Sample records for release significantly decreased

  1. Blue-blocking IOLs decrease photoreception without providing significant photoprotection.

    Mainster, Martin A; Turner, Patricia L


    Violet and blue light are responsible for 45% of scotopic, 67% of melanopsin, 83% of human circadian (melatonin suppression) and 94% of S-cone photoreception in pseudophakic eyes (isoilluminance source). Yellow chromophores in blue-blocking intraocular lenses (IOLs) eliminate between 43 and 57% of violet and blue light between 400 and 500 nm, depending on their dioptric power. This restriction adversely affects pseudophakic photopic luminance contrast, photopic S-cone foveal threshold, mesopic contrast acuity, scotopic short-wavelength sensitivity and circadian photoreception. Yellow IOL chromophores provide no tangible clinical benefits in exchange for the photoreception losses they cause. They fail to decrease disability glare or improve contrast sensitivity. Most epidemiological evidence shows that environmental light exposure and cataract surgery are not significant risk factors for the progression of age-related macular degeneration (AMD). Thus, the use of blue-blocking IOLs is not evidence-based medicine. Most AMD occurs in phakic adults over 60 years of age, despite crystalline lens photoprotection far greater than that of blue-blocking IOLs. Therefore, if light does play some role in the pathogenesis of AMD, then 1) senescent crystalline lenses do not prevent it, so neither can blue-blocking IOLs that offer far less photoprotection, and 2) all pseudophakes should wear sunglasses in bright environments. Pseudophakes have the freedom to remove their sunglasses for optimal photoreception whenever they choose to do so, provided that they are not encumbered permanently by yellow IOL chromophores. In essence, yellow chromophores are placebos for prevention of AMD that permanently restrict a pseudophake's dim light and circadian photoreception at ages when they are needed most. If yellow IOLs had been the standard of care, then colorless UV-blocking IOLs could be advocated now as "premium" IOLs because they offer dim light and circadian photoreception roughly 15

  2. EPA Analysis Shows 2014 Decrease of Toxic Chemical Releases in Maine

    EPA's most recent Toxic Release Inventory (TRI) data is now available for the reporting year of 2014. In Maine, the reporting data show that overall releases of pollutants to the environment decreased since the previous reporting year (2013).

  3. EPA Analysis Shows 2014 Decrease of Toxic Chemical Releases in Massachusetts

    EPA’s most recent Toxic Release Inventory (TRI) data is now available for the reporting year of 2014. In Massachusetts, the reporting data show that overall releases of pollutants to the environment decreased since the previous reporting year (2013).

  4. EPA Analysis Shows 2014 Decrease of Toxic Chemical Releases in Connecticut

    EPA’s most recent Toxic Release Inventory (TRI) data is now available for the reporting year of 2014. In Connecticut, the reporting data show that overall releases of pollutants to the environment decreased since the previous reporting year (2013).

  5. Upregulating Nonneuronal Cholinergic Activity Decreases TNF Release from Lipopolysaccharide-Stimulated RAW264.7 Cells

    Yi Lv


    Full Text Available Nonneuronal cholinergic system plays a primary role in maintaining homeostasis. It has been proved that endogenous neuronal acetylcholine (ACh could play an anti-inflammatory role, and exogenous cholinergic agonists could weaken macrophages inflammatory response to lipopolysaccharide (LPS stimulation through activation of α7 subunit-containing nicotinic acetylcholine receptor (α7nAChR. We assumed that nonneuronal cholinergic system existing in macrophages could modulate inflammation through autocrine ACh and expressed α7nAChR on the cells. Therefore, we explored whether LPS continuous stimulation could upregulate the nonneuronal cholinergic activity in macrophages and whether increasing autocrine ACh could decrease TNF release from the macrophages. The results showed that, in RAW264.7 cells incubated with LPS for 20 hours, the secretion of ACh was significantly decreased at 4 h and then gradually increased, accompanied with the enhancement of α7nAChR expression level. The release of TNF was greatly increased from RAW264.7 cells at 4 h and 8 h exposure to LPS; however, it was suppressed at 20 h. Upregulating choline acetyltransferase (ChAT expression through ChAT gene transfection could enhance ACh secretion and reduce TNF release from the infected RAW264. 7cells. The results indicated that LPS stimulation could modulate the activity of nonneuronal cholinergic system of RAW264.7 cells. Enhancing autocrine ACh production could attenuate TNF release from RAW264.7 cells.

  6. C1-Inhibitor Decreases the Release of Vasculitis-Like Chemotactic Endothelial Microvesicles.

    Mossberg, Maria; Ståhl, Anne-Lie; Kahn, Robin; Kristoffersson, Ann-Charlotte; Tati, Ramesh; Heijl, Caroline; Segelmark, Mårten; Leeb-Lundberg, L M Fredrik; Karpman, Diana


    The kinin system is activated during vasculitis and may contribute to chronic inflammation. C1-inhibitor is the main inhibitor of the kinin system. In this study, we investigated the presence of the kinin B1 receptor on endothelial microvesicles and its contribution to the inflammatory process. Compared with controls (n=15), patients with acute vasculitis (n=12) had markedly higher levels of circulating endothelial microvesicles, identified by flow cytometry analysis, and significantly more microvesicles that were positive for the kinin B1 receptor (Pmicrovesicles from wild-type cells, B1 receptor-positive microvesicles derived from transfected human embryonic kidney cells induced a significant neutrophil chemotactic effect, and a B1 receptor antagonist blocked this effect. Likewise, patient plasma induced neutrophil chemotaxis, an effect decreased by reduction of microvesicle levels and by blocking the B1 receptor. We used a perfusion system to study the effect of patient plasma (n=6) and control plasma (n=6) on the release of microvesicles from glomerular endothelial cells. Patient samples induced the release of significantly more B1 receptor-positive endothelial microvesicles than control samples, an effect abrogated by reduction of the microvesicles in the perfused samples. Perfusion of C1-inhibitor-depleted plasma over glomerular endothelial cells promoted excessive release of B1 receptor-positive endothelial microvesicles compared with normal plasma, an effect significantly decreased by addition of C1-inhibitor or B1 receptor-antagonist. Thus, B1 receptor-positive endothelial microvesicles may contribute to chronic inflammation by inducing neutrophil chemotaxis, and the reduction of these microvesicles by C1-inhibitor should be explored as a potential treatment for neutrophil-induced inflammation. Copyright © 2017 by the American Society of Nephrology.

  7. EPA Analysis Shows 2014 Decrease of Toxic Chemical Releases in New Hampshire

    EPA’s most recent Toxic Release Inventory (TRI) data is now available for the reporting year of 2014. In New Hampshire, the reporting data show that overall releases of pollutants to the environment decreased since the previous reporting year (2013).

  8. Decreased atmospheric sulfur deposition across the southeastern U.S.: When will watersheds release stored sulfate?

    Rice, Karen C.; Scanlon, Todd M.; Lynch, Jason A.; Cosby, Bernard J.


    Emissions of sulfur dioxide (SO2) to the atmosphere lead to atmospheric deposition of sulfate (SO42-), which is the dominant strong acid anion causing acidification of surface waters and soils in the eastern United States (U.S.). Since passage of the Clean Air Act and its Amendments, atmospheric deposition of SO2 in this region has declined by over 80%, but few corresponding decreases in stream-water SO42- concentrations have been observed in unglaciated watersheds. We calculated SO42- mass balances for 27 forested, unglaciated watersheds from Pennsylvania to Georgia, by using total atmospheric deposition (wet plus dry) as input. Many of these watersheds still retain SO42-, unlike their counterparts in the northeastern U.S. and southern Canada. Our analysis showed that many of these watersheds should convert from retaining to releasing SO42- over the next two decades. The specific years when the watersheds crossover from retaining to releasing SO42- correspond to a general geographical pattern of later net watershed release from north to south. The single most important variable that explained the crossover year was the runoff ratio, defined as the ratio of annual mean stream discharge to precipitation. Percent clay content and mean soil depth were secondary factors in predicting crossover year. The conversion of watersheds from net SO42- retention to release anticipates more widespread reductions in stream-water SO42- concentrations in this region.

  9. Decreased absorption as a possible cause for the lower bioavailability of a sustained-release propranolol.

    Takahashi, H; Ogata, H; Warabioka, R; Kashiwada, K; Ohira, M; Someya, K


    The influence of sustained absorption on the oral availability of propranolol (P) and the metabolic disposition of P were investigated by obtaining the partial metabolic clearances (CLm) following long-acting P (LA) dosing in comparison with the conventional propranolol tablet (CP). Ten healthy volunteers were given a single oral dose of an LA capsule (60 mg) and CP (20 mg x 3) using a crossover design. Blood and urine samples were collected over 24- and 48-h postdose periods, respectively. Concentrations of P, propranolol glucuronide (PG), 4-hydroxypropranolol (4P), 4-hydroxypropranolol glucuronide (4PG), 4-hydroxypropranolol sulfate (4PS), and naphthoxylactic acid (NLA) were determined by HPLC with fluorescence and UV detection. Significant differences were observed between LA and CP in the area under the plasma concentration-time curves (AUCs) for P, PG, and NLA and in the amounts excreted into urine (Ae) for all measured metabolites (i.e., PG, 4P, 4PG, 4PS, and NLA). The parallel decrease of the AUC for P and the excreted amounts of all measured metabolites following LA dosing resulted in partial metabolic clearances (CLm) and renal clearances (CL) for P and its metabolites that were similar to those observed for CP. Therefore, the hepatic metabolism of P would not be affected by the slower absorption at a single oral dose of 60 mg. These results indicate that the poor absorption of P from the gastrointestinal tract might be one of the factors causing the low bioavailability of P observed after administration of the sustained-release formulation.

  10. Krill oil significantly decreases 2-arachidonoylglycerol plasma levels in obese subjects.

    Banni, Sebastiano; Carta, Gianfranca; Murru, Elisabetta; Cordeddu, Lina; Giordano, Elena; Sirigu, Anna Rita; Berge, Kjetil; Vik, Hogne; Maki, Kevin C; Di Marzo, Vincenzo; Griinari, Mikko


    We have previously shown that krill oil (KO), more efficiently than fish oil, was able to downregulate the endocannabinoid system in different tissues of obese zucker rats.We therefore aimed at investigating whether an intake of 2 g/d of either KO or menhaden oil (MO), which provides 309 mg/d of EPA/DHA 2:1 and 390 mg/d of EPA/DHA 1:1 respectively, or olive oil (OO) for four weeks, is able to modify plasma endocannabinoids in overweight and obese subjects.The results confirmed data in the literature describing increased levels of endocannabinoids in overweight and obese with respect to normo-weight subjects. KO, but not MO or OO, was able to significantly decrease 2-arachidonoylglycerol (2-AG), although only in obese subjects. In addition, the decrease of 2-AG was correlated to the plasma n-6/n-3 phospholipid long chain polyunsaturated fatty acid (LCPUFA) ratio. These data show for the first time in humans that relatively low doses of LCPUFA n-3 as KO can significantly decrease plasma 2-AG levels in obese subjects in relation to decrease of plasma phospholipid n-6/n-3 LCPUFA ratio. This effect is not linked to changes of metabolic syndrome parameters but is most likely due to a decrease of 2-AG biosynthesis caused by the replacement of 2-AG ultimate precursor, arachidonic acid, with n-3 PUFAs, as previously described in obese Zucker rats.

  11. Krill oil significantly decreases 2-arachidonoylglycerol plasma levels in obese subjects

    Giordano Elena


    Full Text Available Abstract We have previously shown that krill oil (KO, more efficiently than fish oil, was able to downregulate the endocannabinoid system in different tissues of obese zucker rats. We therefore aimed at investigating whether an intake of 2 g/d of either KO or menhaden oil (MO, which provides 309 mg/d of EPA/DHA 2:1 and 390 mg/d of EPA/DHA 1:1 respectively, or olive oil (OO for four weeks, is able to modify plasma endocannabinoids in overweight and obese subjects. The results confirmed data in the literature describing increased levels of endocannabinoids in overweight and obese with respect to normo-weight subjects. KO, but not MO or OO, was able to significantly decrease 2-arachidonoylglycerol (2-AG, although only in obese subjects. In addition, the decrease of 2-AG was correlated to the plasma n-6/n-3 phospholipid long chain polyunsaturated fatty acid (LCPUFA ratio. These data show for the first time in humans that relatively low doses of LCPUFA n-3 as KO can significantly decrease plasma 2-AG levels in obese subjects in relation to decrease of plasma phospholipid n-6/n-3 LCPUFA ratio. This effect is not linked to changes of metabolic syndrome parameters but is most likely due to a decrease of 2-AG biosynthesis caused by the replacement of 2-AG ultimate precursor, arachidonic acid, with n-3 PUFAs, as previously described in obese Zucker rats.

  12. A significant decrease in diagnosis of primary progressive multiple sclerosis: A cohort study.

    Westerlind, Helga; Stawiarz, Leszek; Fink, Katharina; Hillert, Jan; Manouchehrinia, Ali


    Several reports indicate changes to prevalence, incidence, female-to-male ratio in multiple sclerosis. Diagnostic criteria, course definitions and clinical management of the disease have also undergone change during the recent decades. To investigate temporal trends in the diagnosis of primary progressive multiple sclerosis (PPMS) in Sweden. Through the Swedish MS registry we investigated the proportion of PPMS diagnosis in birth, diagnosis and age period cohorts using Poisson regression. A total of 16,915 patients were categorised into six birth-cohorts from 1946 to 1975 and seven date-of-diagnosis-cohorts from 1980 to 2014. We observed a decrease in the uncorrected analysis of diagnosis of PPMS from 19.2% to 2.2% and an average decrease of 23% (p decrease per diagnosis-cohort was seen. In the age-specific diagnosis period cohorts the same decreasing trend of PPMS diagnosis was observed in almost all groups. The diagnosis of PPMS has significantly decreased in Sweden specifically after introduction of disease-modifying treatments. Such decrease can have severe impacts on the future research on PPMS. Our data also suggest that the current trend to emphasise presence or absence of inflammatory activity is already reflected in clinical practice. © The Author(s), 2016.


    Jing Zhao; Yi Zhang; Edmond Ⅰ. Eger Ⅱ; James Sonner


    Objective To evaluate the effect of intrathecal administration of glycine on the minimum alveolar concentration (MAC) of isoflurane in rats.Methods Intrathecal catheters were implanted in 40 adult male rats anesthetized with isoflurane. Baseline MAC of isoflurane was measured during the infusion of artificial cerebrospinal fluid (CSF) alone. Subsequently, 10, 40, 80,160, and 300 mmol/L of glycine dissolved in artificial CSF were infused for two hours at the same rate as under control conditions, and MAC for isoflurane was re-determined.Results Intrathecal administration of glycine produced a significant, dose-dependent decrease in MAC for isoflu-rane (upto -65.2% ±16.2%).Conclusisons Intrathecal administration of glycine decreases anesthetic requirement. This result supports the idea that glycine receptors may be important to the immobilizing effect of anesthetics that enhance glycine receptor function such as isoflurane.

  14. Decreased diversion by doctor-shopping for a reformulated extended release oxycodone product (OxyContin).

    Chilcoat, Howard D; Coplan, Paul M; Harikrishnan, Venkatesh; Alexander, Louis


    Doctor-shopping (obtaining prescriptions from multiple prescribers/pharmacies) for opioid analgesics produces a supply for diversion and abuse, and represents a major public health issue. An open cohort study assessed changes in doctor-shopping in the U.S. for a brand extended release (ER) oxycodone product (OxyContin) and comparator opioids before (July, 2009 to June, 2010) versus after (January, 2011 to June, 2013) introduction of reformulated brand ER oxycodone with abuse-deterrent properties, using IMS LRx longitudinal data covering >150 million patients and 65% of retail U.S. prescriptions. After its reformulation, the rate of doctor-shopping decreased 50% (for 2+ prescribers/3+ pharmacies) for brand ER oxycodone, but not for comparators. The largest decreases in rates occurred among young adults (73%), those paying with cash (61%) and those receiving the highest available dose (62%), with a 90% decrease when stratifying by all three characteristics. The magnitude of doctor-shopping reductions increased with increasing number of prescribers/pharmacies (e.g., 75% reduction for ≥2 prescribers/≥4 pharmacies). The rate of doctor-shopping for brand ER oxycodone decreased substantially after its reformulation, which did not occur for other prescription opioids. The largest reductions in doctor-shopping occurred with characteristics associated with higher abuse risk such as youth, cash payment and high dose, and with more specific thresholds of doctor-shopping. A higher prescriber and/or pharmacy threshold also increased the magnitude of the decrease, suggesting that it better captured the effect of the reformulation on actual doctor-shoppers. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  15. Vagotomy diminishes obesity in cafeteria rats by decreasing cholinergic potentiation of insulin release.

    Balbo, Sandra Lucinei; Ribeiro, Rosane Aparecida; Mendes, Mariana Carla; Lubaczeuski, Camila; Maller, Ana Claudia Paiva Alegre; Carneiro, Everardo Magalhães; Bonfleur, Maria Lúcia


    Herein, we investigated whether subdiaphragmatic vagotomy has benefits on obesity, body glucose homeostasis, and insulin secretion in cafeteria (CAF)-obese rats. Wistar rats were fed a standard or CAF diet for 12 weeks. Subsequently, CAF rats were randomly submitted to truncal vagotomy (CAF Vag) or sham operation (CAF Sham). CAF Sham rats were hyperphagic, obese, and presented metabolic disturbances, including hyperinsulinemia, glucose intolerance, insulin resistance, hyperglycemia, and hypertriglyceridemia. Twelve weeks after vagotomy, CAF Vag rats presented reductions in body weight and perigonadal fat stores. Vagotomy did not modify glucose tolerance but normalized fed glycemia, insulinemia, and insulin sensitivity. Isolated islets from CAF Sham rats secreted more insulin in response to the cholinergic agent, carbachol, and when intracellular cyclic adenine monophosphate (cAMP) is enhanced by forskolin or 3-isobutyl-1-methylxanthine. Vagotomy decreased glucose-induced insulin release due to a reduction in the cholinergic action on β-cells. This effect also normalized islet secretion in response to cAMP. Therefore, vagotomy in rats fed on a CAF-style diet effectively decreases adiposity and restores insulin sensitivity. These effects were mainly associated with the lack of cholinergic action on the endocrine pancreas, which decreases insulinemia and may gradually reduce fat storage and improve insulin sensitivity.

  16. The long sunspot cycle 23 predicts a significant temperature decrease in cycle 24

    Solheim, Jan-Erik; Humlum, Ole


    Relations between the length of a sunspot cycle and the average temperature in the same and the next cycle are calculated for a number of meteorological stations in Norway and in the North Atlantic region. No significant trend is found between the length of a cycle and the average temperature in the same cycle, but a significant negative trend is found between the length of a cycle and the temperature in the next cycle. This provides a tool to predict an average temperature decrease of at least 1.0 "C from solar cycle 23 to 24 for the stations and areas analyzed. We find for the Norwegian local stations investigated that 25-56% of the temperature increase the last 150 years may be attributed to the Sun. For 3 North Atlantic stations we get 63-72% solar contribution. This points to the Atlantic currents as reinforcing a solar signal.

  17. Intensity of HLA-A2 Expression Significantly Decreased in Occult Hepatitis B Infection.

    Askari, Azam; Hassanshahi, Gholam Hossein; Ghalebi, Seyed Razi; Jafarzadeh, Abdollah; Mohit, Maryam; Hajghani, Masomeh; Kazemi Arababadi, Mohammad


    Occult hepatitis B infected (OBI) patients cannot eradicate hepatitis B virus (HBV)-DNA from their liver and peripheral blood, completely. The main aim of this study was to investigate the rate of HLA-A2 expression on peripheral blood mononuclear cells (PBMCs) of patients with OBI. In this experimental study, intensity of HLA-A2 was measured on the PBMCs of 57 OBI patients and 100 HBsAg-/anti-HBc+/HBV-DNA samples were enrolled as controls; measurements were performed using the flow cytometry technique. Flow cytometric analysis indicated that 19 (33.3%) OBI patients and 28 (28%) controls expressed HLA-A2 antigen on their PBMCs. There was no significant difference between the two groups regarding the rate of individuals expressing HLA-A2 antigen. Statistical analyses showed that the intensity of HLA-A2 expression significantly decreased in OBI patients (3.58 ± 0.1) in comparison to healthy controls (4.21 ± 0.25; P < 0.001). According to these results it can be concluded that decreased intensity of HLA-A2 on the PBMCs of OBI patients may lead to resistance of HBV in the patients.

  18. Bioactive dietary polyphenols decrease heme iron absorption by decreasing basolateral iron release in human intestinal Caco-2 cells.

    Ma, Qianyi; Kim, Eun-Young; Han, Okhee


    Because dietary polyphenolic compounds have a wide range of effects in vivo and vitro, including chelation of metals such as iron, it is prudent to test whether the regular consumption of dietary bioactive polyphenols impair the utilization of dietary iron. Because our previous study showed the inhibitory effect of (-) -epigallocatechin-3-gallate (EGCG) and grape seed extract (GSE) on nonheme iron absorption, we investigated whether EGCG and GSE also affect iron absorption from heme. The fully differentiated intestinal Caco-2 cells grown on microporous membrane inserts were incubated with heme (55)Fe in uptake buffer containing EGCG or GSE in the apical compartment for 7 h. Both EGCG and GSE decreased (P heme-derived iron. However, apical heme iron uptake was increased (P heme (55)Fe, the transfer of iron across the intestinal basolateral membrane was extremely low, indicating that basolateral export was impaired by GSE. In contrast, EGCG moderately decreased the cellular assimilation of heme (55)Fe, but the basolateral iron transfer was extremely low, suggesting that the basolateral efflux of heme iron was also inhibited by EGCG. Expression of heme oxygenase, ferroportin, and hephaestin protein was not changed by EGCG and GSE. The apical uptake of heme iron was temperature dependent and saturable in fully differentiated Caco-2 cells. Our data show that bioactive dietary polyphenols inhibit heme iron absorption mainly by reducing basolateral iron exit rather than decreasing apical heme iron uptake in intestinal cells.

  19. L-carnitine significantly decreased aging of rat adipose tissue-derived mesenchymal stem cells.

    Mobarak, Halimeh; Fathi, Ezzatollah; Farahzadi, Raheleh; Zarghami, Nosratollah; Javanmardi, Sara


    Mesenchymal stem cells are undifferentiated cells that have the ability to divide continuously and tissue regeneration potential during the transplantation. Aging and loss of cell survival, is one of the main problems in cell therapy. Since the production of free radicals in the aging process is effective, the use of antioxidant compounds can help in scavenging free radicals and prevent the aging of cells. The aim of this study is evaluate the effects of L-carnitine (LC) on proliferation and aging of rat adipose tissue-derived mesenchymal stem cells (rADSC). rADSCs were isolated from inguinal region of 5 male Rattus rats. Oil red-O, alizarin red-S and toluidine blue staining were performed to evaluate the adipogenic, osteogenic and chondrogenic differentiation of rADSCs, respectively. Flow cytometric analysis was done for investigating the cell surface markers. The methyl thiazol tetrazolium (MTT) method was used to determine the cell proliferation of rADSCs following exposure to different concentrations of LC. rADSCs aging was evaluated by beta-galactosidase staining. The results showed significant proliferation of rADSCs 48 h after treatment with concentrations of 0.2 mM LC. In addition, in the presence of 0.2 mM LC, rADSCs appeared to be growing faster than control group and 0.2 mM LC supplementation could significantly decrease the population doubling time and aging of rADSCs. It seems that LC would be a good antioxidant to improve lifespan of rADSCs due to the decrease in aging.

  20. The magnitude and significance of Ca2+ domains for release of neurotransmitter.

    Aharon, S; Parnas, H; Parnas, I


    It is now widely accepted that localized high concentrations of Ca2+ (Ca2+ domains) play a major role in controlling the time course of neurotransmitter release. In the present work we calculate the magnitude and the time course of Ca2+ domains that evolve in the vicinity of a Ca2+ channel and an adjacent release site. In the calculations we consider a accurately dimensioned Ca2+ channel. Moreover, the Ca2+ current is continuously adjusted with regard to the accumulated intracellular Ca2+ and, in addition, endogenous buffers are considered. The calculations, carried out by the software FIDAP, based on finite element method, show that the Ca2+ concentrations achieved near the release sites are significantly lower than claimed by other investigators. Furthermore, we present arguments indicating that the Ca2+ domains, regardless of their magnitude, do not play a role in controlling the time course of release of neurotransmitter.

  1. Serum ionic fluoride concentrations are significantly decreased after treatment with alendronate in patients with osteoporosis.

    Sato, Hironori; Tanno, Kozo; Muro-oka, Genyoh; Itai, Kazuyoshi


    We determined serum ionic fluoride (SIF) concentrations before and after treatment of osteoporosis with alendronate to clarify whether SIF concentrations directly reflect a change in bone metabolism. A total of 45 postmenopausal women with primary osteoporosis who were treated with alendronate over a 6-month period were enrolled (mean age, 64.2 years). SIF concentrations were measured by the flow injection method with an ion-selective electrode. Concentrations of bone turnover markers (serum bone alkaline phosphatase, serum osteocalcin, serum type I collagen cross-linked N-telopeptide and urinary deoxypryridinoline) and lumbar spine BMD (LsBMD) were also measured. SIF, bone turnover markers and LsBMD before and after treatment were compared. Concentrations of SIF as well as concentrations of all bone turnover markers were significantly decreased after treatment: means (standard deviations) before and after treatment were 0.62 (0.13) and 0.32 (0.09) μmol/l, respectively (P<0.001) and the percent change was -46.3%. LsBMD was also significantly increased by 6.7% after treatment. The reduction of SIF concentrations is probably caused by inhibition of bone resorption due to the action of alendronate. The findings suggest that SIF concentrations directly reflect a change in bone metabolism. Copyright © 2011 Elsevier B.V. All rights reserved.

  2. Intravenous Iron Repletion Does Not Significantly Decrease Platelet Counts in CKD Patients with Iron Deficiency Anemia

    Neville R. Dossabhoy


    Full Text Available Purpose. We sought to investigate the effect of IV iron repletion on platelet (PLT counts in CKD patients with iron deficiency anemia (IDA. Methods. We conducted a retrospective chart review, including all patients with CKD and IDA who were treated with iron dextran total dose infusion (TDI between 2002 and 2007. Patient demographics were noted, and laboratory values for creatinine, hemoglobin (Hgb, iron stores and PLT were recorded pre- and post-dose. Results. 153 patients received a total of 251 doses of TDI (mean ± SD = 971 ± 175 mg; age years and Creatinine  mg/dL. All CKD stages were represented (stage 4 commonest. Hgb and Fe stores improved post-TDI (. There was a very mild decrease in PLT (pre-TDI 255 versus post-TDI 244, . The mild reduction in PLT after TDI remained non-significant ( when data was stratified by molecular weight (MW of iron dextran used (low versus high, as well as by dose administered (<1000 versus ≥1000 mg. Linear regression analysis between pre-dose PLT and Tsat and Fe showed R2 of 0.01 and 0.04, respectively. Conclusion. Correction of iron deficiency did not significantly lower PLT in CKD patients, regardless of MW or dose used. Correlation of PLT to severity of iron deficiency was very weak.

  3. Psyllium decreased serum glucose and glycosylated hemoglobin significantly in diabetic outpatients.

    Ziai, Seyed Ali; Larijani, Bagher; Akhoondzadeh, Shahin; Fakhrzadeh, Hossein; Dastpak, Arezoo; Bandarian, Fatemeh; Rezai, Afsaneh; Badi, Hassanali Naghdi; Emami, Tara


    Psyllium is a bulk-forming laxative and is high in both fiber and mucilage. The beneficial effect of dietary fiber in the management of type II diabetes, has not been totally demonstrated. The purpose of this study was to determine the plasma-lowering effects of 5.1g b.i.d. of psyllium husk fiber, as an adjunct to dietary and drug therapy on lipid and glucose levels, in patients with type II diabetes. Patients were randomly selected from an outpatient clinic of primary care to participate in a double-blind placebo-controlled study in which Plantago ovata Forsk., or placebo was given in combination with their anti-diabetic drugs. Forty-nine subjects were included in the study that were given diet counseling before the study and then followed for 8 weeks in the treatment period. Fasting plasma glucose (FBS) was measured every 2 weeks, and total plasma cholesterol (TC), LDL-cholesterol (LDL-C), HDL-cholesterol (HDL-C), triglyceride (TG), and insulin levels were measured every 4 weeks. Glycosylated hemoglobin (HbA1c) was also measured at the beginning and ending of the study. The test products (psyllium or placebo) were supplied to subjects in identically labeled foil packets containing a 5.1g dose of product, to consume two doses per day, half an hour before breakfast and dinner. Both products were well tolerated, with no serious adverse events related to treatment was reported in either. Better gastric tolerance to metformin was recorded in the psyllium group. FBS, and HbA1c, showed a significant reduction (p<0.05), whereas HDL-C increased significantly (p<0.05) following psyllium treatment. LDL/HDL ratio was significantly decreased (p<0.05). Our results show that 5.1g b.i.d. of psyllium for persons with type II diabetes is safe, well tolerated, and improves glycemic control.

  4. Fasting increases human skeletal muscle net phenylalanine release and this is associated with decreased mTOR signaling.

    Mikkel Holm Vendelbo

    Full Text Available Fasting is characterised by profound changes in energy metabolism including progressive loss of body proteins. The underlying mechanisms are however unknown and we therefore determined the effects of a 72-hour-fast on human skeletal muscle protein metabolism and activation of mammalian target of rapamycin (mTOR, a key regulator of cell growth.Eight healthy male volunteers were studied twice: in the postabsorptive state and following 72 hours of fasting. Regional muscle amino acid kinetics was measured in the forearm using amino acid tracers. Signaling to protein synthesis and breakdown were assessed in skeletal muscle biopsies obtained during non-insulin and insulin stimulated conditions on both examination days.Fasting significantly increased forearm net phenylalanine release and tended to decrease phenylalanine rate of disappearance. mTOR phosphorylation was decreased by ∼50% following fasting, together with reduced downstream phosphorylation of 4EBP1, ULK1 and rpS6. In addition, the insulin stimulated increase in mTOR and rpS6 phosphorylation was significantly reduced after fasting indicating insulin resistance in this part of the signaling pathway. Autophagy initiation is in part regulated by mTOR through ULK1 and fasting increased expression of the autophagic marker LC3B-II by ∼30%. p62 is degraded during autophagy but was increased by ∼10% during fasting making interpretation of autophagic flux problematic. MAFbx and MURF1 ubiquitin ligases remained unaltered after fasting indicating no change in protesomal protein degradation.Our results show that during fasting increased net phenylalanine release in skeletal muscle is associated to reduced mTOR activation and concomitant decreased downstream signaling to cell growth.

  5. Fasting Increases Human Skeletal Muscle Net Phenylalanine Release and This Is Associated with Decreased mTOR Signaling

    Vendelbo, Mikkel Holm; Møller, Andreas Buch; Christensen, Britt; Nellemann, Birgitte; Clasen, Berthil Frederik Forrest; Nair, K. Sreekumaran; Jørgensen, Jens Otto Lunde; Jessen, Niels; Møller, Niels


    Aim Fasting is characterised by profound changes in energy metabolism including progressive loss of body proteins. The underlying mechanisms are however unknown and we therefore determined the effects of a 72-hour-fast on human skeletal muscle protein metabolism and activation of mammalian target of rapamycin (mTOR), a key regulator of cell growth. Methods Eight healthy male volunteers were studied twice: in the postabsorptive state and following 72 hours of fasting. Regional muscle amino acid kinetics was measured in the forearm using amino acid tracers. Signaling to protein synthesis and breakdown were assessed in skeletal muscle biopsies obtained during non-insulin and insulin stimulated conditions on both examination days. Results Fasting significantly increased forearm net phenylalanine release and tended to decrease phenylalanine rate of disappearance. mTOR phosphorylation was decreased by ∼50% following fasting, together with reduced downstream phosphorylation of 4EBP1, ULK1 and rpS6. In addition, the insulin stimulated increase in mTOR and rpS6 phosphorylation was significantly reduced after fasting indicating insulin resistance in this part of the signaling pathway. Autophagy initiation is in part regulated by mTOR through ULK1 and fasting increased expression of the autophagic marker LC3B-II by ∼30%. p62 is degraded during autophagy but was increased by ∼10% during fasting making interpretation of autophagic flux problematic. MAFbx and MURF1 ubiquitin ligases remained unaltered after fasting indicating no change in protesomal protein degradation. Conclusions Our results show that during fasting increased net phenylalanine release in skeletal muscle is associated to reduced mTOR activation and concomitant decreased downstream signaling to cell growth. PMID:25020061

  6. (-)-Epigallocatechin-3-O-gallate (EGCG) attenuates the hemodynamics stimulated by caffeine through decrease of catecholamines release.

    Han, Jin-Yi; Moon, Yong-Jin; Han, Jong-Hyun; Kim, Jong-Hoon; Woo, Jae-Hoon; Yoo, Hwan-Soo; Hong, Jin Tae; Ahn, Hee-Yul; Hong, Jong-Myeon; Oh, Ki-Wan


    A human study of the effects on hemodynamics of caffeine and epigallocatechin-3-O-gallate (EGCG) was performed. Caffeine tablets (200 mg) were orally administered to healthy males aged between 25 and 35 years 30 min after oral administration of EGCG tablets (100 and 200 mg). The increase in BP induced by caffeine was inhibited when co-administrated with EGCG. We found that caffeine slightly decreased heart rate (HR) in the volunteers. Although EGCG enhanced HR reduction, the effect was not significant. In addition, caffeine increased blood catecholamine levels, but EGCG inhibited the increase in noradrenaline, adrenaline and dopamine levels induced by caffeine. Whether EGCG decreases the elevated HR and systolic perfusion pressure, and ventricular contractility induced by adrenergic agonists in the isolated rat heart was investigated. The modified Krebs-Henseleit solution was perfused through a Langendorff apparatus to the isolated hearts of rats. HR, systolic perfusion pressure, and developed maximal rates of contraction (+dP/dtmax) and relaxation (-dP/dtmax) were increased by epinephrine (EP) and isoproterenol (IP). In contrast, EGCG decreased the elevated HR, systolic perfusion pressure, and left ventricular ±dp/dtmax induced by EP and/or IP. In conclusion, EGCG could attenuate the hemodynamics stimulated by caffeine through decreasing catecholamine release.

  7. Significant decrease in prevalence of Helicobacter pylori in the Czech Republic

    Jan Bure(s); Marcela Kopá(c)ová; Ilona Koupil; Bohumil Seifert; Milu(s)ka (S)kodová Fendrichová; Jana (S)pirková; Viktor Vo(r)í(s)ek


    AIM:To study possible decrease in prevalence of Helicobacter pylori (H.pylori) infection in the Czech Republic within a 10-year period.METHODS:A total of 22 centres entered the study.The catchment areas of these centres covered cities and towns with more than 20 000 inhabitants,smaller towns (≤ 20 000 inhabitants) with surrounding villages and rural areas,and were spread over the whole country,corresponding well to the geographical distribution of the Czech population.A total of 1 837 subjects (aged 5-98 years) took part in the study,randomly selected out of 38 147 people from the general population.H.pylori infection was investigated by means of a 13C-urea breath test.Breath samples in duplicates were analysed using isotope ratio mass spectrometry.The cut-off point was 3.5.Social and demographic characteristics were based on data from self-completed questionnaires.RESULTS:The overall prevalence of H.pylori infection was 23.5% (430/1826),and 4.8% (20/420) in children aged 15 or less.There was no statistically significant difference in prevalence between males (24.3%; 208/857) and females (22.9%,222/969,P =0.494).H.pylori infection was strongly associated with higher age,among subjects aged 55+ years,prevalence of H.pylori infection was 39.8% (252/633,P <0.001).The highest prevalence of H.pylori infection was found among persons aged 55-64 years (43.9%,97/221) and 75+ years (37.9%,58/153).Among study subjects aged 15+ years,prevalence of H.pylori infection was significantly increased in those with lowest education (odds risk 3.19,95% CI 1.87-5.47).Compared to never married (14.1%),the prevalence of H.pylori infection was statistically significantly higher among married (35.4%,246/694,P < 0.001),divorced (36.8%,49/133,P < 0.001) and widowed study subjects (40.2%,45/112,P < 0.001),both in minimally and fully adjusted analysis.There was no significant difference in the prevalence of H.pylori infection between married and widowed

  8. Mildly oxidized HDL decrease agonist-induced platelet aggregation and release of pro-coagulant platelet extracellular vesicles.

    Tafelmeier, M; Fischer, A; Orsó, E; Konovalova, T; Böttcher, A; Liebisch, G; Matysik, S; Schmitz, G


    Stored platelet concentrates (PLCs) for therapeutic purpose, develop a platelet storage lesion (PSL), characterized by impaired platelet (PLT) viability and function, platelet extracellular vesicle (PL-EV) release and profound lipidomic changes. Whereas oxidized low-density lipoprotein (oxLDL) activates PLTs and promotes atherosclerosis, effects linked to oxidized high-density lipoprotein (oxHDL) are poorly characterized. PLCs from blood donors were treated with native (nHDL) or mildly oxidized HDL (moxHDL) for 5days under blood banking conditions. Flow cytometry, nanoparticle tracking analysis (NTA), aggregometry, immunoblot analysis and mass spectrometry were carried out to analyze PL-EV and platelet exosomes (PL-EX) release, PLT aggregation, protein expression, and PLT and plasma lipid composition. In comparison to total nHDL, moxHDL significantly decreased PL-EV release by -36% after 5days of PLT storage and partially reversed agonist-induced PLT aggregation. PL-EV release positively correlated with PLT aggregation. MoxHDL improved PLT membrane lipid homeostasis through enhanced uptake of lysophospholipids and their remodeling to corresponding phospholipid species. This also appeared for sphingomyelin (SM) and d18:0/d18:1 sphingosine-1-phosphate (S1P) at the expense of ceramide (Cer) and hexosylceramide (HexCer) leading to reduced Cer/S1P ratio as PLT-viability indicator. This membrane remodeling was associated with increased content of CD36 and maturation of scavenger receptor-B1 (SR-B1) protein in secreted PL-EVs. MoxHDL, more potently than nHDL, improves PLT-membrane lipid homeostasis, partially antagonizes PL-EV release and agonist-induced PLT aggregation. Altogether, this may be the result of more efficient phospho- and sphingolipid remodeling mediated by CD36 and SR-B1 in the absence of ABCA1 on PLTs. As in vitro supplement in PLCs, moxHDL has the potential to improve PLC quality and to prolong storage. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Neuronal calcium sensor-1 deletion in the mouse decreases motivation and dopamine release in the nucleus accumbens.

    Ng, Enoch; Varaschin, Rafael K; Su, Ping; Browne, Caleb J; Hermainski, Joanna; Le Foll, Bernard; Pongs, Olaf; Liu, Fang; Trudeau, Louis-Eric; Roder, John C; Wong, Albert H C


    Calcium sensors detect intracellular calcium changes and interact with downstream targets to regulate many functions. Neuronal Calcium Sensor-1 (NCS-1) or Frequenin is widely expressed in the nervous system, and involved in neurotransmission, synaptic plasticity and learning. NCS-1 interacts with and regulates dopamine D2 receptor (D2R) internalization and is implicated in disorders like schizophrenia and substance abuse. However, the role of NCS-1 in behaviors dependent on dopamine signaling in the striatum, where D2R is most highly expressed, is unknown. We show that Ncs-1 deletion in the mouse decreases willingness to work for food. Moreover, Ncs-1 knockout mice have significantly lower activity-dependent dopamine release in the nucleus accumbens core in acute slice recordings. In contrast, food preference, responding for conditioned reinforcement, ability to represent changes in reward value, and locomotor response to amphetamine are not impaired. These studies identify novel roles for NCS-1 in regulating activity-dependent striatal dopamine release and aspects of motivated behavior.

  10. Decreased TGF-β1 and VEGF Release in Cystic Fibrosis Platelets: Further Evidence for Platelet Defects in Cystic Fibrosis

    Maloney, James P.; Narasimhan, Jayashree; Biller, Julie


    Purpose Cystic fibrosis (CF) patients suffer from chronic lung inflammation. This inflammation may activate platelets. There are limited data on the role of platelet-secreted cytokines in CF. Platelet cytokines with inflammatory effects include vascular endothelial growth factor (VEGF) and transforming growth factor-β1 (TGF-β1). As levels of these cytokines are tenfold greater in serum than plasma due to platelet release, serum levels may be one index of platelet content; but a more specific index is release during the aggregation of isolated platelets. We postulated that altered release of these platelet cytokines occurs in CF. Methods We obtained sera and plasma from CF outpatients (n=21) and from healthy controls (n=20), measured VEGF and TGF-β1, assessed for correlations with platelet number, analyzed cytokine release during platelet aggregation to collagen, and analyzed differences in maximal platelet aggregation. Results Platelet number and maximal aggregation levels were higher in CF. Plasma and serum levels of TGF-β1 and VEGF were higher in CF, but these levels were similar after adjusting for platelet number (serum cytokines correlated with platelet count). The release of VEGF and TGF-β1 during aggregation was decreased in CF platelets (by 52% and 29%, respectively). Conclusion Platelet release is not a source of the elevated blood proinflammatory cytokines TGF-β1 and VEGF in CF, as platelets from CF patients actually release less of these cytokines. These data provide further evidence for platelet defects in CF. PMID:27423781

  11. Early Decrease in Respiration and Uncoupling Event Independent of Cytochrome c Release in PC12 Cells Undergoing Apoptosis

    Berghella, Libera; Ferraro, Elisabetta


    Cytochrome c is a key molecule in mitochondria-mediated apoptosis. It also plays a pivotal role in cell respiration. The switch between these two functions occurs at the moment of its release from mitochondria. This process is therefore extremely relevant for the fate of the cell. Since cytochrome c mediates respiration, we studied the changes in respiratory chain activity during the early stages of apoptosis in order to contribute to unravel the mechanisms of cytochrome c release. We found that, during staurosporine (STS)- induced apoptosis in PC12 cells, respiration is affected before the release of cytochrome c, as shown by a decrease in the endogenous uncoupled respiration and an uncoupling event, both occurring independently of cytochrome c release. The decline in the uncoupled respiration occurs also upon Bcl-2 overexpression (which inhibits cytochrome c release), while the uncoupling event is inhibited by Bcl-2. We also observed that the first stage of nuclear condensation during STS-induced apoptosis does not depend on the release of cytochrome c into the cytosol and is a reversibile event. These findings may contribute to understand the mechanisms affecting mitochondria during the early stages of apoptosis and priming them for the release of apoptogenic factors. PMID:22666257

  12. Significant decrease in yield under future climate conditions: Stability and production of 138 spring barley accessions

    Ingvordsen, Cathrine Heinz; Backes, Gunter; Lyngkjær, Michael Foged


    The response in production parameters to projected future levels of temperature, atmospheric carbondioxide ([CO2]), and ozone ([O3]) was investigated in 138 spring barley accessions. The comprehensive setof landraces, cultivars, and breeder-lines, were during their entire life cycle exposed...... to a two-factor treat-ment of combined elevated temperature (+5◦C day/night) and [CO2] (700 ppm), as well as single-factortreatments of elevated temperature (+5◦C day/night), [CO2] (700 ppm), and [O3] (100–150 ppb). Thecontrol treatment was equivalent to present average South Scandinavian climate...... (temperature: 19/12◦C(day/night), [CO2]: 385 ppm). Overall grain yield was found to decrease 29% in the two-factor treatmentwith concurrent elevation of [CO2] and temperature, and this response could not be predicted from theresults of treatments with elevated [CO2] and temperature as single factors, where...

  13. Significant decrease in congenital malformations in newborn infants of an unselected population of diabetic women

    Damm, P; Mølsted-Pedersen, L


    In an unselected and consecutive series of 1858 newborn infants of diabetic mothers, born in the Rigshospital, Copenhagen, in the period 1967 to 1986, congenital malformations were studied. The malformation rate in White Classes B to F was remarkably constant from 1967 to 1981, but a significant...

  14. Spore release of Bremia lactucae on lettuce is affected by timing of light initiation and decrease in relative humidity

    Su, H.; Bruggen, van A.H.C.; Subbarao, K.V.


    A suction-impaction mini-spore trap was developed to study the effect of light initiation and decreasing relative humidity (RH) on spore release of Bremia lactucae in a controlled environment. Three light periods (from 0400 to 1600, 0600 to 1800, and 0800 to 2000 h, circadian time) at a constant RH

  15. Apnea–hypopnea index decreased significantly after nasal surgery for obstructive sleep apnea

    Wu, Jun; Zhao, Guoqiang; Li, Yunchuan; Zang, Hongrui; Wang, Tong; Wang, Dongbo; Han, Demin


    Abstract Background: Nasal surgeries have been applied to obstructive sleep apnea (OSA) patients with nasal obstruction for decades. However, the efficiency of nasal surgery in improving OSA remains controversial. The aim of this study was to identify whether isolated nasal surgery can improve apnea–hypopnea index (AHI). Methods: Computerized searches were performed in MEDLINE, Web of Science, Cochrane Library, and Scopus from January 1, 2000 to April 30, 2016. A total of 18 articles and 587 participants were included. There were 1 randomized controlled trials, 2 nonrandomized trials, 11 prospective studies, and 4 retrospective studies. Data regarding study design (prospective/retrospective clinical trial, randomized, and controlled), population size, participant characteristics (age, gender, and body mass index), surgical intervention, and outcomes (AHI, Epworth sleep scale [ESS]) was collected. Results: Statistically significant improvement in AHI (subgroup 1: weighted mean difference [WMD] [95%confidence interval (CI)], −4.17 [−7.62, −0.73]; subgroup 2: WMD [95%CI], −4.19 [−7.51, −0.88]; overall: WMD [95%CI], −4.15 [−6.48, −1.82]) and ESS (subgroup 1: WMD [95%CI], −2.14 [−3.08, −1.19]; subgroup 2: WMD [95%CI], −4.70 [−5.95, −3.44]; overall: WMD [95%CI], −4.08 [−5.27, −2.88]) was revealed. Conclusion: Both AHI and ESS improved significantly after isolated nasal surgery, but the improvement of AHI is slightly significant. Future randomized controlled trials are needed to confirm the long-term benefits of nasal surgery on OSA. PMID:28151900

  16. Inactive corrinoid-compound significantly decreases in Spirulina platensis grown in a cobalt-deficient medium.

    Watanabe, F; Miyamoto, E; Nakano, Y


    Spirulina platensis NIES-39 was grown under open culture system in the presence or absence of CoSO(4) (12 microg/L) and/or vitamin B(12) (10 microg/L) to confirm whether CoSO(4) and/or vitamin B(12) stimulate or are essential for growth of the algal cells and for accumulation of vitamin B(12). The addition of CoSO(4) and/or vitamin B(12) could not affect both cell growth and cell yield of the alga. The amount of corrinoid-compound was increased significantly by the addition of CoSO(4) but not by vitamin B(12). A C18 reversed-phase HPLC pattern of the Spirulina corrinoid-compound increased by the addition of CoSO(4) was identical to that of authentic pseudovitamin B(12), which is inactive for human. These results indicate that the algal cells grown in the absence of CoSO(4) are suitable for use of human health foods because the inactive corrinoid-compound can be reduced significantly.

  17. A Novel Thin Film Nitinol Covered Neurovascular Stent Significantly Decreases Intra-Aneurysmal Flow In Vitro

    Chun, Youngjae; Hur, Soojung; Shayan, Mahdis; Kealey, Colin; Levi, Daniel; Mohanchandra, Kp; di Carlo, Dino; Carman, Gregory


    A novel thin film nitinol (TFN) stent has been developed to promote aneurysm quiescence by diminishing flow across the aneurysm's neck. Laboratory aneurysm models were used to assess the flow changes produced by stents covered with different patterns of TFN. Flow diversion stents were constructed by covering Wingspan stents (Boston Scientific, DxL:4x20mm) with TFNs (i.e., 77 and 82 percent porosity). The flow changes that occur after deployment of two different porous TFN covered stent in intracranial aneurysm models were evaluated in vitro. The 82 percent porous TFN covered stent reduced the intra-aneurysmal mean flow velocity by 86.42 percent, while a 77 percent porous TFN covered stent reduced to intra-aneurysmal mean flow velocity to 93.44 percent compared to a nonstented model. Local wall shear rates were also significantly reduced in wide-neck aneurysm model (i.e., 97.52 - 98.92 percent) with TFN stent placement. The results showed that TFN covered stents significantly reduced intra-aneurysmal flow velocity magnitudes and local wall shear rates. This suggests that TFN covered stents with both 77 and 82 percent porosity have great potential to promote thrombosis in both wide-necked and fusiform aneurysm sacs.

  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. Angiogenic activity in patients with psoriasis is significantly decreased by Goeckerman's therapy

    Andrys, C.; Borska, L.; Pohl, D.; Fiala, Z.; Hamakova, K.; Krejsek, J. [Faculty Hospital, Hradec Kralove (Czech Republic). Dept. of Clinical Immunology & Allergy


    Goeckerman's therapy (GT) of psoriasis is based on daily application of pharmacy grade coal tar on affected skin with subsequent exposure to UV light. Goeckerman's therapy is still the first line therapy of psoriasis in the Czech Republic because of its low cost and long-term efficacy. Disturbances in angiogenic activity are characteristic for the immunopathogenesis of psoriasis. An abnormal spectrum of cytokines, growth factors and proangiogenic mediators is produced by keratinocytes and inflammatory cells in patients suffering from the disease. The aim of this study was to evaluate the influence of GT of psoriasis on angiogenic activities by comparing serum levels of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in 44 patients with psoriasis in peripheral blood samples collected before and after therapy. It was found that the angiogenic potential which is abnormally increased in patients with psoriasis is significantly alleviated by GT.

  20. Moderate Hypothermia Significantly Decreases Hippocampal Cell Death Involving Autophagy Pathway after Moderate Traumatic Brain Injury.

    Jin, Yichao; Lin, Yingying; Feng, Jun-feng; Jia, Feng; Gao, Guo-yi; Jiang, Ji-yao


    Here, we evaluated changes in autophagy after post-traumatic brain injury (TBI) followed by moderate hypothermia in rats. Adult male Sprague-Dawley rats were randomly divided into four groups: sham injury with normothermia group (37 °C); sham injury with hypothermia group (32 °C); TBI with normothermia group (TNG; 37 °C); and TBI with hypothermia group (THG; 32 °C). Injury was induced by a fluid percussion TBI device. Moderate hypothermia (32 °C) was achieved by partial immersion in a water bath (0 °C) under general anesthesia for 4 h. All rats were killed at 24 h after fluid percussion TBI. The ipsilateral hippocampus in all rats was analyzed with hematoxylin and eosin staining; terminal deoxynucleoitidyl transferase-mediated nick end labeling staining was used to determine cell death in ipsilateral hippocampus. Immunohistochemistry and western blotting of microtubule-associated protein light chain 3 (LC3), Beclin-1, as well as transmission electron microscopy performed to assess changes in autophagy. At 24 h after TBI, the cell death index was 27.90 ± 2.36% in TNG and 14.90 ± 1.52% in THG. Expression level of LC3 and Beclin-1 were significantly increased after TBI and were further up-regulated after post-TBI hypothermia. Further, ultrastructural observations showed that there was a marked increase of autophagosomes and autolysosomes in ipsilateral hippocampus after post-TBI hypothermia. Our data demonstrated that moderate hypothermia significantly attenuated cell death and increased autophagy in ipsilateral hippocampus after fluid percussion TBI. In conclusion, autophagy pathway may participate in the neuroprotective effect of post-TBI hypothermia.

  1. Air Embolism During TEVAR: Carbon Dioxide Flushing Decreases the Amount of Gas Released from Thoracic Stent-Grafts During Deployment.

    Rohlffs, Fiona; Tsilimparis, Nikolaos; Saleptsis, Vasilis; Diener, Holger; Debus, E Sebastian; Kölbel, Tilo


    To investigate the amount of gas released from Zenith thoracic stent-grafts using standard saline flushing vs the carbon dioxide flushing technique. In an experimental bench setting, 20 thoracic stent-grafts were separated into 2 groups of 10 endografts. One group of grafts was flushed with 60 mL saline and the other group was flushed with carbon dioxide for 5 minutes followed by 60 mL saline. All grafts were deployed into a water-filled container with a curved plastic pipe; the deployment was recorded and released gas was measured using a calibrated setup. Gas was released from all grafts in both study groups during endograft deployment. The average amount of released gas per graft was significantly lower in the study group with carbon dioxide flushing (0.79 vs 0.51 mL, p=0.005). Thoracic endografts release significant amounts of air during deployment if flushed according to the instructions for use. Application of carbon dioxide for the flushing of thoracic stent-grafts prior to standard saline flush significantly reduces the amount of gas released during deployment. The additional use of carbon dioxide should be considered as a standard flush technique for aortic stent-grafts, especially in those implanted in proximal aortic segments, to reduce the risk of air embolism and stroke.

  2. Significance of decreased serum interleukin-10 levels in the progression of cerebral infarction.

    Diao, Zeng-Yan; Wang, Cui-Lan; Qi, Hong-Shun; Jia, Guo-Yong; Yan, Chuan-Zhu


    Anti-inflammatory cytokine and its serological detection may have an important role in the process of cardiovascular and cerebrovascular diseases. We investigated whether serum interleukin-10 (IL-10) is associated with cerebral infarction or not in the general population. Identified comprehensive searching was performed covering PubMed, EMBASE, Web of Science, Cochrane Library, CISCOM, CINAHL, Google Scholar, China BioMedicine, and China National Knowledge Infrastructure databases. Two reviewers extracted data and assessed studies independently. Information was extracted separately and classed into Asians and Caucasians. Summary standardized mean differences (SMDs) with 95 % confidence intervals (CI) were used with the utilization of Z test. Nine studies ranged from 2003 to 2014 were collected for meta-analysis. Results identified a negative association between serum IL-10 levels and cerebral infarction (SMD = 1.80, 95 % CI 0.79-2.81, P IL-10 level may be the main risk factor for cerebral infarction in India (SMD = 1.44, 95 % CI 1.13-1.75, P IL-10 levels were negatively correlated with cerebral infarction in Asians (SMD = 2.52, 95 % CI 0.47-4.57, P = 0.016), while not in Caucasians (P > 0.05). The lower serum IL-10 concentration was significantly associated with an increased likelihood of cerebral infarction in this meta-analysis. More prospective studies should be conducted to provide stronger evidence justifying the use of IL-10 as new biomarker to identify a predisposition toward cerebral infarction.

  3. Type 2 diabetes risk allele near CENTD2 is associated with decreased glucose-stimulated insulin release

    Nielsen, T; Sparsø, T; Grarup, N;


    By combining multiple genome-wide association (GWA) studies and comprehensive replication efforts, 12 novel type 2 diabetes associated loci have recently been discovered. Here we evaluate the effect of lead variants of these loci on estimates of insulin release and insulin resistance derived from...... an oral glucose tolerance test. We examined 12 lead variants in or near HMGA2, CENTD2 (also known as ARAP1), KLF14, PRC1, TP53INP1, ZBED3, ZFAND6, CHCHD9, DUSP9, KCNQ1, BCL11A and HNF1A in 5,722 middle-aged people from the population-based Inter99 sample. Carriers of the major diabetogenic allele of rs...... decreased BIGTT-AIR (2.6%, p = 0.01). No associations with intermediate metabolic traits were found in women. For the remaining ten lead variants no consistent associations were demonstrated. Of the lead variants from 12 novel type 2 diabetes associated loci, CENTD2 significantly associated with increased...

  4. Administration of caffeine inhibited adenosine receptor agonist-induced decreases in motor performance, thermoregulation, and brain neurotransmitter release in exercising rats.

    Zheng, Xinyan; Hasegawa, Hiroshi


    We examined the effects of an adenosine receptor agonist on caffeine-induced changes in thermoregulation, neurotransmitter release in the preoptic area and anterior hypothalamus, and endurance exercise performance in rats. One hour before the start of exercise, rats were intraperitoneally injected with either saline alone (SAL), 10 mg kg(-1) caffeine and saline (CAF), a non-selective adenosine receptor agonist (5'-N-ethylcarboxamidoadenosine [NECA]: 0.5 mg kg(-1)) and saline (NECA), or the combination of caffeine and NECA (CAF+NECA). Rats ran until fatigue on the treadmill with a 5% grade at a speed of 18 m min(-1) at 23 °C. Compared to the SAL group, the run time to fatigue (RTTF) was significantly increased by 52% following caffeine administration and significantly decreased by 65% following NECA injection (SAL: 91 ± 14.1 min; CAF: 137 ± 25.8 min; NECA: 31 ± 13.7 min; CAF+NECA: 85 ± 11.8 min; pcaffeine injection inhibited the NECA-induced decreases in the RTTF, Tcore, heat production, heat loss, and extracellular DA release. Neither caffeine nor NECA affected extracellular noradrenaline or serotonin release. These results support the findings of previous studies showing improved endurance performance and overrides in body limitations after caffeine administration, and imply that the ergogenic effects of caffeine may be associated with the adenosine receptor blockade-induced increases in brain DA release.

  5. Melatonin supplementation decreases prolactin synthesis and release in rat adenohypophysis: correlation with anterior pituitary redox state and circadian clock mechanisms.

    Jiménez-Ortega, Vanesa; Barquilla, Pilar Cano; Pagano, Eleonora S; Fernández-Mateos, Pilar; Esquifino, Ana I; Cardinali, Daniel P


    In the laboratory rat, a number of physiological parameters display seasonal changes even under constant conditions of temperature, lighting, and food availability. Since there is evidence that prolactin (PRL) is, among the endocrine signals, a major mediator of seasonal adaptations, the authors aimed to examine whether melatonin administration in drinking water resembling in length the exposure to a winter photoperiod could affect accordingly the 24-h pattern of PRL synthesis and release and some of their anterior pituitary redox state and circadian clock modulatory mechanisms. Melatonin (3 µg/mL drinking water) or vehicle was given for 1 mo, and rats were euthanized at six time intervals during a 24-h cycle. High concentrations of melatonin (>2000 pg/mL) were detected in melatonin-treated rats from beginning of scotophase (at 21:00 h) to early photophase (at 09:00 h) as compared with a considerably narrower high-melatonin phase observed in controls. By cosinor analysis, melatonin-treated rats had significantly decreased MESOR (24-h time-series average) values of anterior pituitary PRL gene expression and circulating PRL, with acrophases (peak time) located in the middle of the scotophase, as in the control group. Melatonin treatment disrupted the 24-h pattern of anterior pituitary gene expression of nitric oxide synthase (NOS)-1 and -2, heme oxygenase-1 and -2, glutathione peroxidase, glutathione reductase, Cu/Zn- and Mn-superoxide dismutase, and catalase by shifting their acrophases to early/middle scotophase or amplifying the maxima. Only the inhibitory effect of melatonin on pituitary NOS-2 gene expression correlated temporally with inhibition of PRL production. Gene expression of metallothionein-1 and -3 showed maxima at early/middle photophase after melatonin treatment. The 24-h pattern of anterior pituitary lipid peroxidation did not vary after treatment. In vehicle-treated rats, Clock and Bmal1 expression peaked in the anterior pituitary at middle

  6. Corticortophin releasing factor 2 receptor agonist treatment significantly slows disease progression in mdx mice

    Stevens Paula J


    Full Text Available Abstract Background Duchenne muscular dystrophy results from mutation of the dystrophin gene, causing skeletal and cardiac muscle loss of function. The mdx mouse model of Duchenne muscular dystrophy is widely utilized to evaluate the potential of therapeutic regimens to modulate the loss of skeletal muscle function associated with dystrophin mutation. Importantly, progressive loss of diaphragm function is the most consistent striated muscle effect observed in the mdx mouse model, which is the same as in patients suffering from Duchenne muscular dystrophy. Methods Using the mdx mouse model, we have evaluated the effect that corticotrophin releasing factor 2 receptor (CRF2R agonist treatment has on diaphragm function, morphology and gene expression. Results We have observed that treatment with the potent CRF2R-selective agonist PG-873637 prevents the progressive loss of diaphragm specific force observed during aging of mdx mice. In addition, the combination of PG-873637 with glucocorticoids not only prevents the loss of diaphragm specific force over time, but also results in recovery of specific force. Pathological analysis of CRF2R agonist-treated diaphragm muscle demonstrates that treatment reduces fibrosis, immune cell infiltration, and muscle architectural disruption. Gene expression analysis of CRF2R-treated diaphragm muscle showed multiple gene expression changes including globally decreased immune cell-related gene expression, decreased extracellular matrix gene expression, increased metabolism-related gene expression, and, surprisingly, modulation of circadian rhythm gene expression. Conclusion Together, these data demonstrate that CRF2R activation can prevent the progressive degeneration of diaphragm muscle associated with dystrophin gene mutation.

  7. Bundling of Reimbursement for Inferior Vena Cava Filter Placement Resulted in Significantly Decreased Utilization between 2012 and 2014.

    Glocker, Roan J; TerBush, Matthew J; Hill, Elaine L; Guido, Joseph J; Doyle, Adam; Ellis, Jennifer L; Raman, Kathleen; Morrow, Gary R; Stoner, Michael C


    On January 1, 2012, reimbursement for inferior vena cava filters (IVCFs) became bundled by the Centers for Medicare and Medicaid Services. This resulted in ICVF placement (CPT code 37191) now yielding 4.71 relative value units (RVUs), a decrease from 15.6 RVUs for placement and associated procedures (CPT codes 37620, 36010, 75825-26, 75940-26). Our hypothesis was that IVCF utilization would decrease in response to this change as other procedures had done once they had become bundled. Including data from 2010 to 2011 (before bundling) and 2012 to 2014 (after bundling), we utilized 5% inpatient, outpatient, and carrier files of Medicare limited data sets and analyzed IVCF utilization before and after bundling across specialty types, controlling for total diagnosis of deep vein thrombosis (DVT) and pulmonary embolism (PE) (ICD-9 codes 453.xx and 415.xx, respectively) and placement location. In 2010 and 2011, the rates/10,000 DVT/PE diagnoses were 918 and 1,052, respectively (average 985). In 2012, 2013, and 2014, rates were 987, 877, and 605, respectively (average 823). Comparing each year individually, there is a significant difference (P utilization. Comparing averages in the 2010-2011 and 2012-2014 groups, there is also a significant decrease in utilization after bundling (P utilization decreased significantly. More data from subsequent years will be needed to show if this decrease utilization continues to persist. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Prognostic Significance of Decreased Expression of Six Large Common Fragile Site Genes in Oropharyngeal Squamous Cell Carcinomas

    Ge Gao


    Full Text Available Common fragile sites (CFSs are large regions with profound genomic instability that often span extremely large genes a number of which have been found to be important tumor suppressors. RNA sequencing previously revealed that there was a group of six large CFS genes which frequently had decreased expression in oropharyngeal squamous cell carcinomas (OPSCCs and real-time reverse transcriptase polymerase chain reaction experiments validated that these six large CFS genes (PARK2, DLG2, NBEA, CTNNA3, DMD, and FHIT had decreased expression in most of the tumor samples. In this study, we investigated whether the decreased expression of these genes has any clinical significance in OPSCCs. We analyzed the six CFS large genes in 45 OPSCC patients and found that 27 (60% of the OPSCC tumors had decreased expression of these six genes. When we correlated the expression of these six genes to each patient’s clinical records, for 11 patients who had tumor recurrence, 10 of them had decreased expression of almost all 6 genes. When we divided the patients into two groups, one group with decreased expression of the six genes and the other group with either slight changes or increased expression of the six genes, we found that there is significant difference in the incidence of tumor recurrence between these two groups by Kaplan-Meier plot analysis (P < .05. Our results demonstrated that those OPSCC tumors with decreased expression of this select group of six large CFS genes were much more likely to be associated with tumor recurrence and these genes are potential prognostic markers for predicting tumor recurrence in OPSCC.

  9. Significance of air humidity and air velocity for fungal spore release into the air

    Pasanen, A.-L.; Pasanen, P.; Jantunen, M. J.; Kalliokoski, P.

    Our previous field studies have shown that the presence of molds in buildings does not necessarily mean elevated airborne spore counts. Therefore, we investigated the release of fungal spores from cultures of Aspergillus fumigatus, Penicillium sp. and Cladosporium sp. at different air velocities and air humidities. Spores of A. fumigatus and Penicillium sp. were released from conidiophores already at air velocity of 0.5 ms -1, whereas Cladosporium spores required at least a velocity of 1.0 ms -1. Airborne spore counts of A. fumigatus and Penicillium sp. were usually higher in dry than moist air, being minimal at relative humidities (r.h.) above 70%, while the effect of r.h. on the release of Cladosporium sp. was ambivalent. The geometric mean diameter of released spores increased when the r.h. exceeded a certain level which depends on fungal genus. Thus, spores of all three fungi were hygroscopic but the hygroscopicity of various spores appeared at different r.h.-ranges. This study indicates that spore release is controlled by external factors and depends on fungal genus which can be one reason for considerable variation of airborne spore counts in buildings with mold problems.

  10. Significant decrease in thermal conductivity of multi-walled carbon nanotube induced by inter-wall van der Waals interactions

    Zhang, Xue; Zhou, Wu-Xing, E-mail:; Chen, Xue-Kun; Liu, Yue-Yang; Chen, Ke-Qiu, E-mail:


    The thermal transport properties of multi-walled carbon nanotubes (MWCNTs) were investigated by using non-equilibrium molecular dynamics simulation. The results show that the thermal conductivity of MWCNTs decreases significantly comparing to that of single-walled carbon nanotubes (SWCNTs) due to the inter-wall van der Waals interactions. The more interesting is a fact that the thermal conductance of MWCNTs is significantly greater than the thermal conductance summation of each SWCNTs. This is because the thermal conductance of a carbon nanotube protected by an outer tube is much larger than that of one that is not protected. Moreover, we also studied the thermal flux distribution of MWCNTs, and found that the outer tube plays a dominant role in heat energy transfer. - Highlights: • Significant decrease in thermal conductivity of multi-walled carbon nanotube induced by inter-wall interactions. • The thermal conductivity of the inner tube is increased significantly due to protected by outer tube. • The outer tube plays a dominant role in heat energy transfer in multi-walled carbon nanotube.

  11. Decreasing but still significant facilitation effect of cold-season macrophytes on wetlands purification function during cold winter

    Zou, Xiangxu; Zhang, Hui; Zuo, Jie; Wang, Penghe; Zhao, Dehua; An, Shuqing


    To identify the facilitation effect of a cool-season aquatic macrophyte (FEam) for use in effluent purification via constructed floating wetlands (CFWs) and to determine the possible pathways used during a winter period with an average temperature of less than 5 °C, pilot-scale CFWs were planted with the cold-season macrophyte Oenanthe clecumbens and were operated as batch systems. Although some leaves withered, the roots retained relatively high levels of activity during the winter, which had average air and water temperatures of 3.63 and 5.04 °C, respectively. The N and P removal efficiencies in CFWs decreased significantly in winter relative to those in late autumn. The presence of cool-season plants resulted in significant improvements in N and P removal, with a FEam of 15.23-25.86% in winter. Microbial N removal accounted for 71.57% of the total N removed in winter, and the decrease in plant uptake was the dominant factor in the wintertime decrease in N removal relative to that in late autumn. These results demonstrate the importance of cold-season plants in CFWs for the treatment of secondary effluent during cold winters.

  12. Decreasing but still significant facilitation effect of cold-season macrophytes on wetlands purification function during cold winter.

    Zou, Xiangxu; Zhang, Hui; Zuo, Jie; Wang, Penghe; Zhao, Dehua; An, Shuqing


    To identify the facilitation effect of a cool-season aquatic macrophyte (FEam) for use in effluent purification via constructed floating wetlands (CFWs) and to determine the possible pathways used during a winter period with an average temperature of less than 5 °C, pilot-scale CFWs were planted with the cold-season macrophyte Oenanthe clecumbens and were operated as batch systems. Although some leaves withered, the roots retained relatively high levels of activity during the winter, which had average air and water temperatures of 3.63 and 5.04 °C, respectively. The N and P removal efficiencies in CFWs decreased significantly in winter relative to those in late autumn. The presence of cool-season plants resulted in significant improvements in N and P removal, with a FEam of 15.23-25.86% in winter. Microbial N removal accounted for 71.57% of the total N removed in winter, and the decrease in plant uptake was the dominant factor in the wintertime decrease in N removal relative to that in late autumn. These results demonstrate the importance of cold-season plants in CFWs for the treatment of secondary effluent during cold winters.

  13. Significant decrease in thermal conductivity of multi-walled carbon nanotube induced by inter-wall van der Waals interactions

    Zhang, Xue; Zhou, Wu-Xing; Chen, Xue-Kun; Liu, Yue-Yang; Chen, Ke-Qiu


    The thermal transport properties of multi-walled carbon nanotubes (MWCNTs) were investigated by using non-equilibrium molecular dynamics simulation. The results show that the thermal conductivity of MWCNTs decreases significantly comparing to that of single-walled carbon nanotubes (SWCNTs) due to the inter-wall van der Waals interactions. The more interesting is a fact that the thermal conductance of MWCNTs is significantly greater than the thermal conductance summation of each SWCNTs. This is because the thermal conductance of a carbon nanotube protected by an outer tube is much larger than that of one that is not protected. Moreover, we also studied the thermal flux distribution of MWCNTs, and found that the outer tube plays a dominant role in heat energy transfer.

  14. Flavonol-rich dark cocoa significantly decreases plasma endothelin-1 and improves cognitive responses in urban children.

