lellis, C


    The main activity of IRE (Institute for Radio-Element) is radioisotope production of bulk (99)Mo and (131)I for medical application (diagnosis and therapy). Those isotopes are chemically extracted from HEU (High Enriched Uranium) targets activated in reactors. During this process, fission products are released from the targets, including noble gases isotopes (Xe and Kr). Like any nuclear plant, IRE has release limits which are given by the Belgium authority and moreover IRE is in the process of continuously reducing the level of its releases. To achieve this mission, the need of an accurate tool is necessary and IRE has developed a specific monitoring system using a high resolution detector in order to identify and accurately estimate its gaseous releases. This system has a continuous air sampling system in the plant main stack. The sampled gases cross charcoal cartridges where they are slowed down and concentrated for higher detection efficiency. In front of those cartridges is installed an HPGe detector with a detection chain connected to a specific analysis system allowing on-line spectrum analysis. Each isotope can be separately followed without interferences, especially during the production process where high activity can be released. Due to its conception, the system also allows to measure iodine isotopes by integration on the charcoal cartridges. This device is of great help for accurately estimate IRE releases and to help for understanding specific releases and their origin in the production or maintenance process.

  15. Arsenic release during managed aquifer recharge (MAR)

    Pichler, T.; Lazareva, O.; Druschel, G.


    The mobilization and addition of geogenic trace metals to groundwater is typically caused by anthropogenic perturbations of the physicochemical conditions in the aquifer. This can add dangerously high levels of toxins to groundwater, thus compromising its use as a source of drinking water. In several regions world-wide, aquifer storage and recovery (ASR), a form of managed aquifer recharge (MAR), faces the problem of arsenic release due to the injection of oxygenated storage water. To better understand this process we coupled geochemical reactive transport modeling to bench-scale leaching experiments to investigate and verify the mobilization of geogenic arsenic (As) under a range of redox conditions from an arsenic-rich pyrite bearing limestone aquifer in Central Florida. Modeling and experimental observations showed similar results and confirmed the following: (1) native groundwater and aquifer matrix, including pyrite, were in chemical equilibrium, thus preventing the release of As due to pyrite dissolution under ambient conditions; (2) mixing of oxygen-rich surface water with oxygen-depleted native groundwater changed the redox conditions and promoted the dissolution of pyrite, and (3) the behavior of As along a flow path was controlled by a complex series of interconnected reactions. This included the oxidative dissolution of pyrite and simultaneous sorption of As onto neo-formed hydrous ferric oxides (HFO), followed by the reductive dissolution of HFO and secondary release of adsorbed As under reducing conditions. Arsenic contamination of drinking water in these systems is thus controlled by the re-equilibration of the system to more reducing conditions rather than a purely oxidative process.

  16. Lactoferrin Suppresses Neutrophil Extracellular Traps Release in Inflammation.

    Okubo, Koshu; Kamiya, Mako; Urano, Yasuteru; Nishi, Hiroshi; Herter, Jan M; Mayadas, Tanya; Hirohama, Daigoro; Suzuki, Kazuo; Kawakami, Hiroshi; Tanaka, Mototsugu; Kurosawa, Miho; Kagaya, Shinji; Hishikawa, Keiichi; Nangaku, Masaomi; Fujita, Toshiro; Hayashi, Matsuhiko; Hirahashi, Junichi


    Neutrophils are central players in the innate immune system. They generate neutrophil extracellular traps (NETs), which protect against invading pathogens but are also associated with the development of autoimmune and/or inflammatory diseases and thrombosis. Here, we report that lactoferrin, one of the components of NETs, translocated from the cytoplasm to the plasma membrane and markedly suppressed NETs release. Furthermore, exogenous lactoferrin shrunk the chromatin fibers found in released NETs, without affecting the generation of oxygen radicals, but this failed after chemical removal of the positive charge of lactoferrin, suggesting that charge-charge interactions between lactoferrin and NETs were required for this function. In a model of immune complex-induced NET formation in vivo, intravenous lactoferrin injection markedly reduced the extent of NET formation. These observations suggest that lactoferrin serves as an intrinsic inhibitor of NETs release into the circulation. Thus, lactoferrin may represent a therapeutic lead for controlling NETs release in autoimmune and/or inflammatory diseases.

  17. Controlled release of chlorhexidine from UDMA-TEGDMA resin.

    Anusavice, K J; Zhang, N-Z; Shen, C


    Chlorhexidine salts are available in various formulations for dental applications. This study tested the hypothesis that the release of chlorhexidine from a urethane dimethacrylate and triethylene glycol dimethacrylate resin system can be effectively controlled by the chlorhexidine diacetate content and pH. The filler concentrations were 9.1, 23.1, or 33.3 wt%, and the filled resins were exposed to pH 4 and pH 6 acetate buffers. The results showed that Fickian diffusion was the dominant release mechanism. The rates of release were significantly higher in pH 4 buffer, which was attributed to the increase of chlorhexidine diacetate solubility at lower pH. The higher level of filler loading reduced the degree of polymerization, leading to a greater loss of organic components and higher chlorhexidine release rates.


    Liandong Hu*, Hailei Zhang, and Weihua Song


    Full Text Available In recent years, there has been a great deal of interests in developing sustained-release systems which can prolong the therapeutic effect, decrease adverse side effects, and reduce administration frequency. Nowadays, the oral sustained-release preparations account for a larger market share comparing to other sustained-release forms, mainly because of its noninvasive pain-free administration. However, the hostile environment of gastrointestinal tract and first-pass effect may lead to low bioavailability of some drugs, such as some proteins, peptides, and hormones. In this paper, the latest research progresses of some new-model sustained-release injectable dosage forms were introduced, including microsphere, microcapsule, liposome, polymeric micelle, and in situ forming system.

  19. Drug release from porous silicon for stable neural interface

    Sun, Tao, E-mail: [Institute of Microelectronics, Agency for Science, Technology and Research (A-STAR) (Singapore); Tsang, Wei Mong [Institute of Microelectronics, Agency for Science, Technology and Research (A-STAR) (Singapore); Park, Woo-Tae [Institute of Microelectronics, Agency for Science, Technology and Research (A-STAR) (Singapore); Department of Mechanical and Automotive Engineering, Seoul National University of Science and Technology, Seoul (Korea, Republic of)


    70 μm-thick porous Si (PSi) layer with the pore size of 11.1 ± 7.6 nm was formed on an 8-in. Si wafer via an anodization process for the microfabrication of a microelectrode to record neural signals. To reduce host tissue responses to the microelectrode and achieve a stable neural interface, water-soluble dexamethesone (Dex) was loaded into the PSi via incubation with the drug solution overnight. After the drug loading process, the pore size of PSi reduced to 4.7 ± 2.6 nm on the basis of scanning electron microscopic (SEM) images, while its wettability was remarkably enhanced. Fluorescence images demonstrated that Dex was loaded into the porous structure of the PSi. Degradation rate of the PSi was investigated by incubation in distilled water for 21 days. Moreover, the drug release profile of the Dex-loaded PSi was a combination of an initial burst release and subsequent sustained release. To evaluate cellular responses to the drug release from the PSi, primary astrocytes were seeded on the surface of samples. After 2 days of culture, the Dex-loaded PSi could not only moderately prevent astrocyte adhesion in comparison with Si, but also more effectively suppress the activation of primary astrocytes than unloaded PSi due to the drug release. Therefore, it might be an effective method to reduce host tissue responses and stabilize the quality of the recorded neural signal by means of loading drugs into the PSi component of the microelectrode.

  20. Aluminum corrosion product release kinetics

    Edwards, Matt, E-mail:; Semmler, Jaleh; Guzonas, Dave; Chen, Hui Qun; Toor, Arshad; Hoendermis, Seanna


    Highlights: • Release of Al corrosion product was measured in simulated post-LOCA sump solutions. • Increased boron was found to enhance Al release kinetics at similar pH. • Models of Al release as functions of time, temperature, and pH were developed. - Abstract: The kinetics of aluminum corrosion product release was examined in solutions representative of post-LOCA sump water for both pressurized water and pressurized heavy-water reactors. Coupons of AA 6061 T6 were exposed to solutions in the pH 7–11 range at 40, 60, 90 and 130 °C. Solution samples were analyzed by inductively coupled plasma atomic emission spectroscopy, and coupon samples were analyzed by secondary ion mass spectrometry. The results show a distinct “boron effect” on the release kinetics, expected to be caused by an increase in the solubility of the aluminum corrosion products. New models were developed to describe both sets of data as functions of temperature, time, and pH (where applicable)

  1. Investigation of serum thyroxine in obstructive sleep apnea-hypopnea syndrome patients%阻塞性睡眠呼吸暂停低通气综合征患者血清甲状腺素的研究

    何志红; 郭丽萍; 吴雅丽; 段争; 高英; 彭少舫; 吴颂时; 张敏


    Objective To investigate the changes of serum thyroxine level in obstructive sleep apnea-hy-popnea syndrome(OSAHS) patients and to assess the role of serum thyroxine in the development of OSAHS. Meth-ods Polysomnography was used to examine the patients with OSAHS and fasting plasma serum thyroxine level were higher in obese OSAHS patients than in obese controls[ (43.56±3.48)cm vs (38.33±3.08)cm,t =4. 258,P < 0.05 ], in non-obese OSAHS patients than in non-obese control group [ (40.50±1.05 )cm vs (36.17±3.13 )cm, t = 3. 146 ,P < 0.05 ] . The levels of FT3 was (6.35±3.15 ) pmol/L in obese OSAHS patients and ( 4.08±2.37 ) pmol/L in control subjects ( t = 2.203 ,P < 0.05 ). That was ( 3.42±0.57 ) pmol/L in non-obese OSAHS patients related with AHI and microarousal index (r = 0. 500, P < 0.05;r = 0.561, P < 0.05 ), and FT4 was also positively with neck circumference( t = 0.489, P < 0.05 ), TSH level was negatively correlated with neck circumference ( t = - 0.500, P < 0.05 ) and was positively correlated with the percentage of body fat ( r = 0.498, P < 0.05 ). Conclu-sions The FT3 levels are significantly higher in the OSAHS patients than that in control subjects, though all FT3 lev-els are normal, suggesting that there are possibility to have abnormal metabolism. At the same time, FT3 level is posi-tively correlated with neck circumference ,suggesting that the OSAHS patients' higher neck circumference is correla-ted with thyroxine.%目的 探讨阻塞性睡眠呼吸暂停低通气综合征(OSAHS)患者血清甲状腺素水平以及在OSAHS病情进展中的作用.方法 选择OSAHS患者和健康者(对照组)各40例,均为男性,分别行多导睡眠图检查,并测定空腹甲状腺素水平.结果 ①OSAHS肥胖组的颈围为(43.56±3.48)cm,对照肥胖组为(38.33±3.08)cm,2组比较差异有统计学意义(t=4.258,P<0.05);OSAHS非肥胖组的颈围为(40.50±1.05)cm,对照非肥胖组为(36.17±3.13)cm,2组比较差异有统计学意义(t=3.146,P<0

  2. Deep Sludge Gas Release Event Analytical Evaluation

    Sams, Terry L.


