Sample records for administration significantly increased

  1. Continues administration of Nano-PSO significantly increased survival of genetic CJD mice.

    PubMed

    Binyamin, Orli; Keller, Guy; Frid, Kati; Larush, Liraz; Magdassi, Shlomo; Gabizon, Ruth

    2017-12-01

    We have shown previously that Nano-PSO, a nanodroplet formulation of pomegranate seed oil, delayed progression of neurodegeneration signs when administered for a designated period of time to TgMHu2ME199K mice, modeling for genetic prion disease. In the present work, we treated these mice with a self-emulsion formulation of Nano-PSO or a parallel Soybean oil formulation from their day of birth until a terminal disease stage. We found that long term Nano-PSO administration resulted in increased survival of TgMHu2ME199K lines by several months. Interestingly, initiation of treatment at day 1 had no clinical advantage over initiation at day 70, however cessation of treatment at 9months of age resulted in the rapid loss of the beneficial clinical effect. Pathological studies revealed that treatment with Nano-PSO resulted in the reduction of GAG accumulation and lipid oxidation, indicating a strong neuroprotective effect. Contrarily, the clinical effect of Nano-PSO did not correlate with reduction in the levels of disease related PrP, the main prion marker. We conclude that long term administration of Nano-PSO is safe and may be effective in the prevention/delay of onset of neurodegenerative conditions such as genetic CJD. Copyright © 2017. Published by Elsevier Inc.

  2. Repeated administration of fresh garlic increases memory retention in rats.

    PubMed

    Haider, Saida; Naz, Nosheen; Khaliq, Saima; Perveen, Tahira; Haleem, Darakhshan J

    2008-12-01

    Garlic (Allium sativum) is regarded as both a food and a medicinal herb. Increasing attention has focused on the biological functions and health benefits of garlic as a potentially major dietary component. Chronic garlic administration has been shown to enhance memory function. Evidence also shows that garlic administration in rats affects brain serotonin (5-hydroxytryptamine [5-HT]) levels. 5-HT, a neurotransmitter involved in a number of physiological functions, is also known to enhance cognitive performance. The present study was designed to investigate the probable neurochemical mechanism responsible for the enhancement of memory following garlic administration. Sixteen adult locally bred male albino Wistar rats were divided into control (n = 8) and test (n = 8) groups. The test group was orally administered 250 mg/kg fresh garlic homogenate (FGH), while control animals received an equal amount of water daily for 21 days. Estimation of plasma free and total tryptophan (TRP) and whole brain TRP, 5-HT, and 5-hydroxyindole acetic acid (5-HIAA) was determined by high-performance liquid chromatography with electrochemical detection. For assessment of memory, a step-through passive avoidance paradigm (electric shock avoidance) was used. The results showed that the levels of plasma free TRP significantly increased (P < .01) and plasma total TRP significantly decreased (P < .01) in garlic-treated rats. Brain TRP, 5-HT, and 5-HIAA levels were also significantly increased following garlic administration. A significant improvement in memory function was exhibited by garlic-treated rats in the passive avoidance test. Increased brain 5-HT levels were associated with improved cognitive performance. The present results, therefore, demonstrate that the memory-enhancing effect of garlic may be associated with increased brain 5-HT metabolism in rats. The results further support the use of garlic as a food supplement for the enhancement of memory.

  3. Aripiprazole maintenance increases smoked cocaine self-administration in humans

    PubMed Central

    Rubin, Eric; Foltin, Richard W.

    2011-01-01

    Rationale Partial dopamine receptor agonists have been proposed as candidate pharmacotherapies for cocaine dependence. Objective This 42-day, within-subject, human laboratory study assessed how maintenance on aripiprazole, a partial D2 receptor agonist, influenced smoked cocaine self-administration, cardiovascular measures, subjective effects, and cocaine craving in nontreatment-seeking, cocaine-dependent volunteers. Methods In order to achieve steady-state concentrations, participants (n=8 men) were administered placebo and aripiprazole (15 mg/day) capsules in counter-balanced order for 21 days. A smoked cocaine dose–response curve (0, 12, 25, 50 mg) was determined twice under placebo and aripiprazole maintenance. Sessions comprised a “sample” trial, when participants smoked the cocaine dose available that session, and five choice trials, when they responded on a progressive-ratio schedule of reinforcement to receive the cocaine dose or receive $5.00. Results Cocaine’s reinforcing, subjective, and cardiovascular effects were dose-dependent. Aripiprazole significantly increased cocaine (12, 25 mg) self-administration. Following a single administration of cocaine (25 mg), aripiprazole decreased ratings of how much participants would pay for that dose. Following repeated cocaine (50 mg) self-administration, aripiprazole decreased ratings of cocaine quality, craving, and good drug effect as compared to placebo. Conclusions These data suggest that aripiprazole may have increased self-administration to compensate for a blunted subjective cocaine effect. Overall, the findings do not suggest aripiprazole would be useful for treating cocaine dependence. PMID:21373790

  4. In Vivo Administration of a JAK3 Inhibitor during Acute SIV Infection Leads to Significant Increases in Viral Load during Chronic Infection

    PubMed Central

    Takahashi, Yoshiaki; Byrareddy, Siddappa N.; Albrecht, Christina; Brameier, Markus; Walter, Lutz; Mayne, Ann E.; Dunbar, Paul; Russo, Robert; Little, Dawn M.; Villinger, Tara; Khowawisetsut, Ladawan; Pattanapanyasat, Kovit; Villinger, Francois; Ansari, Aftab A.

    2014-01-01

    The studies reported herein are the first to document the effect of the in vivo administration of a JAK3 inhibitor for defining the potential role of NK cells during acute SIV infection of a group of 15 rhesus macaques (RM). An additional group of 16 MHC/KIR typed RM was included as controls. The previously optimized in vivo dose regimen (20 mg/kg daily for 35 days) led to a marked depletion of each of the major NK cell subsets both in the blood and gastro-intestinal tissues (GIT) during acute infection. While such depletion had no detectable effects on plasma viral loads during acute infection, there was a significant sustained increase in plasma viral loads during chronic infection. While the potential mechanisms that lead to such increased plasma viral loads during chronic infection remain unclear, several correlates were documented. Thus, during acute infection, the administration of the JAK3 inhibitor besides depleting all NK cell subsets also decreased some CD8+ T cells and inhibited the mobilization of the plasmacytoid dendritic cells in the blood and their localization to the GIT. Of interest is the finding that the administration of the JAK3 inhibitor during acute infection also resulted in the sustained maintenance during chronic infection of a high number of naïve and central memory CD4+ T cells, increases in B cells in the blood, but decreases in the frequencies and function of NKG2a+ NK cells within the GIT and blood, respectively. These data identify a unique role for JAK3 inhibitor sensitive cells, that includes NK cells during acute infection that in concert lead to high viral loads in SIV infected RM during chronic infection without affecting detectable changes in antiviral humoral/cellular responses. Identifying the precise mechanisms by which JAK3 sensitive cells exert their influence is critical with important implications for vaccine design against lentiviruses. PMID:24603870

  5. Oral Administration of Cilostazol Increases Ocular Blood Flow in Patients with Diabetic Retinopathy.

    PubMed

    Hwang, Duck Jin; Shin, Joo Young; Yu, Hyeong Gon

    2017-04-01

    To investigate the effect of cilostazol on ocular hemodynamics and to determine whether the administration of cilostazol increases the ocular blood flow in patients with diabetic retinopathy. This prospective observational study investigated the effect of orally administered cilostazol on diabetic retinopathy. Before and after administration for 1 week, pulsatile ocular blood flow (POBF) and retrobulbar hemodynamics were measured using a POBF analyzer and transcranial Doppler imaging, respectively. Visual acuity, intraocular pressure, and blood pressure were also evaluated before and after treatment. Twenty-five eyes of 25 patients were included in this study. POBF increased significantly (16.8 ± 4.6 µL/sec vs. 19.6 ± 6.2 µL/sec, p < 0.001) after administration of cilostazol, while no significant change was identified in visual acuity, intraocular pressure, and blood pressure. Mean flow velocity in the ophthalmic artery as measured with transcranial Doppler imaging also increased significantly after medication (23.5 ± 5.6 cm/sec vs. 26.0 ± 6.9 cm/sec, p = 0.001). The change in POBF directly correlated with the change in mean flow velocity (r = 0.419, p = 0.007). Cilostazol was effective in increasing ocular blood flow in patients with diabetic retinopathy, possibly by modulating retrobulbar circulation.

  6. Why Block Grants Should Increase Administrative Costs.

    ERIC Educational Resources Information Center

    Baker, Keith

    1983-01-01

    Federal education programs increase costs because they attach fewer strings to funds than state or local grants, and this is likely to lead to administrative empire-building. Bureaucracy tends pathologically as it grows to generate more work for itself independent of true administrative needs. Some policy implications are drawn. (MJL)

  7. Neuropeptide Y administration into the third ventricle does not increase sucrose or ethanol self-administration but does affect the cortical EEG and increases food intake.

    PubMed

    Katner, S N; Slawecki, C J; Ehlers, C L

    2002-03-01

    Several studies have provided indirect evidence that neuropeptide Y (NPY) may play a role in the regulation of ethanol consumption. However, the direct effects of central NPY administration on ethanol drinking are unclear. This study examined the effects of NPY on ethanol, sucrose, and food consumption as well as its concomitant effects on the cortical EEG. Wistar rats were implanted with cortical recording electrodes and a cannula in the third ventricle after using a sucrose substitution procedure to establish ethanol self-administration. NPY (0-15 microg/3.0 microl) was infused into the third ventricle prior to drinking sessions, when 10% ethanol (10E), 2% sucrose (2S), 0.5% sucrose (0.5S), or food were available. Behavior and cortical EEG were monitored during the sessions. NPY had no effect on the intake of 10E, 2S, or 0.5S, but NPY (15 microg/3.0 microl) significantly increased food intake. Under baseline drinking conditions, EEG power in the 6-8 Hz range was significantly greater when 2S was consumed compared to 10E. NPY decreased power in the 8-16 Hz range, decreased peak frequency in the 6-8 Hz range, and increased peak frequency in the 32-50 Hz range when 10E or 2S was available. These data suggest that NPY administration into the third ventricle preferentially regulates feeding compared to ethanol or sucrose drinking. In addition, since NPY significantly altered the cortical EEG in the absence of effects on ethanol and sucrose consumption, these data may indicate that NPY's cortical EEG effects are more related to its sedative or anxiolytic properties, rather than any effect on consumption.

  8. Long-term administration of inulin-type fructans has no significant lipid-lowering effect in normolipidemic humans.

    PubMed

    Forcheron, Fabien; Beylot, Michel

    2007-08-01

    Short-term studies have shown that the addition to diet of inulin-type fructans, a nondigestible carbohydrate, may have a plasma lipid-lowering effect in humans. Whether this beneficial effect persists during long-term administration has not been determined. The study was aimed at determining whether a prolonged (6 months) administration of inulin-type fructans to healthy subjects has a lipid-lowering action. In a double-blind, randomized, placebo-controlled study, 17 healthy subjects were studied before and after 6 months of daily administration of placebo (8 subjects) or 10 g of a mix of inulin and oligofructose (9 subjects). During this 6-month period, they consumed their usual diet and did not modify their everyday way of life. We measured plasma lipid concentrations; cholesterol synthesis and hepatic lipogenesis; and adipose tissue and circulating mononuclear cell messenger RNA concentrations of key regulatory genes of cholesterol metabolism. Compared with the administration of placebo, the administration of inulin-type fructans had no effect on plasma triacylglycerol concentrations and hepatic lipogenesis and induced only a nonsignificant trend for decreased plasma total and low-density lipoprotein cholesterol levels and increased high-density lipoprotein cholesterol concentration. Cholesterol synthesis was not significantly modified. Of all the messenger RNA concentrations measured, none was significantly modified by the administration of inulin-type fructans. In conclusion, contrary to what was observed in short-term studies, we observed no significant beneficial effect of a long-term (6-month) administration of inulin-type fructans on plasma lipids in healthy human subjects.

  9. Heat increases MDMA-enhanced NAcc 5-HT and body temperature, but not MDMA self-administration.

    PubMed

    Feduccia, Allison A; Kongovi, Nundhun; Duvauchelle, Christine L

    2010-12-01

    There is a concern that hot environments enhance adverse effects of 3,4-methylenedioxymethamphetamine (MDMA or "Ecstasy"). In this study, long-term (4-weeks) daily MDMA self-administration sessions and an MDMA Challenge test were conducted with rats under normal and high thermal conditions (23° or 32°C). During MDMA self-administration sessions, activity and body temperature were increased by heat or MDMA experience, while MDMA self-administration rates increased with experience, but were comparable between thermal conditions. At the MDMA Challenge test (3.0 mg/kg, i.v.), in vivo microdialysis showed that nucleus accumbens serotonin (NAcc 5-HT) and dopamine (DA) responses were significantly increased in both thermal conditions. In the heated environment, MDMA-stimulated 5-HT responses and core temperature (but not DA) were significantly greater than at room temperature. Though the heated environment did not acutely boost MDMA intake, exaggerated NAcc 5-HT responses to MDMA may result in 5-HT depletion; a condition associated with Ecstasy use escalation and neural dysfunctions altering mood and cognition. Copyright © 2010 Elsevier B.V. All rights reserved.

  10. Heat increases MDMA-enhanced NAcc 5-HT and body temperature, but not MDMA self-administration

    PubMed Central

    Feduccia, Allison A.; Kongovi, Nundhun

    2011-01-01

    There is concern that hot environments enhance adverse effects of 3,4-methylenedioxymethamphetamine (MDMA or “Ecstasy”). In this study, long-term (4-wks) daily MDMA self-administration sessions and an MDMA challenge test were conducted with rats under normal and high thermal conditions (23° or 32° C). During MDMA self-administration sessions, activity and body temperature were increased by heat or MDMA experience, while MDMA self-administration rates increased with experience, but were comparable between thermal conditions. At the MDMA challenge test (3.0 mg/kg, i.v.), in vivo microdialysis showed nucleus accumbens serotonin (NAcc 5-HT) and dopamine (DA) responses were significantly increased in both thermal conditions. In the heated environment, MDMA-stimulated 5-HT responses and core temperature (but not DA) were significantly greater than at room temperature. Though the heated environment did not acutely boost MDMA intake, exaggerated NAcc 5-HT responses to MDMA may result in 5-HT depletion; a condition associated with Ecstasy use escalation and neural dysfunctions altering mood and cognition. PMID:20888192

  11. Increased analgesia administration in emergency medicine after implementation of revised guidelines.

    PubMed

    Van Woerden, Geesje; Van Den Brand, Crispijn L; Den Hartog, Cornelis F; Idenburg, Floris J; Grootendorst, Diana C; Van Der Linden, M Christien

    2016-12-01

    The most common complaint of patients attending the emergency department (ED) is pain, caused by different diseases. Yet the treatment of pain at the ED is suboptimal, and oligoanalgesia remains common. The objective of this study is to determine whether the administration of analgesia at the ED increases by implementation of revised guidelines in pain management. We conducted a prospective pre-post intervention cohort study with implementation of a revised guideline for pain management at our ED, in which nurses are allowed to administer analgesia (including low-dosage piritramid (opioid) intravenous) without doctor intervention. Numeric Rating Scales (NRS) were measured, and administration of medication (main outcome) was documented. We included every adult patient presenting with pain (NRS 4-10) at the ED. A total of 2107 patients (1089 pre-implementation phase and 1018 post-implementation phase) were included in our study. During pre-implementation, 25.4 % of the patients with NRS between 4 and 10 received analgesia. After implementation, 32.0 % of these patients received analgesia (p < 0.001). After implementation of the revised guidelines in pain management at the ED, the administration of pain medication increased significantly. Nevertheless, the percentage of patients in pain receiving analgesia remain low (32 % after implementation).

  12. Daily morphine administration increases impulsivity in rats responding under a 5‐choice serial reaction time task

    PubMed Central

    Maguire, DR; Henson, C

    2016-01-01

    Background and Purpose Repeated administration of a μ opioid receptor agonist can enhance some forms of impulsivity, such as delay discounting. However, it is unclear whether repeated administration alters motor impulsivity. Experimental Approach We examined the effects of acute administration of morphine and amphetamine prior to and during daily morphine administration in rats responding under a five‐choice serial reaction time task. Rats (n = 5) were trained to detect a brief flash of light presented randomly in one of five response holes; responding in the target hole delivered food, whereas responding in the wrong hole or responding prior to illumination of the target stimulus (premature response) initiated a timeout. Premature responding served as an index of motor impulsivity. Key Results Administered acutely, morphine (0.1–10 mg·kg−1, i.p.) increased omissions and modestly, although not significantly, premature responding without affecting response accuracy; amphetamine (0.1–1.78 mg·kg−1, i.p.) increased premature responding without changing omissions or response accuracy. After 3 weeks of 10 mg·kg−1·day−1 morphine, tolerance developed to its effects on omissions whereas premature responding increased approximately fourfold, compared with baseline. Effects of amphetamine were not significantly affected by daily morphine administration. Conclusions and Implications These data suggest that repeated administration of morphine increased effects of morphine on motor impulsivity, although tolerance developed to other effects, such as omissions. To the extent that impulsivity is a risk factor for drug abuse, repeated administration of μ opioid receptor agonists, for recreational or therapeutic purposes, might increase impulsivity and thus the risk for drug abuse. PMID:26776751

  13. Midlevel Administrators' Pay Increases Slightly but Doesn't Match Inflation

    ERIC Educational Resources Information Center

    Fuller, Andrea

    2012-01-01

    Salaries for midlevel administrators rose by a median of 2 percent this year over last year, matching the median pay increase for senior administrators and coming in slightly higher than the 1.9-percent median increase for faculty members, says an annual report released by the College and University Professional Association for Human Resources.…

  14. Repeated Administration of Cigarette Smoke Condensate Increases Glutamate Levels and Behavioral Sensitization

    PubMed Central

    Ryu, In Soo; Kim, Jieun; Seo, Su Yeon; Yang, Ju Hwan; Oh, Jeong Hwan; Lee, Dong Kun; Cho, Hyun-Wook; Lee, Kyuhong; Yoon, Seong Shoon; Seo, Joung-Wook; Shim, Insop; Choe, Eun Sang

    2018-01-01

    Nicotine, a nicotinic acetylcholine receptor agonist, produces the reinforcing effects of tobacco dependence by potentiating dopaminergic and glutamatergic neurotransmission. Non-nicotine alkaloids in tobacco also contribute to dependence by activating the cholinergic system. However, glutamatergic neurotransmission in the dorsal striatum associated with behavioral changes in response to cigarette smoking has not been investigated. In this study, the authors investigated alterations in glutamate levels in the rat dorsal striatum related to behavioral alterations after repeated administration of cigarette smoke condensate (CSC) using the real-time glutamate biosensing and an open-field behavioral assessment. Repeated administration of CSC including 0.4 mg nicotine (1.0 mL/kg/day, subcutaneous) for 14 days significantly increased extracellular glutamate concentrations more than repeated nicotine administration. In parallel with the hyperactivation of glutamate levels, repeated administration of CSC-evoked prolonged hypersensitization of psychomotor activity, including locomotor and rearing activities. These findings suggest that the CSC-induced psychomotor activities are closely associated with the elevation of glutamate concentrations in the rat dorsal striatum. PMID:29615877

  15. Intrahippocampal administration of anandamide increases REM sleep.

    PubMed

    Rueda-Orozco, Pavel Ernesto; Soria-Gómez, Edgar; Montes-Rodríguez, Corinne Jennifer; Pérez-Morales, Marcel; Prospéro-García, Oscar

    2010-04-05

    A nascent literature has postulated endocannabinoids (eCBs) as strong sleep-inducing lipids, particularly rapid-eye-movement sleep (REMs), nevertheless the exact mechanisms behind this effect remain to be determined. Anandamide and 2-arachidonyl glycerol, two of the most important eCBS, are synthesized in the hippocampus. This structure also expresses a high concentration of cannabinoid receptor 1 (CB1). Recent extensive literature supports eCBs as important regulators of hippocampal activity. It has also been shown that these molecules vary their expression on the hippocampus depending on the light-dark cycle. In this context we decided to analyze the effect of intrahippocampal administration of the eCB anandamide (ANA) on the sleep-waking cycle at two points of the light-dark cycle. Our data indicate that the administration of ANA directly into the hippocampus increases REMs in a dose dependent manner during the dark but not during the light phase of the cycle. The increase of REMs was blocked by the CB1 antagonist AM251. This effect was specific for the hippocampus since ANA administrations in the surrounding cortex did not elicit any change in REMs. These results support the idea of a direct relationship between hippocampal activity and sleep mechanisms by means of eCBs. The data presented here show, for the first time that eCBs administered into the hippocampus trigger REMs and support previous studies where chemical stimulation of limbic areas triggered sleep.

  16. Moderate high fat diet increases sucrose self-administration in young rats.

    PubMed

    Figlewicz, Dianne P; Jay, Jennifer L; Acheson, Molly A; Magrisso, Irwin J; West, Constance H; Zavosh, Aryana; Benoit, Stephen C; Davis, Jon F

    2013-02-01

    We have previously reported that a moderately high fat diet increases motivation for sucrose in adult rats. In this study, we tested the motivational, neurochemical, and metabolic effects of the high fat diet in male rats transitioning through puberty, during 5-8 weeks of age. We observed that the high fat diet increased motivated responding for sucrose, which was independent of either metabolic changes or changes in catecholamine neurotransmitter metabolites in the nucleus accumbens. However, AGRP mRNA levels in the hypothalamus were significantly elevated. We demonstrated that increased activation of AGRP neurons is associated with motivated behavior, and that exogenous (third cerebroventricular) AGRP administration resulted in significantly increased motivation for sucrose. These observations suggest that increased expression and activity of AGRP in the medial hypothalamus may underlie the increased responding for sucrose caused by the high fat diet intervention. Finally, we compared motivation for sucrose in pubertal vs. adult rats and observed increased motivation for sucrose in the pubertal rats, which is consistent with previous reports that young animals and humans have an increased preference for sweet taste, compared with adults. Together, our studies suggest that background diet plays a strong modulatory role in motivation for sweet taste in adolescent animals. Published by Elsevier Ltd.

  17. Moderate High Fat Diet Increases Sucrose Self-Administration In Young Rats

    PubMed Central

    Figlewicz, Dianne P.; Jay, Jennifer L.; Acheson, Molly A.; Magrisso, Irwin J.; West, Constance H.; Zavosh, Aryana; Benoit, Stephen C.; Davis, Jon F.

    2012-01-01

    We have previously reported that a moderately high fat diet increases motivation for sucrose in adult rats. In this study, we tested the motivational, neurochemical, and metabolic effects of the high fat diet in male rats transitioning through puberty, during 5-8 weeks of age. We observed that the high fat diet increased motivated responding for sucrose, which was independent of either metabolic changes or changes in catecholamine neurotransmitter metabolites in the nucleus accumbens. However, AGRP mRNA levels in the hypothalamus were significantly elevated. We demonstrated that increased activation of AGRP neurons is associated with motivated behavior, and that exogenous (third cerebroventricular) AGRP administration resulted in significantly increased motivation for sucrose. These observations suggest that increased expression and activity of AGRP in the medial hypothalamus may underlie the increased responding for sucrose caused by the high fat diet intervention. Finally, we compared motivation for sucrose in pubertal vs. adult rats and observed increased motivation for sucrose in the pubertal rats, which is consistent with previous reports that young animals and humans have an increased preference for sweet taste, compared with adults. Together, our studies suggest that background diet plays a strong modulatory role in motivation for sweet taste in adolescent animals. PMID:23023044

  18. Increased oxidative stress in patients with amyotrophic lateral sclerosis and the effect of edaravone administration.

    PubMed

    Nagase, Midori; Yamamoto, Yorihiro; Miyazaki, Yusuke; Yoshino, Hiide

    2016-05-01

    Compared to age-matched healthy controls (n = 55), patients with amyotrophic lateral sclerosis (ALS) (n = 26) showed increased oxidative stress as indicated by a significantly increased percentage of oxidized coenzyme Q10 (%CoQ10) in total plasma coenzyme Q10, a significantly decreased level of plasma uric acid, and a significantly decreased percentage of polyunsaturated fatty acids in total plasma free fatty acids (FFA). Therefore, the efficacy of edaravone, a radical scavenger, in these ALS patients was examined. Among 26 ALS patients, 17 received edaravone (30 mg/day, one to four times a week) for at least 3 months, and 13 continued for 6 months. Changes in revised ALS functional rating scale (ALSFRS-R) were significantly smaller in these patients than in edaravone-untreated ALS patients (n = 19). Edaravone administration significantly reduced excursions of more than one standard deviation from the mean for plasma FFA levels and the contents of palmitoleic and oleic acids, plasma markers of tissue oxidative damage, in the satisfactory progress group (ΔALSFRS-R ≥ 0) as compared to the ingravescent group (ΔALSFRS-R < -5). Edaravone treatment increased plasma uric acid, suggesting that it is an effective scavenger of peroxynitrite. However, edaravone administration did not decrease %CoQ10. Therefore, combined treatment with agents such as coenzyme Q10 may further reduce oxidative stress in ALS patients.

  19. Testosterone Administration Inhibits Hepcidin Transcription and is Associated with Increased Iron Incorporation into Red Blood Cells

    PubMed Central

    Guo, Wen; Bachman, Eric; Li, Michelle; Roy, Cindy N.; Blusztajn, Jerzy; Wong, Siu; Chan, Stephen Y.; Serra, Carlo; Jasuja, Ravi; Travison, Thomas G.; Muckenthaler, Martina U.; Nemeth, Elizabeta; Bhasin, Shalender

    2013-01-01

    Testosterone administration increases hemoglobin levels and has been used to treat anemia of chronic disease. Erythrocytosis is the most frequent adverse event associated with testosterone therapy of hypogonadal men, especially older men. However, the mechanisms by which testosterone increases hemoglobin remain unknown. Testosterone administration in male and female mice was associated with a greater increase in hemoglobin and hematocrit, reticulocyte count, reticulocyte hemoglobin concentration, and serum iron and transferring saturation than placebo. Testosterone downregulated hepatic hepcidin mRNA expression, upregulated renal erythropoietin mRNA expression, and increased erythropoietin levels. Testosterone-induced suppression of hepcidin expression was independent of its effects on erythropoietin or hypoxia-sensing mechanisms. Transgenic mice with liver-specific constitutive hepcidin over-expression failed to exhibit the expected increase in hemoglobin in response to testosterone administration. Testosterone upregulated splenic ferroportin expression and reduced iron retention in spleen. After intravenous administration of transferrin-bound 58Fe, the amount of 58Fe incorporated into red blood cells was significantly greater in testosterone-treated mice than in placebo-treated mice. Serum from testosterone-treated mice stimulated hemoglobin synthesis in K562 erythroleukemia cells more than that from vehicle-treated mice. Testosterone administration promoted the association of androgen receptor (AR) with Smad1 and Smad4 to reduce their binding to BMP-response elements in hepcidin promoter in the liver. Ectopic expression of AR in hepatocytes suppressed hepcidin transcription; this effect was blocked dose-dependently by AR antagonist flutamide. Testosterone did not affect hepcidin mRNA stability. Conclusion: Testosterone inhibits hepcidin transcription through its interaction with BMP-Smad signaling. Testosterone administration is associated with increased iron

  20. A quality improvement project to increase self-administration of medicines in an acute hospital.

    PubMed

    Garfield, S; Bell, H; Nathan, C; Randall, S; Husson, F; Boucher, C; Taylor, A; Lloyd, J; Backhouse, A; Ritchie, L; Franklin, B D

    2018-03-24

    A patient survey found significantly fewer patients reported they had self-administered their medicines while in hospital (20% of 100 patients) than reported that they would like to (44% of 100). We aimed to make self-administration more easily available to patients who wanted it. We conducted a failure, modes and effects analysis, collected baseline data on four wards and carried out observations. Our initial assessment suggested that the main areas we should focus on were raising patient awareness of self-administration, changing the patient assessment process and creating a storage solution for medicines being self-administered. We developed new patient information leaflets and posters and a doctor's assessment form using Plan-Do-Study-Act cycles. We developed initial designs for a storage solution. We piloted the new materials on three wards; the fourth withdrew due to staff shortages. Following collection of baseline data, we continued to collect weekly data. We found that the proportion of patients who wished to self-administer who reported that they were able to do so, significantly increased from 41% (of 155 patients) to 66% (of 118 patients) during the study, despite a period when the hospital was over capacity. Raising and maintaining healthcare professionals' awareness of self-administration can greatly increase the proportion of patients who wish to self-administer who actually do so. Healthcare professionals prefer multi-disciplinary input into the assessment process.