    Lilian eCalderon-Garciduenas


    Full Text Available Air pollution exposures are linked to systemic inflammation, cardiovascular and respiratory morbidity and mortality, neuroinflammation and neuropathology in young urbanites. In particular, most Mexico City Metropolitan Area (MCMA children exhibit subtle cognitive deficits, and neuropathology studies show 40% of them exhibiting frontal tau hyperphosphorylation and 51% amyloid-β diffuse plaques (compared to 0% in low pollution control children. We assessed whether a short cocoa intervention can be effective in decreasing plasma endothelin 1 (ET-1 and/or inflammatory mediators in MCMA children. Thirty g of dark cocoa with 680 mg of total flavonols were given daily for 10.11± 3.4 days (range 9 to 24 days to 18 children (10.55yrs, SD =1.45; 11F/7M. Key metabolite ratios in frontal white matter and in hippocampus pre and during cocoa intervention were quantified by magnetic resonance spectroscopy. ET-1 significantly decreased after cocoa treatment (p=0.0002. Fifteen children (83% showed a marginally significant individual improvement in one or both of the applied simple short memory tasks. Endothelial dysfunction is a key feature of exposure to particulate matter and decreased endothelin-1 bioavailability is likely useful for brain function in the context of air pollution. Our findings suggest that cocoa interventions may be critical for early implementation of neuroprotection of highly exposed urban children. Multi-domain nutraceutical interventions could limit the risk for endothelial dysfunction, cerebral hypoperfusion, neuroinflammation, cognitive deficits, structural volumetric detrimental brain effects, and the early development of the neuropathological hallmarks of Alzheimer’s and Parkinson’s diseases.

  15. The flavanone homoeriodictyol increases SGLT-1-mediated glucose uptake but decreases serotonin release in differentiated Caco-2 cells

    Hoi, Julia Katharina; Holik, Ann-Katrin; Geissler, Katrin; Hans, Joachim; Friedl, Barbara; Liszt, Kathrin; Krammer, Gerhard E.; Ley, Jakob P.; Somoza, Veronika


    Flavanoids and related polyphenols, among them hesperitin, have been shown to modulate cellular glucose transport by targeting SGLT-1 and GLUT-2 transport proteins. We aimed to investigate whether homoeriodictyol, which is structurally related to hesperitin, affects glucose uptake in differentiated Caco-2 cells as a model for the intestinal barrier. The results revealed that, in contrast to other polyphenols, the flavanon homoeriodictyol promotes glucose uptake by 29.0 ± 3.83% at a concentration of 100 μM. The glucose uptake stimulating effect was sensitive to phloridzin, but not to phloretin, indicating an involvement of the sodium-coupled glucose transporter SGLT-1, but not of sodium-independent glucose transporters (GLUT). In addition, in contrast to the increased extracellular serotonin levels by stimulation with 500 mM D-(+)-glucose, treatment with 100 μM homoeriodictyol decreased serotonin release by –48.8 ± 7.57% in Caco-2 cells via a phloridzin-sensitive signaling pathway. Extracellular serotonin levels were also reduced by –57.1 ± 5.43% after application of 0.01 μM homoeriodictyol to human neural SH-SY5Y cells. In conclusion, we demonstrate that homoeriodictyol affects both the glucose metabolism and the serotonin system in Caco-2 cells via a SGLT-1-meditated pathway. Furthermore, the results presented here support the usage of Caco-2 cells as a model for peripheral serotonin release. Further investigations may address the value of homoeriodictyol in the treatment of anorexia and malnutrition through the targeting of SGLT-1. PMID:28192456

  16. Deletion of the NMDA receptor GluN2A subunit significantly decreases dendritic growth in maturing dentate granule neurons.

    Timal S Kannangara

    Full Text Available It is known that NMDA receptors can modulate adult hippocampal neurogenesis, but the contribution of specific regulatory GluN2 subunits has been difficult to determine. Here we demonstrate that mice lacking GluN2A (formerly NR2A do not show altered cell proliferation or neuronal differentiation, but present significant changes in neuronal morphology in dentate granule cells. Specifically, GluN2A deletion significantly decreased total dendritic length and dendritic complexity in DG neurons located in the inner granular zone. Furthermore, the absence of GluN2A also resulted in a localized increase in spine density in the middle molecular layer, a region innervated by the medial perforant path. Interestingly, alterations in dendritic morphology and spine density were never seen in dentate granule cells located in the outer granular zone, a region that has been hypothesized to contain older, more mature, neurons. These results indicate that although the GluN2A subunit is not critical for the cell proliferation and differentiation stages of the neurogenic process, it does appear to play a role in establishing synaptic and dendritic morphology in maturing dentate granule cells localized in the inner granular zone.

  17. Sequence variants of interleukin 6 (IL-6 are significantly associated with a decreased risk of late-onset Alzheimer's disease

    Chen Shih-Yuan


    Full Text Available Abstract Background Interleukin 6 (IL-6 has been related to beta-amyloid aggregation and the appearance of hyperphosphorylated tau in Alzheimer's disease (AD brain. However, previous studies relating IL-6 genetic polymorphisms to AD included few and unrepresentative single nucleotide polymorphisms (SNPs and the results were inconsistent. Methods This is a case-control study. A total of 266 patients with AD, aged≧65, were recruited from three hospitals in Taiwan (2007-2010. Controls (n = 444 were recruited from routine health checkups and volunteers of the hospital during the same period of time. Three common IL-6 haplotype-tagging SNPs were selected to assess the association between IL-6 polymorphisms and the risk of late-onset AD (LOAD. Results Variant carriers of IL-6 rs1800796 and rs1524107 were significantly associated with a reduced risk of LOAD [(GG + GC vs. CC: adjusted odds ratio (AOR = 0.64 and (CC + CT vs. TT: AOR = 0.60, respectively]. Haplotype CAT was associated with a decreased risk of LOAD (0 and 1 copy vs. 2 copies: AOR = 0.65, 95% CI = 0.44-0.95. These associations remained significant in ApoE e4 non-carriers only. Hypertension significantly modified the association between rs2069837 polymorphisms and the risk of LOAD (pinteraction = 0.03. Conclusions IL-6 polymorphisms are associated with reduced risk of LOAD, especially in ApoE e4 non-carriers. This study identified genetic markers for predicting LOAD in ApoE e4 non-carriers.

  18. Deletion of fabN in Enterococcus faecalis results in unsaturated fatty acid auxotrophy and decreased release of inflammatory cytokines.

    Diederich, Ann-Kristin; Duda, Katarzyna A; Romero-Saavedra, Felipe; Engel, Regina; Holst, Otto; Huebner, Johannes


    The Gram-positive bacterium Enterococcus faecalis can cause life-threatening infections and is resistant to several commonly used antibiotics. The type II fatty acid pathway in bacteria is discussed as a potential target for antimicrobial therapy. However, it was shown that inhibition or deletion of its enzymes can be rescued in Gram-positive bacteria by supplementation with fatty acids. Here we show that by deletion of the fabN gene, which is essential for unsaturated fatty acid (UFA) synthesis in E. faecalis, growth is impaired but can be rescued by supplementation with oleic acid or human serum. Nonetheless, we demonstrate alterations of the UFA profile after supplementation with oleic acid in the ΔfabN mutant using a specific glycolipid. In addition, we demonstrate that cytokine release in vitro is almost abolished after stimulation of mouse macrophages by the mutant in comparison to the wild type. The results indicate that fabN is not a suitable target for antimicrobials as UFA auxotrophy can be overcome. However, deletion of fabN resulted in a decreased inflammatory response indicating that fabN and resulting UFA synthesis are relevant for virulence.

  19. Endogenous pancreatic polypeptide in different vascular beds: relationship to release and degradation in subjects with normal and decreased kidney function

    Henriksen, Jens Henrik Sahl; Schwartz, T W; Bülow, J B


    The plasma concentration of pancreatic polypeptide (PP-like immunoreactivity) was measured in different vascular beds in order to determine regional kinetics of endogenous PP in fasting, supine subjects with normal or moderately decreased kidney function. Patients with kidney disease (n = 10) had...... a progressively increasing rate of PP secretion in subjects with raised circulating PP. No statistically significant difference could be detected between systemic and renal venous PP or across the lung, left adrenal gland, or lower limb. Assuming steady state between secretion and biodegradation, the metabolic...

  20. Is antibiotic prophylaxis mandatory after the insertion of levonorgestrel-releasing intrauterine systemin order to decrease the risk of pelvic inflammatory disease?

    Munteanu, O; Radulescu, L; Bodean, O; Cirstoiu, C; Secara, D; Cirstoiu, M


    This study was undertaken in order to determine if antibiotic prophylaxis is mandatory, after the insertion of levonorgestrel-releasing intrauterine system in order to decrease the risk of pelvic inflammatory disease. We prospectively evaluated 44 patients, admitted in the Bucharest Emergency Hospital between the 1ⁱ of February 2012 and the 1ⁱ of October 2012, in whom the levonorgestrel-releasing intrauterine system was inserted. The patients enrolled were divided into two groups. In group A, a number of 22 patients, received, after the insertion of levonorgestrel-releasing intrauterine system, 875mg Amoxicillin Trihydrate + 125 mg Potassium Clavulanate, a dose every 12 hours for 5 days. Group B was represented by the other 22 patients who did not receive antibiotic prophylaxis. All patients were reevaluated at 4 and 12 weeks after the insertion of levonorgestrel-releasing intrauterine system. During the first 4 weeks after the insertion of levonorgestrel-releasing intrauterine system only two patients, one from group A and one from group B were diagnosed with pelvic inflammatory disease. At a second follow up visit - 12 weeks after the insertion of levonorgestrel-releasing intrauterine system, no other patient was diagnosed with pelvic inflammatory disease. Antibiotic prophylaxis is not mandatory, after the insertion of levonorgestrel-releasing intrauterine system in order to decrease the risk of pelvic inflammatory disease.

  1. Chemoembolization of unresectable hepatocellular carcinoma: Decreased toxicity with slow-release doxorubicin‑eluting beads compared with lipiodol.

    Recchia, Francesco; Passalacqua, Giovanni; Filauri, Pietro; Doddi, Marco; Boscarato, Pietro; Candeloro, Giampiero; Necozione, Stefano; Desideri, Giovambattista; Rea, Silvio


    Chemoembolization with lipiodol (TACE) improves survival of selected patients with unresectable hepatocellular carcinoma (HCC), but results in substantial toxicity. To improve treatment tolerance, we conducted this phase II study using doxorubicin-loaded beads (DC Beads®) delivered by selective transcatheter arterial chemoembolization (DEB-TACE). We compared the results with those obtained with TACE in our historical controls. Thirty-five patients were recruited with diagnoses of HCC. Patients received DEB-TACE with doxorubicin loaded on DC Beads. Computed tomography of the upper abdomen was performed one month after DEB-TACE. Historical controls were a group of 70 patients with matched characteristics treated with TACE. After a median follow-up of 14.1 months (range, 6-36 months), 22 patients (63%) had an objective response. There was a statistically significant decrease in liver enzymes (p<0.001), lactate dehydrogenase, (p<0.001) in DEB-TACE-treated patients compared to TACE-treated patients. DEB-TACE with doxorubicin-loaded DC Beads, a safe and reliable treatment for HCC, leads to decreased toxicity compared to TACE.

  2. Significant decrease of broth viscosity and glucose consumption in erythromycin fermentation by dynamic regulation of ammonium sulfate and phosphate.

    Chen, Yong; Wang, Zejian; Chu, Ju; Zhuang, Yingping; Zhang, Siliang; Yu, Xiaoguang


    In this study, the effects of nitrogen sources on broth viscosity and glucose consumption in erythromycin fermentation were investigated. By controlling ammonium sulfate concentration, broth viscosity and glucose consumption were decreased by 18.2% and 61.6%, respectively, whereas erythromycin biosynthesis was little affected. Furthermore, erythromycin A production was increased by 8.7% still with characteristics of low broth viscosity and glucose consumption through the rational regulations of phosphate salt, soybean meal and ammonium sulfate. It was found that ammonium sulfate could effectively control proteinase activity, which was correlated with the utilization of soybean meal as well as cell growth. The pollets formation contributed much to the decrease of broth viscosity. The accumulation of extracellular propionate and succinate under the new regulation strategy indicated that higher propanol consumption might increase the concentration of methylmalonyl-CoA and propionyl-CoA and thus could increase the flux leading to erythromycin A. Copyright © 2013 Elsevier Ltd. All rights reserved.

  3. Juxtaglomerular cell CaSR stimulation decreases renin release via activation of the PLC/IP(3) pathway and the ryanodine receptor.

    Ortiz-Capisano, M Cecilia; Reddy, Mahendranath; Mendez, Mariela; Garvin, Jeffrey L; Beierwaltes, William H


    The calcium-sensing receptor (CaSR) is a G-coupled protein expressed in renal juxtaglomerular (JG) cells. Its activation stimulates calcium-mediated decreases in cAMP content and inhibits renin release. The postreceptor pathway for the CaSR in JG cells is unknown. In parathyroids, CaSR acts through G(q) and/or G(i). Activation of G(q) stimulates phospholipase C (PLC), and inositol 1,4,5-trisphosphate (IP(3)), releasing calcium from intracellular stores. G(i) stimulation inhibits cAMP formation. In afferent arterioles, the ryanodine receptor (RyR) enhances release of stored calcium. We hypothesized JG cell CaSR activation inhibits renin via the PLC/IP(3) and also RyR activation, increasing intracellular calcium, suppressing cAMP formation, and inhibiting renin release. Renin release from primary cultures of isolated mouse JG cells (n = 10) was measured. The CaSR agonist cinacalcet decreased renin release 56 ± 7% of control (P PLC inhibitor U73122 reversed cinacalcet inhibition of renin (104 ± 11% of control). The IP(3) inhibitor 2-APB also reversed inhibition of renin from 56 ± 6 to 104 ± 11% of control (P PLC/IP(3) pathway, activating RyR, increasing intracellular calcium, and resulting in calcium-mediated renin inhibition.

  4. Carbon monoxide-releasing molecule-2 enhances coagulation in rabbit plasma and decreases bleeding time in clopidogrel/aspirin-treated rabbits.

    Nielsen, Vance G; Chawla, Nikhil; Mangla, Dipty; Gomes, Sheldon B; Arkebauer, Matthew R; Wasko, Kimberly A; Sadacharam, Kesavan; Vosseller, Keith


    Administration of carbon monoxide derived from carbon monoxide-releasing molecules has been demonstrated to enhance coagulation in vitro at small concentrations (100-200 μmol/l) in human and rabbit plasma. We sought to determine if carbon monoxide-releasing molecule-2 [tricarbonyldichlororuthenium (II) dimer, CORM-2] would improve coagulation in rabbit plasma in vitro via thrombelastography and in an in vivo preclinical rabbit model of ear bleeding time following administration of clopidogrel (20 mg/kg) with aspirin (10 mg/kg) via gavage. Addition of 100 μmol/l CORM-2 to rabbit plasma significantly improved coagulation. This procoagulant effect was blocked by pre-exposure of plasma to an agent that converts hemefibrinogen to methemefibrinogen in human plasma, preventing carbon monoxide binding and enhancement of coagulation. Rabbit ear bleeding time was 5.8 ± 1.1 min 2-3 h after clopidogrel/aspirin administration. Bleeding time significantly decreased to 2.6 ± 0.6 min, 5 min after administration of CORM-2 (10 mg/kg; 279 μmol/l 'best-case' instantaneous concentration) intravenously. CORM-2 enhances plasmatic coagulation in a manner similar to that of human plasma in vitro, and plasmatic coagulation is enhanced in vivo by CORM-2 as well. Additional preclinical investigation of the effects of CORM-2 on coagulopathy (e.g. heparin or hemodilution mediated) utilizing this rabbit model is planned.

  5. Releases of surgically deafened homing pigeons indicate that aural cues play a significant role in their navigational system.

    Hagstrum, Jonathan T; Manley, Geoffrey A


    Experienced homing pigeons with extirpated cochleae and lagenae were released from six sites in upstate New York and western Pennsylvania on 17 days between 1973 and 1975 by William T. Keeton and his co-workers at Cornell University. The previously unpublished data indicate that departure directions of the operated birds were significantly different from those of sham-operated control birds (314 total), indicating that aural cues play an important part in the pigeon's navigational system. Moreover, propagation modeling of infrasonic waves using meteorological data for the release days supports the possibility that control birds used infrasonic signals to determine their homeward direction. Local acoustic 'shadow' zones, therefore, could have caused initial disorientation of control birds at release sites where they were normally well oriented. Experimental birds plausibly employed an alternate 'route-reversal' strategy to return home perhaps using their ocular-based magnetic compass. We suggest, based on Keeton's results from another site of long-term disorientation, that experienced pigeons depend predominantly on infrasonic cues for initial orientation, and that surgical removal of their aural sense compelled them to switch to a secondary navigational strategy.

  6. Effect of low severity dilute-acid pretreatment of barley straw and decreased enzyme loading hydrolysis on the production of fermentable substrates and the release of inhibitory compounds

    Panagiotopoulos, I.A.; Lignos, G.D.; Bakker, R.R.C.; Koukios, E.G.


    The objective of this work was to investigate the feasibility of combining low severity dilute-acid pretreatment of barley straw and decreased enzyme loading hydrolysis for the high production of fermentable substrates and the low release of inhibitory compounds. For most of the pretreatments at 160

  7. Mesothelin expression in triple negative breast carcinomas correlates significantly with basal-like phenotype, distant metastases and decreased survival.

    Gary Tozbikian

    Full Text Available Mesothelin is a cell surface associated antigen expressed on mesothelial cells and in some malignant neoplasms. Mesothelin-targeted therapies are in phase I/II clinical trials. The clinicopathologic and prognostic significance of mesothelin expression in triple negative breast carcinomas (TNBC has not been fully assessed. We evaluated the expression of mesothelin and of basal markers in tissue microarrays of 226 TNBC and 88 non-TNBC and assessed the clinicopathologic features of mesothelin-expressing breast carcinomas. Furthermore, we investigated the impact of mesothelin expression on the disease-free and overall survival of patients with TNBC. We found that mesothelin expression is significantly more frequent in TNBC than in non-TNBC (36% vs 16%, respectively; p = 0.0006, and is significantly correlated with immunoreactivity for basal keratins, but not for EGFR. Mesothelin-positive and mesothelin-negative TNBC were not significantly different by patients' race, tumor size, histologic grade, tumor subtype, lymphovascular invasion and lymph node metastases. Patients with mesothelin-positive TNBC were older than patients with mesothelin-negative TNBC, developed more distant metastases with a shorter interval, and had significantly lower overall and disease-free survival. Based on our results, patients with mesothelin-positive TNBC could benefit from mesothelin-targeted therapies.

  8. Fossil plants indicate that the most significant decrease in atmospheric CO2 happened prior to the Eocene-Oligocene boundary

    Steinthorsdottir, Margret; Porter, Amanda; Holohan, Aidan; Kunzmann, Lutz; Collinson, Margaret; McElwain, Jennifer


    A unique stratigraphic sequence of fossil leaves of Eotrigonobalanus furcinervis (extinct trees of the beech family, Fagaceae) from central Germany was utilized to derive an atmospheric pCO2 record with multiple data points spanning the late middle to late Eocene, two sampling levels which may be earliest Oligocene, and two samples from later in the Oligocene. Using the stomatal proxy, which relies on the inverse relationship between pCO2 and leaf stomatal density, we show that a ~40% decrease in pCO2 preceded the large shift in marine oxygen isotope records that characterizes the Eocene-Oliogocene climate transition. The results endorse the theory that pCO2 drawdown was the main forcer of the Eocene-Oligocene climate change, and a 'tipping point' was reached in the latest Eocene, triggering the plunge of the Earth System into icehouse conditions.

  9. Extremely decreased release of prostaglandin E2-like activity from chopped lung of ethyl linolenate-supplemented rats.

    Hansen, H S; Fjalland, B; Jensen, B


    Three groups of weanling male rats were reared on a fat-free diet for 13 weeks. One group received only the fat-free diet (FF rats), the other 2 groups received the fat-free diet and a daily supplement of 2 energy% ethyl linoleate ([n-6] rats), or 2 energy% ethyl linolenate ([n-3] rats). The chopped lung preparation was used to illustrate an in vitro prostaglandin formation. PGE2-like activity was quantified on rat stomach strip. The release of PGE2-like activity expressed as ng PGE2-equivalent per g lung tissue (mean +/- SD) was 23 +/- 7, less than 6, and 65 +/- 20 for the FF rats, the (n-3) rats, and the (n-6) rats, respectively. PGE2 quantification by radioimmunoassay of the chopped lung effluent collected after passing over the rat stomach strip revealed the same release pattern as the bioassay. Fractionation of chopped lung effluent on HPLC with radioimmunoassay detection indicated that the lung tissue from (n-3) rats released very little PGE3, if any, in spite of a 20:5(n-3)/20:4(n-6) ratio of 5.2 in the lipids of the lung. It is suggested that the pool of arachidonic acid for prostaglandin production in vitro is different from the one which functions in vivo, and the these pools are differently affected by dietary EFA.

  10. Iontophoresis on minoxidil sulphate-loaded chitosan nanoparticles accelerates drug release, decreasing their targeting effect to hair follicles

    Breno N. Matos

    Full Text Available The experiments described in this paper tested the hypothesis whether iontophoresis applied on a chitosan nanoparticle formulation could combine the enhanced drug accumulation into the follicular casts obtained using iontophoresis and the sustained drug release, reducing dermal exposure, provided by nanoparticles. Results showed that even though iontophoresis presented comparable minoxidil targeting potential to hair follicles than passive delivery of chitosan-nanoparticles (4.1 ± 0.9 and 5.3 ± 1.0 µg cm-2, respectively, it was less effective on preventing dermal exposure, since chitosan-nanoparticles presented a drug permeation in the receptor solution of 15.3 ± 4.3 µg cm-2 after 6 h of iontophoresis, while drug amounts from passive nanoparticle delivery were not detected. Drug release experiments showed particles were not able to sustain the drug release under the influence of a potential gradient. In conclusion, the application of MXS-loaded chitosan nanoparticles remains the best way to target MXS to the hair follicles while preventing dermal exposure.

  11. Optimization of temperature, sugar concentration, and inoculum size to maximize ethanol production without significant decrease in yeast cell viability.

    Laluce, Cecilia; Tognolli, João Olimpio; de Oliveira, Karen Fernanda; Souza, Crisla Serra; Morais, Meline Rezende


    Aiming to obtain rapid fermentations with high ethanol yields and a retention of high final viabilities (responses), a 2(3) full-factorial central composite design combined with response surface methodology was employed using inoculum size, sucrose concentration, and temperature as independent variables. From this statistical treatment, two well-fitted regression equations having coefficients significant at the 5% level were obtained to predict the viability and ethanol production responses. Three-dimensional response surfaces showed that increasing temperatures had greater negative effects on viability than on ethanol production. Increasing sucrose concentrations improved both ethanol production and viability. The interactions between the inoculum size and the sucrose concentrations had no significant effect on viability. Thus, the lowering of the process temperature is recommended in order to minimize cell mortality and maintain high levels of ethanol production when the temperature is on the increase in the industrial reactor. Optimized conditions (200 g/l initial sucrose, 40 g/l of dry cell mass, 30 degrees C) were experimentally confirmed and the optimal responses are 80.8 +/- 2.0 g/l of maximal ethanol plus a viability retention of 99.0 +/- 3.0% for a 4-h fermentation period. During consecutive fermentations with cell reuse, the yeast cell viability has to be kept at a high level in order to prevent the collapse of the process.

  12. Inhibition of basophil histamine release by gangliosides. Further studies on the significance of cell membrane sialic acid in the histamine release process

    Jensen, C; Norn, S; Thastrup, Ole


    with the glucolipid mixture increased the sialic acid content of the cells, and this increase was attributed to an insertion of gangliosides into the cell membrane. The inhibition of histamine release was abolished by increasing the calcium concentration, which substantiates our previous findings that cell membrane......Histamine release from human basophils was inhibited by preincubation of the cells with a glucolipid mixture containing sialic acid-containing gangliosides. This was true for histamine release induced by anti-IgE, Concanavalin A and the calcium ionophore A23187, whereas the release induced by S....... aureus Wood 46 was not affected. It was demonstrated that the inhibitory capacity of the glucolipid mixture could be attributed to the content of gangliosides, since no inhibition was obtained with cerebrosides or with gangliosides from which sialic acid was removed. Preincubation of the cells...

  13. Neurochemical evidence that cocaine- and amphetamine-regulated transcript (CART) 55-102 peptide modulates the dopaminergic reward system by decreasing the dopamine release in the mouse nucleus accumbens.

    Rakovska, Angelina; Baranyi, Maria; Windisch, Katalin; Petkova-Kirova, Polina; Gagov, Hristo; Kalfin, Reni


    CART (Cocaine- and Amphetamine-Regulated Transcript) peptide is a neurotransmitter naturally occurring in the CNS and found mostly in nucleus accumbens, ventrotegmental area, ventral pallidum, amygdalae and striatum, brain regions associated with drug addiction. In the nucleus accumbens, known for its significant role in motivation, pleasure, reward and reinforcement learning, CART peptide inhibits cocaine and amphetamine-induced dopamine-mediated increases in locomotor activity and behavior, suggesting a CART peptide interaction with the dopaminergic system. Thus in the present study, we examined the effect of CART (55-102) peptide on the basal, electrical field stimulation-evoked (EFS-evoked) (30V, 2Hz, 120 shocks) and returning basal dopamine (DA) release and on the release of the DA metabolites 3,4-dihydroxyphenyl acetaldehyde (DOPAL), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), 3,4-dihydroxyphenylethanol (DOPET), 3-methoxytyramine (3-MT) as well as on norepinephrine (NE) and dopamine-o-quinone (Daq) in isolated mouse nucleus accumbens, in a preparation, in which any CART peptide effects on the dendrites or soma of ventral tegmental projection neurons have been excluded. We further extended our study to assess the effect of CART (55-102) peptide on basal cocaine-induced release of dopamine and its metabolites DOPAL, DOPAC, HVA, DOPET and 3-MT as well as on NE and Daq. To analyze the amount of [(3)H]dopamine, dopamine metabolites, Daq and NE in the nucleus accumbens superfusate, a high-pressure liquid chromatography (HPLC), coupled with electrochemical, UV and radiochemical detections was used. CART (55-102) peptide, 0.1μM, added alone, exerted: (i) a significant decrease in the basal and EFS-evoked levels of extracellular dopamine (ii) a significant increase in the EFS-evoked and returning basal levels of the dopamine metabolites DOPAC and HVA, major products of dopamine degradation and (iii) a significant decrease in the returning basal

  14. Dehydration-induced drinking decreases Fos expression in hypothalamic paraventricular neurons expressing vasopressin but not corticotropin-releasing hormone.

    Wotus, Cheryl; Arnhold, Michelle M; Engeland, William C


    Water-restricted (WR) rats exhibit a rapid suppression of plasma corticosterone following drinking. The present study monitored Fos-like immunoreactivity (Fos) to assess the effect of WR-induced drinking on the activity of vasopressin (VP)-positive magnocellular and parvocellular neurons and corticotropin-releasing hormone (CRH)-positive parvocellular neurons in the paraventricular nucleus of the hypothalamus. Adult male rats received water for 30 min (WR) in the post meridiem (PM) each day for 6 days and were killed without receiving water or at 1 h after receiving water for 15 min. In WR rats, Fos increased in VP magnocellular and parvocellular neurons but not CRH neurons. After drinking, Fos was reduced in VP magnocellular and parvocellular neurons but did not change in CRH neurons. To assess the severity of osmotic stress, rats were sampled throughout the final day of WR. Plasma osmolality, hematocrit and plasma VP were increased throughout the day before PM rehydration, and plasma ACTH and corticosterone were elevated at 1230 and 1430, respectively, showing that WR activates hypothalamic-pituitary-adrenal activity during the early PM before the time of rehydration. To determine the effects of WR-induced drinking on CRH neurons activated by acute stress, WR rats underwent restraint. Restraint increased plasma ACTH and corticosterone and Fos in CRH neurons; although rehydration reduced plasma ACTH and Fos expression in VP neurons, Fos in CRH neurons was not affected. These results suggest that inhibition of VP magnocellular and parvocellular neurons, but not CRH parvocellular neurons, contributes to the suppression of corticosterone after WR-induced drinking.

  15. Cystine accumulation attenuates insulin release from the pancreatic β-cell due to elevated oxidative stress and decreased ATP levels.

    McEvoy, Bernadette; Sumayao, Rodolfo; Slattery, Craig; McMorrow, Tara; Newsholme, Philip


    The pancreatic β-cell has reduced antioxidant defences making it more susceptible to oxidative stress. In cystinosis, a lysosomal storage disorder, an altered redox state may contribute to cellular dysfunction. This rare disease is caused by an abnormal lysosomal cystine transporter, cystinosin, which causes excessive accumulation of cystine in the lysosome. Cystinosis associated kidney damage and dysfunction leads to the Fanconi syndrome and ultimately end-stage renal disease. Following kidney transplant, cystine accumulation in other organs including the pancreas leads to multi-organ dysfunction. In this study, a Ctns gene knockdown model of cystinosis was developed in the BRIN-BD11 rat clonal pancreatic β-cell line using Ctns-targeting siRNA. Additionally there was reduced cystinosin expression, while cell cystine levels were similarly elevated to the cystinotic state. Decreased levels of chronic (24 h) and acute (20 min) nutrient-stimulated insulin secretion were observed. This decrease may be due to depressed ATP generation particularly from glycolysis. Increased ATP production and the ATP/ADP ratio are essential for insulin secretion. Oxidised glutathione levels were augmented, resulting in a lower [glutathione/oxidised glutathione] redox potential. Additionally, the mitochondrial membrane potential was reduced, apoptosis levels were elevated, as were markers of oxidative stress, including reactive oxygen species, superoxide and hydrogen peroxide. Furthermore, the basal and activated phosphorylated forms of the redox-sensitive transcription factor NF-κB were increased in cells with silenced Ctns. From this study, the cystinotic-like pancreatic β-cell model demonstrated that the altered oxidative status of the cell, resulted in depressed mitochondrial function and pathways of ATP production, causing reduced nutrient-stimulated insulin secretion.

  16. The Decreased Growth Hormone Response to Growth Hormone Releasing Hormone in Obesity Is Associated to Cardiometabolic Risk Factors

    Fernando Cordido


    Premenopausal obese women, aged 35–52 years, were studied. GH secretion, IGF-I, serum cardiovascular risk markers, insulin, leptin, mid-waist and hip circumference, total body fat, and truncal fat were measured. Subjects were classified as meeting the criteria for GH deficiency (GHD when peak GH after stimulation with GHRH was ≤3 μg/L. Mean total and LDL cholesterol, fasting insulin, and HOMA-IR were all higher, in subjects who would have been classified as GH-deficient compared with GH-sufficient. Peak GH secretion after stimulation was inversely associated with fasting insulin (R=−0.650, P=.012, HOMA-IR (R=−0.846, P=.001, total cholesterol (R=−0.532, P=.034, and LDL cholesterol (R=−0.692, P=.006 and positively associated with HDL cholesterol (R=0.561, P=.037. These data strongly suggest a role for insulin resistance in the decreased GH secretion of obesity and that the blunted GH secretion of central obesity could be the pituitary expression of the metabolic syndrome.

  17. Human intestinal dendritic cells decrease cytokine release against Salmonella infection in the presence of Lactobacillus paracasei upon TLR activation.

    Miriam Bermudez-Brito

    Full Text Available Probiotic bacteria have been shown to modulate immune responses and could have therapeutic effects in allergic and inflammatory disorders. However, little is known about the signalling pathways that are engaged by probiotics. Dendritic cells (DCs are antigen-presenting cells that are involved in immunity and tolerance. Monocyte-derived dendritic cells (MoDCs and murine DCs are different from human gut DCs; therefore, in this study, we used human DCs generated from CD34+ progenitor cells (hematopoietic stem cells harvested from umbilical cord blood; those DCs exhibited surface antigens of dendritic Langerhans cells, similar to the lamina propria DCs in the gut. We report that both a novel probiotic strain isolated from faeces of exclusively breast-fed newborn infants, Lactobacillus paracasei CNCM I-4034, and its cell-free culture supernatant (CFS decreased pro-inflammatory cytokines and chemokines in human intestinal DCs challenged with Salmonella. Interestingly, the supernatant was as effective as the bacteria in reducing pro-inflammatory cytokine expression. In contrast, the bacterium was a potent inducer of TGF-β2 secretion, whereas the supernatant increased the secretion of TGF-β1 in response to Salmonella. We also showed that both the bacteria and its supernatant enhanced innate immunity through the activation of Toll-like receptor (TLR signalling. These treatments strongly induced the transcription of the TLR9 gene. In addition, upregulation of the CASP8 and TOLLIP genes was observed. This work demonstrates that L. paracasei CNCM I-4034 enhanced innate immune responses, as evidenced by the activation of TLR signalling and the downregulation of a broad array of pro-inflammatory cytokines. The use of supernatants like the one described in this paper could be an effective and safe alternative to using live bacteria in functional foods.

  18. Efavirenz- but not nevirapine-based antiretroviral therapy decreases exposure to the levonorgestrel released from a sub-dermal contraceptive implant

    Kimberly Scarsi


    Full Text Available Introduction: Sub-dermal hormone implants, such as levonorgestrel (LNG, are a safe and desirable form of long-acting contraception, but their use among HIV-positive women on antiretroviral therapy (ART may be compromised given the potential for a cytochrome P450 3A-mediated drug–drug interaction. Our study aimed to characterize the pharmacokinetics of LNG released from a sub-dermal implant over six months in HIV-positive Ugandan women on nevirapine (NVP- or efavirenz (EFV-based ART. Material and Methods: This non-randomized, parallel group study compared LNG pharmacokinetics between HIV-positive Ugandan women not yet eligible for ART (control group, n=18 and those on stable NVP- (n=20 or EFV- (n=20 based ART. The two-rod (75 mg/rod LNG sub-dermal implant was inserted at study enrolment. LNG sampling was obtained pre-implant and at weeks 1, 4, 12 and 24 post-insertion. LNG concentrations were analyzed using a validated LC-MS/MS method, with an assay calibration range of 50–1500 pg/mL. Safety monitoring, including a pregnancy test, was conducted at each study visit. Results: At enrolment, participants had a mean age of 31 years; CD4+ cell counts were similar between the control, NVP and EFV groups (758, 645 and 568 cells/mm3, respectively; p=0.09; all women in the NVP and EFV groups had an undetectable HIV-RNA. Women in the control group had a higher baseline body weight (73 kg compared to those in the NVP (63 kg; p=0.03 or EFV groups (60 kg; p<0.01. By linear regression, weight was a significant predictor of LNG concentrations (1 kg increase in weight=5 pg/mL decrease in LNG, p=0.03. LNG concentrations are reported in the table. Conclusions: Over a 24-week period, LNG concentrations were 40–54% lower in women on EFV-based ART, despite their having a significantly lower body weight, compared to those not on ART. In women on NVP-based ART, LNG concentrations were 32–39% higher than those observed in the control group, a difference partially

  19. r-bPiDI, an α6β2* Nicotinic Receptor Antagonist, Decreases Nicotine-Evoked Dopamine Release and Nicotine Reinforcement

    Beckmann, Joshua S.; Meyer, Andrew C.; Pivavarchyk, M.; Horton, David B.; Zheng, Guangrong; Smith, Andrew M.; Wooters, Thomas E.; McIntosh, J. Michael; Crooks, Peter A.; Bardo, Michael T.


    α6β2* nicotinic acetylcholine receptors (nACh Rs) expressed by dopaminergic neurons mediate nicotine-evoked dopamine (DA) release and nicotine reinforcement. α6β2* antagonists inhibit these effects of nicotine, such that α6β2* receptors serve as therapeutic targets for nicotine addiction. The present research assessed the neuropharmacology of 1,10-bis(3-methyl-5,6-dihydropyridin-1(2H)-yl)decane (r-bPiDI), a novel small-molecule, tertiary amino analog of its parent compound, N,N-decane-1,10-diyl-bis-3-picolinium diiodide (bPiDI). bPiDI was previously shown to inhibit both nicotine-evoked DA release and the reinforcing effects of nicotine. In the current study, r-bPiDI inhibition of [3H]nicotine and [3H]methyllyca-conitine binding sites was evaluated to assess interaction with the recognition binding sites on α4β2* and α7* nAChRs, respectively. Further, r-bPiDI inhibition of nicotine-evoked DA release in vitro in the absence and presence of α-conotoxin MII and following chronic in vivo nicotine administration were determined. The ability of r-bPiDI to decrease nicotine self-administration and food-maintained responding was also assessed. Results show that r-bPiDI did not inhibit [3H]nicotine or [3H]methylly-caconitine binding, but potently (IC50 = 37.5 nM) inhibited nicotine-evoked DA release from superfused striatal slices obtained from either drug naïve rats or from those repeatedly treated with nicotine. r-bPiDI inhibition of nicotine-evoked DA release was not different in the absence or presence of α-conotoxin MII, indicating that r-bPiDI acts as a potent, selective α6β2* nAChR antagonist. Acute systemic administration of r-bPiDI specifically decreased nicotine self-administration by 75 %, and did not alter food-maintained responding, demonstrating greater specificity relative to bPiDI and bPiDDB, as well as the tertiary amino analog r-bPiDDB. The current work describes the discovery of r-bPiDI, a tertiary amino, α-conotoxin MII-like small molecule

  20. Omega-3 fatty acid therapy dose-dependently and significantly decreased triglycerides and improved flow-mediated dilation, however, did not significantly improve insulin sensitivity in patients with hypertriglyceridemia.

    Oh, Pyung Chun; Koh, Kwang Kon; Sakuma, Ichiro; Lim, Soo; Lee, Yonghee; Lee, Seungik; Lee, Kyounghoon; Han, Seung Hwan; Shin, Eak Kyun


    Experimental studies demonstrate that higher intake of omega-3 fatty acids (n-3 FA) improves insulin sensitivity, however, we reported that n-3 FA 2g therapy, most commonly used dosage did not significantly improve insulin sensitivity despite reducing triglycerides by 21% in patients. Therefore, we investigated the effects of different dosages of n-3 FA in patients with hypertriglyceridemia. This was a randomized, single-blind, placebo-controlled, parallel study. Age, sex, and body mass index were matched among groups. All patients were recommended to maintain a low fat diet. Forty-four patients (about 18 had metabolic syndrome/type 2 diabetes mellitus) in each group were given placebo, n-3 FA 1 (O1), 2 (O2), or 4 g (O4), respectively daily for 2 months. n-3 FA therapy dose-dependently and significantly decreased triglycerides and triglycerides/HDL cholesterol and improved flow-mediated dilation, compared with placebo (by ANOVA). However, each n-3 FA therapy did not significantly decrease high-sensitivity C-reactive protein and fibrinogen, compared with placebo. O1 significantly increased insulin levels and decreased insulin sensitivity (determined by QUICKI) and O2 significantly decreased plasma adiponectin levels relative to baseline measurements. Of note, when compared with placebo, each n-3 FA therapy did not significantly change insulin, glucose, adiponectin, glycated hemoglobin levels and insulin sensitivity (by ANOVA). We observed similar results in a subgroup of patients with the metabolic syndrome. n-3 FA therapy dose-dependently and significantly decreased triglycerides and improved flow-mediated dilation. Nonetheless, n-3 FA therapy did not significantly improve acute-phase reactants and insulin sensitivity in patients with hypertriglyceridemia, regardless of dosages. Copyright © 2014. Published by Elsevier Ireland Ltd.

  1. The significance of post-stress decrease in left ventricular ejection fraction in patients undergoing regadenoson stress gated SPECT myocardial perfusion imaging.

    Gomez, Javier; Golzar, Yasmeen; Fughhi, Ibtihaj; Olusanya, Adebayo; Doukky, Rami


    The significance of post-stress decrease in left ventricular ejection fraction (LVEF) with regadenoson stress gated SPECT (GSPECT) myocardial perfusion imaging (MPI) has not been studied. Consecutive patients who underwent rest/regadenoson stress GSPECT-MPI followed by coronary angiography within 6 months were analyzed. Change in LVEF by GSPECT-MPI was calculated as stress LVEF minus rest LVEF; a significant decrease was tested at 5% and 10% thresholds. In a diagnostic cohort of 793 subjects, LVEF change was not predictive of severe/extensive coronary artery disease (area under the curve, 0.50; 95% confidence interval, 0.44-0.57; P = 0.946). There was no significant difference in the rates of severe/extensive coronary artery disease in patients with or without a decrease in LVEF, irrespective of MPI findings. In an outcome cohort of the 929 subjects followed for 30 ± 16 months, post-regadenoson stress decrease in LVEF was not associated with increased risk of the composite endpoint of cardiac death or myocardial infarction or in the risk of coronary revascularization. In patients selected to undergo coronary angiography following regadenoson stress GSPECT-MPI, a decrease in LVEF after regadenoson stress is not predictive of severe/extensive CAD or adverse clinical outcomes, irrespective of MPI findings.

  2. Extended-release niacin/laropiprant significantly improves lipid levels in type 2 diabetes mellitus irrespective of baseline glycemic control

    Bays HE


    Full Text Available Harold E Bays,1 Eliot A Brinton,2 Joseph Triscari,3 Erluo Chen,3 Darbie Maccubbin,3 Alexandra A MacLean,3 Kendra L Gibson,3 Rae Ann Ruck,3 Amy O Johnson-Levonas,3 Edward A O’Neill,3 Yale B Mitchel3 1Louisville Metabolic & Atherosclerosis Research Center (L-MARC, Louisville, KY, USA; 2Utah Foundation for Biomedical Research, Salt Lake City, UT, USA; 3Merck & Co, Inc., Whitehouse Station, NJ, USA Background: The degree of glycemic control in patients with type 2 diabetes mellitus (T2DM may alter lipid levels and may alter the efficacy of lipid-modifying agents. Objective: Evaluate the lipid-modifying efficacy of extended-release niacin/laropiprant (ERN/LRPT in subgroups of patients with T2DM with better or poorer glycemic control. Methods: Post hoc analysis of clinical trial data from patients with T2DM who were randomized 4:3 to double-blind ERN/LRPT or placebo (n=796, examining the lipid-modifying effects of ERN/LRPT in patients with glycosylated hemoglobin or fasting plasma glucose levels above and below median baseline levels. Results: At Week 12 of treatment, ERN/LRPT significantly improved low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C, non-high-density lipoprotein cholesterol, triglycerides, and lipoprotein (a, compared with placebo, with equal efficacy in patients above or below median baseline glycemic control. Compared with placebo, over 36 weeks of treatment more patients treated with ERN/LRPT had worsening of their diabetes and required intensification of antihyperglycemic medication, irrespective of baseline glycemic control. Incidences of other adverse experiences were generally low in all treatment groups. Conclusion: The lipid-modifying effects of ERN/LRPT are independent of the degree of baseline glycemic control in patients with T2DM (NCT00485758. Keywords: lipid-modifying agents, hyperglycemia, LDL, HDL, triglycerides

  3. Lipopolysaccharide (LPS) processing by Kupffer cells releases a modified LPS with increased hepatocyte binding and decreased tumor necrosis factor-alpha stimulatory capacity.

    Treon, S P; Thomas, P; Broitman, S A


    Normal physiological clearance of gut-derived endotoxin lipopolysaccharide [LPS] has been described previously; initially, there is uptake by Kupffer cells (KC), then release of modified LPS, followed by hepatocyte uptake. Previous work in our laboratories indicated that LPS is structurally modified with loss of carbohydrate prior to its release by KC. In this study, we functionally characterize KC modified LPS. KC-modified 125I-LPS was prepared from primary rat KC. Escherichia coli 0127:B8 native 125I-LPS or KC-modified 125I-LPS (40 ng) was incubated for 1 hr with 1 x 10E6 primary hepatocytes. The binding of KC-modified LPS was 4.33-fold higher than native LPS (P = 0.0024). Binding analysis studies were conducted to determine the region of KC-modified LPS responsible for enhanced hepatocyte binding. KC-modified Salmonella minnesota LPS was competed with 100-fold excess native or mutant (Ra, Rc, Rd, or Re) strains of LPS or Lipid A with no decrease to hepatocyte binding. S. minnesota-native 125I-LPS was compared with KC-modified 125I-LPS in a study to assess induction of tumor necrosis factor (TNF)-gamma by rat peritoneal macrophages. Native or KC-modified 125I-LPS (100 ng) was presented to 1 x 10E7 peritoneal macrophages for 6 hr. TNF-alpha was measured in supernatants using the WEHI-164 cytotoxicity assay. Native LPS induced 5.7-fold higher TNF-alpha levels than KC-modified LPS (P < 0.0001). The above data suggest that structural alterations in KC-modified LPS are accompanied by functional alterations resulting in enhanced hepatocyte binding and decreased TNF-alpha release. The latter result implies that an early step in LPS detoxification occurs in the KC in which LPS is modified to prevent elicitation of biologically active cytokines.

  4. 76 FR 71583 - Notice of Availability of Finding of No Significant Impact for Field Release of Insects for...


    ... FR 21311. On November 12, 2010, APHIS issued an EA that evaluated a range of alternatives and... 15, 2010. See 76 FR 8708. These documents are posted on the APHIS Web site at: http://www.aphis.usda... Field Release of Insects for Biological Control of Carrizo Cane AGENCY: U.S. Customs and...

  5. Angiotensin II and angiotensin-(1-7 decrease sFlt1 release in normal but not preeclamptic chorionic villi: an in vitro study

    Moorefield Cheryl


    Full Text Available Abstract Background During preeclampsia, placental angiogenesis is impaired. Factors released from the placenta including vascular endothelial growth factor (VEGF, placental growth factor (PLGF, soluble VEGF receptor 1 (sFlt1, and soluble endoglin (sEng are regulatory molecules of placental development and function. While the renin angiotensin system has been shown to regulate angiogenic factors in other research fields, these mechanisms have not been extensively studied during pregnancy. Methods We evaluated the effects of angiotensin II (Ang II and angiotensin-(1-7 [Ang-(1-7] on the release of VEGF, PLGF, sFlt1, and sEng from placental chorionic villi (CV. CV were collected from nulliparous third-trimester normotensive and preeclamptic subjects. CV were incubated for 0, 2, 4, and 16 hours with or without Ang II (1 nM and 1 microM or Ang-(1-7 (1 nM and 1 microM. The release of VEGF, PLGF, sFlt1, sEng, lactate dehydrogenase (LDH, and human placenta lactogen (HPL was measured by ELISA. Results The release of sFlt1, PLGF, sEng from normal and preeclamptic CV increased over time. Release of sFlt1 and sEng was significantly higher from preeclamptic CV. VEGF was below the detectable level of the assay in normal and preeclamptic CV. After 2 hours, sFlt1 release from normal CV was significantly inhibited with Ang II (1 nM and 1 microM and Ang-(1-7 (1 nM and 1 microM. There was a time-dependent increase in HPL indicating that the CV were functioning normally. Conclusions Our study demonstrates a critical inhibitory role of angiotensin peptides on sFlt1 in normal pregnancy. Loss of this regulation in preeclampsia may allow sFlt1 to increase resulting in anti-angiogenesis and end organ damage in the mother.

  6. Intraoperative frozen section analysis of margins in breast conserving surgery significantly decreases reoperative rates: one-year experience at an ambulatory surgical center.

    Jorns, Julie M; Visscher, Daniel; Sabel, Michael; Breslin, Tara; Healy, Patrick; Daignaut, Stephanie; Myers, Jeffrey L; Wu, Angela J


    Intraoperative frozen section (FS) margin evaluation is not common practice for patients undergoing breast conservation therapy (BCT), but offers a significant reduction in reoperation. In this study, a technique to allow for more effective freezing of breast tissue was developed to perform FS evaluation of lumpectomy margins (FSM) for all patients undergoing BCT at an ambulatory surgery center. FS evaluation of sentinel lymph node biopsy specimens was performed concurrently. One hundred eighty-one study and 188 control patients, with and without FS evaluation, were compared. Reexcision was reduced 34% (from 48.9% to 14.9%) and reoperation was reduced 36% (from 55.3% to 19.3%) with FS evaluation. Most of the decrease in reoperative rate was because of a decrease in the need for margin reexcision. The number of patients requiring 1, 2, or 3 operations to complete therapy was 84, 92, and 12, respectively, in the control group, and 146, 33, and 2, respectively, in the study group. Lobular subtype, multifocal disease, and larger tumor size (≥2 cm) were significantly associated with failure of FSM to prevent reoperation, but reoperation rates were still significantly decreased in this subgroup of patients (from 75.5% to 43.8%) with FSM. This study highlights an innovative yet simple and adaptable FS approach that resulted in a nearly 3-fold reduction in reoperation for patients undergoing BCT.

  7. The potential role of cobalt ions released from metal prosthesis on the inhibition of Hv1 proton channels and the decrease in Staphyloccocus epidermidis killing by human neutrophils.

    Daou, Samira; El Chemaly, Antoun; Christofilopoulos, Panayiotis; Bernard, Louis; Hoffmeyer, Pierre; Demaurex, Nicolas


    Infection by Staphylococcus epidermidis is a devastating complication of metal-on-metal (MM) total hip arthroplasty (THA). Neutrophils are the first line of defense against infection, and these innate immune cells are potentially exposed to Co(2+) ions released in the peri-prosthetic tissue by the wear of MM THA. The toxicity of Co(2+) is still debated, but Co(2+) is a potential inhibitor of the Hv1 proton channel that sustains the production of superoxide by neutrophils. In this study, we show that the Co(2+) concentration in peri-prosthetic tissue from patients with MM THA averages 53 μM and that such high concentrations of Co(2+) alter the antibacterial activity of human neutrophils in vitro by inhibiting Hv1 proton channels. We show that submillimolar concentrations of Co(2+) inhibit proton currents, impair the extrusion of cytosolic acid, and decrease the production of superoxide in human neutrophils. As a result, Co(2+) reduces the ability of human neutrophils to kill two strains of Staphyloccocus epidermidis by up to 7-fold at the maximal concentration tested of 100 μM Co(2+). By inhibiting proton channels, the Co(2+) ions released by metal prostheses might therefore promote bacterial infections in patients with metal-on-metal total hip arthroplasty.

  8. Deletion of C7L and K1L genes leads to significantly decreased virulence of recombinant vaccinia virus TianTan.

    Liu, Zheng; Wang, Shuhui; Zhang, Qicheng; Tian, Meijuan; Hou, Jue; Wang, Rongmin; Liu, Chang; Ji, Xu; Liu, Ying; Shao, Yiming


    The vaccinia virus TianTan (VTT) has been modified as an HIV vaccine vector in China and has shown excellent performance in immunogenicity and safety. However, its adverse effects in immunosuppressed individuals warrant the search for a safer vector in the following clinic trails. In this study, we deleted the C7L and K1L genes of VTT and constructed six recombinant vaccinia strains VTT△C7L, VTT△K1L, VTT△C7LK1L, VTKgpe△C7L, VTKgpe△K1L and VTT△C7LK1L-gag. The pathogenicity and immunogenicity of these recombinants were evaluated in mouse and rabbit models. Comparing to parental VTT, VTT△C7L and VTT△K1L showed significantly decreased replication capability in CEF, Vero, BHK-21 and HeLa cell lines. In particular, replication of VTT△C7LK1L decreased more than 10-fold in all four cell lines. The virulence of all these mutants were decreased in BALB/c mouse and rabbit models; VTT△C7LK1L once again showed the greatest attenuation, having resulted in no evident damage in mice and erythema of only 0.4 cm diameter in rabbits, compared to 1.48 cm for VTT. VTKgpe△C7L, VTKgpe△K1L and VTT△C7LK1L-gag elicited as strong cellular and humoral responses against HIV genes as did VTKgpe, while humoral immune response against the vaccinia itself was reduced by 4-8-fold. These data show that deletion of C7L and K1L genes leads to significantly decreased virulence without compromising animal host immunogenicity, and may thus be key to creating a more safe and effective HIV vaccine vector.

  9. Deletion of C7L and K1L genes leads to significantly decreased virulence of recombinant vaccinia virus TianTan.

    Zheng Liu

    Full Text Available The vaccinia virus TianTan (VTT has been modified as an HIV vaccine vector in China and has shown excellent performance in immunogenicity and safety. However, its adverse effects in immunosuppressed individuals warrant the search for a safer vector in the following clinic trails. In this study, we deleted the C7L and K1L genes of VTT and constructed six recombinant vaccinia strains VTT△C7L, VTT△K1L, VTT△C7LK1L, VTKgpe△C7L, VTKgpe△K1L and VTT△C7LK1L-gag. The pathogenicity and immunogenicity of these recombinants were evaluated in mouse and rabbit models. Comparing to parental VTT, VTT△C7L and VTT△K1L showed significantly decreased replication capability in CEF, Vero, BHK-21 and HeLa cell lines. In particular, replication of VTT△C7LK1L decreased more than 10-fold in all four cell lines. The virulence of all these mutants were decreased in BALB/c mouse and rabbit models; VTT△C7LK1L once again showed the greatest attenuation, having resulted in no evident damage in mice and erythema of only 0.4 cm diameter in rabbits, compared to 1.48 cm for VTT. VTKgpe△C7L, VTKgpe△K1L and VTT△C7LK1L-gag elicited as strong cellular and humoral responses against HIV genes as did VTKgpe, while humoral immune response against the vaccinia itself was reduced by 4-8-fold. These data show that deletion of C7L and K1L genes leads to significantly decreased virulence without compromising animal host immunogenicity, and may thus be key to creating a more safe and effective HIV vaccine vector.

  10. Bupropion sustained release treatment decreases craving for video games and cue-induced brain activity in patients with Internet video game addiction.

    Han, Doug Hyun; Hwang, Jun Won; Renshaw, Perry F


    Bupropion has been used in the treatment of patients with substance dependence based on its weak inhibition of dopamine and norepinephrine reuptake. We hypothesized that 6 weeks of bupropion sustained release (SR) treatment would decrease craving for Internet game play as well as video game cue-induced brain activity in patients with Internet video game addiction (IAG). Eleven subjects who met criteria for IAG, playing StarCraft (>30 hr/week), and eight healthy comparison subjects (HC) who had experience playing StarCraft (craving for playing the game, and the severity of Internet addiction were evaluated by Beck Depression Inventory, self-report of craving on a 7-point visual analogue scale, and Young's Internet Addiction Scale, respectively. In response to game cues, IAG showed higher brain activation in left occipital lobe cuneus, left dorsolateral prefrontal cortex, and left parahippocampal gyrus than HC. After a 6 week period of bupropion SR, craving for Internet video game play, total game play time, and cue-induced brain activity in dorsolateral prefrontal cortex were decreased in the IAG. We suggest that bupropion SR may change craving and brain activity in ways that are similar to those observed in individuals with substance abuse or dependence. PsycINFO Database Record 2010 APA, all rights reserved.

  11. Development on significance of slow/controlled release fertilizer%积极发展缓控释肥的重大意义

    曲均峰; 傅送保; 操斌


    Based on the status of low fertilizer utilization rate and return rate in china, the necessity of slow / controlled release fertilizer development, development background and great significance are analyzed, and some suggestions on the slow/controlled release fertilizer future development are proposed.%根据我国农业用肥利用率低、回报率低等现状,分析缓控释肥开发的必要性、发展背詈及重大意义,并对缓控释肥未来发展提出了建议。

  12. Fatty acid oxidation products ('green odour') released from perennial ryegrass following biotic and abiotic stress, potentially have antimicrobial properties against the rumen microbiota resulting in decreased biohydrogenation.

    Huws, S A; Scott, M B; Tweed, J K S; Lee, M R F


    In this experiment, we investigated the effect of 'green odour' products typical of those released from fresh forage postabiotic and biotic stresses on the rumen microbiota and lipid metabolism. Hydroperoxyoctadecatrienoic acid (HP), a combination of salicylic and jasmonic acid (T), and a combination of both (HPT) were incubated in vitro in the presence of freeze-dried ground silage and rumen fluid, under rumen-like conditions. 16S rRNA (16S cDNA) HaeIII-based terminal restriction fragment length polymorphism-based (T-RFLP) dendrograms, canonical analysis of principal coordinates graphs, peak number and Shanon-Weiner diversity indices show that HP, T and HPT likely had antimicrobial effects on the microbiota compared to control incubations. Following 6 h of in vitro incubation, 15.3% of 18:3n-3 and 4.4% of 18:2n-6 was biohydrogenated in control incubations, compared with 1.3, 9.4 and 8.3% of 18:3n-3 for HP, T and HPT treatments, respectively, with negligible 18:2n-6 biohydrogenation seen. T-RFLP peaks lost due to application of HP, T and HPT likely belonged to as yet uncultured bacteria within numerous genera. Hydroperoxyoctadecatrienoic acid, T and HPT released due to plant stress potentially have an antimicrobial effect on the rumen microbiota, which may explain the decreased biohydrogenation in vitro. These data suggest that these volatile chemicals may be responsible for the higher summer n-3 content of bovine milk. © 2013 The Society for Applied Microbiology.

  13. Type 2 Diabetes Risk Allele UBE2E2 Is Associated With Decreased Glucose-Stimulated Insulin Release in Elderly Chinese Han Individuals.

    Xu, Kuanfeng; Jiang, Lin; Zhang, Mei; Zheng, Xuqin; Gu, Yong; Wang, Zhixiao; Cai, Yun; Dai, Hao; Shi, Yun; Zheng, Shuai; Chen, Yang; Ji, Li; Xu, Xinyu; Chen, Heng; Sun, Min; Yang, Tao


    Recently, rs163182 in KCNQ1, rs7612463 in UBE2E2, rs7119 in HMG20A, and rs6815464 in MAEA were discovered as type 2 diabetes (T2D) loci unique to Asians, and rs13342692 in SLC16A11 were newly reported as T2D loci in multiethnicities by genome-wide association (GWA) studies. The aim of the present study is to ascertain the potential associations between these variants and T2D risk in the Chinese population, and characterize diabetic-related quantitative traits underlying these variants.A total of 4268 Chinese Han individuals (1754 patients with T2D and 2514 glucose-tolerant health subjects, age ≥40 years) were genotyped for these 5 variants. All the health individuals underwent an oral glucose tolerance test (OGTT), and measures of insulin release and sensitivity were estimated from insulinogenic, BIGTT, Matsuda, and disposition indices. The associations were determined by using logistic regression analysis.After adjustment for age, sex, and BMI, rs163182 in KCNQ1 (P = 0.002) and rs7612463 in UBE2E2 (P = 0.024) were found to be associated with T2D risk in Chinese Han population. The risk C allele of rs7612463 in UBE2E2 is associated with decreased IGI (P = 0.001), BIGTT-AIR (P = 0.002), CIR (P = 0.002), and DI (P = 0.006). The other 4 variants did not associate with insulin release or sensitivity.UBE2E2 rs7612463 may mediate its diabetogenic impact on insulin response, which highly depends on the impairment of β-cell function.

  14. Expression of chicken interleukin-2 by a highly virulent strain of Newcastle disease virus leads to decreased systemic viral load but does not significantly affect mortality in chickens.

    Susta, Leonardo; Diel, Diego G; Courtney, Sean; Cardenas-Garcia, Stivalis; Sundick, Roy S; Miller, Patti J; Brown, Corrie C; Afonso, Claudio L


    In mammals, interleukin 2 (IL-2) has been shown to decrease replication or attenuate pathogenicity of numerous viral pathogens (herpes simplex virus, vaccinia virus, human respiratory syncytial virus, human immunodeficiency virus) by activating natural killer cells (NK), cytotoxic T lymphocytes and expanding subsets of memory cells. In chickens, IL-2 has been shown to activate T cells, and as such it might have the potential to affect replication and pathogenesis of Newcastle disease virus (NDV). To assess the effect of IL-2 during NDV infection in chickens, we produced a recombinant virulent NDV strain expressing chicken IL-2 (rZJ1-IL2). The effects of IL-2 expression were investigated in vivo using the intracerebral pathogenicity index (ICPI) in day-old chicks and pathogenesis experiments in 4-week-old chickens. In these studies, rZJ1-IL2 was compared to a control virus expressing the green fluorescent protein (rZJ1-GFP). Assessed parameters included survival curves, detailed histological and immunohistochemical grading of lesions in multiple organs, and virus isolation in blood, spleen and mucosal secretions of infected birds. At the site of infection (eyelid), expression of IL-2 was demonstrated in areas of rZJ-IL2 replication, confirming IL-2 production in vivo. Compared to rZJ1-GFP strain, rZJ1-IL2 caused milder lesions and displayed decreased viral load in blood, spleen and mucosal secretions of infected birds. In the rZJ1-IL2-infected group, virus level in the blood peaked at day 4 post-infection (pi) (10(3.46) EID50 /0.1 ml) and drastically decreased at day 5 pi (10(0.9) EID50/0.1 ml), while in the rZJ1-GFP-infected group virus levels in the blood reached 10(5.35) EID50/0.1 ml at day 5. However, rZJ1-IL2-infected groups presented survival curves similar to control birds infected with rZJ1-GFP, with comparable clinical signs and 100 % mortality. Further, expression of IL-2 did not significantly affect the ICPI scores, compared to rZJ1-GFP strain. Increased

  15. An acute bout of self-myofascial release increases range of motion without a subsequent decrease in muscle activation or force.

    MacDonald, Graham Z; Penney, Michael D H; Mullaley, Michelle E; Cuconato, Amanda L; Drake, Corey D J; Behm, David G; Button, Duane C


    Foam rolling is thought to improve muscular function, performance, overuse, and joint range of motion (ROM); however, there is no empirical evidence demonstrating this. Thus, the objective of the study was to determine the effect of self-myofascial release (SMR) via foam roller application on knee extensor force and activation and knee joint ROM. Eleven healthy male (height 178.9 ± 3.5 cm, mass 86.3 ± 7.4 kg, age 22.3 ± 3.8 years) subjects who were physically active participated. Subjects' quadriceps maximum voluntary contraction force, evoked force and activation, and knee joint ROM were measured before, 2 minutes, and 10 minutes after 2 conditions: (a) 2, 1-minute trials of SMR of the quadriceps via a foam roller and (b) no SMR (Control). A 2-way analysis of variance (condition × time) with repeated measures was performed on all dependent variables recorded in the precondition and postcondition tests. There were no significant differences between conditions for any of the neuromuscular dependent variables. However, after foam rolling, subjects' ROM significantly (p foam rolling, which no longer existed after foam rolling. In conclusion, an acute bout of SMR of the quadriceps was an effective treatment to acutely enhance knee joint ROM without a concomitant deficit in muscle performance.

  16. “金正大”缓控释肥发展的重大意义%Development on significance of Jinzhengda Slow-release Fertilizer

    杨露; 韩奎恒


    Aiming at the continuous decrease of agricultural land use area with food total demand is increasing. To improve the quality of crop seeds at the same time, also pay attention to the quality of the fertilizer, provide the necessary nutrients for the growth of crops. “Jinzhengda” Slow -release Fertilizer is coming. In this paper, based on the background of the development on the slow controlled release fertilizer in China were analyzed, Explore“Jinzhengda”slow controlled release fertilizer in today's important role in the development of agricultural modernization.%针对我国农业土地利用面积的不断减少与粮食总需求量不断增加的矛盾,在提高农作物种子质量的同时,还要注重化肥的质量,为农作物的生长提供必需的营养物质。“金正大”缓控释肥应运而生,本文就通过对我国缓控释肥发展的背景进行分析,探究“金正大”缓控释肥在当今农业现代化发展中的重要作用。

  17. Decreased expression of Kallmann syndrome 1 sequence gene (KAL1) contributes to oral squamous cell carcinoma progression and significantly correlates with poorly differentiated grade.

    Liu, Jiannan; Cao, Wei; Chen, Wantao; Xu, Liqun; Zhang, Chenping


    Kallmann syndrome 1 sequence gene (KAL1) protein is an extracellular matrix associated protein which plays vital roles in neurons development and cell migration. However, its biological functions and clinical implications have yet not been revealed in oral carcinogenesis. The objective of the study was to evaluate the role of KAL1 in oral cancer and determine clinical significance of KAL1 in oral squamous cell carcinomas (OSCCs). The expression pattern of KAL1 was examined in a testing cohort including OSCCs (n = 42) and paired adjacent tissues (PATs) (n = 14) by real-time PCR. The result was further validated in a validating cohort of OSCCs (n = 32). Correlation between clinicopathological parameters and KAL1 mRNA levels was analyzed by Kruskal-Wallis test. In vitro, the effects of KAL1 ablation through siRNA-mediated knockdown on the proliferation of OSCC cells were determined by CCK-8, BrdU, and colonies formation assays, respectively. In addition, cell cycle distribution was further evaluated by cytometry. We observed that remarkably decreased expression of KAL1 mRNA in two independent cohorts (P = 0.0002 and P = 0.033, respectively). Furthermore, downregulated KAL1 mRNA was significantly associated with worse pathological grade (P = 0.013 and P = 0.035, respectively). Upon KAL1 silencing, the proliferation and colonies formation potentials of OSCC cells were notably promoted by accelerating G1 to M phase transition. These data indicated that KAL1 plays a potential suppressive role on OSCC initiation and progression, and KAL1 gene may serve as an adjuvant biomarker for the identification of pathological grade. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. Delaying discharge after the stimulus significantly decreases muscle activation thresholds with small impact on the selectivity: an in vivo study using TIME.

    Maciejasz, Paweł; Badia, Jordi; Boretius, Tim; Andreu, David; Stieglitz, Thomas; Jensen, Winnie; Navarro, Xavier; Guiraud, David


    The number of devices for electrical stimulation of nerve fibres implanted worldwide for medical applications is constantly increasing. Stimulation charge is one of the most important parameters of stimulation. High stimulation charge may cause tissue and electrode damage and also compromise the battery life of the electrical stimulators. Therefore, the objective of minimizing stimulation charge is an important issue. Delaying the second phase of biphasic stimulation waveform may decrease the charge required for fibre activation, but its impact on stimulation selectivity is not known. This information is particularly relevant when transverse intrafascicular multichannel electrode (TIME) is used, since it has been designed to provide for high selectivity. In this in vivo study, the rat sciatic nerve was electrically stimulated using monopolar and bipolar configurations with TIME. The results demonstrated that the inclusion of a 100-μs delay between the cathodic and the anodic phase of the stimulus allows to reduce charge requirements by around 30 %, while only slightly affecting stimulation selectivity. This study shows that adding a delay to the typical stimulation waveform significantly ([Formula: see text]) reduces the charge required for nerve fibres activation. Therefore, waveforms with the delayed discharge phase are more suitable for electrical stimulation of nerve fibres.

  19. Surface deformation associated with the 2013 Mw7.7 Balochistan earthquake: Geologic slip rates may significantly underestimate strain release

    Gold, Ryan; Reitman, Nadine; Briggs, Richard; Barnhart, William; Hayes, Gavin


    sections with narrow deformation zones in order to capture the full deformation field. Our results imply that hazard analyses based on geologically-determined fault slip rates (e.g., near-field) should consider the significant and heterogeneous mismatch we document between on- and off-fault coseismic deformation.

  20. A decrease in serum estradiol levels after human chorionic gonadotrophin administration predicts significantly lower clinical pregnancy and live birth rates in in vitro fertilization cycles.

    Kondapalli, L A; Molinaro, T A; Sammel, M D; Dokras, A


    Although close observation of serum estradiol (E2) levels remains a mainstay of assessing clinical response to controlled ovarian stimulation, the prognostic value of any change in E2 levels after administration of hCG remains unclear. The objective of this study is to evaluate the relationship between serum E2 response after hCG administration and the clinical pregnancy and live birth rates in fresh IVF cycles. We conducted a retrospective cohort study of women aged 21-45 years undergoing their first IVF cycle from 1999 to 2008 at a single practice. We compared the post-hCG serum E2 level with values on the day of hCG trigger. IVF cycles were stratified by post-hCG E2 response and appropriate parametric and non-parametric statistics were performed. Clinical intrauterine pregnancy and live births were the primary outcomes of interest. Multivariable logistic regression models were created to identify predictive factors associated with outcomes while adjusting for potential confounders. Among the 1712 IVF cycles, 1065 exhibited a >10% increase (Group A), 525 had a plateau (± 10%, Group B) and 122 showed a >10% decrease (Group C) in post-hCG E2 levels. While the E2 levels on the day of hCG were similar across groups, Group C had more patients with diminished ovarian reserve, required higher gonadotrophin doses and had the lowest implantation rates. After adjusting for age, total gonadotrophin dose, infertility diagnosis, number of oocytes and number of transferred embryos, the associations between post-hCG E2 decline (Group C) and clinical pregnancy [adjusted odds ratio (aOR): 0.53; 95% confidence interval (CI): 0.33-0.84, P= 0.007] and live birth (aOR: 0.40; 95% CI: 0.22-0.71, P= 0.002) were significant. We also found significant associations between E2 plateau (Group B) and clinical pregnancy (aOR: 0.73; 95% CI: 0.57-0.94, P= 0.013) and live birth (aOR: 0.74; 95% CI: 0.56-0.97, P= 0.032) when adjusting for the same factors. In our study, >10% decrease in E2 levels

  1. Cranberry juice concentrate does not significantly decrease the incidence of acquired bacteriuria in female hip fracture patients receiving urine catheter: a double-blind randomized trial

    Gunnarsson AK


    Full Text Available Anna-Karin Gunnarsson,1 Lena Gunningberg,2 Sune Larsson,1 Kenneth B Jonsson1 1Institution of Surgical Sciences, Uppsala University, Uppsala, Sweden; 2Institution of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden Background: Urinary tract infection (UTI is a common complication among patients with hip fractures. Receiving an indwelling urinary catheter is a risk factor for developing UTIs. Treatment of symptomatic UTIs with antibiotics is expensive and can result in the development of antimicrobial resistance. Cranberries are thought to prevent UTI. There is no previous research on this potential effect in patients with hip fracture who receive urinary catheters. Aim: The aim of this study is to investigate whether intake of cranberry juice concentrate preoperatively decreases the incidence of postoperative UTIs in hip fracture patients that received a urinary catheter. Design: This study employed a randomized, placebo-controlled double-blind trial. Method: Female patients, aged 60 years and older, with hip fracture (n=227 were randomized to receive cranberry or placebo capsules daily, from admission, until 5 days postoperatively. Urine cultures were obtained at admission, 5 and 14 days postoperatively. In addition, Euro Qual five Dimensions assessments were performed and patients were screened for UTI symptoms. Result: In the intention-to-treat analysis, there was no difference between the groups in the proportion of patients with hospital-acquired postoperative positive urine cultures at any time point. When limiting the analysis to patients that ingested at least 80% of the prescribed capsules, 13 of 33 (39% in the placebo group and 13 of 47 (28% in the cranberry group (P=0.270 had a positive urine culture at 5 days postoperatively. However, this difference was not statistically significant (P=0.270. Conclusion: Cranberry concentrate does not seem to effectively prevent UTIs in female patients with hip fracture and

  2. Expression of chicken interleukin-2 by a highly virulent strain of Newcastle disease virus leads to decreased systemic viral load but does not significantly affect mortality in chickens

    In mammals, interleukin 2 (IL-2) has been shown to decrease replication or attenuate pathogenicity of numerous viral pathogens by activating natural killer cells (NK), cytotoxic T lymphocytes, and expanding subsets of memory cells. In chickens, IL-2 has been shown to activate T cells, and as such i...