    Long Abstract. Full Text. The purpose of the Deep Sludge Gas Release Event Analytical Evaluation (DSGRE-AE) is to evaluate the postulated hypothesis that a hydrogen GRE may occur in Hanford tanks containing waste sludges at levels greater than previously experienced. There is a need to understand gas retention and release hazards in sludge beds which are 200 -300 inches deep. These sludge beds are deeper than historical Hanford sludge waste beds, and are created when waste is retrieved from older single-shell tanks (SST) and transferred to newer double-shell tanks (DST).Retrieval of waste from SSTs reduces the risk to the environment from leakage or potential leakage of waste into the ground from these tanks. However, the possibility of an energetic event (flammable gas accident) in the retrieval receiver DST is worse than slow leakage. Lines of inquiry, therefore, are (1) can sludge waste be stored safely in deep beds; (2) can gas release events (GRE) be prevented by periodically degassing the sludge (e.g., mixer pump); or (3) does the retrieval strategy need to be altered to limit sludge bed height by retrieving into additional DSTs? The scope of this effort is to provide expert advice on whether or not to move forward with the generation of deep beds of sludge through retrieval of C-Farm tanks. Evaluation of possible mitigation methods (e.g., using mixer pumps to release gas, retrieving into an additional DST) are being evaluated by a second team and are not discussed in this report. While available data and engineering judgment indicate that increased gas retention (retained gas fraction) in DST sludge at depths resulting from the completion of SST 241-C Tank Farm retrievals is not expected and, even if gas releases were to occur, they would be small and local, a positive USQ was declared (Occurrence Report EM-RP--WRPS-TANKFARM-2012-0014, "Potential Exists for a Large Spontaneous Gas Release Event in Deep Settled Waste Sludge"). The purpose of this technical

  3. 减量控释氮肥对大棚甜椒产量及土壤硝态氮、铵态氮分布的影响%Effect of Reduced Controlled Release Nitrogen Fertilizer on the Sweet Pepper Yield and Distribution of Soil Nitrate,Ammonium Nitrogen

    彭强; 李絮花; 王克安; 吕晓慧; 杨宁; 刘旭凤


    采用田间试验方法研究不同控释氮肥施用量对大棚甜椒生长及硝态氮、铵态氮含量分布的影响。结果表明,控释氮肥处理对大棚甜椒的产量、肥料利用率、氮肥农学效率、氮肥偏生产力较常规施肥有不同程度的提高,以RF30处理最佳。各施肥处理均显著增加了土壤全氮、甜椒Vc、可溶性糖、硝酸盐的含量,降低了可滴定酸的含量。施肥处理显著增加了0-60cm土层硝态氮含量,满足了甜椒在不同时期对氮素的需求。控释氮肥处理0-60cm土层铵态氮含量差异不大,常规施肥铵态氮含量明显下降。综合考虑在农民习惯性施肥基础上施用70%控释氮肥可以保证较高的产量和较好的果实品质。%Field experiment was carried out on the growth of greenhouse sweet pepper and distribution of ammonium,nitrate nitrogen content in different controlled-release nitrogen fertilizer.The results showed that in controlled-release nitrogen fertilizer treatment,the greenhouse sweet pepper yield,fertilizer utilization efficiency,nitrogen agronomic efficiency and nitrogen partial productivity were higher than the conventional fertilization increased to different extent,and the best treatment was RF30.The fertilizer treatment significantly increased the total nitrogen,pepper Vc,soluble sugar,and nitrate content,decreased titratable acid content.The fertilization treatments significantly increased the content of nitrate nitrogen in soil layer 0-60 cm,meeting the nitrogen demand in the different stages of the sweet pepper.With controlled release nitrogen fertilizer treatments,ammonium nitrogen content in soil layer 0-60 cm were not significant,but with conventional fertilizer treatments,ammonium nitrogen concentration decreased significantly.Considering farmer habitual fertilization,70% controlled-release nitrogen fertilizer can ensure higher yield and better quality of sweet pepper.

  4. Controlled release from recombinant polymers.

    Price, Robert; Poursaid, Azadeh; Ghandehari, Hamidreza


    Recombinant polymers provide a high degree of molecular definition for correlating structure with function in controlled release. The wide array of amino acids available as building blocks for these materials lend many advantages including biorecognition, biodegradability, potential biocompatibility, and control over mechanical properties among other attributes. Genetic engineering and DNA manipulation techniques enable the optimization of structure for precise control over spatial and temporal release. Unlike the majority of chemical synthetic strategies used, recombinant DNA technology has allowed for the production of monodisperse polymers with specifically defined sequences. Several classes of recombinant polymers have been used for controlled drug delivery. These include, but are not limited to, elastin-like, silk-like, and silk-elastinlike proteins, as well as emerging cationic polymers for gene delivery. In this article, progress and prospects of recombinant polymers used in controlled release will be reviewed.

  5. Nuclear energy release from fragmentation

    Li, Cheng; Tsang, M B; Zhang, Feng-Shou


    Nuclear energy released by splitting Uranium and Thorium isotopes into two, three, four, up to eight fragments with nearly equal size are studied. We found that the energy released come from equally splitting the $^{235,238}$U and $^{230,232}$Th nuclei into to three fragments is largest. The statistical multifragmentation model is employed to calculate the probability of different breakup channels for the excited nuclei. Weighing the the probability distributions of fragments multiplicity at different excitation energies for the $^{238}$U nucleus, we found that an excitation energy between 1.2 and 2 MeV/u is optimal for the $^{235}$U, $^{238}$U, $^{230}$Th and $^{232}$Th nuclei to release nuclear energy of about 0.7-0.75 MeV/u.

  6. Training Materials for Release 3

    Wake, Jo Dugstad; Hansen, Cecilie; Debus, Kolja;

    This document, D7.4 – training materials for release 3, provides an overview of the training material for version 3 of the NEXT-TELL tools and methods. Previous documents submitted as part of work package 7, which is about teacher training, are D7.1 – Training Concept, D7.2 – Training Materials...... for Release 1 and D7.3 – Training Materials for Release 2. D7.4 builds on D7.1 and D7.2 and D7.3. D7.4 contains further development of previous work within WP7, essentially a revised theoretical approach to the teacher training, and expansion of the notion of tool training. The media in use have been expanded...

  7. Reducing the Risk of Methadone Overdose


    This podcast is based on the July 2012 CDC Vital Signs report. Approximately 14 people die every day of overdoses related to methadone. Listen to learn how to reduce your risk of an overdose.  Created: 7/3/2012 by Centers for Disease Control and Prevention (CDC).   Date Released: 7/3/2012.

  8. A Remote Controlled Valve in Liposomes for Triggered Liposomal Release

    Koçer, Armağan


    In order to reduce the toxicity and increase the efficacy of drugs, there is a need for smart drug delivery systems. Liposomes are one of the promising tools for this purpose. An ideal liposomal delivery system should be stable, long-circulating, accumulate at the target site and release its drug in

  9. Precision Departure Release Capability (PDRC) Concept of Operations

    Engelland, Shawn; Capps, Richard A.; Day, Kevin Brian


    Center scheduling tool. The PDRC concept also incorporates earlier NASA and FAA research into automation-assisted CFR coordination. The PDRC concept helps reduce uncertainty by automatically communicating coordinated release times with seconds-level precision enabling TMCs to work with target times rather than windows. NASA has developed a PDRC prototype system that integrates the Center's TMA system with a research prototype Tower decision support tool. A two-phase field evaluation was conducted at NASA's North Texas Research Station (NTX) in DallasFort Worth. The field evaluation validated the PDRC concept and demonstrated reduced release time uncertainty while being used for tactical departure scheduling of more than 230 operational flights over 29 weeks of operations. This paper presents the Concept of Operations. Companion papers include the Final Report and a Technology Description. ? SUBJECT:

  10. Precision Departure Release Capability (PDRC): NASA to FAA Research Transition

    Engelland, Shawn; Davis, Thomas J.


    departure runway assignments to the Center scheduling tool. The PDRC concept also incorporates earlier NASA and FAA research into automation-assisted CFR coordination. The PDRC concept reduces uncertainty by automatically communicating coordinated release times with seconds-level precision enabling TMCs and FLMs to work with target times rather than windows. NASA has developed a PDRC prototype system that integrates the Center's TMA system with a research prototype Tower decision support tool. A two-phase field evaluation was conducted at NASA's North Texas Research Station in Dallas-Fort Worth. The field evaluation validated the PDRC concept and demonstrated reduced release time uncertainty while being used for tactical departure scheduling of more than 230 operational flights over 29 weeks of operations.


    Md. M. Rahman*, A. B. Ripon Khalipha , Md. A. K. Azad , MD. Z. Faruki , A. K. Chaurasiya and H. Hossain


    Full Text Available ABSTRACT: With the blend of Methocel K15, a synthetic polymer and xanthan gum, a natural polymer (3:1 was used in the formulation of matrix tablets to find out the effect of natural polymer in the sustained release dosage form. Direct compression process was applied for the preparation of Ketotifen fumarate tablets. The dissolution profiles were carried out by USP apparatus 2 (paddle at 50 rpm in 500 ml 0.1 N HCl and distilled water. For interpreting the results a one way analysis of variance (ANOVA was exploited. Statistically significant differences were found among the drug release profile from different matrices. At a higher polymeric content (60% of the total tablet weight, drug release from the combination of Methocel K15M and xanthan gum (3:1 was slower. On the contrary, at a lower polymeric level (30% of the total tablet weight; the rate of drug release was prominent. The best-fit release kinetics was accomplished with the Higuchi model followed by the zero-order plot, Korsmeyer and Hixson Crowell equations. One formulation showed drug release is more controlled. The data obtained proved that the formulations are useful for a sustained release of ketotifen fumarate. From these formulations corresponded more controlled of the drug release by the higher polymeric level of methocel K15M & xanthan gum and vice versa. The extended release of the model drug found from the higher proportion of methocel K15M and xanthan gum. As a result, the frequency of administration of such type of drug reduced.

  12. Growth hormone secretion from chicken adenohypophyseal cells in primary culture: effects of human pancreatic growth hormone-releasing factor, thyrotropin-releasing hormone, and somatostatin on growth hormone release.

    Perez, F M; Malamed, S; Scanes, C G


    A primary culture of chicken adenohypophyseal cells has been developed to study the regulation of growth hormone (GH) secretion. Following collagenase dispersion, cells were exposed for 2 hr to vehicle (control) or test agents. Human pancreatic (tumor) growth hormone-releasing factor (hpGRF) and rat hypothalamic growth hormone-releasing factor stimulated GH release to similar levels. GH release was increased by the presence of dibutyryl cyclic AMP. Thyrotropin-releasing hormone (TRH) alone did not influence GH release; however, TRH plus hpGRF together exerted a synergistic (greater than additive) effect, increasing GH release by 100 to 300% over the sum of the values for each secretagogue acting alone. These relationships between TRH and hpGRF were further examined in cultured cells exposed to secretagogues for two consecutive 2-hr incubations. TRH pretreatment enhanced subsequent hpGRF-stimulated GH release by about 80% over that obtained if no secretagogue was present during the first incubation. In other experiments, somatostatin (SRIF) alone did not alter GH secretion. However, SRIF reduced hpGRF-stimulated GH release to levels found in controls. Furthermore, GH release stimulated by the presence of both TRH and hpGRF was lowered to control values by SRIF. The results of these studies demonstrate that a primary culture of chicken adenohypophyseal cells is a useful model for the study of GH secretion. Indeed, these results suggest that TRH and hpGRF regulate GH secretion by mechanisms which are not identical.