  1. Significant increase in salivary substance p level after a single oral dose of cevimeline in humans.

    PubMed

    Suzuki, Yosuke; Itoh, Hiroki; Amada, Kohei; Yamamura, Ryota; Sato, Yuhki; Takeyama, Masaharu

    2013-01-01

    Cevimeline is a novel muscarinic acetylcholine receptor agonist currently being developed as a therapeutic agent for xerostomia. We examined the effects of cevimeline on salivary and plasma levels of substance-P- (SP-), calcitonin-gene-related-peptide- (CGRP-), and vasoactive-intestinal-polypeptide- (VIP-) like immunoreactive substances (ISs) in humans. An open-labeled crossover study was conducted on seven healthy volunteers. Saliva volume was measured, and saliva and venous blood samples were collected before and 30-240 min after a single oral dose of cevimeline or placebo. Salivary and plasma levels of SP-, CGRP-, and VIP-IS were measured using a highly sensitive enzyme immunoassay. A single oral dose of cevimeline resulted in significant increases in salivary but not plasma SP-IS level compared to placebo. Cevimeline administration did not alter the salivary or plasma levels of CGRP-IS or VIP-IS compared to placebo. Significant increases in salivary volume were observed after cevimeline administration compared to placebo. A significant correlation was observed between the total release of SP-IS and that of salivary volume. These findings suggest an association of SP with the enhancement of salivary secretion by cevimeline.

  2. Significant Increase in Salivary Substance P Level after a Single Oral Dose of Cevimeline in Humans

    PubMed Central

    Suzuki, Yosuke; Itoh, Hiroki; Amada, Kohei; Yamamura, Ryota; Sato, Yuhki; Takeyama, Masaharu

    2013-01-01

    Cevimeline is a novel muscarinic acetylcholine receptor agonist currently being developed as a therapeutic agent for xerostomia. We examined the effects of cevimeline on salivary and plasma levels of substance-P- (SP-), calcitonin-gene-related-peptide- (CGRP-), and vasoactive-intestinal-polypeptide- (VIP-) like immunoreactive substances (ISs) in humans. An open-labeled crossover study was conducted on seven healthy volunteers. Saliva volume was measured, and saliva and venous blood samples were collected before and 30–240 min after a single oral dose of cevimeline or placebo. Salivary and plasma levels of SP-, CGRP-, and VIP-IS were measured using a highly sensitive enzyme immunoassay. A single oral dose of cevimeline resulted in significant increases in salivary but not plasma SP-IS level compared to placebo. Cevimeline administration did not alter the salivary or plasma levels of CGRP-IS or VIP-IS compared to placebo. Significant increases in salivary volume were observed after cevimeline administration compared to placebo. A significant correlation was observed between the total release of SP-IS and that of salivary volume. These findings suggest an association of SP with the enhancement of salivary secretion by cevimeline. PMID:23589717

  3. NAD+ administration significantly attenuates synchrotron radiation X-ray-induced DNA damage and structural alterations of rodent testes

    PubMed Central

    Sheng, Caibin; Chen, Heyu; Wang, Ban; Liu, Tengyuan; Hong, Yunyi; Shao, Jiaxiang; He, Xin; Ma, Yingxin; Nie, Hui; Liu, Na; Xia, Weiliang; Ying, Weihai

    2012-01-01

    Synchrotron radiation (SR) X-ray has great potential for its applications in medical imaging and cancer treatment. In order to apply SR X-ray in clinical settings, it is necessary to elucidate the mechanisms underlying the damaging effects of SR X-ray on normal tissues, and to search for the strategies to reduce the detrimental effects of SR X-ray on normal tissues. However, so far there has been little information on these topics. In this study we used the testes of rats as a model to characterize SR X-ray-induced tissue damage, and to test our hypothesis that NAD+ administration can prevent SR X-ray-induced injury of the testes. We first determined the effects of SR X-ray at the doses of 0, 0.5, 1.3, 4 and 40 Gy on the biochemical and structural properties of the testes one day after SR X-ray exposures. We found that 40 Gy of SR X-ray induced a massive increase in double-strand DNA damage, as assessed by both immunostaining and Western blot of phosphorylated H2AX levels, which was significantly decreased by intraperitoneally (i.p.) administered NAD+ at doses of 125 and 625 mg/kg. Forty Gy of SR X-ray can also induce marked increases in abnormal cell nuclei as well as significant decreases in the cell layers of the seminiferous tubules one day after SR X-ray exposures, which were also ameliorated by the NAD+ administration. In summary, our study has shown that SR X-ray can produce both molecular and structural alterations of the testes, which can be significantly attenuated by NAD+ administration. These results have provided not only the first evidence that SR X-ray-induced tissue damage can be ameliorated by certain approaches, but also a valuable basis for elucidating the mechanisms underlying SR X-ray-induced tissue injury. PMID:22518270

  4. Chronic Cladribine Administration Increases Amyloid Beta Peptide Generation and Plaque Burden in Mice

    PubMed Central

    Hayes, Crystal D.; Dey, Debleena; Palavicini, Juan Pablo; Wang, Hongjie; Araki, Wataru; Lakshmana, Madepalli K.

    2012-01-01

    Background The clinical uses of 2-chloro-2′-deoxyadenosine (2-CDA) or cladribine which was initially prescribed to patients with hematological and lymphoid cancers is now extended to treat patients with multiple sclerosis (MS). Previous data has shown that 2-CDA has high affinity to the brain and readily passes through the blood brain barrier reaching CSF concentrations 25% of that found in plasma. However, whether long-term administration of 2-CDA can lead to any adverse effects in patients or animal models is not yet clearly known. Methodology Here we show that exposure of 2-CDA to CHO cells stably expressing wild-type APP751 increased generation and secretion of amyloid β peptide (Aβ) in to the conditioned medium. Interestingly, increased Aβ levels were noticed even at non-toxic concentrations of 2-CDA. Remarkably, chronic treatment of APdE9 mice, a model of Alzheimer's disease with 2-CDA for 60 days increased amyloid plaque burden by more than 1-fold. Increased Aβ generation appears to result from increased turnover of APP as revealed by cycloheximide-chase experiments. Additionally, surface labeling of APP with biotin and immunoprecipitation of surface labeled proteins with anti-biotin antibody also indicated increased APP at the cell surface in 2-CDA treated cells compared to controls. Increased turnover of APP by 2-CDA in turn might be a consequence of decreased protein levels of PIN 1, which is known to regulate cis-trans isomerization and phosphorylation of APP. Most importantly, like many other oncology drugs, 2-CDA administration led to significant delay in acquiring a reward-based learning task in a T maze paradigm. Conclusions Taken together, these data provide compelling evidence for the first time that chronic 2-CDA administration can increase amyloidogenic processing of APP leading to robustly increased plaque burden which may be responsible for the observed deficits in learning skills. Thus chronic treatment of mice with 2-CDA can have

  5. Intranasal administration of oxytocin increases human aggressive behavior.

    PubMed

    Ne'eman, R; Perach-Barzilay, N; Fischer-Shofty, M; Atias, A; Shamay-Tsoory, S G

    2016-04-01

    Considering its role in prosocial behaviors, oxytocin (OT) has been suggested to diminish levels of aggression. Nevertheless, recent findings indicate that oxytocin may have a broader influence on increasing the salience of social stimuli and may therefore, under certain circumstances, increase antisocial behaviors such as aggression. This controversy led to the following speculations: If indeed oxytocin promotes primarily prosocial behavior, administration of OT is expected to diminish levels of aggression. However, if oxytocin mainly acts to increase the salience of social stimuli, it is expected to elevate levels of aggression following provocation. In order to test this assumption we used the Social Orientation Paradigm (SOP), a monetary game played against a fictitious partner that allows measuring three types of responses in the context of provocation: an aggressive response - reducing a point from the fictitious partner, an individualistic response - adding a point to oneself, and a collaborative response - adding half a point to the partner and half a point to oneself. In the current double-blind, placebo-controlled, within-subject study design, 45 participants completed the SOP task following the administration of oxytocin or placebo. The results indicated that among subjects naïve to the procedure oxytocin increased aggressive responses in comparison with placebo. These results support the saliency hypothesis of oxytocin and suggest that oxytocin plays a complex role in the modulation of human behavior. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Oral Administration of Probiotics Increases Paneth Cells and Intestinal Antimicrobial Activity.

    PubMed

    Cazorla, Silvia I; Maldonado-Galdeano, Carolina; Weill, Ricardo; De Paula, Juan; Perdigón, Gabriela D V

    2018-01-01

    The huge amount of intestinal bacteria represents a continuing threat to the intestinal barrier. To meet this challenge, gut epithelial cells produce antimicrobial peptides (AMP) that act at the forefront of innate immunity. We explore whether this antimicrobial activity and Paneth cells, the main intestinal cell responsible of AMP production, are influenced by probiotics administration, to avoid the imbalance of intestinal microbiota and preserve intestinal barrier. Administration of Lactobacillus casei CRL 431 (Lc 431) and L. paracasei CNCM I-1518 (Lp 1518) to 42 days old mice, increases the number of Paneth cells on small intestine, and the antimicrobial activity against the pathogens Staphylococcus aureus and Salmonella Typhimurium in the intestinal fluids. Specifically, strong damage of the bacterial cell with leakage of cytoplasmic content, and cellular fragmentation were observed in S. Typhimurium and S. aureus . Even more important, probiotics increase the antimicrobial activity of the intestinal fluids at the different ages, from weaning (21 days old) to old age (180 days old). Intestinal antimicrobial activity stimulated by oral probiotics, do not influence significantly the composition of total anaerobic bacteria, lactobacilli and enterobacteria in the large intestine, at any age analyzed. This result, together with the antimicrobial activity observed against the same probiotic bacteria; endorse the regular consumption of probiotics without adverse effect on the intestinal homeostasis in healthy individuals. We demonstrate that oral probiotics increase intestinal antimicrobial activity and Paneth cells in order to strengthen epithelial barrier against pathogens. This effect would be another important mechanism by which probiotics protect the host mainly against infectious diseases.

  7. Enhanced AMPA Receptor Activity Increases Operant Alcohol Self-administration and Cue-Induced Reinstatement

    PubMed Central

    Cannady, Reginald; Fisher, Kristen R.; Durant, Brandon; Besheer, Joyce; Hodge, Clyde W.

    2012-01-01

    Long-term alcohol exposure produces neuroadaptations that contribute to the progression of alcohol abuse disorders. Chronic alcohol consumption results in strengthened excitatory neurotransmission and increased AMPA receptor signaling in animal models. However, the mechanistic role of enhanced AMPA receptor activity in alcohol reinforcement and alcohol-seeking behavior remains unclear. This study examined the role of enhanced AMPA receptor function using the selective positive allosteric modulator, aniracetam, in modulating operant alcohol self-administration and cue-induced reinstatement. Male alcohol-preferring (P-) rats, trained to self-administer alcohol (15%, v/v) versus water were pretreated with aniracetam to assess effects on maintenance of alcohol self-administration. To determine reinforcer specificity, P-rats were trained to self-administer sucrose (0.8%, w/v) versus water, and effects of aniracetam were tested. The role of aniracetam in modulating relapse of alcohol-seeking was assessed using a response-contingent cue-induced reinstatement procedure in P-rats trained to self-administer 15% alcohol. Aniracetam pretreatment significantly increased alcohol-reinforced responses relative to vehicle treatment. This increase was not attributed to aniracetam-induced hyperactivity as aniracetam pretreatment did not alter locomotor activity. AMPA receptor involvement was confirmed because DNQX (AMPA receptor antagonist) blocked the aniracetam-induced increase in alcohol self-administration. Aniracetam did not alter sucrose-reinforced responses in sucrose-trained P-rats, suggesting that enhanced AMPA receptor activity is selective in modulating the reinforcing function of alcohol. Finally, aniracetam pretreatment potentiated cue-induced reinstatement of alcohol-seeking behavior versus vehicle treated-P-rats. These data suggest that enhanced glutamate activity at AMPA receptors may be key in facilitating alcohol consumption and seeking behavior which could

  8. Enhanced AMPA receptor activity increases operant alcohol self-administration and cue-induced reinstatement.

    PubMed

    Cannady, Reginald; Fisher, Kristen R; Durant, Brandon; Besheer, Joyce; Hodge, Clyde W

    2013-01-01

    Long-term alcohol exposure produces neuroadaptations that contribute to the progression of alcohol abuse disorders. Chronic alcohol consumption results in strengthened excitatory neurotransmission and increased α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptors (AMPA) receptor signaling in animal models. However, the mechanistic role of enhanced AMPA receptor activity in alcohol-reinforcement and alcohol-seeking behavior remains unclear. This study examined the role of enhanced AMPA receptor function using the selective positive allosteric modulator, aniracetam, in modulating operant alcohol self-administration and cue-induced reinstatement. Male alcohol-preferring (P-) rats, trained to self-administer alcohol (15%, v/v) versus water were pre-treated with aniracetam to assess effects on maintenance of alcohol self-administration. To determine reinforcer specificity, P-rats were trained to self-administer sucrose (0.8%, w/v) versus water, and effects of aniracetam were tested. The role of aniracetam in modulating relapse of alcohol-seeking was assessed using a response contingent cue-induced reinstatement procedure in P-rats trained to self-administer 15% alcohol. Aniracetam pre-treatment significantly increased alcohol-reinforced responses relative to vehicle treatment. This increase was not attributed to aniracetam-induced hyperactivity as aniracetam pre-treatment did not alter locomotor activity. AMPA receptor involvement was confirmed because 6,7-dinitroquinoxaline-2,3-dione (AMPA receptor antagonist) blocked the aniracetam-induced increase in alcohol self-administration. Aniracetam did not alter sucrose-reinforced responses in sucrose-trained P-rats, suggesting that enhanced AMPA receptor activity is selective in modulating the reinforcing function of alcohol. Finally, aniracetam pre-treatment potentiated cue-induced reinstatement of alcohol-seeking behavior versus vehicle-treated P-rats. These data suggest that enhanced glutamate activity at AMPA

  9. Central irisin administration suppresses thyroid hormone production but increases energy consumption in rats.

    PubMed

    Tekin, Suat; Erden, Yavuz; Ozyalin, Fatma; Onalan, Ebru Etem; Cigremis, Yilmaz; Colak, Cemil; Tekedereli, Ibrahim; Sandal, Suleyman

    2018-05-01

    Irisin, which is secreted from the skeletal muscle in response to physical exercise and defined as a thermogenic peptide, may play an important role in energy metabolism. Thyroid hormones, which are one of the other influential factors on the metabolic status, increase heat production and are the main regulators of energy metabolism. This study was conducted to determine the possible effects of irisin administration on thyroid hormones. Forty adult male Wistar albino rats were used in the study. The rats were equally divided into 4 groups (n = 10). The brain infusion kit was implanted in the groups, and irisin (or solvent as control) was centrally administered to the rats via osmotic mini pumps for 7 days. During the experiment, food consumption, body weights, and body temperatures of the animals were recorded. Food intake was significantly increased in the groups treated with irisin (p < 0.05), but their body weights were not changed. Hypothalamic TRH gene expression, serum TSH, fT3, and fT4 levels were significantly lower in the groups treated with irisin as compared to the naive and control groups (p < 0.05). In addition, irisin increased UCP1 mRNA expression in white and brown adipose tissue and UCP3 mRNA expression in muscle tissue in rats and also raised their body temperature (p < 0.05). Consequently, although central irisin administration has inhibitory effects on the hypothalamic-pituitary-thyroid axis, it seems to be an important agent in the regulation of food intake and energy metabolism. Copyright © 2018 Elsevier B.V. All rights reserved.

  10. Moderate traumatic brain injury increases the vulnerability to neurotoxicity induced by systemic administration of 6-hydroxydopamine in mice.

    PubMed

    de Oliveira, Paulo Alexandre; Ben, Juliana; Matheus, Filipe Carvalho; Schwarzbold, Marcelo Liborio; Moreira, Eduardo Luiz Gasnhar; Rial, Daniel; Walz, Roger; Prediger, Rui Daniel

    2017-05-15

    Moderate traumatic brain injury (TBI) might increase the vulnerability to neuronal neurodegeneration, but the basis of such selective neuronal susceptibility has remained elusive. In keeping with the disruption of the blood-brain barrier (BBB) caused by TBI, changes in BBB permeability following brain injury could facilitate the access of xenobiotics into the brain. To test this hypothesis, here we evaluated whether TBI would increase the susceptibility of nigrostriatal dopaminergic fibers to the systemic administration of 6-hydroxydopamine (6-OHDA), a classic neurotoxin used to trigger a PD-like phenotype in mice, but that in normal conditions is unable to cross the BBB. Adult Swiss mice were submitted to a moderate TBI using a free weight-drop device and, 5h later, they were injected intraperitoneally with a single dose of 6-OHDA (100mg/kg). Afterwards, during a period of 4weeks, the mice were submitted to a battery of behavioral tests, including the neurological severity score (NSS), the open field and the rotarod. Animals from the TBI plus 6-OHDA group displayed significant motor and neurological impairments that were improved by acute l-DOPA administration (25mg/kg, i.p.). Moreover, the observation of the motor deficits correlates with (i) a significant decrease in the tyrosine hydroxylase levels mainly in the rostral striatum and (ii) a significant increase in the levels of striatal glial fibrillary acidic protein (GFAP) levels. On the whole, the present findings demonstrate that a previous moderate TBI event increases the susceptibility to motor, neurological and neurochemical alterations induced by systemic administration of the dopaminergic neurotoxin 6-OHDA in mice. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Oral Administration of Recombinant Lactococcus lactis Expressing the Cellulase Gene Increases Digestibility of Fiber in Geese.

    PubMed

    Zhou, Haizhu; Gao, Yunhang; Gao, Guang; Lou, Yujie

    2015-12-01

    Enhancing cellulose digestibility in animals is important for improving the utilization of forage, which can decrease the amount of food used in animal production. The aim of the present study was to achieve recombinant expression of the cellulase gene in Lactococcus lactis and evaluate the effects of oral administration of the recombinant L. lactis on fiber digestibility in geese. Cellulase (Cell) and green fluorescent protein (GFP) genes were cloned into a L. lactis expression vector (pNZ8149) to construct the recombinant expression plasmid (pNZ8149-GFP-Cell). Then, the recombinant expression plasmid was transformed into L. lactis (NZ3900) competent cells by electroporation to obtain recombinant L. lactis (pNZ8149-GFP-Cell/NZ3900) in which protein expression was induced by Nisin. Expression of GFP and Cell by the recombinant L. lactis was confirmed using SDS-PAGE, fluorescence detection, and Congo red assays. A feeding experiment showed that oral administration of pNZ8149-GFP-Cell/NZ3900 significantly increased the digestibility of dietary fiber in geese fed either a maize stalk diet or a rice chaff diet. Therefore, oral administration of recombinant L. lactis cells expressing the cellulase gene increases fiber digestibility in geese, offering a way to increase the utilization of dietary fiber in geese.

  12. [Significance of vitamin K (VK) administration in patients under chemotherapy during postoperative fasting period].

    PubMed

    Ojiro, M; Takenoshita, M; Toshinaga, T; Shimazu, H

    1992-01-01

    Recently coagulopathy caused by vitamin K (VK) deficiency following antibiotic therapy in malnourished patients has been reported. We studied on the same problem particularly in patients under chemotherapy during postoperative fasting period. For this purpose, prothrombin time (PT), vitamin K-dependent coagulation factors (Factor II (F-II), VII (F-VII) and protein C), PIVKA-II (PK-II) and plasma level of VK in two groups of patients with or without VK administration were measured in esophageal cancer patients. In the group with VK, VK2 were given intravenously everyday. In the group without VK, PT prolonged and F-II decreased from the seventh postoperative day, especially on the 14th day significantly. Although F-VII and protein C decreased on the first day and returned subsequently on the seventh day, no significance was observed between two groups. PK-II increased clearly in the group without VK from the seventh day, whereas no significant changes were observed in the group with VK. The plasma level of VK1 decreased in both groups, but VK2, especially MK-4, was high in the group with VK.

  13. Anti-tau antibody administration increases plasma tau in transgenic mice and patients with tauopathy

    PubMed Central

    Yanamandra, Kiran; Patel, Tirth K.; Jiang, Hong; Schindler, Suzanne; Ulrich, Jason D.; Boxer, Adam L.; Miller, Bruce L.; Kerwin, Diana R.; Gallardo, Gilbert; Stewart, Floy; Finn, Mary Beth; Cairns, Nigel J.; Verghese, Philip B.; Fogelman, Ilana; West, Tim; Braunstein, Joel; Robinson, Grace; Keyser, Jennifer; Roh, Joseph; Knapik, Stephanie S.; Hu, Yan; Holtzman, David M.

    2017-01-01

    Tauopathies are a group of disorders in which the cytosolic protein tau aggregates and accumulates in cells within the brain, resulting in neurodegeneration. A promising treatment being explored for tauopathies is passive immunization with anti-tau antibodies. We previously found that administration of an anti-tau antibody to human tau transgenic mice increased the concentration of plasma tau. We further explored the effects of administering an anti-tau antibody on plasma tau. After peripheral administration of an anti-tau antibody to human patients with tauopathy and to mice expressing human tau in the central nervous system, there was a dose-dependent increase in plasma tau. In mouse plasma, we found that tau had a short half-life of 8 min that increased to more than 3 hours after administration of anti-tau antibody. As tau transgenic mice accumulated insoluble tau in the brain, brain soluble and interstitial fluid tau decreased. Administration of anti-tau antibody to tau transgenic mice that had decreased brain soluble tau and interstitial fluid tau resulted in an increase in plasma tau, but this increase was less than that observed in tau transgenic mice without these brain changes. Tau transgenic mice subjected to acute neuronal injury using 3-nitropropionic acid showed increased interstitial fluid tau and plasma tau. These data suggest that peripheral administration of an anti-tau antibody results in increased plasma tau, which correlates with the concentration of extracellular and soluble tau in the brain. PMID:28424326

  14. The Contingency of Cocaine Administration Accounts for Structural and Functional Medial Prefrontal Deficits and Increased Adrenocortical Activation

    PubMed Central

    Anderson, Rachel M.; Cosme, Caitlin V.; Glanz, Ryan M.; Miller, Mary C.; Romig-Martin, Sara A.; LaLumiere, Ryan T.

    2015-01-01

    The prelimbic region (PL) of the medial prefrontal cortex (mPFC) is implicated in the relapse of drug-seeking behavior. Optimal mPFC functioning relies on synaptic connections involving dendritic spines in pyramidal neurons, whereas prefrontal dysfunction resulting from elevated glucocorticoids, stress, aging, and mental illness are each linked to decreased apical dendritic branching and spine density in pyramidal neurons in these cortical fields. The fact that cocaine use induces activation of the stress-responsive hypothalamo-pituitary-adrenal axis raises the possibility that cocaine-related impairments in mPFC functioning may be manifested by similar changes in neuronal architecture in mPFC. Nevertheless, previous studies have generally identified increases, rather than decreases, in structural plasticity in mPFC after cocaine self-administration. Here, we use 3D imaging and analysis of dendritic spine morphometry to show that chronic cocaine self-administration leads to mild decreases of apical dendritic branching, prominent dendritic spine attrition in PL pyramidal neurons, and working memory deficits. Importantly, these impairments were largely accounted for in groups of rats that self-administered cocaine compared with yoked-cocaine- and saline-matched counterparts. Follow-up experiments failed to demonstrate any effects of either experimenter-administered cocaine or food self-administration on structural alterations in PL neurons. Finally, we verified that the cocaine self-administration group was distinguished by more protracted increases in adrenocortical activity compared with yoked-cocaine- and saline-matched controls. These studies suggest a mechanism whereby increased adrenocortical activity resulting from chronic cocaine self-administration may contribute to regressive prefrontal structural and functional plasticity. SIGNIFICANCE STATEMENT Stress, aging, and mental illness are each linked to decreased prefrontal plasticity. Here, we show that chronic

  15. Intranasal administration of testosterone increased immobile-sniffing, exploratory behavior, motor behavior and grooming behavior in rats.

    PubMed

    Zhang, Guoliang; Shi, Geming; Tan, Huibing; Kang, Yunxiao; Cui, Huixian

    2011-04-01

    Currently, testosterone (T) replacement therapy is typically provided by oral medication, injectable T esters, surgically implanted T pellets, transdermal patches and gels. However, most of these methods of administration are still not ideal for targeting the central nervous system. Recently, therapeutic intranasal T administration (InT) has been considered as another option for delivering T to the brain. In the present study, the effects of 21-day InT treatment were assessed on open field behavior in gonadectomized (GDX) rats and intact rats. Subcutaneous injections of T at same dose were also tested in GDX rats. A total of 12 behavioral events were examined in GDX groups with or without T and in intact groups with or without InT. Significant decreases in open field activity were observed in rats after GDX without InT compared to sham-operated rats. The open field activity scores for most tests significantly increased with InT treatment in GDX rats and in intact rats compared with the corresponding GDX rats and intact rats. Intranasal administration of T improved the reduced behaviors resulted from T deficiency better than subcutaneous injection of T, demonstrating that T can be delivered to the brain by intranasal administration. Our results suggest that intranasal T delivery is an effective option for targeting the central nervous system. Copyright © 2011 Elsevier Inc. All rights reserved.

  16. Increase in cocaine- and amphetamine-regulated transcript (CART) in specific areas of the mouse brain by acute caffeine administration.

    PubMed

    Cho, Jin Hee; Cho, Yun Ha; Kim, Hyo Young; Cha, Seung Ha; Ryu, Hyun; Jang, Wooyoung; Shin, Kyung Ho

    2015-04-01

    Caffeine produces a variety of behavioral effects including increased alertness, reduced food intake, anxiogenic effects, and dependence upon repeated exposure. Although many of the effects of caffeine are mediated by its ability to block adenosine receptors, it is possible that other neural substrates, such as cocaine- and amphetamine-regulated transcript (CART), may be involved in the effects of caffeine. Indeed, a recent study demonstrated that repeated caffeine administration increases CART in the mouse striatum. However, it is not clear whether acute caffeine administration alters CART in other areas of the brain. To explore this possibility, we investigated the dose- and time-dependent changes in CART immunoreactivity (CART-IR) after a single dose of caffeine in mice. We found that a high dose of caffeine (100 mg/kg) significantly increased CART-IR 2 h after administration in the nucleus accumbens shell (AcbSh), dorsal bed nucleus of the stria terminalis (dBNST), central nucleus of the amygdala (CeA), paraventricular hypothalamic nucleus (PVN), arcuate hypothalamic nucleus (Arc), and locus coeruleus (LC), and returned to control levels after 8 h. But this increase was not observed in other brain areas. In addition, caffeine administration at doses of 25 and 50 mg/kg appears to produce dose-dependent increases in CART-IR in these brain areas; however, the magnitude of increase in CART-IR observed at a dose of 50 mg/kg was similar or greater than that observed at a dose of 100 mg/kg. This result suggests that CART-IR in AcbSh, dBNST, CeA, PVN, Arc, and LC is selectively affected by caffeine administration. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Acute and subchronic administration of anandamide or oleamide increases REM sleep in rats.

    PubMed

    Herrera-Solís, Andrea; Vásquez, Khalil Guzmán; Prospéro-García, Oscar

    2010-03-01

    Anandamide and oleamide, induce sleep when administered acutely, via the CB1 receptor. Their subchronic administration must be tested to demonstrate the absence of tolerance to this effect, and that the sudden withdrawal of these endocannabinoids (eCBs) does not affect sleep negatively. The sleep-waking cycle of rats was evaluated for 24h, under the effect of an acute or subchronic administration of eCBs, and during sudden eCBs withdrawal. AM251, a CB1 receptor antagonist (CB1Ra) was utilized to block eCBs effects. Our results indicated that both acute and subchronic administration of eCBs increase REMS. During eCBs withdrawal, rats lack the expression of an abstinence-like syndrome. AM251 was efficacious to prevent REMS increase caused by both acute and subchronic administration of these eCBs, suggesting that this effect is mediated by the CB1 receptor. Our data further support a role of the eCBs in REMS regulation. (c) 2009 Elsevier Inc. All rights reserved.

  18. 77 FR 5027 - Food and Drug Administration Transparency Initiative: Exploratory Program To Increase Access to...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-01

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2009-N-0247] Food and Drug Administration Transparency Initiative: Exploratory Program To Increase Access to the... responsible for a broad range of compliance and enforcement activities. Increasing the transparency of these...

  19. Pediatricians' perceptions of vaccine effectiveness and safety are significant predictors of vaccine administration in India

    PubMed Central

    Gargano, Lisa M.; Thacker, Naveen; Choudhury, Panna; Weiss, Paul S.; Russ, Rebecca M.; Pazol, Karen; Arora, Manisha; Orenstein, Walter A.; Omer, Saad B.; Hughes, James M.