  3. Intrathecal co-administration of ketamine and morphine preventing activation of astrocytes and decreasing releases of IL-1β and IL-6 from spinal cord in rats of morphine tolerance


    Objective: To investigate the effects of intrathecal administration of ketamine, a non-competitive N-methy-D-aspartate receptor antagonist, combined with morphine on the activation of astrocytes and releases of IL-1β and IL-6 from spinal cord in the rats of morphine tolerance. Methods: Twenty-seven Sprague-Dawley male rats were randomly divided into sham-operated, morphine tolerance, and morphine plus ketamine group. The subarachnoid catheterization of all the rats was prepared by the method of Jianping Yang.Morphine 20 μg in 10 μl was administrated intrathecally to induce spinal morphine tolerance once daily for 5 consecutive days. Morphine and ketamine 250 μg in 10 μl total volume was given in morphine plus ketamine group. Three groups all received intrathecal morphine 5 μg in 10 μl for morphine challenge test at 24 h after last administration of the morphine. After morphine challenge test, lumbar spinal tissues were taken for measurement of glial fibrillary acidic protein (GFAP) of astrocyte in lumbar spinal horn cord by immunohistochemistry and IL-1βand IL-6 of spinal cord by ELISA. Results: The decrease of %MPE induced by chronic intrathecal morphine was inhibited by ketamine and hyperalgesia and allodynia induced by morphine-withdrawl were alleviated. The average areas, the average absorbency (-A), the integral absorbency (A) of GFAP immuno-reactive cells in the dorsal horn, and IL-1β and IL-6 of spinal cord were significantly larger in morphine tolerance group than in morphine plus ketamine group. Conclusion: Co-administration of ketamine and morphine enhance antinociceptive effect of morphine and prevent the development of morphine tolerance. Ketamine might attenuate the activation of astrocytes and inhibit the release of IL-1β and IL-6 from spinal cord in repeated intrathecal morphine rats.

  4. Tenofovir disoproxil fumarate significantly decreases serum lipoprotein levels compared with entecavir nucleos(t)ide analogue therapy in chronic hepatitis B carriers.

    Shaheen, A A; AlMattooq, M; Yazdanfar, S; Burak, K W; Swain, M G; Congly, S E; Borman, M A; Lee, S S; Myers, R P; Coffin, C S


    Tenofovir disoproxil fumarate (TDF) and entecavir (ETV) are first-line treatments for chronic hepatitis B (CHB). Studies suggest lipid lowering effect of TDF in human immunodeficiency virus positive (HIV+) individuals, but the effect on lipids and cardiovascular disease (CVD) risk in CHB is unknown. To compare TDF vs ETV effects on lipid levels in CHB. In this retrospective cohort study, data on serum lipids and CVD risk factors at baseline and ~1 year on TDF or ETV were collected from CHB carriers. We used propensity score matched models to assess the effect on total cholesterol (TC), LDL-C, HDL and triglycerides (TGL). In 348 patients, median age was 57 (IQR: 47-65 years), 63% were male, 77% were Asian, 19% were cirrhotic, 25% were HBeAg positive at baseline, and 72% received TDF vs 28% ETV. ETV-treated patients were older (median age: 60 vs 55, P<.01), had similar smoking and hypertension rates, but diabetes and dyslipidemia were more prevalent (19% vs 9%, P=.01; 14% vs 6%, P=.05, respectively). In propensity score matched models for age, gender, usage of lipid lowering agents, dyslipidemia and diabetes, TDF-treated patients were more likely to show a 20% decrease in TC (95% CI: 3%-25%), LDL-C (95% CI: 1%-25%) and HDL-C (CI: 10%-30%) levels compared with those on ETV. No change in TGL was observed in either group. A greater decline in TC, LDL-C and HDL was observed in CHB carriers receiving TDF compared with ETV. These data may influence anti-viral choice in CHB carriers at risk for CVD. © 2017 John Wiley & Sons Ltd.

  5. Human circulating plasma DNA significantly decreases while lymphocyte DNA damage increases under chronic occupational exposure to low-dose gamma-neutron and tritium β-radiation

    Korzeneva, Inna B., E-mail: [Russian Federal Nuclear Center – All-Russian Research Institute of Experimental Physics (RFNC-VNIIEF) 607190, Sarov, 37 Mira ave., Nizhniy Novgorod Region (Russian Federation); Kostuyk, Svetlana V.; Ershova, Liza S. [Research Centre for Medical Genetics, Russian Academy of Medical Sciences, 115478 Moscow, 1 Moskvorechye str. (Russian Federation); Osipov, Andrian N. [Federal Medial and Biological Center named after Burnazyan of the Federal Medical and Biological Agency (FMBTz named after Burnazyan of FMBA), Moscow (Russian Federation); State Research Center - Burnasyan Federal Medical Biophysical Center of Federal Medical Biological Agency, Zhivopisnaya, 46, Moscow, 123098 (Russian Federation); Zhuravleva, Veronika F.; Pankratova, Galina V. [Russian Federal Nuclear Center – All-Russian Research Institute of Experimental Physics (RFNC-VNIIEF) 607190, Sarov, 37 Mira ave., Nizhniy Novgorod Region (Russian Federation); Porokhovnik, Lev N.; Veiko, Natalia N. [Research Centre for Medical Genetics, Russian Academy of Medical Sciences, 115478 Moscow, 1 Moskvorechye str. (Russian Federation)


    Highlights: • The chronic exposure to low-dose IR induces DSBs in human lymphocytes (TM index). • Exposure to IR decreases the level of human circulating DNA (cfDNA index). • IR induces an increase of DNase1 activity (DNase1 index) in plasma. • IR induces an increase of the level of antibodies to DNA (Ab DNA index) in plasma. • The ratio cfDNA/(DNase 1 × Ab DNA × TM) is a potential marker of human exposure to IR. - Abstract: The blood plasma of healthy people contains cell-fee (circulating) DNA (cfDNA). Apoptotic cells are the main source of the cfDNA. The cfDNA concentration increases in case of the organism’s cell death rate increase, for example in case of exposure to high-dose ionizing radiation (IR). The objects of the present research are the blood plasma and blood lymphocytes of people, who contacted occupationally with the sources of external gamma/neutron radiation or internal β-radiation of tritium N = 176). As the controls (references), blood samples of people, who had never been occupationally subjected to the IR sources, were used (N = 109). With respect to the plasma samples of each donor there were defined: the cfDNA concentration (the cfDNA index), DNase1 activity (the DNase1 index) and titre of antibodies to DNA (the Ab DNA index). The general DNA damage in the cells was defined (using the Comet assay, the tail moment (TM) index). A chronic effect of the low-dose ionizing radiation on a human being is accompanied by the enhancement of the DNA damage in lymphocytes along with a considerable cfDNA content reduction, while the DNase1 content and concentration of antibodies to DNA (Ab DNA) increase. All the aforementioned changes were also observed in people, who had not worked with the IR sources for more than a year. The ratio cfDNA/(DNase1 × Ab DNA × TM) is proposed to be used as a marker of the chronic exposure of a person to the external low-dose IR. It was formulated the assumption that the joint analysis of the cfDNA, DNase1, Ab

  6. Label-free LC-MSMS analysis of vitreous from autoimmune uveitis reveals a significant decrease in secreted Wnt signalling inhibitors DKK3 and SFRP2.

    Hauck, Stefanie M; Hofmaier, Florian; Dietter, Johannes; Swadzba, Margarete E; Blindert, Marcel; Amann, Barbara; Behler, Jennifer; Kremmer, Elisabeth; Ueffing, Marius; Deeg, Cornelia A


    Equine recurrent uveitis is a severe and frequent blinding disease in horses which presents with auto-reactive invading T-cells, resulting in the destruction of the inner eye. Infiltration of inflammatory cells into the retina and vitreous is driven by currently unknown guidance cues, however surgical removal of the vitreous (vitrectomy) has proven therapeutically successful. Therefore, proteomic analyses of vitrectomy samples are likely to result in detection of proteins contributing to disease pathogenesis. Vitreous from healthy and ERU diseased horses were directly compared by quantitative mass spectrometry based on label-free quantification of peak intensities across samples. We found a significant upregulation of complement and coagulation cascades and downregulation of negative paracrine regulators of canonical Wnt signalling including the Wnt signalling inhibitors DKK3 and SFRP2. Based on immunohistochemistry, both proteins are expressed in equine retina and suggest localisation to retinal Müller glial cells (RMG), which may be the source cells for these proteins. Furthermore, retinal expression levels and patterns of DKK3 change in response to ERU. Since many other regulated proteins identified here are associated with RMG cells, these cells qualify as the prime responders to autoimmune triggers.

  7. Pediatric residents experience a significant decline in their response capabilities to simulated life-threatening events as their training frequency in cardiopulmonary resuscitation decreases.

    Roy, Kevin M; Miller, Michael P; Schmidt, Kathleen; Sagy, Mayer


    To determine the frequency of cardiopulmonary resuscitation education using high-fidelity patient simulators during pediatric residency training. Randomized controlled trial. Suburban tertiary care children's hospital residency training program. Twenty-four second year pediatric residents. Twenty-four second year pediatric residents were randomized into two study groups, 12 residents in each. Both groups completed a formal resuscitation training course utilizing lectures, skill stations, and six scenarios on high-fidelity patient stimulators. Group A was retested on three scenarios 4 months after training and group B was similarly retested 8 months after training. Time intervals from induction of a clinical problem to its definitive management were recorded for each resident. Residents were also asked to complete surveys following each episode of training and testing. The mean time intervals, for group A, to start effective bag mask ventilation and chest compressions in response to apnea and cardiac arrest were 17.75 secs (± 3.39 secs) and 23.42 secs (± 9.33 secs), respectively. These were significantly shorter than 32.7 secs (± 18.6 secs) and 81.2 secs (± 74.9 secs), for group B, respectively (p training, when compared to 4 months after training. These results may indicate that residents require more frequent training than currently recommended.

  8. Ghrelin decreases firing activity of gonadotropin-releasing hormone (GnRH neurons in an estrous cycle and endocannabinoid signaling dependent manner.

    Imre Farkas

    Full Text Available The orexigenic peptide, ghrelin is known to influence function of GnRH neurons, however, the direct effects of the hormone upon these neurons have not been explored, yet. The present study was undertaken to reveal expression of growth hormone secretagogue receptor (GHS-R in GnRH neurons and elucidate the mechanisms of ghrelin actions upon them. Ca(2+-imaging revealed a ghrelin-triggered increase of the Ca(2+-content in GT1-7 neurons kept in a steroid-free medium, which was abolished by GHS-R-antagonist JMV2959 (10 µM suggesting direct action of ghrelin. Estradiol (1nM eliminated the ghrelin-evoked rise of Ca(2+-content, indicating the estradiol dependency of the process. Expression of GHS-R mRNA was then confirmed in GnRH-GFP neurons of transgenic mice by single cell RT-PCR. Firing rate and burst frequency of GnRH-GFP neurons were lower in metestrous than proestrous mice. Ghrelin (40 nM-4 μM administration resulted in a decreased firing rate and burst frequency of GnRH neurons in metestrous, but not in proestrous mice. Ghrelin also decreased the firing rate of GnRH neurons in males. The ghrelin-evoked alterations of the firing parameters were prevented by JMV2959, supporting the receptor-specific actions of ghrelin on GnRH neurons. In metestrous mice, ghrelin decreased the frequency of GABAergic mPSCs in GnRH neurons. Effects of ghrelin were abolished by the cannabinoid receptor type-1 (CB1 antagonist AM251 (1µM and the intracellularly applied DAG-lipase inhibitor THL (10 µM, indicating the involvement of retrograde endocannabinoid signaling. These findings demonstrate that ghrelin exerts direct regulatory effects on GnRH neurons via GHS-R, and modulates the firing of GnRH neurons in an ovarian-cycle and endocannabinoid dependent manner.

  9. Precision intrauterine contraception may significantly increase continuation of use: a review of long-term clinical experience with frameless copper-releasing intrauterine contraception devices

    Wildemeersch D


    Full Text Available Dirk Wildemeersch,1 Ansgar Pett,2 Sohela Jandi,2 Thomas Hasskamp,3 Patrick Rowe,4 Marc Vrijens5 1Gynecological Outpatient Clinic and IUD Training Center, Ghent, Belgium; 2Gynecological Outpatient Clinic, Berlin, Germany; 3Gynecological Outpatient Clinic, Münster, Germany; 4Formely IUD Research Group at the UNDP/UNFPA/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction, World Health Organization, Geneva, Switzerland; 5Gynecological Outpatient Clinic, Ghent, Belgium Objective: The purpose of this paper is to review the experience with the frameless, anchored, GyneFix copper-releasing intrauterine contraceptive devices (IUCDs/IUDs (Contrel Europe, Belgium, and to demonstrate their high acceptability and low rate of discontinuation of use, which could contribute to current efforts that aim to reduce radically the high number of unintended pregnancies and induced abortions, particularly in young women. Materials and methods: This paper is based on studies that examined the differences in uterine volume and cavity size, related to age and parity, and on original clinical research data and practical experience with frameless copper IUDs, as well as on literature data on the IUD–endometrial cavity relationship of conventional IUDs, with special reference to side effects and user discontinuation. Results: The mean transverse diameter in nulliparous and parous women is significantly less than the length of the transverse arm of the TCu380A IUD (ParaGard, Duramed, NY, USA or the levonorgestrel intrauterine system (Mirena, Bayer, Germany. Small, frameless, flexible, and unidimensional copper IUDs appear to be well tolerated, with less impact on menstrual bleeding, resulting in low discontinuation rates when compared with standard-size conventional IUDs, which often result in increased expulsion rates, complaints of pain and erratic or increased menstrual bleeding, and subsequent high rates of

  10. A circle dance in a psychiatric setting : can a circle dance intervention decrease levels of depressed affect among patients with mental health illnesses and, if so, what aspect of this dance is most significant?

    Beard, Ella King


    This study investigates the role of the circle dance in decreasing depressed affect amongst a group of 45 patients with severe mental health illnesses and highlights the most significant aspect of that dance. Patients participated in one of four conditions: a group performing a regular traditional upbeat Irish circle dance holding hands and with a jump step [jump+hands]; a group performing the same dance holding hands with no jump step [hands]; a group performing the same dance without holdin...

  11. Flouride release from various restorative materials.

    Bala, O; Uçtaşli, M; Can, H; Türköz, E; Can, M


    Fluoride release from six light-activated restorative materials, including two resinmodified glass-ionomers, two composites, and two compomers, was evaluated and compared with one conventional acid-based glass-ionomer cement. The amount and rate of release varied among the tested materials. Both resin-modified glass-ionomers and the conventional acid-base glass-ionomer cements released more fluoride then the composites and compomers (p < 0.05). Additionally, composite materials released less fluoride than compomer materials (p < 0.05). Release of fluoride by the tested materials showed a significant decrease after all the tested time intervals.

  12. [Evaluating the Significance of Odor Gas Released During the Directly Drying Process of Sludge: Based on the Multi-index Integrated Assessment Method].

    Ding, Wen-jie; Chen, Wen-he; Deng, Ming-jia; Luo, Hui; Li, Lin; Liu, Jun-xin


    Co-processing of sewage sludge using the cement kiln can realize sludge harmless treatment, quantity reduction, stabilization and reutilization. The moisture content should be reduced to below 30% to meet the requirement of combustion. Thermal drying is an effective way for sludge desiccation. Odors and volatile organic compounds are generated and released during the sludge drying process, which could lead to odor pollution. The main odor pollutants were selected by the multi-index integrated assessment method. The concentration, olfactory threshold, threshold limit value, smell security level and saturated vapor pressure were considered as indexes based on the related regulations in China and foreign countries. Taking the pollution potential as the evaluation target, and the risk index and odor emission intensity as evaluation indexes, the odor pollution potential rated evaluation model of the pollutants was built according to the Weber-Fechner law. The aim of the present study is to form the rating evaluation method of odor potential pollution capacity suitable for the directly drying process of sludge.

  13. The highly selective 5-hydroxytryptamine (5-HT)2A receptor antagonist, EMD 281014, significantly increases swimming and decreases immobility in male congenital learned helpless rats in the forced swim test.

    Patel, Jignesh G; Bartoszyk, Gerd D; Edwards, Emmeline; Ashby, Charles R


    We examined the effect of the highly selective 5-hydroxytryptamine (5-HT)(2A) receptor antagonist 7-[4-[2-(4-fluoro-phenyl)-ethyl]-piperazine-1-carbonyl]-1H-indole-3-carbonitrile HCl (EMD 281014) in congenital learned helpless male rats in the forced swim test. The administration of EMD-281014 (0.3-30 mg/kg i.p.) to congenital learned helpless rats dose-dependently and significantly (at 10 and 30 mg/kg) decreased immobility and increased swimming compared to vehicle-treated animals. Thus, EMD 281014 produces effects in the forced swim test resembling those of antidepressants.

  14. Plasma levels of angiopoietin-like protein 4 (ANGPTL4) are significantly lower preoperatively in colorectal cancer patients than in cancer-free patients and are further decreased during the first month after minimally invasive colorectal resection.

    Shantha Kumara, H M C; Kirchoff, Daniel; Herath, Sajith A; Jang, Joon Ho; Yan, Xiaohong; Grieco, Michael; Cekic, Vesna; Whelan, Richard L


    Surgery has been associated with proangiogenic plasma protein changes that may promote tumor growth. Angiopoietin-like protein 4 (ANGPTL4) is expressed by endothelial cells and other tissues in response to hypoxia. Both intact ANGPTL4 and its partly degraded C-terminal fragment may promote tumor angiogenesis. This study had two purposes: to measure and compare preoperative plasma ANGPTL4 levels in patients with colorectal cancer (CRC) and benign colorectal disease (BCD) and to determine plasma levels after minimally invasive colorectal resection (MICR) for CRC. Plasma was obtained from an IRB-approved plasma/data bank. Preoperative plasma ANGPTL4 levels were measured for CRC and BCD patients, but postoperative levels were determined only for CRC patients for whom a preoperative, a postoperative day (POD) 3, and at least one late postoperative sample (POD 7-55) were available. Late samples were bundled into four time blocks and considered as single time points. ANGPTL4 levels (mean ± SD) were measured via ELISA and compared (significance, p MICR for CRC, levels are significantly lower for over a month compared with the preoperative level; the cause for this persistent decrease is unclear. The implications of both the lower preoperative level and the persistently decreased postoperative levels are unclear. Further studies are needed.

  15. A dual acting compound releasing nitric oxide (NO) and ibuprofen, NCX 320, shows significant therapeutic effects in a mouse model of muscular dystrophy.

    Sciorati, Clara; Miglietta, Daniela; Buono, Roberta; Pisa, Viviana; Cattaneo, Dario; Azzoni, Emanuele; Brunelli, Silvia; Clementi, Emilio


    A resolutive therapy for muscular dystrophies, a heterogeneous group of genetic diseases leading to muscular degeneration and in the severe forms to death, is still lacking. Since inflammation and defects in nitric oxide generation are recognized key pathogenic events in muscular dystrophy, we have analysed the effects of a derivative of ibuprofen, NCX 320, belonging to the class of cyclooxygenase inhibiting nitric oxide donator (CINOD), in the α-sarcoglycan null mice, a severe mouse model of dystrophy. NCX 320 was administered daily in the diet for 8months starting 1month from weaning. Muscle functional recovery was evaluated by free wheel and treadmill tests at 8months. Serum creatine kinase activity, as well as the number of diaphragm inflammatory infiltrates and necrotic fibres, was measured as indexes of skeletal muscle damage. Muscle regeneration was evaluated in diaphragm and tibialis anterior muscles, measuring the numbers of centronucleated fibres and of myogenic precursor cells. NCX 320 mitigated muscle damage, reducing significantly serum creatine kinase activity, the number of necrotic fibres and inflammatory infiltrates. Moreover, NCX 320 stimulated muscle regeneration increasing significantly the number of myogenic precursor cells and regenerating fibres. All these effects concurred in inducing a significant improvement of muscle function, as assessed by both free wheel and treadmill tests. These results describe the properties of a new compound incorporating nitric oxide donation together with anti-inflammatory properties, showing that it is effective in slowing muscle dystrophy progression long term. Of importance, this new compound deserves specific attention for its potential in the therapy of muscular dystrophy given that ibuprofen is well tolerated in paediatric patients and with a profile of safety that makes it suitable for chronic treatment such as the one required in muscular dystrophies.

  16. What is the best treatment to decrease pro-inflammatory cytokine release in acute skeletal muscle injury induced by trauma in rats: low-level laser therapy, diclofenac, or cryotherapy?

    de Almeida, Patrícia; Tomazoni, Shaiane Silva; Frigo, Lucio; de Carvalho, Paulo de Tarso Camillo; Vanin, Adriane Aver; Santos, Larissa Aline; Albuquerque-Pontes, Gianna Móes; De Marchi, Thiago; Tairova, Olga; Marcos, Rodrigo Labat; Lopes-Martins, Rodrigo Álvaro Brandão; Leal-Junior, Ernesto Cesar Pinto


    Currently, treatment of muscle injuries represents a challenge in clinical practice. In acute phase, the most employed therapies are cryotherapy and nonsteroidal anti-inflammatory drugs. In the last years, low-level laser therapy (LLLT) has becoming a promising therapeutic agent; however, its effects are not fully known. The aim of this study was to analyze the effects of sodium diclofenac (topical application), cryotherapy, and LLLT on pro-inflammatory cytokine levels after a controlled model of muscle injury. For such, we performed a single trauma in tibialis anterior muscle of rats. After 1 h, animals were treated with sodium diclofenac (11.6 mg/g of solution), cryotherapy (20 min), or LLLT (904 nm; superpulsed; 700 Hz; 60 mW mean output power; 1.67 W/cm(2); 1, 3, 6 or 9 J; 17, 50, 100 or 150 s). Assessment of interleukin-1β and interleukin-6 (IL-1β and IL-6) and tumor necrosis factor-alpha (TNF-α) levels was performed at 6 h after trauma employing enzyme-linked immunosorbent assay method. LLLT with 1 J dose significantly decreased (p cryotherapy groups. On the other hand, treatment with diclofenac and cryotherapy does not decrease pro-inflammatory cytokine levels compared to the non-treated injured group. Therefore, we can conclude that 904 nm LLLT with 1 J dose has better effects than topical application of diclofenac or cryotherapy in acute inflammatory phase after muscle trauma.


    ANDREWS, MALCOLM J. [Los Alamos National Laboratory; BERCHANE, NADER S. [Los Alamos National Laboratory; CARSON, KENNETH H. [Los Alamos National Laboratory; RICE-FICHT, ALLISON C. [Los Alamos National Laboratory


    Piroxicam containing PLG microspheres having different size distributions were fabricated, and in vitro release kinetics were determined for each preparation. Based on the experimental results, a suitable mathematical theory has been developed that incorporates the effect of microsphere size distribution and polymer degradation on drug release. We show from in vitro release experiments that microsphere size has a significant effect on drug release rate. The initial release rate decreased with an increase in microsphere size. In addition, the release profile changed from first order to concave-upward (sigmoidal) as the system size was increased. The mathematical model gave a good fit to the experimental release data.

  18. Human circulating ribosomal DNA content significantly increases while circulating satellite III (1q12) content decreases under chronic occupational exposure to low-dose gamma- neutron and tritium beta-radiation.

    Korzeneva, Inna B; Kostuyk, Svetlana V; Ershova, Elizaveta S; Skorodumova, Elena N; Zhuravleva, Veronika F; Pankratova, Galina V; Volkova, Irina V; Stepanova, Elena V; Porokhovnik, Lev N; Veiko, Natalia N

    A single exposure to ionizing radiation (IR) results in an elevated cell-free DNA (cfDNA) content in the blood plasma. In this case, the cfDNA concentration can be a marker of the cell death in the organism. However, a chronic exposure to a low-dose IR enhances both the endonuclease activity and titer of antibodies to DNA in blood plasma, resulting in a decrease of the total concentration of circulating cfDNA in exposed people. In this case, the total cfDNA concentration should not be considered as a marker of the cell death in an exposed body. We assumed that a pool of the cfDNA circulating in the exposed people contains DNA fragments, which are resistant to a double-strand break formation in the environment of the elevated plasma endonuclease activity, and can be accumulated in the blood plasma. In order to test this hypothesis, we studied the content of GC-rich sequences (69%GC) of the transcribed region of human ribosomal repeat (rDNA), as well as the content of AT-rich repeat (63%AT) of satellite III (1q12) in the cfDNA samples obtained from 285 individuals. We have found that a chronic exposure to gamma-neutron radiation (N=88) and tritium β-radiation (N=88) evokes an increase of the rDNA content (RrDNA index) and a decrease of the satellite III content (RsatIII index) in the circulating cfDNA as compared with the cfDNA of non-exposed people (N=109). Such index that simultaneously displays both the increase of rDNA content and decrease of satellite III content in the cfDNA (RrDNA/RsatIII) can be recommended as a marker of chronic processes in the body that involve the elevated cell death rate and/or increased blood plasma endonuclease activity. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Clinical Significance of Pro-gastrin-releasing Peptide for Lung Carcinoma%胃泌素释放肽前体在肺癌中的临床意义



    小细胞肺癌和少数非小细胞肺癌肿瘤细胞产生和分泌胃泌素释放肽前体(ProGRP),小细胞肺癌患者血清中ProGRP浓度显著升高.胃泌素释放肽前体对小细胞肺癌(SCLC)诊断灵敏度和特异度明显高于其他肺癌相关肿瘤标志物;对可疑肺癌而不能获得病理的患者,ProGRP有助于鉴别诊断SCLC和非小细胞肺癌;对SCLC患者疗效监测和复发诊断优于神经元特异性烯醇化酶.%Small cell lung carcinoma( SCLC )and a small number of non-small cell lung carcinoma cells ( NSCLC )produce and secrete pro-gastrin-releasing( ProGRP ), ProGRP concentrations in patients with SCLC are significantly elevated. The sensitivity and specificity of ProGRP for the diagnosis of small cell lung cancer is significantly higher than other relevant lung tumor markers; when histology of patients with primary lung masses is not taken, ProGRP is helpful for the differential diagnosis of SCLC and NSCLC; ProGRP is superior to neuron-specific enolase for officacy monitoring and diagnosis of SCLC recurrence.

  20. 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.

  1. Dual trigger with combination of gonadotropin-releasing hormone agonist and human chorionic gonadotropin significantly improves the live-birth rate for normal responders in GnRH-antagonist cycles.

    Lin, Ming-Huei; Wu, Frank Shao-Ying; Lee, Robert Kuo-Kuang; Li, Sheng-Hsiang; Lin, Shyr-Yeu; Hwu, Yuh-Ming


    To investigate whether dual triggering of final oocyte maturation with a combination of gonadotropin-releasing hormone (GnRH) agonist and human chorionic gonadotropin (hCG) can improve the live-birth rate for normal responders in GnRH-antagonist in vitro fertilization/intracytoplasmic sperm injection (IVF-ICSI) cycles. Retrospective cohort study. Infertility unit of a university-affiliated medical center. Normal responders to controlled ovarian hyperstimulation who were undergoing IVF-ICSI with a GnRH antagonist protocol. Standard dosage of hCG trigger (6,500 IU of recombinant hCG) versus dual trigger (0.2 mg of triptorelin and 6,500 IU of recombinant hCG). Live-birth, clinical pregnancy, and implantation rates per cycle. A total of 376 patients with 378 completed cycles with embryo transfer were enrolled (hCG trigger/control group: n = 187; dual trigger/study group: n = 191). The dual trigger group demonstrated statistically significantly higher implantation (29.6% vs. 18.4%), clinical pregnancy (50.7% vs. 40.1%), and live-birth (41.3% vs. 30.4%) rates as compared with the hCG trigger group. There was no statistically significant difference in terms of patient demographics, cycle parameters, or embryo quality. Dual trigger of final oocyte maturation with a GnRH-agonist and a standard dosage of hCG in normal responders statistically significantly improves implantation, clinical pregnancy, and live-birth rates in GnRH-antagonist IVF cycles. Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  2. Effects of Decreasing Controlled- release Fertilizer Application Rate on Yield and Quality of Potato, and Soil Nitrate Nitrogen Content%控释肥减量施用对马铃薯产量、品质及土壤硝态氮含量的影响

    董亮; 张玉凤; 刘苹; 于淑芳; 杨力; 杨鹏


    The effects of decreasing the application rate of controlled - release coated urea on the yield and quality of potato, and soil nitrate nitrogen content were studied through field experiments. The results indicated that the controlled - release fertilizer treatment increased the first grade rate of potato tube as compared with the traditional fertilization, enhanced potato yield by 8. 00% -25.59% , and the best yield - increasing effect was obtained in the treatment of applying 100% controlled - release fertilizer. Decreasing the application rate of controlled - release fertilizer improved potato quality, increased the utilization rate of nitrogen fertilizer by 10.53% ~22.69% , and the utilization rate of nitrogen fertilizer was the highest in the treatment of decreasing 40% nitrogen of controlled - release fertilizer. The controlled - release fertilizer treatment reduced soil nitrate nitrogen accumulation in each soil layer, and decreasing 30% ~ 40% nitrogen of controlled - release fertilizer achieved the least soil nitrate nitrogen accumulation.%通过田间试验,研究了包膜尿素减量化施用对马铃薯产量、品质及土壤硝态氮含量的影响.结果表明,与习惯施肥处理相比,花用控释肥可以提高马铃薯的一级品率,并且能较好地保证马铃薯产量,马铃薯产量增加8.00%~25.59%,以100%控释肥增产效果最好.马铃薯品质方面,减氮控释肥处理能提高马铃薯品质.施用控释肥可以提高氮肥利用率10.53%~22.69%,其中,以减氮40%控释肥的氮肥利用率最高.在马铃薯土壤硝态氮含量方面,施用控释肥能降低硝态氮在各个土层的累积,其中减氮30%~40%控释肥处理土壤硝态氮的累积量最低.

  3. Near infra-red photoimmunotherapy with anti-CEA-IR700 results in extensive tumor lysis and a significant decrease in tumor burden in orthotopic mouse models of pancreatic cancer.

    Ali A Maawy

    Full Text Available Photoimmunotherapy (PIT of cancer utilizes tumor-specific monoclonal antibodies conjugated to a photosensitizer phthalocyanine dye IR700 which becomes cytotoxic upon irradiation with near infrared light. In this study, we aimed to evaluate the efficacy of PIT on human pancreatic cancer cells in vitro and in vivo in an orthotopic nude mouse model. The binding capacity of anti-CEA antibody to BxPC-3 human pancreatic cancer cells was determined by FACS analysis. An in vitro cytotoxicity assay was used to determine cell death following treatment with PIT. For in vivo determination of PIT efficacy, nude mice were orthotopically implanted with BxPC-3 pancreatic tumors expressing green fluorescent protein (GFP. After tumor engraftment, the mice were divided into two groups: (1 treatment with anti-CEA-IR700 + 690 nm laser and (2 treatment with 690 nm laser only. Anti-CEA-IR700 (100 μg was administered to group (1 via tail vein injection 24 hours prior to therapy. Tumors were then surgically exposed and treated with phototherapy at an intensity of 150 mW/cm2 for 30 minutes. Whole body imaging was done subsequently for 5 weeks using an OV-100 small animal imaging system. Anti-CEA-IR700 antibody bound to the BxPC3 cells to a high degree as shown by FACS analysis. Anti-CEA-IR700 caused extensive cancer cell killing after light activation compared to control cells in cytotoxicity assays. In the orthotopic models of pancreatic cancer, the anti-CEA-IR700 group had significantly smaller tumors than the control after 5 weeks (p<0.001. There was no significant difference in the body weights of mice in the anti-CEA-IR700 and control groups indicating that PIT was well tolerated by the mice.

  4. 钙结合蛋白在前列腺癌中的下调表达及其临床意义%The clinical significance of decreased expression of calcium binding protein 39 in prostate cancer

    朱建国; 陈卫红; 徐述雄; 王元林; 孙兆林; 何慧婵; 钟惟德


    目的 探讨钙结合蛋白(CAB39)在前列腺癌中的作用及其临床意义.方法 应用蛋白组学二维荧光差异凝胶电泳(2D-DIGE)技术筛选出在局限性前列腺癌与癌旁组织差异性表达的CAB39蛋白,质谱分析(MS)鉴定、免疫组织化学技术检测CAB39蛋白在24例前列腺癌与癌旁组织中的表达,结合CAB39免疫组织化学评分和前列腺癌患者的临床病理参数进行分析.结果 CAB39蛋白在癌旁组织中的免疫组织化学染色阳性率高于前列腺癌组织(70.8%比33.3%,P<0.01),CAB39蛋白表达在前列腺癌患者年龄、血清前列腺特异抗原(PSA)水平、Gleason评分和肿瘤TNM分期各不同分组中的差异均无统计学意义(P>0.05).结论 CAB39蛋白在前列腺癌患者中下调表达,它可能是前列腺癌抑制因子.%Objective To explore the role and clinical significance of calcium binding protein 39 (CAB39) protein in prostate cancer (PCa).Methods Using the two-dimensional fluorescence difference gel electrophoresis (2D-DIGE) to screen CAB39 protein in PCa and adjacent tissues,and mass spectrometry analysis verification,to analyze the differentially expressed degree of CAB39 protein in 24 cases of PCa and adjacent tissues by immunohistochemical (IHC) technology,the combination of CAB39 IHC score and clinicopathological parameters of PCa patients were analyzed.Results Using the method of IHC,we found that the expression of CAB39 protein in adjacent tissues was significantly higher than that in PCa tissues (70.8% vs 33.3%,P <0.01).The expression of CAB39 protein in different age stages of PCa patients,serum PSA levels,Gleason score and TNM stage in tumor group had no significant difference(P >0.05).Conclusion CAB39 protein is down-regulated expression in PCa,it may be prostate tumor suppressor.

  5. Liposome-siRNA-peptide complexes cross the blood-brain barrier and significantly decrease PrP on neuronal cells and PrP in infected cell cultures.

    Bruce Pulford

    Full Text Available BACKGROUND: Recent advances toward an effective therapy for prion diseases employ RNA interference to suppress PrP(C expression and subsequent prion neuropathology, exploiting the phenomenon that disease severity and progression correlate with host PrP(C expression levels. However, delivery of lentivirus encoding PrP shRNA has demonstrated only modest efficacy in vivo. METHODOLOGY/PRINCIPAL FINDINGS: Here we describe a new siRNA delivery system incorporating a small peptide that binds siRNA and acetylcholine receptors (AchRs, acting as a molecular messenger for delivery to neurons, and cationic liposomes that protect siRNA-peptide complexes from serum degradation. CONCLUSIONS/SIGNIFICANCE: Liposome-siRNA-peptide complexes (LSPCs delivered PrP siRNA specifically to AchR-expressing cells, suppressed PrP(C expression and eliminated PrP(RES formation in vitro. LSPCs injected intravenously into mice resisted serum degradation and delivered PrP siRNA throughout the brain to AchR and PrP(C-expressing neurons. These data promote LSPCs as effective vehicles for delivery of PrP and other siRNAs specifically to neurons to treat prion and other neuropathological diseases.

  6. 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.

  7. 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.

  8. Influence of alcohol on the release of tramadol from 24-h controlled-release formulations during in vitro dissolution experiments.

    Traynor, M J; Brown, M B; Pannala, A; Beck, P; Martin, G P


    Recent warnings by regulatory bodies and a product recall by the FDA have generated much interest in the area of dose dumping from controlled-release opioid analgesic formulations when coingested with alcohol. It was the aim of this study to address this issue and in doing so, gain understanding on how alcohol-induced effects may be avoided. In this study, tramadol release from Ultram ER tablets and T-long capsules was significantly increased in the presence of ethanol. Conversely, a decrease in the rate of tramadol release was seen from Tridural extended-release tablets in the presence of alcohol.

  9. Consecutive Acupuncture Stimulations Lead to Significantly Decreased Neural Responses

    Yeo, S.; Choe, I.H.; Noort, M.W.M.L. van den; Bosch, M.P.C.; Lim, S.


    Objective: Functional magnetic resonance imaging (fMRI), in combination with block design paradigms with consecutive acupuncture stimulations, has often been used to investigate the neural responses to acupuncture. In this study, we investigated whether previous acupuncture stimulations can affect

  10. Lateral Squats Significantly Decrease Sprint Time in Collegiate Baseball Athletes

    Jason B. White


    Full Text Available The purpose was to examine the effect of prior performance of dumbbell lateral squats (DBLS on an agility movement-into-a-sprint (AMS test. Twelve collegiate, resistance-trained, baseball athletes participated in three sessions separated by three days. Session One consisted of AMS baseline test, DBLS 5-RM test, and experimental protocol familiarization. Subjects were randomly assigned the protocol order for Sessions Two and Three, which consisted of warm up followed by 1-min sitting (no-DBLS or performing the DBLS for 1 × 5 repetitions @ 5RM for each leg. Four minutes of slow recovery walking preceded the AMS test, which consisted of leading off a base and waiting for a visual stimulus. In reaction to stimulus, subjects exerted maximal effort while moving to the right by either pivoting or drop stepping and sprinting for 10 yards (yd. In Session Three, subjects switched protocols (DBLS, no-DBLS. Foot contact time (FCT, stride frequency (SF, stride length (SL, and 10-yd sprint time were measured. There were no differences between conditions for FCT, SF, or SL. Differences existed between DBLS (1.85 ± 0.09 s and no-DBLS (1.89 ± 0.10 s for AMS (p = 0.03. Results from the current study support the use of DBLS for performance enhancement prior to performing the AMS test.

  11. Consecutive Acupuncture Stimulations Lead to Significantly Decreased Neural Responses

    Yeo, S.; Choe, I.H.; Noort, M.W.M.L. van den; Bosch, M.P.C.; Lim, S.


    Objective: Functional magnetic resonance imaging (fMRI), in combination with block design paradigms with consecutive acupuncture stimulations, has often been used to investigate the neural responses to acupuncture. In this study, we investigated whether previous acupuncture stimulations can affect b

  12. Decreasing strabismus surgery

    Arora, A; Williams, B; Arora, A K; McNamara, R; Yates, J; Fielder, A


    Aim: To determine whether there has been a consistent change across countries and healthcare systems in the frequency of strabismus surgery in children over the past decade. Methods: Retrospective analysis of data on all strabismus surgery performed in NHS hospitals in England and Wales, on children aged 0–16 years between 1989 and 2000, and between 1994 and 2000 in Ontario (Canada) hospitals. These were compared with published data for Scotland, 1989–2000. Results: Between 1989 and 1999–2000 the number of strabismus procedures performed on children, 0–16 years, in England decreased by 41.2% from 15 083 to 8869. Combined medial rectus recession with lateral rectus resection decreased from 5538 to 3013 (45.6%) in the same period. Bimedial recessions increased from 489 to 762, oblique tenotomies from 43 to 121, and the use of adjustable sutures from 29 to 44, in 2000. In Ontario, operations for squint decreased from 2280 to 1685 (26.1%) among 0–16 year olds between 1994 and 2000. Conclusion: The clinical impression of decrease in the frequency of paediatric strabismus surgery is confirmed. In the authors’ opinion this cannot be fully explained by a decrease in births or by the method of healthcare funding. Two factors that might have contributed are better conservative strabismus management and increased subspecialisation that has improved the quality of surgery and the need for re-operation. This finding has a significant impact upon surgical services and also on the training of ophthalmologists. PMID:15774914

  13. Stimulatory effects of neuronally released norepinephrine on renin release in vitro

    Matsumura, Yasuo; Kawazoe, Shinka; Ichihara, Toshio; Shinyama, Hiroshi; Kageyama, Masaaki; Morimoto, Shiro (Osaka Univ. of Pharmaceutical Sciences (Japan))


    Extracellular high potassium inhibits renin release in vitro by increasing calcium concentrations in the juxtaglomerular cells. The authors found that the decreased response of renin release from rat kidney cortical slices in high potassium solution changed to a strikingly increased one in the presence of nifedipine at doses over 10{sup {minus}6} M. They then examined the stimulatory effect of extracellular high potassium in the presence of nifedipine on renin release. The enhancement of release was significantly suppressed either by propranolol or by metoprolol but not by prazosin. High potassium plus nifedipine-induced increase in renin release was markedly attenuated by renal denervation. The enhancing effect was not observed when the slices were incubated in calcium-free medium. Divalent cations such as Cd{sup 2+}, Co{sup 2+}, and Mn{sup 2+} blocked this enhancement in a concentration-dependent manner. High potassium elicited an increase in {sup 3}H efflux from the slices preloaded with ({sup 3}H)-norepinephrine. The increasing effect was not influenced by nifedipine but was abolished by the removal of extracellular calcium or by the addition of divalent cations. These observations suggest to us that the high potassium plus nifedipine-induced increase in renin release from the slices is mediated by norepinephrine derived from renal sympathetic nerves and that this neuronally released norepinephrine stimulates renin release via activation of {beta}-adrenoceptors.

  14. Significance of interferon-gamma release assay in child tuberculosis infection%干扰素-γ释放试验在儿童结核感染中的应用价值

    钟华清; 徐梦华; 卢丽娟; 杜亚娟; 张洁琼; 徐锦


    目的:评价干扰素-γ(IFN-γ)释放试验(IGRA)对儿童结核感染的诊断价值。方法采用以结核分枝杆菌特异性抗原——早期分泌抗原靶6(ESAT-6)和培养滤液蛋白10(CFP-10)为基础,基于酶联免疫斑点法(ELISPOT)的 IGRA(即 T-SPOT)检测了2200例非结核病患儿和34例活动性结核病患儿体内特异性 T 淋巴细胞分泌的 IFN-γ水平,评价其在儿童活动性结核病和结核分枝杆菌潜伏感染中的敏感性和特异性,同时分析了该实验的各项影响因素。结果T-SPOT 诊断活动性结核病的敏感性为73.5%、特异性为99.0%。T-SPOT检测结果与性别、年龄、卡介苗接种史、结核病接触史、机体免疫状态和感染部位无关。结论T-SPOT 敏感性较高,特异性强,有助于儿童活动性结核病的早期快速诊断。%Objective To evaluate the significance of interferon-gamma(IFN-γ)release assay(IGRA)for diagnosis of tuberculosis infection in child. Methods Mycobacterium tuberculosis-specific antigen [early-secreted antigenic target-6 (ESAT-6)and culture filtrate protein-10(CFP-10)] was used. By IGRA enzyme-linked immunospot assay(ELISPOT) (T-SPOT),34 active tuberculosis children and 2 200 non-tuberculosis children were enrolled and determined for IFN-γlevels,and the sensitivity and specificity were evaluated. Some of influential factors were analyzed. Results The sensitivity and specificity of T-SPOT for the diagnosis of active tuberculosis were 73.5% and 99.0%,respectively. The results of T-SPOT had no relationship with sex,age,Bacillus Calmette-Guerin vaccination status,the history of exposure to source case,immunity state and infection position. Conclusion T-SPOT is sensitive,specific and helpful for early and rapid diagnosis of active tuberculosis in children.

  15. 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.

  16. 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.

  17. 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.

  18. Releases of radioactive substances from Swedish nuclear power plants (RAKU)

    Ingemansson, T.; Bergstroem, C. [ALARA Engineering AB, Skultuna (Sweden)


    Releases of radioactivity to air and water from Swedish nuclear power plants have been studied and compared with those from foreign reactors. Averaged over the years from commissioning of the reactors to the last year data are available, the release of radioactive noble gas from the Swedish BWRs has been about the same as from comparable foreign reactors. The oldest Swedish BWRs, Oskarshamn 1 and 2 (O1 and O2) and Ringhals 1 (R1), have simple off-gas systems with only one delay volume. All BWRs in US, Germany, Japan and Switzerland are equipped with more sophisticated off-gas systems. It can be expected that O1, O2 and R1 therefore will have the highest release of noble gas activity at an international comparison if they do not modernize their off-gas system. BWRs in US, Germany and Japan are today equipped with recombiners and with one exception also charcoal columns. Japanese BWRs report zero releases to air. Releases of radioactivity to water after commissioning was about the same for most of the studied reactors. Some of the newest German plants have had low annual releases already at commissioning. Improvements of the treatment systems at old German, Swiss and US reactors have significantly lowered the releases. For most of the Swedish plants the annual releases to water have remained at the initial level. Forsmark 3 has succeeded in decreasing the release of radionuclides to water by a factor of almost one hundred compared to other Swedish reactors. Also O3 has managed to decrease the liquid effluents. Japanese plants have zero release of radioactivity excluding tritium to water. The release of tritium is about the same for all reactors of the same type in the world. 35 refs, 31 figs, 24 tabs.

  19. 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.

  20. Análogo de GnRH disminuye la secreción de hormona folículo estimulante (FSH en ovejas prepúberes A gonadotropin releasing hormone analogue decreases follicle stimulating hormone (FSH secretion in prepubertal female sheep

    S E Recabarren


    RH on the FSH secretion in prepubertal female sheep. A GnRH agonist analogue in slow release microcapsule preparation was used (Trp6-GnRH, (Decapeptyl® whose blocking effect on the LH release has been previously demonstrated. The analogue was injected intramuscularly every 4 weeks beginning at 20 weeks of age three times in five Suffolk ewe lambs. Another group of five lambs received the vehicle of Decapeptyl. Studies of FSH pulsatility were carried out at 20 (before the analogue agonist administration, 26 and 30 weeks of age. The CLUSTER program was used to identify characteristics of FSH secretion: transversal mean (ng/ml/5h, frequency of pulses (number of pulses/5h, amplitude of pulses (ng/ml and nadir (ng/ml . In the control group, FSH secretion characteristics did not change between 20 and 30 weeks of age. In the experimental group, mean FSH concentrations decreased from 3.4±0.3 ng/ml/5h at 20 weeks of age to 0.36 ±0.1 ng/mL/ 5h at 30 weeks of age (P<0,05, which was also significantly lower than in the control group of the same age. Amplitude of FSH pulses in lambs of 30 weeks of age were significantly lower than in lambs of 20 weeks of age (4.4 ± 0.5 versus 0.5 ± 0.1 ng/mL respectively, P<0.05, and lower than that exhibited by control ewe lambs of 30 weeks of age. FSH pulse frequency did not change between lambs of 20 and 30 weeks of age in either group. Results show that the GnRH analogue is able to block the FSH secretion suggesting that the FSH secretion is dependant on GnRH stimulation in prepubertal female sheep.

  1. 胃泌素释放肽前体的研究进展及其临床意义%Research progress and clinical significance of pro-gastrin-releasing peptide

    李凤增; 江涛


    Pro-gastrin-releasing peptide(ProGRP)is a specific tumor marker of small cell lung cancer(SCLC)discovered recently.Many domestic and foreign studies have found that ProGRP level in serum of normal individuals mostly fluctuates in the normal range,and only that of a small number of patients with benign disease exceeds the upper normal limit,which focuses on patients with renal insufficiency.In malignant tumors,higher level of ProGRP appears in neuroendocrine tumors and lung cancer,particularly SCLC.The sensitivity and specificity of ProGRP to SCLC is up to 79.7%and 95%,respectively.Compared with neurone specific enolase(NSE),ProGRP can more accurately monitor disease process and predict tumor recurrence.But NSE indicates the effect of chemotherapy preferably.ProGRP and NSE are complementary,so the joint detection of them will make the diagnosis,prognosis and recurrence monitoring of SCLC more accurate.%胃泌素释放肽前体(ProGRP)是一种最近发现的小细胞肺癌(SCLC)的特异性的肿瘤标志物.国内外大量研究发现ProGRP在正常个体的血清水平大都在正常范围,仅在少量的良性疾病患者中超过正常上限,这主要集中在肾功能不全患者.在恶性肿瘤中,血ProGRP水平增高主要集中在神经内分泌肿瘤及肺癌,尤其SCLC.ProGRP对SCLC的敏感度和特异性分别高达79.7%和95%,较神经元特异性烯醇化酶更能准确监测疾病过程和预测肿瘤复发,但神经元特异性烯醇化酶较ProGRP能更好地预示化疗效果.两者具有互补性,联合检测将使SCLC的诊断、预后和监测复发更加准确.

  2. 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...

  3. Decreasing relative risk premium

    Hansen, Frank


    such that the corresponding relative risk premium is a decreasing function of present wealth, and we determine the set of associated utility functions. We find a new characterization of risk vulnerability and determine a large set of utility functions, closed under summation and composition, which are both risk vulnerable...... and have decreasing relative risk premium. We finally introduce the notion of partial risk neutral preferences on binary lotteries and show that partial risk neutrality is equivalent to preferences with decreasing relative risk premium...

  4. 胃泌素释放肽前体在小细胞肺癌中的表达水平及其意义%Expression of Pro - gastrin - releasing Peptide in Small Cell Lung Cancer and Its Significance

    吴培生; 徐爱晖


    目的:探讨胃泌素释放肽前体(ProGRP)在小细胞肺癌(SCLC)中的表达水平及临床意义。方法选择2011年5月-2013年5月安徽医科大学第一附属医院收治的初诊 SCLC 患者88例为 SCLC 组、非 SCLC 患者84例为 NSCLC 组、肺部良性病变患者50例为良性病变组,另选择同期在本院行体检健康者40例为对照组。采用 ELISA 法检测受试者血清ProGRP水平;采用放射免疫法检测血清神经元特异性烯醇化酶(NSE)水平。结果4组血清ProGRP和 NSE 水平比较,差异均有统计学意义(P 0.05);治疗后 SCLC 缓解期、好转期和进展期ProGRP水平比较,差异有统计学意义( P 0. 05). After treatment,there was significant differ-ence in ProGRP level of SCLC patients among remission stage,resolving stage and progressive stage(P < 0. 05),ProGRP level in progressive stage was significantly higher than that in remission stage and in resolving stage,respectively(P < 0. 05). In re-mission stage and resolving stage,ProGRP level after treatment was significantly lower than that before treatment(P < 0. 05). In progressive stage,ProGRP level after treatment was significantly lower than that before treatment(P < 0. 05). Conclusion Se-rum ProGRP level is high among SCLC patients,especially among SCLC patients in extended stage and in progressive stage. ProGRP provides clinical value to the tumor staging and prognosis judgement.

  5. 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.


    Zamecnik, J; Michael Bronikowski, M; Alex Cozzi, A; Russell Eibling, R; Charles Nash, C


    The Modular Caustic-Side Solvent Extraction (CSSX) Unit (MCU) and the Salt Waste Processing Facility (SWPF) will produce a Decontaminated Salt Solution (DSS) that will go to the Saltstone Production Facility (SPF). Recent information indicates that solvent entrainment in the DSS is larger than expected. The main concern is with Isopar{reg_sign} L, the diluent in the solvent mixture, and its flammability in the saltstone vault. If it is assumed that all the Isopar{reg_sign} L is released instantaneously into the vault from the curing grout before each subsequent pour, the Isopar{reg_sign} L in the vault headspace is well mixed, and each pour displaces an equivalent volume of headspace, the maximum concentration of Isopar{reg_sign} L in the DSS to assure 25% of the lower flammable limit is not exceeded has been determined to be about 4 ppm. The amount allowed would be higher if the release from grout were significantly less. The Savannah River National Laboratory was tasked with determining the release of Isopar{reg_sign} L from saltstone prepared with a simulated DSS with Isopar{reg_sign} L concentrations ranging from 50 to 200 mg/L in the salt fraction and with test temperatures ranging from ambient to 95 C. The results from the curing of the saltstone showed that the amount of Isopar{reg_sign} L released versus time can be treated as a percentage of initial amount present; there was no statistically significant dependence of the release rate on the initial concentration. The majority of the Isopar{reg_sign} L that was released over the test duration was released in the first few days. The release of Isopar{reg_sign} L begins immediately and the rate of release decreases over time. At higher temperatures the immediate release rate is larger than at lower temperatures. Initial curing temperature was found to be very important as slight variations during the first few hours or days had a significant effect on the amount of Isopar{reg_sign} L released. Short scoping

  7. Decreasing Relative Risk Premium

    Hansen, Frank

    We consider the risk premium demanded by a decision maker with wealth x in order to be indifferent between obtaining a new level of wealth y1 with certainty, or to participate in a lottery which either results in unchanged present wealth or a level of wealth y2 > y1. We define the relative risk...... premium as the quotient between the risk premium and the increase in wealth y1–x which the decision maker puts on the line by choosing the lottery in place of receiving y1 with certainty. We study preferences such that the relative risk premium is a decreasing function of present wealth, and we determine...... relative risk premium in the small implies decreasing relative risk premium in the large, and decreasing relative risk premium everywhere implies risk aversion. We finally show that preferences with decreasing relative risk premium may be equivalently expressed in terms of certain preferences on risky...

  8. Decreasing Serial Cost Sharing

    Hougaard, Jens Leth; Østerdal, Lars Peter

    The increasing serial cost sharing rule of Moulin and Shenker [Econometrica 60 (1992) 1009] and the decreasing serial rule of de Frutos [Journal of Economic Theory 79 (1998) 245] have attracted attention due to their intuitive appeal and striking incentive properties. An axiomatic characterization...... of the increasing serial rule was provided by Moulin and Shenker [Journal of Economic Theory 64 (1994) 178]. This paper gives an axiomatic characterization of the decreasing serial rule...

  9. Preparation, Characterization and in vivo Evaluation of Simple Monolithic Ethylcellulose-coated Pellets Containing Topiramate with Biphasic Release Characteristics.

    Gong, Wei; Wang, Yuli; Shao, Shuai; Xie, Si; Shan, Li; Yang, Meiyan; Gao, Chunsheng; Zhong, Wu


    In our previous study, polyvinylpyrrolidone (PVP) was used both as a binder and a pore-former to prepare ethylcellulose (EC)-coated pellets to deliver topiramate (TPM) for a controlled release profile. The objective of this work was to further optimize the formulation and evaluate the in vivo profiles of TPM sustained-release pellets. Similar to the previous formulation with no binder, the in vitro drug release of TPM sustained-release pellets with 50% PVP binder in drug layer was sensitive to pore-former PVP level ranged from 27.0% to 29.0%. The higher the level of PVP was, the quicker release rate in vitro was. Moreover, when the proportion of poreformer PVP decreased, the Cmax decreased, and the tmax and mean residence time of TPM coated pellets were both prolonged. The in vitro release profile of optimal formulation showed biphasic release characteristics similar to reference formulation Trokendi XR(®), i.e., involving immediate release of TPM in initial release stage followed by a sustained release up to 24 h. Moreover, the impact of the pH of release medium on the drug release rate of TPM sustained-release pellets was not significant. The release mechanism of TPM from the sustained-release pellets might be the interaction of diffusion (coating-film) and corrosion (drug layer). The in vivo pharmacokinetics results showed the TPM sustained-release pellets had the similar in vivo pattern compared with Trokendi XR(®). These studies provide valuable basis for further development of TPM sustained-release pellets.

  10. Decreasing relative risk premium

    Hansen, Frank


    We consider the risk premium demanded by a decision maker in order to be indifferent between obtaining a new level of wealth with certainty, or to participate in a lottery which either results in unchanged wealth or an even higher level than what can be obtained with certainty. We study preferences...... such that the corresponding relative risk premium is a decreasing function of present wealth, and we determine the set of associated utility functions. We find a new characterization of risk vulnerability and determine a large set of utility functions, closed under summation and composition, which are both risk vulnerable...... and have decreasing relative risk premium. We finally introduce the notion of partial risk neutral preferences on binary lotteries and show that partial risk neutrality is equivalent to preferences with decreasing relative risk premium...

  11. 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.

  12. 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.

  13. Decreasing serial cost sharing

    Hougaard, Jens Leth; Østerdal, Lars Peter Raahave


    The increasing serial cost sharing rule of Moulin and Shenker (Econometrica 60:1009-1037, 1992) and the decreasing serial rule of de Frutos (J Econ Theory 79:245-275, 1998) are known by their intuitive appeal and striking incentive properties. An axiomatic characterization of the increasing serial...

  14. Decreasing Serial Cost Sharing

    Hougaard, Jens Leth; Østerdal, Lars Peter

    The increasing serial cost sharing rule of Moulin and Shenker [Econometrica 60 (1992) 1009] and the decreasing serial rule of de Frutos [Journal of Economic Theory 79 (1998) 245] have attracted attention due to their intuitive appeal and striking incentive properties. An axiomatic characterization...

  15. Photoresponsive lipid-polymer hybrid nanoparticles for controlled doxorubicin release

    Yao, Cuiping; Wu, Ming; Zhang, Cecheng; Lin, Xinyi; Wei, Zuwu; Zheng, Youshi; Zhang, Da; Zhang, Zhenxi; Liu, Xiaolong


    Currently, photoresponsive nanomaterials are particularly attractive due to their spatial and temporal controlled drug release abilities. In this work, we report a photoresponsive lipid-polymer hybrid nanoparticle for remote controlled delivery of anticancer drugs. This hybrid nanoparticle comprises three distinct functional components: (i) a poly(D,L-lactide-co-glycolide) (PLGA) core to encapsulate doxorubicin; (ii) a soybean lecithin monolayer at the interface of the core and shell to act as a molecular fence to prevent drug leakage; (iii) a photoresponsive polymeric shell with anti-biofouling properties to enhance nanoparticle stability, which could be detached from the nanoparticle to trigger the drug release via a decrease in the nanoparticle’s stability under light irradiation. In vitro results revealed that this core-shell nanoparticle had excellent light-controlled drug release behavior (76% release with light irradiation versus 10% release without light irradiation). The confocal microscopy and flow cytometry results also further demonstrated the light-controlled drug release behavior inside the cancer cells. Furthermore, a CCK8 assay demonstrated that light irradiation could significantly improve the efficiency of killing cancer cells. Meanwhile, whole-animal fluorescence imaging of a tumor-bearing mouse also confirmed that light irradiation could trigger drug release in vivo. Taken together, our data suggested that a hybrid nanoparticle could be a novel light controlled drug delivery system for cancer therapy.

  16. Release Kinetics of Urea from Polymer Coated Urea and Its Relationship with Coating Penetrability

    ZHANG Hai-jun; WU Zhi-jie; CHEN Li-jun; LIANG Wen-ju


    Four kinds of polymer coated urea (PCU) were put in distilled water at 30C to determine the variation of coating penetrability and give a precise description of the urea release kinetics. The urea release from PCU could be divided into four stages: lag stage, swell stage, steady stage and decay stage. The release rate coefficient K, a measure of coating penetrability, was linearly increased at swell stage, but almost not variable at steady stage. At decay stage, the relation of K to time t could be described by the equation K= mtn-1(where m and n are the coefficients). When n>1, the coating penetrability was gradually increased, and the urea release from PCU was accelerated; when n=1, the coating penetrability was steady, and the urea release from PCU obeyed the first-order kinetics; and when n<1, the coating penetrability was gradually decreased,and the urea release from PCU was delayed, resulting in a significant "tailing effect".

  17. 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....

  18. 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.

  19. Life satisfaction decreases during adolescence.

    Goldbeck, Lutz; Schmitz, Tim G; Besier, Tanja; Herschbach, Peter; Henrich, Gerhard


    Adolescence is a developmental phase associated with significant somatic and psychosocial changes. So far there are few studies on developmental aspects of life satisfaction. This cross-sectional study examines the effects of age and gender on adolescent's life satisfaction. 1,274 German adolescents (aged 11-16 years) participated in a school-based survey study. They completed the adolescent version of the Questions on Life Satisfaction (FLZ(M) - Fragen zur Lebenszufriedenheit), a multidimensional instrument measuring the subjective importance and satisfaction with eight domains of general and eight domains of health-related life satisfaction. Effects of gender and age were analysed using ANOVAs. Girls reported significantly lower general (F = 5.0; p = .025) and health-related life satisfaction (F = 25.3; p life domains, there was a significant decrease in general (F = 14.8; p life satisfaction (F = 8.0; p Satisfaction with friends remained on a high level, whereas satisfaction with family relations decreased. Only satisfaction with partnership/sexuality increased slightly, however this effect cannot compensate the general loss of satisfaction. Decreasing life satisfaction has to be considered as a developmental phenomenon. Associations with the increasing prevalence of depression and suicidal ideation during adolescence are discussed. Life satisfaction should be considered a relevant aspect of adolescent's well-being and functioning.

  20. Properties and glial origin of osmotic-dependent release of taurine from the rat supraoptic nucleus.

    Deleuze, C; Duvoid, A; Hussy, N


    1. Taurine, prominently concentrated in glial cells in the supraoptic nucleus (SON), is probably involved in the inhibition of SON vasopressin neurones by peripheral hypotonic stimulus, via activation of neuronal glycine receptors. We report here the properties and origin of the osmolarity-dependent release of preloaded [3H]taurine from isolated whole SO nuclei. 2. Hyposmotic medium induced a rapid, reversible and dose-dependent increase in taurine release. Release showed a high sensitivity to osmotic change, with a significant enhancement with less than a 5% decrease in osmolarity. Hyperosmotic stimulus decreased basal release. 3. Evoked release was independent of extracellular Ca2+ and Na+, and was blocked by the Cl- channel blockers DIDS (4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid) and DPC (N-phenylanthranilic acid), suggesting a diffusion process through volume-sensitive Cl- channels. 4. Evoked release was transient for large osmotic reductions (> or = 15%), probably reflecting regulatory volume decrease (RVD). However, it was sustained for smaller changes, suggesting that taurine release induced by physiological variations in osmolarity is not linked to RVD. 5. Basal and evoked release were strongly inhibited by an incubation of the tissue with the glia-specific toxin fluorocitrate, but were unaffected by a neurotoxic-treatment with NMDA, demonstrating the glial origin of the release of taurine in the SON. 6. The high osmosensitivity of taurine release suggests an important role in the osmoregulation of the SON function. These results strengthen the notion of an implication of taurine and glial cells in the regulation of the whole-body fluid balance through the modulation of vasopressin release.

  1. 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...

  2. Release kinetics of coated, donut-shaped tablets for water soluble drugs.

    Kim, C J


    Coated, donut-shaped tablets (CDST) were designed to achieve parabolic and linear drug release profiles. When rapidly erodible polymers (HPMC E3, HPC, PEG8000, PEOs (Mw=100000 and 200000)) were used, the release profiles of diltiazem HCl from the tablets becomes parabolic whereas zero-order release was achieved by using slowly erodible polymers (HPMC E5, HPMC E15, PEO (Mw=300000)). Drug release from the rapidly erodible polymers was governed by the pure erosion of the polymer while both polymer erosion and drug diffusion controlled drug release from the slowly erodible polymers. As drug loading was increased from 10% to 39% w/w, the drug release rate from CDST based on HPMC E3 became faster and parabolic whereas that from CDST based on HPMC E5 was linear. The slowly erodible polymer (HPMC E5) provided parabolic release profiles when drug loading was greater than 49% w/w. In this case, drug release mechanisms likely shifted from a combination of polymer erosion and drug diffusion to pure polymer erosion due to the enhancement of polymer erosion by faster influx of water. As drug solubility decreased from 61.6% w/v (diltiazem HCl), 1.0% w/v (theophylline), to 0.5% w/v (nicardipine HCl), the drug release rate from CDST based on HPMC E3 decreased due to polymer erosion mechanism but there was little difference in release rate from CDST based on HPMC E5 due to the greater contribution of drug diffusion to drug release kinetics along with polymer erosion. As expected, the drug release rate of diltiazem HCl from HPMC E3 and E5 was significantly influenced by stirring rate and hole size.

  3. Sustained release of fungicide metalaxyl by mesoporous silica nanospheres

    Wanyika, Harrison, E-mail: [Jomo Kenyatta University of Agriculture and Technology, Department of Chemistry (Kenya)


    The use of nanomaterials for the controlled delivery of pesticides is nascent technology that has the potential to increase the efficiency of food production and decrease pollution. In this work, the prospect of mesoporous silica nanoparticles (MSN) for storage and controlled release of metalaxyl fungicide has been investigated. Mesoporous silica nanospheres with average particle diameters of 162 nm and average pore sizes of 3.2 nm were prepared by a sol-gel process. Metalaxyl molecules were loaded into MSN pores from an aqueous solution by a rotary evaporation method. The loaded amount of metalaxyl as evaluated by thermogravimetric analysis was about 14 wt%. Release of the fungicide entrapped in the MSN matrix revealed sustained release behavior. About 76 % of the free metalaxyl was released in soil within a period of 30 days while only 11.5 and 47 % of the metalaxyl contained in the MSN carrier was released in soil and water, respectively, within the same period. The study showed that MSN can be used to successfully store metalaxyl molecules in its mesoporous framework and significantly delay their release in soil.

  4. Sustained release of fungicide metalaxyl by mesoporous silica nanospheres

    Wanyika, Harrison


    The use of nanomaterials for the controlled delivery of pesticides is nascent technology that has the potential to increase the efficiency of food production and decrease pollution. In this work, the prospect of mesoporous silica nanoparticles (MSN) for storage and controlled release of metalaxyl fungicide has been investigated. Mesoporous silica nanospheres with average particle diameters of 162 nm and average pore sizes of 3.2 nm were prepared by a sol-gel process. Metalaxyl molecules were loaded into MSN pores from an aqueous solution by a rotary evaporation method. The loaded amount of metalaxyl as evaluated by thermogravimetric analysis was about 14 wt%. Release of the fungicide entrapped in the MSN matrix revealed sustained release behavior. About 76 % of the free metalaxyl was released in soil within a period of 30 days while only 11.5 and 47 % of the metalaxyl contained in the MSN carrier was released in soil and water, respectively, within the same period. The study showed that MSN can be used to successfully store metalaxyl molecules in its mesoporous framework and significantly delay their release in soil.

  5. 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.

  6. Histamine H3 receptor antagonist decreases cue-induced alcohol reinstatement in mice.

    Nuutinen, Saara; Mäki, Tiia; Rozov, Stanislav; Bäckström, Pia; Hyytiä, Petri; Piepponen, Petteri; Panula, Pertti


    We have earlier found that the histamine H3 receptor (H3R) antagonism diminishes motivational aspects of alcohol reinforcement in mice. Here we studied the role of H3Rs in cue-induced reinstatement of alcohol seeking in C57BL/6J mice using two different H3R antagonists. Systemic administration of H3R antagonists attenuated cue-induced alcohol seeking suggesting that H3R antagonists may reduce alcohol craving. To understand how alcohol affects dopamine and histamine release, a microdialysis study was performed on C57BL/6J mice and the levels of histamine, dopamine and dopamine metabolites were measured in the nucleus accumbens. Alcohol administration was combined with an H3R antagonist pretreatment to reveal whether modulation of H3R affects the effects of alcohol on neurotransmitter release. Alcohol significantly increased the release of dopamine in the nucleus accumbens but did not affect histamine release. Pretreatment with H3R antagonist ciproxifan did not modify the effect of alcohol on dopamine release. However, histamine release was markedly increased with ciproxifan. In conclusion, our findings demonstrate that H3R antagonism attenuates cue-induced reinstatement of alcohol seeking in mice. Alcohol alone does not affect histamine release in the nucleus accumbens but H3R antagonist instead increases histamine release significantly suggesting that the mechanism by which H3R antagonist inhibits alcohol seeking found in the present study and the decreased alcohol reinforcement, reward and consumption found earlier might include alterations in the histaminergic neurotransmission in the nucleus accumbens. These findings imply that selective antagonists of H3Rs could be a therapeutic strategy to prevent relapse and possibly diminish craving to alcohol use. This article is part of the Special Issue entitled 'Histamine Receptors'.

  7. Sulphate release from building rubble of WWII

    Mekiffer, Beate; Wessolek, Gerd; Vogeler, Iris; Brettholle, Mareike


    Sulphate concentration in the upper aquifer of Berlin, Germany is increasing continuously since 40 years. In downtown Berlin they particular exceed the precaution values of drinking water ordinance. We assume that the main source of sulphate in the groundwater is technogenic material, which is part of building rubble from WW II bombing. Nearly 115 Mio t of this material have been deposited in Berlin. Our aim is, ­ to identify rubble components which contain S and to quantify the S-pool of this material ­ to identify factors, influencing the release of SO4 and ­ to predict sulphate release from building rubble of WW II We analyzed total and water soluble S of various components and the fine earth fraction of the soils containing the rubble. We investigated the influence of physical and chemical parameters on the release of SO4 using unsaturated column experiments (With an automatic percolation system). Thereby, the particle size, the flow rate and the pH of the solution has been varied. Among the components, slag shows the highest total S-contents of up to 0,7% . Lignite Coal-ashes from Lusatia, Germany are also rich in SO4. The total S of brick varies between 0,01% and 0,3%. Mortar shows S-Values between 0,08 and 0,12%. In 75% of all samples show total S of less than 0,14%. There was no significant correlation between total S-amount and water-soluble SO4, which is caused by different chemical compounds in the samples. In the percolation experiments technogenic components with grain size <2mm cause a higher density, resulting in a lower percolation velocity. The concentration of ions in the according leachate is higher than in the leachate of coarse fraction (2 - 20mm). Gypsum-rich material (10%) released constant SO4 -concentration over the whole experiment. Slag-rich material released high initial SO4-concentrations which then fastly decreased. We concluded, that the kind of technogenic component and its grain size strongly influences the release of SO4 to the

  8. Kinetics of metribuzin release from bentonite-polymer composites in water.

    Sahoo, Sonalika; Manjaiah, K M; Datta, S C; Ahmed Shabeer, T P; Kumar, Jitendra


    A series of bentonite polymer-composites (BPCs) loaded with metribuzin were studied for their controlled release in aqueous medium. The release of active ingredient from BPCs was significantly lower as compared to commercial metribuzin formulation. The results revealed that the cumulative metribuzin release was highest (81%) from the BPCs containing 8% clay (commercial bentonite) and 2% metribuzin which correspond to the lowest (14 days) half-life values i.e., time required for 50% release of active ingredient (t1/2). The metribuzin release from the BPCs decreased with increased concentration of clays in polymer matrix and the release was further decreased with BPCs prepared with pure nano-bentonite. BPCs containing 12% clay and 2% metribuzin showed maximum t1/2 values i.e., 25 and 51 days for commercial bentonite and pure nano-bentonite as clay sources, respectively. The differential behaviour in the metribuzin release rates from BPCs was ascribed due to variations in crosslinking of metribuzin in the composites. As metribuzin release was found to be slower in BPCs compared to commercial formulation, it could be used for control of weeds tailored to different crops.