  13. Reduced waste generation, FY 1986


    The United States Department of Energy is committed to the principles of minimizing the quantity and transuranic content of its transuranium (TRU) waste being generated at its nuclear facilities. The reasons are to reduce costs associated with waste handling and disposal, and also to reduce radiation exposure to workers and risk for radionuclide release to man and the environment. The purpose of this document is to provide the USDOE with a plan of research and development tasks for waste minimization, and is prepared so as to provide the maximum impact on volumes based on cost/benefit factors. The document is to be updated annually or as needed to reflect current and future tasks. The Reduced Waste Generation (RWG) tasks encompass a wide range of activities with the principal goals of (1) preventing the generation of waste and (2) converting TRU waste into low-level wastes (LLW) by sorting or decontamination. Concepts for reducing the volume such as in incineration and compaction are considered within the discipline of Reduced Waste Generation, but are considered as somewhat developed technology with only a need for implementation. 33 refs.

  14. 7 CFR 550.29 - Press releases.


    ... 7 Agriculture 6 2010-01-01 2010-01-01 false Press releases. 550.29 Section 550.29 Agriculture... Program Management § 550.29 Press releases. Press releases or other forms of public notification will be... opportunity to review, in advance, all written press releases and any other written information to be...

  15. 28 CFR 2.83 - Release planning.


    ... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Release planning. 2.83 Section 2.83... Release planning. (a) All grants of parole shall be conditioned on the development of a suitable release... parole date for purposes of release planning for up to 120 days without a hearing. If efforts to...

  16. Lignin based controlled release coatings

    Mulder, W.J.; Gosselink, R.J.A.; Vingerhoeds, M.H.; Harmsen, P.F.H.; Eastham, D.


    Urea is a commonly used fertilizer. Due to its high water-solubility, misuse easily leads to excess nitrogen levels in the soil. The aim of this research was to develop an economically feasible and biodegradable slow-release coating for urea. For this purpose, lignin was selected as coating material

  17. Heparin release from thermosensitive hydrogels

    Gutowska, Anna; Bae, You Han; Feijen, Jan; Kim, Sung Wan


    Thermosensitive hydrogels (TSH) were synthesized and investigated as heparin releasing polymers for the prevention of surface induced thrombosis. TSH were synthesized with N-isopropyl acrylamide (NiPAAm) copolymerized with butyl methacrylate (BMA) (hydrophobic) or acrylic acid (AAc) (hydrophilic) co

  18. Flavor Release from French Fries

    Loon, W.A.M.; Linssen, J.P.H.; Boelrijk, A.E.M.; Burgering, M.J.M.; Voragen, A.G.J.


    Flavor release from French fries was measured with the MS-NOSE using both panelists and a mouth-model system. The identity of several volatiles measured with the MS-NOSE was verified with MS-MS. The effect of frying time and the effect of adding salt on I-max (maximum intensity of compounds) and on

  19. Spatial release from informational masking

    Rakerd, Brad; Aaronson, Neil L.


    A new method for investigating spatial release from informational masking was developed and employed in two experiments. The new method is computer controlled and efficient. It employs the versatile coordinate response measure speech stimulus set [Bolia et al., J. Acoust. Soc. Am. 107, 1065 (2000)]. The experiments were conducted in an anechoic room, with a primary loudspeaker in front of the listener and a secondary loudspeaker at 60 deg to the right. Target messages were presented from the primary speaker only. For a standard, distractor messages, simultaneous with the target, were also presented from the primary speaker only. Spatial release was measured by presenting the distractors from both primary and secondary speakers with a temporal offset. Experiment 1 fixed the offset (secondary leading, +4 ms) and varied the number of distractors (1 to 3) and the target-to-distractor ratio (-12 to +4 dB). Masking release, sometimes as large as 10 dB, was found for all combinations of these variables. Experiment 2 varied the offset over a wide range of values. Substantial release from masking was found for both positive and negative offsets, but only in the range in which speech echoes are suppressed (<50 ms). [Work supported by NIDCD grant DC 00181.

  20. Lignin based controlled release coatings

    Mulder, W.J.; Gosselink, R.J.A.; Vingerhoeds, M.H.; Harmsen, P.F.H.; Eastham, D.


    Urea is a commonly used fertilizer. Due to its high water-solubility, misuse easily leads to excess nitrogen levels in the soil. The aim of this research was to develop an economically feasible and biodegradable slow-release coating for urea. For this purpose, lignin was selected as coating

  1. Lignin based controlled release coatings

    Mulder, W.J.; Gosselink, R.J.A.; Vingerhoeds, M.H.; Harmsen, P.F.H.; Eastham, D.


    Urea is a commonly used fertilizer. Due to its high water-solubility, misuse easily leads to excess nitrogen levels in the soil. The aim of this research was to develop an economically feasible and biodegradable slow-release coating for urea. For this purpose, lignin was selected as coating material

  2. Neither bovine somatotropin nor growth hormone-releasing factor alters expression of thyroid hormone receptors in liver and mammary tissues.

    Capuco, A V; Binelli, M; Tucker, H A


    Physiological effects of thyroid hormones are mediated primarily by binding of triiodothyronine to specific nuclear receptors. Organ-specific changes in production of triiodothyronine from its prohormone, thyroxine, have been hypothesized to target the action of thyroid hormones on the mammary gland and play a role in mediating or augmenting a galactopoietic response to bovine somatotropin (bST). Additionally, tissue responsiveness to thyroid hormones may be altered by changes in the number or affinity of nuclear receptors for thyroid hormones. In the present study, effects of bST and bovine growth hormone-releasing factor (bGRF) on thyroid hormone receptors in liver and mammary gland were studied. Lactating Holstein cows received continuous infusions of bST or bGRF for 63 d or served as uninfused controls. Nuclei were isolated from harvested mammary and liver tissues and incubated with [(125)I]-triiodothyronine. Treatments did not alter the capacity or affinity of specific binding sites for triiodothyronine in liver or mammary nuclei. Evaluation of transcript abundance for thyroid hormone receptors showed that isoforms of thyroid hormone receptor or retinoid receptor (which may influence thyroid receptor action) expressed in the mammary gland were not altered by bST or bGRF treatment. Data do not support the hypothesis that administration of bST or bGRF alters sensitivity of mammary tissue by changing expression of thyroid hormone receptors.

  3. Effect of MgO nanofillers on burst release reduction from hydrogel nanocomposites.

    Hezaveh, Hadi; Muhamad, Ida Idayu


    In this study, MgO nanoparticles are applied to control the initial burst release by modification of matrix structure, thereby affecting the release mechanism. The effects of MgO nanofiller loading on the in vitro release of a model drug are investigated. Surface topography and release kinetics of hydrogel nanocomposites are also studied in order to have better insight into the release mechanism. It was found that the incorporation of MgO nanofillers can significantly decrease the initial burst release. The effect of genipin (GN) on burst release was also compared with MgO nanoparticles, and it was found that the impact of MgO on burst release reduction is more obvious than GN; however, GN cross-linking caused greater final release compared to blanks and nanocomposites. To confirm the capability of nanocomposite hydrogels to reduce burst release, the release of β-carotene in Simulated Gastric Fluid and Simulated Intestinal Fluid was also carried out. Thus, the application of MgO nanoparticles seems to be a promising strategy to control burst release.

  4. Modelling and simulations of controlled release fertilizer

    Irfan, Sayed Ameenuddin; Razali, Radzuan; Shaari, Ku Zilati Ku; Mansor, Nurlidia


    The recent advancement in controlled release fertilizer has provided an alternative solution to the conventional urea, controlled release fertilizer has a good plant nutrient uptake they are environment friendly. To have an optimum plant intake of nutrients from controlled release fertilizer it is very essential to understand the release characteristics. A mathematical model is developed to predict the release characteristics from polymer coated granule. Numerical simulations are performed by varying the parameters radius of granule, soil water content and soil porosity to study their effect on fertilizer release. Understanding these parameters helps in the better design and improve the efficiency of controlled release fertilizer.

  5. Resolve to Reduce Your Cancer Risk This Year

    ... to reduce the risk of heart disease and diabetes, and can improve hormone levels and the immune system," Vijayvergia said in a center news release. Don't use tobacco. Smoking has been linked to many types of ...

  6. Reducing Supply Chain GHG Emissions from LCD Panel Manufacturing Webinar

    Fluorinated greenhouse gases (F-GHGs) are among the most potent and persistent greenhouse gases contributing to global climate change. Learn about the manufacturing processes which release F-GHGs, and how LCD suppliers are working to reduce emissions.

  7. Changes in parasite transmission stage excretion after pheasant release.

    Villanúa, D; Acevedo, P; Höfle, U; Rodríguez, O; Gortázar, C


    The production of parasite transmission stages was investigated in the faeces of 77 farm-bred ring-necked pheasants (Phasianus colchicus). Coccidian oocysts (Eimeria sp.), and nematode eggs (Heterakis sp., and Capillaria-like eggs) were recovered before and after release but all birds were treated prior to release. Treatment with fenbendazole significantly reduced the abundance of transmission-stage excretion for all parasites, and reduced the prevalence in the case of Eimeria sp. and Heterakis sp. Nonetheless, a significant increase in the excretion abundance for all parasites and in the prevalence of Eimeria sp. and Heterakis sp. was found after release. Eggs of Ascaridia sp. were found only after releasing, suggesting infection ocurred in the wild. A negative relationship was found between the pheasant body condition and Heterakis excretion abundance and a higher abundance of Capillaria sp. eggs in female birds. No significant relationship was found between parasite excretion abundance and pheasant survival. Despite this, results suggest that an increase in the excretion of parasite transmission stages follows the release of captive pheasants into the wild. This can in part explain restocking failures, but also means that autochtonous free-living birds may become exposed to new and potentially harmful pathogens. To avoid these risks it is proposed that improved prophylactic measures should be taken.