    2013-01-01

    Background New vaccine introduction is important to decrease morbidity and mortality in India. The goal of this study was to identify perceptions that are associated with administration of four selected vaccines for prevention of Japanese encephalitis (JE), typhoid fever, influenza and human papillomavirus (HPV) infection. Methods A random sample of 785 pediatricians from a national list of Indian Academy of Pediatrics members was selected for a survey to assess perceptions of vaccine effectiveness and safety, and vaccine administration practices. Logistic regression was used to assess factors associated with selective or routine use. Results Pediatricians reported administering typhoid (91.6%), influenza (60.1%), HPV (46.0%) and JE (41.9%) vaccines selectively or routinely. Pediatricians who perceived the vaccine to be safe were significantly more likely to report administration of JE (OR 2.6, 95% CI 1.3 to 5.3), influenza (OR 4.3, 95% CI 2.0 to 9.6) and HPV vaccine (OR 6.2, 95% CI 3.1 to 12.7). Pediatricians who perceived the vaccine to be effective were significantly more likely to report administration of JE (OR 3.3, 95% CI 1.6 to 6.5), influenza (OR 7.7, 95% CI 2.5 to 23.1) and HPV vaccine (OR 3.2, 95% CI 1.6 to 6.4) Conclusion Understanding the role perceptions play provides an opportunity to design strategies to build support for vaccine use. PMID:24030271

  20. Progress toward acetate supplementation therapy for Canavan disease: glyceryl triacetate administration increases acetate, but not N-acetylaspartate, levels in brain.

    PubMed

    Mathew, Raji; Arun, Peethambaran; Madhavarao, Chikkathur N; Moffett, John R; Namboodiri, M A Aryan

    2005-10-01

    Canavan disease (CD) is a fatal genetic neurodegenerative disorder caused by mutations in the gene for aspartoacylase, an enzyme that hydrolyzes N-acetylaspartate (NAA) into L-aspartate and acetate. Because aspartoacylase is localized in oligodendrocytes, and NAA-derived acetate is incorporated into myelin lipids, we hypothesize that an acetate deficiency in oligodendrocytes is responsible for the pathology in CD, and we propose acetate supplementation as a possible therapy. In our preclinical efforts toward this goal, we studied the effectiveness of orally administered glyceryl triacetate (GTA) and calcium acetate for increasing acetate levels in the murine brain. The concentrations of brain acetate and NAA were determined simultaneously after intragastric administration of GTA. We found that the acetate levels in brain were increased in a dose- and time-dependent manner, with a 17-fold increase observed at 1 to 2 h in 20- to 21-day-old mice at a dose of 5.8 g/kg GTA. NAA levels in the brain were not significantly increased under these conditions. Studies using mice at varying stages of development showed that the dose of GTA required to maintain similarly elevated acetate levels in the brain increased with age. Also, GTA was significantly more effective as an acetate source than calcium acetate. Chronic administration of GTA up to 25 days of age did not result in any overt pathology in the mice. Based on these results and the current Food and Drug Administration-approved use of GTA as a food additive, we propose that it is a potential candidate for use in acetate supplementation therapy for CD.

  1. Extension Master Gardener Intranet: Automating Administration, Motivating Volunteers, Increasing Efficiency, and Facilitating Impact Reporting

    ERIC Educational Resources Information Center

    Bradley, Lucy K.; Cook, Jonneen; Cook, Chris

    2011-01-01

    North Carolina State University has incorporated many aspects of volunteer program administration and reporting into an on-line solution that integrates impact reporting into daily program management. The Extension Master Gardener Intranet automates many of the administrative tasks associated with volunteer management, increasing efficiency, and…

  2. NOAA - National Oceanic and Atmospheric Administration - Significant Ozone

    Science.gov Websites

    RESEARCH COASTS CAREERS National Oceanic and Atmospheric Administration, United States Department of smallest since 1986. The record low of 89 DU was recorded on Oct. 6, 1993. The atmospheric ozone layer nearly completed a year-long assignment at South Pole Station where they collect atmospheric data and

  3. Systemic administration of WIN 55,212-2 increases norepinephrine release in the rat frontal cortex.

    PubMed

    Oropeza, V C; Page, M E; Van Bockstaele, E J

    2005-06-07

    Cannabinoid agonists modulate a variety of behavioral functions by activating cannabinoid receptors that are widely distributed throughout the central nervous system. In the present study, norepinephrine efflux was assessed in the frontal cortex of rats that received a systemic administration of the cannabinoid agonist, WIN 55,212-2. The synthetic cannabinoid agonist dose-dependently increased the release of norepinephrine in this brain region. Pretreatment with the cannabinoid receptor antagonist, SR 141716A, blocked the increase in norepinephrine release. To identify sites of cellular activation, immunocytochemical detection of c-Fos was combined with detection of the catecholamine synthesizing enzyme, tyrosine hydroxylase (TH), in the brainstem nucleus locus coeruleus (LC), a region that is the sole source of norepinephrine to the frontal cortex. Systemic administration of WIN 55,212-2 significantly increased the number of c-Fos immunoreactive cells within TH-containing neurons in the LC compared to vehicle-treated rats. Pretreatment with SR 141716A inhibited the WIN 55,212-2 induced c-Fos expression, while the antagonist alone did not affect c-Fos expression. Taken together, these data indicate that systemically administered cannabinoid agonists stimulate norepinephrine release in the frontal cortex by activating noradrenergic neurons in the coeruleo-frontal cortex pathway. These effects may partially underlie changes in attention, arousal and anxiety observed following exposure to cannabis-based drugs.

  4. Impact of an electronic medication administration record on medication administration efficiency and errors.

    PubMed

    McComas, Jeffery; Riingen, Michelle; Chae Kim, Son

    2014-12-01

    The study aims were to evaluate the impact of electronic medication administration record implementation on medication administration efficiency and occurrence of medication errors as well as to identify the predictors of medication administration efficiency in an acute care setting. A prospective, observational study utilizing time-and-motion technique was conducted before and after electronic medication administration record implementation in November 2011. A total of 156 cases of medication administration activities (78 pre- and 78 post-electronic medication administration record) involving 38 nurses were observed at the point of care. A separate retrospective review of the hospital Midas+ medication error database was also performed to collect the rates and origin of medication errors for 6 months before and after electronic medication administration record implementation. The mean medication administration time actually increased from 11.3 to 14.4 minutes post-electronic medication administration record (P = .039). In a multivariate analysis, electronic medication administration record was not a predictor of medication administration time, but the distractions/interruptions during medication administration process were significant predictors. The mean hospital-wide medication errors significantly decreased from 11.0 to 5.3 events per month post-electronic medication administration record (P = .034). Although no improvement in medication administration efficiency was observed, electronic medication administration record improved the quality of care with a significant decrease in medication errors.

  5. Antibiotic administration routes significantly influence the levels of antibiotic resistance in gut microbiota.

    PubMed

    Zhang, Lu; Huang, Ying; Zhou, Yang; Buckley, Timothy; Wang, Hua H

    2013-08-01

    This study examined the impact of oral exposure to antibiotic-resistant bacteria and antibiotic administration methods on antibiotic resistance (AR) gene pools and the profile of resistant bacteria in host gastrointestinal (GI) tracts using C57BL/6J mice with natural gut microbiota. Mice inoculated with a mixture of tet(M)-carrying Enterococcus spp. or blaCMY-2-carrying Escherichia coli were treated with different doses of tetracycline hydrochloride (Tet) or ampicillin sodium (Amp) and delivered via either feed or intravenous (i.v.) injection. Quantitative PCR assessment of mouse fecal samples revealed that (i) AR gene pools were below the detection limit in mice without prior inoculation of AR gene carriers regardless of subsequent exposure to corresponding antibiotics; (ii) oral exposure to high doses of Tet and Amp in mice inoculated with AR gene carriers led to rapid enrichment of corresponding AR gene pools in feces; (iii) significantly less or delayed development of AR in the GI tract of the AR carrier-inoculated mice was observed when the same doses of antibiotics were administered via i.v. injection rather than oral administration; and (iv) antibiotic dosage, and maybe the excretion route, affected AR in the GI tract. The shift of dominant AR bacterial populations in the gut microbiota was consistent with the dynamics of AR gene pools. The emergence of endogenous resistant bacteria in the gut microbiota corresponding to drug exposure was also observed. Together, these data suggest that oral administration of antibiotics has a prominent effect on AR amplification and development in gut microbiota, which may be minimized by alternative drug administration approaches, as illustrated by i.v. injection in this study and proper drug selection.

  6. Chronic administration of nandrolone increases susceptibility to morphine dependence without correlation with LVV-hemorphin 7 in rats.

    PubMed

    Huang, Eagle Yi-Kung; Chen, Yuan-Hao; Huang, Tzu-Ying; Chen, Ying-Jie; Chow, Lok-Hi

    2016-10-01

    LVV-hemorphin 7 (LVVYPWTQRF; LVV-H7), an N-terminal fragment of the β-chain of hemoglobin cleaved by cathepsin D/pepsin, is an atypical endogenous opioid peptide that is found in high concentration in blood. LVV-H7 acts as a μ-opioid agonist and an inhibitor of insulin-regulated aminopeptidase. Subchronic administration of anabolic androgenic steroids (AAS) has been clinically proven to induce the synthesis of erythrocytes and increase hemoglobin concentrations. Patients with a history of AAS abuse are more susceptible to opioid abuse. We hypothesized that this association could be at least partially attributed to the sensitization of the mesocorticolimbic dopaminergic pathway by LVV-H7. Using the conditioned place preference test and neurochemical analysis, we investigated the possible mechanism underlying the effect of chronic nandrolone administration on morphine-induced reward and its correlation with LVV-H7 in rats. Either LVV-H7 may not sensitize the rewarding neural circuits or its inhibition on locomotor activity could mask reward-related behaviors. Chronic nandrolone pretreatment indeed caused a significant reward by low dose morphine, which did not cause any reward in control rats. However, coadministration of anti-LVV-H7 antiserum with nandrolone did not block this effect. This may rule out the possibility of the involvement of LVV-H7 in the action of nandrolone to intensify morphine-induced reward. Moreover, the serum level of LVV-H7 was mildly increased in response to chronic nandrolone administration in our animal model. According to the current clinical observations, we may conclude that the chronic administration of nandrolone can increase susceptibility to morphine dependence, but that this effect is not related to elevated LVV-H7. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Inflammatory Pain Promotes Increased Opioid Self-Administration: Role of Dysregulated Ventral Tegmental Area μ Opioid Receptors

    PubMed Central

    Hipólito, Lucia; Wilson-Poe, Adrianne; Campos-Jurado, Yolanda; Zhong, Elaine; Gonzalez-Romero, Jose; Virag, Laszlo; Whittington, Robert; Comer, Sandra D.; Carlton, Susan M.; Walker, Brendan M.; Bruchas, Michael R.

    2015-01-01

    Pain management in opioid abusers engenders ethical and practical difficulties for clinicians, often resulting in pain mismanagement. Although chronic opioid administration may alter pain states, the presence of pain itself may alter the propensity to self-administer opioids, and previous history of drug abuse comorbid with chronic pain promotes higher rates of opioid misuse. Here, we tested the hypothesis that inflammatory pain leads to increased heroin self-administration resulting from altered mu opioid receptor (MOR) regulation of mesolimbic dopamine (DA) transmission. To this end, the complete Freund's adjuvant (CFA) model of inflammation was used to assess the neurochemical and functional changes induced by inflammatory pain on MOR-mediated mesolimbic DA transmission and on rat intravenous heroin self-administration under fixed ratio (FR) and progressive ratio (PR) schedules of reinforcement. In the presence of inflammatory pain, heroin intake under an FR schedule was increased for high, but attenuated for low, heroin doses with concomitant alterations in mesolimbic MOR function suggested by DA microdialysis. Consistent with the reduction in low dose FR heroin self-administration, inflammatory pain reduced motivation for a low dose of heroin, as measured by responding under a PR schedule of reinforcement, an effect dissociable from high heroin dose PR responding. Together, these results identify a connection between inflammatory pain and loss of MOR function in the mesolimbic dopaminergic pathway that increases intake of high doses of heroin. These findings suggest that pain-induced loss of MOR function in the mesolimbic pathway may promote opioid dose escalation and contribute to opioid abuse-associated phenotypes. SIGNIFICANCE STATEMENT This study provides critical new insights that show that inflammatory pain alters heroin intake through a desensitization of MORs located within the VTA. These findings expand our knowledge of the interactions between

  8. Antibiotic Administration Routes Significantly Influence the Levels of Antibiotic Resistance in Gut Microbiota

    PubMed Central

    Zhang, Lu; Huang, Ying; Zhou, Yang; Buckley, Timothy

    2013-01-01

    This study examined the impact of oral exposure to antibiotic-resistant bacteria and antibiotic administration methods on antibiotic resistance (AR) gene pools and the profile of resistant bacteria in host gastrointestinal (GI) tracts using C57BL/6J mice with natural gut microbiota. Mice inoculated with a mixture of tet(M)-carrying Enterococcus spp. or blaCMY-2-carrying Escherichia coli were treated with different doses of tetracycline hydrochloride (Tet) or ampicillin sodium (Amp) and delivered via either feed or intravenous (i.v.) injection. Quantitative PCR assessment of mouse fecal samples revealed that (i) AR gene pools were below the detection limit in mice without prior inoculation of AR gene carriers regardless of subsequent exposure to corresponding antibiotics; (ii) oral exposure to high doses of Tet and Amp in mice inoculated with AR gene carriers led to rapid enrichment of corresponding AR gene pools in feces; (iii) significantly less or delayed development of AR in the GI tract of the AR carrier-inoculated mice was observed when the same doses of antibiotics were administered via i.v. injection rather than oral administration; and (iv) antibiotic dosage, and maybe the excretion route, affected AR in the GI tract. The shift of dominant AR bacterial populations in the gut microbiota was consistent with the dynamics of AR gene pools. The emergence of endogenous resistant bacteria in the gut microbiota corresponding to drug exposure was also observed. Together, these data suggest that oral administration of antibiotics has a prominent effect on AR amplification and development in gut microbiota, which may be minimized by alternative drug administration approaches, as illustrated by i.v. injection in this study and proper drug selection. PMID:23689712

  9. Isosorbide 5 mononitrate administration increases nitric oxide blood levels and reduces proteinuria in IgA glomerulonephritis patients with abnormal urinary endothelin/cyclic GMP ratio.

    PubMed

    Roccatello, D; Mengozzi, G; Ferro, M; Cesano, G; Polloni, R; Mosso, R; Bonetti, G; Inconis, T; Paradisi, L; Sena, L M

    1995-09-01

    An endothelin urinary hyperexcretion, which is not counterbalanced by an adequate increase in cGMP biosynthesis, was previously detected in some patients with IgA Nephropathy (IgAN). Since this imbalance might potentiate local ET1-mediated hemodynamics effects, 9 IgAN patients with an increased (> or = 0.1) urinary ET1/cGMP ratio (group 1) and 5 IgAN patients with comparable renal function and reduced ET1/cGMP ratio (group 2) were given standard doses of isosorbide 5 mononitrate (as a nitric oxide source). Blood nitric oxide (NO) levels, as detected by electron paramagnetic resonance, significantly increased after isosorbide administration (p < 0.01) and decreased after drug discontinuation in both groups. Nitric oxide levels were significantly related with those of the effective renal plasma flow (p < 0.02), but not with the glomerular filtration rate. Proteinuria levels significantly decreased after drug administration (p < 0.009) in group 1 and returned to baseline levels thereafter, except two cases showing persisting low levels. Values of filtration fraction in the same group decreased after iso5M administration (p < 0.02 compared to basal levels). These results may possibly be related to the counterbalancing effects of nitric oxide on endothelin-mediated mesangial contraction.

  10. Intraperitoneal administration of docosahexaenoic acid for 14days increases serum unesterified DHA and seizure latency in the maximal pentylenetetrazol model.

    PubMed

    Trépanier, Marc-Olivier; Lim, Joonbum; Lai, Terence K Y; Cho, Hye Jin; Domenichiello, Anthony F; Chen, Chuck T; Taha, Ameer Y; Bazinet, Richard P; Burnham, W M

    2014-04-01

    Docosahexaenoic acid (DHA) is an omega-3 polyunsaturated fatty acid (n-3 PUFA) which has been shown to raise seizure thresholds following acute administration in rats. The aims of the present experiment were the following: 1) to test whether subchronic DHA administration raises seizure threshold in the maximal pentylenetetrazol (PTZ) model 24h following the last injection and 2) to determine whether the increase in seizure threshold is correlated with an increase in serum and/or brain DHA. Animals received daily intraperitoneal (i.p.) injections of 50mg/kg of DHA, DHA ethyl ester (DHA EE), or volume-matched vehicle (albumin/saline) for 14days. On day 15, one subset of animals was seizure tested in the maximal PTZ model (Experiment 1). In a separate (non-seizure tested) subset of animals, blood was collected, and brains were excised following high-energy, head-focused microwave fixation. Lipid analysis was performed on serum and brain (Experiment 2). For data analysis, the DHA and DHA EE groups were combined since they did not differ significantly from each other. In the maximal PTZ model, DHA significantly increased seizure latency by approximately 3-fold as compared to vehicle-injected animals. This increase in seizure latency was associated with an increase in serum unesterified DHA. Total brain DHA and brain unesterified DHA concentrations, however, did not differ significantly in the treatment and control groups. An increase in serum unesterified DHA concentration reflecting increased flux of DHA to the brain appears to explain changes in seizure threshold, independent of changes in brain DHA concentrations. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Chronic binge alcohol administration increases intestinal T cell proliferation and turnover in rhesus macaques

    PubMed Central

    Veazey, Ronald S.; Amedee, Angela; Wang, Xiaolei; Kaack, M. Bernice; Porretta, Constance; Dufour, Jason; Welsh, David; Happel, Kyle; Pahar, Bapi; Molina, Patricia E.; Nelson, Steve; Bagby, Gregory J.

    2015-01-01

    Background Alcohol use results in changes in intestinal epithelial cell turnover and microbial translocation, yet less in known about the consequences on intestinal lymphocytes in the gut. Here we compared T cell subsets in the intestine of macaques before and after 3 months of chronic alcohol administration to examine the effects of alcohol on intestinal T cell subsets. Methods Rhesus macaques received either alcohol or isocaloric sucrose as a control treatment daily over a 3 month period via indwelling gastric catheters. Intestinal lymphocytes subsets were identified in biopsy samples by flow cytometry. Twenty-four hours prior to sampling, animals were inoculated with BrdU to assess lymphocyte proliferation. Immunohistochemistry was performed on tissue samples to quantitate CD3+ cells. Results Animals receiving alcohol had increased rates of intestinal T cell turnover of both CD4+ and CD8+ T cells as reflected by increased BrdU incorporation. However, absolute numbers of T cells were decreased in intestinal tissues as evidenced by immunohistochemistry for total CD3 expression per mm2 intestinal lamina propria in tissue sections. Combining immunohistochemistry and flow cytometry data showed that the absolute numbers of CD8+ T cells were significantly decreased, whereas total of CD4+ T cells were minimally decreased. Conclusions Collectively, these data indicate alcohol exposure to the small intestine results in marked loss of CD3+ T cells, accompanied by marked increases in CD4+ and CD8+ T cell proliferation and turnover, which we speculate is an attempt to maintain stable numbers of T cells in tissues. This suggests alcohol results in accelerated T cell turnover in the gut, which may contribute to premature T cell senescence. Further these data indicate that chronic alcohol administration results in increased levels of HIV target cells (proliferating CD4+ T cells) that may support higher levels of HIV replication in intestinal tissues. PMID:26146859

  12. Daily Administration of Short-Acting Liothyronine Is Associated with Significant Triiodothyronine Excursions and Fails to Alter Thyroid-Responsive Parameters.

    PubMed

    Jonklaas, Jacqueline; Burman, Kenneth D

    2016-06-01

    Although most studies of levothyroxine-liothyronine combination therapy employ once-daily hormone administration, the kinetics of once-daily liothyronine have been studied infrequently. The aim of this study was to document both the peak and trough serum triiodothyronine (T3) levels that occur with once-daily liothyronine administration, along with changes in thyroid-responsive parameters. Participants with hypothyroidism were studied prospectively at an academic institution. Patients were switched from levothyroxine monotherapy to liothyronine monotherapy with 15 μg liothyronine for two weeks, and then continued liothyronine at doses of 30-45 μg for a further four weeks in an open-label, single-arm study. Weekly trough levels of T3 were documented. In addition, hourly T3 concentrations immediately following liothyronine tablet administration were documented for eight hours during the sixth week of therapy. Serum thyrotropin (TSH) and free thyroxine (fT4) concentrations were documented. Biochemical markers, markers of energy metabolism, anthropometric parameters, well-being, and hyperthyroid symptoms were also assessed. Mean serum TSH levels increased from 1.56 ± 0.81 mIU/L at baseline to 5.90 ± 5.74 mIU/L at two weeks and 3.84 ± 3.66 mIU/L at six weeks. Trough T3 levels decreased from 99.5 ± 22.9 to 91.9 ± 40.2 at two weeks and recovered to 96.1 ± 32.2 at six weeks. The peak T3 concentration after dosing of liothyronine during week 6 was 292.8 ± 152.3 ng/dL. fT4 levels fell once levothyroxine was discontinued and plateaued at 0.44 ng/dL at week 4. The sex hormone binding globulin (SHBG) concentration decreased at week 2 (p = 0.002). Hyperthyroid symptoms and SF36-PCS scores increased significantly at weeks 4-5 of liothyronine therapy (p = 0.04-0.005). Preference for liothyronine therapy increased from 6% to 39% over the study period. Once-daily dosing of liothyronine at doses of 30-45 μg did not return serum

  13. Factors increasing the risk of inactivity among administrative, technical, and manual workers in Warszawa public institutions.

    PubMed

    Biernat, Elżbieta

    2015-01-01

    The research aims to assess the level of physical activity among administrative, technical, and manual workers employed in Warszawa public institutions and to analyze the factors that increase the risk of failing to meet World Health Organization (WHO) recommendations. The study comprised 373 employees of randomly selected institutions. A short version of International Physical Activity Questionnaire (IPAQ) was applied. The correlation between the mean values of duration, days, MET-min/week of efforts, gender, and type of work was analyzed using the Tukey's honest significant difference (HSD) test, while the correlation between the level of physical activity and the socio-demographic characteristics was assessed with the Chi2 test. The strength of the relationship between socio-demographic characteristics and fulfilment of WHO standards was expressed by the odds ratio (OR) and 95% confidence interval (95% CI). The significance level was p = 0.05. High levels of physical activity were declared by 41.8% of the manual workers, 14.7% of the administration staff, and 7.3% of the technicians; 19%, 31.5% and 54.5%, respectively, reported low levels of physical activity. Factors determining the fulfilment of the WHO recommendations include: the nature of work (p = 0.003), education (p = 0.004), and income (p = 0.003). The risk of being inactive nearly doubles in the case of administration staff (31.5%) and increases more than 4 times in the case of technicians (54.5%). Respondents with secondary school education (31.6%) are exposed to a 3-fold higher risk of inactivity, while in respondents with higher education (37.2%), the level of the risk is 4-fold higher. Compared to those in the highest income group (23.4%), people who earn less (34.1%) are inactive almost twice as often. Urgent intervention is necessary in all studied groups: increased energy expenditure for recreation and locomotion, educational offers of employers to promote healthy lifestyle

  14. Increased bioavailability of tacrolimus after rectal administration in rats.

    PubMed

    Sakai, Masayuki; Hobara, Norio; Hokama, Nobuo; Kameya, Hiromasa; Ohshiro, Susumu; Sakanashi, Matao; Saitoh, Hiroshi

    2004-09-01

    The oral bioavailability of tacrolimus is low and varies considerably in humans due to first-pass metabolism by cytochrome P450 (CYP) 3A4 and the active efflux mediated by P-glycoprotein. This study was undertaken to elucidate the usefulness of rectal administration of tacrolimus as an alternative route to improve its bioavailability. Tacrolimus powder was suspended in a suppository base (witepsol H-15) and the tacrolimus suppository was inserted into the anus of the rats. For comparison, tacrolimus was suspended in 0.5% sodium methylcellulose solution and administered orally to rats. The dose of tacrolimus was fixed to 2 mg/kg. Blood samples were collected periodically up to 24 h after dosing, and tacrolimus concentrations were assayed by microparticle enzyme immunoassay. The whole blood concentrations of tacrolimus after rectal administration were much greater than those after oral administration. The C(max) and AUC(0-24 h) values after rectal administration were 3.9- and 6.9-fold greater than those after oral administration, respectively. These results clearly suggest a possibility that rectal administration of tacrolimus is capable of improving its bioavailability and cutting the costs of tacrolimus treatment.

  15. Administration of the non-steroidal anti-inflammatory drug ibuprofen increases macrophage concentrations but reduces necrosis during modified muscle use

    NASA Technical Reports Server (NTRS)

    Cheung, E. V.; Tidball, J. G.

    2003-01-01

    OBJECTIVE: To test the hypothesis that ibuprofen administration during modified muscle use reduces muscle necrosis and invasion by select myeloid cell populations. METHODS: Rats were subjected to hindlimb unloading for 10 days, after which they experienced muscle reloading by normal weight-bearing to induce muscle inflammation and necrosis. Some animals received ibuprofen by intraperitoneal injection 8 h prior to the onset of muscle reloading, and then again at 8 and 16 h following the onset of reloading. Other animals received buffer injection at 8 h prior to reloading and then ibuprofen at 8 and 16 h following the onset of reloading. Control animals received buffer only at each time point. Quantitative immunohistochemical analysis was used to assess the presence of necrotic muscle fibers, total inflammatory infiltrate, neutrophils, ED1+ macrophages and ED2+ macrophages at 24 h following the onset of reloading. RESULT: Administration of ibuprofen beginning 8 h prior to reloading caused significant reduction in the concentration of necrotic fibers, but increased the concentration of inflammatory cells in muscle. The increase in inflammatory cells was attributable to a 2.6-fold increase in the concentration of ED2+ macrophages. Animals treated with ibuprofen 8 h following the onset of reloading showed no decrease in muscle necrosis or increase in ED2+ macrophage concentrations. CONCLUSION: Administration of ibuprofen prior to increased muscle loading reduces muscle damage, but increases the concentration of macrophages that express the ED2 antigen. The increase in ED2+ macrophage concentration and decrease in necrosis may be mechanistically related because ED2+ macrophages have been associated with muscle regeneration and repair.

  16. Cocaine Self-Administration Produces a Persistent Increase in Dopamine D2High Receptors

    PubMed Central

    Briand, Lisa A.; Flagel, Shelly B.; Seeman, Philip; Robinson, Terry E.

    2008-01-01

    Cocaine addicts are reported to have decreased numbers of striatal dopamine D2 receptors. However, in rodents, repeated cocaine administration consistently produces hypersensitivity to the psychomotor activating effects of both indirect dopamine agonists, such as cocaine itself, and importantly, to direct-acting D2 receptor agonists. The current study reports a possible resolution to this long-standing paradox. The dopamine D2 receptor exists in both a low and a high affinity state, and dopamine exerts its effects via the more functionally relevant high-affinity D2 receptor (D2High). We report here that cocaine self-administration experience produces a large (approximately 150%) increase in the proportion of D2High receptors in the striatum with no change in the total number of D2 receptors, and this effect is evident both 3 and 30 days after the discontinuation of cocaine self-administration. Changes in D2High receptors would not be evident with the probes used in human (and non-human primate) imaging studies. We suggest, therefore, that cocaine addicts and animals previously treated with cocaine may be hyper-responsive to dopaminergic drugs in part because an increase in D2High receptors results in dopamine supersensitivity. This may also help explain why stimuli that increase dopamine neurotransmission, including drugs themselves, are so effective in producing relapse in individuals with a history of exposure to cocaine. PMID:18284941

  17. Diet, physical exercise and Orlistat administration increase serum anti-Müllerian hormone (AMH) levels in women with polycystic ovary syndrome (PCOS).

    PubMed

    Vosnakis, Christos; Georgopoulos, Neoklis A; Rousso, David; Mavromatidis, Georgios; Katsikis, Ilias; Roupas, Nikolaos D; Mamali, Irene; Panidis, Dimitrios

    2013-03-01

    The present study investigates the combined effect of diet, physical exercise and Orlistat for 24 weeks, on serum anti-Müllerian hormone (AMH) levels in overweight and obese women with polycystic ovary syndrome (PCOS) and in overweight and obese controls. Sixty-one (61) selected women with PCOS and 20 overweight and obese controls followed an energy-restricted diet, physical exercise plus Orlistat administration (120 mg, 3 times per day) for 24 weeks. At baseline, week 12 and week 24, serum levels of AMH, FSH, LH, PRL, androgens, sex hormone-binding globulin (SHBG), glucose, and insulin were measured and Free Androgen Index (FAI) and Insulin Resistance (IR) indices were calculated. In PCOS women, serum AMH levels increased after 12 and 24 weeks of treatment. After 12 weeks LH and SHBG were increased, while Testosterone decreased. After 12 and 24 weeks, FAI was decreased and all indices of IR were significantly improved. We concluded that in overweight and obese women with PCOS Orlistat administration, combined with diet and physical exercise, for 24 weeks, resulted in significant weight loss, improvement of hyperandrogenism and insulin sensitivity, and increased serum AMH levels.

  18. Increase of antioxidative potential of rat plasma by oral administration of proanthocyanidin-rich extract from grape seeds.