  9. 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.

  10. Inhibitory effects of HS014 on glutamate release in astrocytes chronically treated with morphine

    Haichen Chu; Zejun Niu; Zhao Yang; Xuefeng Zhang


    Previous studies have confirmed that the number of glial fibrillary acidic protein-positive cells significantly increases during morphine tolerance.However,morphine tolerance is reversed with melanocortin receptor antagonists,and analgesic action is enhanced accordingly.However,these mechanisms remain unclear.In the present study,following addition of morphine to Wistar rat spinal cord astrocytes,glutamate levels in the supematant significantly increased(P<0.05).At 30-120minutes following addition of intervention agent to spinal cord astrocytes,naloxone significantly increased glutamate release in morphine-tolerant model cells(P < 0.05),while melanocortin receptor antagonist HS014 decreased glutamate release(P < 0.05).Additional naloxone and HS014 to astrocytes significantly decreased glutamate release compared with additional naloxone alone(P < 0.01).Results from the present study demonstrated that glutamate release was increased in spinal cord astrocytes co-cultured with morphine.Naloxone increased glutamate release,and HS014 reduced glutamate release.

  11. Release Characteristics of Different N Forms in an Uncoated Slow/Controlled Release Compound Fertilizer

    DONG Yan; WANG Zheng-yin


    This study examined the release characteristics of different N forms in an uncoated slow/controlled-release compound fertilizer (UCRF) and the N uptake and N-use efficiency by rice plants. Water dissolution, soil leaching, and pot experiments were employed. The dynamics of N release from the UCRF could be quantitatively described by three equations: the first-order kinetics equation [Nt = N0 (1-e-kt)], Elovich equation (Nt = a + blnt), and parabola equation (Nt = a + bt0.5), with the best fitting by the first-order kinetics equation for different N (r= 0.9569**-0.9999**). The release potentials (N0 values estimated by the first-order kinetics equation) of different N in the UCRF decreased in the order of total N > DON > urea-N > NH4+-N > NO3--N in water, and total N > NH4+-N > DON > urea-N > NO3--N in soil, respectively,being in accordance with cumulative amounts of N release. The constants of N release rate (k values and b values) for different N forms were in decreasing order of total N > DON > NH4+-N > NO3--N in water, whereas the k values were urea-N >DON > NH4+-N > total N > NO3--N, and the b values were total N > NH4+-N > DON > NO3--N > urea-N in soil. Compared with a common compound fertilizer, the N-use efficiency, N-agronomy efficiency, and N-physiological efficiency of the UCRF were increased by 11.4%, 8.32 kg kg-1, and 5.17 kg kg-1, respectively. The ratios of different N to total N in the UCRF showed significant correlation with N uptake by rice plants. The findings showed that the first-order kinetics equation [Nt=N0(1-e-kt)] could be used to describe the release characteristics of different N forms in the fertilizer. The UCRF containing different N forms was more effective in facilitating N uptake by rice compared with the common compound fertilizer containing single urea-N form.


    Shetty Aditya


    Full Text Available Exposure to mercury from dental amalgam restoration, with possible negative health effects, has generally been considered to occur via either erosion or evaporation directly from the surface of fillings, followed by ingestion. This study aims to assess the mercury release from dental amalgam and provide a basis for comparison between mercury release in oral cavities with single and multiple amalgam restorations at different time intervals. This study was conducted in A.B. Shetty Memorial Institute of Dental Sciences, Mangalore, Karnataka, and included three groups I , II and III containing one, four and eight teeth respectively. The level of mercury vapors released from dental amalgam restorations was calculated from artificial saliva and measured using an atomic absorption spectrophotometer. The obtained results concluded that the continuous release of Hg vapor from dental amalgam tooth restorations decreases as the restoration ages, after 30 days there was no significant difference between the amount of mercury released from multiple and single tooth restorations.

  13. Effect of beta-cyclodextrin on aroma release and flavor perception.

    Kant, Avinash; Linforth, Robert S T; Hort, Joanne; Taylor, Andrew J


    Binding and release of volatile compounds to and from beta-cyclodextrin were measured in model aqueous systems using static equilibrium headspace and dynamic headspace dilution. Beta-cyclodextrin decreased the static equilibrium headspace for some volatiles (e.g., ethyl octanoate and decanone) due to binding, but dilution studies demonstrated that binding was readily reversible. Dynamic release of hydrophobic volatile compounds was similar to that observed from emulsions. When beta-cyclodextrin was added to fat free yogurt, the release of a commercial lemon flavoring was modified and was similar to release from a regular fat yogurt. Sensory difference testing confirmed the release results. The data demonstrate that beta-cyclodextrin can be used to modify flavor delivery in both model and real systems; the effects in the latter are sensorially significant.

  14. Acute fasting increases somatodendritic dopamine release in the ventral tegmental area.

    Roseberry, Aaron G


    Fasting and food restriction alter the activity of the mesolimbic dopamine system to affect multiple reward-related behaviors. Food restriction decreases baseline dopamine levels in efferent target sites and enhances dopamine release in response to rewards such as food and drugs. In addition to releasing dopamine from axon terminals, dopamine neurons in the ventral tegmental area (VTA) also release dopamine from their soma and dendrites, and this somatodendritic dopamine release acts as an autoinhibitory signal to inhibit neighboring VTA dopamine neurons. It is unknown whether acute fasting also affects dopamine release, including the local inhibitory somatodendritic dopamine release in the VTA. In these studies, I have tested whether fasting affects the inhibitory somatodendritic dopamine release within the VTA by examining whether an acute 24-h fast affects the inhibitory postsynaptic current mediated by evoked somatodendritic dopamine release (D2R IPSC). Fasting increased the contribution of the first action potential to the overall D2R IPSC and increased the ratio of repeated D2R IPSCs evoked at short intervals. Fasting also reduced the effect of forskolin on the D2R IPSC and led to a significantly bigger decrease in the D2R IPSC in low extracellular calcium. Finally, fasting resulted in an increase in the D2R IPSCs when a more physiologically relevant train of D2R IPSCs was used. Taken together, these results indicate that fasting caused a change in the properties of somatodendritic dopamine release, possibly by increasing dopamine release, and that this increased release can be sustained under conditions where dopamine neurons are highly active.

  15. Significance of thickness of epithelial corneum layer of prepuce in circumcision and decreasing HIV infection%包皮上皮角质层厚度对包皮环切术降低HIV感染率的指导意义

    胡金天; 李森恺; 梁浩; 高云周; 李强; 谢林海; 丁健; 周传德; 李峰永; 周宇


    目的 探讨包皮内板、外板上皮角质层的厚度及对成年人包皮环切术降低HIV感染率的指导意义.方法 共取19例包皮标本,分为纵向(7例)、横向(12例),分别测量包皮内板、外板上皮角质层厚度.并以1例变性手术切取的包皮内板、阴茎头及阴茎皮肤的上皮角质层作为比较.结果 包皮内板的角质层比外板薄,靠近冠状沟的远端包皮内板角质层比近端的包皮内板角质层薄.远端及近端的包皮外板上皮角质层无统计学意义.1例阴茎标本的包皮内板角质层比阴茎皮肤角质层薄.结论 为了减少HIV感染率,包皮环切术中应保留较少的包皮内板,包皮外板可以适当多保留.%Objective To investigate the significance of thickness of epithelial corneum layer of prepuce in circumcision and decreasing HIV infection. Methods Nineteen preputial specimen were harvested and divided into 7 cases (longitudinal) and 12 cases (horizontal). The corneum layer thickness of epithelial inner plate and epithelial outer plate was measured respectively. The epithelial corneum layer of foreskin from the case who underwent the transsexual operation was as the control sample. Results The corneum layer of the inner plate was thinner than that of the outer plate. The corneum layer of the inner plate of distal prepuce was thinner than that of the proximal prepuce. Conclusion To reduce HIV infection, less inner plate of prepuce should be reserved, whde more outer plate of prepuce should be retained during the circumcision.

  16. Impaired acetylcholine release from the myenteric plexus of Trichinella-infected rats

    Collins, S.M.; Blennerhassett, P.A.; Blennerhassett, M.G.; Vermillion, D.L. (McMaster Univ., Hamilton, Ontario (Canada))


    We examined the release of acetylcholine (ACh) from jejunal longitudinal muscle-myenteric plexus preparations in noninfected control rats and in rats infected 6, 23, or 40 days previously with Trichinella spiralis. ACh release was assessed by preincubating the tissue with ({sup 3}H)choline and measuring the evoked release of tritium. The uptake of {sup 3}H was significantly less in tissue from T. spiralis-infected rats compared with control. In tissues from either infected or control animals, electrical field stimulation (30 V, 0.5 ms, 10 Hz for 1 min), or veratridine (6-30 microM) induced {sup 3}H release that was tetrodotoxin sensitive. Depolarization by KCl (25-75 mM) also caused {sup 3}H release, but this was only partially reduced by tetrodotoxin. Radiochromatographic analysis indicated evoked release of {sup 3}H to be almost entirely ({sup 3}H)ACh. In rats infected 6 days previously with T. spiralis, ({sup 3}H)ACh release induced by KCl, veratridine, and field stimulation were decreased at least 80%. The suppression of ({sup 3}H)ACh release induced by veratridine or KCl was fully reversible after 40 days postinfection, but field-stimulated responses remained approximately 50% of control values. These results indicate that T. spiralis infection in the rat is accompanied by a reversible suppression of ACh release from the longitudinal muscle-myenteric plexus of the jejunum.

  17. Fouling-release Property of Water-filled Porous Elastomers

    Lai-yong Xie; Fei Hong; Chuan-xin He; Jian-hong Liu; Chi Wu


    Since the fouling-releasing ability of silicone elastomers increased as their modulus decreases,we designed and prepared composites with embedded tiny NaCl crytals that were soluble after their immersion in water,resulting in water-filled porous elastomers.The scanning electron microscope images confirmed such a designed water-filling porous structure.The existence of many micro-drops of water in these specially designed elastomers decreased the shear storage modulus and increased the loss factors.The decrease of shear modulus plays a leading role here and is directly related to a lower critical peeling-off stress of a pseudo-barnacle on them.Therefore,such a novel preparation with cheap salts instead of an expensive silicone provides a better way to make fouling-release paints with a lower modulus,a lower critical peeling-off stress and a better fouling-release property without a significant decrease of the cross-linking density.

  18. Response of sulphur dynamics in European catchments to decreasing sulphate deposition

    A. Prechtel


    Full Text Available Following the decline in sulphur deposition in Europe, sulphate dynamics of catchments and the reversibility of anthropogenic acidification of soils and freshwaters became of major interest. Long-term trends in sulphate concentrations and fluxes in precipitation/throughfall and freshwaters of 20 European catchments were analysed to evaluate catchment response to decreasing sulphate deposition. Sulphate deposition in the catchments studied declined by 38-82% during the last decade. Sulphate concentrations in all freshwaters decreased significantly, but acidification reversal was clearly delayed in the German streams. In Scandinavian streams and Czech/Slovakian lakes sulphate concentrations responded quickly to decreased input. Sulphate fluxes in run-off showed no clear trend in Germany and Italy but decreased in Scandinavia, the Czech Republic and Slovakia. The decrease, however, was less than the decline in input fluxes. While long-term sulphate output fluxes from catchments were generally correlated to input fluxes, most catchments started a net release of sulphate during the early 1990s. Release of stored sulphate leads to a delay of acidification reversal and can be caused by four major processes. Desorption and excess mineralisation were regarded as the most important for the catchments investigated, while oxidation and weathering were of lesser importance for the long-term release of sulphate. Input from weathering has to be considered for the Italian catchments. Sulphate fluxes in German catchments, with deeply weathered soils and high soil storage capacity, responded more slowly to decreased deposition than catchments in Scandinavia and the Czech Republic/Slovakia, which have thin soils and relatively small sulphate storage. For predictions of acidification reversal, soil characteristics, sulphur pools and their dynamics have to be evaluated in future research. Keywords: acidification reversal, sulphur, sulphate release, Europe

  19. A method for producing controlled fluoride release from an orthodontic bracket.

    Li, Song; Hobson, Ross S; Bai, Yuxing; Yan, Zhuoqun; Carrick, Thomas E; McCabe, John F


    The aim of this study was to manufacture and test, in vitro, a novel modification to provide fluoride-releasing orthodontic brackets. Thirty-two orthodontic brackets were drilled to produce a recess (approximately 1.3 mm in diameter and 0.7 mm in depth) at the centre of the bracket base. Four materials, with and without the addition of sodium fluoride, a glass ionomer cement (Ketac Cem micro), a resin-modified glass ionomer cement (RMGIC; GC Fuji Ortho LC), a zinc phosphate (Zinc Cement Improved), and a resin (Transbond XT) were used to fill the recess in the bracket base. Fluoride release was measured daily during the first week and then weekly for 10 weeks. An ion chromatograph with suppressed conductivity was used for free fluoride ion determination. Statistical analysis to determine the amount of flouride release was undertaken using analysis of variance and Tukey's test. During the first 2 weeks, the resin group, with the addition of 38 per cent sodium fluoride added, released significantly more free fluoride (P < 0.05), but after 2 weeks the fluoride release markedly decreased. After 5 weeks, the RMGIC group, with 15 per cent added sodium fluoride, had significantly higher (P < 0.05) daily fluoride release than the other groups. The findings demonstrated that an appropriate fluoridated material can be used as a fluoride-releasing reservoir in a modified orthodontic bracket to enable it to release fluoride over the period of fixed appliance treatment.



    Objective To study the releases of endothelin-1 and prostacyclin by endothelial cells in culture and to elucidate how these releases were influenced by smoke-treated low density lipoprotein. Methods We exposed endothelial cell cultures to native or oxidized Iow density lipoproteins,low density lipoproteins treated by dimethylsulfoxide-soluble particles from cigarette smoke or dimethylsulfoxide alones. The release of endothelin-1 was assayed by bioassay and the release of prostacyclin was assayed by radioimmunoassay. Results Low density lipoproteins treated by smoke significantly increased the release of endothelin-l (P<0. 025) and decreased the release of prostacyclin (P<0. 02) by endothelial cells in culture, contrast to native or dimethylsulfoxide-treated lipoproteins. Conclusion The main part of vasoconstrictor activity in conditioned medium from bovine aortic EC is endothelin-1.

  1. CD14 mediated endogenous TNF-alpha release in HL60 AML cells: a potential model for CD14 mediated endogenous cytokine release in the treatment of AML.

    Treon, S P; Anand, B; Ulevitch, R; Broitman, S A


    In previous studies, HL60 AML cells treated with tumor necrosis factor-alpha (TNF), interferon-gamma (IFN), and lipopolysaccharides (LPS) displayed decreased growth and viability, enhanced monocytic pathway differentiation and endogenous TNF release. Endogenous TNF release by LPS/TNF/IFN treated HL60 cells was postulated to play a role with the above findings. In these studies, HL60 cells expressed CD14 when treated with TNF, IFN, and LPS. CD14 mediates TNF release in monocytes/macrophages in response to binding of LPS with LPS binding protein (LBP). CD14 was not expressed in either untreated or LPS only treated HL60 cells. CD14 expression was present and greater with HL60 cells cultured with LPS/TNF/IFN vs TNF/IFN (47.47% vs 9.07% positive, respectively) suggesting synergism for LPS in CD14 induction. CD14 expression was associated with endogenous TNF release, and with significantly higher levels by HL60 cells treated with LPS/TNF/IFN vs TNF/IFN (p < 0.001). Addition of anti-CD14 antibody significantly reduced release of TNF in TNF/IFN (p < 0.001) and LPS/TNF/IFN (p = 0.0013) treated cells. KG1 and U937 AML cells treated with LPS, TNF, and IFN did not express CD14, nor release TNF. A model for inducing release of endogenous growth inhibitory cytokines by CD14 bearing AML cells is proposed as an approach to AML therapy.

  2. Hyperhomocysteinemia decreases bone blood flow

    Neetu T


    Full Text Available Neetu Tyagi*, Thomas P Vacek*, John T Fleming, Jonathan C Vacek, Suresh C TyagiDepartment of Physiology and Biophysics, School of Medicine, University of Louisville, Louisville, KY, USA *These authors have equal authorshipAbstract: Elevated plasma levels of homocysteine (Hcy, known as hyperhomocysteinemia (HHcy, are associated with osteoporosis. A decrease in bone blood flow is a potential cause of compromised bone mechanical properties. Therefore, we hypothesized that HHcy decreases bone blood flow and biomechanical properties. To test this hypothesis, male Sprague–Dawley rats were treated with Hcy (0.67 g/L in drinking water for 8 weeks. Age-matched rats served as controls. At the end of the treatment period, the rats were anesthetized. Blood samples were collected from experimental or control rats. Biochemical turnover markers (body weight, Hcy, vitamin B12, and folate were measured. Systolic blood pressure was measured from the right carotid artery. Tibia blood flow was measured by laser Doppler flow probe. The results indicated that Hcy levels were significantly higher in the Hcy-treated group than in control rats, whereas vitamin B12 levels were lower in the Hcy-treated group compared with control rats. There was no significant difference in folate concentration and blood pressure in Hcy-treated versus control rats. The tibial blood flow index of the control group was significantly higher (0.78 ± 0.09 flow unit compared with the Hcy-treated group (0.51 ± 0.09. The tibial mass was 1.1 ± 0.1 g in the control group and 0.9 ± 0.1 in the Hcy-treated group. The tibia bone density was unchanged in Hcy-treated rats. These results suggest that Hcy causes a reduction in bone blood flow, which contributes to compromised bone biomechanical properties.Keywords: homocysteine, tibia, bone density

  3. 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.

  4. Lyophilized Oral Sustained Release Polymeric Nanoparticles of Nateglinide

    Kaleemuddin, Mohammad; Srinivas, Prathima


    The objective of this study is to formulate lyophilized oral sustained release polymeric nanoparticles of nateglinide in order to decrease dosing frequency, minimize side effects, and increase bioavailability...

  5. Comparative study of fluoride released and recharged from conventional pit and fissure sealants versus surface prereacted glass ionomer technology

    Elias Nahum Salmerón-Valdés


    Full Text Available Context: The fluoride release of sealants in vitro shows a marked decrease. Giomers are distinguishable from manufactured resin-based sealants and contain prereacted glass-ionomer particles (PRG. Aims: To compare the amounts of fluoride released from the main pit and fissure of a resin-based sealant with that from a Giomer and to assess the abilities of the sealant and the Giomer to recharge when exposed to regular use of fluoride rinse. Materials and Methods: The readings for the fluoride concentration were carried out for 60 days using a fluoride ion-specific electrode. After this period, the samples were recharged using a fluoride mouth rinse. The amount of fluoride released after this recharge was determined for 5 days. The data were analyzed using Student′s t- and analysis of variance tests. Results: In general, all materials presented higher fluoride release in the first 24 h; G1 and G4 showed a higher fluoride release in this period. On the other hand, G3 and G1 presented the most constant fluoride release until the 8 th day, wherein all the sealants considerably decreased in the amount of fluoride released. Conclusion: G1 and G3 released higher concentrations of fluoride, although no significant differences were found. Giomers recharged in the first 24 h after polymerization presented an improved and sustained fluoride release.

  6. Neuropeptide release from airways of young and fully-grown rabbits.

    Larsen, Gary L; Fratelli, Cori; Loader, Joan; Kang, June-Ku Brian; Dakhama, Azzeddine


    Nerve growth factor (NGF), a neurotrophin that regulates neuronal development, enhances production of neuropeptides that control airway caliber including substance P (SP). Little is known about the developmental interplay between neurotrophins and neuropeptides. Our goal was to assess release of NGF, SP, and vasoactive intestinal peptide (VIP) from tracheal segments of young (2-week-old) and fully-grown (13-week-old) rabbits, and ascertain location of neuropeptides in airways with mechanical denudation of epithelium and immunohistochemistry. After electrical field stimulation of nerves, bath solutions were collected and immunoassays performed to quantify NGF, SP, and VIP release. There were significant decreases in NGF, SP, and VIP release from airways in 13- versus 2-week-old rabbits. There were also significant decreases in SP and VIP release from denuded versus normal tissues at 2 weeks of age. A similar pattern for SP was seen in 13-week-old rabbits. Immunohistochemistry demonstrated increased neuropeptides in airways from younger rabbits. Although SP was seen in the epithelium and submucosal nerves in the younger group, it was localized to the latter location in fully-grown rabbits. VIP was seen in only submucosal nerves at both ages. Thus, release of NGF, SP, and VIP with neural stimulation decreases in rabbit tracheal segments with age. Decreases in SP with maturation and epithelial denudation appear related in part to decreases in epithelial SP with growth. However, decreases in VIP that occur normally and with epithelial denudation are not explained by location of VIP within the epithelium. The epithelium may be a source of factors that inhibit release of neuropeptides.

  7. Algorithmic complexity of growth hormone release in humans.

    Prank, K; Wagner, M; Brabant, G


    Most hormones are secreted in an pulsatile rather than in a constant manner. This temporal pattern of pulsatile hormone release plays an important role in the regulation of cellular function and structure. In healthy humans growth hormone (GH) secretion is characterized by distinct pulses whereas patients bearing a GH producing tumor accompanied with excessive secretion (acromegaly) exhibit a highly irregular pattern of GH release. It has been hypothesized that this highly disorderly pattern of GH release in acromegaly arises from random events in the GH-producing tumor under decreased normal control of GH secretion. Using a context-free grammar complexity measure (algorithmic complexity) in conjunction with random surrogate data sets we demonstrate that the temporal pattern of GH release in acromegaly is not significantly different from a variety of stochastic processes. In contrast, normal subjects clearly exhibit deterministic structure in their temporal patterns of GH secretion. Our results support the hypothesis that GH release in acromegaly is due to random events in the GH-producing tumorous cells which might become independent from hypothalamic regulation.

  8. Algorithmic complexity of growth hormone release in humans

    Prank, K.; Wagner, M.; Brabant, G. [Medical School Hannover (Germany)


    Most hormones are secreted in an pulsatile rather than in a constant manner. This temporal pattern of pulsatile hormone release plays an important role in the regulation of cellular function and structure. In healthy humans growth hormone (GH) secretion is characterized by distinct pulses whereas patients bearing a GH producing tumor accompanied with excessive secretion (acromegaly) exhibit a highly irregular pattern of GH release. It has been hypothesized that this highly disorderly pattern of GH release in acromegaly arises from random events in the GH-producing tumor under decreased normal control of GH secretion. Using a context-free grammar complexity measure (algorithmic complexity) in conjunction with random surrogate data sets we demonstrate that the temporal pattern of GH release in acromegaly is not significantly different from a variety of stochastic processes. In contrast, normal subjects clearly exhibit deterministic structure in their temporal patterns of GH secretion. Our results support the hypothesis that GH release in acromegaly is due to random events in the GH-producing tumorous cells which might become independent from hypothalamic regulation. 17 refs., 1 fig., 2 tabs.

  9. Oxytocin and prolactin release after hypertonic saline administration in melatonin-treated male Syrian hamsters

    Juszczak, M.; Steger, R.W.; Fadden, C.; Bartke, A. [Southern Illinois Univ., Carbondale, IL (United States)


    The aim of the present investigations was to examine the effects of melatonin (Mel) on oxytocin (OT) release under conditions of osmotic stimulation, brought about by hypertonic saline administration, as well as to determine whether osmotically stimulated OT release in Mel-treated Syrian hamster is associated with alterations in the release of prolactin (PRL) and in norepinephrine (NE) and dopamine (DA) content in the hypothalamus. In both Mel- and vehicle-treated hamsters, injection of hypertonic saline was followed by a significant decrease in OT content in the pituitary neurointermediate lobe (NIL) and elevation of plasma OT and PRL levels. Melatonin injections had no significant affect on NIL OT content in either isotonic- or hypertonic-saline treated animals. Pretreatment with Mel did not alter plasma OT or PRL levels in isotonic saline-injected animals. However, Mel facilitated the release of OT, but prevented the release of PRL after hypertonic saline administration. Melatonin treatment reduced hypothalamic NE content (but not that of DA) in isotonic-saline treated animals. After osmotic stimulation, hypothalamic content of NE and DA was significantly lower in Mel-treated than in vehicle-treated animals. Data from the present study suggest that the osmotically-stimulated release of OT and PRL seems to be related to the activation of noradrenergic rather than dopaminergic transmission. Both dopaminergic and noradrenergic transmission may be, however, involved in mediating the effects of Mel on the osmotically-activated OT and PRL release. (author). 48 refs, 3 figs.

  10. 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...

  11. Rac1 regulates the release of Weibel-Palade Bodies in human aortic endothelial cells

    YANG Shui-xiang 杨水祥; YAN Juan 闫娟; Shailesh S. Deshpande; Kaikobad Irani; Charles J. Lowenstein


    Background The release of Weibel-Palade Bodies (WPB) is a form of endothelial cell activation. But the signal transduction pathway leading to WPB release is not yet defined. We hypothesized that small G-protein rac1 and reactive oxygen species (ROS) mediate the ligand induced release of Weibel-Palade Bodies. Methods We tested this hypothesis by using wild-type and mutant adenoviral rac1 expression vectors, and by manipulating the production and destruction of superoxide and hydrogen peroxide in human aortic endothelial cells (HAEC). Results Thrombin (1.0 Unit, 30 min) induced the increase of WPB release by 3.7-fold in HAEC, and that H2O2 (0.1 mmol/L, 30 min) induced by 4.5-fold. These results correlated with thrombin-stimulated activation of rac-GTP binding activity by 3.5-fold, and increase of ROS production by 3.4-fold. The dominant negative adenoviral rac-N17 gene transfer dramatically inhibited the release of WPB by 64.2% (control) and 77.3% (thrombin-stimulation), and decreased ROS production by 65.5% (control) and 83.6% (thrombin-stimulation) compared with non-infected cells, respectively. Anti-oxidants, catalase and N-acetyl-cysteine significantly decreased the release of WPB by 34% and 79% in control cells, and further decreased by 63.6% and 46.7% in rac-N17 transferred cells compared with non-infected cells. We also confirmed that rac1 was located upstream of ROS in the WPB release pathway. Conclusions Small G-protein rac1 medicates ligand-induced release of Weibel-Palade Bodies in human aortic endothelial cells, and the signal pathway of WPB release is a rac1-dependent ROS regulating mechanism.

  12. Influence of olive oil phenolic compounds on headspace aroma release by interaction with whey proteins.

    Genovese, Alessandro; Caporaso, Nicola; De Luca, Lucia; Paduano, Antonello; Sacchi, Raffaele


    The release of volatile compounds in an oil-in-water model system obtained from olive oil-whey protein (WP) pairing was investigated by considering the effect of phenolic compounds. Human saliva was used to simulate mouth conditions by retronasal aroma simulator (RAS) analysis. Twelve aroma compounds were quantified in the dynamic headspace by SPME-GC/MS. The results showed significant influences of saliva on the aroma release of virgin olive oil (VOO) volatiles also in the presence of WP. The interaction between WP and saliva leads to lower headspace release of ethyl esters and hexanal. Salivary components caused lower decrease of the release of acetates and alcohols. A lower release of volatile compounds was found in the RAS essay in comparison to that in orthonasal simulation of only refined olive oil (without addition of saliva or WP), with the exception of hexanal and 1-penten-3-one, where a significantly higher release was found. Our results suggest that the extent of retronasal odor (green, pungent) of these two volatile compounds is higher than orthonasal odor. An extra VOO was used to verify the release in model systems, indicating that WP affected aroma release more than model systems, while saliva seems to exert an opposite trend. A significant increase in aroma release was found when phenolic compounds were added to the system, probably due to the contrasting effects of binding of volatile compounds caused by WP, for the polyphenol-protein interaction phenomenon. Our study could be applied to the formulation of new functional foods to enhance flavor release and modulate the presence and concentrations of phenolics and whey proteins in food emulsions/dispersions.

  13. Effect of nitric oxide donor SNAP on GABA release from rat brain nerve terminals

    A. S. Tarasenko


    Full Text Available In this work we investigated the effect of nanomolar concentrations of nitric oxide on the release of gamma-aminobutyric acid (GABA from rat brain nerve terminals using a radioisotope method with [3H]GABA and a spectrofluorimetric method with Ca2+-sensitive probe Fluo-4 AM. It was shown that in the presen­ce of dithiothreitol (DTT, nitric oxide donor SNAP at concentration, in which it produces NO in the nanomolar range, caused Ca2+-independent [3H]GABA release from nerve terminals. The applications of 4-aminopyridine (4-AP and nipecotic acid (NA, as the inducers of GABA release from vesicular and cytoplasmic pools, showed that the maximum of SNAP/+DTT-induced [3H]GABA release was registered at 10th min of incubation and coincided in time with significant increase (almost double in NA-induced [3H]GABA release. At this time point, 4-AP-induced release of [3H]GABA was drastically reduced. At the 15th min of incubation of nerve terminals with SNAP/+DTT, the opposite picture was observed: the decrease in NA- and increase in 4-AP-induced [3H]GABA release. Thus, nitric oxide in the form of S-nitrosothiols at nanomolar concentrations causes Ca2+-independent GABA leakage from synaptic vesicles into cytosol with subsequent release from nerve terminals. The reuptake of the neurotransmitter and its re-accumulation in synaptic vesicles occur later.

  14. Gum Ghatti--a pharmaceutical excipient: development, evaluation and optimization of sustained release mucoadhesive matrix tablets of domperidone.

    Gurpreetarora; Malik, Karan; Rana, Vikas; Singh, Inderbir


    The objective of this study was to extend the GI residence time of the dosage form and to control the release of domperidone using directly compressible sustained release mucoadhesive matrix (SRMM) tablets. A 2-factor centre composite design (CCD) was employed to study the influence of independent variables like gum ghatti (GG) (X1) and hydroxylpropylmethyl cellulose K 15M (HPMC K 15M) (X2) on dependent variable like mucoadhesive strength, tensile strength, release exponent (n), t50 (time for 50% drug release), rel(10 h) (release after 10 h) and rel(18 h) (release after 18 h). Tablets were prepared by direct compression technology and evaluated for tablet parametric test (drug assay, diameter, thickness, hardness and tensile strength), mucoadhesive strength (using texture analyzer) and in vitro drug release studies. The tensile strength and mucoadhesive strength were found to be increased from 0.665 +/- 0.1 to 1.591 +/- 0.1 MN/cm2 (Z1 to Z9) and 10.789 +/- 0.985 to 50.924 +/- 1.150 N (Z1 to Z9), respectively. The release kinetics follows first order and Hixson Crowell equation indicating drug release following combination of diffusion and erosion. The n varies between 0.834 and 1.273, indicating release mechanism shifts from non fickian (anomalous release) to super case II, which depict that drug follows multiple drug release mechanism. The t50 time was found to increase from 5 +/- 0.12 to 11.4 +/- 0.14 h (Z1 to Z9) and release after 10 and 18 h decreases with increasing concentration of both polymers concluding with release controlling potential of polymers. The accelerated stability studies were performed on optimized formulation as per ICH guideline and the result showed that there was no significant change in tensile strength, mucoadhesive strength and drug assay.


    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. Fluoride release from newly marketed fluoride varnishes.

    Jablonowski, Beth L; Bartoloni, Joseph A; Hensley, Donna M; Vandewalle, Kraig S


    New fluoride varnishes have been marketed that reportedly release more fluoride (Enamel Pro) or release fluoride more slowly (Vanish XT). The purpose of this study was to compare the amount and rate of fluoride release of new fluoride varnishes with other traditional fluoride varnishes. Extracted molars were cut into block sections. The enamel surfaces of the sections were painted with Enamel Pro, Duraphat, Vanish, or Vanish XT fluoride varnishes. One group was not treated and served as a negative control. The tooth sections were immersed in artificial saliva. The concentration of fluoride in parts per million was measured after the first 30 minutes, daily for the first week, and weekly until the level was below the limit of detection. Fluoride release was plotted over time. Cumulative fluoride release and rate of release (slope) were analyzed using one-way ANOVA/Tukey (α = .05). Enamel Pro had the greatest cumulative fluoride release. There was no significant difference between Duraphat and Vanish. Vanish XT had the lowest cumulative fluoride release. The rate of fluoride release from 1 week to limit of detection was Enamel Pro > Vanish > Duraphat > Vanish XT. The two newly marketed fluoride varnishes (Enamel Pro and Vanish XT) had significantly different fluoride release from the two conventional fluoride varnishes (Duraphat and Vanish).

  17. Open Versus Arthroscopic Tennis Elbow Release

    Leiter, Jeff; Clark, Tod; McRae, Sheila; Dubberley, James; MacDonald, Peter B.


    Objectives: The primary objective of this study was to determine if quality of life and function are different following arthroscopic versus open tennis elbow release surgery. Based on retrospective studies, both approaches have been found to be beneficial, but no prospective randomized comparison has been conducted to date. Methods: Following a minimum six-months of conservative treatment, seventy-one patients (>16 yrs old) were randomized intraoperatively to undergo either arthroscopic or open lateral release. Outcome measures were the Disabilities of the Arm, Shoulder and Hand questionnaire (DASH), a 5-question VAS Pain Scale, and grip strength. Study assessments took place pre-, and 6-week, 3-, 6-, and 12-months post-surgery. Comparisons between groups and within groups over time were conducted using repeated measures ANOVA. A minimal clinically significant difference for the DASH had been previously identified as 15 points, and was used to compare groups as well at 12-months post-operative (Beaton et al. 2001). Results: Fifteen women and 19 men underwent the open procedure with a mean age of 47.1 years (6.7) and 13 women and 21 men were in the arthroscopic group with a mean age of 45.0 (6.9). No pre-surgery differences were found between groups based on age, sex, DASH or VAS scores. Both groups demonstrated a significant improvement in subjective measures and grip strength by 12-months post-surgery, and no significant differences were found between groups at any time point. The DASH, our primary outcome, decreased from a mean (SD) of 47.5 (14.5) pre-surgery to 21.9 (21.8) at 12-months post-surgery in the Open group and from 52.7 (16.0) to 22.6 (21.1) in the Arthroscopic group. VAS-pain scores (%) decreased in the Open group from 62.5 (17.2) pre-operatively to 30.0 (26.5) at 12-months. In the arthroscopic group, scores decreased from 63.7 (15.9) to 26.2 (24.6). Grip strength (kg) increased on the affected side from 23.6 (14.9) to 29.3 (16.3) and 21.4 (15.4) to

  18. ISOPAR L Release Rates from Saltstone Using Simulated Salt Solutions

    Bronikowski, M


    The Modular Caustic-Side Solvent Extraction (CSSX) Unit (MCU) and the Salt Waste Processing Facility (SWPF) will produce a Deactivated Salt Solution (DSS) that will go to the Saltstone Production Facility (SPF). Recent information indicates that solvent entrainment in the DSS is larger than expected. The main concern is with Isopar{reg_sign} L, the diluent in the solvent mixture, and its flammability in the saltstone vault. If it is assumed that all the Isopar{reg_sign} L is released instantaneously into the vault from the curing grout before each subsequent pour; the Isopar{reg_sign} L in the vault headspace is well mixed; and each pour displaces an equivalent volume of headspace, the allowable concentration of Isopar{reg_sign} L in the DSS sent to SPF has been calculated at approximately 4 ppm. The amount allowed would be higher, if the release from grout were significantly less. The Savannah River National Laboratory was tasked with determining the release of Isopar{reg_sign} L from saltstone prepared with a simulated DSS with Isopar{reg_sign} L concentrations ranging from 50 mg/L to 200 mg/L in the salt fraction and with test temperatures ranging from ambient to 95 C. The results from the curing of the saltstone showed that the Isopar{reg_sign} L release data can be treated as a percentage of initial concentration in the concentration range studied. The majority of the Isopar{reg_sign} L that was released over the test duration was released in the first few days. The release of Isopar{reg_sign} L begins immediately and the rate of release decreases over time. At higher temperatures the immediate release is larger than at lower temperatures. In one test at 95 C essentially all of the Isopar{reg_sign} L was released in three months. Initial curing temperature was found to be very important as slight variations during the first few days affected the final Isopar{reg_sign} L amount released. Short scoping tests at 95 C with solvent containing all components (Isopar

  19. Pressure-morphology relationship of a released carpal tunnel.

    Kim, Dong Hee; Marquardt, Tamara L; Gabra, Joseph N; Shen, Zhilei Liu; Evans, Peter J; Seitz, William H; Li, Zong-Ming


    We investigated morphological changes of a released carpal tunnel in response to variations of carpal tunnel pressure. Pressure within the carpal tunnel is known to be elevated in patients with carpal tunnel syndrome and dependent on wrist posture. Previously, increased carpal tunnel pressure was shown to affect the morphology of the carpal tunnel with an intact transverse carpal ligament (TCL). However, the pressure-morphology relationship of the carpal tunnel after release of the TCL has not been investigated. Carpal tunnel release (CTR) was performed endoscopically on cadaveric hands and the carpal tunnel pressure was dynamically increased from 10 to 120 mmHg. Simultaneously, carpal tunnel cross-sectional images were captured by an ultrasound system, and pressure measurements were recorded by a pressure transducer. Carpal tunnel pressure significantly affected carpal arch area (p 62 mm(2) at 120 mmHg. Carpal arch height, length, and width also significantly changed with carpal tunnel pressure (p carpal tunnel pressure increased, carpal arch height and length increased, but the carpal arch width decreased. Analyses of the pressure-morphology relationship for a released carpal tunnel revealed a nine times greater compliance than that previously reported for a carpal tunnel with an intact TCL. This change of structural properties as a result of transecting the TCL helps explain the reduction of carpal tunnel pressure and relief of symptoms for patients after CTR surgery.

  20. Tissue engineering scaffold for sequential release of vancomycin and rhBMP2 to treat bone infections.

    Pacheco, Hernando; Vedantham, Kumar; Aniket; Young, Amy; Marriott, Ian; El-Ghannam, Ahmed


    The ability of silica calcium phosphate nanocomposite (SCPC75) for the controlled sequential delivery of vancomycin (Vanc) and rhBMP2 was evaluated. Fourier transform infrared spectroscopy analyses of the SCPC75 showed an increase in the bond energy of the PO4 (-3) due to the interactions with negatively charged moieties of Vanc. Furthermore, a decrease in the bond energy of the Si-O-Si functional groups was observed after rhBMP2 adsorption. In conjunction with the differences in bond site and bond energy at the ceramic/drug interface, significant differences in drug release kinetics and bioceramic dissolution rate were found. UV-vis spectrometry showed a burst release of Vanc in the first 8 h followed by a sustained release stage for up to 28 days. ELISA showed first-order release kinetics of rhBMP2 without burst release. The rhBMP2 release from SCPC75 was associated with a significantly lower rate of Ca and a higher rate of Si dissolutions when compared with Vanc release over identical time periods. Differences in the release kinetic profiles of Vanc and rhBMP2 from the SCPC75-Vanc/SCPC75-rhBMP2 scaffolds at 70/30, 50/50, or 20/80 ratios allowed for sequential drug release profiles that could be exploited to customize doses and release duration of each drug. The released rhBMP2 significantly upregulated MC3T3-E1 expression of collagen type I, osteopontin, and osteocalcin mRNA by 12.6-, 3.3-, and 2.4-fold, respectively. The released Vanc demonstrated bactericidal effects on Staphylococcus aureus in vitro. These results suggest the potential of SCPC75-Vanc-rhBMP2 scaffolds in the treatment of damaged and/or infected bone. © 2014 Wiley Periodicals, Inc.

  1. Daidzin decreases ethanol consumption in rats.

    Heyman, G M; Keung, W M; Vallee, B L


    In a previous study, daidzin, a constituent of an ancient Chinese herbal treatment for alcoholism, decreased home-cage ethanol consumption in laboratory Syrian golden hamsters. The present study tested the generality of daidzin's antidipsotropic effects. Rats served as subjects in a two-lever choice procedure. At one lever, responses earned 10% ethanol, flavored with saccharin. At the other lever, responses earned an isocaloric starch solution. Daidzin decreased both ethanol and starch consumption, but the decreases in ethanol intake were larger. Changes in consumption were dose dependent, and differences in ethanol and food consumption increased slightly (but significantly) as dose increased. Daidzin produced a similar pattern of decreases in lever pressing. In baseline, there was an approximately equal distribution of responses between the two levers; at the highest daidzin dose, the relative number of responses at the ethanol lever decreased to 30%. These results replicate and extend earlier findings, and they encourage further research on daidzin's capacity to decrease ethanol consumption.

  2. 血清胃泌素释放肽前体在小细胞肺癌诊断和分期中的临床意义%The clinical significance of serum progastrin releasing peptide in the diagnosis and staging of small cell lung cancer

    高振远; 欧毅梅; 张竞竞; 张浩然; 毕明宏


    Objective:To explore the clinical value of the levels of serum progastrin releasing peptide(proGRP)in the differential diagnosis and clinical staging of small cell lung cancer( SCLC) and non-small cell lung cancer( NSCLC) . Methods:The serum levels of proGRP in 62 patients with SCLC( including 25 cases of limited stage and 37 cases of extensive stage) and 38 patients with NSCLC were measured by chemiluminescent immunoassay,which was compared with neuron specific enolase( NSE) . The sensitivity,specificity and tumor staging in all patients were analyzed. Results:The sensitivities of the single detection of proGRP, NSE and combination detection of proGRP and NSE in diagnosing SCLC were 82. 93%, 64. 15% and 71. 58%, respectively. The positive rate of the combination detection of proGRP and NSE in diagnosing SCLC was significantly higher than that of the single detection of NSE, the difference of the positive rate between combination detection proGRP and NSE and single detection of proGRP was not statistically significant(P>0. 05). The serum levels of proGRP and NSE in patients with SCLC were obviously higher than those in NSCLC patients (P0.05)。 SCLC组患者血清proGRP和NSE水平均显著高于NSCLC 组(P<0.01)。 SCLC广泛期患者血清proGRP和NSE值均显著高于其局限期患者(P<0.01)。结论:proGRP作为SCLC的标志物,具有敏感度高的特点,并可反映SCLC的分期。 proGRP和NSE联合检测可提高SCLC诊断的准确率。

  3. Development of novel sustained release matrix pellets of betahistine dihydrochloride: effect of lipophilic surfactants and co-surfactants.

    Shamma, Rehab Nabil; Basalious, Emad B; Shoukri, Raguia


    Sustained release matrix pellets of the freely water soluble drug, betahistine dihydrochloride (BH), were prepared using freeze pelletization technique. Different waxes and lipids (cetyl alcohol, beeswax, glyceryl tripalmitate (GTP) and glyceryl tristearate) were evaluated for the preparation of matrix pellets. A D-optimal design was employed for the optimization and to explore the effect of drug loading (X(1)), concentration of lipophilic surfactant (X(2)), concentration of co-surfactant (X(3)) and wax type (X(4)) on the release extent of the drug from matrix pellets. The entrapment efficiency (Y(1)), pellet diameter (Y(2)), and the percentage drug released at given times were selected as dependent variables. Results revealed a significant impact of all independent variables on drug release from the formulated pellets. The lipophilic surfactant significantly increased both the entrapment efficiency and the in vitro drug release and significantly decreased the pellet size. The optimized BH-loaded pellets were composed of 19.95% drug loading, 9.95% Span(®) 80 (surfactant), 0.25% Capmul(®) (co-surfactant) using glyceryl tripalmitate as a matrix former. The release profiles of the drug from hard gelatin capsule containing optimized pellets equivalent to 32 mg BH was similar to that of target release model for once-daily administration based on similarity factor. It could be concluded that a promising once-daily capsule containing sustained release pellets of BH was successfully designed.

  4. 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.

  5. [Effects of controlled-release N and K fertilizers on N, P, and K use efficiency of mauls (Manlus robusta)].

    Shao, Lei; Wang, Li-xia; Zhang, Min; Sun, Zhi-jun


    A pot experiment was conducted to study the effects of controlled-release N and K fertilizers on mauls seedlings growth, their P and K use efficiency, and the N balance in soil-plant system. The results showed that the nutrient release from controlled-release fertilizers accorded well with the nutrient requirement of mauls seedlings. Controlled-release N fertilizer significantly increased the K use efficiency, and controlled-release K fertilizer significantly increased the N use efficiency. Under the same K application rate, the plant height and stem diameter under the application of controlled-release N fertilizer (CN) and controlled-release N and K fertilizers (NK) had no significant difference, while those under the application of common fertilizer (SF) were all higher. The plant dry mass and the P and K use efficiency were in the order of NK>CN>SF. Under the application of NK, the application rate of K had no significant effects on the plant height and stem diameter, but significantly affected the plant dry mass. The P use efficiency increased with increasing application rate of controlled-release K fertilizer, but was less affected by application rate common K fertilizer. The K use efficiency decreased with increasing application rate of K. The N use efficiency was in the order of NK>CN>SF, while the N loss rate was in adverse. The residual rate of NK and CN had no significant difference, but was higher than that of SF. The application rate of controlled-release K fertilizer had significant effects on the N use efficiency and N loss rate, but no significant effects on N residual rate.

  6. CO-releasing molecule (CORM) conjugate systems.

    Kautz, Anna Christin; Kunz, Peter C; Janiak, Christoph


    The development of CORMs (CO-releasing molecules) as a prodrug for CO administration in living organisms has attracted significant attention. CORMs offer the promising possibility of a safe and controllable release of CO in low amounts triggered by light, ligands, enzymes, etc. For the targeting of specific tissues or diseases and to prevent possible side effects from metals and other residues after CO release, these CORMs are attached to biocompatible systems, like peptides, polymers, nanoparticles, dendrimers, protein cages, non-wovens, tablets, and metal-organic frameworks. We discuss in this review the known CORM carrier conjugates, in short CORM conjugates, with covalently-bound or incorporated CORMs for medicinal and therapeutic applications. Most conjugates are nontoxic, show increasing half-lives of CO release, and make use of the EPR-effect, but still show problems because of a continuous background of CO release and the absence of an on/off-switch for the CO release.

  7. Hyperoxia decreases muscle glycogenolysis, lactate production, and lactate efflux during steady-state exercise.

    Stellingwerff, Trent; Leblanc, Paul J; Hollidge, Melanie G; Heigenhauser, George J F; Spriet, Lawrence L


    The aim of this study was to determine whether the decreased muscle and blood lactate during exercise with hyperoxia (60% inspired O2) vs. room air is due to decreased muscle glycogenolysis, leading to decreased pyruvate and lactate production and efflux. We measured pyruvate oxidation via PDH, muscle pyruvate and lactate accumulation, and lactate and pyruvate efflux to estimate total pyruvate and lactate production during exercise. We hypothesized that 60% O2 would decrease muscle glycogenolysis, resulting in decreased pyruvate and lactate contents, leading to decreased muscle pyruvate and lactate release with no change in PDH activity. Seven active male subjects cycled for 40 min at 70% VO2 peak on two occasions when breathing 21 or 60% O2. Arterial and femoral venous blood samples and blood flow measurements were obtained throughout exercise, and muscle biopsies were taken at rest and after 10, 20, and 40 min of exercise. Hyperoxia had no effect on leg O2 delivery, O2 uptake, or RQ during exercise. Muscle glycogenolysis was reduced by 16% with hyperoxia (267 +/- 19 vs. 317 +/- 21 mmol/kg dry wt), translating into a significant, 15% reduction in total pyruvate production over the 40-min exercise period. Decreased pyruvate production during hyperoxia had no effect on PDH activity (pyruvate oxidation) but significantly decreased lactate accumulation (60%: 22.6 +/- 6.4 vs. 21%: 31.3 +/- 8.7 mmol/kg dry wt), lactate efflux, and total lactate production over 40 min of cycling. Decreased glycogenolysis in hyperoxia was related to an approximately 44% lower epinephrine concentration and an attenuated accumulation of potent phosphorylase activators ADPf and AMPf during exercise. Greater phosphorylation potential during hyperoxia was related to a significantly diminished rate of PCr utilization. The tighter metabolic match between pyruvate production and oxidation resulted in a decrease in total lactate production and efflux over 40 min of exercise during hyperoxia.

  8. Biological significance of soluble IL-2 receptor

    Calogero Caruso


    Full Text Available A NUMBER of receptors for growth factors and differentiation antigens have been found to be secreted or released by cells. Following mononuclear cell (MNC activation and interleukin-2 receptor (IL-2R expression, a soluble form of the Alpha;-chain of IL-2R (sIL-2R is released. The sIL-2R has been shown to be present in the culture supernatants of activated MNCs as well as in normal sera and, in higher amounts, in sera from subjects affected by several diseases including neoplastic, infectious and autoimmune ones, and in sera from transplanted patients suffering allograft rejection. The blood sIL-2R levels depend on the number of producing cells and the number of molecules per cell, so that sIL-2R blood values may represent an index of the number and the functional state of producing cells, both normal and neoplastic. Thus, monitoring of the immune system, mostly T-cells and haematological malignancies might be targets for the measurement of sIL-2R. Since many conditions may influence sIL-2R production, little diagnostic use may result from these measurements. However, since blood sIL-2R levels may correlate with disease progression and/or response to therapy, their measurement may be a useful index of activity and extent of disease. The precise biological role of the soluble form of the IL-2R is still a matter of debate. However, we know that increased sIL-2R levels may be observed in association with several immunological abnormalities and that sIL-2R is able to bind IL-2. It is conceivable then that in these conditions the excess sIL-2R released in vivo by activated lymphoid cells or by neoplastic cells may somehow regulate IL-2-dependent processes. On the other hand, it cannot exclude that sIL-2R is a by-product without biological significance. Finally, it is puzzling that in many conditions in which an increase of blood sIL-2R values has been observed, MNCs display a decreased in vitro capacity to produce sIL-2R. These seemingly contrasting

  9. 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.…

  10. Linking snow depth to avalanche release area size: measurements from the Vallée de la Sionne field site

    Veitinger, Jochen; Sovilla, Betty


    One of the major challenges in avalanche hazard assessment is the correct estimation of avalanche release area size, which is of crucial importance to evaluate the potential danger that avalanches pose to roads, railways or infrastructure. Terrain analysis plays an important role in assessing the potential size of avalanche releases areas and is commonly based on digital terrain models (DTMs) of a snow-free summer terrain. However, a snow-covered winter terrain can significantly differ from its underlying, snow-free terrain. This may lead to different, and/or potentially larger release areas. To investigate this hypothesis, the relation between avalanche release area size, snow depth and surface roughness was investigated using avalanche observations of artificially triggered slab avalanches over a period of 15 years in a high-alpine field site. High-resolution, continuous snow depth measurements at times of avalanche release showed a decrease of mean surface roughness with increasing release area size, both for the bed surface and the snow surface before avalanche release. Further, surface roughness patterns in snow-covered winter terrain appeared to be well suited to demarcate release areas, suggesting an increase of potential release area size with greater snow depth. In this context, snow depth around terrain features that serve as potential delineation borders, such as ridges or trenches, appeared to be particularly relevant for release area size. Furthermore, snow depth measured at a nearby weather station was, to a considerable extent, related to potential release area size, as it was often representative of snow depth around those critical features where snow can accumulate over a long period before becoming susceptible to avalanche release. Snow depth - due to its link to surface roughness - could therefore serve as a highly useful variable with regard to potential release area definition for varying snow cover scenarios, as, for example, the avalanche

  11. Obesity Decreases Perioperative Tissue Oxygenation

    Kabon, Barbara; Nagele, Angelika; Reddy, Dayakar; Eagon, Chris; Fleshman, James W.; Sessler, Daniel I.; Kurz, Andrea


    Background: Obesity is an important risk factor for surgical site infections. The incidence of surgical wound infections is directly related to tissue perfusion and oxygenation. Fat tissue mass expands without a concomitant increase in blood flow per cell, which might result in a relative hypoperfusion with decreased tissue oxygenation. Consequently, we tested the hypotheses that perioperative tissue oxygen tension is reduced in obese surgical patients. Furthermore, we compared the effect of supplemental oxygen administration on tissue oxygenation in obese and non-obese patients. Methods: Forty-six patients undergoing major abdominal surgery were assigned to one of two groups according to their body mass index (BMI): BMI < 30 kg/m2 (non-obese) and BMI ≥ 30 kg/m2 (obese). Intraoperative oxygen administration was adjusted to arterial oxygen tensions of ≈150 mmHg and ≈300 mmHg in random order. Anesthesia technique and perioperative fluid management were standardized. Subcutaneous tissue oxygen tension was measured with a polarographic electrode positioned within a subcutaneous tonometer in the lateral upper arm during surgery, in the recovery room, and on the first postoperative day. Postoperative tissue oxygen was also measured adjacent to the wound. Data were compared with unpaired two tailed t-tests and Wilcoxon rank-sum tests; P < 0.05 was considered statistically significant. Results: Intraoperative subcutaneous tissue oxygen tension was significantly less in the obese patients at baseline (36 vs. 57 mmHg, P = 0.002) and with supplemental oxygen administration (47 vs. 76 mmHg, P = 0.014). Immediate postoperative tissue oxygen tension was also significantly less in subcutaneous tissue of the upper arm (43 vs. 54 mmHg, P = 0.011) as well as near the incision (42 vs. 62 mmHg, P = 0.012) in obese patients. In contrast, tissue oxygen tension was comparable in each group on the first postoperative morning. Conclusion: Wound and tissue hypoxia were common in obese

  12. Octyl-methoxycinnamate (OMC), an ultraviolet (UV) filter, alters LHRH and amino acid neurotransmitters release from hypothalamus of immature rats.

    Szwarcfarb, B; Carbone, S; Reynoso, R; Bollero, G; Ponzo, O; Moguilevsky, J; Scacchi, P


    OMC (octyl-methoxycinnamate), is an endocrine disruptor with estrogenic activity, which is used in sunscreen creams as a UV filter. We studied its " IN VITRO" effects on the hypothalamic release of LHRH as well as on the amino acid neurotransmitter system in immature rats of 15 (prepubertal) and 30 (peripubertal) days of age. OMC decreased the LH-RH release significantly in male and female rats of both age. In male rats OMC increased the release of GABA while in the female ones It diminished the excitatory amino acid aspartate (ASP) and Glutamate (GLU) without modifications in the hypothalamic GABA release. These results suggest that during sexual maturation the inhibitory effect of OMC on LH-RH release appears to be related to its action on the inhibitory and excitatory amino acid neurotransmitters in male and female rats.

  13. Fluoride release, recharge and flexural properties of polymethylmethacrylate containing fluoridated glass fillers.

    Al-Bakri, I A; Swain, M V; Naoum, S J; Al-Omari, W M; Martin, E; Ellakwa, A


    The purpose of this study was to investigate the effect of fluoridated glass fillers on fluoride release, recharge and the flexural properties of modified polymethylmethacrylate (PMMA). Specimens of PMMA denture base material with various loading of fluoridated glass fillers (0%, 1%, 2.5%, 5% and 10% by weight) were prepared. Flexural properties were evaluated on rectangular specimens (n = 10) aged in deionized water after 24 hours, 1 and 3 months. Disc specimens (n = 10) were aged for 43 days in deionized water and lactic acid (pH 4.0) and fluoride release was measured at numerous intervals. After ageing, specimens were recharged and fluoride re-release was recorded at 1, 3 and 7 days after recharge. Samples containing 2.5%, 5% and 10% glass fillers showed significantly (p glass fillers specimens. All experimental specimens exhibited fluoride release in both media. The flexural strength of specimens decreased in proportion to the percentage filler inclusion with the modulus of elasticity values remaining within ISO Standard 1567. The modified PMMA with fluoridated glass fillers has the ability to release and re-release fluoride ion. Flexural strength decreased as glass filler uploading increased. © 2014 Australian Dental Association.

  14. 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

  15. Fluoride Release From Three Different Types of Giass- lonomer Cements After Exposure to Acidic and Neutral NaF Solution

    Kousari A


    Full Text Available The purpose of this study was to assess the fluoride release of three fluoride- containing materials exposed to fluoride solutions. This study compared the initial fluoride release and release following re-fluoridation (neutral or acidic 2% NaF of three different filling materials, conventional glass ionomer cement (CG1C, resin- modified glass ionomer cement (RMGIC, polyacid- modified composite resin (PAMCR. Twenty discs of each material, measuring 2mm height and 6mm diameter, were suspended in separate vials of 2" laboratory artificial saliva. The amount of fluoride release was measured over two periods of 28 days each. Fluoride release was determined at 1,3,7,14 and 28 days of each period. Fluoride was measured with a fluoride ion- specific electrode and an ion analyzer previously calibrated with standard solution .T- test and ANOVA were used to evaluate the data. Fluoride release for all products at days 1 and 3 was significantly greater than the rest of the time intervals. Then, the fluoride release decreased significantly. CGIC released significantly more fluoride than the other products. This was followed by RMGIC, which exhibited significantly more fluoride release than PAMCR. In second period of experiment, the specimens were assigned to two subgroups often each. The samples exposed to two different solution of NaF (neutral or acidic. All groups showed the capacity of re-fluoridation and fluoride uptake. The specimens exposed to acidic NaF solution showed statistically more significant rechargeability than the neutral NaF solution. It may be concluded that glass ionomer cements act as a rechargeable slow fluoride release systems and as an effective caries preventive material in caries preventing programs for caries susceptible children.

  16. 40 CFR 721.90 - Release to water.


    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Release to water. 721.90 Section 721... SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Certain Significant New Uses § 721.90 Release to water. Whenever a... predict the surface water concentration which will result from the intended release of the substance,...

  17. Fluoride release from restorative materials coated with an adhesive.

    Miranda, Letícia Algarves; Weidlich, Patrícia; Samuel, Susana Maria Werner; Maltz, Marisa


    The retention of both fluoride resins and resin-modified glass ionomer cements to dental tissues can be improved by the association of an adhesive system which promotes the bonding between the resin component and dentin, forming a hybrid layer. The purpose of this investigation was to evaluate if the presence of the adhesive, being part of the hybrid layer composition, interfered with the fluoride released to tooth tissues. The restorative materials studied were: Vitremer (3M), Heliomolar (Vivadent) and Z100 (3M) using an adhesive application (Scotch Bond MultiPurpose Plus--3M). Ten discs of each material were prepared: 5 were covered with the adhesive and 5 were not. The discs were immersed in individual flasks containing artificial saliva which was changed daily. Fluoride release was measured at days 1, 5, 10, 15 and 20 by a fluoride combined electrode (9609 BN--Orion) coupled to an ion analyzer (SA-720 Procyon). One-way ANOVA and the Student-Newman-Keuls test were applied to compare the materials. The results showed that the use of a dental adhesive significantly decreased the fluoride release of Vitremer and reduced the fluoride release of Heliomolar to undetectable levels with the methodology used.

  18. [Nutrient release characteristics and use efficiency of slow- and controlled release fertilizers].

    Duan, Lu-Lu; Zhang, Min; Liu, Gang; Shang, Zhao-Cong; Yang, Yi


    Water extraction method and soil incubation method were used to study the nutrient release characteristics of four slow- and controlled release fertilizers (CRF1, CRF2, SCU, and IBDU), and pot experiment was conducted to assess the effects of the release characteristics on the nutrient requirements of canola (Brassica napus L.). The nutrient release curves of test fertilizers in water were S pattern for CRF1 and CRF2, burst pattern for SCU, and reverse L pattern for IBDU. The nutrient release characteristics of the four fertilizers in water and in soil all fitted binomial equations, suggesting that there existed some similarities in the nutrient release in the two media. The nutrient uptake and biomass of canola plants treated with CRF1 and CRF2 were significantly higher than those treated with SCU and IBDU, and CRF2 had the greatest effect. The nutrient release curves of CRF1 and CRF2 accorded more closely with the nutrient requirements of canola.

  19. Opioid/naloxone prolonged release combinations for opioid induced constipation

    Shailendra Kapoor


    I read with great interest the recent article by Chen et a/in a recent issue of your esteemed journal.The article is highly thought provoking.One emerging therapeutic alternative for opioid induced constipation is the emergence of opioid/naloxone prolonged release combinations.For instance,naloxone when administered in a 1∶2 ratio with oxycodone reverses the inhibitory effect of oxycodone on the gastrointestinal tract.The advantage of oxycodone/naloxone prolonged release (OXN) is that while its anti-nociceptive efficacy is equivalent to that of oxycodone prolonged release (OXC),it significantly decreases the "Bowel Function Index" thereby ameliorating symptoms of opioid induced constipation to a large extent.Schutter et al in a recent study have reported a decrease in the bowel function index from 38.2 to 15.1.Similarly,L(o)wenstein et al in another recent study have reported that following a month of therapy,complete spontaneous bowel movements per week is increased from one in OXC therapy to three in OXN therapy.

  20. pH-independent release of propranolol hydrochloride from HPMC-based matrices using organic acids


    Full Text Available Background and purpose of the study: Propranolol HCl, a widely used drug in the treatment of cardiac arrhythmias and hypertension, is a weak basic drug with pH-dependent solubility that may show release problems from sustained release dosage forms at higher pH of small intestine. This might decrease drug bioavailability and cause variable oral absorption. Preparation of a sustained release matrix system with a pH-independent release profile was the aim of the present study. Methods: Three types of organic acids namely tartaric, citric and fumaric acid in the concentrations of 5, 10 and 15 % were added to the matrices prepared by hydroxypropyl methylcellulose (HPMC and dicalcium phosphate. The drug release studies were carried out at pH 1.2 and pH 6.8 separately and mean dissolution time (MDT as well as similarity factor (¦2 were calculated for all formulations. Results and discussion: It was found that incorporation of 5 and 10 % tartaric acid in tablet formulations with 30 % HPMC resulted in a suitable pH-independent release profiles with significant higher ¦2 values (89.9 and 87.6 respectively compared to acid free tablet (58.03. The other two acids did not show the desirable effects. It seems that lower pKa of tartaric acid accompanied by its higher solubility were the main factors in the achievement of pH-independent release profiles.

  1. FSAP-mediated nucleosome release from late apoptotic cells is inhibited by autoantibodies present in SLE.

    Marsman, Gerben; Stephan, Femke; de Leeuw, Karina; Bulder, Ingrid; Ruinard, Jessica T; de Jong, Jan; Westra, Johanna; Bultink, Irene E M; Voskuyl, Alexandre E; Aarden, Lucien A; Luken, Brenda M; Kallenberg, Cees G M; Zeerleder, Sacha


    Inefficient clearance of apoptotic cells and the subsequent exposure of the immune system to nuclear contents are crucially involved in the pathogenesis of systemic lupus erythematosus (SLE). Factor VII-activating protease (FSAP) is activated in serum upon contact with dead cells, and releases nucleosomes from late apoptotic cells into the extracellular environment. We investigated whether FSAP-mediated nucleosome release from late apoptotic cells is affected in SLE patients. Nucleosome release in sera of 27 SLE patients and 30 healthy controls was investigated by incubating late apoptotic Jurkat cells with serum and analyzing the remaining DNA content by flow cytometry. We found that nucleosome release in sera of SLE patients with high disease activity was significantly decreased when compared with that in SLE sera obtained during low disease activity or from healthy individuals. Upon removal of IgG/IgM antibodies from SLE sera, nucleosome release was restored. Similarly, monoclonal antinuclear antibodies inhibited nucleosome release in healthy donor serum or by plasma-purified FSAP. This inhibition was lost when Fab fragments were used, suggesting that antigen cross-linking is involved. In conclusion, FSAP-mediated nucleosome release from late apoptotic cells is greatly impaired in SLE patient sera, possibly hampering the clearance of these cells and thereby propagating inflammation.

  2. Correlation and clinical significance of the decreased cervical mobility in ankylosing spondylitis patient with thoracolumbar kyphosis%强直性脊柱炎胸腰椎后凸畸形患者颈椎活动受限的相关因素及临床意义

    冯帆; 钱邦平; 邱勇; 王斌; 俞杨; 朱泽章; 季明亮; 胡俊; 史本龙


    Objectives:To investigate the risk factors and its clinical significance of limited cervical range of motion in ankylosing spondylitis(AS) patients with thoracolumbar kyphosis.Methods:From May 2012 to Octobcr 2012,38 AS patients (with complete medical records) from the 51 consecutive AS patients with thoracolumbar kyphosis in our hospital werc cnrolled.There were 36 males and 2 females,with an average age of 32.6 years(range,17-53 years).The clinical data consisted of age,discase course,erythrocyte sedimentation rate(ESR),C-reaction protein(CRP).The radiographic parameters were composed by global kyphosis(GK),cervical mSASSS(the modified Stokes ankylosing spondylitis spinal score),cervical curve and C2-C7 SVA.The quality of life questionnaires consisted of bath ankylosing spondylitis disease activity index (BASDAI),bath ankylosing spondylitis functional index(BASFI) and Oswestry disability index(ODI).According to the value of cervical range of motion(CROM),the subjects were divided into two groups:group A,CROM >40°; group B,CROM <20°.The independent t-test was used to compare the parameters between the two groups.Furthermore,the Pearson correlation test was performed to investigate the risk factors correlated with CROM.Results:In group A,there were 16 patients with an average CROM of 65.8°±14.3°(41°-92°),while 17 patients in group B with an average CROM of 9.2°±6.6°(1°-19°).With respect to the disease course,BASFI,GK,mSASSS,cervical curve and C2-C7 SVA,significant differences were found between two groups(P<0.05).However,the age,ODI,BASDAI,ESR or CRP showed no significant difference between group A and B(P>0.05).There were remarkable correlations between CROM and disease course,mSASSS,cervical curve,C2-C7 SVA and BASFI(r=-0.524,-0.895,0.494,-0.813,and-0.501 respectively,P<0.05).Especially,there was no significant correlation between GK and CROM(r=-0.275,P=0.122).Conclusions:Longer disease course and cervical structural damage are high risk

  3. Effects of cold stress on hypothalamic corticotrophin-releasing and thyrotropin-releasing hormone messenger RNA levels in chickens

    WANG Jintao; XU Shiwen


    There is increasing evidence that stress can activate the hypothalamic-pituitary-adrenal-axis and hypothalamic-pituitarythyroid-axis, and further affect the synthesis and secretion of corticotrophin-releasing hormone (CRH) and thyrotropin-releasing hormone (TRH). To evaluate the effect of cold stress on the hypothalamic CRH and TRH messenger RNA (mRNA) levels in Yisha chickens, male Yisha chickens were subjected to acute (1, 6, 12 h) and chronic (5, 10, 20 d) cold stress (12±1)℃. Hypothalami were collected for assessment of mRNA levels by semi-quantitative RT-PCR. Acute stress resulted in a significant decrease of CRH mRNA levels at 6 and 12 h, and a significant increase of TRH mRNA levels at every stress time point. Chronic cold stress resulted in a significant increase of CRH mRNA levels and a significant decrease of TRH mRNA levels compared with the control group at every stress time point. The results suggest that the two genes differently respond to cold stress at the mRNA levels. And the different degrees of cold stress will produce different effects on the identical gene.

  4. Is replenishment of the readily releasable pool associated with vesicular movement?

    Bui, Loc; Glavinović, Mladen I


    At the excitatory synapse of rat hippocampus the short-term synaptic depression observed during long high-frequency stimulation is associated with slower replenishment of the readily-releasable pool. Given that the replenishment rate is also not [Ca(++)]o sensitive this puts into question a widely held notion that the vesicles-constrained by the cytoskeleton and rendered free from such constraints by Ca(++) entry that renders them more mobile-are important in the replenishment of the readily-releasable pool. This raises a question-Is vesicular replenishment of the readily releasable pool associated with significant movement? To answer this question we evaluated how okadaic acid and staurosporine (compounds known to affect vesicular mobility) influence the replenishment rate. We used patterned stimulation on the Schaffer collateral fiber pathway and recorded the excitatory post-synaptic currents (EPSCs) from rat CA1 neurons, in the absence and presence of these drugs. The parameters of a circuit model with two vesicular pools were estimated by minimizing the squared difference between the ESPC amplitudes and simulated model output. [Ca(2+)]o did not influence the progressive decrease of the replenishment rate during long, high frequency stimulation. Okadaic acid did not significantly affect any parameters of the vesicular storage and release system, including the replenishment rate. Staurosporine reduced the replenishment coupling, but not the replenishment rate, and this is owing to the fact that it also reduces the ability of the readily releasable pool to contain quanta. Moreover, these compounds were ineffective in influencing how the replenishment rate decreases during long, high frequency stimulation. In conclusion at the excitatory synapses of rat hippocampus the replenishment of the readily releasable pool does not appear to be associated with a significant vesicular movement, and during long high frequency stimulation [Ca(++)]o does not influence the

  5. In vitro effect of octyl - methoxycinnamate (OMC) on the release of Gn-RH and amino acid neurotransmitters by hypothalamus of adult rats.

    Carbone, S; Szwarcfarb, B; Reynoso, R; Ponzo, O J; Cardoso, N; Ale, E; Moguilevsky, J A; Scacchi, P


    OMC (octyl-methoxycinnamate), an endocrine disruptor having estrogenic activity, is used in sunscreen creams as UV filter. We studied its "in vitro" effects on the hypothalamic release of Gn-RH as well as on the amino acid neurotransmitter system. OMC significantly decreased Gn-RH release in normal male and female rats as well as in castrated rats with substitutive therapy. No effects were observed in castrated rats without substitutive therapy. In males OMC increases the release of GABA, decreasing the production of glutamate (GLU) while in the female decreases the excitatory amino acid aspartate (ASP) and GLU without modifications in the hypothalamic GABA release. These results suggest that OMC acting as endocrine disruptor could alter the sex hormone-neurotransmitter-Gn-RH axis relationships in adult rats.