  8. Therapeutic value of low dose L-thyroxine on patients with dialated cardiomyopathy and refractory heart failure%小剂量左旋甲状腺素治疗扩张性心肌病伴甲状腺功能正常的病态综合征疗效观察

    高红梅; 徐大文; 田巨龙; 兰建军; 周娟; 钱昌明; 唐永江; 曾晓斌; 徐颖


    目的 探讨小剂量左旋甲状腺辅助治疗扩张性心肌病合并顽固性心力衰竭的疗效及可能作用机制.方法 入选因扩张性心肌病难治性心力衰竭同时合并有甲状腺功能正常的病态综合征在本院心内科住院的患者共110例,随机分为小剂量左旋甲状腺治疗组及常规治疗组各55例,比较两组治疗效果.结果 两组心率均较治疗前减慢,治疗组减 慢更明显,较对照组减慢5次以上,差异有统计学意义;饮食、精神、6min步行距离,治疗组均较对照组改善明显、迅速:住院时间明显缩短,差异有统计学意义;12周时,左室射血分数治疗组较对照组改善明显,差异有统计学意义;28周时,左室射学分数和左室大小,治疗组较对照组均改善明显,差异有统计学意义.结论 小剂量左旋甲状腺素治疗扩张性心肌病伴甲状腺功能正常的病态综合征有效.%Objective To study the clinical therapeutic effect and mechanisms of low dose L-thyroxine on dialated cardiomyopathy accompanied by refractory heart failure. Methods llOpatients of dialated cardiomyopathy accompanied by refractory heart failure and thyroxine euthyroid sick syndromewere randomly divided into two groups, low dose L-thyroxine treated group ( 55patients) and generally treatment group( 55patients) . The treatment group used low compare the therapeutic effect . Results Heart rates decline significantly in two groups at the end of the study. Therapy groups, more obvious slow down the five above statistics, there are differences in meaning. Diet、 spirit and 6MWT improved greatly and rapidly in the low dose L-thyroxine treated group ,the duration of hospitalization were shortened significantly in the low dose L-thyroxine treated group, there are differences in meaning. LV ejection fraction( LVEF) improved significantly in two group s at the end of 12 weeks study. The treatment group improved much more( P < 0. 05) . LV ejection fraction( LVEF) and

  9. The effect of loading solution and dissolution media on release of Diclofenac from ion exchange resins

    "Atyabi F


    Full Text Available Drugs can be loaded on ion exchange resins in order to control their release. Loading of diclofenac sodium on the resin beads not only sustain its release but also reduce its gastrointestinal mucosal injury. In this study the effect of loading solution and concentration of diclofenac in loading solution on total amount of drug loaded on the resin beads (Amberlite IRA-900 and the release characteristic of drug in different media were examined. Results showed that diclofenac resin complex did not release their drug content in simulated gastric fluid but released it in simulated intestinal fluid independent of exposure time in acidic conditions. The effect of a number of parameters such as ionic strength and pH on the release characteristic of drug - resin complexes were also examined. Results showed that although ionic strength is an important factor, drug release is more affected by the pH of the media. NO ABSTRACT

  10. Zoledronate and Ion-releasing Resins Impair Dentin Collagen Degradation

    Tezvergil-Mutluay, A.; Seseogullari-Dirihan, R.; Feitosa, V.P.; Tay, F.R.; Watson, T.F.; Pashley, D.H.; Sauro, S.


    This study analyzed the amounts of solubilized telopeptides cross-linked carboxyterminal telopeptide of type I collagen (ICTP) and C-terminal crosslinked telopeptide of type I collagen (CTX) derived from matrix-metalloproteinases (MMPs) and cysteine cathepsins (CTPs) subsequent to application of a filler-free (Res.A) or an ion-releasing resin (Res.B) to ethylenediaminetetraacetic acid (EDTA)-demineralized dentin with or without zoledronate-containing primer (Zol-primer) pre-treatment. The chemical modification induced following treatments and artificial saliva (AS) storage was also analyzed through attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR). Totally EDTA-demineralized specimens were infiltrated with Res.A or Res.B with or without Zol-primer pre-treatment, light-cured, and immersed in AS for up to 4 wk. ICTP release was reduced following infiltration with Res.B and further reduced when Res.B was used with Zol-primer; remarkable phosphate mineral uptake was attained after AS storage. CTX release was increased in Res.A- and Res.B-treated dentin. However, when Zol-primer was used with Res.A, the CTX release fell significantly compared to the other tested resin-infiltration methods. In conclusion, zoledronate offers an additional inhibitory effect to the ion-releasing resins in MMP-mediated collagen degradation. However, Zol-primer induces a modest reduction in CTX release only when used with resin-based systems containing no ion-releasing fillers. PMID:25074494

  11. Effects of 5,5'-diphenylhydantoin on thyroxine and 3,5,3'-triiodothyronine concentrations in several tissues of the rat

    Schroeder-van der Elst, J.Pv.; van der Heide, D. (University Hospital, Leiden (Netherlands))


    We studied the effect of 5,5'-diphenylhydantoin (phenytoin, DPH) on the metabolism of thyroid hormones, the intracellular concentration of T4, and the source and concentration of T3. Two groups of six male Wistar rats received a continuous infusion of 10 ml saline/rat. day. One group received DPH in their food (50 mg/kg BW) for 20 days. For both groups (125I)T4 and (131I)T3 were added to the infusion fluid for the last 10 and 7 days, respectively. At isotopic equilibrium the rats were bled and perfused. Compared to the controls, plasma T4 and T3 in the DPH group were reduced (22% and 31%, respectively); TSH did not change. The rate of production of T4 and the plasma appearance rate for T3 were decreased. Thyroidal T3 production was markedly reduced. From the increased (125I)T3/(125I)T4 ratio for plasma, it follows that total body conversion was enhanced. The tissue T4 concentrations decreased in parallel with the plasma T4 level. Total T3 was reduced in all organs. In tissues in which local conversion does not occur, i.e. heart and muscle, the decrease reflected the decrease in plasma T3. In the liver both plasma-derived T3 and locally produced T3 were diminished. In cerebellum and brain the plasma-derived T3 pool was even smaller than was expected from the decrease in plasma T3. This was partly compensated by an increase in local conversion. Only for these two organs was the decrease in the tissue/plasma ratio for (131I)T3 significant. Our results suggest tissue hypothyroidism, caused by a decrease in the production of T4 and T3, which is partly compensated by increased conversion in several organs. The transport of T3 into cerebellum and brain is disturbed, which can be attributed to the mode of action of DPH.

  12. Materials for Pharmaceutical Dosage Forms: Molecular Pharmaceutics and Controlled Release Drug Delivery Aspects

    Patrick P. DeLuca


    Full Text Available Controlled release delivery is available for many routes of administration and offers many advantages (as microparticles and nanoparticles over immediate release delivery. These advantages include reduced dosing frequency, better therapeutic control, fewer side effects, and, consequently, these dosage forms are well accepted by patients. Advances in polymer material science, particle engineering design, manufacture, and nanotechnology have led the way to the introduction of several marketed controlled release products and several more are in pre-clinical and clinical development.

  13. Pramipexole extended release: in Parkinson's disease.

    Chwieduk, Claudine M; Curran, Monique P


    Pramipexole extended release (ER) is a non-ergolinic dopamine receptor agonist available for use as a once-daily oral treatment for the signs and symptoms of early and advanced idiopathic Parkinson's disease. Once-daily pramipexole ER and three times-daily pramipexole immediate release (IR) have similar exposure over 24 hours. The ER formulation is associated with fewer fluctuations in plasma pramipexole concentrations over this period. Pramipexole ER improved the symptoms of Parkinson's disease in three well designed trials in adults with early or advanced disease, as measured by changes from baseline in the sum of the Unified Parkinson's Disease Rating Scale (UPDRS) parts II and III subtotal scores. In a 9-week study, the majority of patients with early Parkinson's disease who were receiving stable pramipexole IR treatment were successfully switched to pramipexole ER. Relative to placebo at week 18, pramipexole ER 0.375-4.5 mg (of the salt) once daily significantly decreased the sum of the UPDRS parts II and III subtotal scores from baseline in two trials in patients with early or advanced Parkinson's disease, and also reduced the percentage of off-time during waking hours in patients with advanced disease. The efficacy of pramipexole ER was maintained after 33 weeks of treatment in the trials in patients with early or advanced Parkinson's disease. Pramipexole ER was generally well tolerated in patients with Parkinson's disease, with the rate of adverse events being generally similar to that with pramipexole IR.

  14. Cigarette smoke-induced damage-associated molecular pattern release from necrotic neutrophils triggers proinflammatory mediator release.

    Heijink, Irene H; Pouwels, Simon D; Leijendekker, Carin; de Bruin, Harold G; Zijlstra, G Jan; van der Vaart, Hester; ten Hacken, Nick H T; van Oosterhout, Antoon J M; Nawijn, Martijn C; van der Toorn, Marco


    Cigarette smoking, the major causative factor for the development of chronic obstructive pulmonary disease, is associated with neutrophilic airway inflammation. Cigarette smoke (CS) exposure can induce a switch from apoptotic to necrotic cell death in airway epithelium. Therefore, we hypothesized that CS promotes neutrophil necrosis with subsequent release of damage-associated molecular patterns (DAMPs), including high mobility group box 1 (HMGB1), alarming the innate immune system. We studied the effect of smoking two cigarettes on sputum neutrophils in healthy individuals and of 5-day CS or air exposure on neutrophil counts, myeloperoxidase, and HMGB1 levels in bronchoalveolar lavage fluid of BALB/c mice. In human peripheral blood neutrophils, mitochondrial membrane potential, apoptosis/necrosis markers, caspase activity, and DAMP release were studied after CS exposure. Finally, we assessed the effect of neutrophil-derived supernatants on the release of chemoattractant CXCL8 in normal human bronchial epithelial cells. Cigarette smoking caused a significant decrease in sputum neutrophil numbers after 3 hours. In mice, neutrophil counts were significantly increased 16 hours after repeated CS exposure but reduced 2 hours after an additional exposure. In vitro, CS induced necrotic neutrophil cell death, as indicated by mitochondrial dysfunction, inhibition of apoptosis, and DAMP release. Supernatants from CS-treated neutrophils significantly increased the release of CXCL8 in normal human bronchial epithelial cells. Together, these observations show, for the first time, that CS exposure induces neutrophil necrosis, leading to DAMP release, which may amplify CS-induced airway inflammation by promoting airway epithelial proinflammatory responses.

  15. Improved response of growth hormone to growth hormone-releasing hormone and reversible chronic thyroiditis after hydrocortisone replacement in isolated adrenocorticotropic hormone deficiency.

    Inagaki, Miho; Sato, Haruhiro; Miyamoto, Yoshiyasu; Hirukawa, Takashi; Sawaya, Asako; Miyakogawa, Takayo; Tatsumi, Ryoko; Kakuta, Takatoshi


    We report a 44-year-old Japanese man who showed a reversible blunted response of growth hormone (GH) to GH-releasing hormone (GRH) stimulation test and reversible chronic thyroiditis accompanied by isolated ACTH deficiency. He was admitted to our hospital because of severe general malaise, hypotension, and hypoglycemia. He showed repeated attacks of hypoglycemia, and his serum sodium level gradually decreased. Finally, he was referred to the endocrinology division, where his adrenocorticotropic hormone (ACTH) and cortisol values were found to be low, and his GH level was slightly elevated. An increased value of thyroid stimulating hormone (TSH) and decreased values of free triidothyronine and free thyroxine were observed along with anti-thyroglobulin antibody, suggesting chronic thyroiditis. Pituitary stimulation tests revealed a blunted response of ACTH and cortisol to corticotropin-releasing hormone, and a blunted response of GH to GRH. Hydrocortisone replacement was then started, and this improved the patient's general condition. His hypothyroid state gradually ameliorated and his titer of anti-thyroglobulin antibody decreased to the normal range. Pituitary function was re-evaluated with GRH stimulation test under a maintenance dose of 20 mg/day hydrocortisone and showed a normal response of GH to GRH. It is suggested that re-evaluation of pituitary and thyroid function is useful for diagnosing isolated ACTH deficiency after starting a maintenance dose of hydrocortisone in order to avoid unnecessary replacement of thyroid hormone.