    PubMed

    Koga, T; Moro, K; Nakamori, K; Yamakoshi, J; Hosoyama, H; Kataoka, S; Ariga, T

    1999-05-01

    The effect of a single oral administration of proanthocyanidins, oligomeric and polymeric polyhydroxyflavan-3-ol units, on the antioxidative potential of blood plasma was studied in rats. Proanthocyanidin-rich extract from grape seeds was administered by intragastric intubation to fasted rats at 250 mg/kg of body weight. The plasma obtained from water- or proanthocyanidin-administered rats was oxidized by incubation with copper sulfate or 2, 2'-azobis(2-amidinopropane) dihydrochloride (AAPH) at 37 degrees C, and the formation of cholesteryl ester hydroperoxides (CE-OOH) was followed. The plasma obtained from proanthocyanidin-administered rats was significantly more resistant against both copper ion-induced and AAPH-induced formation of CE-OOH than that from control rats. The lag phase in the copper ion-induced oxidation of rat plasma was remarkably increased at 15 min after administration of proanthocyanidins and reached a maximum level at 30 min. When the plasma from proanthocyanidin-administered rat was hydrolyzed by sulfatase and beta-glucuronidase following analysis by high-performance liquid chromatography with electrochemical detection, metabolites of proanthocyanidins occurred in rat plasma at 15 min after administration, three peaks of which were identified as gallic acid, (+)-catechin, and (-)-epicatechin. These results suggest that the intake of proanthocyanidins, the major polyphenols in red wine, increases the resistance of blood plasma against oxidative stress and may contribute to physiological functions of plant food including wine through their in vivo antioxidative ability.

  19. Increased brain and plasma oxytocin after nasal and peripheral administration in rats and mice.

    PubMed

    Neumann, Inga D; Maloumby, Rodrigue; Beiderbeck, Daniela I; Lukas, Michael; Landgraf, Rainer

    2013-10-01

    The possibility to improve socio-emotional behaviors in humans by intranasal administration of synthetic oxytocin (OXT) attracts increasing attention, but its uptake into the brain has never been demonstrated so far. Here we used simultaneous microdialysis in both the dorsal hippocampus and amygdala of rats and mice in combination with concomitant blood sampling from the jugular vein to study the dynamics of the neuropeptide in brain extracellular fluid and plasma after its nasal administration. OXT was found to be increased in microdialysates from both the hippocampus and amygdala with peak levels occurring 30-60min after nasal administration. Despite a similar temporal profile of OXT concentrations in plasma, peripheral OXT is unlikely to contribute to dialysate OXT as calculated from in vitro recovery data, indicating a central route of transport. Moreover, intraperitoneal administration of synthetic OXT in identical amounts caused rapid peak levels in brain dialysates and plasma during the first 30min after treatment and a subsequent return toward baseline. While the precise route(s) of central transport remain to be elucidated, our data provide the first evidence that nasally applied OXT indeed reaches behaviorally relevant brain areas, and this uptake is paralleled by changes in plasma OXT. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. Peripheral Administration of Ethanol Results in a Correlated Increase in Dopamine and Serotonin Within the Posterior Ventral Tegmental Area

    PubMed Central

    Deehan, Gerald A.; Knight, Christopher P.; Waeiss, R. Aaron; Engleman, Eric A.; Toalston, Jamie E.; McBride, William J.; Hauser, Sheketha R.; Rodd, Zachary A.

    2016-01-01

    Aims Two critical neurotransmitter systems regulating ethanol (EtOH) reward are serotonin (5-HT) and dopamine (DA). Within the posterior ventral tegmental area (pVTA), 5-HT receptors have been shown to regulate DA neuronal activity. Increased pVTA neuronal activity has been linked to drug reinforcement. The current experiment sought to determine the effect of EtOH on 5-HT and DA levels within the pVTA. Methods Wistar rats were implanted with cannula aimed at the pVTA. Neurochemical levels were determined using standard microdialysis procedures with concentric probes. Rats were randomly assigned to one of the five groups (n = 41; 7–9 per group) that were treated with 0–3.0 g/kg EtOH (intraperitoneally). Results Ethanol produced increased extracellular DA levels in the pVTA that resembled an inverted U-shape dose–response curve with peak levels (~200% of baseline) at the 2.25 g/kg dose. The increase in DA levels was observed for an extended period of time (~100 minutes). The effects of EtOH on extracellular 5-HT levels in the pVTA also resembled an inverted U-shape dose–response curve. However, increased 5-HT levels were only observed during the initial post-injection sample. The increases in extracellular DA and 5-HT levels were significantly correlated. Conclusion The data indicate intraperitoneal EtOH administration stimulated the release of both 5-HT and DA within the pVTA, the levels of which were significantly correlated. Overall, the current findings suggest that the ability of EtOH to stimulate DA activity within the mesolimbic system may be modulated by increases in 5-HT release within the pVTA. Short summary Two critical neurotransmitter systems regulating ethanol reward are serotonin and dopamine. The current experiment determined that intraperitoneal ethanol administration increased serotonin and dopamine levels within the pVTA (levels were significantly correlated). The current findings suggest the ability of EtOH to stimulate serotonin and

  1. Acute administration of ketamine in rats increases hippocampal BDNF and mTOR levels during forced swimming test.

    PubMed

    Yang, Chun; Hu, Yi-Min; Zhou, Zhi-Qiang; Zhang, Guang-Fen; Yang, Jian-Jun

    2013-03-01

    Previous studies have shown that a single sub-anesthetic dose of ketamine exerts fast-acting antidepressant effects in patients and in animal models of depression. However, the underlying mechanisms are not totally understood. This study aims to investigate the effects of acute administration of different doses of ketamine on the immobility time of rats in the forced swimming test (FST) and to determine levels of hippocampal brain-derived neurotrophic factor (BDNF) and mammalian target of rapamycin (mTOR). Forty male Wistar rats weighing 180-220 g were randomly divided into four groups (n = 10 each): group saline and groups ketamine 5, 10, and 15 mg/kg. On the first day, all animals were forced to swim for 15 min. On the second day ketamine (5, 10, and 15 mg/kg, respectively) was given intraperitoneally, at 30 min before the second episode of the forced swimming test. Immobility times of the rats during the forced swimming test were recorded. The animals were then decapitated. The hippocampus was harvested for determination of BDNF and mTOR levels. Compared with group saline, administration of ketamine at a dose of 5, 10, and 15 mg/kg decreased the duration of immobility (P < 0.05 for all doses). Ketamine at doses of both 10 and 15 mg/kg showed a significant increase in the expression of hippocampal BDNF (P < 0.05 for both doses). Ketamine given at doses of 5, 10, and 15 mg/kg showed significant increases in relative levels of hippocampal p-mTOR (P < 0.05 for all doses) The antidepressant effect of ketamine might be related to the increased expression of BDNF and mTOR in the hippocampus of rats.

  2. Daily Administration of Short-Acting Liothyronine Is Associated with Significant Triiodothyronine Excursions and Fails to Alter Thyroid-Responsive Parameters

    PubMed Central

    Burman, Kenneth D.

    2016-01-01

    Background: Although most studies of levothyroxine–liothyronine combination therapy employ once-daily hormone administration, the kinetics of once-daily liothyronine have been studied infrequently. The aim of this study was to document both the peak and trough serum triiodothyronine (T3) levels that occur with once-daily liothyronine administration, along with changes in thyroid-responsive parameters. Methods: Participants with hypothyroidism were studied prospectively at an academic institution. Patients were switched from levothyroxine monotherapy to liothyronine monotherapy with 15 μg liothyronine for two weeks, and then continued liothyronine at doses of 30–45 μg for a further four weeks in an open-label, single-arm study. Weekly trough levels of T3 were documented. In addition, hourly T3 concentrations immediately following liothyronine tablet administration were documented for eight hours during the sixth week of therapy. Serum thyrotropin (TSH) and free thyroxine (fT4) concentrations were documented. Biochemical markers, markers of energy metabolism, anthropometric parameters, well-being, and hyperthyroid symptoms were also assessed. Results: Mean serum TSH levels increased from 1.56 ± 0.81 mIU/L at baseline to 5.90 ± 5.74 mIU/L at two weeks and 3.84 ± 3.66 mIU/L at six weeks. Trough T3 levels decreased from 99.5 ± 22.9 to 91.9 ± 40.2 at two weeks and recovered to 96.1 ± 32.2 at six weeks. The peak T3 concentration after dosing of liothyronine during week 6 was 292.8 ± 152.3 ng/dL. fT4 levels fell once levothyroxine was discontinued and plateaued at 0.44 ng/dL at week 4. The sex hormone binding globulin (SHBG) concentration decreased at week 2 (p = 0.002). Hyperthyroid symptoms and SF36-PCS scores increased significantly at weeks 4–5 of liothyronine therapy (p = 0.04–0.005). Preference for liothyronine therapy increased from 6% to 39% over the study period. Conclusions: Once-daily dosing of

  3. Increased densities of monocarboxylate transport protein MCT1 after chronic administration of nicotine in rat brain.

    PubMed

    Canis, Martin; Mack, Brigitte; Gires, Olivier; Maurer, Martin H; Kuschinsky, Wolfgang; Duembgen, Lutz; Duelli, Roman

    2009-08-01

    Chronic administration of nicotine is followed by a general stimulation of brain metabolism that results in a distinct increase of glucose transport protein densities for Glut1 and Glu3, and local cerebral glucose utilization (LCGU). This increase of LCGU might be paralleled by an enhanced production of lactate. Therefore, the question arose as to whether chronic nicotine infusion is accompanied by increased local densities of monocarboxylate transporter MCT1 in the brain. Secondly, we inquired whether LCGU might be correlated with local densities of MCT1 during normal conditions and after chronic nicotine infusion. Nicotine was given subcutaneously for 1 week by osmotic mini-pumps and local densities of MCT1 were measured by immunoautoradiographic methods in cryosections of rat brains. MCT1 density was significantly increased in 21 of 32 brain structures investigated (median increase 15.0+/-3.6%). Immunohistochemical stainings of these substructures revealed an over-expression of MCT1 within endothelial cells and astrocytes of treated animals. A comparison of 23 MCT1 densities with LCGU measured in the same structures in a previous study revealed a partial correlation between both parameters under control conditions and after chronic nicotine infusion. 10 out of 23 brain areas, which showed a significant increase of MCT1 density due to chronic nicotine infusion, also showed a significant increase of LCGU. In summary, our data show that chronic nicotine infusion induces a moderate increase of local and global density of MCT1 in defined brain structures. However, in terms of brain topologies and substructures this phenomenon did partially match with increased LCGU. It is concluded that MCT1 transporters were upregulated during chronic nicotine infusion at the level of brain substructures and, at least partially, independently of LCGU.

  4. Preweaning iron deficiency increases non-contingent responding during cocaine self-administration in rats.

    PubMed

    Jenney, Christopher B; Alexander, Danielle N; Jones, Byron C; Unger, Erica L; Grigson, Patricia S

    2016-12-01

    Iron deficiency (ID) is the most prevalent single-nutrient deficiency worldwide. There is evidence that ID early in development (preweaning in rat) causes irreversible neurologic, behavioral, and motor development deficits. Many of these effects have been attributed to damage to dopamine systems, including ID-induced changes in transporter and receptor numbers in the striatum and nucleus accumbens. These mesolimbic dopaminergic neurons are, in part, responsible for mediating reward and thus play a key role in addiction. However, there has been relatively little investigation into the behavioral effects of ID on drug addiction. In 2002, we found that rats made ID from weaning (postnatal day 21) and throughout the experiment acquired cocaine self-administration significantly more slowly than controls and failed to increase responding when the dose of the drug was decreased. In the present study, we assessed addiction for self-administered cocaine in rats with a history of preweaning ID only during postnatal days 4 through 21, and iron replete thereafter. The results showed that while ID did not affect the number of cocaine infusions or the overall addiction-like behavior score, ID rats scored higher on a measure of continued responding for drug than did iron replete controls. This increase in responding, however, was less goal-directed as ID rats also responded more quickly to the non-rewarded manipulandum than did control rats. Thus, while ID early in infancy did not significantly increase addiction-like behaviors for cocaine in this small study, the pattern of data suggests a possible underlying learning or performance impairment. Future studies will be needed to elucidate the exact neuro-behavioral deficits that lead to the increase in indiscriminate responding for drug in rats with a history of perinatal ID. Copyright © 2016. Published by Elsevier Inc.

  5. Report: Management Alert - Salary Increases for Certain Administratively Determined Positions

    EPA Pesticide Factsheets

    Report #18-N-0154, April 16, 2018. The purpose of this alert is to notify the EPA of certain factual info while our audit of the Office of the Administrator's (present and prior administrations) use of administratively determined positions continues.

  6. Transient increase in alcohol self-administration following a period of chronic exposure to corticosterone

    PubMed Central

    Besheer, Joyce; Fisher, Kristen R.; Lindsay, Tessa G.; Cannady, Reginald

    2013-01-01

    Stressful life events and chronic stressors have been associated with escalations in alcohol drinking. Stress exposure leads to the secretion of glucocorticoids (cortisol in the human; corticosterone (CORT) in the rodent). To model a period of heightened elevations in CORT, the present work assessed the effects of chronic exposure to the stress hormone CORT on alcohol self-administration. Male Long Evans rats were trained to self-administer a sweetened alcohol solution (2% sucrose/15% alcohol) resulting in moderate levels of daily alcohol intake (0.5–0.7 g/kg). Following stable baseline operant self-administration, rats received CORT in the drinking water for 7 days. A transient increase in alcohol self-administration was observed on the first self-administration session following CORT exposure, and behavior returned to control levels by the second session. Control experiments determined that this increase in alcohol self-administration was specific to alcohol, unrelated to general motor activation, and functionally dissociated from decreased CORT levels at the time of testing. These results indicate that repeated exposure to heightened levels of stress hormone (e.g., as may be experienced during stressful episodes) has the potential to lead to exacerbated alcohol intake in low to moderate drinkers. Given that maladaptive drinking patterns, such as escalated alcohol drinking following stressful episodes, have the potential to put an individual at risk for future drinking disorders, utilization of this model will be important for examination of neuroadaptations that occur as a consequence of CORT exposure in order to better understand escalated drinking following stressful episodes in nondependent individuals. PMID:23643750

  7. Chronic Binge Alcohol Administration Increases Intestinal T-Cell Proliferation and Turnover in Rhesus Macaques.

    PubMed

    Veazey, Ronald S; Amedee, Angela; Wang, Xiaolei; Bernice Kaack, M; Porretta, Constance; Dufour, Jason; Welsh, David; Happel, Kyle; Pahar, Bapi; Molina, Patricia E; Nelson, Steve; Bagby, Gregory J

    2015-08-01

    Alcohol use results in changes in intestinal epithelial cell turnover and microbial translocation, yet less is known about the consequences on intestinal lymphocytes in the gut. Here, we compared T-cell subsets in the intestine of macaques before and after 3 months of chronic alcohol administration to examine the effects of alcohol on intestinal T-cell subsets. Rhesus macaques received either alcohol or isocaloric sucrose as a control treatment daily over a 3-month period via indwelling gastric catheters. Intestinal lymphocyte subsets were identified in biopsy samples by flow cytometry. Twenty-four hours prior to sampling, animals were inoculated with bromo-deoxyuridine (BrdU) to assess lymphocyte proliferation. Immunohistochemistry was performed on tissue samples to quantitate CD3+ cells. Animals receiving alcohol had increased rates of intestinal T-cell turnover of both CD4+ and CD8+ T cells as reflected by increased BrdU incorporation. However, absolute numbers of T cells were decreased in intestinal tissues as evidenced by immunohistochemistry for total CD3 expression per mm(2) intestinal lamina propria in tissue sections. Combining immunohistochemistry and flow cytometry data showed that the absolute numbers of CD8+ T cells were significantly decreased, whereas absolute numbers of total CD4+ T cells were minimally decreased. Collectively, these data indicate that alcohol exposure to the small intestine results in marked loss of CD3+ T cells, accompanied by marked increases in CD4+ and CD8+ T-cell proliferation and turnover, which we speculate is an attempt to maintain stable numbers of T cells in tissues. This suggests that alcohol results in accelerated T-cell turnover in the gut, which may contribute to premature T-cell senescence. Further, these data indicate that chronic alcohol administration results in increased levels of HIV target cells (proliferating CD4+ T cells) that may support higher levels of HIV replication in intestinal tissues. Copyright

  8. Increased prandial insulin secretion after administration of a single preprandial oral dose of repaglinide in patients with type 2 diabetes.

    PubMed

    Owens, D R; Luzio, S D; Ismail, I; Bayer, T

    2000-04-01

    To examine the dose-related pharmacodynamics and pharmacokinetics of a single preprandial oral dose of repaglinide in patients with type 2 diabetes. A total of 16 Caucasian men with type 2 diabetes participated in two placebo-controlled double-blind randomized cross-over studies. Patients were randomized to receive a single oral dose of repaglinide (0.5, 1.0, and 2.0 mg in study 1 and 4.0 mg in study 2) or placebo (both studies) administered 15 min before the first of two sequential identical standard meals (breakfast and lunch) that were 4 h apart. During each of the study days, which were 1 week apart, blood samples were taken at frequent intervals over a period of approximately 8 h for measurement of plasma glucose, insulin, C-peptide, and repaglinide concentrations. During the first meal period (0-240 min), administration of repaglinide reduced significantly the area under the curve (AUC) for glucose concentration and significantly increased the AUC for insulin levels, C-peptide levels, and the insulin secretion rate. These results, compared with those of administering placebo, were dose dependent and log linear. The effect of repaglinide administration on insulin secretion was most pronounced in the early prandial period. Within 30 min, it caused a relative increase in insulin secretion of up to 150%. During the second meal period (240-480 min), there was no difference between repaglinide and placebo administration in the AUC for glucose concentration, C-peptide concentration, and the estimated insulin secretion rate. A single dose of repaglinide (0.5-4.0 mg) before breakfast improves insulin secretion and reduces prandial hyperglycemia dose-dependently Administration of repaglinide had no effect on insulin secretion with the second meal, which was consumed 4 h after breakfast.

  9. High ambient temperature increases intravenous methamphetamine self-administration on fixed and progressive ratio schedules in rats.

    PubMed

    Cornish, Jennifer L; Clemens, Kelly J; Thompson, Murray R; Callaghan, Paul D; Dawson, Bronwyn; McGregor, Iain S

    2008-01-01

    Methamphetamine is a drug that is often consumed at dance parties or nightclubs where the ambient temperature is high. The present study determined whether such high ambient temperatures alter intravenous methamphetamine self-administration in the rat. Male Hooded Wistar rats were trained to self-administer intravenous methamphetamine (0.1 mg/kg/infusion) under a fixed ratio 1 (FR1) or progressive ratio (PR) schedule of reinforcement at an ambient temperature of 23 +/- 1 degrees C. They were then given their daily self-administration session at a raised ambient temperature of 30 +/- 1 degrees C. Methamphetamine self-administration was increased at 30 degrees C under both FR1 and PR reinforcement schedules, with the latter effect indicating that heat enhances the motivation to obtain methamphetamine. High temperatures did not alter self-administration of the D1 receptor agonist SKF 82958 in methamphetamine-experienced rats suggesting some specificity in the methamphetamine effect. When rats were given access to drink isotonic saline solution during methamphetamine self-administration sessions they drank much more solution at 30 degrees C than 23 degrees C. However, availability of isotonic saline to drink did not alter the heat-induced facilitation of methamphetamine self-administration (PR schedule) indicating that the heat effect does not simply reflect increased motivation for intravenous fluids. Hyperthermia was evident in rats self-administering methamphetamine at high ambient temperatures and fluid consumption did not prevent this effect. Heat did not affect blood levels of methamphetamine, or its principal metabolite amphetamine indicating that the facilitatory effect of heat did not reflect altered methamphetamine pharmacokinetics. Overall, these results show that high ambient temperatures increase the reinforcing efficacy of methamphetamine and encourage higher levels of drug intake.

  10. Acute administration of ketamine in rats increases hippocampal BDNF and mTOR levels during forced swimming test

    PubMed Central

    Hu, Yi-Min; Zhou, Zhi-Qiang; Zhang, Guang-Fen

    2013-01-01

    Introduction Previous studies have shown that a single sub-anesthetic dose of ketamine exerts fast-acting antidepressant effects in patients and in animal models of depression. However, the underlying mechanisms are not totally understood. This study aims to investigate the effects of acute administration of different doses of ketamine on the immobility time of rats in the forced swimming test (FST) and to determine levels of hippocampal brain-derived neurotrophic factor (BDNF) and mammalian target of rapamycin (mTOR). Methods Forty male Wistar rats weighing 180–220 g were randomly divided into four groups (n = 10 each): group saline and groups ketamine 5, 10, and 15 mg/kg. On the first day, all animals were forced to swim for 15 min. On the second day ketamine (5, 10, and 15 mg/kg, respectively) was given intraperitoneally, at 30 min before the second episode of the forced swimming test. Immobility times of the rats during the forced swimming test were recorded. The animals were then decapitated. The hippocampus was harvested for determination of BDNF and mTOR levels. Results Compared with group saline, administration of ketamine at a dose of 5, 10, and 15 mg/kg decreased the duration of immobility (P < 0.05 for all doses). Ketamine at doses of both 10 and 15 mg/kg showed a significant increase in the expression of hippocampal BDNF (P < 0.05 for both doses). Ketamine given at doses of 5, 10, and 15 mg/kg showed significant increases in relative levels of hippocampal p-mTOR (P < 0.05 for all doses) Conclusion The antidepressant effect of ketamine might be related to the increased expression of BDNF and mTOR in the hippocampus of rats. PMID:22970723

  11. Gradually Increased Oxygen Administration Improved Oxygenation and Mitigated Oxidative Stress after Resuscitation from Severe Hemorrhagic Shock.

    PubMed

    Luo, Xin; Yin, Yujing; You, Guoxing; Chen, Gan; Wang, Ying; Zhao, Jingxiang; Wang, Bo; Zhao, Lian; Zhou, Hong

    2015-11-01

    The optimal oxygen administration strategy during resuscitation from hemorrhagic shock (HS) is still controversial. Improving oxygenation and mitigating oxidative stress simultaneously seem to be contradictory goals. To maximize oxygen delivery while minimizing oxidative damage, the authors proposed the notion of gradually increased oxygen administration (GIOA), which entails making the arterial blood hypoxemic early in resuscitation and subsequently gradually increasing to hyperoxic, and compared its effects with normoxic resuscitation, hyperoxic resuscitation, and hypoxemic resuscitation in severe HS. Rats were subjected to HS, and on resuscitation, the rats were randomly assigned to four groups (n = 8): the normoxic, the hyperoxic, the hypoxemic, and the GIOA groups. Rats were observed for an additional 1 h. Hemodynamics, acid-base status, oxygenation, and oxidative injury were observed and evaluated. Central venous oxygen saturation promptly recovered only in the hyperoxic and the GIOA groups, and the liver tissue partial pressure of oxygen was highest in the GIOA group after resuscitation. Oxidative stress in GIOA group was significantly reduced compared with the hyperoxic group as indicated by the reduced malondialdehyde content, increased catalase activity, and the lower histologic injury scores in the liver. In addition, the tumor necrosis factor-α and interleukin-6 expressions in the liver were markedly decreased in the GIOA group than in the hyperoxic and normoxic groups as shown by the immunohistochemical staining. GIOA improved systemic/tissue oxygenation and mitigated oxidative stress simultaneously after resuscitation from severe HS. GIOA may be a promising strategy to improve resuscitation from HS and deserves further investigation.

  12. Repeated chlorpromazine administration increases a behavioural response of rats to 5-hydroxytryptamine receptor stimulation.

    PubMed Central

    Green, A R

    1977-01-01

    1 The hyperactivity syndrome produced in rats by administration of tranylcypromine (20 mg/kg i.p.) followed 30 min later by L-tryptophan (50 mg/kg i.p.) is generally considered to be due to increased 5-hydroxytryptamine (5-HT) functional activity. It is inhibited by chlorpromazine (30 mg/kg i.p.) injected 60 min before the tranylcypromine. However, chlorpromazine injection for 4 days either at a dose of 30 mg/kg once daily or 5 mg/kg twice daily results in an enhanced hyperactivity response to tranylcypromine and L-tryptophan administration 24 h after the final dose of chlorpromazine. 2 One injection of chlorpromazine (30 mg/kg) did not produce enhancement 24 h later and the inhibition of the tranylcypromine/L-tryptophan hyperactivity observed after acute chlorpromazine injection was seen if the rats were given tranylcypromine and L-tryptophan 1 h after the fourth chlorpromazine (30 mg/kg) dose. 3 Chlorpromazine (30 mg/kg) once daily or 5 mg/kg twice daily for 4 days resulted in rats displaying enhanced behavioral responses to the suggested 5-HT agonist 5-methoxy N,N-dimethyltryptamine (2 mg/kg) on day 5. 4 Chlorpromazine (30 mg/kg) once daily for 4 days produces a slight increase in brain 5-hydroxytryptamine (5-HT) concentration on day 5, but no difference in the rate of brain 5-HT synthesis or the rate of 5-HT accumulation after tranylcypromine and L-tryptophan administration. 5. There is some evidence that chlorpromazine blocks 5-HT receptors. It has also been observed that several other neuroleptic drugs do not produce enhanced 5-HT responses after repeated administration. It is suggested therefore that the enhanced behavioural response to 5-HT receptor stimulation following repeated chlorpromazine administration may be because this drug blocks 5-HT receptors. PMID:264797

  13. Improving Communication Skills among High School Assistant Principals To Increase Administrative Team Effectiveness.

    ERIC Educational Resources Information Center

    Hosack, Mary Browne

    This paper describes a practicum program that was developed to increase the effectiveness of the administrative team at one high school. A lack of communication skills had prevented the target group from working together as a team. Strategies included role-play activities, workshops, and communication skill-development meetings. A series of…

  14. Acute Central Neuropeptide Y Administration Increases Food Intake but Does Not Affect Hepatic Very Low-Density Lipoprotein (Vldl) Production in Mice

    PubMed Central

    Havekes, Louis M.; Romijn, Johannes A.; Rensen, Patrick C. N.

    2013-01-01

    Objective Central neuropeptide Y (NPY) administration stimulates food intake in rodents. In addition, acute modulation of central NPY signaling increases hepatic production of very low-density lipoprotein (VLDL)-triglyceride (TG) in rats. As hypertriglyceridemia is an important risk factor for atherosclerosis, for which well-established mouse models are available, we set out to validate the effect of NPY on hepatic VLDL-TG production in mice, to ultimately investigate whether NPY, by increasing VLDL production, contributes to the development of atherosclerosis. Research Design and Methods Male C57Bl/6J mice received an intracerebroventricular (i.c.v.) cannula into the lateral (LV) or third (3V) ventricle of the brain. One week later, after a 4 h fast, the animals received an intravenous (i.v.) injection of Tran35S (100 µCi) followed by tyloxapol (500 mg/kg body weight; BW), enabling the study of hepatic VLDL-apoB and VLDL-TG production, respectively. Immediately after the i.v. injection of tyloxapol, the animals received either an i.c.v. injection of NPY (0.2 mg/kg BW in artificial cerebrospinal fluid; aCSF), synthetic Y1 receptor antagonist GR231118 (0.5 mg/kg BW in aCSF) or vehicle (aCSF), or an i.v. injection of PYY3–36 (0.5 mg/kg BW in PBS) or vehicle (PBS). Results Administration of NPY into both the LV and 3V increased food intake within one hour after injection (+164%, p<0.001 and +367%, p<0.001, respectively). NPY administration neither in the LV nor in the 3V affected hepatic VLDL-TG or VLDL-apoB production. Likewise, antagonizing central NPY signaling by either PYY3–36 or GR231118 administration did not affect hepatic VLDL production. Conclusion In mice, as opposed to rats, acute central administration of NPY increases food intake without affecting hepatic VLDL production. These results are of great significance when extrapolating findings on the central regulation of hepatic VLDL production between species. PMID:23460782

  15. Repeated MDMA administration increases MDMA-produced locomotor activity and facilitates the acquisition of MDMA self-administration: role of dopamine D2 receptor mechanisms.

    PubMed

    van de Wetering, Ross; Schenk, Susan

    2017-04-01

    Repeated exposure to ±3, 4-methylenedioxymethamphetamine (MDMA) produces sensitization to MDMA-produced hyperactivity, but the mechanisms underlying the development of this sensitized response or the relationship to the reinforcing effects of MDMA is unknown. This study determined the effect of a sensitizing regimen of MDMA exposure on the acquisition of MDMA self-administration and investigated the role of dopamine D 2 receptor mechanisms. Rats received the selective D 2 antagonist, eticlopride (0.0 or 0.3 mg/kg, i.p.) and MDMA (0.0 or 10.0 mg/kg, i.p.) during a five-day pretreatment regimen. Two days following the final session, the locomotor activating effects of MDMA (5 mg/kg, i.p.) and the latency to acquisition of MDMA self-administration were determined. Pretreatment with MDMA enhanced the locomotor activating effects of MDMA and facilitated the acquisition of MDMA self-administration. Administration of eticlopride during MDMA pretreatment completely blocked the development of sensitization to MDMA-produced hyperactivity but failed to significantly alter the facilitated acquisition of MDMA self-administration. Pretreatment with eticlopride alone facilitated the acquisition of self-administration. These data suggest that repeated MDMA exposure sensitized both the locomotor activating and reinforcing effects of MDMA. Activation of D 2 receptors during MDMA pretreatment appears critical for the development of sensitization to MDMA-produced hyperactivity. The role of D 2 receptor mechanisms in the development of sensitization to the reinforcing effects of MDMA is equivocal.