  6. Cholinergic Interneurons Underlie Spontaneous Dopamine Release in Nucleus Accumbens.

    Yorgason, Jordan T; Zeppenfeld, Douglas M; Williams, John T


    The release of dopamine from terminals in the NAc is regulated by a number of factors, including voltage-gated ion channels, D2-autoreceptors, and nAChRs. Cholinergic interneurons (CINs) drive dopamine release through activation of nAChRs on dopamine terminals. Using cyclic voltammetry in mouse brain slices, nAChR-dependent spontaneous dopamine transients and the mechanisms underlying the origin were examined in the NAc. Spontaneous events were infrequent (0.3 per minute), but the rate and amplitude were increased after blocking Kv channels with 4-aminopyridine. Although the firing frequency of CINs was increased by blocking glutamate reuptake with TBOA and the Sk blocker apamin, only 4-aminopyridine increased the frequency of dopamine transients. In contrast, inhibition of CIN firing with the μ/δ selective opioid [Met(5)]enkephalin (1 μm) decreased spontaneous dopamine transients. Cocaine increased the rate and amplitude of dopamine transients, suggesting that the activity of the dopamine transporter limits the detection of these events. In the presence of cocaine, the rate of spontaneous dopamine transients was further increased after blocking D2-autoreceptors. Blockade of muscarinic receptors had no effect on evoked dopamine release, suggesting that feedback inhibition of acetylcholine release was not involved. Thus, although spontaneous dopamine transients are reliant on nAChRs, the frequency was not strictly governed by the activity of CINs. The increase in frequency of spontaneous dopamine transients induced by cocaine was not due to an increase in cholinergic tone and is likely a product of an increase in detection resulting from decreased dopamine reuptake.SIGNIFICANCE STATEMENT The actions of dopamine in the NAc are thought to be responsible for endogenous reward and the reinforcing properties of drugs of abuse, such as psychostimulants. The present work examines the mechanisms underlying nAChR-induced spontaneous dopamine release. This study

  7. Nitric oxide-releasing polymeric nanoparticles against Trypanosoma cruzi

    Seabra, A. B.; Kitice, N. A.; Pelegrino, M. T.; Lancheros, C. A. C.; Yamauchi, L. M.; Pinge-Filho, P.; Yamada-Ogatta, S. F.


    Chagas disease, also known as American trypanosomiasis, is a potentially life-threatening illness caused by the protozoan parasite, Trypanosoma cruzi (T. cruzi), and the disease remains a major health problem in many Latin American countries. Several papers report that the killing of the parasite is dependent on the production of nitric oxide (NO). The endogenous free radical NO is an important cellular signalling molecule that plays a key role in the defense against pathogens, including T. cruzi. As T. cruzi is able to compromise host macrophages decreasing endogenous NO production, the administration of exogenous NO donors represents an interesting strategy to combat Chagas disease. Thus, the aims of this study were to prepare and evaluate the antimicrobial activity of NO-releasing polymeric nanoparticles against T. cruzi. Biocompatible polymeric nanoparticles composed of chitosan/sodium tripolyphosphate(TPP) were prepared and used to encapsulate mercaptosuccinic acid (MSA), which is a thiol-containing molecule. Nitrosation of free thiols (SH) groups of MSA were performed by the addition of equimolar amount of sodium nitrite (NaNO2), leading to the formation of S-nitroso-MSA-containing nanoparticles. These polymeric nanoparticles act as spontaneous NO donors, with free NO release. The results show the formation of nanoparticles with average hydrodynamic diameter ranging from 270 to 500 nm, average of polydispersity index of 0.35, and encapsulation efficiency in the range of 99%. The NO release kinetics from the S-nitroso-MSA-containing nanoparticles showed sustained and controlled NO release over several hours. The microbicidal activity of S-nitroso-MSA-containing nanoparticles was evaluated by incubating NO-releasing nanoparticles (200 - 600 μg/mL) with replicative and non-infective epimastigote, and non-replicative and infective trypomastigote forms of T. cruzi. In addition, a significant decrease in the percentage of macrophage-infected (with amastigotes) and

  8. [Effects of slow/controlled release fertilizers on the growth and nutrient use efficiency of pepper].

    Tang, Shuan-Hu; Zhang, Fa-Bao; Huang, Xu; Chen, Jian-Sheng; Xu, Pei-Zhi


    Pot trails were conducted from 2003 to 2005 to study the effects of slow/controlled release fertilizers on the growth and nutrient use efficiency of pepper. The results indicated that in comparison with conventional splitting fertilization (T1), basal application of polymer-coated controlled release fertilizer (T2) enhanced the single fruit mass and vitamin C concentration, improved the root activity, and increased the fruit yield by 8.4%, but no significant effect was observed on the dissoluble sugar concentration in fruit. NH4MgPO4-coated controlled release fertilizer (T3) increased the dissoluble sugar concentration by 5.67%, but had less effect on single fruit mass and vitamin C concentration. Under the application of T3, the root system had a vigorous growth at early stages but became infirm at later stages, resulting in a lower yield. Comparing with T1, the application of 3 slow release fertilizers increased the dissoluble sugar concentration in fruit, enhanced the root activity, but had less effect on the yield. All test slow/controlled release fertilizers increased the use efficiency of N, P, and K significantly, with an exception for T2 which increased the use efficiency of N and K but decreased that of P. It was demonstrated that an appropriate application of slow/controlled release fertilizers could enhance pepper' s root activity and improve nutrient use efficiency.

  9. 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.

  10. Slit2 is decreased after spontaneous labour in myometrium and regulates pro-labour mediators.

    Lim, Ratana; Liong, Stella; Barker, Gillian; Lappas, Martha


    Preterm birth, a global healthcare problem, is commonly associated with inflammation. As Slit2 plays an emerging role in inflammation, the purpose of this study was to determine the effect of Slit2 on labour mediators in human gestational tissues. Slit2 mRNA and protein expression were assessed using qRT-PCR and immunohistochemistry in foetal membranes and myometrium obtained before and after labour. Slit2 silencing was achieved using siRNA in primary myometrial cells. Pro-inflammatory and pro-labour mediators were evaluated by qRT-PCR, ELISA and gelatin zymography. Slit2 mRNA and protein expression were found to be significantly lower in myometrium after labour onset. There was no effect of term or preterm labour on Slit2 expression in foetal membranes. Slit2 mRNA expression was decreased in myometrium treated with LPS and IL-1β. Slit2 siRNA in myometrial cells increased IL-1β-induced pro-inflammatory cytokine gene expression and release (IL-6 and IL-8), COX-2 expression and prostaglandin PGE2 and PGF2α release, and MMP-9 gene expression and pro MMP-9 release. There was no effect of Slit2 siRNA on IL-1β-induced NF-κB transcriptional activity. Our results demonstrate that Slit2 is decreased in human myometrium after labour and our knock-down studies describe an anti-inflammatory effect of Slit2 in myometrial cells.

  11. Efficient inhibition of infectious prions multiplication and release by targeting the exosomal pathway.

    Vilette, Didier; Laulagnier, Karine; Huor, Alvina; Alais, Sandrine; Simoes, Sabrina; Maryse, Romao; Provansal, Monique; Lehmann, Sylvain; Andreoletti, Olivier; Schaeffer, Laurent; Raposo, Graça; Leblanc, Pascal


    Exosomes are secreted membrane vesicles of endosomal origin present in biological fluids. Exosomes may serve as shuttles for amyloidogenic proteins, notably infectious prions, and may participate in their spreading in vivo. To explore the significance of the exosome pathway on prion infectivity and release, we investigated the role of the endosomal sorting complex required for transport (ESCRT) machinery and the need for ceramide, both involved in exosome biogenesis. Silencing of HRS-ESCRT-0 subunit drastically impairs the formation of cellular infectious prion due to an altered trafficking of cholesterol. Depletion of Tsg101-ESCRT-I subunit or impairment of the production of ceramide significantly strongly decreases infectious prion release. Together, our data reveal that ESCRT-dependent and -independent pathways can concomitantly regulate the exosomal secretion of infectious prion, showing that both pathways operate for the exosomal trafficking of a particular cargo. These data open up a new avenue to regulate prion release and propagation.

  12. Metformin extended release--DepoMed: metformin, metformin gastric retention, metformin GR.


    Metformin extended release [Glumetza, metformin hydrochloride, metformin gastric retention, metformin GR] is a proprietary once-a-day formulation of metformin hydrochloride under development with DepoMed for the treatment of diabetes. In May 2002, DepoMed licensed manufacturing and marketing rights for its proprietary formulation of metformin extended release (500mg dose) to Biovail Corporation for the US (including Puerto Rico) and Canada. Under the terms of the agreement, Biovail would pay a $25 million milestone fee upon approval and also customary royalties on the net sales in the US and Canada. Biovail also agreed to acquire approximately 2.4 million of additionally issued DepoMed shares for $12.3 million. Biovail has subsequently developed a 1000mg dose of metformin extended release. In April 2004, Depomed and Biovail amended their original license agreement of May 2002. Under the terms of the amended agreement, Depomed will receive royalties on sales of Biovail's 1000mg tablet in the US and Canada. In turn, Biovail acquired access to Depomed's clinical data for the metformin 500mg tablet that will be used to accelerate regulatory filings for Biovail's 1000mg tablet and establish equivalence between the two dosages. Metformin GR is available for partnership in Europe and Asia (Bio-Square-2004, Basel, Switzerland). In April 2004, Depomed and Biovail filed an NDA with the US FDA for the once-daily, extended-release formulation of metformin extended release (Glumetza), 500mg and 1000mg tablets. The 500mg dosage was developed by Depomed using its patented drug delivery GR technology, while Biovail developed the metformin 1000mg dose using its proprietary Smartcoat delivery technology. Depomed completed two double-blind, pivotal, phase III clinical trials with metformin extended release 500mg at 60 sites in the US in more than 1000 patients with type 2 diabetes. In three different dosing regimens, metformin extended release significantly decreased the glycosylated

  13. Decreased respiratory symptoms in cannabis users who vaporize

    Barnwell Sara


    Full Text Available Abstract Cannabis smoking can create respiratory problems. Vaporizers heat cannabis to release active cannabinoids, but remain cool enough to avoid the smoke and toxins associated with combustion. Vaporized cannabis should create fewer respiratory symptoms than smoked cannabis. We examined self-reported respiratory symptoms in participants who ranged in cigarette and cannabis use. Data from a large Internet sample revealed that the use of a vaporizer predicted fewer respiratory symptoms even when age, sex, cigarette smoking, and amount of cannabis used were taken into account. Age, sex, cigarettes, and amount of cannabis also had significant effects. The number of cigarettes smoked and amount of cannabis used interacted to create worse respiratory problems. A significant interaction revealed that the impact of a vaporizer was larger as the amount of cannabis used increased. These data suggest that the safety of cannabis can increase with the use of a vaporizer. Regular users of joints, blunts, pipes, and water pipes might decrease respiratory symptoms by switching to a vaporizer

  14. Arsenic Release from Foodstuffs upon Food Preparation.

    Cheyns, Karlien; Waegeneers, Nadia; Van de Wiele, Tom; Ruttens, Ann


    In this study the concentration of total arsenic (As) and arsenic species (inorganic As, arsenobetaine, dimethylarsinate, and methylarsonate) was monitored in different foodstuffs (rice, vegetables, algae, fish, crustacean, molluscs) before and after preparation using common kitchen practices. By measuring the water content of the foodstuff and by reporting arsenic concentrations on a dry weight base, we were able to distinguish between As release effects due to food preparation and As decrease due to changes in moisture content upon food preparation. Arsenic species were released to the broth during boiling, steaming, frying, or soaking of the food. Concentrations declined with maxima of 57% for total arsenic, 65% for inorganic As, and 32% for arsenobetaine. On the basis of a combination of our own results and literature data, we conclude that the extent of this release of arsenic species is species specific, with inorganic arsenic species being released most easily, followed by the small organic As species and the large organic As species.

  15. 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...

  16. Effect of allergen-specific immunotherapy on recombinant human interleukin 3-mediated amplification of allergen-induced basophil histamine release.

    Kowal, Krzysztof; Nolte, Hendrik; Skov, Per Stahl; DuBuske, Lawrence M


    Decreased allergen-induced histamine release from peripheral blood basophils in allergic rhinitis patients treated with specific immunotherapy (SIT) correlates with clinical outcomes of SIT. The aim of this study was to investigate if decreased histamine release is a permanent effect of SIT. Fifty-one patients (mean age, 35.3 years) with allergic rhinitis, diagnosed based on clinical history and positive skin-prick test results to common aeroallergens, were studied. Twenty-three patients had never received SIT (group A), and 28 patients had been treated with inhalant allergen extracts (group B). Eleven patients from group A participated in a prospective part of this study. Basophil histamine release in these patients was evaluated before (TO) and after-1 year (TI) of SIT. Histamine release from peripheral blood with and without interleukin (IL)-3 pretreatment was performed using the glass-fiber-based histamine release test. Brief pretreatment of whole blood basophils with one of the four concentrations (0.01, 0.1, 1, or 10 ng/mL) of recombinant human IL(rhIL)-3, rhIL-5, or rh-granulocyte-macrophage colony-stimulating factor resulted in a significant amplification of allergen-induced basophil histamine release. The amplification using cytokines at the optimal concentrations was the greatest with rhIL-3 and the lowest with rhIL-5; therefore, for further studies rhIL-3 was used. Prospective analysis showed no significant difference in allergen-induced basophil histamine release on rhIL-3 pretreatment after 1 year of SIT (192.7 +/- 75.3 ng and 176.1 +/- 76.4 ng for T0 and T1, respectively; p = 0.18). Short-term SIT does not decrease rhIL-3-mediated amplification of allergen-induced histamine release from peripheral blood basophils.

  17. Growth phase significantly decreases the DHA-to-EPA ratio in marine microalgae

    Boelen, Peter; Van Mastrigt, Audrey; Van De Bovenkamp, Henk H.; Heeres, Hero J.; Buma, Anita G. J.

    Microalgae are the principal producers of long-chain polyunsaturated fatty acids (LC-PUFAs) such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in marine ecosystems. Algae are used in aquaculture systems as direct or indirect feed for zooplankton, filter-feeding mollusks and larval

  18. Intensity of HLA-A2 Expression Significantly Decreased in Occult Hepatitis B Infection

    ASKARI, Azam; Hassanshahi, Gholam Hossein; Ghalebi, Seyed Razi; Jafarzadeh,Abdollah; Mohit, Maryam; Hajghani, Masomeh; Kazemi Arababadi, Mohammad


    Background: Occult hepatitis B infected (OBI) patients cannot eradicate hepatitis B virus (HBV)-DNA from their liver and peripheral blood, completely. Objectives: The main aim of this study was to investigate the rate of HLA-A2 expression on peripheral blood mononuclear cells (PBMCs) of patients with OBI. Materials and Methods: In this experimental study, intensity of HLA-A2 was measured on the PBMCs of 57 OBI patients and 100 HBsAg-/anti-HBc+/HBV-DNA samples were enrolled as controls; measur...

  19. Crystallization: A phase transition process driving by chemical potential decrease

    Sun, Congting; Xue, Dongfeng


    A chemical bonding model is established to describe the chemical potential decrease during crystallization. In the nucleation stage, in situ molecular vibration spectroscopy shows the increased vibration energy of constituent groups, indicating the shortened chemical bonding and the decreased chemical potential towards the formation of nuclei. Starting from the Gibbs free energy formula, the chemical potential decrease during crystallization is scaled, which depends on the released chemical bonding energy per unit phase transition zone. In the crystal growth, the direction-dependent growth rate of inorganic single crystals can be quantitatively determined, their anisotropic thermodynamic morphology can thus be constructed on the basis of relative growth rates.

  20. Release behavior of uranium in uranium mill tailings under environmental conditions.

    Liu, Bo; Peng, Tongjiang; Sun, Hongjuan; Yue, Huanjuan


    Uranium contamination is observed in sedimentary geochemical environments, but the geochemical and mineralogical processes that control uranium release from sediment are not fully appreciated. Identification of how sediments and water influence the release and migration of uranium is critical to improve the prevention of uranium contamination in soil and groundwater. To understand the process of uranium release and migration from uranium mill tailings under water chemistry conditions, uranium mill tailing samples from northwest China were investigated with batch leaching experiments. Results showed that water played an important role in uranium release from the tailing minerals. The uranium release was clearly influenced by contact time, liquid-solid ratio, particle size, and pH under water chemistry conditions. Longer contact time, higher liquid content, and extreme pH were all not conducive to the stabilization of uranium and accelerated the uranium release from the tailing mineral to the solution. The values of pH were found to significantly influence the extent and mechanisms of uranium release from minerals to water. Uranium release was monitored by a number of interactive processes, including dissolution of uranium-bearing minerals, uranium desorption from mineral surfaces, and formation of aqueous uranium complexes. Considering the impact of contact time, liquid-solid ratio, particle size, and pH on uranium release from uranium mill tailings, reducing the water content, decreasing the porosity of tailing dumps and controlling the pH of tailings were the key factors for prevention and management of environmental pollution in areas near uranium mines. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Decrease in TSH Receptor Autoantibodies during Antithyroid Treatment

    Christensen, Niels Juel; Habekost, Gurli; Bratholm, Palle


    that TRAb decrease significantly during treatment with antithyroid drugs. This decrease during treatment cannot be explained by Heg RNA, which remains unchanged. Cdk1 mRNA decreased significantly during treatment to values below values obtained in normal subjects. Thus both Heg RNA and Cdk1 mRNA may...

  2. Distraction decreases prefrontal oxygenation: A NIRS study.

    Ozawa, Sachiyo; Hiraki, Kazuo


    When near-infrared spectroscopy (NIRS) is used to measure emotion-related cerebral blood flow (CBF) changes in the prefrontal cortex regions, the functional distinction of CBF changes is often difficult because NIRS is unable to measure neural activity in deeper brain regions that play major roles in emotional processing. The CBF changes could represent cognitive control of emotion and emotional responses to emotional materials. Supposing that emotion-related CBF changes in the prefrontal cortex regions during distraction are emotional responses, we examined whether oxygenated hemoglobin (oxyHb) decreases. Attention-demanding tasks cause blood flow decreases, and we thus compared the effects of visually paced tapping with different tempos, on distraction. The results showed that the oxyHb level induced by emotional stimulation decreased with fast-tempo tapping significantly more than slow-tempo tapping in ventral medial prefrontal cortex regions. Moreover, a Global-Local task following tapping showed significantly greater local-minus-global response time (RT) difference scores in the fast- and mid-tempo condition compared with those in the slow-tempo, suggesting an increased attentional focus, and decreased negative emotion. The overall findings indicate that oxyHb changes in a relatively long distraction task, as measured by NIRS, are associated with emotional responses, and oxyHb can be decreased by successfully performing attention-demanding distraction tasks.


    Bihourly diagrams were made of Forbush decreases of cosmic ray intensity as observed at Uppsala from 31 Aug 56 to 31 Dec 59, at Kiruna from Nov 56 to 31 Dec 59, and at Murchison Bay from 26 Aug 57 to 30 Apr 59. (Author)

  4. Sustain-release of various drugs from leucaena leucocephala polysaccharide.

    Jeevanandham, S; Sekar, M; Dhachinamoorthi, D; Muthukumaran, M; Sriram, N; Joysaruby, J


    This study examines the sustained release behavior of both water-soluble (acetaminophen, caffeine, theophylline and salicylic acid) and water-insoluble (indomethacin) drugs from Leucaena leucocephala seed Gum isolated from Leucaena leucocephala kernel powder. It further investigates the effect of incorporation of diluents like microcrystalline cellulose and lactose on release of caffeine and partial cross-linking of the gum (polysaccharide) on release of acetaminophen. Applying exponential equation, the mechanism of release of soluble drugs was found to be anomalous. The insoluble drug showed near case II or zero-order release mechanism. The rate of release was in the decreasing order of caffeine, acetaminophen, theophylline, salicylic acid and indomethacin. An increase in release kinetics of drug was observed on blending with diluents. However, the rate of release varied with type and amount of blend in the matrix. The mechanism of release due to effect of diluents was found to be anomalous. The rate of release of drug decreased on partial cross-linking and the mechanism of release was found to be super case II.

  5. Drug release characteristics from chitosan-alginate matrix tablets based on the theory of self-assembled film.

    Li, Liang; Wang, Linlin; Shao, Yang; Ni, Rui; Zhang, Tingting; Mao, Shirui


    The aim of this study was to better understand the underlying drug release characteristics from chitosan-alginate matrix tablets containing different types of drugs. Theophylline, paracetamol, metformin hydrochloride and trimetazidine hydrochloride were used as model drugs exhibiting significantly different solubilities (12, 16, 346 and >1000 mg/ml at 37 °C in water). A novel concept raised was that drugs were released from chitosan-alginate matrix tablets based on the theory of a self-assembled film-controlled release system. The film was only formed on the surface of tablets in gastrointestinal environment and originated from chitosan-alginate polyelectrolyte complex, confirmed by differential scanning calorimetry characterization. The formed film could decrease the rate of polymer swelling to a degree, also greatly limit the erosion of tablets. Drugs were all released through diffusion in the hydrated matrix and polymer relaxation, irrespective of the drug solubility. The effects of polymer level and initial drug loading on release depended on drug properties. Drug release was influenced by the change of pH. In contrast, the impact of ionic strength of the release medium within the physiological range was negligible. Importantly, hydrodynamic conditions showed a key factor determining the superiority of the self-assembled film in controlling drug release compared with conventional matrix tablets. The new insight into chitosan-alginate matrix tablets can help to broaden the application of this type of dosage forms.

  6. Significant NRC Enforcement Actions

    Nuclear Regulatory Commission — This dataset provides a list of Nuclear Regulartory Commission (NRC) issued significant enforcement actions. These actions, referred to as "escalated", are issued by...

  7. Evaluation of Antidiabetic Effects of the Traditional Medicinal Plant Gynostemma pentaphyllum and the Possible Mechanisms of Insulin Release

    Lokman, Ezarul Faradianna; Gu, Harvest F.; Wan Mohamud, Wan Nazaimoon; Östenson, Claes-Göran


    Aims. To evaluate the antidiabetic effects of Gynostemma pentaphyllum (GP) in Goto-Kakizaki (GK) rat, an animal model of type 2 diabetes, and to investigate the mechanisms of insulin release. Methods. Oral glucose tolerance test was performed and plasma insulin levels were measured. Results. An oral treatment with GP (0.3 g/kg of body weight daily) for two weeks in GK rats improved glucose tolerance versus placebo group (P < 0.01). Plasma insulin levels were significantly increased in the GP-treated group. The insulin release from GP-treated GK rats was 1.9-fold higher as compared to the control group (P < 0.001). GP stimulated insulin release in isolated GK rat islets at high glucose. Opening of ATP-sensitive potassium (K-ATP) channels by diazoxide and inhibition of calcium channels by nifedipine significantly decreased insulin response to GP. Furthermore, the protein kinase A (PKA) inhibitor H89 decreased the insulin response to GP (P < 0.05). In addition, GP-induced insulin secretion was decreased after preincubation of GK islets with pertussis toxin to inhibit exocytotic Ge proteins (P < 0.05). Conclusion. The antidiabetic effect of GP is associated with the stimulation of insulin release from the islets. GP-induced insulin release is partly mediated via K-ATP and L-type Ca2+ channels, the PKA system and also dependent on pertussis toxin sensitive Ge-protein. PMID:26199630

  8. Evaluation of Antidiabetic Effects of the Traditional Medicinal Plant Gynostemma pentaphyllum and the Possible Mechanisms of Insulin Release

    Ezarul Faradianna Lokman


    Full Text Available Aims. To evaluate the antidiabetic effects of Gynostemma pentaphyllum (GP in Goto-Kakizaki (GK rat, an animal model of type 2 diabetes, and to investigate the mechanisms of insulin release. Methods. Oral glucose tolerance test was performed and plasma insulin levels were measured. Results. An oral treatment with GP (0.3 g/kg of body weight daily for two weeks in GK rats improved glucose tolerance versus placebo group (P<0.01. Plasma insulin levels were significantly increased in the GP-treated group. The insulin release from GP-treated GK rats was 1.9-fold higher as compared to the control group (P<0.001. GP stimulated insulin release in isolated GK rat islets at high glucose. Opening of ATP-sensitive potassium (K-ATP channels by diazoxide and inhibition of calcium channels by nifedipine significantly decreased insulin response to GP. Furthermore, the protein kinase A (PKA inhibitor H89 decreased the insulin response to GP (P<0.05. In addition, GP-induced insulin secretion was decreased after preincubation of GK islets with pertussis toxin to inhibit exocytotic Ge proteins (P<0.05. Conclusion. The antidiabetic effect of GP is associated with the stimulation of insulin release from the islets. GP-induced insulin release is partly mediated via K-ATP and L-type Ca2+ channels, the PKA system and also dependent on pertussis toxin sensitive Ge-protein.

  9. Effect of gamma irradiation on fluoride release and antibacterial activity of resin dental materials

    Carvalho, Fabiola Galbiatti de; Fucio, Suzana Beatriz Portugal de; Correr-Sobrinho, Lourenco [Universidade Estadual de Campinas (UNICAMP), Piracicaba, SP (Brazil). Piracicaba Dental School. Dept. of Dental Materials; Pascon, Fernanda Miori; Kantovitz, Kamila Rosamilia; Puppin-Rontani, Regina Maria [Universidade Estadual de Campinas (UNICAMP), Piracicaba, SP (Brazil). Piracicaba Dental School. Dept. of Pedriatric Dentistry], e-mail:


    This study evaluated the effect of gamma irradiation on fluoride release and antibacterial activity of FluroShield (FS) and Clearfil Protect Bond (CPB). Four groups were formed: G1-FS + gamma; G2-FS without gamma; G3-CPB + gamma; G4-CPB without gamma. For fluoride release analysis, 12 disks of each material were prepared and covered with nail polish, except for one side (50.4 mm{sup 2} area). G1 and G3 were sterilized with a 14.5 KGy dose at 27 deg C for 24 h, while G2 and G4 (controls) were not sterilized and were maintained under the same time and temperature conditions. Fluoride release measurements were made in duplicate (n=6) by an ion specific electrode. The antibacterial activity of the CPB and FS against Streptococcus mutans after gamma sterilization was evaluated by the agar-disc diffusion method. The diameter of the zones of microbial growth inhibition was recorded after 48 h. Data were analyzed statistically by ANOVA and Tukey's test (alpha=5%). Gamma sterilization decreased the fluoride release of FS by approximately 50%, while CPB was not affected. There was no statistically significant difference (p>0.05) in the antibacterial effect of CPB between gamma and non-gamma sterilization groups. FS presented no antibacterial activity. Gamma irradiation decreased the fluoride release of FS, but did not affect the antibacterial activity of the studied materials. (author)

  10. Metformin extended release: metformin gastric retention, metformin GR, metformin XR.


    approved metformin extended release (Glumetza) 500mg and 1000mg tablets for the treatment of type 2 diabetes mellitus. Biovail plans launching the product in the fourth quarter of 2005. In July 2005, Biovail paid Depomed a 25 million dollars milestone payment following approval of metformin extended release in the US for type 2 diabetes. In March 2005, Biovail Corporation and Depomed announced that they have received an approvable letter from the FDA for the once-daily, extended-release formulation of metformin extended release (Glumetza) 500mg and 1000mg tablets. The letter specified an issue related to finalising one manufacturing specification. There were no clinical labeling issues identified in the letter. Both companies filed a response to a specified issue at the FDA on 8 April 2005. The companies believed that the response will be classified as a Class I response with a 60-day review period. The 500mg dosage was developed by Depomed using its patented drug delivery GR technology, while Biovail developed metformin 1000mg dose using its proprietary Smartcoat delivery technology. Biovail's NDA for a once-daily, extended-release formulation of metformin HCl for the treatment of type II diabetes was filed in April 2004 and accepted for review in June 2004 by the FDA. Depomed completed two double-blind, pivotal, phase III clinical trials with metformin extended release 500mg at 60 sites in the US in more than 1000 patients with type 2 diabetes. In three different dosing regimens, metformin extended release significantly decreased the glycosylated haemoglobin level similarly to that of metformin immediate-release. Biovail successfully compared metformin extended release 1000mg dose with Depomed's 500mg dose in multiple equivalence studies. In these studies, metformin extended release was well tolerated and demonstrated an excellent safety profile in terms of gastrointestinal adverse events. On 1 June 2005, Depomed and Biovail Comporation, the licensee, announced that the

  11. The alpha2C-adrenoceptor modulates GABA release in mouse striatum.

    Zhang, Weilie; Ordway, Gregory A


    The alpha(2C)-adrenoceptor occurs in high density in the striatum relative to other brain regions, but its biological role in striatal physiology is perplexing because of the paucity of noradrenergic terminals in this region. In this study, mice with a targeted inactivation of the alpha(2C)-adrenoceptor gene (alpha(2C)-KO mice), and genetically related mice (WT mice), were used to study the potential role of the striatal alpha(2C)-adrenoceptor in modulating GABA release. Perfused brain slices were pre-loaded with [(3)H]GABA and were stimulated electrically. In WT mice, the alpha(2)-adrenoceptor agonist, UK14304 (brimonidine), significantly enhanced [(3)H]GABA release from striatal slices, while the alpha(2)-adrenoceptor antagonist, RX821002, alone evoked a significant decrease in [(3)H]GABA release. In alpha(2C)-KO mice, the effect of RX821002 was absent, while UK14304 retained its ability to enhance [(3)H]GABA release. Pharmacological depletion of monoamines in WT mice also abolished the effect of RX821002 on [(3)H]GABA release. In hippocampal slices, RX821002-induced reduction in [(3)H]GABA release was present in WT and alpha(2C)-KO mice. In the presence of tetrodotoxin, RX821002 increased [(3)H]GABA release in striatal slices from both WT and alpha(2C)-KO mice. Together, these data imply that alpha(2A)- and alpha(2C)-adrenoceptors are located on different neurons in the striatum, that alpha(2C)-adrenoceptor-mediated effects on striatal GABA release are mediated by an endogenous catecholamine that could be dopamine, and that the alpha(2C)-adrenoceptor effect of RX821002 does not occur at the GABAergic terminal.

  12. Clock-controlled rhythm of ecdysteroid levels in the haemolymph and testes, and its relation to sperm release in the Egyptian cotton leafworm, Spodoptera littoralis.

    Polanska, Marta A; Maksimiuk-Ramirez, Ewa; Ciuk, Marcin A; Kotwica, Joanna; Bebas, Piotr


    In Spodoptera littoralis, testicular sperm release occurs in a daily rhythm, which is controlled by endogenous circadian oscillator located in the male reproductive system. Although this rhythm is essential for male fertility, factors that initiate and maintain daily sperm release are not understood. In this study, we investigated a modulatory role for ecdysteroids in the sperm release rhythm and identified the source of ecdysteroids in adult males. We found that the onset of sperm release occurs two days pre-eclosion and coincides with a significant decrease in haemolymph ecdysteroids levels. 20-HE injection into the pupae prior to the first sperm release delayed its initiation and disrupted the developing rhythm in a dose dependent manner. 20-HE injection into adults depressed the number of sperm bundles leaving the testes. A day before the initial sperm release, ecdysteroid levels in the haemolymph and testes begin to oscillate in a circadian fashion. Ecdysteroid rhythms continue throughout imaginal life and correlate with the rhythm of sperm release. In each cycle, testicular sperm release coincides with a trough in testicular ecdysteroid concentration. Rhythmic changes in ecdysteroid levels are regulated by an endogenous circadian oscillator that continues to function in decapitated males. The generation of a complete cycle of ecdysteroid release by testes cultured in vitro indicates that this oscillator is located in the gonads. The haemolymph ecdysteroid levels are significantly lower and arrhythmic in males with removed testes, indicating that the testes are an important ecdysteroid source that may contribute to oscillations in haemolymph ecdysteroid levels.

  13. The Significance of Science

    Pielke, R.


    Whether global warming, terrestrial carbon sinks, ecosystem functioning, genetically modified organisms, cloning, vaccination or chemicals in the environment, science is increasingly the battlefield on which political advocates, not least lawyers and commercial interests, manipulate `facts' to their preferred direction, which fosters the politicization of science. Debate putatively over science increasingly relies on tactics such as ad hominem attacks and criticism of process (for example, peer review or sources of funding), through paid advertisements, press releases and other publicity campaigns. As political battles are waged through `science', many scientists are willing to adopt tactics of demagoguery and character assassination as well as, or even instead of, reasoned argument, as in aspects of debate over genetically modified crops or global warming. Science is becoming yet another playing field for power politics, complete with the trappings of media spin and a win-at-all-costs attitude. Sadly, much of what science can offer policymakers, and hence society, is lost. This talk will use cases from the atmospheric sciences as points of departure to explore the politicization of science from several perspectives and address questions such as: Is it a problem? For whom and what outcomes? What are the alternatives to business-as-usual?

  14. [Mechanisms of neurotransmitter release facilitation in strontium solutions].

    Mukhamed'iarov, M A; Kochunova, Iu O; Telina, E N; Zefirov, A L


    Mechanisms of neurotransmitter release facilitation were studied using electrophysiological recording of end-plate currents (EPC) and nerve ending (NE) responses after substitution of extracellular Ca ions with Sr ions at the frog neuromuscular junction. The solutions with 0.5 mM concentration of Ca ions (calcium solution) or 1 mM concentration of Sr ions (strontium solution) were used where baseline neurotransmitter release (at low-frequency stimulation) is equal. Decay of paired-pulse facilitation of EPC at calcium solutions with increase of interpulse interval from 5 to 500 ms was well described by three-exponential function consisting of early, first and second components. Facilitation at strontium solutions was significantly diminished due mainly to decrease of early and first components. At the same time, EPC facilitation with rhythmic stimulation (10 or 50 imp/s) at strontium solutions was significantly increased. Also more pronounced decrease of NE response 3rd phase, reflecting potassium currents was detected under rhythmic stimulation of 50 imp/s at strontium solutions comparing to calcium solutions. It was concluded that facilitation sites underlying first and early components had lower affinity to Sr ions than to Ca ions. The enhancement of frequency facilitation at strontium solutions is mediated by two mechanisms: more pronounced broadening of NE action potential and increase of bivalent cation influx due to feebly marked activation of Ca(2+)-dependent potassium current by Sr ions, and slower dynamics of Sr(2+) removal from NE axoplasm comparing to Ca(2+).

  15. Choosing Outcomes of Significance.

    Spady, William G.


    Outcomes are high-quality, culminating demonstrations of significant learning in context. The High Success Network uses the "Demonstration Mountain" to differentiate among three major "learning zones" and six different forms of learning demonstrations that increase in complexity, generalizability, and significance, along with…

  16. Corticotropin-releasing factor has an anxiogenic action in the social interaction test.

    Dunn, A J; File, S E


    The effects of intracerebroventricular (icv) injections of corticotropin-releasing factor (CRF, 100 and 300 ng) were investigated in the social interaction test of anxiety in rats. Both doses of CRF significantly decreased active social interaction without a concomitant decrease in locomotor activity. CRF also significantly increased self-grooming, an effect that was independent of the decrease in social interaction. These results indicate an anxiogenic action for CRF. Chlordiazepoxide (CDP, 5 mg/kg ip) pretreatment reversed the anxiogenic effects of icv CRF (100 ng), but CRF did not prevent the sedative effects of CDP. There were no statistically significant changes due to CRF in locomotor activity or rears or head dipping in the holeboard test. Both doses of CRF significantly increased plasma concentrations of corticosterone. The possible mechanisms of the behavioral effects of CRF are discussed.

  17. The Effect of a Bio-Behavioral Intervention on the Release of Cytokines


    addition of treatment and the treatment by time interaction resulted in a significant decrease in model fit (χ22 = 10.9; p < 0.01), leading to the...release is involved in neurogenic inflammation, which is a local inflammatory response to certain types of infection or injury. 10 6 Principal...function in patients undergoing colonic surgery. British Journal of Anaesthesia . 2006;97(5):640-646. 10 Principal Investigator: Burge, Donna, Mechelle

  18. Abdominal Closure after TRAM Flap Breast Reconstruction with Transversus Abdominis Muscle Release and Mesh

    Avendano-Peza, Héctor; Novitsky, Yuri W.


    Summary: Breast reconstruction with a pedicled transverse rectus abdominis muscle (TRAM) flap can result in significant abdominal wall donor-site morbidity. Although the pedicled TRAM flap donor area reinforced with mesh results in decreased rates of postoperative abdominal bulging and hernias, the best technique to accomplish that is yet to be elucidated. We present our novel technique of posterior components separation with transversus abdominis muscle release and retromuscular mesh reinforcement for donor-area closure during pedicled TRAM flap breast reconstruction.

  19. Decreasing incidence rates of bacteremia

    Nielsen, Stig Lønberg; Pedersen, C; Jensen, T G


    BACKGROUND: Numerous studies have shown that the incidence rate of bacteremia has been increasing over time. However, few studies have distinguished between community-acquired, healthcare-associated and nosocomial bacteremia. METHODS: We conducted a population-based study among adults with first......-time bacteremia in Funen County, Denmark, during 2000-2008 (N = 7786). We reported mean and annual incidence rates (per 100,000 person-years), overall and by place of acquisition. Trends were estimated using a Poisson regression model. RESULTS: The overall incidence rate was 215.7, including 99.0 for community......-acquired, 50.0 for healthcare-associated and 66.7 for nosocomial bacteremia. During 2000-2008, the overall incidence rate decreased by 23.3% from 254.1 to 198.8 (3.3% annually, p bacteremia decreased by 25.6% from 119.0 to 93.8 (3.7% annually, p

  20. Effect of decreasing temperature on the strobilation of Aurelia sp.1

    Shi, Yan; Yu, Zhigang; Zhen, Yu; Wang, Guoshan; Wang, Xungong; Mi, Tiezhu


    The worldwide proliferation of marine jellyfish has become a crucial ecological and social issue, and as a cosmopolitan species, Aurelia spp. have received increasing scientific attentions. In the present study, the responses of strobilation in Aurelia sp.1 to decreasing temperature were illuminated through the expression levels of the retinoid x receptor (RxR) gene and the gene encoding a secreted protein, CL390. We observed that a higher final temperature decreased the strobilation prophase and strobilation interphase periods, and the growth rate of the strobilae ratio increased with increasing CL390 gene expression. The ratio of strobilae at 12°C was highest, and the strobilae showed the higher releasing ratios at both 12°C and 16°C compared with those at 4°C and 8°C. Furthermore, more ephyrae were released at the higher final temperature. Additionally, up-regulation and down-regulation of the CL390 gene were observed in response to the four decreasing temperatures. Although the four CL390 gene transcript levels increased more significantly than the transcript levels of the RxR gene, similar trends were observed in both genes.

  1. Effect of subarachnoid hemorrhage on contractile responses and noradrenaline release evoked in cat cerebral arteries by histamine

    Lobato, R.D.; Marin, J.; Salaices, M.; Rico, M.L.; Sanchez, C.F.


    This study analyzes the changes induced by subarachnoid hemorrhage (SAH) on the contractile responses and the noradrenaline release evoked in cat cerebral arteries by histamine. The dose-dependent vasoconstriction induced by histamine on the cerebral arteries of normal cats was significantly reduced by diphenhydramine and phentolamine. When SAH was produced 3 and 7 days before the experiment, the histamine-induced vasoconstriction also decreased. Thereafter, a tendency to normalization in the contractile vascular responses was observed such that in 15 days after the hemorrhage it was not significantly different from that found in controls animals. The decrease in the contractile responses to histamine provoked by SAH was similar to that seen after pretreatment with intracisternal injections of 6-hydroxydopamine. The amount of radioactivity released by histamine following preincubation with /sup 3/H-noradrenaline from the cerebral arteries of cats exposed to SAH 3, 7, and 15 days before the experiment was significantly reduced when compared with controls. Moreover, the basal level of tritium release and the radioactivity retained at the end of the experiment were also decreased after SAH. Results indicate histamine releases noradrenaline from cat cerebral arteries, and SAH produce a transient denervation of the perivascular adrenergic nerve endings, which explained by the impairment of the indirect adrenergic mechanism involved in the overall contractile response elicited by this amine in cerebral arteries. Histamine does not seem to play a significant role in the production of the cerebral vasospasm occurring after SAH.

  2. Effect of angiotensin II, catecholamines and glucocorticoid on corticotropin releasing factor (CRF-induced ACTH release in pituitary cell cultures.



    Full Text Available The effects of angiotensin II, catecholamines and glucocorticoid on CRF-induced ACTH release were examined using rat anterior pituitary cells in monolayer culture. Synthetic ovine CRF induced a significant ACTH release in this system. Angiotensin II produced an additive effect on CRF-induced ACTH release. The ACTH releasing activity of CRF was potentiated by epinephrine and norepinephrine. Dopamine itself at 0.03-30 ng/ml did not show any significant effect on ACTH release, but it inhibited CRF-induced ACTH release. Corticosterone at 10(-7 and 10(-6M inhibited CRF-induced ACTH release. These results indicate that angiotensin II, catecholamines and glucocorticoid modulate ACTH release at the pituitary level.

  3. Nanoparticles with entrapped α-tocopherol: synthesis, characterization, and controlled release

    Zigoneanu, Imola Gabriela; Astete, Carlos Ernesto; Mirela Sabliov, Cristina


    An emulsion evaporation method was used to synthesize spherical poly(DL-lactide-co-glycolide) (PLGA) nanoparticles with entrapped α-tocopherol. Two different surfactants were used: sodium dodecyl sulfate (SDS) and poly(vinyl alcohol) (PVA). For SDS nanoparticles, the size of the nanoparticles decreased significantly with the entrapment of α-tocopherol in the PLGA matrix, while the size of PVA nanoparticles remained unchanged. The polydispersity index after synthesis was under 0.100 for PVA nanoparticles and around 0.150 for SDS nanoparticles. The zeta potential was negative for all PVA nanoparticles. The entrapment efficiency of α-tocopherol in the polymeric matrix was approximately 89% and 95% for nanoparticles with 8% and 16% α-tocopherol theoretical loading, respectively. The residual PVA associated with the nanoparticles after purification was approximately 6% ( w/w relative to the nanoparticles). The release profile showed an initial burst followed by a slower release of the α-tocopherol entrapped inside the PLGA matrix. The release for nanoparticles with 8% α-tocopherol theoretical loading (86% released in the first hour) was faster than the release for the nanoparticles with 16% α-tocopherol theoretical loading (34% released in the first hour).

  4. Formulation and evaluation of sustained release matrix tablet of rabeprazole using wet granulation technique

    Ruqaiyah Khan


    Full Text Available Introduction: Rabeprazole, a member of substituted benzimidazoles, inhibits the final step in gastric acid secretions. This drug claims to cause fastest acid separation (due to higher pKa, and more rapidly converts to the active species to aid gastric mucin synthesis. The most significant pharmacological action of Rabeprazole is dose dependent suppression of gastric acid secretion; without anticholinergic or H2-blocking action. It completely abolishes the hydrochloric acid secretion as it is powerful inhibitor of gastric acid. Rabeprazole is acid labile and hence commonly formulated as an enteric coated tablet. The absorption of rabeprazole occurs rapidly as soon as tablet leaves the stomach. Aim: In the present study an attempt was made to formulate and evaluate Rabeprazole sustained release matrix tablet using wet granulation technique incorporating various polymers like HPMC-E15, Carbopol934, and sodium carboxymethyl cellulose (CMC. Materials and Methods: The Formulated tablets were evaluated for different physicochemical properties like rheological properties, weight variation, thickness, hardness, % friability, in vitro release studies and drug content. Results: Studies revealed that all the physicochemical parameters comply with the official standards. The in vitro release studies exhibits the release up to 90%, over a prolonged period of time which confirms the extended release profile of formulation, having better bioavailability as well as decreased dosing frequency with reduced doses. Conclusion: The sustained release matrix tablets of rabiprazole shown better bioavailability, efficacy and potency, when compared with official standards.

  5. Novel H2S Releasing Nanofibrous Coating for In Vivo Dermal Wound Regeneration.

    Wu, Jiang; Li, Yi; He, Chaochao; Kang, Jianming; Ye, Jingjing; Xiao, Zecong; Zhu, Jingjing; Chen, Anqi; Feng, Sheng; Li, Xiaokun; Xiao, Jian; Xian, Ming; Wang, Qian


    Hydrogen sulfide (H2S), together with nitric oxide and carbon monoxide, has been recognized as an important gasotransmitter. It plays an essential physiological role in regulating cyto-protective signal process, and H2S-based therapy is considered as the next generation of promising therapeutic strategies for many biomedical applications, such as the treatment of cardiovascular disease. Through electrospinning of polycaprolactone (PCL) containing JK1, a novel pH-controllable H2S donor, nanofibers with H2S releasing function, PCL-JK1, are fabricated. This fibrous scaffold showed a pH-dependent H2S releasing behavior, i.e., lower pH induced greater and faster H2S release. In addition, the H2S release of JK1 was prolonged by the fibrous matrix as shown by decreased releasing rates compared to JK1 in solutions. In addition, in vitro studies indicated that PCL-JK1 exhibited excellent cyto-compatibility, similar to PCL fibers. Finally, we investigated PCL-JK1 as a wound dressing toward a cutaneous wound model in vivo and found that PCL-JK1 could significantly enhance the wound repair and regeneration compared with the control PCL scaffold, likely due to the release of H2S, which results in a broad range of physiologically protective functions toward the wound.

  6. Inhibition of adenosine deaminase attenuates endotoxin-induced release of cytokines in vivo in rats.

    Tofovic, S P; Zacharia, L; Carcillo, J A; Jackson, E K


    The purpose of this study was to investigate in vivo the effects of modulating the adenosine system on endotoxin-induced release of cytokines and changes in heart performance and neurohumoral status in early, profound endotoxemia in rats. Time/pressure variables of heart performance and blood pressure were recorded continuously, and plasma levels of tumor necrosis factor alpha (TNFalpha), interleukin 1-beta (IL-1beta), plasma renin activity (PRA), and catecholamines were determined before and 90 min after administration of endotoxin (30 mg/kg of lipopolysaccharide, i.v.). Erythro-9[2-hydroxyl-3-nonyl] adenine (EHNA; an adenosine deaminase inhibitor) had no effects on measured time-pressure variables of heart performance under baseline conditions and during endotoxemia, yet significantly attenuated endotoxin-induced release of cytokines and PRA. Pretreatment with the non-selective adenosine receptor antagonist DPSPX not only prevented the effects of EHNA but also increased the basal release of cytokines and augmented PRA. At baseline, caffeine (a non-selective adenosine receptor antagonist) increased HR, +dP/dtmax, heart rate x ventricular pressure product (HR x VPSP) and +dP/dtmax normalized by pressure (+dP/dtmax/VPSP), and these changes persisted during endotoxemia. Caffeine attenuated endotoxin-induced release of cytokines and augmented endotoxin-induced increases in plasma catecholamines and PRA. Pretreatment with propranolol abolished the effects of caffeine on heart performance and neurohumoral activation during the early phase of endotoxemia. 6N-cyclopentyladenosine (CPA; selective A1 adenosine receptor agonist) induced bradicardia and negative inotropic effects, reduced work load (i.e., decreased HR, VPSP, +dP/dtmax, +dP/dtmax/VPSP and HR x VPSP) and inhibited endotoxin-induced tachycardia and renin release. CGS 21680 (selective A2A adenosine receptor agonist) decreased blood pressure under basal condition but did not potentiate decreases in blood pressure

  7. Decreased group velocity in compositionally graded films.

    Gao, Lei


    A theoretical formalism is presented that describes the group velocity of electromagnetic signals in compositionally graded films. The theory is first based on effective medium approximation or the Maxwell-Garnett approximation to obtain the equivalent dielectric function in a z slice. Then the effective dielectric tensor of the graded film is directly determined, and the group velocities for ordinary and extraordinary waves in the film are derived. It is found that the group velocity is sensitively dependent on the graded profile. For a power-law graded profile f(x)=ax(m), increasing m results in the decreased extraordinary group velocity. Such a decreased tendency becomes significant when the incident angle increases. Therefore the group velocity in compositionally graded films can be effectively decreased by our suitable adjustment of the total volume fraction, the graded profile, and the incident angle. As a result, the compositionally graded films may serve as candidate material for realizing small group velocity.

  8. 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.

  9. 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.

  10. Significance Testing Without Truth


    ICES REPORT 12-34 August 2012 Significance testing without truth by William Perkins, Mark Tygert, and Rachel Ward The Institute for Computational...testing without truth , ICES REPORT 12-34, The Institute for Computational Engineering and Sciences, The University of Texas at Austin, August 2012...2. REPORT TYPE 3. DATES COVERED 00-00-2012 to 00-00-2012 4. TITLE AND SUBTITLE Significance testing without truth 5a. CONTRACT NUMBER 5b

  11. Release of potassium accompanying the dissolution of rice straw phytolith.

    Nguyen, Minh Ngoc; Dultz, Stefan; Picardal, Flynn; Bui, Anh Thi Kim; Pham, Quang Van; Schieber, Juergen


    In rice, Si assimilated from the soil solution is deposited in inter- and intracellular spaces throughout the leaf and stems to form silicified structures (so-called phytoliths). Because K is also present in significant concentrations in rice stems and leaves, the question arises if K is immobilized in the mineralized silica during the precipitation of Si. This work determined whether desilification of the phytolith is a factor regulating K release by implementing batch experiments. Solubility of Si and K of the rice straw heated at different temperatures were examined to identify effect of pretreatment. Analyses of phytoliths using SEM-EDX and X-ray tomographic microscopy in conjunction with the results from batch experiments revealed that K might co-exist with occluded organic matter inside the phytolith structure. In the kinetic experiments, corresponding increases of K and Si concentrations in the supernatants were observed which suggested that desilification of the phytolith is a main factor regulating K release. The extent of heat pretreatment of the rice straw is of significant importance with respect to dissolution of the phytolith by affecting organic removal and surface modification. At temperatures lower than 600 °C, corresponding increases of the soluble Si and K with heating temperature have been obviously observed. In contrast, the solubility of Si and K gradually decreased at temperatures above 600 °C. This work provides insights into factors that control release of K and Si from phytolith and a practical recommendation for practices of burning rice straw that may maximize subsequent release of Si and K for crops. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. Subconjunctival sustained release 5-fluorouracil for glaucoma filtration surgery

    Li-jun CUI; Nai-xue SUN; Xing-hua LI; Jie HUANG; Jian-gang YANG


    Aim:To determine the release characteristics of a 5-fluorouracil-loaded poly (lactic acid) disc (5-FU-PLA-DS) and the effect of sustained drug delivery on the success of glaucoma filtration surgery in rabbit eyes. Methods: A method of microspheres accumulated by excessive carriers was used in the preparation of the 5-FU-PLA-DS. The disc was characterized for drug loading, entrapment efficiency, in vitro release, and external morphology. It was then implanted sub-conjunctivally into rabbit eyes with trabeculectomy. Intraocular pressure, ocular inflammatory reaction, filtration bleb appearance, and persistence were evalu-ated up to postoperative d 90. A quantitative analysis of 5-fluorouracil (5-FU) was performed in the aqueous humor. Ultrasound biomicroscopy was used to assess the appearance of the filtering fistula. Results: The 5-FU-PLA-DS was produced with the drug-loading of 3.07±0.08 mg (mean±SD). 5-FU was released for 91 d with suppressive concentrations. The decrease in intraocular pressure from baseline was significantly more marked in the 5-FU-PLA-DS-implanted eyes during postoperative d 3-90, and the persistence of bleb and filtration fistula was longer than the control eyes (P<0.05). Corneal toxicity and hyperemia triggered by 5-FU was lower in the 5-FU-PLA-DS-implanted eyes than those exposed to 5-FU intraoperatively. The 5-FU concentration in the aqueous humor was insufficient for corneal endothelial damage. No evidence of toxic reaction was found in the conjunctival biopsy. Conclusion: 5-FU-PLA-DS displaying sustained intraocular release of 5-FU, reduced intraocular pres-sure, and prolonged bleb persistence, while significantly reducing 5-FU toxicity.

  13. Waste Isolation Pilot Plant Performance Assessment: Radionuclide Release Sensitivity to Diminished Brine and Gas Flows to/from Transuranic Waste Disposal Areas

    Brad A. Day


    Full Text Available Waste Isolation Pilot Plant repository releases are evaluated through the application of modified parameters to simulate accelerated creep closure, include capillary pressure effects on relative permeability, and increase brine and gas saturation in the operations and experimental (OPS/EXP areas. The modifications to the repository model result in increased pressures and decreased brine saturations in waste areas and increased pressures and brine saturations in the OPS/EXP areas. Brine flows up the borehole during a hypothetical drilling intrusion are nearly identical and brine flows up the shaft are decreased. The modified parameters essentially halt the flow of gas from the southern waste areas to the northern nonwaste areas, except as transported through the marker beds and anhydrite layers. The combination of slightly increased waste region pressures and very slightly decreased brine saturations result in a modest increase in spallings and no significant effect on direct brine releases, with total releases from the Culebra and cutting and caving releases unaffected. Overall, the effects on total high-probability mean releases from the repository are insignificant, with total low-probability mean releases minimally increased. It is concluded that the modified OPS/EXP area parameters have an insignificant effect on the prediction of total releases.

  14. Waste isolation pilot plant performance assessment: Radionuclide release sensitivity to diminished brine and gas flows to/from transuranic waste disposal areas

    Day, Brad A.; Camphouse, R. C.; Zeitler, Todd R. [Sandia National Laboratories, Carlsbad (United States)


    Waste Isolation Pilot Plant repository releases are evaluated through the application of modified parameters to simulate accelerated creep closure, include capillary pressure effects on relative permeability, and increase brine and gas saturation in the operations and experimental (OPS/EXP) areas. The modifications to the repository model result in increased pressures and decreased brine saturations in waste areas and increased pressures and brine saturations in the OPS/EXP areas. Brine flows up the borehole during a hypothetical drilling intrusion are nearly identical and brine flows up the shaft are decreased. The modified parameters essentially halt the flow of gas from the southern waste areas to the northern nonwaste areas, except as transported through the marker beds and anhydrite layers. The combination of slightly increased waste region pressures and very slightly decreased brine saturations result in a modest increase in spallings and no significant effect on direct brine releases, with total releases from the Culebra and cutting and caving releases unaffected. Overall, the effects on total high-probability mean releases from the repository are insignificant, with total low-probability mean releases minimally increased. It is concluded that the modified OPS/EXP area parameters have an insignificant effect on the prediction of total releases.

  15. Effects of anesthetic propofol on release of amino acids from the spinal cord during visceral pain.

    Mu, Xiaobo; Wu, Anshi; Wu, Jing; Liu, Yang; Zhang, Yongqian; Yue, Yun; Fang, Li; Wang, Yun


    As one of general anesthetics, propofol, has been used for surgical procedures of visceral organs. However, the mechanisms underlying the action of propofol on visceral nociception remain controversial. The aim of this study is to test whether the antinociception of systemic administration of propofol against visceral stimuli is related to the changes in release of excitatory and inhibitory amino acids in the spinal cord. The spinal microdialysis catheters were implanted subarachnoidally via the atlanto-occipital membrane in healthy SD rats. The rats received an intraperitoneal injection of acetic acid for visceral pain induction 10min after intraperitoneal pretreatment with vehicle or propofol (100mg/kg). The acetic acid-induced writhing assay was used to determine the degree of antinociception. Cerebrospinal fluid dialysate was collected by microdialysis from the spinal subarachnoid space before pretreatment and after visceral pain induction. Visceral pain-induced release of amino acids into the dialysate, including glutamate, aspartate, and γ-amino butyric acid was evaluated by measuring the changes in the concentrations of these amino acids. Acetic acid increased release of aspartate and glutamate, and decreased release of γ-amino butyric acid in the cerebrospinal fluid as measured by microdialysis. Pretreatment with propofol significantly decreased writhing responses induced by visceral pain, suppressed the visceral pain-induced aspartate and glutamate release, and reversed the decreased release of γ-amino butyric acid in the cerebrospinal fluid. These data provide evidence for a potential mechanism for the antinociceptive effects of propofol on visceral nociception. 2010 Elsevier Ireland Ltd. All rights reserved.

  16. Decreasing Fires in Mediterranean Europe.

    Marco Turco

    Full Text Available Forest fires are a serious environmental hazard in southern Europe. Quantitative assessment of recent trends in fire statistics is important for assessing the possible shifts induced by climate and other environmental/socioeconomic changes in this area. Here we analyse recent fire trends in Portugal, Spain, southern France, Italy and Greece, building on a homogenized fire database integrating official fire statistics provided by several national/EU agencies. During the period 1985-2011, the total annual burned area (BA displayed a general decreasing trend, with the exception of Portugal, where a heterogeneous signal was found. Considering all countries globally, we found that BA decreased by about 3020 km2 over the 27-year-long study period (i.e. about -66% of the mean historical value. These results are consistent with those obtained on longer time scales when data were available, also yielding predominantly negative trends in Spain and France (1974-2011 and a mixed trend in Portugal (1980-2011. Similar overall results were found for the annual number of fires (NF, which globally decreased by about 12600 in the study period (about -59%, except for Spain where, excluding the provinces along the Mediterranean coast, an upward trend was found for the longer period. We argue that the negative trends can be explained, at least in part, by an increased effort in fire management and prevention after the big fires of the 1980's, while positive trends may be related to recent socioeconomic transformations leading to more hazardous landscape configurations, as well as to the observed warming of recent decades. We stress the importance of fire data homogenization prior to analysis, in order to alleviate spurious effects associated with non-stationarities in the data due to temporal variations in fire detection efforts.

  17. Technologies for Decreasing Mining Losses

    Valgma, Ingo; Väizene, Vivika; Kolats, Margit; Saarnak, Martin


    In case of stratified deposits like oil shale deposit in Estonia, mining losses depend on mining technologies. Current research focuses on extraction and separation possibilities of mineral resources. Selective mining, selective crushing and separation tests have been performed, showing possibilities of decreasing mining losses. Rock crushing and screening process simulations were used for optimizing rock fractions. In addition mine backfilling, fine separation, and optimized drilling and blasting have been analyzed. All tested methods show potential and depend on mineral usage. Usage in addition depends on the utilization technology. The questions like stability of the material flow and influences of the quality fluctuations to the final yield are raised.

  18. Decreased Brain Neurokinin-1 Receptor Availability in Chronic Tennis Elbow

    Linnman, Clas; Catana, Ciprian; Svärdsudd, Kurt; Appel, Lieuwe; Engler, Henry; Långström, Bengt; Sörensen, Jens; Furmark, Tomas; Fredrikson, Mats; Borsook, David; Peterson, Magnus


    Substance P is released in painful and inflammatory conditions, affecting both peripheral processes and the central nervous system neurokinin 1 (NK1) receptor. There is a paucity of data on human brain alterations in NK1 expression, how this system may be affected by treatment, and interactions between central and peripheral tissue alterations. Ten subjects with chronic tennis elbow (lateral epicondylosis) were selected out of a larger (n = 120) randomized controlled trial evaluating graded exercise as a treatment for chronic tennis elbow (lateral epicondylosis). These ten subjects were examined by positron emission tomography (PET) with the NK1-specific radioligand 11C-GR205171 before, and eight patients were followed up after treatment with graded exercise. Brain binding in the ten patients before treatment, reflecting NK1-receptor availability (NK1-RA), was compared to that of 18 healthy subjects and, longitudinally, to the eight of the original ten patients that agreed to a second PET examination after treatment. Before treatment, patients had significantly lower NK1-RA in the insula, vmPFC, postcentral gyrus, anterior cingulate, caudate, putamen, amygdala and the midbrain but not the thalamus and cerebellum, with the largest difference in the insula contralateral to the injured elbow. No significant correlations between brain NK1-RA and pain, functional severity, or peripheral NK1-RA in the affected limb were observed. In the eight patients examined after treatment, pain ratings decreased in everyone, but there were no significant changes in NK1-RA. These findings indicate a role for the substance P (SP) / NK1 receptor system in musculoskeletal pain and tissue healing. As neither clinical parameters nor successful treatment response was reflected in brain NK1-RA after treatment, this may reflect the diverse function of the SP/NK1 system in CNS and peripheral tissue, or a change too small or slow to capture over the three-month treatment. PMID:27658244

  19. Optogenetically-induced tonic dopamine release from VTA-nucleus accumbens projections inhibits reward consummatory behaviors.

    Mikhailova, Maria A; Bass, Caroline E; Grinevich, Valentina P; Chappell, Ann M; Deal, Alex L; Bonin, Keith D; Weiner, Jeff L; Gainetdinov, Raul R; Budygin, Evgeny A


    Recent optogenetic studies demonstrated that phasic dopamine release in the nucleus accumbens may play a causal role in multiple aspects of natural and drug reward-related behaviors. The role of tonic dopamine release in reward consummatory behavior remains unclear. The current study used a combinatorial viral-mediated gene delivery approach to express ChR2 on mesolimbic dopamine neurons in rats. We used optical activation of this dopamine circuit to mimic tonic dopamine release in the nucleus accumbens and to explore the causal relationship between this form of dopamine signaling within the ventral tegmental area (VTA)-nucleus accumbens projection and consumption of a natural reward. Using a two bottle choice paradigm (sucrose vs. water), the experiments revealed that tonic optogenetic stimulation of mesolimbic dopamine transmission significantly decreased reward consummatory behaviors. Specifically, there was a significant decrease in the number of bouts, licks and amount of sucrose obtained during the drinking session. Notably, activation of VTA dopamine cell bodies or dopamine terminals in the nucleus accumbens resulted in identical behavioral consequences. No changes in water intake were evident under the same experimental conditions. Collectively, these data demonstrate that tonic optogenetic stimulation of VTA-nucleus accumbens dopamine release is sufficient to inhibit reward consummatory behavior, possibly by preventing this circuit from engaging in phasic activity that is thought to be essential for reward-based behaviors.

  20. 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...

  1. 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...

  2. Bioavailability of sustained-release theophylline formulations.

    Bonora Regazzi, M; Rondanelli, R; Vidale, E; Cristiani, D


    Sustained-release formulations of theophylline as well as of other drugs are designed to effect a delayed but constant release of the active principle in the gastrointestinal tract, thus ensuring more prolonged blood level curves. This study was made to assess the bioavailability of two sustained-release microencapsulated formulations and one sustained-release Diffucaps formulation, in comparison with an equivalent dose of theophylline solution. As regards bioavailability, none of the three formulations differed significantly from the reference formulation. The blood levels at steady state were estimated on the basis of data obtained after a single-dose study. All three sustained release formulations showed good results after prolonged administration in terms of peaks and troughs. The time duration at which the theophylline plasma levels remain higher than 75% of the maximum steady-state levels, following 12-h dosing interval, was evaluated: for the sustained-release microencapsulated formulations this time duration reaches 100% of the dosing interval. A multiple-dose administration of the sustained-release formulations used in this study should guarantee almost complete time coverage, with blood levels sharply exceeding the minimum threshold level of the theophylline therapeutic range.

  3. Fluoride release and uptake capacities of fluoride-releasing restorative materials.

    Attar, Nuray; Turgut, Melek D


    Many fluoride-releasing dental materials are being sold on the basis of their cariostatic properties. However, the amount fluoride release of these materials is still uncertain. This study investigated the fluoride release and uptake characteristics of four flowable resin composites (Heliomolar Flow, Tetric Flow, Wave, Perma Flo), one flowable compomer (Dyract flow), one conventional glass ionomer cement mixed with two different powder/liquid ratios (ChemFlex Syringeable and ChemFlex Condensable), one packable resin composite (SureFil), one ion-releasing composite (Ariston pHc) and one resin-modified glass ionomer cement (Vitremer). Seven discs (6-mm diameter and 1.5-mm height) were prepared for each material. Each disc was immersed in 3.5 ml of deionized water within a plastic vial and stored at 37 degrees C. The deionized water was changed every 24 hours and the release of fluoride was measured for 30 days. At the end of this period, the samples were recharged with 2 ml of 1.23% acidulated phosphate fluoride (APF) gel for four minutes. Then, all samples were reassessed for an additional 10 days. The fluoride release of all samples was measured with a specific fluoride electrode and an ionanalyzer. Statistical analyses were conducted using two-way repeated measure ANOVA and Duncan's multiple range tests. For all tested materials, the greatest fluoride release was observed after the first day of the study (p0.05). Ariston pHc released the highest amount of fluoride, followed by ChemFlex Syringeable, Vitremer and ChemFlex Condensable. There were statistically significant differences among these materials (p<0.05). Fluoride release of all materials were significantly increased after the first day following refluoridation and Ariston pHc released the greatest among all materials (p<0.01). At the end of two days of refluoridation, the fluoride release rate for each material dropped quickly and stabilized within three days.

  4. A Significant Play

    梁海光; 陈明


    Yesterday evening, I went to see a play. It was really significant. It was about Zheng Xiaoyue, a very clever and diligent middle school student. Unfortunately, her mother died when she and her brother were very young. Her father was out of work and,

  5. The Release of Egg White Lysozyme Containing EDTA from Composite Edible Film Based on Whey Protein, Konjac Flour and Lipid

    Mulia W. Apriliyani


    Full Text Available The objectives of this research were to find out the effect of EDTA addition on antibacterial spectrum broadening of lysozyme on Gram negative bacteria and the release of lysozyme from composite edible film made of whey protein, konjac glucomannan and several lipids type and content. The research were conducted with 2 steps. Step I: The addition of EDTA on lysozyme aquaeous (Lysozyme (mg/mL: EDTA (mg/mL = 11.14:8.14; 11.14:11.14 and 11.14:14.14 using Randomyzed Block Design, the variables were, antibacterial of lysozyme on Micrococcus lysodeikticus and Escherichia coli. Step II: Lipid content (5 and 10% and kind of lipid (butter, margarine, palm oil and beeswax using nested Randomyzed Block Design, the variables were lysozyme release, Water Vapor Permeability (WVP, protein solublity and microstructure of composite edible film. The results were, step I: the treatment didn’t gave significantly effect (p>0.05 on lysozyme activity. EDTA decrease cell membrane stabilization and lysozyme made lysis of cell membrane. EDTA chelate Ca2+ and Mg2+ salts as bridge between Lypopolysachcharide (LPS in outer membrane so LPS released from cell wall of Gram negative bacteria. Step II: The treatment didn’t gave significantly effect (p>0.05 on release of lysozyme and water vapour permeability, but gave significantly effect (p<0.05 on protein solubility. The release of lysozyme from composite edible film gave the best lysozyme release from beeswax 10% addition.

  6. Influence of paints formulations on nanoparticles release during their life cycle

    Fiorentino, Brice, E-mail:; Golanski, Luana; Guiot, Arnaud; Damlencourt, Jean-François; Boutry, Delphine [Commissariat à l’énergie atomique et aux énergies alternatives (France)


    Pristine nanoparticles (NPs) may present a hazard to humans and the environment, and hence it is important to know to what extent NPs can be freely released from commercialized products in which they are added. The purpose of this study was to identify the parameters of the paint formulation containing SiO{sub 2} NPs of 19-nm diameter that could have an impact on the release induced by aging and abrasion. In order to simulate outdoor aging during the life cycle of the product, painted panels were exposed to accelerated weathering experiments in accordance with the norm EN ISO 16474-3:2013. The surface modification of these paints was characterized by scanning electron microscope coupled with energy dispersive spectrometry (SEM–EDS). These analyses showed that the acrylic copolymer binder has undergone a more significant chemical degradation compared with the styrene-acrylic copolymer. To simulate a mechanical aging, abrasion tests were conducted using a Taber Abraser, simulating critical scenarios of the abrasion standard. The particle size distributions and particle concentrations of the abraded particles were measured using an electric low-pressure impactor. After accelerated aging and abrasion tests, we observed a link between the paint degradations occurring with the release of pristine NPs and the embedded pristine NPs. Surface degradation of acrylic copolymer paints was more significant than that of the styrene-acrylic copolymer paints, and this induced a release of NPs 2.7 times higher. Other parameters like TiO{sub 2} addition as pigments induced a strong stability of paint against light and water, decreasing the total number of NPs released from paints from 30,000 to 1200 particles/cm{sup 3}. These results revealed that formulations can be tuned to decrease the number of free NPs released and get a “safe-by-design” product.

  7. Compounding of slow-release niacinamide capsules: feasibility and characterization.

    Radojkovic, Branko; Milić, Jela; Calija, Bojan


    The purpose of this study was to assess the feasibility of extemporaneous compounding of slow-release oral dosage form of niacinamide and to evaluate its release kinetics. The model formulation (preparation) was developed in the form of powder-filled hard gelatin capsules. Two slow-release preparations with different ratios of hypromellose have been prepared and evaluated in comparison with an immediate-release preparation. The dissolution tests were performed as per United States Pharmacopoeia requirements: Type I Apparatus, over 7 hours. Both slow-release preparations, containing 40% and 60% v/v hypromellose, respectively, have showed slow release kinetics. The dissolution profiles were significantly different, with similarity factor f2niacinamide capsules can be successfully compounded using hypromellose as a sole release rate modifier, and that the release mechanism is comparable to hydrophilic polymer matrix-based systems.

  8. Cyanocobalamin, vitamin B12, depresses glutamate release through inhibition of voltage-dependent Ca2+ influx in rat cerebrocortical nerve terminals (synaptosomes).

    Hung, Kun-Long; Wang, Chia-Chuan; Huang, Chia-Yu; Wang, Su-Jane


    The effect of cyanocobalamin, vitamin B12, on glutamate release in isolated nerve terminals (synaptosomes) prepared from rat prefrontal cortex was examined. Cyanocobalamin inhibited the release of glutamate evoked by 4-aminopyridine in a concentration-dependent manner. The inhibitory action of cyanocobalamin was blocked by the vesicular transporter inhibitor bafilomycin A1, not by the glutamate transporter inhibitor L-transpyrrolidine-2,4-dicarboxylic acid or the nontransportable glutamate inhibitor DL-threo-beta-benzyloxyaspartate, indicating that this release inhibition results from a reduction of vesicular exocytosis and not from an inhibition of Ca(2+)-independent efflux via glutamate transporter. Examination of the effect of cyanocobalamin on cytosolic free Ca(2+) concentration revealed that the inhibition of glutamate release could be attributed to a reduction in voltage-dependent Ca(2+) influx. Consistent with this, the N- and P/Q-type Ca(2+) channel blocker omega-conotoxin MVIIC, largely attenuated the inhibitory effect of cyanocobalamin on 4-aminopyridine-evoked glutamate release, but the Ca(2+) release inhibitor dantrolene had no effect. Cyanocobalamin did not alter the resting synaptosomal membrane potential or 4-aminopyridine-mediated depolarization; thus, the inhibition of 4-aminopyridine-evoked Ca(2+) influx and glutamate release produced by cyanocobalamin was not due to its decreasing synaptosomal excitability. In addition, cyanocobalamin-mediated inhibition of 4-aminopyridine-evoked Ca(2+) influx and glutamate release was significantly attenuated by protein kinase C inhibitors GF109203X and Ro318220. Furthermore, 4-aminopyridine-induced phosphorylation of protein kinase C was significantly reduced by cyanocobalamin. These results suggest that cyanocobalamin effects a decrease in protein kinase C activation, which subsequently reduces the Ca(2+) entry through voltage-dependent N- and P/Q-type Ca(2+) channels to cause a decrease in evoked glutamate

  9. Rigidity spectrum of Forbush decrease

    Sakakibara, S.; Munakata, K.; Nagashima, K.