  16. Early release of neonatal ureteral obstruction preserves renal function

    Shi, Yimin; Pedersen, Michael; Li, Chunling;


    .05) after 24 wk. Similarly, glomerular filtration rate of the obstructed kidney was severely reduced at 24 wk: 172 ± 36 vs. 306 ± 42 μl·min−1·100 g body wt−1 (P reduction in total protein content...... downregulation of Na-K-ATPase to 62 ± 7%, aquaporin-1 to 53 ± 3%, and aquaporin-3 to 53 ± 7% of sham levels. Release after 1 wk completely prevented development of hydronephrosis, reduction in RBF and glomerular filtration rate, and downregulation of renal transport proteins, whereas release after 4 wk had...

  17. Sulfur Release from Cement Raw Materials during Solid Fuel Combustion

    Nielsen, Anders Rooma; Larsen, Morten B.; Glarborg, Peter


    During combustion of solid fuels in the material inlet end of cement rotary kilns, local reducing conditions can occur and cause decomposition of sulfates from cement raw materials. Decomposition of sulfates is problematic because it increases the gas-phase SO2 concentration, which may cause...... deposit formation in the kiln system. SO2 release from cement raw materials during combustion of solid fuels has been studied experimentally in a high temperature rotary drum. The fuels were tire rubber, pine wood, petcoke, sewage sludge, and polypropylene. The SO2 release from the raw materials...

  18. Nitric oxide-releasing porous silicon nanoparticles

    Kafshgari, Morteza Hasanzadeh; Cavallaro, Alex; Delalat, Bahman; Harding, Frances J.; McInnes, Steven JP; Mäkilä, Ermei; Salonen, Jarno; Vasilev, Krasimir; Voelcker, Nicolas H.


    In this study, the ability of porous silicon nanoparticles (PSi NPs) to entrap and deliver nitric oxide (NO) as an effective antibacterial agent is tested against different Gram-positive and Gram-negative bacteria. NO was entrapped inside PSi NPs functionalized by means of the thermal hydrocarbonization (THC) process. Subsequent reduction of nitrite in the presence of d-glucose led to the production of large NO payloads without reducing the biocompatibility of the PSi NPs with mammalian cells. The resulting PSi NPs demonstrated sustained release of NO and showed remarkable antibacterial efficiency and anti-biofilm-forming properties. These results will set the stage to develop antimicrobial nanoparticle formulations for applications in chronic wound treatment.

  19. AMPA receptor inhibition by synaptically released zinc.

    Kalappa, Bopanna I; Anderson, Charles T; Goldberg, Jacob M; Lippard, Stephen J; Tzounopoulos, Thanos


    The vast amount of fast excitatory neurotransmission in the mammalian central nervous system is mediated by AMPA-subtype glutamate receptors (AMPARs). As a result, AMPAR-mediated synaptic transmission is implicated in nearly all aspects of brain development, function, and plasticity. Despite the central role of AMPARs in neurobiology, the fine-tuning of synaptic AMPA responses by endogenous modulators remains poorly understood. Here we provide evidence that endogenous zinc, released by single presynaptic action potentials, inhibits synaptic AMPA currents in the dorsal cochlear nucleus (DCN) and hippocampus. Exposure to loud sound reduces presynaptic zinc levels in the DCN and abolishes zinc inhibition, implicating zinc in experience-dependent AMPAR synaptic plasticity. Our results establish zinc as an activity-dependent, endogenous modulator of AMPARs that tunes fast excitatory neurotransmission and plasticity in glutamatergic synapses.

  20. 14 CFR 125.373 - Original flight release or amendment of flight release.


    ... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Original flight release or amendment of flight release. 125.373 Section 125.373 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT... Flight Release Rules § 125.373 Original flight release or amendment of flight release. (a) A...

  1. Counting Vesicular Release Events Reveals Binomial Release Statistics at Single Glutamatergic Synapses.

    Malagon, Gerardo; Miki, Takafumi; Llano, Isabel; Neher, Erwin; Marty, Alain


    Many central glutamatergic synapses contain a single presynaptic active zone and a single postsynaptic density. However, the basic functional properties of such "simple synapses" remain unclear. One important step toward understanding simple synapse function is to analyze the number of synaptic vesicles released in such structures per action potential, but this goal has remained elusive until now. Here, we describe procedures that allow reliable vesicular release counting at simple synapses between parallel fibers and molecular layer interneurons of rat cerebellar slices. Our analysis involves local extracellular stimulation of single parallel fibers and deconvolution of resulting EPSCs using quantal signals as template. We observed a reduction of quantal amplitudes (amplitude occlusion) in pairs of consecutive EPSCs due to receptor saturation. This effect is larger (62%) than previously reported and primarily reflects receptor activation rather than desensitization. In addition to activation-driven amplitude occlusion, each EPSC reduces amplitudes of subsequent events by an estimated 3% due to cumulative desensitization. Vesicular release counts at simple synapses follow binomial statistics with a maximum that varies from 2 to 10 among experiments. This maximum presumably reflects the number of docking sites at a given synapse. These results show striking similarities, as well as significant quantitative differences, with respect to previous results at simple GABAergic synapses. It is generally accepted that the output signal of individual central synapses saturates at high release probability, but it remains unclear whether the source of saturation is presynaptic, postsynaptic, or both presynaptic and postsynaptic. To clarify this and other issues concerning the function of synapses, we have developed new recording and analysis methods at single central glutamatergic synapses. We find that individual release events engage a high proportion of postsynaptic

  2. Microwave Activation of Drug Release

    Jónasson, Sævar Þór

    Due to current limitations in control of pharmaceutical drug release in the body along with increasing medicine use, methods of externally-controlled drug release are of high interest. In this thesis, the use of microwaves is proposed as a technique with the purpose of externally activating...... setup, called the microwave activation system has been developed and tested on a body phantom that emulates the human torso. The system presented in this thesis, operates unobtrusively, i.e. without physically interfering with the target (patient). The torso phantom is a simple dual-layered cylindrical...... the phantom is of interest for disclosing essential information about the limitations of the concept, the phantom and the system. For these purposes, a twofold operation of the microwave activation system was performed, which are reciprocal of each other. In the first operation phase, named mapping...

  3. Zegerid--immediate-release omeprazole.


    The FDA has approved marketing of Zegerid powder for oral suspension (Santarus), an immediate-release formulation of the proton-pump inhibitor (PPI) omeprazole (Prilosec, and others). All other oral PPIs are delayed-release, enteric-coated formulations designed to prevent degradation of the drug by gastric acid. Each 20- or 40-mg packet of Zegerid contains 1680 mg sodium bicarbonate, which protects the drug from gastric acid degradation. A dose of Zegerid contains 460 mg of sodium, which may be excessive for some patients. Zegerid is the first oral PPI to be approved by the FDA for reduction of risk of upper GI bleeding in critically ill patients. The drug may be useful for patients who are unable to swallow and have nasogastric (NG) tubes in place. Zegerid cost $70.00 for 14 days' treatment, compared to less than $10 for 14 tablets of Prilosec OTC.

  4. Neutron-absorber release device

    VAN Erp, Jan B.; Kimont, Edward L.


    A resettable device is provided for supporting an object, sensing when an environment reaches a critical temperature and releasing the object when the critical temperature is reached. It includes a flexible container having a material inside with a melting point at the critical temperature. The object's weight is supported by the solid material which gives rigidity to the container until the critical temperature is reached at which point the material in the container melts. The flexible container with the now fluid material inside has insufficient strength to support the object which is thereby released. Biasing means forces the container back to its original shape so that when the temperature falls below the melting temperature the material again solidifies, and the object may again be supported by the device.


    Sanely Lourenço da Costa


    Full Text Available The aim of this study was to investigate the interaction of human FSH (10ng/ml with T4 (20ng/mL on survival, activation and growth of preantral follicles cultured in vitro for 28 days. Fragments of non-cultured and cultured ovarian tissue were processed for classic histology and transmission electron microscopy. The results showed a reduction in the survival rate in all the media tested (one to 28 days when compared to the fresh control. However the treatment with T4/hFSH for seven days of culture maintained the rate similar to the control. The media tested by one and 28 days reduced the percentage of primordial follicles in all periods of culture. However, T4/hFSH on day one of culture remained similar to the fresh control. None of the media were able to keep the percentage of the developing follicles. It was observed that the follicular diameter in the medium with T4/hFSH remained similar to the fresh control. The ultrastructural analysis confirmed the integrity of follicles cultured for seven days in a medium supplemented with T4/hFSH. In conclusion, the medium with T4/hFSH is able to maintain the survival, promote the activation, and the ultrastructural integrity of caprine preantral follicles for until seven days.

  6. Effects of thyroxine on metamorphosis of orange-spotted grouper (Epinephelus coioides) larvae%甲状腺素对斜带石斑鱼仔鱼变态的影响

    唐啸尘; 刘晓春; 林浩然; 张海发; 刘付永忠


    用甲状腺素(Thyroxine,T4)处理斜带石斑鱼Epinephelus coioides仔鱼,研究T4对仔鱼变态的影响.仔鱼在变态前期和变态高峰期,用0.01mg·L-1T4处理7d后仔鱼完成变态,用0.10mg·L-1T4处理4d后仔鱼完成变态,用1.00mg·L-1T4处理3d后仔鱼完成变态,对照组仔鱼在实验期间未能完成变态.用0.01mg·L-1T4处理变态高峰期仔鱼其存活率明显提高和全长增长明显变慢,但对变态前期仔鱼无影响;用0.10和1.00mg·L-1T4处理变态前期和变态高峰期仔鱼,其存活率显著降低和全长增长明显变慢.结果表明,在变态高峰期用0.01mg·L-1T4处理仔鱼能加速它的变态并提高其存活率.

  7. The effects of thyroxine or a GnRH analogue on thyroid hormone deiodination in the olfactory epithelium and retina of rainbow trout, Oncorhynchus mykiss, and sockeye salmon, Oncorhynchus nerka.

    Plate, E M; Adams, B A; Allison, W T; Martens, G; Hawryshyn, C W; Eales, J G


    Using low (0.5nM) substrate levels we determined the activities of thyroxine (T4) outer-ring deiodination (ORD), T4 inner-ring deiodination (T4IRD) and 3,5,3(')-triiodothyronine (T3) IRD activities in the olfactory epithelium (OLF) and retina (RET) of laboratory-held immature 1-year-old rainbow trout and immature 2.5-year-old sockeye salmon. In both species all three deiodination activities were detected in OLF and RET. For OLF, no particular pathway predominated and activities were similar to those of brain. For RET, T3IRD activity was greater than T4ORD activity and in sockeye RET T3IRD activity exceeded that of liver. Trout immersion for 6 weeks in 100ppm T4 increased plasma T4 levels 3-fold and plasma T3 levels by 50% and caused the anticipated autoregulatory responses in brain and liver deiodination ( downward arrow T4ORD, upward arrow T4IRD, and upward arrow T3IRD); OLF deiodination and RET T4ORD activity were unaltered but RET T4IRD and T3IRD activities increased dramatically. Two injections of a GnRH analogue (20 microgkg(-1)) into sockeye increased plasma T3 levels but not T4 levels and decreased RET T4IRD and T3IRD activities without changing liver, brain, or OLF deiodination. We conclude that in salmonids the main TH deiodination pathways occur in OLF but show no regulation by T4 or GnRH. In contrast, T3IRD activity predominates in RET and can be regulated by T4 and GnRH, suggesting that for RET plasma may be the major T3 source. These findings have implications for thyroidal regulation of sensory functions during salmonid diadromous migrations.