  16. [Significant increase of glucose transport activity in breast cancer].

    PubMed

    Li, Juan; Yang, Shou-jing; Zhao, Xi-long; Zhang, Ya-qing; Li, Kai-nan; Cui, Ji-hong; Li, Jing

    2008-02-01

    To study the expression level and significance of glucose transporter 1 (Glut-1) in normal breast tissue, adenosis, adenoma and breast carcinoma. A total of 147 cases of female breast tissue samples, including 92 cases of invasive ductal carcinoma, 26 cases of breast fibroadenoma, 24 cases of breast adenosis and 5 cases of normal breast tissues, were collected for quantitative detection of the expression of Glut-1 protein by immunohistochemistry (EnVision method) and Western blot, and its mRNA by reverse transcriptase-polymerase chain reaction (RT-PCR). In normal breast tissue and benign lesions of the breast, Glut-1 was undetectable or only weakly detectable in cytoplasm of ductal and acinar epithelia. In contrast, the intensity of Glut-1 staining was significantly higher in invasive ductal carcinomas (P = 0.0002) with protein expression predominantly in cellular membrane and lesser in cytoplasm. Western blot and RT-PCR analyses showed that the expression of Glut-1 protein and mRNA were significantly increased in invasive ductal carcinoma than fibroadenoma (P =0.001 for protein; P <0.05 for mRNA) and adenosis (P =0.001 for protein; P < 0.05 for mRNA). There was a significant difference among groups (P = 0.0002 for protein; P = 0.0001 for mRNA). Glucose transport activity, as indicated by Glut-1 protein and its mRNA expression, significantly increases in breast carcinoma than non-cancerous lesions. The over-expression of Glut-1 in breast carcinoma is tightly coupled with tumor cell proliferation, invasion and metastasis, implying that Glut-1 may serve as a new marker in the early diagnosis and prognostication of breast malignancy as well as a new therapeutic target.

  17. Constitutive Knockout of Kalirin-7 Leads to Increased Rates of Cocaine Self-Administration

    PubMed Central

    Kiraly, Drew D.; Nemirovsky, Natali E.; LaRese, Taylor P.; Tomek, Seven E.; Yahn, Stephanie L.; Olive, M. Foster; Eipper, Betty A.

    2013-01-01

    Kalirin-7 (Kal7) is a Rho-guanine nucleotide exchange factor that is localized in neuronal postsynaptic densities. Kal7 interacts with the NR2B subunit of the NMDA receptor and regulates aspects of dendritic spine dynamics both in vitro and in vivo. Chronic treatment with cocaine increases dendritic spine density in the nucleus accumbens (NAc) of rodents and primates. Kal7 mRNA and protein are upregulated in the NAc following cocaine treatment, and the presence of Kal7 is necessary for the normal proliferation of dendritic spines following cocaine use. Mice that constitutively lack Kal7 [Kalirin-7 knockout mice (Kal7KO)] demonstrate increased locomotor sensitization to cocaine and a decreased place preference for cocaine. Here, using an intravenous cocaine self-administration paradigm, Kal7KO mice exhibit increased administration of cocaine at lower doses as compared with wild-type (Wt) mice. Analyses of mRNA transcript levels from the NAc of mice that self-administered saline or cocaine reveal that larger splice variants of the Kalrn gene are increased by cocaine more dramatically in Kal7KO mice than in Wt mice. Additionally, transcripts encoding the NR2B subunit of the NMDA receptor increased in Wt mice that self-administered cocaine but were unchanged in similarly experienced Kal7KO mice. These findings suggest that Kal7 participates in the reinforcing effects of cocaine, and that Kal7 and cocaine interact to alter the expression of genes related to critical glutamatergic signaling pathways in the NAc. PMID:23894151

  18. Antenatal retinoic acid administration increases trophoblastic retinol-binding protein dependent retinol transport in the nitrofen model of congenital diaphragmatic hernia.

    PubMed

    Kutasy, Balazs; Friedmacher, Florian; Pes, Lara; Coyle, David; Doi, Takashi; Paradisi, Francesca; Puri, Prem

    2016-04-01

    Low pulmonary retinol levels and disrupted retinoid signaling pathway (RSP) have been implicated in the pathogenesis of congenital diaphragmatic hernia (CDH) and associated pulmonary hypoplasia (PH). It has been demonstrated that nitrofen disturbs the main retinol-binding protein (RBP)-dependent trophoblastic retinol transport. Several studies have demonstrated that prenatal treatment with retinoic acid (RA) can reverse PH in the nitrofen-induced CDH model. We hypothesized that maternal administration of RA can increase trophoblastic RBP-dependent retinol transport in a nitrofen model of CDH. Pregnant rats were treated with nitrofen or vehicle on gestational day 9 (D9) and sacrificed on D21. RA was given i.p. on D18, D19, and D20. Retinol and RA levels were measured using high-performance liquid chromatography. Immunohistochemistry was performed to evaluate trophoblastic expression of RBP. Expression levels of the primary RSP genes were determined using quantitative real-time PCR and immunohistochemistry. Markedly increased trophoblastic RBP immunoreactivity was observed in CDH+RA compared to CDH. Significantly increased serum and pulmonary retinol and RA levels were detected in CDH+RA compared to CDH. Pulmonary expression of RSP genes and proteins were increased in CDH+RA compared to CDH. Increased trophoblastic RBP expression and retinol transport after antenatal administration of RA suggest that retinol-triggered RSP activation may attenuate CDH-associated PH by elevating serum and pulmonary retinol levels.

  19. Administrative trends in U.S. dental schools.

    PubMed

    Fu, Martin M; Rodriguez, Angel; Chen, Rebecca Y; Fu, Earl; Liao, Shu-Yi; Karimbux, Nadeem Y

    2014-11-01

    The aims of this study were to analyze the administrative trends in U.S. dental schools at the beginning and end of a thirteen-year period and to identify the predictive factors for those changes. Administrative trends were measured by the difference in the number of major administrative positions for 1997 and 2010 reported in American Dental Education Association (ADEA) and American Dental Association (ADA) publications. Secondary measures (program length, student enrollment, and tuition) were also gathered. The mean numbers of administrative positions per school significantly increased over the study period, while the mean number of clinical science departments per school significantly decreased. The change in the number of directors was positively correlated with the change in student enrollment, but inversely correlated with the change in number of vice/associate/assistant deans. The change in the number of clinical science departments was positively correlated with changes in student enrollment and out-of-state tuition, but inversely correlated with the change in in-state tuition. The number of all departments per U.S. dental school significantly decreased in this period. The schools that had consolidation of clinical science departments were less likely to have increases in student enrollment and out-of-state tuition, but more likely to have increases in in-state tuition.

  20. Mineral water administration may increase kidney elimination of urea, creatinine and folic acid in a concentration-dependent fashion.

    PubMed

    Calomino, Francesco; Di Paolo, Nicola; Nicolai, Giulia; Miglio, Antonio

    2010-05-01

    In a previous experimental study we showed that the administration of a large water load in a short time increases the urinary flow and the transport capacity in the excretory tract of the rabbit ureter. In human subjects drinking a water load of 25 ml/kg(BW) in 30 minutes, diuresis, creatinine and urea clearance increase more than in those drinking the same load in 24 hours. The aim of the present study was to investigate possible correlations between percent reduction and baseline values of serum urea, creatinine, folic acid, and magnesium in humans. 20 volunteers were divided in two groups. Subjects in group 1 received a water load of 25 ml/kg(BW) in 24 hours followed by the same load in 30 minutes. Subjects in group 2 received the same water load but in inverse order. Before and after each water administration, the following variables were measured and compared: diuresis, serum urea, creatinine, folic acid and magnesium concentration, and urea and creatinine clearance. Serum urea and folic acid concentration decreased up to 40% after administration of the water load in 24 hours. Serum creatinine concentration decreased up to 20% after administration of the water load in 30 minutes. The concentration drop of these metabolites increased with increasing baseline metabolite concentrations.

  1. Chronic administration of branched-chain amino acids impairs spatial memory and increases brain-derived neurotrophic factor in a rat model.

    PubMed

    Scaini, Giselli; Comim, Clarissa M; Oliveira, Giovanna M T; Pasquali, Matheus A B; Quevedo, João; Gelain, Daniel P; Moreira, José Cláudio F; Schuck, Patrícia F; Ferreira, Gustavo C; Bogo, Maurício R; Streck, Emilio L

    2013-09-01

    Maple syrup urine disease (MSUD) is a neurometabolic disorder that leads to the accumulation of branched-chain amino acids (BCAAs) and their α-keto branched-chain by-products. Because the neurotoxic mechanisms of MSUD are poorly understood, this study aimed to evaluate the effects of chronic administration of a BCAA pool (leucine, isoleucine and valine). This study examined the effects of BCAA administration on spatial memory and the levels of brain-derived neurotrophic factor (BNDF). We examined both pro-BDNF and bdnf mRNA expression levels after administration of BCAAs. Furthermore, this study examined whether antioxidant treatment prevented the alterations induced by BCAA administration. Our results demonstrated an increase in BDNF in the hippocampus and cerebral cortex, accompanied by memory impairment in spatial memory tasks. Additionally, chronic administration of BCAAs did not induce a detectable change in pro-BDNF levels. Treatment with N-acetylcysteine and deferoxamine prevented both the memory deficit and the increase in the BDNF levels induced by BCAA administration. In conclusion, these results suggest that when the brain is chronically exposed to high concentrations of BCAA (at millimolar concentrations) an increase in BDNF levels occurs. This increase in BDNF may be related to the impairment of spatial memory. In addition, we demonstrated that antioxidant treatment prevented the negative consequences related to BCAA administration, suggesting that oxidative stress might be involved in the pathophysiological mechanism(s) underlying the brain damage observed in MSUD.

  2. Climate impacts of oil extraction increase significantly with oilfield age

    NASA Astrophysics Data System (ADS)

    Masnadi, Mohammad S.; Brandt, Adam R.

    2017-08-01

    Record-breaking temperatures have induced governments to implement targets for reducing future greenhouse gas (GHG) emissions. Use of oil products contributes ~35% of global GHG emissions, and the oil industry itself consumes 3-4% of global primary energy. Because oil resources are becoming increasingly heterogeneous, requiring different extraction and processing methods, GHG studies should evaluate oil sources using detailed project-specific data. Unfortunately, prior oil-sector GHG analysis has largely neglected the fact that the energy intensity of producing oil can change significantly over the life of a particular oil project. Here we use decades-long time-series data from twenty-five globally significant oil fields (>1 billion barrels ultimate recovery) to model GHG emissions from oil production as a function of time. We find that volumetric oil production declines with depletion, but this depletion is accompanied by significant growth--in some cases over tenfold--in per-MJ GHG emissions. Depletion requires increased energy expenditures in drilling, oil recovery, and oil processing. Using probabilistic simulation, we derive a relationship for estimating GHG increases over time, showing an expected doubling in average emissions over 25 years. These trends have implications for long-term emissions and climate modelling, as well as for climate policy.

  3. Oral Adenosine-5'-triphosphate (ATP) Administration Increases Postexercise ATP Levels, Muscle Excitability, and Athletic Performance Following a Repeated Sprint Bout.

    PubMed

    Purpura, Martin; Rathmacher, John A; Sharp, Matthew H; Lowery, Ryan P; Shields, Kevin A; Partl, Jeremy M; Wilson, Jacob M; Jäger, Ralf

    2017-01-01

    Oral adenosine-5'-triphosphate (ATP) administration has failed to increase plasma ATP levels; however, chronic supplementation with ATP has shown to increase power, strength, lean body mass, and blood flow in trained athletes. The purpose of this study was to investigate the effects of ATP supplementation on postexercise ATP levels and on muscle activation and excitability and power following a repeated sprint bout. In a double-blind, placebo-controlled, randomized design, 42 healthy male individuals were given either 400 mg of ATP as disodium salt or placebo for 2 weeks prior to an exercise bout. During the exercise bout, muscle activation and excitability (ME, ratio of power output to muscle activation) and Wingate test peak power were measured during all sprints. ATP and metabolites were measured at baseline, after supplementation, and immediately following exercise. Oral ATP supplementation prevented a drop in ATP, adenosine-5'-diphosphate (ADP), and adenosine-5'-monophosphate (AMP) levels postexercise (p < 0.05). No group by time interaction was observed for muscle activation. Following the supplementation period, muscle excitability significantly decreased in later bouts 8, 9, and 10 in the placebo group (-30.5, -28.3, and -27.9%, respectively; p < 0.02), whereas ATP supplementation prevented the decline in later bouts. ATP significantly increased Wingate peak power in later bouts compared to baseline (bout 8: +18.3%, bout 10: +16.3%). Oral ATP administration prevents exercise-induced declines in ATP and its metabolite and enhances peak power and muscular excitability, which may be beneficial for sports requiring repeated high-intensity sprinting bouts.

  4. Subcutaneous Administration of Tramadol after Elective Surgery Is as Effective as Intravenous Administration in Relieving Acute Pain and Inflammation in Dogs

    PubMed Central

    Buhari, Salisu; Hashim, Kalthum; Yong Meng, Goh; Mustapha, Noordin Mohamed; Gan, Siew Hua

    2012-01-01

    Subcutaneous (SC) administration of tramadol was compared with intravenous (IV) administration to evaluate analgesia following canine ovariohysterectomy (OHE). Healthy female dogs (n = 12) between 1 and 3 years of age (1.95 ± 0.65 years), weighing between 10.5 and 17.1 kg (13.12 ± 1.95 kg), were used. Pain was assessed at baseline before surgery and then hourly for 8 hr after surgery. Tramadol was administered both SC and IV at a dose of 3 mg/kg and provided significant postoperative analgesia, as indicated by analgesiometry, β-endorphin levels, and interleukin 6 (IL-6) levels. The respiratory rates and rectal temperatures remained normal and were not significantly different between or within the groups. A significant increase in heart rate was observed at 4 hr for dogs in both groups relative to the baseline, but there was no significant difference in heart rates between the groups at any time point. A significant decrease in mechanical pain threshold was observed within each group after surgery, but both groups responded similarly, suggesting that SC administration of tramadol is as effective as IV administration. Increased serum levels of both IL-6 and β-endorphin 3 hr postoperatively further indicate that both routes of administration achieve similar pain control. Thus, the relative analgesic efficacy of SC tramadol is comparable to that of IV administration and can be used to achieve similar effects for postsurgical pain management in dogs undergoing OHE. PMID:22778699

  5. Oral administration of antimicrobials increase antimicrobial resistance in E. coli from chicken--a systematic review.

    PubMed

    Simoneit, C; Burow, E; Tenhagen, B-A; Käsbohrer, A

    2015-01-01

    Antimicrobials play an important role in animal and human health care. It was the aim of this systematic review to assess the effects of oral administration of antimicrobials on the development of antimicrobial resistance (AMR) in Escherichia coli (E. coli) from chickens. Moreover, the effects of the administration of more than one antimicrobial and of different dosages were studied. Literature was searched in November 2012 from the electronic databases ISI Web of Science, PubMed, Scopus and a national literature database (DIMDI) as well as the database ProQuest LLC. The search was updated in March 2014. Original studies describing a treatment (A) and a control group of either non-treatment (C) or initial value (0) and determining AMR in E. coli at different sample points (SP) were included. The literature search resulted in 35 full text articles on the topic, seven (20%) of which contained sufficient information on the administered antimicrobial and the impact of treatment on AMR. Most papers described the use of more than one antimicrobial, several dosages, controls (non-treatment or pre-treatment) and measured AMR at different SPs leading to a total of 227 SPs on the impact of the use of antimicrobials on AMR in chickens. 74% of the SPs (168/227) described a higher AMR-rate in E. coli from treated animals than from controls. After the administration of a single antimicrobial, AMR increased at 72% of the SPs. Administration of more than one antimicrobial increased AMR at 82% of the SPs. Higher dosages were associated with similar or higher AMR rates. The limited number of studies for each antimicrobial agent and the high variability in the resistance effect call for more well designed studies on the impact of oral administration on AMR development and spread. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. Prenatal administration of retinoic acid increases the trophoblastic insulin-like growth factor 2 protein expression in the nitrofen model of congenital diaphragmatic hernia.

    PubMed

    Kutasy, Balazs; Friedmacher, Florian; Duess, Johannes W; Puri, Prem

    2014-02-01

    The high mortality rate in congenital diaphragmatic hernia (CDH) is attributed to pulmonary hypoplasia (PH). Insulin-like growth factor 2 (IGF2) is an important regulator of fetal growth. The highest levels of IGF2 expression are found in the placenta, which are negatively regulated by decidual retinoid acid receptor alpha (RARα). It has been demonstrated that prenatal administration of retinoic acid (RA) suppresses decidual RARα expression. Previous studies have further shown that prenatal administration of RA can reverse PH in nitrofen-induced CDH model. In IGF2 knockout animals, low levels of IGF2 are associated with decreased placental growth and PH. We therefore hypothesized that nitrofen decreases trophoblastic IGF2 expression and prenatal administration of RA increases it through decidual RARα in the nitrofen-induced CDH model. Pregnant rats were exposed to either olive oil or nitrofen on day 9 of gestation (D9). RA was given intraperitoneally on D18, D19 and D20. Fetuses were harvested on D21 and divided into three groups: control, CDH and nitrofen+RA. Immunohistochemistry was performed to evaluate decidual RARα and trophoblastic IGF2 expression. Protein levels of IGF2 in serum, intra-amniotic fluid and left lungs were measured by enzyme-linked immunosorbent assay. Significant growth retardation of placenta and left lungs was observed in the CDH group compared to control and nitrofen+RA group. Markedly increased decidual RARα and decreased IGF2 immunoreactivity were found in the CDH group compared to control and nitrofen+RA group. Significantly decreased IGF2 protein levels were detected in serum, intra-amniotic fluid and left lungs in the CDH group compared to control and nitrofen+RA group. Our findings suggest that nitrofen may disturb trophoblastic IGF2 expression through decidual RARα resulting in retarded placental growth and PH in the nitrofen-induced CDH. Prenatal administration of RA may promote lung and placental growth by increasing

  7. Perinatal phencyclidine administration decreases the density of cortical interneurons and increases the expression of neuregulin-1.

    PubMed

    Radonjić, Nevena V; Jakovcevski, Igor; Bumbaširević, Vladimir; Petronijević, Nataša D

    2013-06-01

    Perinatal phencyclidine (PCP) administration in rat blocks the N-methyl D-aspartate receptor (NMDAR) and causes symptoms reminiscent of schizophrenia in human. A growing body of evidence suggests that alterations in γ-aminobutyric acid (GABA) interneuron neurotransmission may be associated with schizophrenia. Neuregulin-1 (NRG-1) is a trophic factor important for neurodevelopment, synaptic plasticity, and wiring of GABA circuits. The aim of this study was to determine the long-term effects of perinatal PCP administration on the projection and local circuit neurons and NRG-1 expression in the cortex and hippocampus. Rats were treated on postnatal day 2 (P2), P6, P9, and P12 with either PCP (10 mg/kg) or saline. Morphological studies and determination of NRG-1 expression were performed at P70. We demonstrate reduced densities of principal neurons in the CA3 and dentate gyrus (DG) subregions of the hippocampus and a reduction of major interneuronal populations in all cortical and hippocampal regions studied in PCP-treated rats compared with controls. For the first time, we show the reduced density of reelin- and somatostatin-positive cells in the cortex and hippocampus of animals perinatally treated with PCP. Furthermore, an increase in the numbers of perisomatic inhibitory terminals around the principal cells was observed in the motor cortex and DG. We also show that perinatal PCP administration leads to an increased NRG-1 expression in the cortex and hippocampus. Taken together, our findings demonstrate that perinatal PCP administration increases NRG-1 expression and reduces the number of projecting and local circuit neurons, revealing complex consequences of NMDAR blockade.

  8. Significance of Fractionated Administration of Thalidomide Combined With γ-Ray Irradiation in Terms of Local Tumor Response and Lung Metastasis

    PubMed Central

    Masunaga, Shin-ichiro; Sanada, Yu; Moriwaki, Takahiro; Tano, Keizo; Sakurai, Yoshinori; Tanaka, Hiroki; Suzuki, Minoru; Kondo, Natsuko; Narabayashi, Masaru; Watanabe, Tsubasa; Nakagawa, Yosuke; Maruhashi, Akira; Ono, Koji

    2014-01-01

    Background The aim of this study was to evaluate the significance of fractionated administration of thalidomide combined with γ-ray irradiation in terms of local tumor response and lung metastatic potential, referring to the response of intratumor quiescent (Q) cells. Methods B16-BL6 melanoma tumor-bearing C57BL/6 mice were continuously given 5-bromo-2’-deoxyuridine (BrdU) to label all proliferating (P) cells. The tumor-bearing mice then received γ-ray irradiation after thalidomide treatment through a single or two consecutive daily intraperitoneal administrations up to a total dose of 400 mg/kg in combination with an acute hypoxia-releasing agent (nicotinamide) or mild temperature hyperthermia (MTH). Immediately after the irradiation, cells from some tumors were isolated and incubated with a cytokinesis blocker. The responses of the Q and total (= P + Q) cell populations were assessed based on the frequency of micronuclei using immunofluorescence staining for BrdU. In other tumor-bearing mice, 17 days after irradiation, macroscopic lung metastases were enumerated. Results Thalidomide raised the sensitivity of the total cell population more remarkably than Q cells in both single and daily administrations. Daily administration of thalidomide elevated the sensitivity of both the total and Q cell populations, but especially the total cell population, compared with single administration. Daily administration, especially combined with MTH, decreased the number of lung metastases. Conclusion Daily fractionated administration of thalidomide in combination with γ-ray irradiation was thought to be more promising than single administration because of its potential to enhance local tumor response and repress lung metastatic potential. PMID:29147396

  9. Educational Administration and the Social, Policy, and Administrative Sciences.

    ERIC Educational Resources Information Center

    Kirkpatrick, Samuel A.

    1983-01-01

    The politics of education has been ignored in educational administration programs; it has been not enough taught in American programs for educational administrators and not enough emphasized in discussions of administrative roles. Administration increasingly includes political as well as rational decisions. Thus, administrators need a unified…

  10. Hemodynamic effects of sodium bicarbonate administration.

    PubMed

    Katheria, A C; Brown, M K; Hassan, K; Poeltler, D M; Patel, D A; Brown, V K; Sauberan, J B

    2017-05-01

    To describe the hemodynamic changes that occur with sodium bicarbonate (NaHCO 3 ) administration in premature neonates. This retrospective study included premature neonates 23 to 31+6 weeks of gestational age who underwent continuous cardiac and cerebral monitoring as participants in prospective trials at our institution, and who received NaHCO 3 infused over 30 min in the first 24 h of life. Blood pressure (BP), heart rate, cardiac output (CO), SpO 2 and cerebral oximetry (StO 2 ) were captured every 2 s. A baseline was established for all continuous data and averaged over the 10 min before NaHCO 3 administration. Baseline was compared with measurements over 10 min epochs until 80 min after administration. Arterial blood gases before and within 1 h of administration were also compared. Significance was set at P<0.05. A total of 36 subjects received NaHCO 3 (1.3±0.3 mEq kg -1 ) in the first 24 h (14±8.5 h) of life. NaHCO 3 administration increased pH (7.23 vs 7.28, P<0.01) and decreased base deficit (-8.9 vs -6.8, P<0.01) and PaCO 2 (45 vs 43 mm Hg, P<0.05). There was a transient but significant (P<0.05) decrease in systemic BP coinciding with an increase in cerebral oxygenation without an increase in oxygen extraction. CO did not change. Early postnatal NaHCO 3 administration does not acutely improve CO but does cause transient fluctuations in cerebral and cardiovascular hemodynamics in extremely premature infants.

  11. Significant Impacts of Increasing Aridity on the Arid Soil Microbiome.

    PubMed

    Neilson, Julia W; Califf, Katy; Cardona, Cesar; Copeland, Audrey; van Treuren, Will; Josephson, Karen L; Knight, Rob; Gilbert, Jack A; Quade, Jay; Caporaso, J Gregory; Maier, Raina M

    2017-01-01

    Global deserts occupy one-third of the Earth's surface and contribute significantly to organic carbon storage, a process at risk in dryland ecosystems that are highly vulnerable to climate-driven ecosystem degradation. The forces controlling desert ecosystem degradation rates are poorly understood, particularly with respect to the relevance of the arid-soil microbiome. Here we document correlations between increasing aridity and soil bacterial and archaeal microbiome composition along arid to hyperarid transects traversing the Atacama Desert, Chile. A meta-analysis reveals that Atacama soil microbiomes exhibit a gradient in composition, are distinct from a broad cross-section of nondesert soils, and yet are similar to three deserts from different continents. Community richness and diversity were significantly positively correlated with soil relative humidity (SoilRH). Phylogenetic composition was strongly correlated with SoilRH, temperature, and electrical conductivity. The strongest and most significant correlations between SoilRH and phylum relative abundance were observed for Acidobacteria , Proteobacteria , Planctomycetes , Verrucomicrobia , and Euryarchaeota (Spearman's rank correlation [ r s ] = >0.81; false-discovery rate [ q ] = ≤0.005), characterized by 10- to 300-fold decreases in the relative abundance of each taxon. In addition, network analysis revealed a deterioration in the density of significant associations between taxa along the arid to hyperarid gradient, a pattern that may compromise the resilience of hyperarid communities because they lack properties associated with communities that are more integrated. In summary, results suggest that arid-soil microbiome stability is sensitive to aridity as demonstrated by decreased community connectivity associated with the transition from the arid class to the hyperarid class and the significant correlations observed between soilRH and both diversity and the relative abundances of key microbial phyla

  12. Increased Serum and Urinary Oxytocin Concentrations after Nasal Administration in Beagle Dogs

    PubMed Central

    Temesi, Andrea; Thuróczy, Julianna; Balogh, Lajos; Miklósi, Ádám

    2017-01-01

    In recent years more and more studies have revealed the effect of extraneous oxytocin on the social behavior of dogs. The distribution of administered oxytocin in different physiologically relevant compartments is important because this knowledge forms the basis for the timing of behavior tests after the administration. Most behavioral studies rely on the non-invasive intranasal application of oxytocin. The aim of this study was to determine the time course of intranasal administered oxytocin secretion into blood and urine and also establish a connection between intranasal received oxytocin and urinary cortisol in dogs. In our experiment, four dogs received three puffs, 12 IU intranasal oxytocin treatment, two dogs received three puffs intranasal placebo treatment. Blood and urine samples were collected immediately prior to the administration then regularly during 4 h. After nasal oxytocin application, the serum oxytocin concentration increased, reached a maximum 15 min after the treatment and then rapidly returned to baseline levels 45 min later. The peak urinary oxytocin concentration occurred between 45 and 60 min after administration and returned to baseline levels slowly. We found considerable differences among individuals in the secretion of oxytocin in both the serum and the urinary oxytocin concentration measurements. Our results confirm that intranasally administered oxytocin passes into the blood stream. The time course of intranasally administered oxytocin secretion is similar to the time course of intravenously administered oxytocin secretion, and the peak values are also similar in both the serum and the urinary oxytocin concentration measurements, although there are large individual differences. PMID:28929104

  13. Extending the Administration Time of the Letter Fluency Test Increases Sensitivity to Cognitive Status in Aging

    PubMed Central

    Holtzer, R.; Goldin, Y.; Donovick, P.J.

    2010-01-01

    We examined whether extending the administration time of letter fluency from one minute per letter trial (standard administration) to two minutes increased the sensitivity of this test to cognitive status in aging. Participants (mean age = 84.6) were assigned to cognitive impairment (n=20) and control (n=40) groups. Pearson correlations and scatter plot analyses showed that associations between the Dementia Rating Scale scores and letter fluency were higher and less variable when performance on the latter was extended to two minutes. ANOVA showed that the cognitive impairment group generated fewer words in the second minute of the letter fluency task compared to the control group. Finally, discriminant function analyses revealed that extending the letter fluency trials to two minutes increased discrimination between the control and cognitive impairment groups. PMID:19449244

  14. Increased seizure latency and decreased severity of pentylenetetrazol-induced seizures in mice after essential oil administration.

    PubMed

    Koutroumanidou, Eleni; Kimbaris, Athanasios; Kortsaris, Alexandros; Bezirtzoglou, Eugenia; Polissiou, Moschos; Charalabopoulos, Konstantinos; Pagonopoulou, Olga

    2013-01-01

    The effect of pretreatment with essential oils (EOs) from eight aromatic plants on the seizure latency and severity of pentylenetetrazol- (PTZ-) induced seizures in mice was evaluated. Weight-dependent doses of Rosmarinus officinalis, Ocimum basilicum, Mentha spicata, Mentha pulegium, Lavandula angustifolia, Mentha piperita, Origanum dictamnus, and Origanum vulgare, isolated from the respective aromatic plants from NE Greece, were administered 60 minutes prior to intraperitoneal (i.p.) injection of a lethal dose of PTZ to eight respective groups of Balb-c mice. Control group received only one i.p. PTZ injection. Motor and behavioral activity of the animals after EOs administration, development of tonic-clonic seizures, seizure latency and severity, and percentage of survival after PTZ administration were determined for each group. All groups of mice treated with the EOs showed reduced activity and stability after the administration of the oil, except for those treated with O. vulgare (100% mortality after the administration of the oil). After PTZ administration, mice from the different groups showed increased latency and reduced severity of seizures (ranging from simple twitches to complete seizures). Mice who had received M. piperita demonstrated no seizures and 100% survival. The different drastic component and its concentration could account for the diversity of anticonvulsant effects.