    Using data from neutron monitors and muon telescopes at surface and underground stations, the average rigidity spectrum of Forbush decreases (Fds) during the period of 1978-1982 were obtained. Thirty eight Ed-events are classified into two groups Hard Fd and Soft Fd according to size of Fd at Sakashita station. It is found that a spectral form of fractional-power type (P to the-gamma sub 1 (P+P sub c) to the -gamma sub2) is more suitable for the present purpose than that of power-exponential type or of power type with an upper limiting rigidity. The best fitted spectrum of fractional-power type is expressed by gamma sub1 = 0.37, gamma sub2 = 0.89 and P subc = 10 GV for Hard Fd and gamma sub1 = 0.77, gamma sub2 = 1.02 and P sub c - 14GV for Soft Fd.

  10. Significant Tsunami Events

    Dunbar, P. K.; Furtney, M.; McLean, S. J.; Sweeney, A. D.


    Tsunamis have inflicted death and destruction on the coastlines of the world throughout history. The occurrence of tsunamis and the resulting effects have been collected and studied as far back as the second millennium B.C. The knowledge gained from cataloging and examining these events has led to significant changes in our understanding of tsunamis, tsunami sources, and methods to mitigate the effects of tsunamis. The most significant, not surprisingly, are often the most devastating, such as the 2011 Tohoku, Japan earthquake and tsunami. The goal of this poster is to give a brief overview of the occurrence of tsunamis and then focus specifically on several significant tsunamis. There are various criteria to determine the most significant tsunamis: the number of deaths, amount of damage, maximum runup height, had a major impact on tsunami science or policy, etc. As a result, descriptions will include some of the most costly (2011 Tohoku, Japan), the most deadly (2004 Sumatra, 1883 Krakatau), and the highest runup ever observed (1958 Lituya Bay, Alaska). The discovery of the Cascadia subduction zone as the source of the 1700 Japanese "Orphan" tsunami and a future tsunami threat to the U.S. northwest coast, contributed to the decision to form the U.S. National Tsunami Hazard Mitigation Program. The great Lisbon earthquake of 1755 marked the beginning of the modern era of seismology. Knowledge gained from the 1964 Alaska earthquake and tsunami helped confirm the theory of plate tectonics. The 1946 Alaska, 1952 Kuril Islands, 1960 Chile, 1964 Alaska, and the 2004 Banda Aceh, tsunamis all resulted in warning centers or systems being established.The data descriptions on this poster were extracted from NOAA's National Geophysical Data Center (NGDC) global historical tsunami database. Additional information about these tsunamis, as well as water level data can be found by accessing the NGDC website

  11. Design and Comparative Evaluation of In-vitro Drug Release, Pharmacokinetics and Gamma Scintigraphic Analysis of Controlled Release Tablets Using Novel pH Sensitive Starch and Modified Starch- acrylate Graft Copolymer Matrices

    Kumar, Pankaj; Ganure, Ashok Laxmanrao; Subudhi, Bharat Bhushan; Shukla, Shubhanjali


    The present investigation deals with the development of controlled release tablets of salbutamol sulphate using graft copolymers (St-g-PMMA and Ast-g-PMMA) of starch and acetylated starch. Drug excipient compatibility was spectroscopically analyzed via FT-IR, which confirmed no interaction between drug and other excipients. Formulations were evaluated for physical characteristics like hardness, friability, weight variations, drug release and drug content analysis which satisfies all the pharmacopoeial requirement of tablet dosage form. Release rate of a model drug from formulated matrix tablets were studied at two different pH namely 1.2 and 6.8, spectrophotometrically. Drug release from the tablets of graft copolymer matrices is profoundly pH-dependent and showed a reduced release rate under acidic conditions as compared to the alkaline conditions. Study of release mechanism by Korsmeyer’s model with n values between 0.61-0.67, proved that release was governed by both diffusion and erosion. In comparison to starch and acetylated starch matrix formulations, pharmacokinetic parameters of graft copolymers matrix formulations showed a significant decrease in Cmax with an increase in tmax, indicating the effect of dosage form would last for longer duration. The gastro intestinal transit behavior of the formulation was determined by gamma scintigraphy, using 99mTc as a marker in healthy rabbits. The amount of radioactive tracer released from the labelled tablets was minimal when the tablets were in the stomach, whereas it increased as tablets reached to intestine. Thus, in-vitro and in-vivo drug release studies of starch-acrylate graft copolymers proved their controlled release behavior with preferential delivery into alkaline pH environment. PMID:26330856

  12. Radioactivity released from burning gas lantern mantles.

    Luetzelschwab, J W; Googins, S W


    Gas lantern mantles contain thorium to produce incandescence when lantern fuel is burned on the mantle. Although only thorium is initially present on the mantle, the thorium daughters build up, some over a period of weeks and some over a period of years, and significant quantities of these daughters are present when the mantle is used. Some of these daughters are released when the lantern fuel is burned on the mantle. The amounts of radioactivity released during burning is studied by measuring the gamma radiation emitted by the daughters. Results of this study show that some of the radium (224Ra and 228Ra) and more than half the 212Pb and 212Bi is released during the first hour of a burn. The actual amounts release depend on the age of the mantle.

  13. Evaluation of three approaches to meniscal release.

    Austin, B; Montgomery, R D; Wright, J; Bellah, J R; Tonks, C


    Three approaches to medial meniscal release (MMR) were compared using 48 canine cadaver stifles. The approaches included a caudomedial arthrotomy approach, a blind stab incision based on anatomic landmarks, and an arthroscopic guided approach. The cranial cruciate ligament was intact in all specimens. The time required to perform the meniscal release and joint capsule closure was recorded, as well as completeness and location of the meniscal transection. Damage to the caudal cruciate ligament, femoral cartilage, and medial collateral ligament were recorded. The mini-arthrotomy was 81% successful in accomplishment of MMR with a 4% rate of iatrogenic damage. The blind technique was 56% successful in the accomplishment of MMR with a 4% rate of iatrogenic damage. The arthroscopic guided approach was 62.5% successful in accomplishment of MMR, with a 10% rate of iatrogenic damage. Accomplishment and iatrogenic damage rates were not significantly different among procedures (p > 0.05). Significantly less time was required to perform the blind technique, and significantly greater time was required to perform the arthroscopic guided technique (p > 0.05). Significant differences were not noted among the procedures regarding the ability to accomplish the meniscal release or damage surrounding structures. None of the evaluated approaches for meniscal release resulted in a complete and accurate meniscal release for over 81% of the time.

  14. Modeling controlled nutrient release from polymer coated fertilizers: diffusion release from single granules.

    Shaviv, Avi; Raban, Smadar; Zaidel, Elina


    A comprehensive model describing the complex and "non-Fickian" (mathematically nonlinear) nature of the release from single granules of membrane coated, controlled release fertilizers (CRFs) is proposed consisting of three stages: i. a lag period during which water penetrates the coating of the granule dissolving part of the solid fertilizer in it ii. a period of linear release during which water penetration into and release out occur concomitantly while the total volume of the granules remains practically constant; and iii. a period of "decaying release", starting as the concentration inside the granule starts to decrease. A mathematical model was developed based on vapor and nutrient diffusion equations. The model predicts the release stages in terms of measurable geometrical and chemophysical parameters such as the following: the product of granule radius and coating thickness, water and solute permeability, saturation concentration of the fertilizer, and its density. The model successfully predicts the complex and "sigmoidal" pattern of release that is essential for matching plant temporal demand to ensure high agronomic and environmental effectiveness. It also lends itself to more complex statistical formulations which account for the large variability within large populations of coated CRFs and can serve for further improving CRF production and performance.

  15. Pharmacokinetic Study on Lovastatin Sustained-release Tablet and Sustained-release Capsule in Begal Dogs

    付琳; 代宗顺; 侯淑贤; 万元胜


    This study pharmacokinetically examined the lovastatin sustained-release tablet and sustained release capsule in Beagle dogs. An reversed-phase HPLC method was established for the determination of lovastatin in Beagle dog plasma. Pharmacokinetic findings were compared among three preparation(lovastatin sustained-release tablet, TP; sustained-release capsule, TJ and conventional capsule). Our results showed that the pharmacokinetic parameters in 6 dogs after single-dose oral administration of three perparations were calculated. Tmax , Cmax and MRT revealed significant difference (P<0.05). Relative bioavailability was 111. 5 ± 16. 9 % (TP) and 110.4% ± 9.6%(TJ). The pharmacokinetic parameters in the 6 dogs after multiple-dose oral administration of three perparations, Tmax Cmax MRT and DF had significant difference (P<0. 05); Cav, Cmin and AUC0-24 h displayed no significant difference (P>0.05). It is concluded that the lovastatin sustained-release tablet and sustained-release capsule are able to maintain a sustained-release for 24 h.

  16. A Significant Step Forward


    Australia officially ratified the Kyoto Protocol on December 3,the first act of its new government under Prime Minister Kevin Rudd.Rudd signed the instrument of ratification the very day he was sworn in by Australia’s Governor General Michael Jeffery. This is a significant step in Australia’s efforts to fight climate change domestically and with the international community,Rudd said in a statement.The Australian Government will do everything in its power to help Australia meet its Kyoto obligations,he added.

  17. Intellectual disability and patient activation after release from prison: a prospective cohort study.

    Young, J T; Cumming, C; van Dooren, K; Lennox, N G; Alati, R; Spittal, M J; Brophy, L; Preen, D B; Kinner, S A


    Intellectual disability and patient activation may be important drivers of inequities in health service access and health outcomes for people with intellectual disability transitioning from prison to the community. We assessed the association between intellectual disability and patient activation after prison release and examined whether this association varied, depending on whether intellectual disability was identified prior to prison release. Overall, 936 prisoners were screened for intellectual disability by using the Hayes Ability Screening Index and completed the Patient Activation Measure (PAM) within 6 weeks of prison release and again at 1, 3 and 6 months post-release. We estimated the association between intellectual disability status and PAM scores by using a multilevel linear model, adjusting for sociodemographic, behavioural, health and criminogenic factors. We used propensity score matching to estimate the impact of being identified with intellectual disability prior to release from prison on the change in mean PAM score after prison release. Compared with those who screened negative for intellectual disability, ex-prisoners who screened positive, both with and without prior identification of intellectual disability, had significantly decreased mean PAM scores [(B = -4.3; 95% CI: -6.3, -2.4) and (B = -4.5; 95% CI: -6.8, -2.3), respectively] over 6 months of follow-up. Among those who reported being identified with intellectual disability prior to release from prison, a significant increase in PAM score at the 6-month follow-up interview (B = 5.89; 95% CI: 2.35, 9.42; P = 0.001) was attributable to being identified with intellectual disability prior to release. Ex-prisoners screening positive for possible intellectual disability have decreased patient activation for at least 6 months after release from prison. However, individuals whose possible intellectual disability is unidentified appear to be particularly vulnerable. Incarceration is a

  18. Copper release kinetics from a long-term contaminated acid soil using a stirred flow chamber: effect of ionic strength and pH.

    Fernández-Calviño, David; Bermúdez-Couso, Alipio; Garrido-Rodríguez, Beatriz; Peña Rodríguez, Susana; Arias-Estévez, Manuel


    The effect of pH and ionic strength on copper release in a long-term Cu-polluted soil was studied using a stirred flow chamber. The presence of Ca(2+) and Na(+) was also evaluated. More copper was released as the ionic strength increased, and it was significantly higher in the presence of Ca(2+) than in the presence of Na(+). The maximum amount of Cu that could be released under experimental conditions increased logarithmically as the ionic strength increased, and the release rate parameters were not significantly correlated with ionic strength values. The maximum amount of Cu that could be released was similar for solutions with pH values between 5.5 and 8.5. For solutions with a pH value below 4.5, the amount of Cu released increased exponentially as the pH decreased. The release rate parameters and Cu release pattern were affected by pH, especially for more acidic solutions (pH values of 2.5 and 3.5).

  19. Similar risk reduction of death of extended-release metoprolol once daily and immediate-release metoprolol twice daily during 5 years after myocardial infarction.

    Herlitz, J; Dellborg, M; Karlson, B W; Lindqvist, J; Sandèn, W; Svensson, H; Sjölin, M; Wedel, H


    The pooled results from five placebo-controlled postinfarction studies with metoprolol have shown a significant reduction in total mortality. All five studies used immediate-release metoprolol twice daily. An extended-release formulation of metoprolol for once-daily use has since been developed. The aim of the present study was to compare the two different forms of metoprolol with regard to the risk reduction of death for 5 years postinfarction and to analyze whether treatment with the beta-blocker metoprolol is associated with a reduced mortality after the introduction of modern therapies such as thrombolysis, aspirin, and ACE inhibitors. All patients discharged after an acute myocardial infarction (AMI) from Sahlgrenska University Hospital (SU) during 1986-1987 (n = 740, Period I) and during 1990-1991 (n = 1446, Period II) from both SU and Ostra Hospital, Göteborg, Sweden, were included in the study. During Period I, 56% were prescribed immediate-release metoprolol compared with 61% prescribed extended-release metoprolol during Period II. Immediate-release metoprolol was not available for outpatient use during Period II. In a multivariate analysis, all variables significantly associated with either increased or decreased postinfarction mortality during Periods I and II (univariate analysis of patient characteristics, medical history, complications during the AMI medication at discharge) studied were with Cox's proportional hazards model. Treatment with immediate-release metoprolol was significantly associated with reduced mortality over 5 years during Period I (relative risk reduction for total mortality, -34%, P = 0.003; 95% CI for RR, 0.51-0.87), and treatment with extended-release metoprolol was significantly associated with reduced mortality during Period II (-34%, P metoprolol given once daily was associated with a similar risk reduction of death over 5 years as immediate-release metoprolol given twice daily. The data, furthermore, indicate that the beta

  20. Keratinocyte Apoptosis is Decreased in Psoriatic Epidermis

    Fatma Eskioğlu


    Full Text Available Background and Design: Abnormal differentiation and hyperproliferation of keratinocytes are the hallmarks of psoriasis vulgaris. Although psoriasis vulgaris is generally accepted as a disease of decreased keratinocyte apoptosis, the results are contradictory. The aim of the current study is to investigate whether decreased keratinocyte apoptosis contributes to the formation of a thickened epidermis as increased keratinocyte proliferation. Material and Method: Forty-three untreated psoriasis vulgaris patients and 20 healthy control subjects were included into the study. Biopsy specimens taken from the enrollee were evaluated by immunohistochemical staining for Ki-67 expressions to show the proliferation of keratinocytes and by the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling (TUNEL method to show the apoptotic keratinocytes. Results: Apoptotic index (percentage of the TUNEL positive cells was significantly lower in psoriatic epidermis (0.33±0.64 than in normal epidermis (0.75±0.85; whereas Ki-67 index (percentage of positively staining cells for Ki-67 was significantly higher in psoriatic epidermis (30.86±10.49 than in normal epidermis (11.65±2.98, (p=0.021 and p=0.00; respectively. Conclusion: Decreased keratinocyte apoptosis also contribute to increased epidermal thickness in psoriasis as well as increased keratinocyte proliferation.

  1. 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.

  2. 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.

  3. Beta-tricalcium phosphate release from brushite cement surface.

    Alkhraisat, M Hamdan; Mariño, F Tamimi; Retama, J Rubio; Jerez, L Blanco; López-Cabarcos, E


    Different in vivo studies demonstrated that brushite cements are biocompatible, bioresorbable, and osteoconductive. However, the decay of brushite cements has been scarcely studied even though it may be of great concern for clinical applications in highly blood-perfused regions. This work was elaborated to elucidate factors that determine brushite cement surface disintegration. For that, brushite cements were modified using in their preparation different aqueous solutions of phosphoric, glycolic, tartaric, and citric acids in concentrations that were reported to improve the cement properties. Two-viscosity enhancing polysaccharides, chondroitin-4 sulfate and hyaluronic acid, were also assayed. Thereafter, pre- and set cement samples were immersed in distilled water for 24 h. The cement-solid weight loss, microstructure, liquid phase viscosity, mean size of the released particles, and zeta potential were analyzed using X-ray diffraction, FTIR spectroscopy, light scattering, scanning electron microscopy and optical microscopy. It was found that the particles released from the cement surface were beta-TCP, and their amount depends on the carboxylic acid used in the preparation of the cement. The addition of hyaluronic acid and chondroitin-4 sulfate decreased the amount of released particles from the surface of the set brushite cement made with citric acid. Furthermore, the hyaluronic acid increased significantly the viscosity of the citric acid solution and the cement paste prepared with this liquid phase showed a pronounced step down in particle release. In this study, we showed that the water solubility of calcium carboxylate and the viscosity of mixing liquid may dictate the superficial disintegration of brushite cements.

  4. 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.

  5. Metal release from coffee machines and electric kettles.

    Müller, Frederic D; Hackethal, Christin; Schmidt, Roman; Kappenstein, Oliver; Pfaff, Karla; Luch, Andreas


    The release of elemental ions from 8 coffee machines and 11 electric kettles into food simulants was investigated. Three different types of coffee machines were tested: portafilter espresso machines, pod machines and capsule machines. All machines were tested subsequently on 3 days before and on 3 days after decalcification. Decalcification of the machines was performed with agents according to procedures as specified in the respective manufacturer's manuals. The electric kettles showed only a low release of the elements analysed. For the coffee machines decreasing concentrations of elements were found from the first to the last sample taken in the course of 1 day. Metal release on consecutive days showed a decreasing trend as well. After decalcification a large increase in the amounts of elements released was encountered. In addition, the different machine types investigated clearly differed in their extent of element release. By far the highest leaching, both quantitatively and qualitatively, was found for the portafilter machines. With these products releases of Pb, Ni, Mn, Cr and Zn were in the range and beyond the release limits as proposed by the Council of Europe. Therefore, a careful rinsing routine, especially after decalcification, is recommended for these machines. The comparably lower extent of release of one particular portafilter machine demonstrates that metal release at levels above the threshold that triggers health concerns are technically avoidable.

  6. Formulation and Evaluation of Nateglinide Sustained Release Tablets

    Sridevi Gowripattapu


    Full Text Available The objective of the present investigation was to design suitable sustained release tablet formulation of Nateglinide by using different polymers such as hydroxy propyl methyl cellulose K15M, xanthan gum, guar gum as release rate retarding polymers. The tablets were prepared by direct compression technique. Nateglinide is used as anti diabetic drug. The objective of the treatment is to achieve hypoglycemia, by using an ideal dosage regimen. The sustained release formulation provides extend duration of action in therapeutic range without reaching toxic levels as in the case of conventional dosage forms. The real formulation trails are carried from F1 to F9 in which Drug: Polymer ratio was set as 1:9 respectively. The prepared formulations F1 to F9 were evaluated for pre and post compression characteristics, along with the in vitro dissolution Studies. It was found that the release of drug from F1, F2, and F3 gave the better release than other formulations. In these three formulations F2 showing highest release following first order kinetics. From the Higuchi plot good correlation coefficient was observed showing diffusion mechanism. From the peppas plot it was observed that the release model was non fickian anomalous. The release rate was decreased as polymer concentration increased so it shows that increase in diffusion length of polymer decreases the release rate.

  7. Predicting significant torso trauma.

    Nirula, Ram; Talmor, Daniel; Brasel, Karen


    Identification of motor vehicle crash (MVC) characteristics associated with thoracoabdominal injury would advance the development of automatic crash notification systems (ACNS) by improving triage and response times. Our objective was to determine the relationships between MVC characteristics and thoracoabdominal trauma to develop a torso injury probability model. Drivers involved in crashes from 1993 to 2001 within the National Automotive Sampling System were reviewed. Relationships between torso injury and MVC characteristics were assessed using multivariate logistic regression. Receiver operating characteristic curves were used to compare the model to current ACNS models. There were a total of 56,466 drivers. Age, ejection, braking, avoidance, velocity, restraints, passenger-side impact, rollover, and vehicle weight and type were associated with injury (p < 0.05). The area under the receiver operating characteristic curve (83.9) was significantly greater than current ACNS models. We have developed a thoracoabdominal injury probability model that may improve patient triage when used with ACNS.

  8. Anthropological significance of phenylketonuria.

    Saugstad, L F


    The highest incidence rates of phenylketonuria (PKU) have been observed in Ireland and Scotlant. Parents heterozygous for PKU in Norway differ significantly from the general population in the Rhesus, Kell and PGM systems. The parents investigated showed an excess of Rh negative, Kell plus and PGM type 1 individuals, which makes them similar to the present populations in Ireland and Scotlant. It is postulated that the heterozygotes for PKU in Norway are descended from a completely assimilated sub-population of Celtic origin, who came or were brought here, 1ooo years ago. Bronze objects of Western European (Scottish, Irish) origin, found in Viking graves widely distributed in Norway, have been taken as evidence of Vikings returning with loot (including a number of Celts) from Western Viking settlements. The continuity of residence since the Viking age in most habitable parts of Norway, and what seems to be a nearly complete regional relationship between the sites where Viking graves contain western imported objects and the birthplaces of grandparents of PKUs identified in Norway, lend further support to the hypothesis that the heterozygotes for PKU in Norway are descended from a completely assimilated subpopulation. The remarkable resemblance between Iceland and Ireland, in respect of several genetic markers (including the Rhesus, PGM and Kell systems), is considered to be an expression of a similar proportion of people of Celtic origin in each of the two countries. Their identical, high incidence rates of PKU are regarded as further evidence of this. The significant decline in the incidence of PKU when one passes from Ireland, Scotland and Iceland, to Denmark and on to Norway and Sweden, is therefore explained as being related to a reduction in the proportion of inhabitants of Celtic extraction in the respective populations.

  9. Happy mood decreases self-focused attention.

    Green, Jeffrey D; Sedikides, Constantine; Saltzberg, Judith A; Wood, Joanne V; Forzano, Lori-Ann B


    Research addressing the influence of happy mood on self-focused attention has yielded inconsistent results. Some studies found that happy mood decreased self-focus relative to sad mood. Other studies did not detect a significant difference between happy and neutral mood, and still other studies found that happy mood, relative to neutral mood, increased self-focus. These investigations have potential shortcomings, such as an insufficiently powerful happy mood induction and a confound between visualization mood inductions and self-focus itself. The present experiment addressed these shortcomings by inducing mood via musical selections, equalizing the approximate potency between happy and sad moods, and using a within-participants design. Relative to neutral mood, happy mood decreased self-focused attention.

  10. Gas Release as a Deformation Signal

    Bauer, Stephen J. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)


    Radiogenic noble gases are contained in crustal rock at inter and intra granular sites. The gas composition depends on lithology, geologic history, fluid phases, and the aging effect by decay of U, Th, and K. The isotopic signature of noble gases found in rocks is vastly different than that of the atmosphere which is contributed by a variety of sources. When rock is subjected to stress conditions exceeding about half its yield strength, micro-cracks begin to form. As rock deformation progresses a fracture network evolves, releasing trapped noble gases and changing the transport properties to gas migration. Thus, changes in gas emanation and noble gas composition from rocks could be used to infer changes in stress-state and deformation. The purpose of this study has been to evaluate the effect of deformation/strain rate upon noble gas release. Four triaxial experiments were attempted for a strain rate range of %7E10-8 /s (180,000s) to %7E 10-4/s (500s); the three fully successful experiments (at the faster strain rates) imply the following: (1) helium is measurably released for all strain rates during deformation, this release is in amounts 1-2 orders of magnitude greater than that present in the air, and (2) helium gas release increases with decreasing strain rate.

  11. 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.

  12. 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

  13. Glucocorticoid regulation of gonadotropin release from gonadotropes of ovine pituitary gland in vitro

    Nangalama, A.W.


    In order to understand the role of glucocorticoids in the regulation of gonadotropin release by the pituitary gland, the short-term effects of cortisol perifusion (1.5 h to 8 hrs) on GnRH-induced LH secretion were investigated. To determine the biochemical mechanism(s) by which cortisol can act to modulate GnRH-induced LH release, the interactions of cortisol and arachidonic acid in GnRH-stimulated LH release were examined. Cortisol perifusion for 1.5 hr had no effect on GnRH-induced LH release, but longer treatment periods (4 hr-8 hrs) significantly reduced GnRH-stimulated LH release (4.0 hr, p < 0.01; 6.0 hr, p < 0.001; 8.0 hr, p < 0.01). Treatment and animal effects were highly significant (p < 0.001). There were significant interactions (p < 0.001) between treatment and animal as determined by a two-way ANOVA. Cortisol treatment also produced progressive increases in basal LH secretion with time (1.5 hr, p < 0.05; 4.0 hr, p < 0.01; 6.0 hr, p < 0.01; 8.0 hr, p < 0.001). Incubation of pituitary tissue with arachidonic acid (AA) resulted in a linear dose-response of LH (p < 0.001). Cortisol infusion failed to inhibit GnRH-induced LH release in which 10{sup {minus}4}M AA was administered for 20 min before a 10 min, 10{sup {minus}10}M GnRH pulse. Like cortisol, chloroquine also failed to inhibit AA-induced LH release. Perifusion with 10{sup {minus}6}M cortisol for 6.0 hours significantly (p < 0.001) blocked GnRH-stimulated (H{sup 3})AA release 24% below the basal (100%) ({sup 3}H)AA secretion. Reduction of ({sup 3}H)AA release was accompanied by decreased GnRH-stimulated LH secretion.

  14. Moderate systemic hypothermia decreases burn depth progression.

    Rizzo, Julie A; Burgess, Pamela; Cartie, Richard J; Prasad, Balakrishna M


    Therapeutic hypothermia has been proposed to be beneficial in an array of human pathologies including cardiac arrest, stroke, traumatic brain and spinal cord injury, and hemorrhagic shock. Burn depth progression is multifactorial but inflammation plays a large role. Because hypothermia is known to reduce inflammation, we hypothesized that moderate hypothermia will decrease burn depth progression. We used a second-degree 15% total body surface area thermal injury model in rats. Burn depth was assessed by histology of biopsy sections. Moderate hypothermia in the range of 31-33°C was applied for 4h immediately after burn and in a delayed fashion, starting 2h after burn. In order to gain insight into the beneficial effects of hypothermia, we analyzed global gene expression in the burned skin. Immediate hypothermia decreased burn depth progression at 6h post injury, and this protective effect was sustained for at least 24h. Burn depth was 18% lower in rats subjected to immediate hypothermia compared to control rats at both 6 and 24h post injury. Rats in the delayed hypothermia group did not show any significant decrease in burn depth at 6h, but had 23% lower burn depth than controls at 24h. Increased expression of several skin-protective genes such as CCL4, CCL6 and CXCL13 and decreased expression of tissue remodeling genes such as matrix metalloprotease-9 were discovered in the skin biopsy samples of rats subjected to immediate hypothermia. Systemic hypothermia decreases burn depth progression in a rodent model and up-regulation of skin-protective genes and down-regulation of detrimental tissue remodeling genes by hypothermia may contribute to its beneficial effects. Published by Elsevier Ltd.

  15. 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.

  16. Meaning and significance of

    Ph D Student Roman Mihaela


    Full Text Available The concept of "public accountability" is a challenge for political science as a new concept in this area in full debate and developement ,both in theory and practice. This paper is a theoretical approach of displaying some definitions, relevant meanings and significance odf the concept in political science. The importance of this concept is that although originally it was used as a tool to improve effectiveness and eficiency of public governance, it has gradually become a purpose it itself. "Accountability" has become an image of good governance first in the United States of America then in the European Union.Nevertheless,the concept is vaguely defined and provides ambiguous images of good governance.This paper begins with the presentation of some general meanings of the concept as they emerge from specialized dictionaries and ancyclopaedies and continues with the meanings developed in political science. The concept of "public accontability" is rooted in economics and management literature,becoming increasingly relevant in today's political science both in theory and discourse as well as in practice in formulating and evaluating public policies. A first conclusin that emerges from, the analysis of the evolution of this term is that it requires a conceptual clarification in political science. A clear definition will then enable an appropriate model of proving the system of public accountability in formulating and assessing public policies, in order to implement a system of assessment and monitoring thereof.

  17. Glucose and TGF β2 Modulate the Viability of Cultured Human Retinal Pericytes and Their VEGF Release

    Vidro, Eileen K.; Gee, Stephen; Unda, Richard; Ma, Jian-xing; Tsin, Andrew


    Purpose Determine the effects of glucose and exogenous TGFβ2 on viability and VEGF release by human retinal pericytes (HRP). Methods Human retinal pericytes (HRP) were cultured in 5 mM (physiologic) or high (18 mM) glucose with or without added TGFβ2. Viable cells were counted; TGFβ2 and VEGF in the conditioned media (CM) were measured by ELISA. Results High glucose significantly reduced viable cell number and increased the levels of TGFβ2 and VEGF. TGFβ2 caused a significant dose-dependent effect on viable cell number and on the level of VEGF secreted into the CM by HRP in physiologic glucose, decreasing viable cell number, and increasing VEGF release per 1000 cells at a low concentration (0.1 ng/ml) and increasing viable cell number and decreasing VEGF release per 1000 cells at higher concentrations (1.0 and 10 ng/ml). TGFβ2 affected neither parameter in high glucose. Conclusions Elevated glucose decreased HRP viability and modulated changes in TGFβ2 and VEGF release. This suggests a novel mechanism for HRP dropout in diabetic retinopathy. PMID:19085381

  18. Dexmedetomidine decreases the oral mucosal blood flow.

    Kawaai, Hiroyoshi; Yoshida, Kenji; Tanaka, Eri; Togami, Kohei; Tada, Hitoshi; Ganzberg, Steven; Yamazaki, Shinya


    There is an abundance of blood vessels in the oral cavity, and intraoperative bleeding can disrupt operations. There have been some interesting reports about constriction of vessels in the oral cavity, one of which reported that gingival blood flow in cats is controlled by sympathetic α-adrenergic fibres that are involved with vasoconstriction. Dexmedetomidine is a sedative and analgesic agent that acts through the α-2 adrenoceptor, and is expected to have a vasoconstrictive action in the oral cavity. We have focused on the relation between the effects of α-adrenoceptors by dexmedetomidine and vasoconstriction in oral tissues, and assessed the oral mucosal blood flow during sedation with dexmedetomidine. The subjects comprised 13 healthy male volunteers, sedated with dexmedetomidine in a loading dose of 6 μg/kg/h for 10 min and a continuous infusion of 0.7 μg/kg/h for 32 min. The mean arterial pressure (MAP), heart rate (HR), cardiac output (CO), stroke volume (SV), systemic vascular resistance (SVR), and palatal mucosal blood flow (PMBF) were measured at 0, 5, 10, 12, 22, and 32 min after the start of the infusion. The HR, CO, and PBMF decreased significantly during the infusion even though there were no differences in the SV. The SVR increased significantly but the PMBF decreased significantly. In conclusion, PMBF was reduced by the mediating effect of dexmedetomidine on α-2 adrenoceptors.

  19. Evaluation of Fluoride Release, pH and Microhardness of Glass Ionomer Cements

    Andreia Medeiros Rodrigues Cardoso


    Full Text Available Objective: To evaluate fluoride release, pH and microhardness of glass ionomer cements (GIC. Material and Methods: Four different cements: Vidrion ® R (G1, Vitro Fil ® (G2, Maxxion ® (G3 and Magic Glass ® (G4 and a composite resin (G5 - control group comprised the sample. Thirty specimens were manufactured (10 mm x 3 mm and stored in deionized water. Analyses were performed after 24 hours, 7 days and 28 days. The following devices were used for measurements: fluorometer, pH meter and microhardness tester. Data were analyzed by Kruskal-Wallis, Mann-Whitney, Friedman and Wilcoxon tests (α = 0.05 using the SPSS ® software (Statistical Package for Social Sciences version 17. Results: GICs were able to release fluoride; however, the amount released decreased with increasing immersion time (p <0.002. The pH of all products increased over time, the lowest value was identified for Magic Glass (5.93 and the highest for Maxxion (6.94 at time of 24 h. Materials showed significant decrease in surface microhardness, especially G4 for presenting the lowest recorded values (p <0.05. Conclusion: GICs are fluoride-releasing restorative materials with pH favorable to oral homeostasis and good mechanical behavior.

  20. Studies on indomethacin intraocular implants using different in vitro release methods

    Balasubramaniam J


    Full Text Available Intra ocular implants of sodium alginate alone and in combination with hydroxypropylmethylcellulose with or without calcium chloride were formulated with indomethacin as a model drug. The drug release from the implants was evaluated using static method, continuous flow through apparatus (developed in house, USP dissolution and agar diffusion. Except in the static method, indomethacin particle size did not impart any effect on the drug release. In agar diffusion method, an increase in agar concentration from 1 to 2% resulted in a significant decrease (P< 0.005 in the amount of drug released. Inclusion of hydroxypropylmethylcellulose (33.3, 41.6 and 50% w/w, resulted in decrease of indomethacin release irrespective of the method of dissolution study. The agar diffusion method and the continuous flow through methods seem to simulate to a certain extent the in vivo conditions as far as the placement of the device and the hydrodynamic diffusion layer around the intra ocular implant is concerned. The static method and USP method affected the hydrodynamic diffusion layer either too slowly or too fast.

  1. Release of small water-soluble drugs from multiblock copolymer microspheres: a feasibility study.

    Sohier, J; van Dijkhuizen-Radersma, R; de Groot, K; Bezemer, J M


    Poly(ethylene glycol)-terephthalate/poly(butylene terephthalate) (PEGT/PBT) multiblock copolymer was investigated as a possible matrix for controlled delivery of small water-soluble drugs. Two molecules were selected as sustained release candidates from microspheres: leuprorelin acetate (peptide of Mw = 1270 D) and vitamin B(12) (Mw = 1355 D). First, vitamin B(12)-loaded microspheres were prepared using a double emulsion method and preparation parameters were varied (surfactant in the first emulsion and copolymer composition). The resulting microsphere structure, entrapment efficiency and release rate were evaluated. Vitamin B(12)-loaded microsphere parameters could easily be tailored to achieve specific requirements. The addition of surfactant in the first preparation process led to a significant increase of the microsphere entrapment efficiency, whereas the decrease of the PEGT copolymer content allowed the release rates from microspheres to be precisely decreased. However, leuprorelin acetate-loaded microspheres did not show the same characteristics when prepared with the same parameters, possibly because of a high water solubility discrepancy between the vitamin B(12) and the peptide. This study shows the suitability of PEGT/PBT microspheres as a controlled release system for vitamin B(12), but not for leuprorelin acetate. It also underlines the necessity of tailored development for each individual drug and emphasizes the risk of using model molecules. Copyright 2002 Elsevier Science B.V.

  2. Tritium release from neutron irradiated beryllium pebbles

    Scaffidi-Argentina, F.; Werle, H. [Forschungszentrum Karlsruhe GmbH Technik und Umwelt (Germany). Inst. fuer Neutronenphysik und Reactortechnik


    One of the most important open issues related to beryllium for fusion applications refers to the kinetics of the tritium release as a function of neutron fluence and temperature. The EXOTIC-7 as well as the `Beryllium` experiments carried out in the HFR reactor in Petten are considered as the most detailed and significant tests for investigating the beryllium response under neutron irradiation. This paper reviews the present status of beryllium post-irradiation examinations performed at the Forschungszentrum Karlsruhe with samples from the above mentioned irradiation experiments, trying to elucidate the tritium release controlling processes. In agreement with previous studies it has been found that release starts at about 500-550degC and achieves a maximum at about 700-750degC. The observed release at about 500-550degC is probably due to tritium escaping from chemical traps, while the maximum release at about 700-750degC is due to tritium escaping from physical traps. The consequences of a direct contact between beryllium and ceramics during irradiation, causing tritium implanting in a surface layer of beryllium up to a depth of about 40 mm and leading to an additional inventory which is usually several times larger than the neutron-produced one, are also presented and the effects on the tritium release are discussed. (author)

  3. Effect of Food Emulsifiers on Aroma Release

    Jia-Jia Li


    Full Text Available This study aimed to determine the influence of different emulsifiers or xanthan-emulsifier systems on the release of aroma compounds. Solid-phase microextraction (SPME and GC-MS were used to study the effects of varying concentrations of xanthan gum, sucrose fatty acid ester, Tween 80 and soybean lecithin on the release of seven aroma compounds. The effects of the emulsifier systems supplemented with xanthan gum on aroma release were also studied in the same way. The results showed varying degrees of influence of sucrose fatty acid ester, soybean lecithin, Tween 80 and xanthan gum on the release of aroma compounds. Compared with other aroma compounds, ethyl acetate was more likely to be conserved in the solution system, while the amount of limonene released was the highest among these seven aroma compounds. In conclusion, different emulsifiers and complexes showed different surface properties that tend to interact with different aroma molecules. The present studies showed that the composition and structure of emulsifiers and specific interactions between emulsifiers and aroma molecules have significant effects on aroma release.

  4. Effect of Food Emulsifiers on Aroma Release.

    Li, Jia-Jia; Dong, Man; Liu, Yan-Long; Zhang, Lu-Lu; Zhang, Yan; Yang, Zi-Yu; Ren, Jing-Nan; Pan, Si-Yi; Fan, Gang


    This study aimed to determine the influence of different emulsifiers or xanthan-emulsifier systems on the release of aroma compounds. Solid-phase microextraction (SPME) and GC-MS were used to study the effects of varying concentrations of xanthan gum, sucrose fatty acid ester, Tween 80 and soybean lecithin on the release of seven aroma compounds. The effects of the emulsifier systems supplemented with xanthan gum on aroma release were also studied in the same way. The results showed varying degrees of influence of sucrose fatty acid ester, soybean lecithin, Tween 80 and xanthan gum on the release of aroma compounds. Compared with other aroma compounds, ethyl acetate was more likely to be conserved in the solution system, while the amount of limonene released was the highest among these seven aroma compounds. In conclusion, different emulsifiers and complexes showed different surface properties that tend to interact with different aroma molecules. The present studies showed that the composition and structure of emulsifiers and specific interactions between emulsifiers and aroma molecules have significant effects on aroma release.

  5. 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.

  6. Quantification of Kinetic Rate Law Parameters of Uranium Release from Sodium Autunite as a Function of Aqueous Bicarbonate Concentrations

    Gudavalli, Ravi; Katsenovich, Yelena; Wellman, Dawn M.; Lagos, Leonel; Tansel, Berrin


    ABSTRACT: Hydrogen carbonate is one of the most significant components within the uranium geochemical cycle. In aqueous solutions, hydrogen carbonate forms strong complexes with uranium. As such, aqueous bicarbonate may significantly increase the rate of uranium release from uranium minerals. Quantifying the relationship of aqueous hydrogen carbonate solutions to the rate of uranium release during dissolution is critical to understanding the long-term fate of uranium within the environment. Single-pass flow-through (SPTF) experiments were conducted to estimate the rate of uranium release from Na meta-autunite as a function of bicarbonate solutions (0.0005-0.003 M) under the pH range of 6-11 and temperatures of 5-60oC. Consistent with the results of previous investigation, the rate of uranium release from sodium autunite exhibited minimal dependency on temperature; but were strongly dependent on pH and increasing concentrations of bicarbonate solutions. Most notably at pH 7, the rate of uranium release exhibited 370 fold increases relative to the rate of uranium release in the absence of bicarbonate. However, the effect of increasing concentrations of bicarbonate solutions on the release of uranium was significantly less under higher pH conditions. It is postulated that at high pH values, surface sites are saturated with carbonate, thus the addition of more bicarbonate would have less effect on uranium release. Results indicate the activation energies were unaffected by temperature and bicarbonate concentration variations, but were strongly dependent on pH conditions. As pH increased from 6 to 11, activation energy values were observed to decrease from 29.94 kJ mol-1 to 13.07 kJ mol-1. The calculated activation energies suggest a surface controlled dissolution mechanism.

  7. Compression-Coated Tablet for Colon Targeting: Impact of Coating and Core Materials on Drug Release.

    Maity, Siddhartha; Sa, Biswanath


    This work was envisaged to develop compression-coated tablets using a blend of Ca(+2) ion cross-linked carboxymethyl xanthan gum (CMXG) and sodium alginate (SAL) for delayed release of immediate pulse release tablets of prednisolone (PDL) in the colon without the need of colonic bacterial intervention for degradation of the polysaccharide coat. The core tablets containing PDL and other compatible excipients were prepared by direct compression method and subsequently compression coated with different ratios of CMXG and SAL. Long T lag, the time required to restrict the drug release below 10%, and short T rap, the time required for immediate release following the T lag, were considered as suitable release parameters for evaluation of colon targeting of PDL tablets. Among the various compression coats, a blend of CMXG and SAL in a ratio of 1.5:3.5 provided T lag of 5.12 ± 0.09 h and T rap of 6.50 ± 0.05 h. The increase in microcrystalline cellulose (MCC) and crospovidone (CP) in the core tablets did not change T lag significantly although decreased the T rap marginally. Inclusion of an osmogen in the core tablets decreased the T lag to 4.05 ± 0.08 h and T rap to 3.56 ± 0.06 h. The increase in coat weight to 225 mg provided a reasonably long T lag (6.06 ± 0.09 h) and short T rap (4.36 ± 0.20 h). Drug release from most of the formulations followed the Hixson-Crowell equation and sigmoidal pattern as confirmed by the Weibull equation. In conclusion, tablets, compression coated with CMXG and SAL in a ratio of 1.5:3.5 and having 225-mg coat weight, were apparently found suitable for colon targeting.

  8. Obtaining the palygorskite:chitosan composite for modified release of 5-aminosalicylic acid.

    Santana, Ana Cristina Sousa Gramoza Vilarinho; Sobrinho, José Lamartine Soares; Silva Filho, Edson Cavalcanti da; Nunes, Livio Cesar Cunha


    This study's aim was to obtain composites from palygorskite (PLG) and chitosan (CS) in order to modify 5-aminosalicylic (5-ASA) release. Initially, the PLG:CS composite was obtained using glutaraldehyde (GLA) as a reticular agent. Then, PLG, CS and PLG:CS were characterized by means of analytical techniques such as CHN elemental analysis, surface area analysis, XRD, FTIR, DSC and TG, SEM, adsorption tests and release profiles. Based on analytical data, the formation of the PLG:CS composite which showed the presence about 19% of CS, decrease in specific surface area, morphological analysis modified, visible change of crystallinity, of FTIR and thermal analysis. In relation to the drug-composite interaction, PLG:CS exhibited a significant increase in adsorption with 5-ASA at 58.24% in relation to PLG and CS which were at 16.29% and 23.96% respectively. The release profiles show that the PLG:CS composite changed the 5-ASA release speed in analyzed simulated fluids (intestinal and stomach) unlike other systems. Thus, the PLG:CS composite with proven synergy of the PLG and CS inherent properties showing 5-ASA effective modified release. Hence, this composite has potential benefits for the vectorization of drugs. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. The impact of calcium current reversal on neurotransmitter release in the electrically stimulated retina

    Werginz, Paul; Rattay, Frank


    Objective. In spite of intense theoretical and experimental investigations on electrical nerve stimulation, the influence of reversed ion currents on network activity during extracellular stimulation has not been investigated so far. Approach. Here, the impact of calcium current reversal on neurotransmitter release during subretinal stimulation was analyzed with a computational multi-compartment model of a retinal bipolar cell (BC) that was coupled with a four-pool model for the exocytosis from its ribbon synapses. Emphasis was laid on calcium channel dynamics and how these channels influence synaptic release. Main results. Stronger stimulation with anodic pulses caused transmembrane voltages above the Nernst potential of calcium in the terminals and, by this means, forced calcium ions to flow in the reversed direction from inside to the outside of the cell. Consequently, intracellular calcium concentration decreased resulting in a reduced vesicle release or preventing release at all. This mechanism is expected to lead to a pronounced ring-shaped pattern of exocytosis within a group of neighbored BCs when the stronger stimulated cells close to the electrode fail in releasing vesicles. Significance. Stronger subretinal stimulation causes failure of synaptic exocytosis due to reversal of calcium flow into the extracellular space in cells close to the electrode.

  10. Intercalation of urea into kaolinite for preparation of controlled release fertilizer

    Mahdavi Fariba


    Full Text Available In this study urea was intercalated between layers of kaolinite by dry grinding technique to be used for preparing controlled release fertilizer. X-ray powder diffraction (XRPD patterns confirmed the intercalation of urea into kaolinite by the significant expansion of the basal spacing of kaolinite layers from 0.710 nm to 1.090 nm. Fourier transform infrared spectroscopy (FT-IR also confirmed the hydrogen bonding between urea and kaolinite. Based on CHNS elemental analysis, 20% (wt. urea was intercalated between kaolinite layers. The urea-intercalated kaolinite was mixed with hydroxypropyl methylcellulose (HPMC binder and was granulated to prepare the nitrogen-based controlled release fertilizer. To study the nitrogen release behavior of granules, ultraviolet/visible (UV-Vis spectroscopy was used through the diacetyl monoxime (DAM colorimetric method. The result of UV-Vis spectroscopy showed that intercalation of urea into kaolinite decreased the nitrogen release from 25.50 to 13.66 % after 24 hours and from 98.15 to 70.01% after 30 days incubation in water. According to the results, the prepared controlled release fertilizer (CRF behaved according to the standard for CRFs.

  11. Benzydamine hydrochloride buccal bioadhesive gels designed for oral ulcers: preparation, rheological, textural, mucoadhesive and release properties.

    Karavana, Sinem Yaprak; Güneri, Pelin; Ertan, Gökhan


    This study developed and examined the characterization of Benzidamine hydrochloride (BNZ) bioadhesive gels as platforms for oral ulcer treatments. Bioadhesive gels were prepared with four different hydroxypropylmethylcellulose (HPMC) types (E5, E15, E50 and K100M) with different ratios. Each formulation was characterized in terms of drug release, rheological, mechanical properties and adhesion to a buccal bovine mucosa. Drug release was significantly decreased as the concentration and individual viscosity of each polymeric component increased due to improved viscosity of the gel formulations. The amount of drug released for the formulations ranged from 0.76 +/- 0.07 and 1.14 +/- 0.01 (mg/cm2 +/- SD). Formulations exhibited pseudoplastic flow and all formulations, increasing the concentration of HPMC content significantly raised storage modulus (G'), loss modulus (G''), dynamic viscosity (eta') at 37 degrees C. Increasing concentration of each polymeric component also significantly improved the hardness, compressibility, adhesiveness, cohesiveness and mucoadhesion but decreased the elasticity of the gel formulations. All formulations showed non-Fickian diffusion due to the relaxation and swelling of the polymers with water. In conclusion, the formulations studied showed a wide range of mechanical and drug diffusion characteristics. On the basis of the obtained data, the bioadhesive gel formulation which was prepared with 2.5% HPMC K 100M was determined as the most appropriate formulation for buccal application in means of possessing suitable mechanical properties, exhibiting high cohesion and bioadhesion.

  12. Determination of rheological property and its effect on key aroma release of Shanxi aged vinegar.

    Zhu, Hong; Qiu, Ju; Li, Zaigui


    The rheological property of Shanxi aged vinegar (SAV) was determined by rheometer, and its effects on release in eight key aroma components of SAV was investigated by SPME-GC-MS. In order to simulate the change of rheological property of SAV, a modified SAV system was developed from a finished SAV using carboxymethylcellulose, pectin, glucose, fructose, sodium chloride and tannic acid at indicate levels. The consistency coefficients (K) of SAV ranged from 1.09e(-5) to 0.0137, which was correlated to glucose, polyphenol, acids and (o)Bx. SAV changed from shear-thickening to Newtonian fluid during long-time ageing. In the modified SAV system, the K values increased significantly, and two modified vinegar became quasi-Newtonian fluids too. Furthermore, release of the eight key aroma compounds decreased significantly and decreased was pronounced, for acetic acid, furfural and tetramethylpyrazine. The results demonstrated rheological property correlated to the concentrate of sugar, salt, polyphenol, acids and macromolecule, which significantly affected the release of major aroma compounds.

  13. 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...

  14. 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.

  15. Age-related changes in the dynamics of potassium-evoked L-glutamate release in the striatum of Fischer 344 rats.

    Nickell, J; Pomerleau, F; Allen, J; Gerhardt, G A


    In the present studies we used a multisite ceramic-based microelectrode for rapid (800 ms) and low level measures of L-glutamate in vivo. We measured the amplitude and clearance rate of phasic changes in L-glutamate release produced by local application of potassium by a micropipette placed adjacent to the recording sites in the striatum of young (6 month), late middle aged (18 month) and aged (24 month) Fischer 344 rats. Our results showed that the amplitudes and clearance rates of potassium-evoked release of L-glutamate in the striatum were significantly decreased in aged rats as compared to the other age groups. In addition, the sensitivity of glutamate fibers to depolarization with potassium was significantly decreased in the aged rats as compared to young animals. Taken together, these data are consistent with age-related alterations in glutamate release dynamics, which may involve a compensatory mechanism for maintaining static glutamate concentrations within the striatum.

  16. 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.

  17. Precision Departure Release Capability (PDRC) Technology Description

    Engelland, Shawn A.; Capps, Richard; Day, Kevin; Robinson, Corissia; Null, Jody R.


    After takeoff, aircraft must merge into en route (Center) airspace traffic flows which may be subject to constraints that create localized demand-capacity imbalances. When demand exceeds capacity, Traffic Management Coordinators (TMCs) often use tactical departure scheduling to manage the flow of departures into the constrained Center traffic flow. Tactical departure scheduling usually involves use of a Call for Release (CFR) procedure wherein the Tower must call the Center TMC to coordinate a release time prior to allowing the flight to depart. In present-day operations release times are computed by the Center Traffic Management Advisor (TMA) decision support tool based upon manual estimates of aircraft ready time verbally communicated from the Tower to the Center. The TMA-computed release is verbally communicated from the Center back to the Tower where it is relayed to the Local controller as a release window that is typically three minutes wide. The Local controller will manage the departure to meet the coordinated release time window. Manual ready time prediction and verbal release time coordination are labor intensive and prone to inaccuracy. Also, use of release time windows adds uncertainty to the tactical departure process. Analysis of more than one million flights from January 2011 indicates that a significant number of tactically scheduled aircraft missed their en route slot due to ready time prediction uncertainty. Uncertainty in ready time estimates may result in missed opportunities to merge into constrained en route flows and lead to lost throughput. Next Generation Air Transportation System (NextGen) plans call for development of Tower automation systems capable of computing surface trajectory-based ready time estimates. NASA has developed the Precision Departure Release Capability (PDRC) concept that uses this technology to improve tactical departure scheduling by automatically communicating surface trajectory-based ready time predictions to the

  18. Precision Departure Release Capability (PDRC) Final Report

    Engelland, Shawn A.; Capps, Richard; Day, Kevin Brian; Kistler, Matthew Stephen; Gaither, Frank; Juro, Greg


    After takeoff, aircraft must merge into en route (Center) airspace traffic flows that may be subject to constraints that create localized demand/capacity imbalances. When demand exceeds capacity, Traffic Management Coordinators (TMCs) and Frontline Managers (FLMs) often use tactical departure scheduling to manage the flow of departures into the constrained Center traffic flow. Tactical departure scheduling usually involves a Call for Release (CFR) procedure wherein the Tower must call the Center to coordinate a release time prior to allowing the flight to depart. In present-day operations release times are computed by the Center Traffic Management Advisor (TMA) decision support tool, based upon manual estimates of aircraft ready time verbally communicated from the Tower to the Center. The TMA-computed release time is verbally communicated from the Center back to the Tower where it is relayed to the Local controller as a release window that is typically three minutes wide. The Local controller will manage the departure to meet the coordinated release time window. Manual ready time prediction and verbal release time coordination are labor intensive and prone to inaccuracy. Also, use of release time windows adds uncertainty to the tactical departure process. Analysis of more than one million flights from January 2011 indicates that a significant number of tactically scheduled aircraft missed their en route slot due to ready time prediction uncertainty. Uncertainty in ready time estimates may result in missed opportunities to merge into constrained en route flows and lead to lost throughput. Next Generation Air Transportation System plans call for development of Tower automation systems capable of computing surface trajectory-based ready time estimates. NASA has developed the Precision Departure Release Capability (PDRC) concept that improves tactical departure scheduling by automatically communicating surface trajectory-based ready time predictions and departure

  19. Forbush Decrease: A New Perspective with Classification

    Raghav, Anil; Shaikh, Zubair; Bhaskar, Ankush; Datar, Gauri; Vichare, Geeta


    Sudden short-duration decreases in cosmic ray flux, known as Forbush decreases (FDs), are mainly caused by interplanetary disturbances. A generally accepted view is that the first step of an FD is caused by a shock sheath and the second step is due to the magnetic cloud (MC) of the interplanetary coronal mass ejection (ICME). This simplistic picture does not consider several physical aspects, such as whether the complete shock sheath or MC (or only part of these) contributes to the decrease or the effect of internal structure within the shock-sheath region or MC. We present an analysis of 16 large ({≥} 8 %) FD events and the associated ICMEs, a majority of which show multiple steps in the FD profile. We propose a reclassification of FD events according to the number of steps observed in their respective profiles and according to the physical origin of these steps. This study determines that 13 out of 16 major events ({˜} 81%) can be explained completely or partially on the basis of the classic FD model. However, it cannot explain all the steps observed in these events. Our analysis clearly indicates that not only broad regions (shock sheath and MC), but also localized structures within the shock sheath and MC have a significant role in influencing the FD profile. The detailed analysis in the present work is expected to contribute toward a better understanding of the relationship between FD and ICME parameters.

  20. Masoprocol decreases rat lipolytic activity by decreasing the phosphorylation of HSL.

    Gowri, M S; Azhar, R K; Kraemer, F B; Reaven, G M; Azhar, S


    Masoprocol (nordihydroguaiaretic acid), a lipoxygenase inhibitor isolated from the creosote bush, has been shown to decrease adipose tissue lipolytic activity both in vivo and in vitro. The present study was initiated to test the hypothesis that the decrease in lipolytic activity by masoprocol resulted from modulation of adipose tissue hormone-sensitive lipase (HSL) activity. The results indicate that oral administration of masoprocol to rats with fructose-induced hypertriglyceridemia significantly decreased their serum free fatty acid (FFA; P HSL activity were significantly lower (P HSL protein. Incubation of masoprocol with adipocytes from chow-fed rats significantly inhibited isoproterenol-induced lipolytic activity and HSL activity, associated with a decrease in the ability of isoproterenol to phosphorylate HSL. Masoprocol had no apparent effect on adipose tissue phosphatidylinositol 3-kinase activity, but okadaic acid, a serine/threonine phosphatase inhibitor, blocked the antilipolytic effect of masoprocol. The results of these in vitro and in vivo experiments suggest that the antilipolytic activity of masoprocol is secondary to its ability to inhibit HSL phosphorylation, possibly by increasing phosphatase activity. As a consequence, masoprocol administration results in lower serum FFA and TG concentrations in hypertriglyceridemic rodents.

  1. 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

  2. Neurotensin Decreases the Proinflammatory Status of Human Skin Fibroblasts and Increases Epidermal Growth Factor Expression

    Lucília Pereira da Silva


    Full Text Available Fibroblasts colonization into injured areas during wound healing (WH is responsible for skin remodelling and is also involved in the modulation of inflammation, as fibroblasts are immunologically active. Herein, we aimed to determine neurotensin effect on the immunomodulatory profile of fibroblasts, both in homeostatic and inflammatory conditions. Neurotensin mediated responses occurred through NTR1 or NTR3 receptors, while under inflammatory conditions NTR1 expression increase seemed to modulate neurotensin responses. Among different immunomodulatory genes, CCL11, IL-8, and IL-6 were the most expressed genes, while CCL4 and EGF were the less expressed genes. After neurotensin exposure, IL-8 mRNA expression was increased while CCL11 was decreased, suggesting a proinflammatory upregulation and chemoattractant ability downregulation of fibroblasts. Under inflammatory conditions, gene expression was significantly increased. After neurotensin exposure, CCL4 and IL-6 mRNA expression were decreased while CCL11 was increased, suggesting again a decrease in the chemoattractant capacity of fibroblasts and in their proinflammatory status. Furthermore, the expression of EGF, a crucial growth factor for skin cells proliferation and WH, was increased in all conditions. Overall, neurotensin, released by nerve fibers or skin cells, may be involved in the decrease of the chemotaxis and the proinflammatory status in the proliferation and remodelling phases of WH.

  3. Inhibition by drugs of passive cutaneous anaphylaxis-induced skin histamine decrease.



    Full Text Available Passive cutaneous anaphylaxis (PCA was produced in the rat with mouse IgE-rich antiserum. The effect of drugs on the PCA-induced skin histamine decrease and leakage of protein-bound dye was studied. Salbutamol (0.5 mg/kg i.v. or 1.0 mg/kg s.c. and cromoglycate (10 mg/kg i.v. significantly inhibited the skin histamine decrease. A combination of salbutamol (0.5 mg/kg i.v. or 1.0 mg/kg s.c. and aminophylline (25 mg/kg i.v. or 75 mg/kg s.c. had an additive or greater than additive effect on the histamine decrease. Salbutamol (1.0 mg/kg s.c. inhibited the dye leakage markedly, and aminophylline (75 mg/kg s.c. slightly. These results indicate that the decrease in the skin histamine content is useful as an index of the in vivo inhibitory effect of antiallergic drugs on the antigen-induced histamine release.

  4. Regulatory analysis on criteria for the release of patients administered radioactive material

    Schneider, S.; McGuire, S.A. [Nuclear Regulatory Commission, Washington, DC (United States). Div. of Regulatory Applications; Behling, U.H.; Behling, K.; Goldin, D. [Cohen (S.) and Associates, Inc., McLean, VA (United States)


    The Nuclear Regulatory Commission (NRC) has received two petitions to amend its regulations in 10 CFR Parts 20 and 35 as they apply to doses received by members of the public exposed to patients released from a hospital after they have been administered radioactive material. While the two petitions are not identical they both request that the NRC establish a dose limit of 5 millisieverts (0.5 rem) per year for individuals exposed to patients who have been administered radioactive materials. This Regulatory Analysis evaluates three alternatives. Alternative 1 is for the NRC to amend its patient release criteria in 10 CFR 35.75 to use the more stringent dose limit of 1 millisievert per year in 10 CFR 20.1301(a) for its patient release criteria. Alternative 2 is for the NRC to continue using the existing patient release criteria in 10 CFR 35.75 of 1,110 megabecquerels of activity or a dose rate at one meter from the patient of 0.05 millisievert per hour. Alternative 3 is for the NRC to amend the patient release criteria in 10 CFR 35.75 to specify a dose limit of 5 millisieverts for patient release. The evaluation indicates that Alternative 1 would cause a prohibitively large increase in the national health care cost from retaining patients in a hospital longer and would cause significant personal and psychological costs to patients and their families. The choice of Alternatives 2 or 3 would affect only thyroid cancer patients treated with iodine-131. For those patients, Alternative 3 would result in less hospitalization than Alternative 2. Alternative 3 has a potential decrease in national health care cost of $30,000,000 per year but would increase the potential collective dose from released therapy patients by about 2,700 person-rem per year, mainly to family members.

  5. Effects of experimental releases of oil and dispersed oil on Arctic nearshore macrobenthos. 1. Infauna

    Cross, W.E.; Thomson, D.H.


    An experimental subsurface release of chemically dispersed oil at Cape Hatt, northern Baffin Island, resulted in short-term, relatively high oil concentrations in the waters of two adjacent bays, whereas untreated oil released onto the surface of a third bay could not be detected in the water below a depth of 1 m. Observations revealed no apparent short-term effects of untreated oil on shallow water infauna, whereas market acute effects on infauna, including emergence from the substrate and narcosis, were apparent in the dipsersed oil bays within 24 h of the release. Analysis of systematic samples at depths of 3 and 7 m showed that most affected animals recovered. Neither type of oil release caused any large-scale mortality of benthic infauna. Multivariate analyses showed no significant change in infaunal community structure, and effects attributable to oil were found in only 3 of 72 univariate analyses of density, biomass or size data for individual taxa. A progressive decrease in the condition of the filter-feeding bivalve Serripes groenlandicus in the reference bay was apparently the result of exposure to dilute dispersed oil for several days. A similar effect on condition in the surface deposit-feeding bivalve Mocoma calcarea was apparently caused by relatively low oil concentrations in the sediments of the dispersed and surface oil release bays. There were no apparent effects on recruitment in bivalve species with plantonic larvae, but density changes in the polychaete Spio indicated that oil in the sediments of the surface oil release and dispersed oil release bays affected reproductive processes. Effects on the condition of the bivalves were still evident two years post-spill in 1983, the last year of sampling. 75 refs., 7 figs., 7 tabs.

  6. Development and evaluation of Ketoprofen sustained release matrix tablet using Hibiscus rosa-sinensis leaves mucilage

    M. Kaleemullah


    Full Text Available Currently, the use of natural gums and mucilage is of increasing importance in pharmaceutical formulations as valuable drug excipient. Natural plant-based materials are economic, free of side effects, biocompatible and biodegradable. Therefore, Ketoprofen matrix tablets were formulated by employing Hibiscus rosa-sinensis leaves mucilage as natural polymer and HPMC (K100M as a synthetic polymer to sustain the drug release from matrix system. Direct compression method was used to develop sustained released matrix tablets. The formulated matrix tablets were evaluated in terms of physical appearance, weight variation, thickness, diameter, hardness, friability and in vitro drug release. The difference between the natural and synthetic polymers was investigated concurrently. Matrix tablets developed from each formulation passed all standard physical evaluation tests. The dissolution studies of formulated tablets revealed sustained drug release up to 24 h compared to the reference drug Apo Keto® SR tablets. The dissolution data later were fitted into kinetic models such as zero order equation, first order equation, Higuchi equation, Hixson Crowell equation and Korsmeyer-Peppas equation to study the release of drugs from each formulation. The best formulations were selected based on the similarity factor (f2 value of 50% and more. Through the research, it is found that by increasing the polymers concentration, the rate of drug release decreased for both natural and synthetic polymers. The best formulation was found to be F3 which contained 40% Hibiscus rosa-sinensis mucilage polymer and showed comparable dissolution profile to the reference drug with f2 value of 78.03%. The release kinetics of this formulation has shown to follow non-Fickian type which involved both diffusion and erosion mechanism. Additionally, the statistical results indicated that there was no significant difference (p > 0.05 between the F3 and reference drug in terms of MDT and


    S. R. Mettu


    Full Text Available The objective of this work was to study the effect of concentration and viscosity grade of HPMC, different diluents and inclusion of solid dispersions on the matrix tablets of aceclofenac. In present study, aceclofenac, a novel NSAID used for symptomatic treatment of pain and inflammation was formulated into matrix tablets with HPMC of two different viscosity grades (E50 LV and K15 M by direct compression method. Before compression the formulations were evaluated for angle of repose, % compressibility and Hausner’s ratio. Tablets were evaluated for hardness, friability, weight variation, uniformity of thickness and diameter, and drug content. All pre-compressional and post-compressional parameters were found within the official limits. In vitro drug release studies were conducted for a period of 8 hrs using USP paddle method (II at 37±0.5oC and at 75rpm speed in pH 7.2 phosphate buffer. Type of polymer and its concentration has influenced the drug release from matrix tablets. With increasing concentrations and increasing polymer viscosity the release rate decreased. Release rate increased with the addition of PEG and PVP. There was significant increase in drug release by inclusion of solid dispersions in the matrix tablets. It can be concluded that by incorporating water soluble excipients such as PEG and PVP and solid dispersions of drug with PVP into the matrix, drug release can be increased. Dissolution data was analysed by Power law expression, Mt / M¥ = ktn. Release of drug from the tablets varied on the basis of formulation and was found to be non-Fickian and case II transport with different formulations.

  8. HDT-1, a new synthetic compound, inhibits glutamate release in rat cerebral cortex nerve terminals (synaptosomes)

    Su-jane WANG; Shiu-huey CHOU; Yuh-chi KUO; Shang-shing Peter CHOU; Woan-fang TZENG; Jxh-yih LEU; Rwei-fen S HUANG; Yih-fong LIEW


    Aim: Excessive glutamate release has been proposed to be involved in the pathogenesis of several neurological diseases. In this study, we investigated the effect of HDT-1 (3, 4, 4a, 5, 8, 8a-hexahydro-6,7-dimethyl-4a-(phenyisulfonyl)-2-tosylisoquinolin-1(2H)-one), a novel synthetic compound, on glutamate release in rat cerebrocortical nerve terminals and explored the possible mechanism. Methods: The release of glutamate was evoked by the K+ channel blocker 4-aminopyridine (4-AP) or the high external [K+] and measured by one-line enzyme-coupled fluorometric assay. We also determined the loci at which HDT-1 impinges on cerebrocortical nerve terminals by using membrane potential-sensitive dye to assay nerve terminal excitability and depolarization, and Ca2+ indicator Fura-2 to monitor Ca2+ influx. Results: HDT-1 inhibited the release of glutamate evoked by 4-AP and KCI in a concentration-dependent manner. HDT-1 did not alter the resting synaptosomal membrane potential or 4-AP-evoked depolarization. Examination of the effect of HDT-1 on cytosolic [Ca2+] revealed that the diminution of glutamate release could be attributed to reduction in voltage-dependent Ca2+ influx. Consistent with this, the HDT-1-mediated inhibition of glutamate release was significantly prevented in synaptosomes pretreated with the N- and P/Q-type Ca2+ channel blocker ω-conotoxin MVIIC. Conclusion: In rat cerebrocortical nerve terminals, HDT-1 inhibits glutamate release through a reduction of voltage-dependent Ca2+ channel activity and subsequent decrease of Ca2+ influx into nerve terminals, rather than any upstream effect on nerve terminal excitability.

  9. 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.

  10. 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

  11. Decreased range of motion following arthroscopic remplissage.

    Deutsch, Allen A; Kroll, Derek G


    The Hill-Sachs lesion is an impression fracture of the posterolateral margin of the humeral head that commonly results from impaction with the anterior glenoid rim during subluxation or dislocation of the shoulder. This bony defect has been implicated as an etiology of recurrent instability of the shoulder. The "remplissage" technique described by Wolf is an arthroscopic method of filling the Hill-Sachs defect via infraspinatus tenodesis and posterior capsulodesis. The purpose of this technique is to prevent recurrent instability by making the Hill-Sachs lesion extra-articular thereby eliminating engagement of the defect with the anterior glenoid rim. In addition, the infraspinatus tenodesis acts as a checkrein by preventing anterior translation of the humeral head. We report a complication of this recently described technique. A 28-year-old man who failed conservative management underwent an arthroscopic Bankart repair with a concomitant remplissage procedure. Two years postoperatively, the patient continued to struggle with the loss of external rotation. Conservative management with physical therapy and range of motion exercises failed. The patient was treated with an arthroscopic release of the tenodesed infraspinatus, which improved external rotation by 202 in circle intraoperatively. At 6 months postoperatively, the patient has maintained a significant increase external rotation. We hypothesize that the loss in external rotation occurred as a result of the tenodesis of the infraspinatus and posterior capsule into the Hill-Sachs defect. The tenodesed cuff and capsular tissue acted as a mechanical block to external rotation of the shoulder.

  12. Effects of free oxygen radicals on Ca2+ release mechanisms in the sarcoplasmic reticulum of scallop (Pecten jacobaeus) adductor muscle.

    Burlando, B; Viarengo, A; Pertica, M; Ponzano, E; Orunesu, M


    In vitro oxyradical effects on SR Ca2+ regulation were studied by using a SR-containing cell-free preparation from scallop (Pecten jacobaeus) adductor muscle. Ca2+ variations were fluorimetrically detected after incubation with Fluo-3 in the presence of ATP. Exposure to Fe3+/ascorbate produced dose-dependent Ca2+ release from SR vesicles, eventually leading to massive Ca2+ loss. Exposure to hypoxanthine/xanthine oxidase also caused Ca2+ release but at a much slower rate. Pre-incubations with catalase or with the hydroxyl radical scavenger KMBA led to a significant decrease in the Fe3+/ascorbate-induced Ca2+ release rate and to a delay of massive Ca2+ loss. Pre-incubations with GSH or DTT strongly reduced the Ca2+ release caused by Fe3+/ascorbate and, moreover, they prevented massive Ca2+ loss from SR vesicles. Addition of GSH or DTT after Fe3+/ascorbate promptly reduced the Ca2+ release rate and delayed massive Ca2+ release. Pre-incubation with the SR Ca2+ channel blocker ruthenium red strongly reduced the Ca2+ release caused by Fe3+/ascorbate, and also prevented massive Ca2+ loss. In the presence of ruthenium red, Fe3+/ascorbate treatments followed by Ca2+ addition revealed that Ca2+ uptake inhibition was slower than Ca2+ release. Taken together, data showed that free radicals and, in particular, hydroxyl radicals, affected the scallop SR Ca2+ regulation. This mainly occurred through Ca2+ channel opening, most likely triggered by sulfhydryl oxidation, which eventually led to massive Ca2+ release from SR vesicles. The demonstration of a specific effect of oxyradicals on SR Ca2+ channels is in line with their possible involvement in cell signaling.

  13. Levonorgestrel-releasing intrauterine system use in premenopausal women with symptomatic uterine leiomyoma: a systematic review.