  8. Optimization of release locations for small self-stress large stiffness flexure mechanisms

    Brouwer, D.M.; Boer, S.E.; Meijaard, J.P.; Aarts, R.G.K.M.


    In overconstrained mechanisms inherent alignment errors cause self-stress. The level of stress can be reduced by inserting flexure releases making the mechanism exactly constrained. The location and orientation of releases can be optimized for a combination of minimum self-stress and maximum stiffne

  9. The influence of cyclic loading on gentamicin release from acrylic bone cements

    Hendriks, JGE; Neut, D; Hazenberg, JG; Verkerke, GJ; van Horn, [No Value; van der Mei, HC; Busscher, HJ


    Antibiotic-loaded acrylic bone cement is widely used in total joint replacement to reduce infections. Walking results in cyclic loading, which has been suggested to stimulate antibiotic release. The goal of this study is to compare antibiotic release from cyclically loaded bone cement with the relea

  10. China's First Luxury Brands Released

    Richard Zhu


    @@ China now has its own luxury brands.The four brands Feitian (Moutai spirit), Yong-Qi Zitan (furniture), Rongbaozhai (works of art) and Dongding Oolong (tea) were released as the first Chinese luxury brands by the China Luxury Institute on Nov.11.Based on the Institute's investigation of over 500 enterprises and brands within over 30 kinds of industries like garments, tea, wine, china and jade, in combination with market questionnaire, the first four brands have made their debut.

  11. 精神分裂症患者攻击行为与血清甲状腺素睾酮水平的相关性%Correlation between aggressive behavior and serum thyroxine or testosterone level in schizophrenic

    王小全; 马素杰; 张永录; 周海晓; 丁志杰


    目的:探讨精神分裂症患者攻击行为与血清甲状腺素、睾酮水平的相关性。方法对120例精神分裂症患者采用简明精神病量表评定精神症状,依据既往暴力史及外显攻击行为量表评定攻击行为,将有攻击行为的70例患者设为研究组,无攻击行为的50例患者设为对照组。检测两组促甲状腺激素、血清游离三碘甲状腺原氨酸、血清游离甲状腺素、总三碘甲状腺原氨酸、总甲状腺激素及血清睾酮水平。对检测结果进行对比分析及相关分析。结果研究组血清总三碘甲状腺原氨酸、血清游离三碘甲状腺原氨酸水平显著高于对照组(P<0.05),促甲状腺激素水平显著低于对照组(P<0.01)。研究组血清总三碘甲状腺原氨酸水平与外显攻击行为量表中言语攻击、财产攻击因子分呈正相关(P<0.05),与简明精神病量表中缺乏活力因子分呈负相关(P<0.05);血清游离三碘甲状腺原氨酸与外显攻击行为量表中财产攻击、自身攻击因子分呈正相关(P<0.05);男性血清睾酮水平与外显攻击行为量表中言语攻击、自身攻击因子分呈正相关(P<0.05),与简明精神病量表中缺乏活力因子分呈负相关(P<0.05);女性血清睾酮水平与外显攻击行为量表中自身攻击因子分呈正相关(P<0.05),与简明精神病量表中缺乏活力因子分呈负相关(P<0.05)。结论精神分裂症患者攻击行为与血清总三碘甲状腺原氨酸、血清游离三碘甲状腺原氨酸水平及血清睾酮水平的变化呈正相关。临床上对伴有攻击行为的精神分裂症患者可定期监测甲状腺激素及睾酮水平进行预测性评估,为早期干预提供依据。%Objective To explore the correlation between aggressive behavior and serum thyroxine or tes‐tosterone level in schizophrenic .Methods Mental symptoms of 120

  12. Controlled Release Formulations of Auxinic Herbicides

    Kowalski, Witold J.; Siłowiecki, Andrzej.; Romanowska, Iwona; Glazek, Mariola; Bajor, Justyna; Cieciwa, Katarzyna; Rychter, Piotr


    ingredient in the HBA oligomers was chemically bound to the oligomer matrix and a controlled release followed in concert with the hydrolysis of ester bonds in the oligomer systems. Due to the high volatility and high water solubility of the DMA salts, significant amounts of active ingredients were predisposed to be dispersed in the environment. On the other hand, the HBA oligomers exhibit low volatility and low solubility in water, so they tend to exhibit lover migrating rates from the target site. The obtained plots suggested that in the case of the HBA oligomers the effectiveness were delayed in time when compared with the DMA salts. The integral effectiveness of the studied HBA oligomers was practically equivalent to the conventional DMA salts, but the release of the HBA herbicides was delayed in time vs. DMA salts. The mixtures of oligo (R,S)-3-hydroxybutyric acid containing chemically bonded 2,4-D, Dicamba and MCPA (HBA) were proposed as carriers of active ingredients that could be released to control the sensitive weeds. The synthesized HBA oligomers could be particularly useful in a number of practical applications, because they release the herbicide to plants at a controlled rate and in amounts required over a specified period of time, their degradation products are identical to metabolites formed in plant cells, the physicochemical and operational parameters of the carrier oligomers might be optimized by fine-tuning of synthesis conditions. The decreased vapor pressure and increased lipophilicity of the studied materials could reduce the risk exposure of the operational personnel, as well as, a decrease the environmental pollution. Acknowledgments The authors would like to thank the Polish Ministry of Science and Higher Education for supporting this work through the grant No. NN 310 303039. References [1] S. Dubey, V. Jhelum, P.K. Patanjali, Controlled release agrochemical formulations: A review, J. Scientific &Industrial Research (India) 70 (2011) 105-112. [2] W. J


    Mithilesh Kumar Jha


    Full Text Available Modified Release (MR Formulations have a modification in the release mechanism. Modified release dosage forms are developed by altering drug absorption or the site of drug release in order to achieve predetermined clinical objectives. Modified drug release from dosage forms is complemented by the allied processes of drug design, of dosage administration, and of membrane transport and absorption of drug to the biological site of action. Modified-release drugs have complex formulations that can offer an advantage over standard medication for some patients. Modified-release preparations should only be used where there is a clear clinical advantage over conventional-release preparations. In general, Modified-release preparations should be reserved for specific patients where there is a problem with compliance, effectiveness or side-effects which these preparations could help overcome. Modified–release technologies have become indispensable to resolving critical technical, therapeutic, and marketing challenges, such as improving patience compliance, less dosage timings, better safety, better indications, delivering poorly soluble and poorly absorbable API’s, product differentiation, patent protection, product life-cycle extension, and better margins. Modified-release formulation design can be conducted for oral and non-oral administration routes. Possible therapeutic benefits of an MR product include improved efficacy and reduced adverse events, increased convenience and patient compliance, optimized performance, a greater selectivity of activity, or new indications.

  14. Influence of dental biofilm on release of mercury from amalgam exposed to carbamide peroxide.

    Steinberg, Doron; Blank, Ori; Rotstein, Ilan


    Tooth bleaching is a popular procedure in modern aesthetic dentistry. Bleaching agents may affect amalgam restorations by altering the release of mercury. The aim of this study was to explore the effect of biofilm-coated amalgam restorations on the release of mercury in the presence of carbamide peroxide. Samples of SDI and Valliant amalgams were submerged for either 14 days or 7 months in buffered KCl after which they were coated with saliva, bacteria, and polysaccharides. The samples were exposed to 10% carbamide peroxide (CP) for 24 h. The amount of mercury released was examined for 120 h. Results showed that most of mercury release occurred within the first 24 h, after which the release rate decreased sharply. After 120 h the release of mercury from the tested samples was minimal and similar to the control group. The presence of biofilm coating on the amalgam samples did not induce the release of mercury but tended to reduce mercury release into the surrounding environment. CP induces the release of mercury from amalgam samples. However, the presence of biofilm did not prevent large amounts of mercury release from amalgam coated with biofilms and exposed to CP. This study indicates that dental biofilm may retard the release of mercury from amalgam restorations.

  15. A noncanonical release of GABA and glutamate modulates neuronal migration.

    Manent, Jean-Bernard; Demarque, Michaël; Jorquera, Isabel; Pellegrino, Christophe; Ben-Ari, Yehezkel; Aniksztejn, Laurent; Represa, Alfonso


    Immature neurons express GABA and glutamate receptors before synapse formation, and both transmitters are released at an early developmental stage. We have now tested the hypothesis that the ongoing release of GABA and glutamate modulates neuronal migration. Using 5-bromo-2'-deoxyuridine labeling and cocultures of hippocampal slices obtained from naive and green fluorescent protein-transgenic mice, we report that migration is severely affected by GABA(A) or NMDA receptor antagonist treatments. These effects were also present in munc18-1 knock-out slices in which soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE)-dependent vesicular secretion of transmitters has been deleted. GABA(A) antagonists were more efficient than NMDA antagonists to reduce cell migration, in keeping with the earlier maturation of GABAergic mechanisms. We conclude that GABA and, to a lesser degree, glutamate released in a SNARE-independent mechanism exert a paracrine action on neuronal migration.

  16. Microelectromechanical high-density energy storage/rapid release system

    Rodgers, M. Steven; Allen, James J.; Meeks, Kent D.; Jensen, Brian D.; Miller, Samuel L.


    One highly desirable characteristic of electrostatically driven microelectromechanical systems (MEMS) is that they consume very little power. The corresponding drawback is that the force they produce may be inadequate for many applications. It has previously been demonstrated that gear reduction units or microtransmissions can substantially increase the torque generated by microengines. Operating speed, however, is also reduced by the transmission gear ratio. Some applications require both high speed and high force. If this output is only required for a limited period of time, then energy could be stored in a mechanical system and rapidly released upon demand. We have designed, fabricated, and demonstrated a high-density energy storage/rapid release system that accomplishes this task. Built using a 5-level surface micromachining technology, the assembly closely resembles a medieval crossbow. Energy releases on the order of tens of nanojoules have already been demonstrated, and significantly higher energy systems are under development.

  17. MRI monitoring of nanocarrier accumulation and release using Gadolinium-SPIO co-labelled thermosensitive liposomes

    Lorenzato, Cyril; Oerlemans, Chris; van Elk, Merel; Geerts, Willie J C|info:eu-repo/dai/nl/149264399; Denis de Senneville, Baudouin; Moonen, Chrit; Bos, Clemens


    Encapsulation of anticancer drugs in triggerable nanocarriers can beneficially modify pharmacokinetics and biodistribution of chemotherapeutic drugs, and consequently increase tumor drug concentration and efficacy, while reducing side effects. Thermosensitive liposomes release their contents trigger

  18. The Effect of Ethanol on the Release of Opioids from Oral Prolonged-Release Preparations

    Walden, Malcolm; Nicholls, Fiona A.; Smith, Kevin J.; Tucker, Geoffrey T


    Recent experience has prompted the US FDA to consider whether ethanol ingestion may modify the release characteristics of prolonged-release formulations, where dose dumping may be an issue for patient safety. The influence of ethanol on the in vitro release of opioid drugs from some prolonged-release formulations utilizing different release technologies was examined. Results indicated that the prolonged-release mechanisms remained intact under the testing conditions, although one product show...