  15. The effects of co-administration of butter on the absorption, metabolism and excretion of catechins in rats after oral administration of tea polyphenols.

    PubMed

    Zhang, Liang; Han, Yuhui; Xu, Liwei; Liang, Yuhong; Chen, Xin; Li, Junsong; Wan, Xiaochun

    2015-07-01

    In Southwest China, tea polyphenols are usually utilized by way of butter tea. Tea polyphenols inhibit the absorption and biosynthesis of fatty acids in vivo, but the effects of butter on the pharmacokinetics of tea polyphenols have drawn less concern. A rapid UHPLC-MS/MS method was used to quantitatively determine the catechins in the plasma, feces and bile of rats after the oral administration of tea polyphenol or its combination with butter. In comparison with the single tea polyphenol treatment, the maximum plasma concentrations (Cmax) of the free EGCG, EGC, EC, GCG, GC and ECG significantly decreased after the co-administration of butter. The mean residence times (MRT) of the free EGCG, EGC, EC, GC and ECG were also significantly prolonged. When the plasma samples were treated with β-glucuronidase and arylsulfatase, the pharmacokinetic parameters of the total catechins (free and conjugated forms) were not affected by the co-administration of butter. These results indicated that the total absorption of catechins was not affected by butter, but the metabolism of catechins had been changed. Furthermore, the fecal catechins were significantly increased by butter. The total fecal amount and excretion ratio of all catechins were increased highly. The biliary excretion of EGCG, EGC, EC, GCG and GC was significantly increased by the co-administration of butter. To sum up, the butter changed the metabolism of catechins in vivo by decreasing the plasma concentration of the free catechins but increasing the conjugated catechins.

  16. The Leadership Roles of Distance Learning Administrators (DLAs) in Increasing Educational Value and Quality Perceptions

    ERIC Educational Resources Information Center

    McFarlane, Donovan A.

    2011-01-01

    This paper examines the leadership roles of distance learning administrators (DLAs) in light of the demand and need for value and quality in educational distance learning programs and schools. The author explores the development of distance learning using available and emerging technologies in relation to increased demand for education, training,…

  17. Simian Immunodeficiency Virus Infection Increases Blood Ethanol Concentration Duration After Both Acute and Chronic Administration.

    PubMed

    Simon, Liz; Siggins, Robert; Winsauer, Peter; Brashear, Meghan; Ferguson, Tekeda; Mercante, Don; Song, Kejing; Vande Stouwe, Curtis; Nelson, Steve; Bagby, Gregory; Amedee, Angela; Molina, Patricia E

    2018-02-01

    Alcohol use disorder (AUD) is a frequent comorbidity among people living with HIV/AIDS (PLWHA). Alcohol consumption is a significant predictor of nonadherence to antiretroviral therapy (ART), as well as worsening immunological and virological indicators among PLWHA. Clinical studies indicate that higher viral loads increase sensitivity to alcohol in PLWHA. The factors that influence alcohol kinetics after HIV infection and initiation of ART are not well understood, limiting the information upon which interventions can be designed to ameliorate the impact of alcohol misuse on this vulnerable patient population. To better understand the relationship between viral load and alcohol kinetics, we measured changes in doses of intragastric ethanol administration to achieve target blood ethanol concentration (BEC) in a rhesus macaque model of chronic binge alcohol (CBA) administration and acute changes following a single acute binge dose of alcohol (ABA) pre- and post-simian immunodeficiency virus (SIV) infection, and following ART initiation. Our results from CBA (14 months)-administered SIV-infected male macaques showed that, following ART initiation, macaques required higher doses of alcohol to achieve a target peak BEC compared with non-ART-treated SIV-infected macaques. In animals given ABA, we found prolonged duration of elevated BEC and decreased elimination rate of alcohol that was not corrected following 7 weeks of ART. These findings suggest that binge drinking associated with AUD could negatively interact with HIV infection and enhance disease progression. These findings further support the need for implementation of behavioral or therapeutic interventions to decrease alcohol consumption to improve the quality of life in PLWHA.

  18. Brown adipose tissue thermogenesis does not explain the intra-administration hyperthermic sign-reversal induced by serial administrations of 60% nitrous oxide to rats.

    PubMed

    Al-Noori, Salwa; Ramsay, Douglas S; Cimpan, Andreas; Maltzer, Zoe; Zou, Jessie; Kaiyala, Karl J

    2016-08-01

    Initial administration of ≥60% nitrous oxide (N2O) to rats promotes hypothermia primarily by increasing whole-body heat loss. We hypothesized that the drug promotes heat loss via the tail and might initially inhibit thermogenesis via brown adipose tissue (BAT), major organs of thermoregulation in rodents. Following repeated administrations, N2O inhalation evokes hyperthermia underlain by increased whole-body heat production. We hypothesized that elevated BAT thermogenesis plays a role in this thermoregulatory sign reversal. Using dual probe telemetric temperature implants and infrared (IR) thermography, we assessed the effects of nine repeated 60% N2O administrations compared to control (con) administrations on core temperature, BAT temperature, lumbar back temperature and tail temperature. Telemetric core temperature, telemetric BAT temperature, and IR BAT temperature were reduced significantly during initial 60% N2O inhalation (p≤0.001 compared to con). IR thermography revealed that acute N2O administration unexpectedly reduced tail temperature (p=0.0001) and also inhibited IR lumbar temperature (p<0.0001). In the 9th session, N2O inhalation significantly increased telemetric core temperature (p=0.007) indicative of a hyperthermic sign reversal, yet compared to control administrations, telemetric BAT temperature (p=0.86), IR BAT temperature (p=0.85) and tail temperature (p=0.47) did not differ significantly. Thus, an initial administration of 60% N2O at 21°C may promote hypothermia via reduced BAT thermogenesis accompanied by tail vasoconstriction as a compensatory mechanism to limit body heat loss. Following repeated N2O administrations rats exhibit a hyperthermic core temperature but a normalized BAT temperature, suggesting induction of a hyperthermia-promoting thermogenic adaptation of unknown origin. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Intranasal administration of oxytocin increases envy and schadenfreude (gloating).

    PubMed

    Shamay-Tsoory, Simone G; Fischer, Meytal; Dvash, Jonathan; Harari, Hagai; Perach-Bloom, Nufar; Levkovitz, Yechiel

    2009-11-01

    Humans have a strong social tendency to compare themselves with others. We tend to feel envious when we receive less valuable rewards and may rejoice when our payoffs are more advantageous. Envy and schadenfreude (gloating over the other's misfortune) are social emotions widely agreed to be a symptom of the human social tendency to compare one's payoffs with those of others. Given the important social components of envy and gloating, we speculated that oxytocin may have a modulating effect on the intensity of these emotions. Fifty-six participants participated in this double-blind, placebo-controlled, within-subject study. Following the administration of oxytocin or a placebo, participants played a game of chance with another (fake) participant who either won more money (envy manipulation), lost more money (schadenfreude manipulation), or won/lost equal amounts of money. In comparison with the placebo, oxytocin increased the envy ratings during unequal monetary gain conditions involving relative loss (when the participant gained less money than another player). Oxytocin also increased the ratings of gloating during relative gain conditions (when the participant gained more money than the other player). By contrast, oxytocin had no effect on the emotional ratings following equal monetary gains nor did it affect general mood ratings. These results suggest that the oxytocinergic system is involved in modulating envy and gloating. Thus, contrary to the prevailing belief that this system is involved solely in positive prosocial behaviors, it probably plays a key role in a wider range of social emotion-related behaviors.

  20. SureClick® (Darbepoetin alfa) can improve perceived satisfaction and competence for anemia treatment and increase self-administration in non-dialyzed patients with chronic kidney disease.

    PubMed

    Bonafont, Xavier; Romero, Ramón; Martínez, Isabel; del Pino, María D; Gil, José M; Aranda, Pedro; Roca, Ramón; Claverol, Joana; Cucala, Mercedes

    2013-01-01

    SureClick® is a prefilled pen for administration of darbepoetin alfa (DA) that is ready-to-use. We explored patient satisfaction with SureClick® compared with prefilled syringes (PFS). Multicenter, prospective, 6-months, observational study in non-dialyzed patients with chronic kidney disease (CKD) treated with DA in PFS who switched to SureClick® at baseline. Main outcomes were: change in Anemia Treatment Satisfaction Questionnaire (ATSQ-S), Perceived Competence for Anemia Scale (PCAS) and self-administration rate. We enrolled 132 patients with a mean(SD) age of 71.3 (14.6) years, 57.6% women. Mean(SD) ATSQ-S scores at baseline and final records were 25.5 (7.9) and 31.6 (4.9) (on a scale from 0 to 36 maximum satisfaction-, mean change: 6.2, 95%CI: 4.6-7.8, p<0.0001). The PCAS also increased significantly (4.3 (2.0) vs 5.6 (1.6), on a scale from 1 to 7 maximum competence, p<0.0001). At baseline 47.7% of patients self-administered DA with PFS, vs 74.2% with SureClick® (p<0.001). No significant changes in hemoglobin were observed (11.4 (0.5) vs 11.6 (1.3) g/dl, p=0.193). Two patients (1.5%) had adverse reactions to SureClick® (pain on application). Our results suggest that the change from PFS to SureClick® could increase patient satisfaction and perceived competence in anemia management in non-dialyzed CKD patients, and could increase the self-administration rate, thereby reducing use of health resources.

  1. Gabapentin potentiates sensitivity to the interoceptive effects of alcohol and increases alcohol self-administration in rats

    PubMed Central

    Besheer, Joyce; Frisbee, Suzanne; Randall, Patrick A.; Jaramillo, Anel A.; Masciello, Maria

    2016-01-01

    Gabapentin, a drug used in the treatment of epileptic seizures and neuropathic pain, has shown efficacy in the treatment of alcohol dependence. Moreover, given that gabapentin is used in the general population (e.g., non-dependent individuals, social drinkers), we sought to utilize preclinical assessments to examine the effects of gabapentin on sensitivity to moderate alcohol doses and alcohol self-administration in rats with a history of moderate drinking. To this end, we assessed whether gabapentin (0, 10, 30, 120 mg/kg, IG) pretreatment alters sensitivity to experimenter- and self-administered alcohol, and whether gabapentin alone has alcohol-like discriminative stimulus effects in rats trained to discriminate a moderate alcohol dose (1 g/kg, IG) vs. water. Second, we assessed whether gabapentin (0, 10, 30, 60 mg/kg, IG) would alter alcohol self-administration in rats with a history of moderate alcohol consumption. Gabapentin pretreatment potentiated the interoceptive effects of both experimenter-administered and self-administered alcohol in discrimination-trained rats. Additionally, the highest gabapentin doses tested (30 and 120 mg/kg) were found to have partial alcohol-like discriminative stimulus effects when administered alone (e.g., without alcohol). In the self-administration trained rats, gabapentin pretreatment (60 mg/kg) resulted in an escalation in alcohol self-administration. Given the importance of interoceptive drug cues in priming and maintaining self-administration, these data define a specific behavioral mechanism (i.e., potentiation of alcohol effects) by which gabapentin may increase alcohol self-administration in non-dependent populations. PMID:26415538

  2. Increased serum bile acid concentration following low-dose chronic administration of thioacetamide in rats, as evidenced by metabolomic analysis

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Jeong, Eun Sook; Kim, Gabin; Shin, Ho Jung

    A liquid chromatography/time-of-flight mass spectrometry (LC/TOF-MS)-based metabolomics approach was employed to identify endogenous metabolites as potential biomarkers for thioacetamide (TAA)-induced liver injury. TAA (10 and 30 mg/kg), a well-known hepatotoxic agent, was administered daily to male Sprague–Dawley (SD) rats for 28 days. We then conducted untargeted analyses of endogenous serum and liver metabolites. Partial least squares discriminant analysis (PLS-DA) was performed on serum and liver samples to evaluate metabolites associated with TAA-induced perturbation. TAA administration resulted in altered levels of bile acids, acyl carnitines, and phospholipids in serum and in the liver. We subsequently demonstrated and confirmed the occurrence ofmore » compromised bile acid homeostasis. TAA treatment significantly increased serum levels of conjugated bile acids in a dose-dependent manner, which correlated well with toxicity. However, hepatic levels of these metabolites were not substantially changed. Gene expression profiling showed that the hepatic mRNA levels of Ntcp, Bsep, and Oatp1b2 were significantly suppressed, whereas those of basolateral Mrp3 and Mrp4 were increased. Decreased levels of Ntcp, Oatp1b2, and Ostα proteins in the liver were confirmed by western blot analysis. These results suggest that serum bile acids might be increased due to the inhibition of bile acid enterohepatic circulation rather than increased endogenous bile acid synthesis. Moreover, serum bile acids are a good indicator of TAA-induced hepatotoxicity. - Highlights: • Endogenous metabolic profiles were assessed in rat after treatment of thioacetamide. • It significantly increased the levels of bile acids in serum but not in the liver. • Expression of the genes related to bile acid secretion and reuptake was decreased. • Increased serum bile acids result from block of enterohepatic circulation of bile acids.« less

  3. Increased Late Sodium Current Contributes to the Electrophysiological Effects of Chronic, but Not Acute, Dofetilide Administration.

    PubMed

    Qiu, Xiaoliang S; Chauveau, Samuel; Anyukhovsky, Evgeny P; Rahim, Tania; Jiang, Ya-Ping; Harleton, Erin; Feinmark, Steven J; Lin, Richard Z; Coronel, Ruben; Janse, Michiel J; Opthof, Tobias; Rosen, Tove S; Cohen, Ira S; Rosen, Michael R

    2016-04-01

    Drugs are screened for delayed rectifier potassium current (IKr) blockade to predict long QT syndrome prolongation and arrhythmogenesis. However, single-cell studies have shown that chronic (hours) exposure to some IKr blockers (eg, dofetilide) prolongs repolarization additionally by increasing late sodium current (INa-L) via inhibition of phosphoinositide 3-kinase. We hypothesized that chronic dofetilide administration to intact dogs prolongs repolarization by blocking IKr and increasing INa-L. We continuously infused dofetilide (6-9 μg/kg bolus+6-9 μg/kg per hour IV infusion) into anesthetized dogs for 7 hours, maintaining plasma levels within the therapeutic range. In separate experiments, myocardial biopsies were taken before and during 6-hour intravenous dofetide infusion, and the level of phospho-Akt was determined. Acute and chronic dofetilide effects on action potential duration (APD) were studied in canine left ventricular subendocardial slabs using microelectrode techniques. Dofetilide monotonically increased QTc and APD throughout 6.5-hour exposure. Dofetilide infusion during ≥210 minutes inhibited Akt phosphorylation. INa-L block with lidocaine shortened QTc and APD more at 6.5 hours than at 50 minutes (QTc) or 30 minutes (APD) dofetilide administration. In comparison, moxifloxacin, an IKr blocker with no effects on phosphoinositide 3-kinase and INa-L prolonged APD acutely but no additional prolongation occurred on chronic superfusion. Lidocaine shortened APD equally during acute and chronic moxifloxacin superfusion. Increased INa-L contributes to chronic dofetilide effects in vivo. These data emphasize the need to include time and INa-L in evaluating the phosphoinositide 3-kinase inhibition-derived proarrhythmic potential of drugs and provide a mechanism for benefit from lidocaine administration in clinical acquired long QT syndrome. © 2016 American Heart Association, Inc.

  4. Hydralazine administration activates sympathetic preganglionic neurons whose activity mobilizes glucose and increases cardiovascular function.

    PubMed

    Parker, Lindsay M; Damanhuri, Hanafi A; Fletcher, Sophie P S; Goodchild, Ann K

    2015-04-16

    Hypotensive drugs have been used to identify central neurons that mediate compensatory baroreceptor reflex responses. Such drugs also increase blood glucose. Our aim was to identify the neurochemical phenotypes of sympathetic preganglionic neurons (SPN) and adrenal chromaffin cells activated following hydralazine (HDZ; 10mg/kg) administration in rats, and utilize this and SPN target organ destination to ascribe their function as cardiovascular or glucose regulating. Blood glucose was measured and adrenal chromaffin cell activation was assessed using c-Fos immunoreactivity (-ir) and phosphorylation of tyrosine hydroxylase, respectively. The activation and neurochemical phenotype of SPN innervating the adrenal glands and celiac ganglia were determined using the retrograde tracer cholera toxin B subunit, in combination with in situ hybridization and immunohistochemistry. Blood glucose was elevated at multiple time points following HDZ administration but little evidence of chromaffin cell activation was seen suggesting non-adrenal mechanisms contribute to the sustained hyperglycemia. 16±0.1% of T4-T11 SPN contained c-Fos and of these: 24.3±1.4% projected to adrenal glands and 29±5.5% projected to celiac ganglia with the rest innervating other targets. 62.8±1.4% of SPN innervating adrenal glands were activated and 29.9±3.3% expressed PPE mRNA whereas 53.2±8.6% of SPN innervating celiac ganglia were activated and 31.2±8.8% expressed PPE mRNA. CART-ir SPN innervating each target were also activated and did not co-express PPE mRNA. Neurochemical coding reveals that HDZ administration activates both PPE+SPN, whose activity increase glucose mobilization causing hyperglycemia, as well as CART+SPN whose activity drive vasomotor responses mediated by baroreceptor unloading to raise vascular tone and heart rate. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Post Chlorine gas exposure administration of nitrite prevents lung injury: effect of administration modality

    PubMed Central

    Samal, Andrey A.; Honavar, Jaideep; Brandon, Angela; Bradley, Kelley M.; Doran, Stephen; Liu, Yanping; Dunaway, Chad; Steele, Chad; Postlethwait, Edward M.; Squadrito, Giuseppe L.; Fanucchi, Michelle V.; Matalon, Sadis; Patel, Rakesh P.

    2012-01-01

    Cl2 gas toxicity is complex and occurs during, and post exposure leading to acute lung injury (ALI) and reactive airway syndrome (RAS). Moreover, Cl2 exposure can occur in diverse situations encompassing mass casualty scenarios underscoring the need for post-exposure therapies that are efficacious and amenable to rapid and easy administration. In this study, we compared the efficacy of a single dose, post (30min) Cl2 exposure administration of nitrite (1mg/kg) via intraperitoneal (IP) or intramuscular (IM) injection in rats, to decrease ALI. Exposure of rats to Cl2 gas (400ppm, 30min) significantly increased ALI and caused RAS 6–24h post exposure as indexed by BAL sampling of lung surface protein, PMN and increased airway resistance and elastance prior to and post methacholine challenge. IP nitrite decreased Cl2 - dependent increases in BAL protein but not PMN. In contrast IM nitrite decreased BAL PMN levels without decreasing BAL protein in a xanthine oxidoreductase independent manner. Histological evaluation of airways 6h post exposure showed significant bronchial epithelium exfoliation and inflammatory injury in Cl2 exposed rats. Both IP and IM nitrite improved airway histology compared to Cl2 gas alone, but more coverage of the airway by cuboidal or columnar epithelium was observed with IM compared to IP nitrite. Airways were rendered more sensitive to methacholine induced resistance and elastance after Cl2 gas exposure. Interestingly, IM nitrite, but not IP nitrite, significantly decreased airway sensitivity to methacholine challenge. Further evaluation and comparison of IM and IP therapy showed a two-fold increase in circulating nitrite levels with the former, which was associated with reversal of post-Cl2 exposure dependent increases in circulating leukocytes. Halving the IM nitrite dose resulted in no effect in PMN accumulation but significant reduction of of BAL protein levels indicating distinct nitrite dose dependence for inhibition of Cl2 dependent

  6. Sixteen-Day Bedrest Significantly Increases Plasma Colloid Osmotic Pressure

    NASA Technical Reports Server (NTRS)

    Hargens, Alan R.; Hsieh, S. T.; Murthy, G.; Ballard, R. E.; Convertino, V. A.; Wade, Charles E. (Technical Monitor)

    1994-01-01

    Upon exposure to microgravity, astronauts lose up to 10% of their total plasma volume, which may contribute to orthostatic intolerance after space flight. Because plasma colloid osmotic pressure (COP) is a primary factor maintaining plasma volume, our objective was to measure time course changes in COP during microgravity simulated by 6 deg. head-down tilt (HDT). Seven healthy male subjects (30-55 years of age) were placed in HDT for 16 days. For the purpose of another study, three of the seven subjects were chosen to exercise on a cycle ergometer on day 16. Blood samples were drawn immediately before bedrest on day 14 of bedrest, 18-24 hours following exercise while all subjects were still in HDT and 1 hour following bedrest termination. Plasma COP was measured in all 20 microliter EDTA-treated samples using an osmometer fitted with a PM 30 membrane. Data were analyzed with paired and unpaired t-tests. Plasma COP on day 14 of bedrest (29.9 +/- 0.69 mmHg) was significantly higher (p less than 0.005) than the control, pre-bedrest value (23.1 +/- 0.76 mmHg). At one hour of upright recovery after HDT, plasma COP remained significantly elevated (exercise: 26.9 +/- 0.87 mmHg; no exercise: 26.3 +/- 0.85 mmHg). Additionally, exercise had no significant effect on plasma COP 18-24 hours following exercise (exercise: 27.8 +/- 1.09 mmHg; no exercise: 27.1 +/- 0.78 mmHg). Our results demonstrate that plasma COP increases significantly with microgravity simulated by HDT. However, preliminary results indicate exercise during HDT does not significantly affect plasma COP.

  7. Increased androgen response to follicle-stimulating hormone administration in women with polycystic ovary syndrome.

    PubMed

    Wachs, Deborah S; Coffler, Mickey S; Malcom, Pamela J; Shimasaki, Shunichi; Chang, R Jeffrey

    2008-05-01

    In women with polycystic ovary syndrome (PCOS), excess ovarian androgen production is driven by increased LH secretion. Studies conducted in animals suggest that the granulosa cell may influence LH-stimulated theca cell androgen production. The objective of this study was to determine whether FSH enhances androgen production in women with PCOS compared with that of normal women. A prospective study was conducted to compare androgen production in response to FSH in two groups of women. The study was conducted in a General Clinical Research Center in a tertiary academic medical center. Women with PCOS, 18-35 yr (n = 20), and normal ovulatory controls, 18-35 yr (n = 10), were recruited for study. Serial blood samples were obtained over a 24-h period after an iv injection of recombinant human FSH (150 IU). The main outcome measures were serum 17-hydroxyprogesterone (17-OHP), androstenedione (A), dehydroepiandrosterone (DHEA), testosterone (T), and inhibin B (Inh B) responses after FSH administration. Basal serum 17-OHP, A, and T levels were markedly increased in women with PCOS compared with that observed in normal women. Basal DHEA and Inh B levels were similar to those of normal controls. After FSH injection, PCOS women demonstrated enhanced production of 17-OHP, A, DHEA, and Inh B, whereas in normal women no increases were observed. T levels declined slightly in both groups. These findings provide evidence that, in PCOS women, theca cell androgen production is enhanced by FSH administration and suggest a granulosa-theca cell paracrine mechanism.

  8. Rheumatoid arthritis significantly increased recurrence risk after ischemic stroke/transient ischemic attack.

    PubMed

    Chen, Yih-Ru; Hsieh, Fang-I; Lien, Li-Ming; Hu, Chaur-Jong; Jeng, Jiann-Shing; Peng, Giia-Sheun; Tang, Sung-Chun; Chi, Nai-Fang; Sung, Yueh-Feng; Chiou, Hung-Yi

    2018-06-02

    The effect of RA on recurrent stroke is unknown. Therefore, we examined effects of rheumatoid arthritis (RA) on risk of stroke recurrence and investigated the interaction between RA and traditional cardiovascular risk factors on recurrence risk after ischemic stroke (IS) or transient ischemic attack (TIA). Of 3190 patients with IS or TIA recruited in this cohort study, 638 were comorbid with RA and 2552 without RA. Stroke recurrence, RA, lifestyle, lipid variables and other comorbidities were identified through linkage between a nationwide stroke database in Taiwan and the National Health Insurance claims database. Cox proportional hazard models with competing risk adjustment were used to evaluate the relationship between RA and recurrent stroke. Patients with RA showed a significantly increased risk of recurrent stroke, particular in recurrent IS/TIA. The increased risk of recurrent IS/TIA in RA patients may through the changes of triglycerides (TG)/high-density lipoprotein cholesterol (HDL-C) ratio. A positive additive interaction was observed between RA and current smoking on the risk of recurrent IS/TIA. Significantly increased risks for recurrent IS/TIA were observed among RA patients who smoked > 40 years or those who smoked > 20 cigarettes/day. This study provides the first evidence that RA significantly increased recurrence IS/TIA risk. The changes of TG/HDL-C ratio may play some roles in the recurrence IS/TIA risk in RA patients. In addition, our results suggest that smoking increases the risk of recurrent IS/TIA in RA patients and reinforces the need for aggressive smoking cessation efforts in RA patients.

  9. Administration of contrast media just before cisplatin-based chemotherapy increases cisplatin-induced nephrotoxicity.

    PubMed

    Sendur, M A N; Aksoy, S; Yaman, S; Arik, Z; Tugba Kos, F; Akinci, M B; Civelek, B; Yildirim Ozdemir, N; Uncu, D; Zengin, N

    2013-01-01

    There is a clinical need to predict the probability of cisplatin-induced nephrotoxicity (CIN) in order to make decisions about patient management and relevant preventive measures. The purpose of this study was to develop a risk prediction methodology of CIN. 197 consecutive cancer patients, whose serum creatinine was measured at least 48 h before every cycle of cisplatin-based chemotherapy, were included in the study. Demographic and clinical data were collected from the patient medical records. Renal function was evaluated at least 48 h before treatment (day 0) of each cycle, based on the Modification of Diet in Renal Disease (MDRD) formula. CIN was defined as a decrease of ≥ 25% in glomerular filtration rate (GFR) compared to baseline GFR values. The mean age of the study population was 54.5±9.6 years. Fifty-eight patients (29.4%) whose GFR had decreased by at least 25% compared to baseline values formed the CIN group, and the remaining 139 patients formed the non-CIN group. No significant differences were noted between the CIN and non-CIN groups in terms of age, gender, body mass index and smoking history. Metastatic disease was similar in both groups (p=0.86). History of hypertension (p=0.81), diabetes mellitus (p=0.72), and cardiovascular disease (p=0.58) were similar in the two groups. Chemotherapeutic agents used concurrently with cisplatin were similar in both groups. Significantly more radiologic examinations using contrast media were performed in the CIN group compared with the non-CIN group (p=0.01). In patients exposed to contrast media within a week before cisplatin administration, the risk of CIN was 2.56-fold higher (957 percent; CI 1.28-5.11) than in patients without such exposure (p=0.009). In patients with exposure to contrast media within a week before cisplatin administration, the risk of CIN was significantly higher than in patients without such an exposure. No additional risk factors for CIN were found in this retrospective observational

  10. Significance in the increase of women psychiatrists in Korea.

    PubMed

    Kim, Ha Kyoung; Kim, Soo In

    2008-01-01

    The number of female doctors has increased in Korea; 18.9% (13,083) of the total medical doctors registered (69,097) were women in 2006, compared to 13.6% (2,216) in 1975. The proportion of female doctors will jump up by 2010 considering that nearly 40% of the medical students are women as of today. This trend has had strong influence on the field of psychiatry; the percentage of women psychiatrists rose from 1.6 (6)% to 18% (453), from 1975 to 2006 and now women residents comprise 39% (206) of all. This is not only a reflection of a social phenomenon of the increase in professional women but also attributed to some specific characteristics of the psychiatry. Psychiatric practice may come more natural to women. While clinical activities of women psychiatrists are expanding, there are few women leaders and much less women are involving in academic activities in this field as yet. Though there is less sexual discrimination in the field of psychiatry, women psychiatrists are still having a lot of difficulties in balancing work and family matters. Many women psychiatrists also report they've ever felt an implied discrimination in their careers. In this study, we are to identify the characteristics of women psychiatrists and to explore the significance of the increase in women psychiatrists in Korea and the situation in which they are.

  11. Clinical supervision for nurses in administrative and leadership positions: a systematic literature review of the studies focusing on administrative clinical supervision.