    Jiang, Wenxiao; Shen, Qi; Chen, Miaomiao; Wang, Ying; Zhou, Qingfeng; Zhu, Xuejie; Zhu, Xueqiong


    A systematic review is done to determine the efficacy and safety of levonorgestrel-releasing intrauterine systems as a treatment using in premenopausal women with symptomatic uterine leiomyoma. We searched the Medline, Central and ICTRP databases for all articles published from inception through July 2013 that examined the following outcomes: uterine volume, uterine leiomyoma volume, endometrial thickness, then menstrual blood loss, blood haemoglobin, ferritin and hematocrit levels, treatment failure rate, device expulsion rate, hysterectomy rate and side effects. From 645 studies, a total of 11 studies met our inclusion criteria with sample sizes ranging from 10 to 104. Evidence suggested that levonorgestrel-releasing intrauterine systems could decrease uterine volume and endometrial thickness, significantly reduce menstrual blood loss, and increase blood haemoglobin, ferritin and hematocrit levels. There was no evidence for decreasing uterine leiomyoma volume. There were no adverse effects on the ovarian function except for ovarian cysts. Device expulsion rates were low, which associated with leiomyoma size (larger than 3cm) but not with leiomyoma location. Irregular bleeding/spotting was observed at the beginning of the follow-up period and then decreased progressively. Results of this systematic review indicate that levonorgestrel-releasing intrauterine systems may be effective and safe treatment for symptomatic uterine leiomyoma in premenopausal women.

  14. Metal release rate from AISI 316L stainless steel and pure Fe, Cr and Ni into a synthetic biological medium--a comparison.

    Herting, G; Wallinder, I Odnevall; Leygraf, C


    Metal release rates from stainless steel grade 316L were investigated in artificial lysosomal fluid (ALF), simulating a human inflammatory cell response. The main focus was placed on release rates of main alloying elements using graphite furnace atomic absorption spectroscopy, and changes in surface oxide composition by means of X-ray photoelectron spectroscopy. To emphasise that alloys and pure metals possess totally different intrinsic properties, comparative studies were performed on the pure alloying constituents: iron, nickel and chromium. Significant differences in release rates were observed due to the presence of a passive surface film on stainless steel. Iron and nickel were released at rates more than 300 times lower from the 316L alloy compared with the pure metals whereas the release rate of chromium was similar. Iron was preferentially released compared with nickel and chromium. Immersion in ALF resulted in the gradual enrichment of chromium in the surface film, a small increase of nickel, and the reduction of oxidized iron with decreasing release rates of alloy constituents as a result. As expected, released metals from stainless steel grade 316L were neither in proportion to the bulk alloy composition nor to the surface film composition.

  15. Frequency-Dependent Modulation of Dopamine Release by Nicotine and Dopamine D1 Receptor Ligands: An In Vitro Fast Cyclic Voltammetry Study in Rat Striatum.

    Goutier, W; Lowry, J P; McCreary, A C; O'Connor, J J


    Nicotine is a highly addictive drug and exerts this effect partially through the modulation of dopamine release and increasing extracellular dopamine in regions such as the brain reward systems. Nicotine acts in these regions on nicotinic acetylcholine receptors. The effect of nicotine on the frequency dependent modulation of dopamine release is well established and the purpose of this study was to investigate whether dopamine D1 receptor (D1R) ligands have an influence on this. Using fast cyclic voltammetry and rat corticostriatal slices, we show that D1R ligands are able to modulate the effect of nicotine on dopamine release. Nicotine (500 nM) induced a decrease in dopamine efflux at low frequency (single pulse or five pulses at 10 Hz) and an increase at high frequency (100 Hz) electrical field stimulation. The D1R agonist SKF-38393, whilst having no effect on dopamine release on its own or on the effect of nicotine upon multiple pulse evoked dopamine release, did significantly prevent and reverse the effect of nicotine on single pulse dopamine release. Interestingly similar results were obtained with the D1R antagonist SCH-23390. In this study we have demonstrated that the modulation of dopamine release by nicotine can be altered by D1R ligands, but only when evoked by single pulse stimulation, and are likely working via cholinergic interneuron driven dopamine release.

  16. Composite poly(vinyl alcohol/poly(vinyl acetate electrospun nanofibrous mats as a novel wound dressing matrix for controlled release of drugs

    Jannesari M


    Full Text Available Marziyeh Jannesari1, Jaleh Varshosaz2, Mohammad Morshed1, Maedeh Zamani11Department of Textile Engineering, Isfahan University of Technology, Isfahan, Iran; 2Department of Pharmaceutics, School of Pharmacy and Pharmaceutical Sciences Research Center, Isfahan University of Medical Sciences, Isfahan, IranAbstract: The aim of this study was to develop novel biomedicated nanofiber electrospun mats for controlled drug release, especially drug release directly to an injury site to accelerate wound healing. Nanofibers of poly(vinyl alcohol (PVA, poly(vinyl acetate (PVAc, and a 50:50 composite blend, loaded with ciprofloxacin HCl (CipHCl, were successfully prepared by an electrospinning technique for the first time. The morphology and average diameter of the electrospun nanofibers were investigated by scanning electron microscopy. X-ray diffraction studies indicated an amorphous distribution of the drug inside the nanofiber blend. Introducing the drug into polymeric solutions significantly decreased solution viscosities as well as nanofiber diameter. In vitro drug release evaluations showed that both the kind of polymer and the amount of drug loaded greatly affected the degree of swelling, weight loss, and initial burst and rate of drug release. Blending PVA and PVAc exhibited a useful and convenient method for electrospinning in order to control the rate and period of drug release in wound healing applications. Also, the thickness of the blend nanofiber mats strongly influenced the initial release and rate of drug release.Keywords: biodegradable polymers, drug delivery, controlled release, electrospun nanofibers, wound dressing

  17. Changes in Therapeutic Intensity Level Following Airway Pressure Release Ventilation in Severe Traumatic Brain Injury.

    Fletcher, Jeffrey J; Wilson, Thomas J; Rajajee, Venkatakrishna; Davidson, Scott B; Walsh, Jon C


    Airway pressure release ventilation (APRV) utilizes high levels of airway pressure coupled with brief expiratory release to facilitate open lung ventilation. The aim of our study was to evaluate the effects of APRV-induced elevated airway pressure mean in patients with severe traumatic brain injury. This was a retrospective cohort study at a 424-bed Level I trauma center. Linear mixed effects models were developed to assess the difference in therapeutic intensity level (TIL), intracranial pressure (ICP), and cerebral perfusion pressure (CPP) over time following the application of APRV. The study included 21 epochs of APRV in 21 patients. In the 6-hour epoch following the application of APRV, the TIL was significantly increased (P = .002) and the ICP significantly decreased (P = .041) compared to that before 6 hours. There was no significant change in CPP (P = .42) over time. The baseline static compliance and time interaction was not significant for TIL (χ(2) = 0.2 [df 1], P = .655), CPP (χ(2) = 0 [df 1], P = 1), or ICP (χ(2) = 0.1 [df 1], P = .752). Application of APRV in patients with severe traumatic brain injury was associated with significantly, but not clinically meaningful, increased TIL and decreased ICP. No significant change in CPP was observed. No difference was observed based on the baseline pulmonary static compliance. © The Author(s) 2016.

  18. [Effects of Organic and Inorganic Slow-Release Compound Fertilizer on Different Soils Microbial Community Structure].

    Wang, Fei; Yuan, Ting; Gu, Shou-kuan; Wang, Zheng-yin


    As a new style fertilizer, slow-control release fertilizer had been an important subject in recent years, but few researches were about soil microbial community structure diversity. Phospholipid fatty acid method was used to determined the microbial community structure diversity of acid soil and slight alkaline soil applied with slow-release compound fertilizer (SRF), chemical fertilizer (CF) and common compound fertilizer (CCF) at the 10th, 30th, 60th and 90th day under the constant temperature incubation condition. Results indicated that various bacteria (i. e 13:0, i14:0,14:0, i15:0, a15:0, i16:0, 16:12OH, 16:1w5c,16:0, i17:0, a17:0, cy17:0, 17:02OH, i18:0, 18:0 and cy19:0w8c), two actinomycetes (10Me17:0 and 10Me18:0) and only one fungus (18:1 w9c) were detected in two soils after applying slow-release compound fertilizer and other fertilizers during the whole incubation period. SRF could significantly increase the fungi PLFA content by 8.3% and 6.8% at the early stage (the 10th day and 30th day) compared with CF, as well as significantly increase by 22.7% and 17.1% at the late stage (the 60th day and 90th day) compared with CCF in acid soil. SRF significantly increased bacteria, fungi and gram positive bacteria compared with CF and CCF in incubation period (except at the 30th day) in slight alkaline soil. SRF could significantly improve the ratio of normal saturated fatty acid and monounsaturated fatty acid at the 30th day and 90th days in acid soil compared with no fertilizer (CK), CF and CCF, while as to slight alkaline soil, SRF was significantly greater than that of CK, CF and CCF only at the 60th day. SRF could significantly decrease the ratio of iso PLFA and anteiso PLFA in acid soil (in 30-90 days) and slight alkaline soil (in 10-60 days). For two soils PLFA varieties, contents and ratios of microbial community, slow-release compound fertilizer increased soil microbial PLFA varieties and contents, and decreased the influence to microbial survival

  19. Reduction of relative centrifugal forces increases growth factor release within solid platelet-rich-fibrin (PRF)-based matrices: a proof of concept of LSCC (low speed centrifugation concept).

    El Bagdadi, K; Kubesch, A; Yu, X; Al-Maawi, S; Orlowska, A; Dias, A; Booms, P; Dohle, E; Sader, R; Kirkpatrick, C J; Choukroun, J; Ghanaati, S


    Purpose The present study evaluated the platelet distribution pattern and growth factor release (VEGF, TGF-β1 and EGF) within three PRF (platelet-rich-fibrin) matrices (PRF, A-PRF and A-PRF+) that were prepared using different relative centrifugation forces (RCF) and centrifugation times. Materials and methods immunohistochemistry was conducted to assess the platelet distribution pattern within three PRF matrices. The growth factor release was measured over 10 days using ELISA. Results The VEGF protein content showed the highest release on day 7; A-PRF+ showed a significantly higher rate than A-PRF and PRF. The accumulated release on day 10 was significantly higher in A-PRF+ compared with A-PRF and PRF. TGF-β1 release in A-PRF and A-PRF+ showed significantly higher values on days 7 and 10 compared with PRF. EGF release revealed a maximum at 24 h in all groups. Toward the end of the study, A-PRF+ demonstrated significantly higher EGF release than PRF. The accumulated growth factor releases of TGF-β1 and EGF on day 10 were significantly higher in A-PRF+ and A-PRF than in PRF. Moreover, platelets were located homogenously throughout the matrix in the A-PRF and A-PRF+ groups, whereas platelets in PRF were primarily observed within the lower portion. ​Discussion the present results show an increase growthfactor release by decreased RCF. However, further studies must be conducted to examine the extent to which enhancing the amount and the rate of released growth factors influence wound healing and biomaterial-based tissue regeneration. ​Conclusion These outcomes accentuate the fact that with a reduction of RCF according to the previously LSCC (described low speed centrifugation concept), growth factor release can be increased in leukocytes and platelets within the solid PRF matrices.

  20. Membrane Properties Involved in Calcium-Stimulated Microparticle Release from the Plasma Membranes of S49 Lymphoma Cells

    Lauryl E. Campbell


    Full Text Available This study answered the question of whether biophysical mechanisms for microparticle shedding discovered in platelets and erythrocytes also apply to nucleated cells: cytoskeletal disruption, potassium efflux, transbilayer phospholipid migration, and membrane disordering. The calcium ionophore, ionomycin, disrupted the actin cytoskeleton of S49 lymphoma cells and produced rapid release of microparticles. This release was significantly inhibited by interventions that impaired calcium-activated potassium current. Microparticle release was also greatly reduced in a lymphocyte cell line deficient in the expression of scramblase, the enzyme responsible for calcium-stimulated dismantling of the normal phospholipid transbilayer asymmetry. Rescue of the scrambling function at high ionophore concentration also resulted in enhanced particle shedding. The effect of membrane physical properties was addressed by varying the experimental temperature (32–42°C. A significant positive trend in the rate of microparticle release as a function of temperature was observed. Fluorescence experiments with trimethylammonium diphenylhexatriene and Patman revealed significant decrease in the level of apparent membrane order along that temperature range. These results demonstrated that biophysical mechanisms involved in microparticle release from platelets and erythrocytes apply also to lymphocytes.

  1. Membrane properties involved in calcium-stimulated microparticle release from the plasma membranes of S49 lymphoma cells.

    Campbell, Lauryl E; Nelson, Jennifer; Gibbons, Elizabeth; Judd, Allan M; Bell, John D


    This study answered the question of whether biophysical mechanisms for microparticle shedding discovered in platelets and erythrocytes also apply to nucleated cells: cytoskeletal disruption, potassium efflux, transbilayer phospholipid migration, and membrane disordering. The calcium ionophore, ionomycin, disrupted the actin cytoskeleton of S49 lymphoma cells and produced rapid release of microparticles. This release was significantly inhibited by interventions that impaired calcium-activated potassium current. Microparticle release was also greatly reduced in a lymphocyte cell line deficient in the expression of scramblase, the enzyme responsible for calcium-stimulated dismantling of the normal phospholipid transbilayer asymmetry. Rescue of the scrambling function at high ionophore concentration also resulted in enhanced particle shedding. The effect of membrane physical properties was addressed by varying the experimental temperature (32-42°C). A significant positive trend in the rate of microparticle release as a function of temperature was observed. Fluorescence experiments with trimethylammonium diphenylhexatriene and Patman revealed significant decrease in the level of apparent membrane order along that temperature range. These results demonstrated that biophysical mechanisms involved in microparticle release from platelets and erythrocytes apply also to lymphocytes.

  2. Peptidoglycan Branched Stem Peptides Contribute to Streptococcus pneumoniae Virulence by Inhibiting Pneumolysin Release.

    Neil G Greene


    Full Text Available Streptococcus pneumoniae (the pneumococcus colonizes the human nasopharynx and is a significant pathogen worldwide. Pneumolysin (Ply is a multi-functional, extracellular virulence factor produced by this organism that is critical for pathogenesis. Despite the absence of any apparent secretion or cell surface attachment motifs, Ply localizes to the cell envelope of actively growing cells. We sought to characterize the consequences of this surface localization. Through functional assays with whole cells and subcellular fractions, we determined that Ply activity and its release into the extracellular environment are inhibited by peptidoglycan (PG structure. The ability of PG to inhibit Ply release was dependent on the stem peptide composition of this macromolecule, which was manipulated by mutation of the murMN operon that encodes proteins responsible for branched stem peptide synthesis. Additionally, removal of choline-binding proteins from the cell surface significantly reduced Ply release to levels observed in a mutant with a high proportion of branched stem peptides suggesting a link between this structural feature and surface-associated choline-binding proteins involved in PG metabolism. Of clinical relevance, we also demonstrate that a hyperactive, mosaic murMN allele associated with penicillin resistance causes decreased Ply release with concomitant increases in the amount of branched stem peptides. Finally, using a murMN deletion mutant, we observed that increased Ply release is detrimental to virulence during a murine model of pneumonia. Taken together, our results reveal a novel role for branched stem peptides in pneumococcal pathogenesis and demonstrate the importance of controlled Ply release during infection. These results highlight the importance of PG composition in pathogenesis and may have broad implications for the diverse PG structures observed in other bacterial pathogens.

  3. Characterization of hydrophobic flavor release profile in oil-in-water emulsions.

    Giroux, H J; Perreault, V; Britten, M


    An instrumental approach to better understand the release and persistence of flavor in oil-in-water emulsions has been developed. Emulsions were prepared with various whey protein (0.1% to 3.16%), sunflower oil (1% to 8%), and ethyl hexanoate (0% to 0.04%) concentrations. Flavor release profile in real time was measured at 37 degrees C using a specially designed glass cell connected directly to a gas chromatograph equipped with a flame ionization detector. The intensity of flavor released from the emulsion stirred at a shear rate of 100 s(-1) was monitored as a function of time and data were fitted to a 1st-order kinetic equation. Maximum intensity and decay rate constant were both determined from the model and the persistence index (inversely associated to decay rate constant) was calculated. For constant aroma concentration in the emulsion, maximum intensity significantly decreased as whey protein and oil concentrations increased. For increasing aroma concentration, maximum intensity was directly proportional to the ethyl hexanoate concentration when the oil content was kept constant but leveled off when oil content was increased. Persistence of flavor significantly increased with increasing protein and oil concentrations while aroma concentrations had no effect when oil content was constant. The results showed that oil concentration had a greater influence on flavor release characteristics than protein concentration. Aroma concentration in the oil phase, rather than in the emulsion, determines the kinetics of hydrophobic flavor release. The method provides a useful tool for the rapid and reproducible measurement of flavor release profile.

  4. The Impact of Arthroscopic Capsular Release in Patients with Primary Frozen Shoulder on Shoulder Muscular Strength

    Michał Waszczykowski


    Full Text Available The aim of this study was to evaluate the impact of arthroscopic capsular release in patients with primary frozen shoulder on muscular strength of nonaffected and treated shoulder after at least two-year follow-up after the surgery. The assessment included twenty-seven patients, who underwent arthroscopic capsular release due to persistent limitation of range of passive and active motion, shoulder pain, and limited function of upper limb despite 6-month conservative treatment. All the patients underwent arthroscopic superior, anteroinferior, and posterior capsular release. After at least two-year follow-up, measurement of muscular strength of abductors, flexors, and external and internal rotators of the operated and nonaffected shoulder, as well as determination of range of motion (ROM and function (ASES in the operated and nonaffected shoulder, was performed. Measurement of muscular strength in the patient group did not reveal statistically significant differences between operated and nonaffected shoulder. The arthroscopic capsular release does not have significant impact on the decrease in the muscular strength of the operated shoulder.

  5. Degassing, gas retention and release in Fe(0) permeable reactive barriers.

    Ruhl, Aki S; Jekel, Martin


    Corrosion of Fe(0) has been successfully utilized for the reductive treatment of multiple contaminants. Under anaerobic conditions, concurrent corrosion leads to the generation of hydrogen and its liberation as a gas. Gas bubbles are mobile or trapped within the irregular pore structure leading to a reduction of the water filled pore volume and thus decreased residence time and permeability (gas clogging). With regard to the contaminant transport to the reactive site, the estimation of surface properties of the reactive material indicated that individual gas bubbles only occupied minor contact areas of the reactive surface. Quantification of gas entrapment by both gravimetrical and tracer investigations revealed that development of preferential flow paths was not significant. A novel continuous gravimetrical method was implemented to record variations in gas entrapment and gas bubble releases from the reactive filling. Variation of grain size fractions revealed that the pore geometry had a significant impact on gas release. Large pores led to the release of comparably large gas amounts while smaller volumes were released from finer pores with a higher frequency. Relevant processes are explained with a simplified pictorial sequence that incorporates relevant mechanisms.

  6. TGF-beta1 release from biodegradable polymer microparticles: its effects on marrow stromal osteoblast function

    Lu, L.; Yaszemski, M. J.; Mikos, A. G.; McIntire, L. V. (Principal Investigator)


    BACKGROUND: Controlled release of transforming growth factor-beta1 (TGF-beta1) to a bone defect may be beneficial for the induction of a bone regeneration cascade. The objectives of this work were to assess the feasibility of using biodegradable polymer microparticles as carriers for controlled TGF-beta1 delivery and the effects of released TGF-beta1 on the proliferation and differentiation of marrow stromal cells in vitro. METHODS: Recombinant human TGF-beta1 was incorporated into microparticles of blends of poly(DL-lactic-co-glycolic acid) (PLGA) and poly(ethylene glycol) (PEG). Fluorescein isothiocynate-labeled bovine serum albumin (FITC-BSA) was co-encapsulated as a porogen. The effects of PEG content (0, 1, or 5% by weight [wt%]) and buffer pH (3, 5, or 7.4) on the protein release kinetics and the degradation of PLGA were determined in vitro for as long as 28 days. Rat marrow stromal cells were seeded on a biodegradable poly(propylene fumarate) (PPF) substrate. The dose response and biological activity of released TGF-beta1 was determined after 3 days in culture. The effects of TGF-beta1 released from PLGA/PEG microparticles on marrow stromal cell proliferation and osteoblastic differentiation were assessed during a 21-day period. RESULTS: TGF-beta1 was encapsulated along with FITC-BSA into PLGA/PEG blend microparticles and released in a multiphasic fashion including an initial burst for as long as 28 days in vitro. Increasing the initial PEG content resulted in a decreased cumulative mass of released proteins. Aggregation of FITC-BSA occurred at lower buffer pH, which led to decreased release rates of both proteins. The degradation of PLGA was increased at higher PEG content and significantly accelerated at acidic pH conditions. Rat marrow stromal cells cultured on PPF substrates showed a dose response to TGF-beta1 released from the microparticles similar to that of added TGF-beta1, indicating that the activity of TGF-beta1 was retained during microparticle

  7. The release of dissolved nutrients and metals from coastal sediments due to resuspension

    Kalnejais, Linda H.; Martin, W. R.; Bothner, Michael H.


    Coastal sediments in many regions are impacted by high levels of contaminants. Due to a combination of shallow water depths, waves, and currents, these sediments are subject to regular episodes of sediment resuspension. However, the influence of such disturbances on sediment chemistry and the release of solutes is poorly understood. The aim of this study is to quantify the release of dissolved metals (iron, manganese, silver, copper, and lead) and nutrients due to resuspension in Boston Harbor, Massachusetts, USA. Using a laboratory-based erosion chamber, a range of typical shear stresses was applied to fine-grained Harbor sediments and the solute concentration at each shear stress was measured. At low shear stress, below the erosion threshold, limited solutes were released. Beyond the erosion threshold, a release of all solutes, except lead, was observed and the concentrations increased with shear stress. The release was greater than could be accounted for by conservative mixing of porewaters into the overlying water, suggesting that sediment resuspension enhances the release of nutrients and metals to the dissolved phase. To address the long-term fate of resuspended particles, samples from the erosion chamber were maintained in suspension for 90. h. Over this time, 5-7% of the particulate copper and silver was released to the dissolved phase, while manganese was removed from solution. Thus resuspension releases solutes both during erosion events and over a longer timescale due to reactions of suspended particles in the water column. The magnitude of the annual solute release during erosion events was estimated by coupling the erosion chamber results with a record of bottom shear stresses simulated by a hydrodynamic model. The release of dissolved copper, lead, and phosphate due to resuspension is between 2% and 10% of the total (dissolved plus particulate phase) known inputs to Boston Harbor. Sediment resuspension is responsible for transferring a significant

  8. Enhanced Neurohypophyseal Vasopressin Release is Associated with Increased Opioid Inhibition of Oxytocin Release.

    Heijning, B J; Herik, I K; Rots, N Y; Greidanus, T B


    Abstract We tested the hypothesis of a cross-inhibition of oxytocin (OT) release by endogenous opioid peptides co-released with vasopressin (VP). This opioid cross-inhibition resulted in a selective block of OT release and hence in preferential release of VP. The effects of the opiate receptor antagonist naloxone were tested on neurohypophyseal VP release during dehydration, ethanol administration and sulphated cholecystokinin octapeptide (CCK-8S) application, assuming that the inhibition of pituitary OT release by endogenous opioids increases as neurohypophyseal VP output increases. A high VP output was found to coincide with increased inhibition of OT release: Subcutaneous injection of graded doses of naloxone (30 min prior to decapitation), augmented OT plasma levels significantly more in 24 h water-deprived male rats than in normally hydrated rats. Naloxone had no effect on VP release. Ethanol (10% in saline) administered intragastrically 50 min prior to decapitation and 20 min before subcutaneous naloxone (5 mg/kg) resulted in the inhibition of VP output. The ethanol treatment resulted in a rise in plasma OT levels that was additional to the effect of naloxone. These features were present in normally hydrated as well as in 24 h water-deprived animals, but were more pronounced in the latter group. Peripheral CCK-8S administration induces an abrupt and selective secretion of OT. Blocking the opioid inhibition of OT release with naloxone resulted in a significant rise of OT compared to that with CCK-8S alone. The magnitude of the opioid inhibition coincided with the activity of the VP system, and a higher dose of naloxone was needed to potentiate the CCK-8S effect on OT release in the water-deprived group than in euhydrated rats. No effect of CCK-8S and/or naloxone was found on VP plasma levels. The data indicate that opioid peptides co-released with VP (like dynorphin) may be responsible for cross-inhibition of OT release during dehydration. This suggests that

  9. Drug release mechanisms of compressed lipid implants.

    Kreye, F; Siepmann, F; Siepmann, J


    The aim of this study was to elucidate the mass transport mechanisms controlling drug release from compressed lipid implants. The latter steadily gain in importance as parenteral controlled release dosage forms, especially for acid-labile drugs. A variety of lipid powders were blended with theophylline and propranolol hydrochloride as sparingly and freely water-soluble model drugs. Cylindrical implants were prepared by direct compression and thoroughly characterized before and after exposure to phosphate buffer pH 7.4. Based on the experimental results, an appropriate mathematical theory was identified in order to quantitatively describe the resulting drug release patterns. Importantly, broad release spectra and release periods ranging from 1 d to several weeks could easily be achieved by varying the type of lipid, irrespective of the type of drug. Interestingly, diffusion with constant diffusivities was found to be the dominant mass transport mechanism, if the amount of water within the implant was sufficient to dissolve all of the drug. In these cases an analytical solution of Fick's second law could successfully describe the experimentally measured theophylline and propranolol hydrochloride release profiles, even if varying formulation and processing parameters, e.g. the type of lipid, initial drug loading, drug particles size as well as compression force and time. However, based on the available data it was not possible to distinguish between drug diffusion control and water diffusion control. The obtained new knowledge can nevertheless significantly help facilitating the optimization of this type of advanced drug delivery systems, in particular if long release periods are targeted, which require time consuming experimental trials.

  10. [Nitrogen Release from Sediment Under Dry and Rainy Season Alternation and Its Contribution to N Export from Xiangxi Watershed in Jiangxi Province].

    Han, Ning; Hao, Zhuo; Xu, Ya-juan; Gao, Yang; Yu, Gui-rui


    In this study, N export from Xiangxi River Basin in Qianyanzhou station was measured by long-term monitoring, and simulation study on N. release law from the sediment in watershed was carried out based on orthogonal experiment, and at last the contributions of N release from sediment to N transport from watershed under dry and rainy season alternation were estimated. The results showed that the maximum of TN release rate was 36 mg x (m2 x d)(-1) in stable status, which decreased with increasing time; the impact of the three controlling factors on the N release followed the order of temperature > disturbance > pH, and the effect of temperature and pH on N release from the sediment was significant when disturbance was considered as the error term; TN release rate increased with increase of temperature, and acidic and alkaline conditions could also promote N release from sediment, wherein the effect of acidic conditions on N release was stronger; the changes of TN and available N content in sediment were 414.7-899.6 mg x kg(-1) and 17.5-58.9 mg x kg(-1), so the percentage of available N only accounted for 3%-10% of TN; the TN transport concentrations were 0.58-2.40 mg x L(-1) and 1.73-4.87 mg x L(-1) in dry and wet seasons, respectively, the N release flux from sediment was about 106.34 kg x a(-1), the total N transport from watershed was 864.15 kg x a(-1), and the contribution rate of N release from sediment to N transport from watershed was about 12.31%, so we should pay much attention to the contribution of N release from sediment to water eutrophication.

  11. Morphogen and proinflammatory cytokine release kinetics from PRGF-Endoret fibrin scaffolds: evaluation of the effect of leukocyte inclusion.

    Anitua, E; Zalduendo, M M; Prado, R; Alkhraisat, M H; Orive, G


    The potential influence of leukocyte incorporation in the kinetic release of growth factors from platelet-rich plasma (PRP) may explain the conflicting efficiency of leukocyte platelet-rich plasma (L-PRP) scaffolds in tissue regeneration. To assess this hypothesis, leukocyte-free (PRGF-Endoret) and L-PRP fibrin scaffolds were prepared, and both morphogen and proinflammatory cytokine release kinetics were analyzed. Clots were incubated with culture medium to monitor protein release over 8 days. Furthermore, the different fibrin scaffolds were morphologically characterized. Results show that leukocyte-free fibrin matrices were homogenous while leukocyte-containing ones were heterogeneous, loose and cellular. Leukocyte incorporation produced a significant increase in the contents of proinflammatory cytokines interleukin (IL)-1β and IL-16 but not in the platelet-derived growth factors release (<1.5-fold). Surprisingly, the availability of vascular endothelial growth factor suffered an important decrease after 3 days of incubation in the case of L-PRP matrices. While the release of proinflammatory cytokines was almost absent or very low from PRGF-Endoret, the inclusion of leukocytes induced a major increase in these cytokines, which was characterized by the presence of a latent period. The PRGF-Endoret matrices were stable during the 8 days of incubation. The inclusion of leukocytes alters the growth factors release profile and also increased the dose of proinflammatory cytokines.

  12. The effects of nabumetone, a cyclooxygenase-2 inhibitor, on cisplatin-induced 5-hydroxytryptamine release from the isolated rat ileum.

    Kudo, C; Minami, M; Hirafuji, M; Endo, T; Hamaue, N; Akita, K; Murakami, T; Kawaguchi, H


    In order to elucidate 5-HT release influenced by PGE2 in the background of the anticancer drug-induced emesis, the effect of nabumetone, a COX-2 inhibitor, on the release of 5-HT from the isolated rat ileum was investigated. PGE2 produced a concentration-dependent increase (10(-9) to 10 M) and decrease (10(-8) to 10(-6) M) in 5-HT release. Arachidonic acid also demonstrated a similar bell-shaped 5-HT release. The arachidonic acid-induced 5-HT release at 3 x 10(-6) M (313.04 +/- 25.90%) was significantly inhibited by the concomitant perfusion with BRL10720 (10(-6) M) (161.98 +/- 19.4%, pnabumetone, or indomethacin (3 x 10(-7) M)(190.01 +/- 16.19%, pnabumetone or BRL10720, but was not affected by the 3-day administration of dexamethasone. After 72 hours, however, the in vivo 3-days administration of nabumetone, BRL10720 or dexamethasone had no effect on the increase in ileal 5-HT levels induced by cisplatin. The use of COX-2 inhibitors to ameliorate delayed emesis induced by cisplatin-based anticancer chemotherapy has been proposed. On the other hand, there is a possibility that dexamethasone works through a mechanism other than 5-HT release in delayed emesis.

  13. Kinetics of Iododeoxyuridine release from sodium alginate hydrogel in vitro

    XU Yong-hua; Mandar R Jagtap; ZHANG Dian-bo; YING Jun; Ronald C McGarry; Marc S. Mendonca; Gordon McLennan


    Objective To investigate the kinetics of Iododeoxyuridine (IUdR)release from sodium alginate hydrogel cross-linked with varying amounts of calcium chloride, and to optimize sustained release for further periadventitial I125-labeled IUdR delivery to suppress intimal hyperplasia following angioplasty in vivo.Methods Four hydrogels,composed of 0.16 mEq sodium alginate and 200 g IUdR, were cross-linked with calcium chloride to yield ion equivalence (IE) ratios (Calcium: alginate) of 3:1, 4:1, 5:1, or 6:1. 2 ml of normal saline was placed on top of each hydrogel and allowed to remain in contact at 37℃ for up to 30 days. At set time intervals, the concentration and amount of IUdR in the eluate were assayed by high performance liquid chromatography using UV detection and Water symmetry C18 column. The data for accumulated release rate and concentration in the eluate were calculated based on the calibration curve of peak area versus IUdR concentration. The hydrogel morphologic degradations were also observed. Results The hydrogels entrapped 92.9%, 98.6%, 98.4% and 98.6% of the IUdR with 3:1, 4:1, 5:1 and 6:1 IE ratios, respectively. IUdR concentration in eluates from 3:1 IE ratio hydrogel decreased faster than that from other hydrogels over time (P < 0.01). The 4:1, 5:1 and 6:1 IE ratio hydrogels produced more than 10 μm IUdR concentrations in eluates for the first 8 days, while the 3:1 IE ratio hydrogel for 4 days. IUdR release rates of the 4:1, 5:1 and 6:1 IE ratio hydrogels were very close, however they were lower than that of the 3:1 IE hydrogel in the first 48 hours (P < 0.05). At day 30, the 3:1 and 4:1 IE ratio hydrogels had 100% and 88% degradation, but no significant degradation was observed in the other hydrogels. Conclusion The sodium alginate hydrogel with 4:1 IE ratio exhibited an optimal IUdR sustained release and almost complete degradation in 30 days. (J Intervent Radiol,2006 , 15: 293-298)

  14. Attending to music decreases inattentional blindness.

    Beanland, Vanessa; Allen, Rosemary A; Pammer, Kristen


    This article investigates how auditory attention affects inattentional blindness (IB), a failure of conscious awareness in which an observer does not notice an unexpected event because their attention is engaged elsewhere. Previous research using the attentional blink paradigm has indicated that listening to music can reduce failures of conscious awareness. It was proposed that listening to music would decrease IB by reducing observers' frequency of task-unrelated thoughts (TUTs). Observers completed an IB task that varied both visual and auditory demands. Listening to music was associated with significantly lower IB, but only when observers actively attended to the music. Follow-up experiments suggest this was due to the distracting qualities of the audio task. The results also suggest a complex relationship between IB and TUTs: during demanding tasks, as predicted, noticers of the unexpected stimulus reported fewer TUTs than non-noticers. During less demanding tasks, however, noticers reported more TUTs than non-noticers.

  15. Assortativity Decreases the Robustness of Interdependent Networks

    Zhou, Di; Scala, Antonio; Stanley, H Eugene


    The protection of critical infrastructures is one of the highest priorities in our technological society. It was recently recognized that interdependencies among different networks can play a crucial role in triggering cascading failures and hence system-wide disasters. A recent model shows how pairs of interdependent networks can exhibit an abrupt percolation transition as failures accumulate. We report on the effects of topology on failure propagation for a model system consisting of two interdependent networks. We find that the internal node correlations in each of the two interdependent networks significantly changes the critical density of failures that triggers the total disruption of the two-network system. We find, in particular, that the assortativity within a single network decreases the robustness of the entire system. The results of this study on the influence of assortativity may provide insights into ways of improving the robustness of network architecture, and thus enhance the level of protecti...

  16. Interaction between NO and oxytocin: Influence on LHRH release

    V. Rettori


    Full Text Available Nitric oxide synthase (NOS-containing neurons have been localized in various parts of the CNS. These neurons occur in the hypothalamus, mostly in the paraventricular and supraoptic nuclei and their axons project to the neural lobe of the pituitary gland. We have found that nitric oxide (NO controls luteinizing hormone-releasing hormone (LHRH release from the hypothalamus acting as a signal transducer in norepinephrine (NE-induced LHRH release. LHRH not only releases LH from the pituitary but also induces sexual behavior. On the other hand, it is known that oxytocin also stimulates mating behavior and there is some evidence that oxytocin can increase NE release. Therefore, it occurred to us that oxytocin may also stimulate LHRH release via NE and NO. To test this hypothesis, we incubated medial basal hypothalamic (MBH explants from adult male rats in vitro. Following a preincubation period of 30 min, MBH fragments were incubated in Krebs-Ringer bicarbonate buffer in the presence of various concentrations of oxytocin. Oxytocin released LHRH at concentrations ranging from 0.1 nM to 1 µM with a maximal stimulatory effect (Pa1-adrenergic receptor antagonist, indicating that NE mediated this effect. Oxytocin at the same concentrations also increased the activity of NOS (P<0.01 as measured by the conversion of [14C]arginine to citrulline, which is produced in equimolar amounts with NO by the action of NOS. The release of LHRH induced by oxytocin was also accompanied by a significant (P<0.02 increase in the release of prostaglandin E2 (PGE2, a mediator of LHRH release that is released by NO. On the other hand, incubation of neural lobes with various concentrations of sodium nitroprusside (NP (300 or 600 µM, a releaser of NO, revealed that NO acts to suppress (P<0.01 the release of oxytocin. Therefore, our results indicate that oxytocin releases LHRH by stimulating NOS via NE, resulting in an increased release of NO, which increases PGE2 release that

  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. Blood platelet-derived microparticles release and bubble formation after an open-sea air dive.

    Pontier, Jean-Michel; Gempp, Emmanuel; Ignatescu, Mihaela


    Bubble-induced platelet aggregation offers an index for evaluating decompression severity in humans and in a rat model of decompression sickness. Endothelial cells, blood platelets, or leukocytes shed microparticles (MP) upon activation and during cell apoptosis. The aim was to study blood platelet MP (PMP) release and bubble formation after a scuba-air dive in field conditions. Healthy, experienced divers were assigned to 1 experimental group (n = 10) with an open-sea air dive to 30 msw for 30 min and 1 control group (n = 5) during head-out water immersion for the same period. Bubble grades were monitored with a pulsed doppler according to Kissman Integrated Severity Score (KISS). Blood samples for platelet count (PC) and PMP (annexin V and CD41) were taken 1 h before and after exposure in both groups. The result showed a decrease in post-dive PC compared with pre-dive values in experimental group with no significant change in the control group. We observed a significant increase in PMP values after the dive while no change was revealed in the control group. There was a significant positive correlation between the PMP values after the dive and the KISS bubble score. The present study highlighted a relationship between the post-dive decrease in PC, platelet MP release, and bubble formation. Release of platelet MPs could reflect bubble-induced platelet aggregation and could play a key role in alteration of the coagulation. Further studies must investigate endothelial and leukocyte MP release in the same field conditions.

  20. Effect of androgen on Kiss1 expression and luteinizing hormone release in female rats.

    Iwata, Kinuyo; Kunimura, Yuyu; Matsumoto, Keisuke; Ozawa, Hitoshi


    Hyperandrogenic women have various grades of ovulatory dysfunction, which lead to infertility. The purpose of this study was to determine whether chronic exposure to androgen affects the expression of kisspeptin (ovulation and follicle development regulator) or release of luteinizing hormone (LH) in female rats. Weaned females were subcutaneously implanted with 90-day continuous-release pellets of 5α-dihydrotestosterone (DHT) and studied after 10 weeks of age. Number of Kiss1-expressing cells in both the anteroventral periventricular nucleus (AVPV) and arcuate nucleus (ARC) was significantly decreased in ovary-intact DHT rats. Further, an estradiol-induced LH surge was not detected in DHT rats, even though significant differences were not observed between DHT and non-DHT rats with regard to number of AVPV Kiss1-expressing cells or gonadotrophin-releasing hormone (GnRH)-immunoreactive (ir) cells in the presence of high estradiol. Kiss1-expressing and neurokinin B-ir cells were significantly decreased in the ARC of ovariectomized (OVX) DHT rats compared with OVX non-DHT rats; pulsatile LH secretion was also suppressed in these animals. Central injection of kisspeptin-10 or intravenous injection of a GnRH agonist did not affect the LH release in DHT rats. Notably, ARC Kiss1-expressing cells expressed androgen receptors (ARs) in female rats, whereas only a few Kiss1-expressing cells expressed ARs in the AVPV. Collectively, our results suggest excessive androgen suppresses LH surge and pulsatile LH secretion by inhibiting kisspeptin expression in the ARC and disruption at the pituitary level, whereas AVPV kisspeptin neurons appear to be directly unaffected by androgen. Hence, hyperandrogenemia may adversely affect ARC kisspeptin neurons, resulting in anovulation and menstrual irregularities. © 2017 Society for Endocrinology.

  1. Long-term pharmacological kindling increases in vitro release of IR-Met and IR-Leu-enkephalin from amygdala.

    Asai, M; Matamoros-Trejo, G; Linares, G


    Met-enkephalin release is increased from amygdala and striatum 1 and 15 days after pharmacological kindling with pentylenetetrazol, following potassium-induced depolarization in vitro via a Ca2+ dependent mechanism. Leu-enkephalin release was only enhanced in amygdala and striatum 1 day after the last seizure. IR-Met-enkephalin amygdala tissue content enhanced 1 and 15 days after seizure. In striatum, we found an IR-Met-enkephalin decrease 35 days after the last stimulus. IR-Leu-enkephalin amygdala tissue content enhanced 1 day after the last seizure, and no significant increases were found in striatum 1, 15 and 35 days after the last seizure. In this paper, we show that opioid peptides release is differentially enhanced in rat brain for several days after the last seizure, thus suggesting that opioid peptides may have a protective action against seizure activity.

  2. Intravenously administered oxotremorine and atropine, in doses known to affect pain threshold, affect the intraspinal release of acetylcholine in rats

    Abelson, Klas S P; Höglund, A Urban


    muscarinic agonists and antagonists modify nociceptive threshold by affecting intraspinal release of acetylcholine (ACh). Catheters were inserted into the femoral vein in rats maintained on isoflurane anaesthesia for administration of oxotremorine (10-300 microg/kg) and atropine (0.1, 10, 5000 microg....../kg). Spinal microdialysis probes were placed intraspinally at approximately the C2-C5 spinal level for sampling of acetylcholine and dialysis delivery of atropine (0.1, 1, 10 nM). Additionally, the tail-flick behaviour was tested on conscious rats injected intraperitoneally with saline, atropine (10, 100....... Intravenously administered atropine, in a dose that produced hyperalgesia (5000 microg/kg) in the tail-flick test, significantly decreased the intraspinal release of acetylcholine. Our results suggest an association between pain threshold and acetylcholine release in spinal cord. It is also suggested...

  3. The effectiveness of the controlled release of simvastatin from β-TCP macrosphere in the treatment of OVX mice.

    Chou, Joshua; Ito, Tomoko; Otsuka, Makoto; Ben-Nissan, Besim; Milthorpe, Bruce


    Simvastatin, a cholesterol treatment drug, has been shown to stimulate bone regeneration. As such, there has been an increase interest in the development of suitable materials and systems for the delivery of simvastatin. Without the appropriate dosage of simvastatin, the therapeutic effects on bone growth will be significantly reduced. Furthermore, similar to many pharmaceutical compounds, at high concentration simvastatin can cause various adverse side-effects. Given the associated side-effects with the usage of simvastatin, the development of suitable controlled drug release system is pertinent. Calcium phosphate in particularly beta-tricalcium phosphate (β-TCP) has been extensively studied and used as a carrier material for drug delivery system. In this study, Foraminifera exoskeletons were used as calcium carbonate precursor materials, which were hydrothermally converted to β-TCP as a carrier material for simvastatin. Natural marine exoskeletons posses interconnected and uniformly porous network capable of improving drug loading and release rate. To prolong the release of simvastatin, an apatite coating was made around the β-TCP sample and in vitro release studies in simulated body fluid (SBF) showed a significant decrease in release rate. Osteoporotic mice were used to examine the compare therapeutic effectiveness of β-TCP, β-TCP with simvastatin, apatite-coated β-TCP with simvastatin and direct injection of simvastatin near the right femur of the mice. Localized and systemic effect were compared with the femur of the non-implanted side (left) and showed that β-TCP with or without simvastatin was able to induce significant bone formation over 6 weeks. Mechanical analysis showed that apatite-coated β-TCP with simvastatin produced significantly stronger bones compared with other experimental groups. This study shows that natural exoskeletons with the appropriate structure can be successfully used as a drug delivery system for simvastatin and can its

  4. Release of Steroids from Plastibase Semisolid Bases

    D.Hassan-Zadeh S.Kararayar


    Full Text Available The present research is carried out in order to study the possibility of replacing the classic semisolid bases in steroidal commercial products with Plastibase."nAs regard to its high lipophilic properties, the plastibase alone is not a suitable base for hydrocortisone acetate and f.luocinolone acetonide. Addition of 5 and 7.5% of Propylene glycol to plastibase can increase the rate of drug release from vehicle. This change in drug release is related to decrease in drug-vehicle interaction and consequently increasing its partition coefficient. It seems that these considerations can be applied to betamethasone and clobetasole ointments, which are the most utilized in Iranian commerce .

  5. 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.


    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

  7. [Intraocular pressure decrease after manual small incision cataract surgery].

    Nganga Ngabou, C G F; Makita, C; Ndalla, S S; Nkokolo, F; Madzou, M


    We decided to evaluate the decrease in intraocular pressure six months after cataract surgery. We evaluated patients' IOP using an applanation tonometer. The patients then underwent cataract surgery. Six months after cataract surgery, we reevaluated the IOP by the same method, and we determined the post-operative change. Among the 147 operated eyes, 123 eyes or 83.67% exhibited a decrease in IOP. The mean preoperative IOP for the operative eye was 15.61±4.5mmHg; the mean post-operative IOP was 12.57±3.5mmHg; the mean IOP decrease after surgery was 3.16±4mmHg, for a mean decrease of 20%. This decrease is statistically significant, Pdecrease in IOP varies proportionally to the initial IOP. In glaucomatous patients, the mean preoperative IOP was 23.16±5.68mmHg and mean post-operative IOP was 14.5±2.7mmHg, a decrease of 37.39%. The decrease in IOP after cataract surgery was generally moderate. However, this IOP decreased proportionally to the initial IOP, thus giving significant decreases for higher IOPs. This decrease in IOP, well known after phacoemulsification, was also obtained after Manual Small Incision Cataract Surgery, a surgical technique which is increasingly employed in developing countries. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  8. Effect of MK-801 on methamphetamine-induced dopaminergic neurotoxicity: long-term attenuation of methamphetamine-induced dopamine release

    Kim, Sang Eun; Kim, Yu Ri; Hwang, Se Hwan [Sungkyunkwan Univ., School of Medicine, Seoul (Korea, Republic of)


    Repeated administration of methamphetamine (METH) produces high extracellular levels of dopamine (DA) and subsequent striatal DA terminal damage. The effect of MK-801, a noncompetitive N-methyl-D-aspartate receptor antagonist, on METH-induced changes in DA transporter (DAT) and DA release evoked by an acute METH challenge was evaluated in rodent striatum using [{sup 3}H] WIN 38,428 ex vivo auto-radiography and in vivo microdialysis. Four injections of METH (10 mg/kg, i.p.), each given 2 h apart, produced 71% decrease in DAT levels in mouse striatum 3 d after administration. Pretreatment with MK-801 (2.5 g/kg, i.p.) 15 min before each of the four METH injections protected completely against striatal DAT depletions. Four injections of MK-801 alone did not significantly change striatal DAT levels. Striatal DA release evoked by an acute METH challenge (4mg/kg, i.p.) at 3 d after repeated administration of METH in rats was decreased but significant compared with controls, which was attenuated by repeated pretreatment with MK-801. Also, repeated injections of MK-801 alone attenuated acute METH-induced striatal DA release 3 d after administration. These results suggest that repeated administration of MK-801 may exert a preventive effect against METH-induced DA terminal injury through long-term attenuation of DA release induced by METH and other stimuli.

  9. Comparison of release of mercury from three dental amalgams.

    Chew, C L; Soh, G; Lee, A S; Yeoh, T S


    Mercury release from dental amalgams has generated considerable concern in recent years and is the subject of this study. Specimens of one admixed high-copper amalgam (Contour), one lathe-cut low-copper amalgam (SDI), and a new tin- and copper-free amalgam claimed to be non-mercury-releasing (Composil) were evaluated for release of mercury when incubated in purified water at 37 degrees C. Measurement of mercury was done by cold-vapor atomic absorption spectrophotometry, and the amount released was expressed as micrograms/cm2/24 hr. Study was conducted over a four-week period. Results show that Contour and SDI released similar insignificant amounts (mean release of less than 0.1 microgram/cm2/24 hr) compared with Composil (mean release of 41.0 micrograms/cm2/24 hr). The difference in release by Composil compared with that by Contour and SDI is highly significant (P less than 0.001). The implications of chronic release of mercury from dental amalgams are discussed. Long-term release studies are in progress.

  10. Interaction of anesthetics with neurotransmitter release machinery proteins.

    Xie, Zheng; McMillan, Kyle; Pike, Carolyn M; Cahill, Anne L; Herring, Bruce E; Wang, Qiang; Fox, Aaron P


    General anesthetics produce anesthesia by depressing central nervous system activity. Activation of inhibitory GABA(A) receptors plays a central role in the action of many clinically relevant general anesthetics. Even so, there is growing evidence that anesthetics can act at a presynaptic locus to inhibit neurotransmitter release. Our own data identified the neurotransmitter release machinery as a target for anesthetic action. In the present study, we sought to examine the site of anesthetic action more closely. Exocytosis was stimulated by directly elevating the intracellular Ca(2+) concentration at neurotransmitter release sites, thereby bypassing anesthetic effects on channels and receptors, allowing anesthetic effects on the neurotransmitter release machinery to be examined in isolation. Three different PC12 cell lines, which had the expression of different release machinery proteins stably suppressed by RNA interference, were used in these studies. Interestingly, there was still significant neurotransmitter release when these knockdown PC12 cells were stimulated. We have previously shown that etomidate, isoflurane, and propofol all inhibited the neurotransmitter release machinery in wild-type PC12 cells. In the present study, we show that knocking down synaptotagmin I completely prevented etomidate from inhibiting neurotransmitter release. Synaptotagmin I knockdown also diminished the inhibition produced by propofol and isoflurane, but the magnitude of the effect was not as large. Knockdown of SNAP-25 and SNAP-23 expression also changed the ability of these three anesthetics to inhibit neurotransmitter release. Our results suggest that general anesthetics inhibit the neurotransmitter release machinery by interacting with multiple SNARE and SNARE-associated proteins.

  11. Light activated nitric oxide releasing materials

    Muizzi Casanas, Dayana Andreina

    The ability to control the location and dosage of biologically active molecules inside the human body can be critical to maximizing effective treatment of cardiovascular diseases like angina. The current standard of treatment relies on the metabolism of organonitrate drugs into nitric oxide (NO), which are not specific, and also show problems with densitization with long-term use. There is a need then to create a treatment method that gives targeted release of NO. Metal-nitrosyl (M-NO) complexes can be used for delivery of NO since the release of NO can be controlled with light. However, the NO-releasing drug must be activated with red light to ensure maximum penetration of light through tissue. However, the release of NO from M-NO complexes with red-light activation is a significant challenge since the energy required to break the metal-NO bond is usually larger than the energy provided by red light. The goal of this project was to create red- sensitive, NO-releasing materials based on Ru-salen-nitrosyl compounds. Our approach was to first modify Ru salen complexes to sensitize the photochemistry for release of NO after red light irradiation. Next, we pursued polymerization of the Ru-salen complexes. We report the synthesis and quantitative photochemical characterization of a series of ruthenium salen nitrosyl complexes. These complexes were modified by incorporating electron donating groups in the salen ligand structure at key locations to increase electron density on the Ru. Complexes with either an --OH or --OCH3 substituent showed an improvement in the quantum yield of release of NO upon blue light irradiation compared to the unmodified salen. These --OH and --OCH3 complexes were also sensitized for NO release after red light activation, however the red-sensitive complexes were unstable and showed ligand substitution on the order of minutes. The substituted complexes remained sensitive for NO release, but only after blue light irradiation. The Ru

  12. Retrograde release of endocannabinoids inhibits presynaptic GABA release to second-order baroreceptive neurons in NTS.

    Chen, Chao-Yin; Bonham, Ann C; Dean, Caron; Hopp, Francis A; Hillard, Cecilia J; Seagard, Jeanne L


    In prior studies, we found that activation of cannabinoid-1 receptors in the nucleus tractus solitarii (NTS) prolonged baroreflex-induced sympathoinhibition in rats. In many regions of the central nervous system, activation of cannabinoid-1 receptors presynaptically inhibits γ-aminobutyric acid (GABA) release, disinhibiting postsynaptic neurons. To determine if cannabinoid-1 receptor-mediated presynaptic inhibition of GABA release occurs in the NTS, we recorded miniature inhibitory postsynaptic currents in anatomically identified second-order baroreceptive NTS neurons in the presence of ionotropic glutamate receptor antagonists and tetrodotoxin. The cannabinoid-1 receptor agonists, WIN 55212-2 (0.3-30 μM) and methanandamide (3 μM) decreased the frequency of miniature inhibitory postsynaptic currents in a concentration-dependent manner, an effect that was blocked by the cannabinoid-1 receptor antagonist, N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (AM 251, 5 μM). Importantly, depolarization of second-order baroreceptive neurons decreased the frequency of miniature inhibitory postsynaptic currents; an effect which was blocked by the cannabinoid-1 receptor antagonist. The data indicate that depolarization of second-order baroreceptive NTS neurons induces endocannabinoid release from the neurons, leading to activation of presynaptic cannabinoid-1 receptors, inhibition of GABA release and subsequent enhanced baroreflex signaling in the NTS. The data suggest that endocannabinoid signaling in the NTS regulates short-term synaptic plasticity and provide a mechanism for endocannabinoid modulation of central baroreflex control.

  13. Mycobacteria attenuate nociceptive responses by formyl peptide receptor triggered opioid peptide release from neutrophils.

    Heike L Rittner


    Full Text Available In inflammation, pain is regulated by a balance of pro- and analgesic mediators. Analgesic mediators include opioid peptides which are secreted by neutrophils at the site of inflammation, leading to activation of opioid receptors on peripheral sensory neurons. In humans, local opioids and opioid peptides significantly downregulate postoperative as well as arthritic pain. In rats, inflammatory pain is induced by intraplantar injection of heat inactivated Mycobacterium butyricum, a component of complete Freund's adjuvant. We hypothesized that mycobacterially derived formyl peptide receptor (FPR and/or toll like receptor (TLR agonists could activate neutrophils, leading to opioid peptide release and inhibition of inflammatory pain. In complete Freund's adjuvant-induced inflammation, thermal and mechanical nociceptive thresholds of the paw were quantified (Hargreaves and Randall-Selitto methods, respectively. Withdrawal time to heat was decreased following systemic neutrophil depletion as well as local injection of opioid receptor antagonists or anti-opioid peptide (i.e. Met-enkephalin, beta-endorphin antibodies indicating an increase in pain. In vitro, opioid peptide release from human and rat neutrophils was measured by radioimmunoassay. Met-enkephalin release was triggered by Mycobacterium butyricum and formyl peptides but not by TLR-2 or TLR-4 agonists. Mycobacterium butyricum induced a rise in intracellular calcium as determined by FURA loading and calcium imaging. Opioid peptide release was blocked by intracellular calcium chelation as well as phosphoinositol-3-kinase inhibition. The FPR antagonists Boc-FLFLF and cyclosporine H reduced opioid peptide release in vitro and increased inflammatory pain in vivo while TLR 2/4 did not appear to be involved. In summary, mycobacteria activate FPR on neutrophils, resulting in tonic secretion of opioid peptides from neutrophils and in a decrease in inflammatory pain. Future therapeutic strategies may aim

  14. Growth hormone (GH)-releasing activity of chicken GH-releasing hormone (GHRH) in chickens.

    Harvey, S; Gineste, C; Gaylinn, B D


    Two peptides with sequence similarities to growth hormone releasing hormone (GHRH) have been identified by analysis of the chicken genome. One of these peptides, chicken (c) GHRH-LP (like peptide) was previously found to poorly bind to chicken pituitary membranes or to cloned and expressed chicken GHRH receptors and had little, if any, growth hormone (GH)-releasing activity in vivo or in vitro. In contrast, a second more recently discovered peptide, cGHRH, does bind to cloned and expressed cGHRH receptors and increases cAMP activity in transfected cells. The possibility that this peptide may have in vivo GH-releasing activity was therefore assessed. The intravenous (i.v.) administration of cGHRH to immature chickens, at doses of 3-100 μg/kg, significantly increased circulating GH concentrations within 10 min of injection and the plasma GH levels remained elevated for at least 30 min after the injection of maximally effective doses. The plasma GH responses to cGHRH were comparable with those induced by human (h) or porcine (p) GHRH preparations and to that induced by thyrotropin releasing hormone (TRH). In marked contrast, the i.v. injection of cGHRH-LP had no significant effect on circulating GH concentrations in immature chicks. GH release was also increased from slaughterhouse chicken pituitary glands perifused for 5 min with cGHRH at doses of 0.1 μg/ml or 1.0 μg/ml, comparable with GH responses to hGHRH1-44. In contrast, the perifusion of chicken pituitary glands with cGHRH-LP had no significant effect on GH release. In summary, these results demonstrate that cGHRH has GH-releasing activity in chickens and support the possibility that it is the endogenous ligand of the cGHRH receptor.

  15. Determination of fungal spore release from wet building materials

    Kildesø, J.; Wurtz, H.; Nielsen, Kristian Fog;


    of fungal spores was induced by well-defined jets of air impacting from rotating nozzles. The spores and other particles released from the surface were transported by the air flowing from the chamber through a top outlet to a particle counter and sizer. For two of the fungi (Penicillium chrysogenum...... and Trichoderma harzianum ), the number of spores produced on the gypsum board and subsequently released was quantified. Also the relationship between air velocities from 0.3 to 3 m/s over the surface and spore release has been measured. The method was found to give very reproducible results for each fungal...... isolate, whereas the spore release is very different for different fungi under identical conditions. Also, the relationship between air velocity and spore release depends on the fungus. For some fungi a significant number of particles smaller than the spore size were released. The method applied...

  16. Subcellular fractionation on Percoll gradient of mossy fiber synaptosomes: evoked release of glutamate, GABA, aspartate and glutamate decarboxylase activity in control and degranulated rat hippocampus.

    Taupin, P; Ben-Ari, Y; Roisin, M P


    Using discontinuous density gradient centrifugation in isotonic Percoll sucrose, we have characterized two subcellular fractions (PII and PIII) enriched in mossy fiber synaptosomes and two others (SII and SIII) enriched in small synaptosomes. These synaptosomal fractions were compared with those obtained from adult hippocampus irradiated at neonatal stage to destroy granule cells and their mossy fibers. Synaptosomes were viable as judged by their ability to release aspartate, glutamate and GABA upon K+ depolarization. After irradiation, compared to the control values, the release of glutamate and GABA was decreased by 57 and 74% in the PIII fraction, but not in the other fractions and the content of glutamate, aspartate and GABA was also decreased in PIII fraction by 62, 44 and 52% respectively. These results suggest that mossy fiber (MF) synaptosomes contain and release glutamate and GABA. Measurement of the GABA synthesizing enzyme, glutamate decarboxylase, exhibited no significant difference after irradiation, suggesting that GABA is not synthesized by this enzyme in mossy fibers.

  17. UVR induce optical changes and phosphorous release of lake water and macrophyte leachates in shallow Andean lakes

    Beatriz MODENUTTI


    Full Text Available We carried out laboratory experiments in order to study the effect of ultraviolet radiation (UVR on optical features and phosphorous release of Dissolved Organic Mater (DOM from lake water and macrophyte leachates. Lake water samples were obtained from lakes Escondido and El Trébol, and macrophytes (Potamogeton linguatus and Schoenoplectus californicus from their littoral zones. After UVR exposure, DOM from lake El Trébol seemed to react more quickly than that from Lake Escondido and this seems to be related with the degree of lability or aromaticity in the DOM bulk of each lake. Leachates from both macrophytes showed different absorbance spectra with differences in photochemical transformations after UVR exposure: S. californicus leachates exhibited the highest photodegradation. A significant Soluble Reactive Phosphorus (SRP release was observed in lake water after UVR exposure. Lake El Trébol showed the highest SRP concentrations, suggesting that the release of orthophosphate was favored by low molecular weight DOM. P. linguatus leachates have more dissolved phosphorus content than S. californicus ones and after UVR exposure, P. linguatus leachate did not react to UVR while S. californicus exhibited a decrease in SRP. However both macrophyte leachates showed the higher P release in darkness. The obtained results indicated that macrophyte leachates could contribute significantly to changes in the optical characteristics and in the nutrient content in shallow Andean lakes. An increasing input of P. linguatus leachates would produce DOM of high molecular size and a higher P release than S. californicus.

  18. Impact of aphid alarm pheromone release on virus transmission efficiency: When pest control strategy could induce higher virus dispersion.

    Lin, Fang-Jing; Bosquée, Emilie; Liu, Ying-Jie; Chen, Ju-Lian; Yong, Liu; Francis, Frédéric


    Aphids cause serious damages to crops not only by tacking sap but also by transmitting numerous viruses. To develop biological control, the aphid alarm pheromone, namely E-β-farnesene (EβF), has been demonstrated to be efficient to repel aphids and as attract beneficials, making it a potential tool to control aphid pests. Considering aphids also as virus vectors, changes of their behavior could also interfere with the virus acquisition and transmission process. Here, a combination of two aphid species and two potato virus models were selected to test the influence of EβF release on aphid and virus dispersion under laboratory conditions. EβF release was found to significantly decrease the population of Myzus persicae and Macrosiphum euphorbiae around the infochemical releaser but simultaneously also increasing the dispersal of Potato Virus Y (PVY). At the opposite, no significant difference for Potato Leaf Roll Virus (PLRV) transmission efficiency was observed with similar aphid alarm pheromone releases for none of the aphid species. These results provide some support to carefully consider infochemical releasers not only for push-pull strategy and pest control but also to include viral disease in a the plant protection to aphids as they are also efficient virus vectors. Impact of aphid kinds and transmission mechanisms will be discussed according to the large variation found between persistent and non persistent potato viruses and interactions with aphids and related infochemicals.

  19. Periodontal Disease and Decreased Kidney Function in Japanese Elderly

    Iwasaki, Masanori; Taylor, George W.; Nesse, Willem; Vissink, Arjan; Yoshihara, Akihiro; Miyazaki, Hideo

    Background: Early detection of decreased kidney function can help prevent the progression of kidney disease to kidney failure and cardiovascular events. Potentially significant associations between kidney function and periodontal disease have been reported in cross-sectional studies. However, no

  20. Eicosanoid release as laboratory indicator of biocompatibility.

    Mahiout, A; Jörres, A; Schultze, G; Meinhold, H; Kessel, M


    Biocompatibility evaluation of extracorporeal devices requires the establishment of sensitive indicators of blood cells/surface interactions. Among others, arachidonic acid derivatives, such as prostaglandins and thromboxanes, play an important role in the cell control systems. Hence, the release of eicosanoids during blood exposure to dialyzer membranes was investigated. Experiments included in vitro incubation of human blood with flat membranes (FM), as well as ex vivo perfusion of hollow fiber membranes (HFM) with blood from healthy volunteers in single-pass fashion. In both models, a significant release of prostaglandin E2 (PGE2) and thromboxane B2 (TXB2) was detected. In addition, the amount of eicosanoid release depended on the type of membrane tested. After a 10-min FM incubation with fresh blood, plasma concentrations of TXB2 and PGE2 were pronounced by polycarbonate when compared to Cuprophan and polyacrylonitrile. During 10 min of open loop perfusion of HFM, polymethylmethacrylate was the most active biomaterial, whereas the reactivity of Cuprophan was significantly lower. Among HFM, Hemophan was by far the less active. These results indicate that the release of eicosanoids represents a sensitive parameter of blood cells/membrane reactivity. Thus, the question arises as to whether or not the extracorporeal process of cyclooxygenase activity could contribute to the clinical side effects of chronical hemodialysis.

  1. 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%).

  2. Decreased cerebral spinal fluid neurotransmitter levels in Smith-Lemli-Opitz syndrome.

    Sparks, S E; Wassif, C A; Goodwin, H; Conley, S K; Lanham, D C; Kratz, L E; Hyland, K; Gropman, A; Tierney, E; Porter, F D


    Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive, multiple congenital anomaly syndrome with cognitive impairment and a distinct behavioral phenotype that includes autistic features. SLOS is caused by a defect in 3β-hydroxysterol Δ(7)-reductase which leads to decreased cholesterol levels and elevated cholesterol precursors, specifically 7- and 8-dehydrocholesterol. However, the pathological processes contributing to the neurological abnormalities in SLOS have not been defined. In view of prior data suggesting defects in SLOS in vesicular release and given the association of altered serotonin metabolism with autism, we were interested in measuring neurotransmitter metabolite levels in SLOS to assess their potential to be used as biomarkers in therapeutic trials. We measured cerebral spinal fluid levels of serotonin and dopamine metabolites, 5-hydroxyindoleacetic acid (5HIAA) and homovanillic acid (HVA) respectively, in 21 SLOS subjects. Results were correlated with the SLOS anatomical severity score, Aberrant Behavior Checklist scores and concurrent sterol biochemistry. Cerebral spinal fluid (CSF) levels of both 5HIAA and HVA were significantly reduced in SLOS subjects. In individual patients, the levels of both 5HIAA and HVA were reduced to a similar degree. CSF neurotransmitter metabolite levels did not correlate with either CSF sterols or behavioral measures. This is the first study demonstrating decreased levels of CSF neurotransmitter metabolites in SLOS. We propose that decreased levels of neurotransmitters in SLOS are caused by a sterol-related defect in synaptic vesicle formation and that CSF 5HIAA and HVA will be useful biomarkers in development of future therapeutic trials.

  3. Na2S, a fast-releasing H2S donor, given as suppository lowers blood pressure in rats.

    Tomasova, Lenka; Drapala, Adrian; Jurkowska, Halina; Wróbel, Maria; Ufnal, Marcin


    Hydrogen sulfide (H2S) is involved in blood pressure control. The available slow-releasing H2S-donors are poorly soluble in water and their ability to release H2S in biologically relevant amounts under physiological conditions is questionable. Therefore, new slow-releasing donors or new experimental approaches to fast-releasing H2S donors are needed. Hemodynamics and ECG were recorded in male, anesthetized Wistar Kyoto rats (WKY) and in Spontaneously hypertensive rats (SHR) at baseline and after: 1) intravenous (iv) infusion of vehicle or Na2S; 2) administration of vehicle suppositories or Na2S suppositories. Intravenously administered vehicle and vehicle suppositories did not affect mean arterial blood pressure (MABP) and heart rate (HR). Na2S administered iv caused a significant, but transient (2-5min) decrease in MABP. Na2S suppositories produced a dose-dependent hypotensive response that lasted ∼45min in WKY and ∼75-80min in SHR. It was accompanied by a decrease in HR in WKY, and an increase in HR in SHR. Na2S suppositories did not produce a significant change in corrected QT, an indicator of cardiotoxicity. Na2S suppositories increased blood level of thiosulfates, products of H2S oxidation. Na2S administered in suppositories exerts a prolonged hypotensive effect in rats, with no apparent cardiotoxic effect. SHR and WKY differ in hemodynamic response to the H2S donor. Suppository formulation of fast-releasing H2S donors may be useful in research, if a reference slow-releasing H2S donor is not available. Copyright © 2017 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  4. A doxycycline loaded, controlled-release, biodegradable fiber for the treatment of aortic aneurysms.

    Yamawaki-Ogata, A; Hashizume, R; Satake, M; Kaneko, H; Mizutani, S; Moritan, T; Ueda, Y; Narita, Y


    The pathogenesis of aortic aneurysm (AA) is characterized by degradation of extracellular matrix with increased matrix metalloproteinases (MMPs) and inflammatory reaction. Doxycycline (DOXY) has been reported to control the extension of AA by regulation of MMP. However, systemic administration may cause adverse side effects. In this study, we demonstrated the possibility of local administration of DOXY controlled-release biodegradable fiber (DCRBF) for AA in mice. DCRBF was fabricated by biodegradable polymer (polylactic acid; PLA) mixed with DOXY using an electrospinning technique. DCRBF was cocultured with SMCs, macrophages and aortic tissue, and placed on an abdominal aortic aneurysm which induced apolipoprotein E-deficient mice. We evaluated gene and protein expression of proteases, elastin and inflammatory markers. In the presence of DCRBF, MMP-12 was significantly decreased, TGF-β1 and Lox were significantly increased in SMC gene expression, MMP-9 and -12 significantly decreased gene expression of macrophages. The DCRBF preserved elastin content and decreased MMP-2 and -9 in aortic tissue. In addition, IGF-1 and TIMP-1 were significantly increased and IL-6 and TNF-α were significantly decreased with DCRBF in vivo. In conclusion, our results suggested that local administration of DCRBF may become a promising alternative therapeutic strategy for AA. Copyright © 2010 Elsevier Ltd. All rights reserved.

  5. Decomposition and nutrient release of leguminous plants in coffee agroforestry systems

    Eduardo da Silva Matos


    Full Text Available Leguminous plants used as green manure are an important nutrient source for coffee plantations, especially for soils with low nutrient levels. Field experiments were conducted in the Zona da Mata of Minas Gerais State, Brazil to evaluate the decomposition and nutrient release rates of four leguminous species used as green manures (Arachis pintoi, Calopogonium mucunoides, Stizolobium aterrimum and Stylosanthes guianensis in a coffee agroforestry system under two different climate conditions. The initial N contents in plant residues varied from 25.7 to 37.0 g kg-1 and P from 2.4 to 3.0 g kg-1. The lignin/N, lignin/polyphenol and (lignin+polyphenol/N ratios were low in all residues studied. Mass loss rates were highest in the first 15 days, when 25 % of the residues were decomposed. From 15 to 30 days, the decomposition rate decreased on both farms. On the farm in Pedra Dourada (PD, the decomposition constant k increased in the order C. mucunoides < S. aterrimum < S. guianensis < A. pintoi. On the farm in Araponga (ARA, there was no difference in the decomposition rate among leguminous plants. The N release rates varied from 0.0036 to 0.0096 d-1. Around 32 % of the total N content in the plant material was released in the first 15 days. In ARA, the N concentration in the S. aterrimum residues was always significantly higher than in the other residues. At the end of 360 days, the N released was 78 % in ARA and 89 % in PD of the initial content. Phosphorus was the most rapidly released nutrient (k values from 0.0165 to 0.0394 d-1. Residue decomposition and nutrient release did not correlate with initial residue chemistry and biochemistry, but differences in climatic conditions between the two study sites modified the decomposition rate constants.

  6. Preparation and release study of Triclosan in polyethylene/Triclosan anti-bacterial blend.

    Kamalipour, Jamshid; Masoomi, Mahmood; Khonakdar, Hossein Ali; Razavi, Seyed Mohammad Reza


    In this study, medium density polyethylene (MDPE) incorporated with Triclosan antibacterial substance has been prepared and Triclosan release rate was investigated. The crystallinity level and matrix polarity, as two significant parameters in antibacterial release control, were studied. Triclosan, a well-established widespread antibacterial agent, was incorporated into medium density polyethylene (MDPE) and Maleic anhydride grafted polyethylene (PE-g-MA) was used to change the polarity of the MDPE matrix. A masterbatch of 10wt% Triclosan incorporated with the MDPE and various PE-g-MA concentrations were prepared using an internal mixer. Then the masterbatch was diluted in the MDPE matrix to produce compounds with 0.1, 0.5, and1wt% Triclosan via twin screw extruder. The compounds were molded by compression molding method and then were cooled in three different cooling rate methods: isothermal cooling (I), quenching (Q),and moderate 5-10°C/min cooling rate (M). Cooling rate effects on crystallinity level were investigated applying sample density measurement. UV-vis absorption spectroscopy was used to probe the release of Triclosan. Antibacterial properties of the compounds against Escherichia coli, Klebsiella pneumoniae, and Staphylococcus aureus were measured. The results showed that by addition of PE-g-MA, Triclosan release rate was increased. It was confirmed that the sample crystallinity was decreased by the cooling rate enhancement. The results also showed that quenched samples indicated higher release of Triclosan. Cooling rate reduction and raising the polarity increased the release of Triclosan and improved the antibacterial properties of the compounds.