  19. Presynaptic kainate receptors that enhance the release of GABA on CA1 hippocampal interneurons.

    Cossart, R; Tyzio, R; Dinocourt, C; Esclapez, M; Hirsch, J C; Ben-Ari, Y; Bernard, C


    We report that kainate receptors are present on presynaptic GABAergic terminals contacting interneurons and that their activation increases GABA release. Application of kainate increased the frequency of miniature inhibitory postsynaptic currents recorded in CA1 interneurons. Local applications of glutamate but not of AMPA or NMDA also increased GABA quantal release. Application of kainate as well as synaptically released glutamate reduced the number of failures of GABAergic neurotransmission between interneurons. Thus, activation of presynaptic kainate receptors increases the probability of GABA release at interneuron-interneuron synapses. Glutamate may selectively control the communication between interneurons by increasing their mutual inhibition.

  20. Toxic Release Inventory Chemicals by Groupings

    U.S. Environmental Protection Agency — The Toxics Release Inventory (TRI) makes available information for more than 600 toxic chemicals that are being used, manufactured, treated, transported, or released...

  1. Section 9: Ground Water - Likelihood of Release

    HRS training. the ground water pathway likelihood of release factor category reflects the likelihood that there has been, or will be, a release of hazardous substances in any of the aquifers underlying the site.

  2. Scavenging effect of Trolox released from brushite cements.

    Mestres, Gemma; Santos, Carlos F; Engman, Lars; Persson, Cecilia; Ott, Marjam Karlsson


    In this study a brushite cement was doped with the chain-breaking antioxidant Trolox. The effect of the antioxidant on the physical properties of the cement was evaluated and the release of Trolox was monitored by UV spectroscopy. The ability of the Trolox set free to scavenge reactive oxygen species (ROS) released by macrophages was determined in vitro using a luminol-amplified chemiluminescence assay. Trolox did not modify the crystalline phases of the set cement, which mainly formed crystalline brushite after 7 days in humid conditions. The setting time, compressive strength and morphology of the cement also remained unaltered after the addition of the antioxidant. Trolox was slowly released from the cement following a non-Fickian transport mechanism and nearly 64% of the total amount was released after 3 days. Moreover, the capacity of Trolox to scavenge the ROS released by macrophages increased in a dose-dependent manner. Trolox-loaded cements are expected to reduce some of the first harmful effects of acute inflammation and can thus potentially protect the surrounding tissue during implantation of these as well as other materials used in conjunction.

  3. Improvement of waste release control in French NPP

    Samson, T.; Lucquin, E.; Dupin, M. [EDF/GDL (France); Florence, D. [EDF/GENV (France); Grisot, M. [EDF/CNPE Saint Laurent (France)


    The new waste release control in French NPP is more restrictive than the old one and needs heavy investment to bring plants to compliance with it. The great evolutions are a chemical follow up on more chemicals with a higher measurement frequency and with lower maximum concentrations and a specific measurement of carbon 14. Regarding radioactive releases, a new counting has been settled and activity of carbon 14 release is now measured and no longer calculated. The evolution of the French regulation leads to develop specific procedures and analytical techniques in chemistry and in radiochemistry (UV spectrometric methods, carbon 14 measurements,..) EDF NPP operators have launched a voluntarist process to reduce their releases since the beginning and before the evolution of the regulation. EDF priorities in terms of environment care lead henceforth to implement a global optimisation of the impact for a better control of releases. The new regulation will help EDF to reach its goals because it covers all the aspects in one administrative document: it is seen as a real simplification and a clarification towards public. In addition, this new regulation fits in with international practices which will allow an easier comparison of results between EDF and foreign NPP. These big environmental concerns lead EDF to create a national dedicated laboratory (LAMEN) in charge of developing specific measurement procedures to be implemented either by NPP or by sub-contractor laboratories. (authors)

  4. Mars Express releases Beagle 2


    At 9:31 CET, the crucial sequence started to separate the Beagle 2 lander from Mars Express. As data from Mars Express confirm, the pyrotechnic device was fired to slowly release a loaded spring, which gently pushed Beagle 2 away from the mother spacecraft. An image from the onboard visual monitoring camera (VMC) showing the lander drifting away is expected to be available later today. Since the Beagle 2 lander has no propulsion system of its own, it had to be put on the correct course for its descent before it was released. For this reason, on 16 December the trajectory of the whole Mars Express spacecraft had to be adjusted to ensure that Beagle 2 would be on course to enter the atmosphere of Mars. This manoeuvre, called "retargeting'' was critical: if the entry angle is too steep, the lander could overheat and burn up in the atmosphere; if the angle is too shallow, the lander might skim like a pebble on the surface of a lake and miss its target. This fine targeting and today's release were crucial manoeuvres for which ESA's Ground Control Team at ESOC (European Space Operations Centre) had trained over the past several months. The next major milestone for Mars Express will be the manoeuvre to enter into orbit around Mars. This will happen at 3:52 CET on Christmas morning, when Beagle 2 is expected to land on the surface of Mars. "Good teamwork by everybody - ESA, industry and the Beagle 2 team - has got one more critical step accomplished. Mars, here comes Europe!" said David Southwood, ESA Director of Science.

  5. DVD With High Gapacity Released


    After two years of research and development, the Center for International Cultural Exchange under the Ministry of Culture of China has recently released a new type of DVD which is double-faced, double-system and bears ten languages. Teststatistics show that all its indicators come up withthose of its foreign counterparts. Now it has beenput into mass production.This new type of DVD features the following performances. It is a high-clarity one, with the horizontal clarity more than 500. It has a superb sound effect, capable of recording various stereo signals such as DOLBY DIGITAL and DTS. It can record dubbing in eight languages and subtitles

  6. Attenuated Tonic and Enhanced Phasic Release of Dopamine in Attention Deficit Hyperactivity Disorder.

    Rajendra D Badgaiyan

    Full Text Available It is unclear whether attention deficit hyperactive disorder (ADHD is a hypodopaminergic or hyperdopaminergic condition. Different sets of data suggest either hyperactive or hypoactive dopamine system. Since indirect methods used in earlier studies have arrived at contradictory conclusions, we directly measured the tonic and phasic release of dopamine in ADHD volunteers. The tonic release in ADHD and healthy control volunteers was measured and compared using dynamic molecular imaging technique. The phasic release during performance of Eriksen's flanker task was measured in the two groups using single scan dynamic molecular imaging technique. In these experiments volunteers were positioned in a positron emission tomography (PET camera and administered a dopamine receptor ligand (11C-raclopride intravenously. After the injection PET data were acquired dynamically while volunteers either stayed still (tonic release experiments or performed the flanker task (phasic release experiments. PET data were analyzed to measure dynamic changes in ligand binding potential (BP and other receptor kinetic parameters. The analysis revealed that at rest the ligand BP was significantly higher in the right caudate of ADHD volunteers suggesting reduced tonic release. During task performance significantly lower ligand BP was observed in the same area, indicating increased phasic release. In ADHD tonic release of dopamine is attenuated and the phasic release is enhanced in the right caudate. By characterizing the nature of dysregulated dopamine neurotransmission in ADHD, the results explain earlier findings of reduced or increased dopaminergic activity.

  7. Individualized optimal release angles in discus throwing.

    Leigh, Steve; Liu, Hui; Hubbard, Mont; Yu, Bing


    The purpose of this study was to determine individualized optimal release angles for elite discus throwers. Three-dimensional coordinate data were obtained for at least 10 competitive trials for each subject. Regression relationships between release speed and release angle, and between aerodynamic distance and release angle were determined for each subject. These relationships were linear with subject-specific characteristics. The subject-specific relationships between release speed and release angle may be due to subjects' technical and physical characteristics. The subject-specific relationships between aerodynamic distance and release angle may be due to interactions between the release angle, the angle of attack, and the aerodynamic distance. Optimal release angles were estimated for each subject using the regression relationships and equations of projectile motion. The estimated optimal release angle was different for different subjects, and ranged from 35 degrees to 44 degrees . The results of this study demonstrate that the optimal release angle for discus throwing is thrower-specific. The release angles used by elite discus throwers in competition are not necessarily optimal for all discus throwers, or even themselves. The results of this study provide significant information for understanding the biomechanics of discus throwing techniques.

  8. 28 CFR 2.33 - Release plans.


    ... Administration DEPARTMENT OF JUSTICE PAROLE, RELEASE, SUPERVISION AND RECOMMITMENT OF PRISONERS, YOUTH OFFENDERS, AND JUVENILE DELINQUENTS United States Code Prisoners and Parolees § 2.33 Release plans. (a) A grant of parole is conditioned upon the approval of release plans by the Regional Commissioner. In general...

  9. Prisoners' Perspectives on Strategies for Release.

    Muhammad, Mika'il A.


    Examines questions regarding the perceptions of New York State prisoners (N=263), their chances of an early release, and their strategies to expedite the release process. Findings suggest that inmates view all activities thought to expedite release as important. Many prisoners wished to eliminate the "game playing" thought associated…

  10. Data release of the LAMOST pilot survey

    A-Li Luo; Jian-Nan Zhang; Shi-Hai Yang; Zheng-Qiu Yao; Yong Yu; Hui Yuan; Chao Zhai; En-Peng Zhang; Jing Zhang; Li-Ping Zhang; Wei Zhang; Yong Zhang; Zhong-Rui Bai; Zhen-Chao Zhang; Ming Zhao; Fang Zhou; Yong-Tian Zhu; Jie Zhu; Si-Cheng Zou; Xiao-Yan Chen; Feng-Fei Wang; Yan-Xin Guo; Jian-Jun Chen; Bing Du; Xiao Kong; Ya-Juan Lei; Yin-Bi Li; Hao-Tong Zhang; Yi-Han Song; Yue Wu; Yan-Xia Zhang; Xin-Lin Zhou; Fang Zuo; Peng Du; Lin He; Wen Hou; Yi-Qiao Dong; Jian Li; Yong-Heng Zhao; Guang-Wei Li; Shuang Li; Jing Song; Yuan Tian; Meng-Xin Wang; Ke-Fei Wu; Hui-Qin Yang; Hai-Long Yuan; Shu-Yun Cao; Hai-Yuan Chen; Gang Zhao; Kun-Xin Chen; Ying Chen; Jia-Ru Chu; Lei Feng; Xue-Fei Gong; Bo-Zhong Gu; Yong-Hui Hou; Zhi-Ying Huo; Hong-Zhuan Hu; Ning-Sheng Hu; Xiang-Qun Cui; Zhong-Wen Hu; Lei Jia; Fang-Hua Jiang; Xiang Jiang; Zi-Bo Jiang; Ge Jin; Ai-Hua Li; Qi Li; Xin-Nan Li; Yan Li; Guo-Ping Li; Ye-Ping Li; Gen-Rong Liu; Guan-Qun Liu; Zhi-Gang Liu; Qi-Shuai Lu; Wen-Zhi Lu; Yu Luo; Yin-Dun Mao; Li Men; Ji-Jun Ni; Yao-Quan Chu; Yong-Jun Qi; Zhao-Xiang Qi; Huo-Ming Shi; Ding-Qiang Su; Shi-Wei Sun; Hong-Jun Su; Zheng-Hong Tang; Qing-Sheng Tao; Liang-Ping Tu; Da-Qing Wang; Jian-Rong Shi; Dan Wang; Guo-Min Wang; Hai Wang; Jia-Ning Wang; Jian Wang; Jian-Ling Wang; Jian-Ping Wang; Lei Wang; Shou-Guan Wang; Shu-Qing Wang; Gang Wang; Ya-Nan Wang; You Wang; Yue-Fei Wang; Ming-Zhi Wei; Xiang-Xiang Xue; Xiao-Zheng Xing; Ling-Zhe Xu; Xin-Qi Xu; Yan Xu; De-Hua Yang


    This paper describes the data release of the LAMOST pilot survey,which includes data reduction,calibration,spectral analysis,data products and data access.The accuracy of the released data and the information about the FITS headers of spectra are also introduced.The released data set includes 319 000 spectra and a catalog of these objects.