    PubMed

    Sirola-Karvinen, Pirjo; Hyrkäs, Kristiina

    2006-11-01

    The aim of this systematic literature review was to describe administrative clinical supervision from the nursing leaders', directors' and administrators' perspective. Administrative clinical supervision is a timely and important topic as organizational structures in health care and nursing leadership are changing in addition to the increasing number of complex challenges present in health care. The material in this review was drawn from national and international databases including doctoral dissertations, distinguished thesis and peer-reviewed articles. The material was analysed by means of content analysis. The theoretical framework for the analysis was based on the three main functions of clinical supervision: administrative, educational and supportive. The findings demonstrated that the experiences of the administrative clinical supervision and its supportiveness were varying. The intervention was seen to provide versatility of learning experiences and support in challenging work experiences. Administrative clinical supervision effects and assures the quality of care. The effects as a means of development were explained through its resemblance to a leading specialist community. The findings support earlier perceptions concerning the importance and significance of administrative clinical supervision for nursing managers and administrators. However, more research is needed to develop administrative clinical supervision and to increase understanding of theoretical assumptions and relationships of the concepts on the background.

  12. Managing ulcerative colitis by increasing hydrogen production via oral administration of Acarbose.

    PubMed

    Zhu, Jian-Hong; Zhang, De-Qing; Chen, Wei-Chang

    2013-01-01

    The objective of the study was to investigate ulcerative colitis management through oral administration of acarbose. Acarbose has gained importance as a drug used widely to treat Diabetes Mellitus Type 2,as it acts on the small intestine by competitively inhibiting enzymes that delay the release of glucose from complex carbohydrates, thereby specifically reducing postprandial glucose excursion. The main side-effect of treatment with Acarbose, flatulence, occurs when undigested carbohydrates are fermented by colonic bacteria, resulting in considerable amounts of hydrogen. We found that the enteric benefits of Acarbose are partly due to be their ability to neutralise oxidative stress via increased production of H₂ in the gastrointestinal tract. Therefore, some symptoms of ulcerative colitis in human beings can be ameliorated by Acarbose.

  13. Intra-articular administration of hyaluronic acid increases the volume of the hyaline cartilage regenerated in a large osteochondral defect by implantation of a double-network gel.

    PubMed

    Fukui, Takaaki; Kitamura, Nobuto; Kurokawa, Takayuki; Yokota, Masashi; Kondo, Eiji; Gong, Jian Ping; Yasuda, Kazunori

    2014-04-01

    Implantation of PAMPS/PDMAAm double-network (DN) gel can induce hyaline cartilage regeneration in the osteochondral defect. However, it is a problem that the volume of the regenerated cartilage tissue is gradually reduced at 12 weeks. This study investigated whether intra-articular administration of hyaluronic acid (HA) increases the volume of the cartilage regenerated with the DN gel at 12 weeks. A total of 48 rabbits were used in this study. A cylindrical osteochondral defect created in the bilateral femoral trochlea was treated with DN gel (Group DN) or left without any implantation (Group C). In both Groups, we injected 1.0 mL of HA in the left knee, and 1.0 mL of saline solution in the right knee. Quantitative histological evaluations were performed at 2, 4, and 12 weeks, and PCR analysis was performed at 2 and 4 weeks after surgery. In Group DN, the proteoglycan-rich area was significantly greater in the HA-injected knees than in the saline-injected knees at 12 weeks (P = 0.0247), and expression of type 2 collagen, aggrecan, and Sox9 mRNAs was significantly greater in the HA-injected knees than in the saline-injected knees at 2 weeks (P = 0.0475, P = 0.0257, P = 0.0222, respectively). The intra-articular administration of HA significantly enhanced these gene expression at 2 weeks and significantly increased the volume of the hyaline cartilage regenerated by implantation of a DN gel at 12 weeks. This information is important to develop an additional method to increase the volume of the hyaline cartilage tissue in a potential cartilage regeneration strategy using the DN gel.

  14. Bisphosphonates Significantly Increase the Activity of Doxorubicin or Vincristine Against Canine Malignant Histiocytosis Cells

    PubMed Central

    Hafeman, S.D.; Varland, D.; Dow, S.W.

    2011-01-01

    Canine malignant histiocytosis (MH) is an aggressive neoplasm of macrophages and dendritic cells. It carries a poor prognosis due to the development of widespread metastasis and poor sensitivity to chemotherapy. Thus, there is a large need for new treatments for MH. We hypothesized that bisphosphonates might be useful to increase the effectiveness of cytotoxic chemotherapy against MH. To address this question, we conducted in vitro screening studies using MH cell lines and a panel of 6 chemotherapy and 5 bisphosphonate drugs. The combination of clodronate with vincristine was found to elicit synergistic killing which was associated with a significant increase in cell cycle arrest. Second, zoledronate combined with doxorubicin also significantly increased cell killing. Zoledronate significantly increased the uptake of doxorubicin by MH cells. Based on these findings, we conclude that certain bisphosphonate drugs may increase the overall effectiveness of chemotherapy for MH in dogs. PMID:22236140

  15. Calcium alpha-ketoglutarate administration to malnourished hemodialysis patients improves plasma arginine concentrations.

    PubMed

    Riedel, E; Hampl, H; Steudle, V; Nündel, M

    1996-01-01

    Calcium alpha-ketoglutarate administration to 24 malnourished hemodialysis patients for 1 year leads to a significant increase in plasma concentrations of L-arginine from 53.6 +/- 18.3 (compared to a healthy control group: 87.5 +/- 27.3) to 71.1 +/- 15.9 mumol/l (p < 0.05). Furthermore, concentrations in plasma of proline and histidine, precursors of glutamate biosynthesis, are increased; inorganic phosphate and urea are significantly decreased in hemodialysis patients after 1 year of calcium alpha-ketoglutarate administration.

  16. Therapeutic doses of oral methylphenidate significantly increase extracellular dopamine in the human brain.

    PubMed

    Volkow, N D; Wang, G; Fowler, J S; Logan, J; Gerasimov, M; Maynard, L; Ding, Y; Gatley, S J; Gifford, A; Franceschi, D

    2001-01-15

    Methylphenidate (Ritalin) is the most commonly prescribed psychoactive drug in children for the treatment of attention deficit hyperactivity disorder (ADHD), yet the mechanisms responsible for its therapeutic effects are poorly understood. Whereas methylphenidate blocks the dopamine transporter (main mechanism for removal of extracellular dopamine), it is unclear whether at doses used therapeutically it significantly changes extracellular dopamine (DA) concentration. Here we used positron emission tomography and [(11)C]raclopride (D2 receptor radioligand that competes with endogenous DA for binding to the receptor) to evaluate whether oral methylphenidate changes extracellular DA in the human brain in 11 healthy controls. We showed that oral methylphenidate (average dose 0.8 +/- 0.11 mg/kg) significantly increased extracellular DA in brain, as evidenced by a significant reduction in B(max)/K(d) (measure of D2 receptor availability) in striatum (20 +/- 12%; p < 0.0005). These results provide direct evidence that oral methylphenidate at doses within the therapeutic range significantly increases extracellular DA in human brain. This result coupled with recent findings of increased dopamine transporters in ADHD patients (which is expected to result in reductions in extracellular DA) provides a mechanistic framework for the therapeutic efficacy of methylphenidate. The increase in DA caused by the blockade of dopamine transporters by methylphenidate predominantly reflects an amplification of spontaneously released DA, which in turn is responsive to environmental stimulation. Because DA decreases background firing rates and increases signal-to-noise in target neurons, we postulate that the amplification of weak DA signals in subjects with ADHD by methylphenidate would enhance task-specific signaling, improving attention and decreasing distractibility. Alternatively methylphenidate-induced increases in DA, a neurotransmitter involved with motivation and reward, could

  17. Bisphosphonates significantly increase the activity of doxorubicin or vincristine against canine malignant histiocytosis cells.

    PubMed

    Hafeman, S D; Varland, D; Dow, S W

    2012-03-01

    Canine malignant histiocytosis (MH) is an aggressive neoplasm of macrophages and dendritic cells. It carries a poor prognosis because of the development of widespread metastasis and poor sensitivity to chemotherapy. Thus, there is a large need for new treatments for MH. We hypothesized that bisphosphonates might be useful to increase the effectiveness of cytotoxic chemotherapy against MH. To address this question, we conducted in vitro screening studies using MH cell lines and a panel of 6 chemotherapy and 5 bisphosphonate drugs. The combination of clodronate with vincristine was found to elicit synergistic killing which was associated with a significant increase in cell cycle arrest. Second, zoledronate combined with doxorubicin also significantly increased cell killing. Zoledronate significantly increased the uptake of doxorubicin by MH cells. On the basis of these findings, we conclude that certain bisphosphonate drugs may increase the overall effectiveness of chemotherapy for MH in dogs. © 2011 Blackwell Publishing Ltd.

  18. Intraarterial route increases the risk of cerebral lesions after mesenchymal cell administration in animal model of ischemia

    PubMed Central

    Argibay, Bárbara; Trekker, Jesse; Himmelreich, Uwe; Beiras, Andrés; Topete, Antonio; Taboada, Pablo; Pérez-Mato, María; Vieites-Prado, Alba; Iglesias-Rey, Ramón; Rivas, José; Planas, Anna M.; Sobrino, Tomás; Castillo, José; Campos, Francisco

    2017-01-01

    Mesenchymal stem cells (MSCs) are a promising clinical therapy for ischemic stroke. However, critical parameters, such as the most effective administration route, remain unclear. Intravenous (i.v.) and intraarterial (i.a.) delivery routes have yielded varied outcomes across studies, potentially due to the unknown MSCs distribution. We investigated whether MSCs reached the brain following i.a. or i.v. administration after transient cerebral ischemia in rats, and evaluated the therapeutic effects of both routes. MSCs were labeled with dextran-coated superparamagnetic nanoparticles for magnetic resonance imaging (MRI) cell tracking, transmission electron microscopy and immunohistological analysis. MSCs were found in the brain following i.a. but not i.v. administration. However, the i.a. route increased the risk of cerebral lesions and did not improve functional recovery. The i.v. delivery is safe but MCS do not reach the brain tissue, implying that treatment benefits observed for this route are not attributable to brain MCS engrafting after stroke. PMID:28091591

  19. Intraarterial route increases the risk of cerebral lesions after mesenchymal cell administration in animal model of ischemia.

    PubMed

    Argibay, Bárbara; Trekker, Jesse; Himmelreich, Uwe; Beiras, Andrés; Topete, Antonio; Taboada, Pablo; Pérez-Mato, María; Vieites-Prado, Alba; Iglesias-Rey, Ramón; Rivas, José; Planas, Anna M; Sobrino, Tomás; Castillo, José; Campos, Francisco

    2017-01-16

    Mesenchymal stem cells (MSCs) are a promising clinical therapy for ischemic stroke. However, critical parameters, such as the most effective administration route, remain unclear. Intravenous (i.v.) and intraarterial (i.a.) delivery routes have yielded varied outcomes across studies, potentially due to the unknown MSCs distribution. We investigated whether MSCs reached the brain following i.a. or i.v. administration after transient cerebral ischemia in rats, and evaluated the therapeutic effects of both routes. MSCs were labeled with dextran-coated superparamagnetic nanoparticles for magnetic resonance imaging (MRI) cell tracking, transmission electron microscopy and immunohistological analysis. MSCs were found in the brain following i.a. but not i.v. administration. However, the i.a. route increased the risk of cerebral lesions and did not improve functional recovery. The i.v. delivery is safe but MCS do not reach the brain tissue, implying that treatment benefits observed for this route are not attributable to brain MCS engrafting after stroke.

  20. Intraarterial route increases the risk of cerebral lesions after mesenchymal cell administration in animal model of ischemia

    NASA Astrophysics Data System (ADS)

    Argibay, Bárbara; Trekker, Jesse; Himmelreich, Uwe; Beiras, Andrés; Topete, Antonio; Taboada, Pablo; Pérez-Mato, María; Vieites-Prado, Alba; Iglesias-Rey, Ramón; Rivas, José; Planas, Anna M.; Sobrino, Tomás; Castillo, José; Campos, Francisco

    2017-01-01

    Mesenchymal stem cells (MSCs) are a promising clinical therapy for ischemic stroke. However, critical parameters, such as the most effective administration route, remain unclear. Intravenous (i.v.) and intraarterial (i.a.) delivery routes have yielded varied outcomes across studies, potentially due to the unknown MSCs distribution. We investigated whether MSCs reached the brain following i.a. or i.v. administration after transient cerebral ischemia in rats, and evaluated the therapeutic effects of both routes. MSCs were labeled with dextran-coated superparamagnetic nanoparticles for magnetic resonance imaging (MRI) cell tracking, transmission electron microscopy and immunohistological analysis. MSCs were found in the brain following i.a. but not i.v. administration. However, the i.a. route increased the risk of cerebral lesions and did not improve functional recovery. The i.v. delivery is safe but MCS do not reach the brain tissue, implying that treatment benefits observed for this route are not attributable to brain MCS engrafting after stroke.

  1. Viewing videotaped identification procedure increases juror sensitivity to single-blind photo-array administration.

    PubMed

    Modjadidi, Karima; Kovera, Margaret Bull

    2018-06-01

    We investigated whether watching a videotaped photo array administration or expert testimony could sensitize jurors to the suggestiveness of single-blind eyewitness identification procedures. Mock jurors recruited from the community (N = 231) watched a videotaped simulation of a robbery trial in which the primary evidence against the defendant was an eyewitness identification. We varied whether the witness made an identification from a single- or double-blind photo array, the evidence included a videotape of the photo array procedure, and an expert testified about the effects of single-blind identification procedures on administrators' behaviors and witness accuracy. Watching the videotaped photo array administration sensitized mock jurors to the suggestiveness of the single-blind procedure, causing them to be less likely to convict a defendant identified through single-rather than double-blind procedures. Exposure to the videotaped procedure also decreased the favorability of mock jurors' ratings of the eyewitness, irrespective of whether the lineup was conducted by a single-blind administrator. Expert testimony did not sensitize jurors to administrator bias. Thus, videotaping identification procedures could serve as an important procedural reform that both preserves a record of whether the lineup administration was suggestive and might improve jurors' evaluations of eyewitness evidence. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

  2. Risk Factors for Increased Severity of Paediatric Medication Administration Errors

    PubMed Central

    Sears, Kim; Goodman, William M.

    2012-01-01

    Patients' risks from medication errors are widely acknowledged. Yet not all errors, if they occur, have the same risks for severe consequences. Facing resource constraints, policy makers could prioritize factors having the greatest severe–outcome risks. This study assists such prioritization by identifying work-related risk factors most clearly associated with more severe consequences. Data from three Canadian paediatric centres were collected, without identifiers, on actual or potential errors that occurred. Three hundred seventy-two errors were reported, with outcome severities ranging from time delays up to fatalities. Four factors correlated significantly with increased risk for more severe outcomes: insufficient training; overtime; precepting a student; and off-service patient. Factors' impacts on severity also vary with error class: for wrong-time errors, the factors precepting a student or working overtime significantly increase severe-outcomes risk. For other types, caring for an off-service patient has greatest severity risk. To expand such research, better standardization is needed for categorizing outcome severities. PMID:23968607

  3. Programmed administration of parathyroid hormone increases bone formation and reduces bone loss in hindlimb-unloaded ovariectomized rats

    NASA Technical Reports Server (NTRS)

    Turner, R. T.; Evans, G. L.; Cavolina, J. M.; Halloran, B.; Morey-Holton, E.

    1998-01-01

    Gonadal insufficiency and reduced mechanical usage are two important risk factors for osteoporosis. The beneficial effects of PTH therapy to reverse the estrogen deficiency-induced bone loss in the laboratory rat are well known, but the influence of mechanical usage in this response has not been established. In this study, the effects of programed administration of PTH on cancellous bone volume and turnover at the proximal tibial metaphysis were determined in hindlimb-unloaded, ovariectomized (OVX), 3-month-old Sprague-Dawley rats. PTH was administered to weight-bearing and hindlimb-unloaded OVX rats with osmotic pumps programed to deliver 20 microg human PTH (approximately 80 microg/kg x day) during a daily 1-h infusion for 7 days. Compared with sham-operated rats, OVX increased longitudinal and radial bone growth, increased indexes of cancellous bone turnover, and resulted in net resorption of cancellous bone. Hindlimb unloading of OVX rats decreased longitudinal and radial bone growth, decreased osteoblast number, increased osteoclast number, and resulted in a further decrease in cancellous bone volume compared with those in weight-bearing OVX rats. Programed administration of PTH had no effect on either radial or longitudinal bone growth in weight-bearing and hindlimb-unloaded OVX rats. PTH treatment had dramatic effects on selected cancellous bone measurements; PTH maintained cancellous bone volume in OVX weight-bearing rats and greatly reduced cancellous bone loss in OVX hindlimb-unloaded rats. In the latter animals, PTH treatment prevented the hindlimb unloading-induced reduction in trabecular thickness, but the hormone was ineffective in preventing either the increase in osteoclast number or the loss of trabecular plates. Importantly, PTH treatment increased the retention of a baseline flurochrome label, osteoblast number, and bone formation in the proximal tibial metaphysis regardless of the level of mechanical usage. These findings demonstrate that

  4. Increased frequency of retinopathy of prematurity over the last decade and significant regional differences.

    PubMed

    Holmström, Gerd; Tornqvist, Kristina; Al-Hawasi, Abbas; Nilsson, Åsa; Wallin, Agneta; Hellström, Ann

    2018-03-01

    Retinopathy of prematurity (ROP) causes childhood blindness globally in prematurely born infants. Although increased levels of oxygen supply lead to increased survival and reduced frequency of cerebral palsy, increased incidence of ROP is reported. With the help of a Swedish register for ROP, SWEDROP, national and regional incidences of ROP and frequencies of treatment were evaluated from 2008 to 2015 (n = 5734), as well as before and after targets of provided oxygen changed from 85-89% to 91-95% in 2014. Retinopathy of prematurity (ROP) was found in 31.9% (1829/5734) of all infants with a gestational age (GA) of <31 weeks at birth and 5.7% of the infants (329/5734) had been treated for ROP. Analyses of the national data revealed an increased incidence of ROP during the 8-year study period (p = 0.003), but there was no significant increase in the frequency of treatment. There were significant differences between the seven health regions of Sweden, regarding both incidence of ROP and frequency of treatment (p < 0.001). Comparison of regional data before and after the new oxygen targets revealed a significant increase in treated ROP in one region [OR: 2.24 (CI: 1.11-4.49), p = 0.024] and a borderline increase in one other [OR: 3.08 (CI: 0.99-9.60), p = 0.052]. The Swedish national ROP register revealed an increased incidence of ROP during an 8-year period and significant regional differences regarding the incidence of ROP and frequency of treatment. © 2017 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  5. Water Reallocation - Increasing Opportunities for Cooperation, Administration and Market

    NASA Astrophysics Data System (ADS)

    Cai, X.; Marston, L.

    2016-12-01

    Nowadays utilizable water in many regions around the world has been allocated among the various users. Increasing demands and limited water supplies necessitates water reallocation given that the existing allocation is economically inefficient, socially unfair, and environmentally unsustainable. Water reallocation, a dynamic adaptation strategy to changing socioeconomic and environmental conditions, offers a flexible water management approach to mitigate water scarcity under changing socioeconomic, climatic, and environmental conditions. Water reallocation can be implemented via collective cooperation, administration, and/or market-based approaches. In spite of the numerous benefits of reallocating water between users, examples of successful water transfers are relatively sparse and the expected benefits are rarely met in full due to several complex impediments. This study discusses the key barriers to wider implementation of water reallocation based on overview of the current body of water reallocation literature. Many examples of water transfers from around the world illustrate both the benefits and challenges associated with reallocation. To overcome the obstacles for more effective reallocation, we propose an interdisciplinary approach to water reallocation that couples developments in the natural sciences and engineering disciplines with current water reallocation scholarship, which is predominately rooted in the social sciences. We conclude by calling for an integrated research platform that focuses on supporting both voluntary and nonvoluntary forms of water reallocation; however, a greater emphasis should be on nonmarket means of water transfer since it is more feasible for many regions where water rights are not well defined and institutional capacity is insufficient.

  6. Late administration of high-frequency electrical stimulation increases nerve regeneration without aggravating neuropathic pain in a nerve crush injury.

    PubMed

    Su, Hong-Lin; Chiang, Chien-Yi; Lu, Zong-Han; Cheng, Fu-Chou; Chen, Chun-Jung; Sheu, Meei-Ling; Sheehan, Jason; Pan, Hung-Chuan

    2018-06-25

    High-frequency transcutaneous neuromuscular electrical nerve stimulation (TENS) is currently used for the administration of electrical current in denervated muscle to alleviate muscle atrophy and enhance motor function; however, the time window (i.e. either immediate or delayed) for achieving benefit is still undetermined. In this study, we conducted an intervention of sciatic nerve crush injury using high-frequency TENS at different time points to assess the effect of motor and sensory functional recovery. Animals with left sciatic nerve crush injury received TENS treatment starting immediately after injury or 1 week later at a high frequency(100 Hz) or at a low frequency (2 Hz) as a control. In SFI gait analysis, either immediate or late admission of high-frequency electrical stimulation exerted significant improvement compared to either immediate or late administration of low-frequency electrical stimulation. In an assessment of allodynia, immediate high frequency electrical stimulation caused a significantly decreased pain threshold compared to late high-frequency or low-frequency stimulation at immediate or late time points. Immunohistochemistry staining and western blot analysis of S-100 and NF-200 demonstrated that both immediate and late high frequency electrical stimulation showed a similar effect; however the effect was superior to that achieved with low frequency stimulation. Immediate high frequency electrical stimulation resulted in significant expression of TNF-α and synaptophysin in the dorsal root ganglion, somatosensory cortex, and hippocampus compared to late electrical stimulation, and this trend paralleled the observed effect on somatosensory evoked potential. The CatWalk gait analysis also showed that immediate electrical stimulation led to a significantly high regularity index. In primary dorsal root ganglion cells culture, high-frequency electrical stimulation also exerted a significant increase in expression of TNF-α, synaptophysin, and

  7. Dronedarone administration prevents body weight gain and increases tolerance of the heart to ischemic stress: a possible involvement of thyroid hormone receptor alpha1.

    PubMed

    Pantos, Constantinos; Mourouzis, Iordanis; Malliopoulou, Vassiliki; Paizis, Ioannis; Tzeis, Stylianos; Moraitis, Panagiotis; Sfakianoudis, Konstantinos; Varonos, Dennis D; Cokkinos, Dennis V

    2005-01-01

    Hypothyroid heart displays a phenotype of cardioprotection against ischemia and this study investigated whether administration of dronedarone, an amiodarone-like compound that has been shown to preferentially antagonize thyroid hormone binding to thyroid hormone receptor alpha1 (TRalpha1), results in a similar effect. Dronedarone was given in Wistar rats (90 mg/kg, once daily (od) for 2 weeks) (DRON), while untreated animals served as controls (CONT). Hypothyroidism (HYPO) was induced by propylthiouracil administration. Isolated rat hearts were perfused in Langendorff mode and subjected to 20 minutes of zero-flow global ischemia (I) followed by 45 minutes of reperfusion (R). 3,5,3' Triiodothyronine remained unchanged while body weight and food intake were reduced. alpha-Myosin heavy chain (alpha-MHC) decreased in DRON while beta-myosin heavy chain (beta-MHC) and sarcoplasmic reticulum Ca2+ adenosine triphosphatase (ATPase) expression (SERCA) was similar to CONT. In HYPO, alpha-MHC and SERCA were decreased while beta-MHC was increased. Myocardial glycogen content was increased in both DRON and HYPO. In DRON, resting heart rate and contractility were reduced and ischemic contracture was significantly suppressed while postischemic left ventricular end-diastolic pressure and lactate dehydrogenase release (IU/L min) after I/R were significantly decreased. In conclusion, dronedarone treatment results in cardioprotection by selectively mimicking hypothyroidism. This is accompanied by a reduction in body weight because of the suppression of food intake. TRs might prove novel pharmacologic targets for the treatment of cardiovascular illnesses.

  8. Funds allocation in NPOs: the role of administrative cost ratios.

    PubMed

    Burkart, Christian; Wakolbinger, Tina; Toyasaki, Fuminori

    2018-01-01

    Performance measurement of Non-Profit Organizations (NPOs) is of increasing importance for aid agencies, policy-makers and donors. A widely used benchmark for measuring the efficiency of NPOs is the overhead cost ratio, consisting of the total money spent on administration and fundraising relative to the budget. Donors generally favor a lower overhead cost ratio as it ensures that more money directly reaches beneficiaries. Unlike fundraising expenses, administrative costs do not contribute to advertising the actions of an NPO even though they account for a significant proportion of overhead cost. Reducing administrative expenses is a logical consequence from a financial viewpoint, but might negatively affect NPOs through the resulting administrative capacities. This phenomenon is known as "Nonprofit Starvation Cycle". This work provides an analytical framework for analyzing NPO decision making concerning administrative costs. The paper provides answers to important research questions on the optimal level of administrative spending, the influencing factors and the effects of available information on NPOs. The research shows that focusing on financial performance measurements can result in reduced utility created for NPOs. Less transparency often leads to increased utility for NPOs, but more transparency can increase NPOs' utility if the information available exceeds a certain threshold. Fluctuating donations are challenging for NPOs' planning and may impact administrative capacities negatively.

  9. Alanine increases blood pressure during hypotension

    NASA Technical Reports Server (NTRS)

    Conlay, L. A.; Maher, T. J.; Wurtman, R. J.

    1990-01-01

    The effect of L-alanine administration on blood pressure (BP) during haemorrhagic shock was investigated using anesthetized rats whose left carotid arteries were cannulated for BP measurement, blood removal, and drug administration. It was found that L-alanine, in doses of 10, 25, 50, 100, and 200 mg/kg, increased the systolic BP of hypotensive rats by 38 to 80 percent (while 100 mg/kg pyruvate increased BP by only 9.4 mmhg, not significantly different from saline). The results suggest that L-alanine might influence cardiovascular function.

  10. FIVE-YEAR OUTCOMES AFTER LONG-TERM OXANDROLONE ADMINISTRATION IN SEVERELY BURNED CHILDREN: A RANDOMIZED CLINICAL TRIAL.

    PubMed

    Reeves, Patrick T; Herndon, David N; Tanksley, Jessica D; Jennings, Kristofer; Klein, Gordon L; Mlcak, Ronald P; Clayton, Robert P; Crites, Nancy N; Hays, Joshua P; Andersen, Clark; Lee, Jong O; Meyer, Walter; Suman, Oscar E; Finnerty, Celeste C

    2016-04-01

    Administration of oxandrolone, a nonaromatizable testosterone analog, to children for 12 months following severe burn injury has been shown to improve height, increase bone mineral content (BMC), reduce cardiac work, and augment muscle strength. Surprisingly, the increase in BMC persists well beyond the period of oxandrolone administration. This study was undertaken to determine if administration of oxandrolone for 2 years yields greater effects on long-term BMC and bone mineral density (BMD). Patients between 0 and 18 years of age with ≥30% of total body surface area burned were consented to an IRB-approved protocol and randomized to receive either placebo (n = 84) or 0.1 mg/kg oxandrolone orally twice daily for 24 months (n = 35). Patients were followed prospectively from the time of admission until 5 years postburn in a single-center, intent-to-treat setting. Height, weight, BMC, and BMD were recorded annually through 5 years postinjury. The long-term administration of oxandrolone for 16 ± 1 months postburn (range, 12.1-25.2 months) significantly increased whole-body (WB) BMC (p < 0.02) and lumbar spine (LS) BMC (p < 0.05); these effects were significantly pronounced for a longer time in patients who were in growth spurt years (7-18 years). When adjusted for height, sex, and age, LS BMD was found to significantly increase with long-term oxandrolone administration (p < 0.0009). Fewer patients receiving oxandrolone exhibited LS BMD z scores below -2.0 as compared with controls, indicating a significantly reduced risk for future fracture with oxandrolone administration. Long-term oxandrolone patients had significantly greater height velocity than controls throughout the first 2-year postburn (p < 0.05). No adverse side effects were attributed to the long-term administration of oxandrolone. A comparison of the current patients receiving long-term oxandrolone to previously described patients receiving 12 months of oxandrolone revealed that long-term oxandrolone

  11. St. John's wort significantly increased the systemic exposure and toxicity of methotrexate in rats

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Yang, Shih-Ying; Juang, Shin-Hun; Department of Medical Research, China Medical University Hospital, Taichung, Taiwan

    2012-08-15

    St. John's wort (SJW, Hypericum perforatum) is one of the popular nutraceuticals for treating depression. Methotrexate (MTX) is an immunosuppressant with narrow therapeutic window. This study investigated the effect of SJW on MTX pharmacokinetics in rats. Rats were orally given MTX alone and coadministered with 300 and 150 mg/kg of SJW, and 25 mg/kg of diclofenac, respectively. Blood was withdrawn at specific time points and serum MTX concentrations were assayed by a specific monoclonal fluorescence polarization immunoassay method. The results showed that 300 mg/kg of SJW significantly increased the AUC{sub 0−t} and C{sub max} of MTX by 163% and 60%,more » respectively, and 150 mg/kg of SJW significantly increased the AUC{sub 0−t} of MTX by 55%. In addition, diclofenac enhanced the C{sub max} of MTX by 110%. The mortality of rats treated with SJW was higher than that of controls. In conclusion, coadministration of SJW significantly increased the systemic exposure and toxicity of MTX. The combined use of MTX with SJW would need to be with caution. -- Highlights: ► St. John's wort significantly increased the AUC{sub 0−t} and C{sub max} of methotrexate. ► Coadministration of St. John's wort increased the exposure and toxicity of methotrexate. ► The combined use of methotrexate with St. John's wort will need to be with caution.« less

  12. Corticosterone administration and dietary glucose supplementation enhance fat accumulation in broiler chickens.

    PubMed

    Jiang, K J; Jiao, H C; Song, Z G; Yuan, L; Zhao, J P; Lin, H

    2008-09-01

    1. The effects of exogenous corticosterone administration and glucose supplementation on energy intake, lipid metabolism and fat deposition of broiler chickens were investigated. 2. A total of 144 three-d-old male chickens were randomly assigned to one of the following 4 treatments for 7 d: a low energy diet (10.9 MJ ME/kg, 200 g/kg CP) with or without corticosterone (30 mg/kg diet) and drinking water supplemented with glucose (80 g/l) or saccharine (2 g/l, control). 3. Body weight (BW) gain and breast and thigh muscle yields (% body mass) were all significantly decreased by corticosterone treatment. The relative cumulative feed intake (RCFI) and relative ME intake (RMEI), rather than the feed (FI) or ME intake (MEI) were increased by corticosterone administration. Both feed efficiency (FE) and caloric efficiency (CE) were decreased by corticosterone administration. Corticosterone administration had no obvious effect on water consumption. 4. Glucose supplementation had no influence on BW gain and breast and thigh muscle yield (as % of body mass). FI or RCFI was decreased while MEI or RMEI was increased by glucose supplementation. FE was improved by glucose treatment, whereas CE was reduced. 5. Liver weight and abdominal, cervical and thigh fat deposits were all significantly increased by either corticosterone or glucose treatment. 6. Plasma concentrations of glucose, urate, triglyceride, non-esterified fatty acids (NEFA), very low density lipoprotein and insulin were all significantly increased by corticosterone treatment. Glucose supplementation had no obvious influence on any of the measured plasma parameters except for NEFA, which were significantly increased. 7. Lipoprotein lipase activities in either cervical or abdominal adipose tissues, rather than in thigh fat tissue, were significantly elevated by either glucose or corticosterone treatment.