  7. Monomer release from nanofilled and microhybrid dental composites after bleaching.

    Masumeh Hasani Tabatabaee


    Full Text Available The aim of this study was to assess the effect of bleaching on elution of monomers from nanofilled and microhybrid composites.80 samples (5mm diameter and 3mm thickness of each composite were prepared. After curing, half of them were randomly polished. Each group was divided into 8 subgroups and immersed in water or 10%, 20% and 30% H2O2 for 3 or 8 hours. Eluted Bis-GMA (Bis-phenol A Glycidyl Dimethacrylate, TEGDMA (Triethyleneglycol Dimethacrylate, UDMA (Urethane Dimethacrylate and BisEMA (Bis-phenol A ethoxylate Dimethacrylate were quantified by high performance liquid chromatography and the results were analyzed by univariate ANOVA and t-test (P<0.05.Bleach significantly increased the overall release of monomers (P<0.001; TEGDMA was released more than Bis-GMA (P<0.001. Supreme released more TEGDMA compared to Z250 (P<0.001. Bleaching increased the release of this monomer (P<0.001. Increasing both the concentration of H2O2, and the immersion time, increased the release of TEGDMA (P<0.001. Polishing had no effect on release of this monomer (P=0.952. Supreme released more Bis-GMA than Z250 (P=0.000. The more concentrated H2O2 caused more elution of Bis-GMA (P= 0.003; while the effect of immersion time was not significant (P=0.824. Polishing increased the release of Bis-GMA (P=0.001. Neither the type of composite nor Bleaching had any effect on release of UDMA (P=0.972 and (P=0.811 respectively. Immersion duration increased the release of UDMA (P=0.002, as well as polishing (P=0.024.Bleaching increased the release of monomers. Nanofilled composites released more monomer than the microfilled.

  8. Interfacial Fast Release Layer in Monodisperse Poly (lactic-co-glycolic acid) Microspheres Accelerates the Drug Release.

    Wu, Jun; Zhao, Xiaoli; Yeung, Kelvin W K; To, Michael K T


    Understanding microstructural evolutions of drug delivery devices during drug release process is essential for revealing the drug release mechanisms and controlling the drug release profiles. In this study, monodisperse poly (lactic-co-glycolic acid) microspheres in different diameters were fabricated by microfluidics in order to find out the relationships between the microstructural evolutions and the drug release profiles. It was found that poly (lactic-co-glycolic acid) microspheres underwent significant size expansion which took place from the periphery to the center, resulting in the formation of interfacial fast release layers. At the same time, inner pores were created and the diffusion rate was increased so that the early stage drug release was accelerated. Due to the different expansion rates, small poly (lactic-co-glycolic acid) microspheres tendered to follow homogeneous drug release while large poly (lactic-co-glycolic acid) microspheres tendered to follow heterogeneous drug release. This study suggests that the size expansion and the occurrence of interfacial fast release layer were important mechanisms for early stage drug release of poly (lactic-co-glycolic acid) microspheres.

  9. Hydrogen Release Studies of Alkali Metal Amidoboranes

    Luedtke, Avery T.; Autrey, Thomas


    A series of metal amido boranes LiNH2BH3 (LAB), NaNH2BH3 (SAB), LiNH(Me)BH3 (LMAB), NaNH(Me)BH3 (SMAB), KNH(Me)BH3 (PMAB), and KNH(tBu)BH3 (PBAB) were synthesized, by solution phase methods, and the thermal release of H2 in the solid state was studied. Based on the observed trends in reaction rates of H > Me > tBu and the kinetic isotope effect, the mechanism of hydrogen release from MAB compounds was found to proceed through a bimolecular mechanism involving the intermediacy of a MH (M = Li, Na, or K). The mechanism of hydrogen release from metal amidoboranes, a metal ion assisted hydride transfer, is very different than the mechanism of hydrogen release from the parent compound ammonia borane (AB). The non-volatile products formed from MAB’s are significantly different than the products formed after hydrogen release from AB. The boron containing resulting from the release of one equivalent of hydrogen from the metal amidoboranes were characterized by MAS 11B NMR spectroscopy and found to contain both BH3 and sp2 hybridized BH groups, consistent with a general structural feature MN(R)=BHN(R)MBH3. This work was funded by the U.S. Department of Energy Office of Energy Efficiency and Renewable Energy as part of the Chemical Hydrogen Storage CoE at Pacific Northwest National Laboratory (PNNL). PNNL is operated for the U.S. DOE by Battelle. MAS NMR studies were performed using EMSL, a national scientific user facility sponsored by the Department of Energy’s Office of Biological and Environmental Research located at PNNL.

  10. Glutamate transport decreases mitochondrial pH and modulates oxidative metabolism in astrocytes.

    Azarias, Guillaume; Perreten, Hélène; Lengacher, Sylvain; Poburko, Damon; Demaurex, Nicolas; Magistretti, Pierre J; Chatton, Jean-Yves


    During synaptic activity, the clearance of neuronally released glutamate leads to an intracellular sodium concentration increase in astrocytes that is associated with significant metabolic cost. The proximity of mitochondria at glutamate uptake sites in astrocytes raises the question of the ability of mitochondria to respond to these energy demands. We used dynamic fluorescence imaging to investigate the impact of glutamatergic transmission on mitochondria in intact astrocytes. Neuronal release of glutamate induced an intracellular acidification in astrocytes, via glutamate transporters, that spread over the mitochondrial matrix. The glutamate-induced mitochondrial matrix acidification exceeded cytosolic acidification and abrogated cytosol-to-mitochondrial matrix pH gradient. By decoupling glutamate uptake from cellular acidification, we found that glutamate induced a pH-mediated decrease in mitochondrial metabolism that surpasses the Ca(2+)-mediated stimulatory effects. These findings suggest a model in which excitatory neurotransmission dynamically regulates astrocyte energy metabolism by limiting the contribution of mitochondria to the metabolic response, thereby increasing the local oxygen availability and preventing excessive mitochondrial reactive oxygen species production.

  11. Decreased catecholamine secretion from the adrenal medullae of chronically diabetic BB-Wistar rats

    Wilke, R. A.; Riley, D. A.; Lelkes, P. I.; Hillard, C. J.


    Many humans with IDDM eventually lose the capacity to secrete epinephrine from their adrenal medullae. The mechanism for this pathological change is unknown. We hypothesized that this abnormality is attributable to neuropathic changes in the greater splanchnic nerves or in the chromaffin cells that they innervate. To study this hypothesis, we isolated rat adrenal glands, perfused them ex vivo, and measured the epinephrine content of the perfusate under various conditions of stimulation. We used transmural electrical stimulation (20-80 V, at 10 Hz) to induce epinephrine secretion indirectly by selectively activating residual splanchnic nerve terminals within the isolated glands. Under these conditions, epinephrine secretion was severely attenuated in glands from female BB-Wistar rats with diabetes of 4 mo duration compared with their age-matched, nondiabetic controls. These perfused diabetic adrenal medullae also demonstrated decreased catecholamine release in response to direct chromaffin cell depolarization with 20 mM K+, evidence that a functional alteration exists within the chromaffin cells themselves. Nonetheless, total catecholamine content of adrenal medullae from these diabetic rats was not significantly different from controls, indicating that the secretory defect was not simply attributable to a difference in the amount of catecholamines stored and available for release. Herein, we also provide histological evidence of degenerative changes within the cholinergic nerve terminals that innervate these glands.

  12. Glutamate decreases the secretion of IL-10 by peripheral blood lymphocytes in persons with autoimmune thyroiditis.

    Kvaratskhelia, E; Dabrundashvili, N; Gagua, M; Maisuradze, E; Mikeladze, D


    Human T lymphocytes expose ionotropic and metabotropic glutamate receptors, which control immune responses, cell activation, maturation, and death. Several cytokines release during inflammation which identification may have important physiological and clinical implications. Main biological function of IL-10 is limitation and termination of inflammatory responses and the regulation of differentiation and proliferation of several immune cells. Various inflammatory molecules regulated the secretion of IL-8 and IL-10, but the action of glutamate on the biosynthesis of cytokines is unknown. We have found that in peripheral blood lymphocytes glutamate at the concentrations within normal plasma levels (1 x 10(-5) M), as well as at lower concentration (0.3 x 10(-6) M) changes the secretion of immunosuppressive cytokine IL-10, whereas synthesis of proinflammatory chemokine, IL-8 did not changed significantly. Moreover, our results have shown that peripheral blood lymphocytes from patients with autoimmune thyroiditis release less IL-10 at both concentration of glutamate than peripheral blood lymphocytes from healthy persons. These data suggest that glutamate decrease the secretion of IL-10 by peripheral blood lymphocytes, especially in patients with autoimmune thyroiditis that may be responsible for prolongation of inflammation.

  13. Decreased chewing activity during mouth breathing.

    Hsu, H-Y; Yamaguchi, K


    This study examined the effect of mouth breathing on the strength and duration of vertical effect on the posterior teeth using related functional parameters during 3 min of gum chewing in 39 nasal breathers. A CO(2) sensor was placed over the mouth to detect expiratory airflow. When no airflow was detected from the mouth throughout the recording period, the subject was considered a nasal breather and enrolled in the study. Electromyographic (EMG) activity was recorded during 3 min of gum chewing. The protocol was repeated with the nostrils occluded. The strength of the vertical effect was obtained as integrated masseter muscle EMG activity, and the duration of vertical effect was also obtained as chewing stroke count, chewing cycle variation and EMG activity duration above baseline. Baseline activity was obtained from the isotonic EMG activity during jaw movement at 1.6 Hz without making tooth contact. The duration represented the percentage of the active period above baseline relative to the 3-min chewing period. Paired t-test and repeated analysis of variance were used to compare variables between nasal and mouth breathing. The integrated EMG activity and the duration of EMG activity above baseline, chewing stroke count and chewing cycle significantly decreased during mouth breathing compared with nasal breathing (Pmouth breathing was significantly greater than nasal breathing (PMouth breathing reduces the vertical effect on the posterior teeth, which can affect the vertical position of posterior teeth negatively, leading to malocclusion.


    Ah. Yusuf


    Full Text Available Introduction: Aging is a natural process in individuals. Most of the elderly have problems in dealing with this natural process. Lost of occupation, friends and loneliness may result in depression in this age group. Cognitive therapy changes pessimistic idea, unrealistic hopes and excessive self evaluation may result and justify depression. Cognitive therapy may help elderly to recognize the problem in life, to develop positive objective of life and to create more positive personality. The aimed of this study was to analyze the effect of cognitive therapy to reduce the level of depression. Method: This study was used a pre experimental pre post test design. Sample were 10 elderly people who met to the inclusion criteria. The independent variable was cognitive therapy and dependent variable was the level of depression in elderly. Data were collected by using Geriatric Depression Scale (GDS 15, then analyzed by using Wilcoxon Signed Rank Test with significance levelα≤0.05. Result: The result showed that cognitive therapy has an effect on reducing depression with significance level p=0.005. Discussion: It can be concluded that cognitive therapy was effective in reducing depression level in elderly. Further studies are recommended to analyze the effect of cognitive therapy on decreasing anxiety in elderly by measuring cathecolamin.

  15. Decreasing seagrass density negatively influences associated fauna.

    McCloskey, Rosemary M; Unsworth, Richard K F


    Seagrass meadows globally are disappearing at a rapid rate with physical disturbances being one of the major drivers of this habitat loss. Disturbance of seagrass can lead to fragmentation, a reduction in shoot density, canopy height and coverage, and potentially permanent loss of habitat. Despite being such a widespread issue, knowledge of how such small scale change affects the spatial distribution and abundances of motile fauna remains limited. The present study investigated fish and macro faunal community response patterns to a range of habitat variables (shoot length, cover and density), including individual species habitat preferences within a disturbed and patchy intertidal seagrass meadow. Multivariate analysis showed a measurable effect of variable seagrass cover on the abundance and distribution of the fauna, with species specific preferences to both high and low seagrass cover seagrass. The faunal community composition varied significantly with increasing/decreasing cover. The faunal species composition of low cover seagrass was more similar to sandy control plots than to higher cover seagrass. Shannon Wiener Diversity (H') and species richness was significantly higher in high cover seagrass than in low cover seagrass, indicating increasing habitat value as density increases. The results of this study underline how the impacts of small scale disturbances from factors such as anchor damage, boat moorings and intertidal vehicle use on seagrass meadows that reduce shoot density and cover can impact upon associated fauna. These impacts have negative consequences for the delivery of ecosystem services such as the provision of nursery habitat.

  16. 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.

  17. Helium irradiation effects on tritium retention and long-term tritium release properties in polycrystalline tungsten

    Nobuta, Y., E-mail: [Laboratory of Plasma Physics and Engineering, Hokkaido University, Kita-13, Nishi-8, Kita-ku, Sapporo 060-8628 (Japan); Hatano, Y.; Matsuyama, M.; Abe, S. [Hydrogen Isotope Research Center, University of Toyama, Gofuku 3190, Toyama 930-8555 (Japan); Yamauchi, Y.; Hino, T. [Laboratory of Plasma Physics and Engineering, Hokkaido University, Kita-13, Nishi-8, Kita-ku, Sapporo 060-8628 (Japan)


    DT{sup +} ion irradiation with energy of 0.5 and 1.0 keV was performed on helium pre-irradiated tungsten and the amount of retained tritium and the long-term release of retained tritium in vacuum was investigated using an IP technique and BIXS. Tritium retention and long-term tritium release were significantly influenced by helium pre-irradiation. The amount of retained tritium increased until it reached 1 × 10{sup 17} He/cm{sup 2}, and at 1 × 10{sup 18} He/cm{sup 2} it became smaller compared to 1 × 10{sup 17} He/cm{sup 2}. The amount of retained tritium in tungsten without helium pre-irradiation largely decreased after several weeks preservation in vacuum, and the long-term release rate during vacuum preservation was retarded by helium pre-irradiation. The results indicate that the long-term tritium release and the helium irradiation effect on it should be taken into account for more precise estimation of tritium retention in the long-term use of tungsten in fusion devices.

  18. Thermosensitive hydrogel for periodontal application: in vitro drug release, antibacterial activity and toxicity evaluation.

    Pakzad, Yousef; Ganji, Fariba


    Injectable thermosensitive chitosan hydrogel is an attractive temperature-induced sol-gel solution that is widely used in drug delivery and biomedical applications. In this study, an injectable antimicrobial delivery system for periodontal treatment based on chitosan/gelatin/β-glycerolphosphate solution has been developed. The result of thermal and mechanical evaluations of chitosan/gelatin/β-glycerolphosphate hydrogel showed that adding gelatin to chitosan/β-glycerolphosphate solution significantly decreased gelling time and increased gel strength at 37℃. The antimicrobial agents chosen for release studies were metronidazole with a low molecular weight and vancomycin hydrochloride with a high molecular weight. The initial burst and total in vitro drug release for metronidazole was 13% and 67%, respectively. The initial burst and total drug release for vancomycin hydrochloride was relatively low at 3% and 23%, respectively. The momentary and total percentage of metronidazole accumulated in the phosphate buffer revealed that chitosan/gelatin/β-glycerolphosphate can develop and maintain sustained release of metronidazole in concentrations that are effective for eliminating pathogenic bacteria over time. Cytotoxicity evaluations show that chitosan/gelatin/β-glycerolphosphate thermosensitive hydrogel is a drug carrier with no cytotoxic effects.

  19. Boiling enriches the linear polysulfides and the hydrogen sulfide-releasing activity of garlic.

    Tocmo, Restituto; Wu, Yuchen; Liang, Dong; Fogliano, Vincenzo; Huang, Dejian


    Garlic is rich in polysulfides, and some of them can be H2S donors. This study was conducted to explore the effect of cooking on garlic's organopolysulfides and H2S-releasing activity. Garlic bulbs were crushed and boiled for a period ranging from 3 to 30min and the solvent extracts were analyzed by GC-MS/FID and HPLC. A cell-based assay was used to measure the H2S-releasing activity of the extracts. Results showed that the amounts of allyl polysulfides increased in crushed garlic boiled for 6-10min; however, prolonging the thermal treatment to 20 or 30min decreased their concentrations. Data of the H2S-releasing activity, expressed as diallyl trisulfide equivalents (DATS-E), parallel this trend, being significantly higher at 6 and 10min boiling. Our results showed enhancement of H2S-releasing activity upon moderate boiling, suggesting that shorter cooking time may maximize its health benefits as a dietary source of natural H2S donors.

  20. Efficacy and safety of gonadotropin-releasing hormone agonists used in the treatment of prostate cancer

    Choi S


    Full Text Available Seungtaek Choi, Andrew K LeeDepartment of Radiation Oncology, MD Anderson Cancer Center, Houston, TX, USAAbstract: Androgen deprivation therapy (ADT is the most effective systemic treatment for prostate cancer. ADT has been shown to have a high rate of response and to improve overall survival in patients with metastatic prostate cancer. In addition, multiple studies have shown that adding ADT to external beam radiation therapy leads to improvement in cure rates and overall survival in prostate cancer patients. The most commonly used ADT is gonadotropin-releasing hormone (GnRH agonist therapy. Although GnRH agonist therapy has significant benefits for patients with prostate cancer, it has also been shown to have significant side effects, including fatigue, hot flashes, decreased libido, decreased quality of life, obesity, diabetes mellitus, coronary artery disease, decreased bone mineral density, and increased risk of fractures. Therefore, it is crucial that the benefits of ADT be weighed against its potential adverse effects before its use.Keywords: androgen deprivation therapy, gonadotropin-releasing hormone agonists, prostate cancer

  1. 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

  2. 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.

  3. Can Diuretics Decrease Your Potassium Level?

    ... and Conditions High blood pressure (hypertension) Can diuretics decrease your potassium level? Answers from Sheldon G. Sheps, ... D. Yes, some diuretics — also called water pills — decrease potassium in the blood. Diuretics are commonly used ...

  4. Effect of neostigmine on the hippocampal noradrenaline release : role of cholinergic receptors

    Kiss, JP; Vizi, ES; Westerink, BHC


    THE effect of the cholinesterase inhibitor neostigmine on hippocampal noradrenaline (NA) release was studied using in vivo microdialysis. Local application of neostigmine significantly increased the release of NA. The effect was potentiated by coperfusion of the nicotinic antagonist mecamylamine but

  5. Experimental study on phosphorus release from sediments of shallow lake in wave flume

    SUN; Xiaojing; ZHU; Guangwei; LUO; Liancong


    Influence of wave on sediment resuspension and nutrients release from sediments, collected from Lake Taihu and Lake Chaohu, was studied in flume experiments. Under strong-wave conditions, concentrations of suspended solids (SS), total phosphorus (TP) and dissolved total phosphorus (DTP) in overlying water were increased significantly following the sediments re-suspension. During the experiments on sediments of Lake Taihu and Lake Chaohu, TP concentrations increased 6 times and 3 times, and DTP concentration increased 100% and 70% more than it in presuspension, respectively. Concentration of soluble reactive phosphorus (SRP) of experiment on sediment of Lake Taihu increased 25%. During the massive sediment suspension, the dissolved phosphorus in pore water and much of the phosphorus adsorbed by the sediment particles were released into overlying water. The phenomena in this wave flume experiment are quite similar to the situation observed in situ of Lake Taihu. The critical wave stresses of sediment re-suspension are nearly equal. The change of concentrations of SS, TP, and SRP was the same as that in situ situation.This study showed that concentrations of TP and SRP in lake water could be increased significantly by wave disturbance. Phosphorus release was significantly enhanced by wave disturbance at the beginning of massive sediment re-suspension, but decreased later.

  6. 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...

  7. NMDAR-mediated calcium transients elicited by glutamate co-release at developing inhibitory synapses

    Abigail Kalmbach


    Full Text Available Before hearing onset, the topographic organization of the inhibitory sound localization pathway from the medial nucleus of the trapezoid body (MNTB to the lateral superior olive (LSO is refined by means of synaptic silencing and strengthening. During this refinement period MNTB-LSO synapses not only release GABA and glycine but also release glutamate. This co-released glutamate can elicit postsynaptic currents that are predominantly mediated by NMDA receptors (NMDARs. To gain a better understanding of how glutamate contributes to synaptic signaling at developing MNTB-LSO inhibitory synapse, we investigated to what degree and under what conditions NMDARs contribute to postsynaptic calcium responses. Our results demonstrate that MNTB-LSO synapses can elicit compartmentalized calcium responses along aspiny LSO dendrites. These responses are significantly attenuated by the NMDARs antagonist APV. APV, however, has no effect on somatically recorded electrical postsynaptic responses, indicating little, if any, contribution of NMDARs to spike generation. Small NMDAR-mediated calcium responses were also observed under physiological levels of extracellular magnesium concentrations indicating that MNTB-LSO synapses activate magnesium sensitive NMDAR on immature LSO dendrites. In Fura-2 AM loaded neurons, blocking GABAA and glycine receptors decreased NMDAR contribution to somatic calcium responses suggesting that GABA and glycine, perhaps by shunting backpropagating action potentials, decrease the level of NMDAR activation under strong stimulus conditions.

  8. Studies on the codling moth (Lepidoptera: Tortricidae) response to different codlemone release rates.

    Vacas, S; Miñarro, M; Bosch, M D; Primo, J; Navarro-Llopis, V


    The response of the codling moth (Cydia pomonella L. (Lepidoptera: Tortricidae)) to different emission values of its main pheromone component, 8E,10E-dodecadien-1-ol (codlemone), was investigated in three field trials conducted in plots without mating disruption treatments. Moth catches obtained in traps baited with pheromone dispensers were correlated with the corresponding codlemone release rates by multiple regression analysis. In a preliminary trial conducted in Lleida (NE Spain), a decreasing trend of captures was observed based on increasing pheromone levels. After this, the pheromone release profiles of the pheromone dispensers were studied, in parallel with the field trials, by residual codlemone extraction and gas chromatography quantification. In the trials carried out in Asturias (NW Spain), a correlation between trap catches and emission levels (within the range from 11 to 1,078 μg/d) was found and fitted a logarithmic model. Captures followed a decreasing linear trend in the range of emission rates from 11 to 134 μg/d. Given that release values comprised between 11 and 67 μg/d did not lead to significantly different catches in traps, this emission range could be considered to develop effective formulations for attraction purposes when mating disruption is not acting in the environment.

  9. Glucose metabolism determines resistance of cancer cells to bioenergetic crisis after cytochrome-c release.

    Huber, Heinrich J


    Many anticancer drugs activate caspases via the mitochondrial apoptosis pathway. Activation of this pathway triggers a concomitant bioenergetic crisis caused by the release of cytochrome-c (cyt-c). Cancer cells are able to evade these processes by altering metabolic and caspase activation pathways. In this study, we provide the first integrated system study of mitochondrial bioenergetics and apoptosis signalling and examine the role of mitochondrial cyt-c release in these events. In accordance with single-cell experiments, our model showed that loss of cyt-c decreased mitochondrial respiration by 95% and depolarised mitochondrial membrane potential ΔΨ(m) from -142 to -88 mV, with active caspase-3 potentiating this decrease. ATP synthase was reversed under such conditions, consuming ATP and stabilising ΔΨ(m). However, the direction and level of ATP synthase activity showed significant heterogeneity in individual cancer cells, which the model explained by variations in (i) accessible cyt-c after release and (ii) the cell\\'s glycolytic capacity. Our results provide a quantitative and mechanistic explanation for the protective role of enhanced glucose utilisation for cancer cells to avert the otherwise lethal bioenergetic crisis associated with apoptosis initiation.

  10. Biodegradable polyesters reinforced with triclosan loaded polylactide micro/nanofibers: Properties, release and biocompatibility

    L. J. del Valle


    Full Text Available Mechanical properties and drug release behavior were studied for three biodegradable polyester matrices (polycaprolactone, poly(nonamethylene azelate and the copolymer derived from 1,9-nonanediol and an equimolar mixture of azelaic and pimelic acids reinforced with polylactide (PLA fibers. Electrospinning was used to produce suitable mats constituted by fibers of different diameters (i.e. from micro- to nanoscale and a homogeneous dispersion of a representative hydrophobic drug (i.e. triclosan. Fabrics were prepared by a molding process, which allowed cold crystallization of PLA micro/nanofibers and hot crystallization of the polyester matrices. The orientation of PLA molecules during electrospinning favored the crystallization process, which was slightly enhanced when the diameter decreased. Incorporation of PLA micro/nanofibers led to a significant increase in the elastic modulus and tensile strength, and in general to a decrease in the strain at break. The brittle fracture was clearer when high molecular weight samples with high plastic deformation were employed. Large differences in the release behavior were detected depending on the loading process, fiber diameter size and hydrophobicity of the polyester matrix. The release of samples with the drug only loaded into the reinforcing fibers was initially fast and then became slow and sustained, resulting in longer lasting antimicrobial activity. Biocompatibility of all samples studied was demonstrated by adhesion and proliferation assays using HEp-2 cell cultures.

  11. Yohimbine increases submaxillary kallikrein release into the saliva in dogs: evidence for alpha 2-adrenoceptor-mediated inhibition of cholinergic pathways.

    Girolami, J. P.; Bascands, J. L.; Pécher, C.; Berlan, M.; Montastruc, J. L.; Montastruc, P.


    1. The effects of the alpha 2-adrenoceptor antagonist, yohimbine (0.5 mg kg-1, i.v.) on basal, sympathetic and parasympathetic stimulation-induced submaxillary kallikrein release were investigated in the anaesthetized dog. Kallikrein was measured by its kininogenase activity before and after trypsin activation which also allowed a study of the proportion of active to total enzyme. 2. Yohimbine induced a rapid, three fold increase in basal kallikrein release correlated with an increase in salivary flow rate which lasted for 60 min following injection. 3. Sectioning the chorda tympani did not affect basal kallikrein release but abolished yohimbine-induced rise in salivary kallikrein secretion. 4. Parasympathetic stimulation alone induced a 3 to 4 fold increase in basal kallikrein release correlated with an increase in salivary flow rate. Yohimbine induced a significant additional increase in parasympathetic-stimulated kallikrein release. 5. When the cervical sympathetic nerve was sectioned the basal kallikrein release decreased by 30 to 40%. 6. Sympathetic stimulation alone also induced a 3 to 4 fold increase in basal kallikrein. This was not correlated with the salivary flow and unaffected by yohimbine. 7. The results indicate that yohimbine increases submaxillary kallikrein release into the saliva by inhibition of presynaptic alpha 2-adrenoceptors located on the chorda tympani nerve endings. PMID:1849766

  12. The polycondensing temperature rather than time determines the degradation and drug release of poly(glycerol-sebacate) doped with 5-fluorouracil.

    Sun, Zhi-Jie; Sun, Cheng-Wu; Sun, Bo; Lu, Xi-Li; Dong, De-Li


    Poly(glycerol-sebacate) (PGS) is an elastomeric biodegradable polyester that could be used as biodegradable drug carrier. We have previously prepared PGS implants doped with 5-fluorouracil (5-FU-PGSs) and found that 5-FU-PGSs exhibited an initial burst of 5-FU release during in vitro degradation. The synthesis temperature and time are two of the most important reaction conditions for polymer synthesis. Therefore, in order to establish a controllable drug-release manner, we prepared a series of 5-FU-PGS with 2% weight of 5-FU under synthesis conditions with different polycondensing temperature and time and characterized the infrared spectrum properties, in vitro degradation and drug release. Results showed that the polycondensing temperature determined the mechanical properties, degradation and drug release of 5-FU-PGSs. With the polycondensing temperature increasing, the elastic modulus and hardness of 5-FU-PGSs increased, and the mass loss and 5-FU release rate decreased. The polycondensing time had no significant influence on the mechanical property, degradation and drug release of 5-FU-PGSs. We suggest that the polycondensing temperature is the factor to control the drug-release manner.

  13. The applicability of ordered mesoporous SBA-15 and its hydrophobic glutaraldehyde-bridge derivative to improve ibuprofen-loading in releasing system.

    Rehman, Fozia; Volpe, Pedro L O; Airoldi, Claudio


    The mesoporous SBA-15 silica with uniform hexagonal pore, narrow pore size distribution and tuneable pore diameter was organofunctionalized with glutaraldehyde-bridged silylating agent. The precursor and its derivative silicas were ibuprofen-loaded for controlled delivery in simulated biological fluids. The synthesized silicas were characterized by elemental analysis, infrared spectroscopy, (13)C and (29)Si solid state NMR spectroscopy, nitrogen adsorption, X-ray diffractometry, thermogravimetry and scanning electron microscopy. Surface functionalization with amine containing bridged hydrophobic structure resulted in significantly decreased surface area from 802.4 to 63.0 m(2) g(-1) and pore diameter 8.0-6.0 nm, which ultimately increased the drug-loading capacity from 18.0% up to 28.3% and a very slow release rate of ibuprofen over the period of 72.5h. The in vitro drug release demonstrated that SBA-15 presented the fastest release from 25% to 27% and SBA-15GA gave near 10% of drug release in all fluids during 72.5 h. The Korsmeyer-Peppas model better fits the release data with the Fickian diffusion mechanism and zero order kinetics for synthesized mesoporous silicas. Both pore sizes and hydrophobicity influenced the rate of the release process, indicating that the chemically modified silica can be suggested to design formulation of slow and constant release over a defined period, to avoid repeated administration.

  14. Composite poly(vinyl alcohol)/poly(vinyl acetate) electrospun nanofibrous mats as a novel wound dressing matrix for controlled release of drugs.

    Jannesari, Marziyeh; Varshosaz, Jaleh; Morshed, Mohammad; Zamani, Maedeh


    The aim of this study was to develop novel biomedicated nanofiber electrospun mats for controlled drug release, especially drug release directly to an injury site to accelerate wound healing. Nanofibers of poly(vinyl alcohol) (PVA), poly(vinyl acetate) (PVAc), and a 50:50 composite blend, loaded with ciprofloxacin HCl (CipHCl), were successfully prepared by an electrospinning technique for the first time. The morphology and average diameter of the electrospun nanofibers were investigated by scanning electron microscopy. X-ray diffraction studies indicated an amorphous distribution of the drug inside the nanofiber blend. Introducing the drug into polymeric solutions significantly decreased solution viscosities as well as nanofiber diameter. In vitro drug release evaluations showed that both the kind of polymer and the amount of drug loaded greatly affected the degree of swelling, weight loss, and initial burst and rate of drug release. Blending PVA and PVAc exhibited a useful and convenient method for electrospinning in order to control the rate and period of drug release in wound healing applications. Also, the thickness of the blend nanofiber mats strongly influenced the initial release and rate of drug release.

  15. Release behavior of copper and zinc from sandy soils

    ZHANG Ming-kui; XIA Yi-ping


    The concentrations and chemical forms of copper(Gu) and zinc(Zn) in surface soils directly influence the movement of Gu and Zn. In this study, thirteen sandy soil samples with a wide range of total Cu and Zn concentrations were collected for evaluating the relationships between Cu and Zn release and extraction time, ratio of soil to water, pH and electrolyte types. The results indicated that Cu released in batch extraction that represents long-term leaching was mainly from exchangeable, and carbonate bound Cu fractions, and Zn released in the batch extraction was mainly from its carbonate bound fraction. However, the Cu and Zn leached from the soils using the column leaching that represents short-term leaching were mainly from their exchangeable fractions. Soil column leaching at different pH values indicated that the amounts of leached Zn and Cu were greatly affected by pH. The Cu and Zn release experiments with varying extraction times and ratio of soil to water suggest that long-term water-logging in the soils after rain may increase contact time of the soils with water and the release of Cu and Zn to water from the soils, and total amounts of Cu or Zn released from the soils increase, but the Cu or Zn concentration in the surface runoff decrease with increasing rainfall intensity. The increased Ca concentration in soil solution increased stability of organic matter-mineral complexes and might decrease the dissolution of organic matter, and thus decreased the release of Cu-binding component of organic matter. However, high concentration of Na in the soil solution increased the dispersion of the organic matter-mineral complexes and increased dissolution of organic matter and the release of Cu from the soils.

  16. Hybridization and Selective Release of DNA Microarrays

    Beer, N R; Baker, B; Piggott, T; Maberry, S; Hara, C M; DeOtte, J; Benett, W; Mukerjee, E; Dzenitis, J; Wheeler, E K


    DNA microarrays contain sequence specific probes arrayed in distinct spots numbering from 10,000 to over 1,000,000, depending on the platform. This tremendous degree of multiplexing gives microarrays great potential for environmental background sampling, broad-spectrum clinical monitoring, and continuous biological threat detection. In practice, their use in these applications is not common due to limited information content, long processing times, and high cost. The work focused on characterizing the phenomena of microarray hybridization and selective release that will allow these limitations to be addressed. This will revolutionize the ways that microarrays can be used for LLNL's Global Security missions. The goals of this project were two-fold: automated faster hybridizations and selective release of hybridized features. The first study area involves hybridization kinetics and mass-transfer effects. the standard hybridization protocol uses an overnight incubation to achieve the best possible signal for any sample type, as well as for convenience in manual processing. There is potential to significantly shorten this time based on better understanding and control of the rate-limiting processes and knowledge of the progress of the hybridization. In the hybridization work, a custom microarray flow cell was used to manipulate the chemical and thermal environment of the array and autonomously image the changes over time during hybridization. The second study area is selective release. Microarrays easily generate hybridization patterns and signatures, but there is still an unmet need for methodologies enabling rapid and selective analysis of these patterns and signatures. Detailed analysis of individual spots by subsequent sequencing could potentially yield significant information for rapidly mutating and emerging (or deliberately engineered) pathogens. In the selective release work, optical energy deposition with coherent light quickly provides the thermal energy

  17. Temporal control of drug release from biodegradable polymer: multicomponent diclofenac sodium releasing PLGA 80/20 rod.

    Nikkola, Lila; Viitanen, Petrus; Ashammakhi, Nureddin


    In our previous studies we have reported on the development of diclofenac sodium (DS) releasing rods. However, their drug release profiles were unsatisfactory. To enhance the drug release properties of the implant, we have developed a system whereby various elements can be combined into one implant. Melt extruded, self-reinforced (SR), and sterilized (S) DS-containing SR-PLGA 80/20 billets were combined to produce multicomponent implants with various compositions. These components were basically heat pressed together to form multicomponent rods. Drug release from single component and multicomponent rods was defined using a UV-Vis spectrophotometer. DS was released from individual components within 82-111 days and from multicomponent rods within 50-70 days. Thermal properties were analyzed using differential scanning calorimetry (DSC). The melting temperature (T(m)) of multicomponent implants was about 157 degrees C, change in heat fusion (DeltaH) was 13.3 J/g, and the glass transition temperature (T(g)) was 55.4 degrees C. Mechanical strength was measured for 2 weeks and it decreased from 55 to 15 MPa. In conclusion, by compression molding three components with different release rates it is possible to control the temporal release from multicomponent rods. Released DS concentrations were within range for 49-74 days depending on the fractions of individual components used.

  18. In vitro release of theophylline from poly(lactic acid) sustained-release pellets prepared by direct compression.

    Kader, A; Jalil, R


    Poly(L-lactic acid), (L-PLA) pellets containing theophylline as a model drug were prepared with increasing bovine serum albumin (BSA) load of 10, 20, 30, 40, or 50% by direct compression. The drug release from pellets was studied in phosphate buffered saline (PBS, pH 7.4) at 37 degrees C. The annealing effect on theophylline release from pellets was also studied at 20, 30, 60, and 80 degrees C. In all cases, release kinetics followed the Higuchian mechanism with an initial burst effect followed by sustained release of theophylline during the experimental period. Increasing BSA load resulted in a linear increase in Higuchian release rates presumably because of the hydrophilic nature of BSA. Furthermore, BSA did not interact chemically with the polymer matrix and was held physically by the dense polymer matrix. However, drug release decreased with an increase in annealing temperature. Release of theophylline was higher from PLA-BSA combination pellets compared to PLA pellets at temperatures below the glass transition temperature (Tg) of the polymer and lower for temperatures above Tg. The temperature effect on drug release may be attributed to both the reduction of core solubility in the bulk phase and the lowering of diffusibility of the polymeric membrane. No drug-polymer interactions or polymer degradation was observed within the experimental setup when studied by differential scanning calorimetry (DSC), infrared (FTIR) spectroscopy, and gravimetric methods. DSC studies of pellets showed no hints of microstructural changes (crystallinity) of the polymers. In our experiments, theophylline was released primarily by leaching through channels and not by polymer degradation. The release rate was dependent on BSA loading and annealing. It may be concluded that PLA pellets can be fabricated suitably using BSA and annealing to design sustained-release preparations of water-soluble drugs.

  19. Ni ion release, osteoblast-material interactions, and hemocompatibility of hafnium-implanted NiTi alloy.

    Zhao, Tingting; Li, Yan; Zhao, Xinqing; Chen, Hong; Zhang, Tao


    Hafnium ion implantation was applied to NiTi alloy to suppress Ni ion release and enhance osteoblast-material interactions and hemocompatibility. The auger electron spectroscopy, x-ray photoelectron spectroscopy, and atomic force microscope results showed that a composite TiO(2)/HfO(2) nanofilm with increased surface roughness was formed on the surface of NiTi, and Ni concentration was reduced in the superficial surface layer. Potentiodynamic polarization tests displayed that 4 mA NiTi sample possessed the highest E(br) - E(corr), 470 mV higher than that of untreated NiTi, suggesting a significant improvement on pitting corrosion resistance. Inductively coupled plasma mass spectrometry tests during 60 days immersion demonstrated that Ni ion release rate was remarkably decreased, for example, a reduction of 67% in the first day. The water contact angle increased and surface energy decreased after Hf implantation. Cell culture and methyl-thiazol-tetrazolium indicated that Hf-implanted NiTi expressed enhanced osteoblasts adhesion and proliferation, especially after 7 days culture. Hf implantation decreased fibrinogen adsorption, but had almost no effect on albumin adsorption. Platelets adhesion and activation were suppressed significantly (97% for 4 mA NiTi) and hemolysis rate was decreased by at least 57% after Hf implantation. Modified surface composition and morphology and decreased surface energy should be responsible for the improvement of cytocompatibility and hemocompatibility. Copyright © 2011 Wiley Periodicals, Inc.

  20. Saliva from obese individuals suppresses the release of aroma compounds from wine.

    Paola Piombino

    Full Text Available BACKGROUND: Recent evidence suggests that a lower extent of the retronasal aroma release correspond to a higher amount of ad libitum food intake. This has been regarded as one of the bases of behavioral choices towards food consumption in obese people. In this pilot study we investigated the hypothesis that saliva from obese individuals could be responsible for an alteration of the retro-nasal aroma release. We tested this hypothesis in vitro, by comparing the release of volatiles from a liquid food matrix (wine after its interaction with saliva from 28 obese (O and 28 normal-weight (N individuals. METHODS AND FINDINGS: Amplicon sequencing of the 16S rRNA V4 region indicated that Firmicutes and Actinobacteria were more abundant in O, while Proteobacteria and Fusobacteria dominated in N. Streptococcaceae were significantly more abundant in the O subjects and constituted 34% and 19% on average of the saliva microbiota of O and N subjects, respectively. The Total Antioxidant Capacity was higher in O vs N saliva samples. A model mouth system was used to test whether the in-mouth wine aroma release differs after the interaction with O or N saliva. In O samples, a 18% to 60% significant decrease in the mean concentration of wine volatiles was detected as a result of interaction with saliva, compared with N. This suppression was linked to biochemical differences in O and N saliva composition, which include protein content. CONCLUSION: Microbiological and biochemical differences were found in O vs N saliva samples. An impaired retronasal aroma release from white wine was detected in vitro and linked to compositional differences between saliva from obese and normal-weight subjects. Additional in vivo investigations on diverse food matrices could contribute to understanding whether a lower olfactory stimulation due to saliva composition can be a co-factor in the development/maintenance of obesity.

  1. Saliva from Obese Individuals Suppresses the Release of Aroma Compounds from Wine

    Piombino, Paola; Genovese, Alessandro; Esposito, Silvia; Moio, Luigi; Cutolo, Pier Paolo; Chambery, Angela; Severino, Valeria; Moneta, Elisabetta; Smith, Daniel P.; Owens, Sarah M.; Gilbert, Jack A.; Ercolini, Danilo


    Background Recent evidence suggests that a lower extent of the retronasal aroma release correspond to a higher amount of ad libitum food intake. This has been regarded as one of the bases of behavioral choices towards food consumption in obese people. In this pilot study we investigated the hypothesis that saliva from obese individuals could be responsible for an alteration of the retro-nasal aroma release. We tested this hypothesis in vitro, by comparing the release of volatiles from a liquid food matrix (wine) after its interaction with saliva from 28 obese (O) and 28 normal-weight (N) individuals. Methods and Findings Amplicon sequencing of the 16S rRNA V4 region indicated that Firmicutes and Actinobacteria were more abundant in O, while Proteobacteria and Fusobacteria dominated in N. Streptococcaceae were significantly more abundant in the O subjects and constituted 34% and 19% on average of the saliva microbiota of O and N subjects, respectively. The Total Antioxidant Capacity was higher in O vs N saliva samples. A model mouth system was used to test whether the in-mouth wine aroma release differs after the interaction with O or N saliva. In O samples, a 18% to 60% significant decrease in the mean concentration of wine volatiles was detected as a result of interaction with saliva, compared with N. This suppression was linked to biochemical differences in O and N saliva composition, which include protein content. Conclusion Microbiological and biochemical differences were found in O vs N saliva samples. An impaired retronasal aroma release from white wine was detected in vitro and linked to compositional differences between saliva from obese and normal-weight subjects. Additional in vivo investigations on diverse food matrices could contribute to understanding whether a lower olfactory stimulation due to saliva composition can be a co-factor in the development/maintenance of obesity. PMID:24465618

  2. Drag reducing polymers decrease hepatic injury and metastases after liver ischemia-reperfusion

    Yazdani, Hamza O.; Sud, Vikas; Goswami, Julie; Loughran, Patricia; Huang, Hai; Simmons, Richard L.; Tsung, Allan


    Introduction Surgery, a crucial therapeutic modality in the treatment of solid tumors, can induce sterile inflammatory processes which can result in metastatic progression. Liver ischemia and reperfusion (I/R) injury, an inevitable consequence of hepatic resection of metastases, has been shown to foster hepatic capture of circulating cancer cells and accelerate metastatic growth. Efforts to reduce these negative consequences have not been thoroughly investigated. Drag reducing polymers (DRPs) are blood-soluble macromolecules that can, in nanomolar concentrations, increase tissue perfusion, decrease vascular resistance and decrease near-wall microvascular concentration of neutrophils and platelets thereby possibly reducing the inflammatory microenvironment. We hypothesize that DRP can potentially be used to ameliorate metastatic capture of tumor cells and tumor growth within the I/R liver. Methods Experiments were performed utilizing a segmental ischemia model of mice livers. Five days prior or immediately prior to ischemia, murine colon adenocarcinoma cells (MC38) were injected into the spleen. DRP (polyethylene oxide) or a control of low-molecular-weight polyethylene glycol without drag reducing properties were administered intraperitoneally at the onset of reperfusion. Results After three weeks from I/R, we observed that liver I/R resulted in an increased ability to capture and foster growth of circulating tumor cells; in addition, the growth of pre-existing micrometastases was accelerated three weeks later. These effects were significantly curtailed when mice were treated with DRPs at the time of I/R. Mechanistic investigations in vivo indicated that DRPs protected the livers from I/R injury as evidenced by significant decreases in hepatocellular damage, neutrophil recruitment into the liver, formation of neutrophil extracellular traps, deposition of platelets, formation of microthrombi within the liver sinusoids and release of inflammatory cytokines

  3. Drag reducing polymers decrease hepatic injury and metastases after liver ischemia-reperfusion.

    Tohme, Samer; Kameneva, Marina V; Yazdani, Hamza O; Sud, Vikas; Goswami, Julie; Loughran, Patricia; Huang, Hai; Simmons, Richard L; Tsung, Allan


    Surgery, a crucial therapeutic modality in the treatment of solid tumors, can induce sterile inflammatory processes which can result in metastatic progression. Liver ischemia and reperfusion (I/R) injury, an inevitable consequence of hepatic resection of metastases, has been shown to foster hepatic capture of circulating cancer cells and accelerate metastatic growth. Efforts to reduce these negative consequences have not been thoroughly investigated. Drag reducing polymers (DRPs) are blood-soluble macromolecules that can, in nanomolar concentrations, increase tissue perfusion, decrease vascular resistance and decrease near-wall microvascular concentration of neutrophils and platelets thereby possibly reducing the inflammatory microenvironment. We hypothesize that DRP can potentially be used to ameliorate metastatic capture of tumor cells and tumor growth within the I/R liver. Experiments were performed utilizing a segmental ischemia model of mice livers. Five days prior or immediately prior to ischemia, murine colon adenocarcinoma cells (MC38) were injected into the spleen. DRP (polyethylene oxide) or a control of low-molecular-weight polyethylene glycol without drag reducing properties were administered intraperitoneally at the onset of reperfusion. After three weeks from I/R, we observed that liver I/R resulted in an increased ability to capture and foster growth of circulating tumor cells; in addition, the growth of pre-existing micrometastases was accelerated three weeks later. These effects were significantly curtailed when mice were treated with DRPs at the time of I/R. Mechanistic investigations in vivo indicated that DRPs protected the livers from I/R injury as evidenced by significant decreases in hepatocellular damage, neutrophil recruitment into the liver, formation of neutrophil extracellular traps, deposition of platelets, formation of microthrombi within the liver sinusoids and release of inflammatory cytokines. DRPs significantly attenuated

  4. Fabrics China Trends Released in Guangzhou


    @@ During April 8th-14th, China Textiles Development center, along with China Textile Information Center, released their newly developed "Fabrics China Trends 10 S/S" in China Fabrics & Accessories Center in the city of Guangzhou, aiming to improve the fashion style of China Fabrics & Accessories Center, upgrade the integration of fabrics and fashion trend development, attract more buyers and talent designers, and enhance the quality competitiveness of the trade center significantly.

  5. 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.

  6. Endoscopic iliotibial band release in snapping hip.

    Zini, Raul; Munegato, Daniele; De Benedetto, Massimo; Carraro, Andrea; Bigoni, Marco


    Several open surgical techniques have been used to treat recalcitrant cases of snapping iliotibial band with varying results. Recently, endoscopic techniques have become available. The purpose of this study was to investigate the results of a modified endoscopic iliotibial band release using a longitudinal retrospective case series.
 Fifteen patients (three men and 12 women) with symptomatic external snapping hip were treated with an endoscopic release of the iliotibial band. The average age was 25 years (range 16-37 years). The procedure was performed in the lateral decubitus position using two portals; the iliotibial band was transversally released using a radiofrequency hook probe. The mean follow-up period was 33.8 months (range 12-84 months).
 The snapping phenomenon was overcome in all the patients. The mean pre-op pain VAS score was 5.5 mm (range 5-7 mm) and the mean post-op pain VAS score was 0.53 mm (range 0-2 mm) with a statistically significant reduction with respect to the preoperative value (piliotibial band release is a safe and reproducible technique with excellent results in terms of snapping phenomenon resolution, patient satisfaction, and return to previous level of activity. After strenuous sporting activities 40% of patients complained of very slight pain.

  7. On significance of VLBI/Gaia offsets

    Petrov, L


    We have cross matched the Gaia Data Release 1 secondary dataset that contains positions of 1.14 billion objects against the most complete to date catalogue of VLBI positions of 11.4 thousand sources, almost exclusively active galactic nuclei. We found 6,064 matches, i.e. 53% radio objects. The median uncertainty of VLBI positions is a factor of 4 smaller than the median uncertainties of their optical counterparts. Our analysis shows that the distribution of normalized arc lengths significantly deviates from Rayleighian shape with an excess of objects with small normalized arc lengths and with a number of outliers. We found that 8% matches have radio optical offsets significant at 99% confidence level. Therefore, we conclude there exists a population of objects with genuine offsets between centroids of radio and optical emission.

  8. Activated human neutrophils release hepatocyte growth factor/scatter factor.

    McCourt, M


    BACKGROUND: Hepatocyte growth factor or scatter factor (HGF\\/SF) is a pleiotropic cytokine that has potent angiogenic properties. We have previously demonstrated that neutrophils (PMN) are directly angiogenic by releasing vascular endothelial growth factor (VEGF). We hypothesized that the acute inflammatory response can stimulate PMN to release HGF. AIMS: To examine the effects of inflammatory mediators on PMN HGF release and the effect of recombinant human HGF (rhHGF) on PMN adhesion receptor expression and PMN VEGF release. METHODS: In the first experiment, PMN were isolated from healthy volunteers and stimulated with tumour necrosis factor-alpha (TNF-alpha), lipopolysaccharide (LPS), interleukin-8 (IL-8), and formyl methionyl-leucyl-phenylalanine (fMLP). Culture supernatants were assayed for HGF using ELISA. In the second experiment, PMN were lysed to measure total HGF release and HGF expression in the PMN was detected by Western immunoblotting. Finally, PMN were stimulated with rhHGF. PMN CD 11a, CD 11b, and CD 18 receptor expression and VEGF release was measured using flow cytometry and ELISA respectively. RESULTS: TNF-alpha, LPS and fMLP stimulation resulted in significantly increased release of PMN HGF (755+\\/-216, 484+\\/-221 and 565+\\/-278 pg\\/ml, respectively) compared to controls (118+\\/-42 pg\\/ml). IL-8 had no effect. Total HGF release following cell lysis and Western blot suggests that HGF is released from intracellular stores. Recombinant human HGF did not alter PMN adhesion receptor expression and had no effect on PMN VEGF release. CONCLUSIONS: This study demonstrates that pro-inflammatory mediators can stimulate HGF release from a PMN intracellular store and that activated PMN in addition to secreting VEGF have further angiogenic potential by releasing HGF.

  9. 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.

  10. PGE2 decreases reactivity of human platelets by activating EP2 and EP4.

    Smith, James P; Haddad, Elias V; Downey, Jason D; Breyer, Richard M; Boutaud, Olivier


    Platelet hyperreactivity associates with cardiovascular events in humans. Studies in mice and humans suggest that prostaglandin E2 (PGE2) regulates platelet activation. In mice, activation of the PGE2 receptor subtype 3 (EP3) promotes thrombosis, but the significance of EP3 in humans is less well understood. To characterize the regulation of thromboxane-dependent human platelet activation by PGE2. Platelets collected from nineteen healthy adults were studied using an agonist of the thromboxane receptor (U46,619), PGE2, and selective agonists and/or antagonists of the EP receptor subtypes. Platelet activation was assayed by (1) optical aggregometry, (2) measurement of dense granule release, and (3) single-platelet counting. Healthy volunteers demonstrated significant interindividual variation in platelet response to PGE2. PGE2 completely inhibited U46,619-induced platelet aggregation and ATP release in 26% of subjects; the remaining 74% had partial or no response to PGE2. Antagonism of EP4 abolished the inhibitory effect of PGE2. In all volunteers, a selective EP2 agonist inhibited U46,619-induced aggregation. Furthermore, the selective EP3 antagonist DG-041 converted all PGE2 nonresponders to full responders. There is significant interindividual variation of platelet response to PGE2 in humans. The balance between EP2, EP3, and EP4 activation determines its net effect. PGE2 can prevent thromboxane-induced platelet aggregation in an EP4-dependent manner. EP3 antagonism converts platelets of nonresponders to a PGE2-responsive phenotype. These data suggest that therapeutic targeting of EP pathways may have cardiovascular benefit by decreasing platelet reactivity. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

  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. Anti-IL5 decreases the number of eosinophils but not the severity of dermatitis in Sharpin-deficient mice.

    Renninger, Matthew L; Seymour, Rosemarie E; Whiteley, Laurence O; Sundberg, John P; Hogenesch, Harm


    Sharpin-deficient (Sharpin(cpdm)) mutant mice develop a chronic eosinophilic dermatitis. To determine the efficacy of eosinophil-depletion in chronic inflammation, Sharpin(cpdm) mice were treated with anti-IL5 antibodies. Mice treated with anti-IL5 had a 90% reduction of circulating eosinophils and a 50% decrease in cutaneous eosinophils after 10 days compared with sham-treated littermates. Reducing the number of eosinophils resulted in increased severity of alopecia and erythema and a significant increase in epidermal thickness. Skin homogenates from mice treated with anti-IL5 had decreased mRNA expression of arylsulfatase B (Arsb), diamine oxidase (amiloride-binding protein 1, also called histaminase; Abp1) and Il10, which are mediators that eosinophils may release to quench inflammation. Skin homogenates from mice treated with anti-IL5 also had decreased mRNA expression of Il4, Il5, Ccl11, kit ligand (Kitl) and Tgfa; and increased mRNA expression of Tgfb1, Mmp12 and tenascin C (Tnc). In order to further decrease the accumulation of eosinophils, Sharpin(cpdm) mice were crossed with IL5 null mice. Il5(-/-), Sharpin(cpdm)/Sharpin(cpdm) mice had a 98% reduction of circulating eosinophils and a 95% decrease in cutaneous eosinophils compared with IL5-sufficient Sharpin(cpdm) mice. The severity of the lesions was similar between IL5-sufficient and IL5-deficient mice. Double mutant mice had a significant decrease in Abp1, and a significant increase in Tgfb1, Mmp12 and Tnc mRNA compared with controls. These data indicate that eosinophils are not essential for the development of dermatitis in Sharpin(cpdm) mice and suggest that eosinophils have both pro-inflammatory and anti-inflammatory roles in the skin of these mice.

  13. The Impact of Stress on Tumor Growth; the Significance of Peripheral Corticotropin Releasing Factor


    visualize the architecture of actin in the cell. Cells treated with CRF showed more intense staining compared to the untreated controls, most extensively...time points. Tumor growth was monitored every 4 days using a Fluorescent Molecular Tomography approach ( FMT ) (13) as shown in Figure 12. During the... FMT analysis of the tumors revealed that in mice not exposed to stress, administration of antalarmin resulted in reduced tumor burden. Upon stress

  14. Arthroscopic releases for arthrofibrosis of the knee.

    Chen, Michael R; Dragoo, Jason L


    Intra-articular inflammation or fibrosis may lead to decreased soft-tissue and capsular compliance, which may result in pain or loss of motion within the knee. Etiology of intra-articular fibrosis may include isolated anterior interval scarring and posterior capsular contracture, as well as fibrosis that involves the suprapatellar pouch or arthrofibrosis that involves the entire synovial space. Initial nonsurgical management, including compression, elevation, and physical therapy, can decrease knee pain and inflammation and maintain range of motion. Surgical management is indicated in the patient who fails conservative treatment. Surgical options include arthroscopic releases of the anterior interval, posterior capsule, and peripatellar and suprapatellar regions. Recent advances in arthroscopic technique have led to improved outcomes in patients with intra-articular fibrosis of the knee.

  15. Effect of low-molecular-weight organic acids on kinetics release and fractionation of phosphorus in some calcareous soils of western Iran.

    Taghipour, M; Jalali, M


    Organic acid has been related to nutrient mobilization, mainly in phosphorus (P) insoluble utilization, and therefore enhances P bioavailability. In this study, we examined the effect of low-molecular-weight organic acids (malic, citric, and oxalic acids) on P release of some calcareous soils from western Iran. Fractionation and speciation of P in the soil solution were studied at the initial and final P release. Significantly different quantities of P were extracted by the organic acids. On average the maximum (1,554.9 mg kg(-1)) and the minimum (1,260.5 mg kg(-1)) P were extracted by 10 mM oxalic and malic acid, respectively. Power equation described well P release. In the initial stage of P release, the solution samples in soils were supersaturated with respect to hydroxyapatite and β-TCP. At the end of P release, all solutions were undersaturated with phosphate minerals. The percentage of Fe-Al oxide fraction generally increased after P release, while carbonate and residual P fractions were decreased in all organic acids. Compared with the native soils, adding malic and citric acids had no effect on Fe-Al oxide fraction, but oxalic acid significantly reduced this fraction.

  16. Inhibition of Calpains Protects Mn-Induced Neurotransmitter release disorders in Synaptosomes from Mice: Involvement of SNARE Complex and Synaptic Vesicle Fusion.

    Wang, Can; Xu, Bin; Ma, Zhuo; Liu, Chang; Deng, Yu; Liu, Wei; Xu, Zhao-Fa


    Overexposure to manganese (Mn) could disrupt neurotransmitter release via influencing the formation of SNARE complex, but the underlying mechanisms are still unclear. A previous study demonstrated that SNAP-25 is one of substrate of calpains. The current study investigated whether calpains were involved in Mn-induced disorder of SNARE complex. After mice were treated with Mn for 24 days, Mn deposition increased significantly in basal nuclei in Mn-treated and calpeptin pre-treated groups. Behaviorally, less time spent in the center of the area and decreased average velocity significantly in an open field test after 24 days of Mn exposure. With the increase in MnCl2 dosage, intracellular Ca(2+) increased significantly, but pretreatment with calpeptin caused a dose-dependent decrease in calpains activity. There were fragments of N-terminal of SNAP-25 protein appearance in Mn-treated groups, but it is decreased with pretreatment of calpeptin. FM1-43-labeled synaptic vesicles also provided evidence that the treatment with Mn resulted in increasing first and then decreasing, which was consistent with Glu release and the 80 kDa protein levels of SNARE complexes. In summary, Mn induced the disorder of neurotransmitter release through influencing the formation of SNARE complex via cleaving SNAP-25 by overactivation of calpains in vivo.

  17. Ion release from copper phosphate cement and influence on Streptococcus mutans growth in vitro: a comparative study.

    Foley, Jennifer; Blackwell, Alison


    The aim of this study was to compare the effects of a black copper cement (BCC), an established restorative material (a conventional glass ionomer cement) and two temporary restorative materials (a zinc phosphate and a zinc polycarboxylate cement) on the growth of Streptococcus mutans in vitro, and to correlate bacterial growth with ion release from each material. Test specimens were eluted in either 0.1 M lactic acid, pH 4, or 0.1 M sodium chloride, pH 7. At 2 days, 7 days, 28 days and 6 months, eluates were inoculated with S. mutans and bacterial growth was recorded. Metal ion (Cu(2+), Zn(2+ )and Mg(2+)) and fluoride release were measured. At most immersion times, the different materials had a statistically significant inhibitory effect on bacterial growth compared to the respective control, at both pH levels. The inhibitory effect decreased with time and in most cases was associated with high levels of ion release at the beginning of the experimental period, followed by significantly lower levels. For BCC, there were statistically significant relationships between the median rates of growth of S. mutans in the presence of BCC eluates and the median values for release of copper and zinc, although not magnesium. Of the different materials, BCC demonstrated greatest antibacterial activity.

  18. 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

  19. Tracking the effect of microspheres size on the drug release from a microsphere/sucrose acetate isobutyrate (SAIB) hybrid depot in vitro and in vivo.

    Lin, Xia; Wang, Jing; Xu, Yuhong; Tang, Xing; Chen, Jian; Zhang, Yu; Zhang, Yan; Yang, Ziyi


    The effects of particle size of microspheres on the drug release from a microsphere/sucrose acetate isobutyrate (SAIB) hybrid depot (m-SAIB) was investigated to develop a long-term sustained release drug delivery system with low burst release both in vitro and in vivo. A model drug, risperidone, was first encapsulated into PLGA microspheres with different particle sizes using conventional emulsification and membrane emulsification methods. The m-SAIB was prepared by dispersing the risperidone-microspheres in the SAIB depot. The drug release from m-SAIB was double controlled by the drug diffusion from the microspheres into SAIB matrix and the drug diffusion from the SAIB matrix into the medium. Large microspheres (18.95 ± 18.88 µm) prepared by the conventional homogenization method exhibited porous interior structure, which contributed to the increased drug diffusion rate from microspheres into SAIB matrix. Consequently, m-SAIB containing such microspheres showed rapid initial drug release (Cmax = 110.1 ±54.2 ng/ml) and subsequent slow drug release (Cs(4-54d)= 2.7 ± 0.8 ng/ml) in vivo. Small microspheres (5.91 ± 2.24 µm) showed dense interior structure with a decreased drug diffusion rate from microspheres into SAIB matrix. The initial drug release from the corresponding m-SAIB was significantly decreased (Cmax = 40.9 ± 13.7 ng/ml), whereas the drug release rate from 4 to 54 d was increased (Cs(4-54d)=4.1 ± 1.0 ng/ml). By further decreasing the size of microspheres to 3.38 ± 0.70 µm, the drug diffusion surface area was increased, which subsequently increased the drug release from the m-SAIB. These results demonstrate that drug release from the m-SAIB can be tailored by varying the size of microspheres to reduce the in vivo burst release of SAIB system alone.

  20. Controlled release implants based on cast lipid blends.

    Kreye, F; Siepmann, F; Zimmer, A; Willart, J F; Descamps, M; Siepmann, J


    The aim of this study was to use lipid:lipid blends as matrix formers in controlled release implants. The systems were prepared by melting and casting and thoroughly characterized before and after exposure to the release medium. Based on the experimental results, a mechanistic realistic mathematical model was used to get further insight into the underlying drug release mechanisms. Importantly, broad spectra of drug release patterns could be obtained by simply varying the lipid:lipid blend ratio in implants based on Precirol ATO 5 (glyceryl palmitostearate):Dynasan 120 (hardened soybean oil) mixtures loaded with propranolol hydrochloride. Release periods ranging from a few days up to several months could be provided. Interestingly, the drug release rate monotonically decreased with increasing Dynasan 120 content, except for implants containing about 20-25% Precirol, which exhibited surprisingly high release rates. This could be attributed to the incomplete miscibility of the two lipids at these blend ratios: DSC thermograms showed phase separation in these systems. This is likely to cause differences in the implants' microstructure, which determines the mobility of water and dissolved drug as well as the mechanical stability of the systems. Purely diffusion controlled drug release was only observed at Precirol ATO 5 contents around 5-10%. In all other cases, limited drug solubility effects or matrix former erosion are also expected to play a major role. Thus, lipid:lipid blends are very interesting matrix formers in controlled release implants. However, care must be taken with respect to the mutual miscibility of the compounds: in case of phase separation, surprisingly high drug release rates might be observed.

  1. 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.

  2. Hyper-arousal decreases human visual thresholds.

    Adam J Woods

    Full Text Available Arousal has long been known to influence behavior and serves as an underlying component of cognition and consciousness. However, the consequences of hyper-arousal for visual perception remain unclear. The present study evaluates the impact of hyper-arousal on two aspects of visual sensitivity: visual stereoacuity and contrast thresholds. Sixty-eight participants participated in two experiments. Thirty-four participants were randomly divided into two groups in each experiment: Arousal Stimulation or Sham Control. The Arousal Stimulation group underwent a 50-second cold pressor stimulation (immersing the foot in 0-2° C water, a technique known to increase arousal. In contrast, the Sham Control group immersed their foot in room temperature water. Stereoacuity thresholds (Experiment 1 and contrast thresholds (Experiment 2 were measured before and after stimulation. The Arousal Stimulation groups demonstrated significantly lower stereoacuity and contrast thresholds following cold pressor stimulation, whereas the Sham Control groups showed no difference in thresholds. These results provide the first evidence that hyper-arousal from sensory stimulation can lower visual thresholds. Hyper-arousal's ability to decrease visual thresholds has important implications for survival, sports, and everyday life.

  3. Hyper-arousal decreases human visual thresholds.

    Woods, Adam J; Philbeck, John W; Wirtz, Philip


    Arousal has long been known to influence behavior and serves as an underlying component of cognition and consciousness. However, the consequences of hyper-arousal for visual perception remain unclear. The present study evaluates the impact of hyper-arousal on two aspects of visual sensitivity: visual stereoacuity and contrast thresholds. Sixty-eight participants participated in two experiments. Thirty-four participants were randomly divided into two groups in each experiment: Arousal Stimulation or Sham Control. The Arousal Stimulation group underwent a 50-second cold pressor stimulation (immersing the foot in 0-2° C water), a technique known to increase arousal. In contrast, the Sham Control group immersed their foot in room temperature water. Stereoacuity thresholds (Experiment 1) and contrast thresholds (Experiment 2) were measured before and after stimulation. The Arousal Stimulation groups demonstrated significantly lower stereoacuity and contrast thresholds following cold pressor stimulation, whereas the Sham Control groups showed no difference in thresholds. These results provide the first evidence that hyper-arousal from sensory stimulation can lower visual thresholds. Hyper-arousal's ability to decrease visual thresholds has important implications for survival, sports, and everyday life.

  4. Ceruloplasmin decreases respiratory burst reaction during pregnancy.

    Varfolomeeva, Elena Y; Semenova, Elena V; Sokolov, Alexey V; Aplin, Kirill D; Timofeeva, Kseniya E; Vasilyev, Vadim B; Filatov, Michael V


    Testing of pregnant women reveals weakening of neutrophil-mediated effector functions, such as reactive oxygen species generation. This study provides data confirming the phenomenon, gained through application of the flow cytometry technique. Key factors influencing neutrophil functional activity in blood plasma of pregnant women have not been detected so far. At the same time, concentration of ceruloplasmin - a copper-containing glycoprotein - is known to increase in blood significantly during pregnancy. We observed the negative correlation between ceruloplasmin concentration in blood plasma of pregnant women and the intensity of respiratory burst of neutrophils. Fractionation of plasma using gel-filtration revealed that ceruloplasmin-containing fraction demonstrated suppression of the respiratory burst reaction. Partial elimination of ceruloplasmin from the blood of pregnant women, performed with the help of specific antibodies and followed by immunoprecipitation, leads to an increased respiratory burst reaction. On the contrary, addition of ceruloplasmin to blood samples of healthy donors noticeably decreases the respiratory burst reaction. The results presented prove that change in ceruloplasmin level in plasma is necessary and sufficient for modulating the ability of neutrophils to produce reactive oxygen species during pregnancy.

  5. Flavour release of aldehydes and diacetyl in oil/water systems

    Haahr, Anne-Mette; Bredie, W. L. P.; Stahnke, Louise Heller


    The concentration- and time-dependent release of three C-6-aldehydes, six C-9-aldehydes and diacetyl was studied in model systems. The systems were water, rapeseed oil and oil-in-water emulsions. Dynamic headspace sampling was used to collect the volatile compounds. In the concentration......-dependent release experiment, the C-6-aldehydes were released in equal proportions from the aqueous and the emulsion systems, but in lower amounts from the pure oil. The amounts of C-9-aldehydes released decreased with increasing oil content. All aldehydes were released more rapidly from the aqueous system than...... from the pure oil. The release over time for diacetyl and (E,E)-2,4-hexadienal showed a linear relationship in all systems. The other compounds followed an exponential relationship between the time and the fraction released in the aqueous systems. It was demonstrated that the release of the volatile...

  6. Monoclonal gammopathy of undetermined significance

    Kyle, Robert A; Vincent Rajkumar, S


    Summary Significant advances have been made in our understanding of the natural history, pathogenesis, mechanisms of progression and prognosis of monoclonal gammopathy of undetermined significance (MGUS...

  7. Red blood cell decreases of microgravity

    Johnson, P. C.


    Postflight decreases in red blood cell mass (RBCM) have regularly been recorded after exposure to microgravity. These 5-25 percent decreases do not relate to the mission duration, workload, caloric intake or to the type of spacecraft used. The decrease is accompanied by normal red cell survivals, increased ferritin levels, normal radioactive iron studies, and increases in mean red blood cell volume. Comparable decreases in red blood cell mass are not found after bed rest, a commonly used simulation of the microgravity state. Inhibited bone marrow erythropoiesis has not been proven to date, although reticulocyte numbers in the peripheral circulation are decreased about 50 percent. To date, the cause of the microgravity induced decreases in RBCM is unknown. Increased splenic trapping of circulating red blood cells seem the most logical way to explain the results obtained.

  8. 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.

  9. Stimuli-free programmable drug release for combination chemo-therapy

    Fan, Li; Jin, Boquan; Zhang, Silu; Song, Chaojun; Li, Quan


    Combinational chemotherapy capable of targeted delivery and programmable multi-drug release leads to enhanced drug efficacy, and is highly desired for cancer treatment. However, effective approaches for achieving both features in a single treatment are limited. In the present work, we demonstrated programmed delivery of both chemotherapeutic and immunotherapeutic agents with tumor cell targeting capability by using SiO2 based self-decomposable nanoparticulate systems. The programmable drug delivery is realized by manipulating drug loading configurations instead of relying on external stimuli. Both in vitro and in vivo results showed specific drug binding to FAT1-expressing colon cancer cells. The loaded dual drugs were demonstrated to be delivered in a sequential manner with specific time intervals between their peak releases, which maximize the synergistic effect of the chemotherapeutics. These features led to significantly enhanced drug efficacy and reduced system toxicity. The tumor weight decreased by 1/350, together with a moderate increase in rats' body weight, which were observed when adopting the dual drug loaded nanoparticles, as compared to those of the control groups. The present system provides a simple and feasible method for the design of targeting and combination chemotherapy with programmed drug release.Combinational chemotherapy capable of targeted delivery and programmable multi-drug release leads to enhanced drug efficacy, and is highly desired for cancer treatment. However, effective approaches for achieving both features in a single treatment are limited. In the present work, we demonstrated programmed delivery of both chemotherapeutic and immunotherapeutic agents with tumor cell targeting capability by using SiO2 based self-decomposable nanoparticulate systems. The programmable drug delivery is realized by manipulating drug loading configurations instead of relying on external stimuli. Both in vitro and in vivo results showed specific drug

  10. Biointerfacing polymeric microcapsules for in vivo near-infrared light-triggered drug release