  11. Reduced Rank Regression

    Johansen, Søren


    The reduced rank regression model is a multivariate regression model with a coefficient matrix with reduced rank. The reduced rank regression algorithm is an estimation procedure, which estimates the reduced rank regression model. It is related to canonical correlations and involves calculating e...

  12. Characterization and in vitro release studies of tetracycline and rolitetracycline imobilized on anionic collagen membranes

    Gilberto Goissis


    Full Text Available This work reports the covalent immobilization of tetracycline and rolitetracycline over anionic collagen membranes and the drug release studies as an effort to develop a two stage drug release based on diffusion (fast release and on the rate of membrane biodegradation (slow release. Independent from casting conditions antibiotics incorporated by dispersion were released in the range from 80 to 100% within 7 hours in concentrations significantly higher than those described for the prevention of bacterial growth. Antibiotic release within this period was predominantly diffusion controlled. Covalent immobilization by a modified azide procedure occurred with preservation of collagen structure independently from pH of casting and reaction conditions. Its expected that anionic collagen membranes with dispersed and covalently bound rolitetracycline or tetracycline, in association with conventional therapy, may significantly reduce membrane induced infections observed post-implantation, one of the major problem associated with periodontal ligaments reconstruction by the Guided Tissue Regeneration procedure.

  13. Application of waterborne acrylic emulsions in coated controlled release fertilizer using reacted layer technology

    Yazhen Shen; Cong Zhao; Jianmin Zhou; Changwen Du


    Waterborne acrylic emulsions modified with organic siloxanes and aziridine crosslinker were synthesized and applied as coating of controlled release fertilizer. The free films were characterized and the nutrient release pro-files of the coated fertilizers were determined. The results show that methyl silicone oil and methylsilanolate so-dium could not improve water resistance performance and glass transition temperature Tg of coatings, while the firmness is enhanced. Aziridine crosslinker improves the water resistance performance, firmness and Tg. Incorpo-ration of methyl silicone oil and aziridine crosslinker gives an excellent aqueous acrylic emulsion for coated con-trol ed release fertilizer, with the 30-day cumulative nutrient release reduced to 16%and an estimated nutrient release duration over 190 days. Therefore, this waterborne coating is promising to meet the requirements for controlled release of nutrient and environmental protection.

  14. Munc13 controls the location and efficiency of dense-core vesicle release in neurons.

    van de Bospoort, Rhea; Farina, Margherita; Schmitz, Sabine K; de Jong, Arthur; de Wit, Heidi; Verhage, Matthijs; Toonen, Ruud F


    Neuronal dense-core vesicles (DCVs) contain diverse cargo crucial for brain development and function, but the mechanisms that control their release are largely unknown. We quantified activity-dependent DCV release in hippocampal neurons at single vesicle resolution. DCVs fused preferentially at synaptic terminals. DCVs also fused at extrasynaptic sites but only after prolonged stimulation. In munc13-1/2-null mutant neurons, synaptic DCV release was reduced but not abolished, and synaptic preference was lost. The remaining fusion required prolonged stimulation, similar to extrasynaptic fusion in wild-type neurons. Conversely, Munc13-1 overexpression (M13OE) promoted extrasynaptic DCV release, also without prolonged stimulation. Thus, Munc13-1/2 facilitate DCV fusion but, unlike for synaptic vesicles, are not essential for DCV release, and M13OE is sufficient to produce efficient DCV release extrasynaptically.

  15. Predicting release and transport of pesticides from a granular formulation during unsaturated diffusion in porous media

    Paradelo Pérez, Marcos; Soto-Gómez, Diego; Pérez-Rodrígez, Paula


    The release and transport of active ingredients (AIs) from controlled-release formulations (CRFs) have potential to reduce groundwater pesticide pollution. These formulations have a major effect on the release rate and subsequent transport to groundwater. Therefore the influence of CRFs should...... be included in modeling non-point source pollution by pesticides. We propose a simplified approach that uses a phase transition equation coupled to the diffusion equation that describes the release rate of AIs from commercial CRFs in porous media; the parameters are as follows: a release coefficient......, the solubility of the AI, and diffusion transport with decay. The model gives acceptable predictions of the pesticides release from commercial CRFs in diffusion cells filled with quartz sand. This approach can be used to study the dynamics of the CRF-porous media interaction. It also could be implemented in fate...

  16. APP and APLP2 interact with the synaptic release machinery and facilitate transmitter release at hippocampal synapses

    Fanutza, Tomas; Del Prete, Dolores; Ford, Michael J; Castillo, Pablo E; D’Adamio, Luciano


    The amyloid precursor protein (APP), whose mutations cause familial Alzheimer’s disease, interacts with the synaptic release machinery, suggesting a role in neurotransmission. Here we mapped this interaction to the NH2-terminal region of the APP intracellular domain. A peptide encompassing this binding domain -named JCasp- is naturally produced by a γ-secretase/caspase double-cut of APP. JCasp interferes with the APP-presynaptic proteins interaction and, if linked to a cell-penetrating peptide, reduces glutamate release in acute hippocampal slices from wild-type but not APP deficient mice, indicating that JCasp inhibits APP function.The APP-like protein-2 (APLP2) also binds the synaptic release machinery. Deletion of APP and APLP2 produces synaptic deficits similar to those caused by JCasp. Our data support the notion that APP and APLP2 facilitate transmitter release, likely through the interaction with the neurotransmitter release machinery. Given the link of APP to Alzheimer’s disease, alterations of this synaptic role of APP could contribute to dementia. DOI: PMID:26551565

  17. APP and APLP2 interact with the synaptic release machinery and facilitate transmitter release at hippocampal synapses.

    Fanutza, Tomas; Del Prete, Dolores; Ford, Michael J; Castillo, Pablo E; D'Adamio, Luciano


    The amyloid precursor protein (APP), whose mutations cause familial Alzheimer's disease, interacts with the synaptic release machinery, suggesting a role in neurotransmission. Here we mapped this interaction to the NH2-terminal region of the APP intracellular domain. A peptide encompassing this binding domain -named JCasp- is naturally produced by a γ-secretase/caspase double-cut of APP. JCasp interferes with the APP-presynaptic proteins interaction and, if linked to a cell-penetrating peptide, reduces glutamate release in acute hippocampal slices from wild-type but not APP deficient mice, indicating that JCasp inhibits APP function.The APP-like protein-2 (APLP2) also binds the synaptic release machinery. Deletion of APP and APLP2 produces synaptic deficits similar to those caused by JCasp. Our data support the notion that APP and APLP2 facilitate transmitter release, likely through the interaction with the neurotransmitter release machinery. Given the link of APP to Alzheimer's disease, alterations of this synaptic role of APP could contribute to dementia.

  18. Nuclear energy release from fragmentation

    Li, Cheng [The Key Laboratory of Beam Technology and Material Modification of Ministry of Education, College of Nuclear Science and Technology, Beijing Normal University, Beijing 100875 (China); Beijing Radiation Center, Beijing 100875 (China); Souza, S.R. [Instituto de Física, Universidade Federal do Rio de Janeiro Cidade Universitária, Caixa Postal 68528, 21945-970 Rio de Janeiro (Brazil); Tsang, M.B. [The Key Laboratory of Beam Technology and Material Modification of Ministry of Education, College of Nuclear Science and Technology, Beijing Normal University, Beijing 100875 (China); Beijing Radiation Center, Beijing 100875 (China); National Superconducting Cyclotron Laboratory and Physics and Astronomy Department, Michigan State University, East Lansing, MI 48824 (United States); Zhang, Feng-Shou, E-mail: [The Key Laboratory of Beam Technology and Material Modification of Ministry of Education, College of Nuclear Science and Technology, Beijing Normal University, Beijing 100875 (China); Beijing Radiation Center, Beijing 100875 (China); Center of Theoretical Nuclear Physics, National Laboratory of Heavy Ion Accelerator of Lanzhou, Lanzhou 730000 (China)


    It is well known that binary fission occurs with positive energy gain. In this article we examine the energetics of splitting uranium and thorium isotopes into various numbers of fragments (from two to eight) with nearly equal size. We find that the energy released by splitting {sup 230,232}Th and {sup 235,238}U into three equal size fragments is largest. The statistical multifragmentation model (SMM) is applied to calculate the probability of different breakup channels for excited nuclei. By weighing the probability distributions of fragment multiplicity at different excitation energies, we find the peaks of energy release for {sup 230,232}Th and {sup 235,238}U are around 0.7–0.75 MeV/u at excitation energy between 1.2 and 2 MeV/u in the primary breakup process. Taking into account the secondary de-excitation processes of primary fragments with the GEMINI code, these energy peaks fall to about 0.45 MeV/u.

  19. Nuclear energy release from fragmentation

    Li, Cheng; Souza, S. R.; Tsang, M. B.; Zhang, Feng-Shou


    It is well known that binary fission occurs with positive energy gain. In this article we examine the energetics of splitting uranium and thorium isotopes into various numbers of fragments (from two to eight) with nearly equal size. We find that the energy released by splitting 230,232Th and 235,238U into three equal size fragments is largest. The statistical multifragmentation model (SMM) is applied to calculate the probability of different breakup channels for excited nuclei. By weighing the probability distributions of fragment multiplicity at different excitation energies, we find the peaks of energy release for 230,232Th and 235,238U are around 0.7-0.75 MeV/u at excitation energy between 1.2 and 2 MeV/u in the primary breakup process. Taking into account the secondary de-excitation processes of primary fragments with the GEMINI code, these energy peaks fall to about 0.45 MeV/u.

  20. Nanoparticle release from dental composites.

    Van Landuyt, K L; Hellack, B; Van Meerbeek, B; Peumans, M; Hoet, P; Wiemann, M; Kuhlbusch, T A J; Asbach, C


    Dental composites typically contain high amounts (up to 60 vol.%) of nanosized filler particles. There is a current concern that dental personnel (and patients) may inhale nanosized dust particles (composite dust was analyzed in real work conditions. Exposure measurements of dust in a dental clinic revealed high peak concentrations of nanoparticles in the breathing zone of both dentist and patient, especially during aesthetic treatments or treatments of worn teeth with composite build-ups. Further laboratory assessment confirmed that all tested composites released very high concentrations of airborne particles in the nanorange (>10(6)cm(-3)). The median diameter of airborne composite dust varied between 38 and 70 nm. Electron microscopic and energy dispersive X-ray analysis confirmed that the airborne particles originated from the composite, and revealed that the dust particles consisted of filler particles or resin or both. Though composite dust exhibited no significant oxidative reactivity, more toxicological research is needed. To conclude, on manipulation with the bur, dental composites release high concentrations of nanoparticles that may enter deeply into the lungs. Copyright © 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.