  13. Tort reform is associated with significant increases in Texas physicians relative to the Texas population.

    PubMed

    Stewart, Ronald M; West, Molly; Schirmer, Richard; Sirinek, Kenneth R

    2013-01-01

    Texas implemented comprehensive tort reform in 2003. We hypothesized that tort reform was followed by a significant increase of physicians practicing in Texas. To test this hypothesis, we compared the rate of physician growth prior to and following tort reform, and the number of licensed physicians and physicians per 100,000. Comparing before and after tort reform, the rate of increase in Texas physicians per 100,000 population increased significantly (p < 0.01). From 2002 to 2012, the Texas population increased 21 %. The number of actively practicing Texas physicians increased by 15,611 a 44 % increase (46 % metro areas vs. 9 % non-metro areas), an increase of 30 physicians per 100,000 population (p < 0.01). Non-metropolitan Texas had a net increase of 215 physicians; however, there was no change in the number of physicians per 100,000. Examining the data by trauma service areas (TSAs), 20 of 22 TSAs had an increase in both number of physicians and physicians per capita, five greater than 50 %. The post-tort reform period in Texas was associated with a significantly increased growth rate of physicians relative to the Texas population. Tort reform, as implemented in Texas, provides a needed framework for improving access to health care.

  14. Abrupt suspension of probiotics administration may increase host pathogen susceptibility by inducing gut dysbiosis

    PubMed Central

    Liu, Zhi; Liu, Wenshu; Ran, Chao; Hu, Jun; Zhou, Zhigang

    2016-01-01

    In this study, we investigated the risk associated with suspension of probiotics administration in tilapia, an animal model that may mimic immune-compromised conditions in humans. Tilapias were fed for 14 days using a probiotics-supplemented diet, followed by a three-day suspension of probiotics treatment and a subsequent challenge by Aeromonas hydrophila. Unexpectedly, the suspension of a probiotic strain Lactobacillus plantarum JCM1149 significantly triggered susceptibility of the host to A. hydrophila. We further observed that suspension of JCM1149 resulted in host gut microbiota dysbiosis and the subsequent disorder in the intestinal metabolites (bile acids, amino acids, and glucose) and damage in the intestinal epithelium, giving rise to a condition similar to antibiotics-induced gut dysbiosis, which collectively impaired tilapia’s gut health and resistance to pathogenic challenges. Additionally, we determined that JCM1149 adhered relatively poorly to tilapia intestinal mucosa and was rapidly released from the gastrointestinal tract (GIT) after suspension, with the rapid loss of probiotic strain probably being the direct cause of gut dysbiosis. Finally, three other probiotic Lactobacillus strains with low intestinal mucosa binding activity showed similar rapid loss phenotype following administration suspension, and induced higher host susceptibility to infection, indicating that the risk is a generic phenomenon in Lactobacillus. PMID:26983596

  15. Is albumin administration in the acutely ill associated with increased mortality? Results of the SOAP study

    PubMed Central

    Vincent, Jean-Louis; Sakr, Yasser; Reinhart, Konrad; Sprung, Charles L; Gerlach, Herwig; Ranieri, V Marco

    2005-01-01

    Introduction Albumin administration in the critically ill has been the subject of some controversy. We investigated the use of albumin solutions in European intensive care units (ICUs) and its relationship to outcome. Methods In a cohort, multicenter, observational study, all patients admitted to one of the participating ICUs between 1 May and 15 May 2002 were followed up until death, hospital discharge, or for 60 days. Patients were classified according to whether or not they received albumin at any time during their ICU stay. Results Of 3,147 admitted patients, 354 (11.2%) received albumin and 2,793 (88.8%) did not. Patients who received albumin were more likely to have cancer or liver cirrhosis, to be surgical admissions, and to have sepsis. They had a longer length of ICU stay and a higher mortality rate, but were also more severely ill, as manifested by higher simplified acute physiology score (SAPS) II and sequential organ failure assessment (SOFA) scores than the other patients. A Cox proportional hazard model indicated that albumin administration was significantly associated with decreased 30-day survival. Moreover, in 339 pairs matched according to a propensity score, ICU and hospital mortality rates were higher in the patients who had received albumin than in those who had not (34.8 versus 20.9% and 41.3 versus 27.7%, respectively, both p < 0.001). Conclusion Albumin administration was associated with decreased survival in this population of acutely ill patients. Further prospective randomized controlled trials are needed to examine the effects of albumin administration in sub-groups of acutely ill patients. PMID:16356223

  16. Long-term administration of tolvaptan increases myocardial remodeling and mortality via exacerbation of congestion in mice heart failure model after myocardial infarction.

    PubMed

    Eguchi, Akiyo; Iwasaku, Toshihiro; Okuhara, Yoshitaka; Naito, Yoshiro; Mano, Toshiaki; Masuyama, Tohru; Hirotani, Shinichi

    2016-10-15

    In contrast to loop diuretics, tolvaptan does not cause neurohormonal activation in several animal heart failure models. However, it remains unknown whether chronic vasopressin type 2 receptor blockade exerts beneficial effects on mortality in murine heart failure after myocardial infarction (MI). In an experimental heart failure model, we tested the hypothesis that tolvaptan reduces myocardial remodeling and mortality. MI was induced in 9-week-old male C57Bl6/J by the left coronary artery ligation. In study 1, animals were randomly assigned to treatment with placebo or tolvaptan starting 14days post-MI. In study 2, animals were randomized to tolvaptan or furosemide+tolvaptan starting 14days post-MI. Interestingly, results showed lower survival rate in tolvaptan group compared to placebo. Tolvaptan group had higher serum osmolality, heavier body weight, more severe myocardial remodeling, and lung congestion at day 28 of drug administration compared to placebo. In study 2, addition of furosemide significantly reduced mortality rate seen with tolvaptan, and presented with decreased osmolality, myocardial remodeling, and lung congestion compared to tolvaptan-treated mice. Increase in proximal tubular expression of aquaporin 1, Angiotensin II, and vasopressin seen with tolvaptan treatments were normalized to basal levels, similar to levels in placebo-treated mice. Contrary to our hypothesis, tolvaptan was associated with increased mortality in murine heart failure after MI. This increase in lung congestion, myocardial remodeling, could be prevented by co-administration of furosemide, which resulted in normalized serum osmolality, neurohormonal activation, and renal aquaporin 1 expression, and hence decreased mortality post-MI. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  17. Increased growth and germination success in plants following hydrogen sulfide administration.

    PubMed

    Dooley, Frederick D; Nair, Suven P; Ward, Peter D

    2013-01-01

    This study presents a novel way of enhancing plant growth through the use of a non-petroleum based product. We report here that exposing either roots or seeds of multicellular plants to extremely low concentrations of dissolved hydrogen sulfide at any stage of life causes statistically significant increases in biomass including higher fruit yield. Individual cells in treated plants were smaller (~13%) than those of controls. Germination success and seedling size increased in, bean, corn, wheat, and pea seeds while time to germination decreases. These findings indicated an important role of H2S as a signaling molecule that can increase the growth rate of all species yet tested. The increased crop yields reported here has the potential to effect the world's agricultural output.

  18. Increased Excitability of Lateral Habenula Neurons in Adolescent Rats following Cocaine Self-Administration

    PubMed Central

    Ishikawa, Masago; Otaka, Mami; Huang, Yanhua H.; Schlüter, Oliver M.

    2015-01-01

    Background: The lateral habenula is a brain region that has been critically implicated in modulating negative emotional states and responses to aversive stimuli. Exposure to addictive drugs such as cocaine negatively impacts affective states, an effect persisting longer than acute drug effects. However, the mechanisms of this effect are poorly understood. We hypothesized that drugs of abuse, such as cocaine, may contribute to drug-induced negative affective states by altering the firing properties of lateral habenula neurons, thus changing the signaling patterns from the lateral habenula to downstream circuits. Methods: Using whole-cell current-clamp recording of acutely prepared brain slices of rats after various periods of withdrawal from cocaine self-administration, we characterized an important heterogeneous subregion of the lateral habenula based on membrane properties. Results: We found two major relevant neuronal subtypes: burst firing neurons and regular spiking neurons. We also found that lateral habenula regular spiking neurons had higher membrane excitability for at least 7 days following cocaine self-administration, likely due to a greater membrane resistance. Both the increase in lateral habenula excitability and membrane resistance returned to baseline when tested after a more prolonged period of 45 days of withdrawal. Conclusion: This is the first study to look at intrinsic lateral habenula neuron properties following cocaine exposure beyond acute drug effects. These results may help to explain how cocaine and other drugs negatively impact affect states. PMID:25548105

  19. Assessing administrative costs of mental health and substance abuse services.

    PubMed

    Broyles, Robert W; Narine, Lutchmie; Robertson, Madeline J

    2004-05-01

    Increasing competition in the market for mental health and substance abuse MHSA services and the potential to realize significant administrative savings have created an imperative to monitor, evaluate, and control spending on administrative functions. This paper develops a generic model that evaluates spending on administrative personnel by a group of providers. The precision of the model is demonstrated by examining a set of data assembled from five MHSA service providers. The model examines a differential cost construction derived from inter-facility comparisons of administrative expenses. After controlling for the scale of operations, the results enable MHSA programs to control the efficiency of administrative personnel and related rates of compensation. The results indicate that the efficiency of using the administrative complement and the scale of operations represent the lion's share of the total differential cost. The analysis also indicates that a modest improvement in the use of administrative personnel results in substantial cost savings, an increase in the net cash flow derived from operations, an improvement in the fiscal performance of the provider, and a decline in opportunity costs that assume the form of foregone direct patient care.

  20. Effects of Streptomycin Administration on Increases in Skeletal Muscle Fiber Permeability and Size Following Eccentric Muscle Contractions.

    PubMed

    Hayao, Keishi; Tamaki, Hiroyuki; Nakagawa, Kouki; Tamakoshi, Keigo; Takahashi, Hideaki; Yotani, Kengo; Ogita, Futoshi; Yamamoto, Noriaki; Onishi, Hideaki

    2018-06-01

    The purpose of this study was to investigate the preventive effect of streptomycin (Str) administration on changes in membrane permeability and the histomorphological characteristics of damaged muscle fibers following eccentric contraction (ECC ). Eighteen 7-week-old male Fischer 344 rats were randomly assigned to three groups: control (Cont), ECC, and ECC with Str (ECC + Str). The tibialis anterior (TA) muscles in both ECC groups were stimulated electrically and exhibited ECC. Evans blue dye (EBD), a marker of muscle fiber damage associated with increased membrane permeability, was injected 24 hr before TA muscle sampling. The number of EBD-positive fibers, muscle fiber cross-sectional area (CSA), and roundness were determined via histomorphological analysis. The ECC intervention resulted in an increased fraction of EBD-positive fibers, a larger CSA, and decreased roundness. The fraction of EBD-positive fibers was 79% lower in the ECC + Str group than in the ECC group. However, there was no difference in the CSA and roundness of the EBD-positive fibers between the two ECC groups. These results suggest that Str administration can reduce the number of myofibers that increase membrane permeability following ECC, but does not ameliorate the extent of fiber swelling in extant EBD-positive fibers. Anat Rec, 301:1096-1102, 2018. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

  1. Cocaine administration dose-dependently increases sexual desire and decreases condom use likelihood: The role of delay and probability discounting in connecting cocaine with HIV.

    PubMed

    Johnson, Matthew W; Herrmann, Evan S; Sweeney, Mary M; LeComte, Robert S; Johnson, Patrick S

    2017-02-01

    Although cocaine use has been linked to sexual HIV risk behavior for decades, the direct effects of cocaine on sexual desire and sexual decision-making are unexamined. Research suggests delay discounting (devaluation of future outcomes) and probability discounting (devaluation of uncertain outcomes) play roles in condom use decisions. This study examined the effect of cocaine administration on sexual desire, hypothetical condom use, and discounting tasks. This double-blind, within-subjects study compared the effects of 0, 125, and 250 mg/70 kg oral cocaine HCl in 12 cocaine users. Measures included sexual desire and other subjective ratings, the Sexual Delay Discounting Task, the Sexual Probability Discounting Task, and monetary delay and probability discounting tasks. Cocaine caused dose-related increases in sexual desire and prototypical stimulant abuse-liability ratings. Relative to placebo, cocaine did not significantly alter condom use likelihood when condoms were immediately available or when sex was associated with 100% certainty of sexually transmitted infection (STI). In contrast, cocaine dose-dependently strengthened the effect of delay (sexual delay discounting) and STI uncertainty (sexual probability discounting) in decreasing condom use likelihood. Cocaine caused no significant change in monetary delay and probability discounting. This is the first study showing that cocaine administration increases sexual desire. Detrimental effects of cocaine on sexual risk were only observed when safer sex required delay, or STI risk was uncertain (representative of many real-world scenarios), suggesting a critical role of discounting processes. Lack of monetary effects highlights the importance of studying clinically relevant outcomes when examining drug effects on behavioral processes.

  2. Oral Administration of Faecalibacterium prausnitzii Decreased the Incidence of Severe Diarrhea and Related Mortality Rate and Increased Weight Gain in Preweaned Dairy Heifers.

    PubMed

    Foditsch, Carla; Pereira, Richard Van Vleck; Ganda, Erika Korzune; Gomez, Marilia Souza; Marques, Eduardo Carvalho; Santin, Thiago; Bicalho, Rodrigo Carvalho

    2015-01-01

    Probiotics are a promising alternative to improve food animal productivity and health. However, scientific evidence that specific microbes can be used to benefit animal health and performance is limited. The objective of this study was to evaluate the effects of administering a live culture of Faecalibacterium prausnitzii to newborn dairy calves on subsequent growth, health, and fecal microbiome. Initially, a safety trial was conducted using 30 newborn bull calves to assess potential adverse effects of the oral and rectal administration of F. prausnitzii to neonatal calves. No adverse reactions, such as increased body temperature or heart and respiratory rates, were observed after the administration of the treatments. All calves survived the experimental period, and there was no difference in fecal consistency score, attitude, appetite or dehydration between the treatment groups. The rectal route was not an efficient practice while the oral route ensures that the full dose is administered to the treated calves. Subsequently, a randomized field trial was completed in a commercial farm with preweaned calves. A total of 554 Holstein heifers were assigned to one of two treatment groups: treated calves (FPTRT) and non-treated calves (control). Treated calves received two oral doses of F. prausnitzii, one at treatment assignment (1st week) and another one week later. The FPTRT group presented significantly lower incidence of severe diarrhea (3.1%) compared with the control group (6.8%). Treated calves also had lower mortality rate associated with severe diarrhea (1.5%) compared to control calves (4.4%). Furthermore, FPTRT calves gained significantly more weight, 4.4 kg over the preweaning period, than controls calves. The relative abundance of F. prausnitzii in the fecal microbiota was significantly higher in the 3rd and 5th weeks of life of FPTRT calves than of the control calves, as revealed by sequencing of the 16S rRNA gene. Our findings showed that oral

  3. Effects of caffeine on alcohol consumption and nicotine self-administration in rats.

    PubMed

    Rezvani, Amir H; Sexton, Hannah G; Johnson, Joshua; Wells, Cori; Gordon, Karen; Levin, Edward D

    2013-09-01

    Caffeine, alcohol, and nicotine are 3 of the most widespread self-administered psychoactive substances, which are known to be extensively co-administered. However, little is known about the degree to which they may mutually potentiate each other's consumption. In the current set of studies, we examined in rats the effect of caffeine administration on alcohol drinking and intravenous (i.v.) self-administration of nicotine. In male alcohol-preferring (P) rats, caffeine (5, 10, and 20 mg/kg) or the saline vehicle was administered acutely either by subcutaneous (S.C.) injection or orally (PO) by gavage. In a chronic study, the effect of PO caffeine (5 and 20 mg/kg) on alcohol intake over a 10-day period was tested. In another experiment, the effect of acute PO administration of caffeine (20 mg/kg) or saline on saccharin intake (0.2% solution) was determined in P rats. Effects of 20 mg/kg caffeine on motor activity were also determined in P rats. Finally, the effects of acute PO caffeine administration on nicotine self-administration in Sprague-Dawley rats were also determined. Both routes of administration of caffeine, S.C. and PO, caused a significant dose-related decrease in alcohol intake and preference during free access to alcohol and after 4-day deprivation of alcohol. However, the low dose of 5 mg/kg caffeine increased alcohol intake. Acute PO caffeine also reduced saccharin intake. Acute systemic administration of 20 mg/kg caffeine did not exert a significant effect on motor activity. In Sprague-Dawley rats trained to self-administer i.v. nicotine, acute PO administration of caffeine significantly increased self-administration of nicotine in a dose-related manner. These results suggest that adenosine receptor systems may play a role in both alcohol and nicotine intake and deserve further study regarding these addictions. Copyright © 2013 by the Research Society on Alcoholism.

  4. Benefits of oxytocin administration in obstructive sleep apnea.

    PubMed

    Jain, Vivek; Marbach, Joseph; Kimbro, Shawn; Andrade, David C; Jain, Arad; Capozzi, Eleanor; Mele, Kyle; Del Rio, Rodrigo; Kay, Matthew W; Mendelowitz, David

    2017-11-01

    Activation of oxytocin receptors has shown benefits in animal models of obstructive sleep apnea (OSA). We tested if nocturnal oxytocin administration could have beneficial effects in OSA patients. Eight patients diagnosed with OSA were administered intranasal oxytocin (40 IU). Changes in cardiorespiratory events during sleep, including apnea and hypopnea durations and frequency, risk of event-associated arousals, and heart rate variability, were assessed. Oxytocin significantly increased indexes of parasympathetic activity, including heart rate variability, total sleep time, and the postpolysommogram sleep assessment score, an index of self-reported sleep satisfaction. Although the apnea-hypopnea index was not significantly changed with oxytocin administration, when apnea and hypopnea events were compared independently, the frequency of hypopneas, but not apneas, was significantly ( P ≤ 0.005) decreased with oxytocin treatment. Both apneas and hypopneas were significantly shortened in duration with oxytocin treatment. Oxytocin treatment significantly decreased the percent of apnea and hypopnea events that were accompanied with an arousal. Oxytocin administration has the potential to restore cardiorespiratory homeostasis and reduce some clinically important (objective and patient-reported) adverse events that occur with OSA. Additional studies are needed to further understand the mechanisms by which oxytocin promotes these changes in cardiorespiratory and autonomic function in OSA patients. Copyright © 2017 the American Physiological Society.

  5. Continuous background light significantly increases flashing-light enhancement of photosynthesis and growth of microalgae.

    PubMed

    Abu-Ghosh, Said; Fixler, Dror; Dubinsky, Zvy; Iluz, David

    2015-01-01

    Under specific conditions, flashing light enhances the photosynthesis rate in comparison to continuous illumination. Here we show that a combination of flashing light and continuous background light with the same integrated photon dose as continuous or flashing light alone can be used to significantly enhance photosynthesis and increase microalgae growth. To test this hypothesis, the green microalga Dunaliella salina was exposed to three different light regimes: continuous light, flashing light, and concomitant application of both. Algal growth was compared under three different integrated light quantities; low, intermediate, and moderately high. Under the combined light regime, there was a substantial increase in all algal growth parameters, with an enhanced photosynthesis rate, within 3days. Our strategy demonstrates a hitherto undescribed significant increase in photosynthesis and algal growth rates, which is beyond the increase by flashing light alone. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Sildenafil Increases Sympathetically Mediated Vascular Tone in Humans

    PubMed Central

    2013-01-01

    BACKGROUND Sildenafil, a selective phosphodiesterase-type-5 (PDE-5) inhibitor, produces vasodilation that improves erectile dysfunction and pulmonary hypertension. Sildenafil could also cause baroreflex sympathetic activation that would enhance vascular tone and oppose direct vasodilation. We tested the hypothesis that sildenafil administration increases sympathetically mediated vascular tone in healthy middle-aged men. METHODS We randomized 9 healthy, middle-aged, male volunteers (mean age 45±2 years) in a double-blind, crossover fashion to receive a single oral dose of sildenafil 100mg or placebo on 2 separate study days. Hemodynamics and forearm blood flow responses were measured at baseline, at 30 and 45 minutes after study drug administration, and then during intra-arterial infusions of vasoactive drugs. After sildenafil and placebo administration, intrabrachial medications were infused to test forearm alpha receptor sensitivity (norepinephrine), cyclic-AMP–mediated vasodilation (isoproterenol), and sympathetically mediated vascular tone (phentolamine) (adenosine was a control vasodilator). Blood samples were taken before and 60 minutes after study drug administration and at the end of the intrabrachial infusions for measurement of plasma norepinephrine concentrations. RESULTS Forearm vascular responses to norepinephrine, isoproterenol, and adenosine were not different after placebo and sildenafil administration. Percentage reduction in forearm vascular resistance during phentolamine was significantly lower after sildenafil than placebo (−73% ± 3% vs −63% ± 3%; P = 0.0002). Sildenafil significantly increased plasma norepinephrine compared with placebo 60 minutes after study drug administration and at the end of the study session (P = 0.02). CONCLUSIONS Sildenafil increased sympathetically mediated vascular tone in middle-aged healthy men. Alpha-adrenergic–mediated vasoconstriction may offset vasodilation during PDE-5 inhibition and may explain the

  7. Breast cancer-associated metastasis is significantly increased in a model of autoimmune arthritis

    PubMed Central

    Das Roy, Lopamudra; Pathangey, Latha B; Tinder, Teresa L; Schettini, Jorge L; Gruber, Helen E; Mukherjee, Pinku

    2009-01-01

    Introduction Sites of chronic inflammation are often associated with the establishment and growth of various malignancies including breast cancer. A common inflammatory condition in humans is autoimmune arthritis (AA) that causes inflammation and deformity of the joints. Other systemic effects associated with arthritis include increased cellular infiltration and inflammation of the lungs. Several studies have reported statistically significant risk ratios between AA and breast cancer. Despite this knowledge, available for a decade, it has never been questioned if the site of chronic inflammation linked to AA creates a milieu that attracts tumor cells to home and grow in the inflamed bones and lungs which are frequent sites of breast cancer metastasis. Methods To determine if chronic inflammation induced by autoimmune arthritis contributes to increased breast cancer-associated metastasis, we generated mammary gland tumors in SKG mice that were genetically prone to develop AA. Two breast cancer cell lines, one highly metastatic (4T1) and the other non-metastatic (TUBO) were used to generate the tumors in the mammary fat pad. Lung and bone metastasis and the associated inflammatory milieu were evaluated in the arthritic versus the non-arthritic mice. Results We report a three-fold increase in lung metastasis and a significant increase in the incidence of bone metastasis in the pro-arthritic and arthritic mice compared to non-arthritic control mice. We also report that the metastatic breast cancer cells augment the severity of arthritis resulting in a vicious cycle that increases both bone destruction and metastasis. Enhanced neutrophilic and granulocytic infiltration in lungs and bone of the pro-arthritic and arthritic mice and subsequent increase in circulating levels of proinflammatory cytokines, such as macrophage colony stimulating factor (M-CSF), interleukin-17 (IL-17), interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), and tumor necrosis factor

  8. Breast-cancer-associated metastasis is significantly increased in a model of autoimmune arthritis.

    PubMed

    Das Roy, Lopamudra; Pathangey, Latha B; Tinder, Teresa L; Schettini, Jorge L; Gruber, Helen E; Mukherjee, Pinku

    2009-01-01

    Sites of chronic inflammation are often associated with the establishment and growth of various malignancies including breast cancer. A common inflammatory condition in humans is autoimmune arthritis (AA) that causes inflammation and deformity of the joints. Other systemic effects associated with arthritis include increased cellular infiltration and inflammation of the lungs. Several studies have reported statistically significant risk ratios between AA and breast cancer. Despite this knowledge, available for a decade, it has never been questioned if the site of chronic inflammation linked to AA creates a milieu that attracts tumor cells to home and grow in the inflamed bones and lungs which are frequent sites of breast cancer metastasis. To determine if chronic inflammation induced by autoimmune arthritis contributes to increased breast cancer-associated metastasis, we generated mammary gland tumors in SKG mice that were genetically prone to develop AA. Two breast cancer cell lines, one highly metastatic (4T1) and the other non-metastatic (TUBO) were used to generate the tumors in the mammary fat pad. Lung and bone metastasis and the associated inflammatory milieu were evaluated in the arthritic versus the non-arthritic mice. We report a three-fold increase in lung metastasis and a significant increase in the incidence of bone metastasis in the pro-arthritic and arthritic mice compared to non-arthritic control mice. We also report that the metastatic breast cancer cells augment the severity of arthritis resulting in a vicious cycle that increases both bone destruction and metastasis. Enhanced neutrophilic and granulocytic infiltration in lungs and bone of the pro-arthritic and arthritic mice and subsequent increase in circulating levels of proinflammatory cytokines, such as macrophage colony stimulating factor (M-CSF), interleukin-17 (IL-17), interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), and tumor necrosis factor-alpha (TNF-alpha) may contribute

  9. Developing Administrative Vision.

    ERIC Educational Resources Information Center

    Chance, Edward W.

    Visionary leadership has emerged as a significant characteristic of high performing school administrators. Vision provides a sense of direction for the school and facilitates accomplishment. Administrators must move from authoritarian and managerial modes of operation to proactive leadership, and maintain a focus on the vision through turmoil and…

  10. Overexpression of the Steroidogenic Enzyme Cytochrome P450 Side Chain Cleavage in the Ventral Tegmental Area Increases 3α,5α-THP and Reduces Long-Term Operant Ethanol Self-Administration

    PubMed Central

    Cook, Jason B.; Werner, David F.; Maldonado-Devincci, Antoniette M.; Leonard, Maggie N.; Fisher, Kristen R.; O'Buckley, Todd K.; Porcu, Patrizia; McCown, Thomas J.; Besheer, Joyce; Hodge, Clyde W.

    2014-01-01

    Neuroactive steroids are endogenous neuromodulators capable of altering neuronal activity and behavior. In rodents, systemic administration of endogenous or synthetic neuroactive steroids reduces ethanol self-administration. We hypothesized this effect arises from actions within mesolimbic brain regions that we targeted by viral gene delivery. Cytochrome P450 side chain cleavage (P450scc) converts cholesterol to pregnenolone, the rate-limiting enzymatic reaction in neurosteroidogenesis. Therefore, we constructed a recombinant adeno-associated serotype 2 viral vector (rAAV2), which drives P450scc expression and neuroactive steroid synthesis. The P450scc-expressing vector (rAAV2-P450scc) or control GFP-expressing vector (rAAV2-GFP) were injected bilaterally into the ventral tegmental area (VTA) or nucleus accumbens (NAc) of alcohol preferring (P) rats trained to self-administer ethanol. P450scc overexpression in the VTA significantly reduced ethanol self-administration by 20% over the 3 week test period. P450scc overexpression in the NAc, however, did not alter ethanol self-administration. Locomotor activity was unaltered by vector administration to either region. P450scc overexpression produced a 36% increase in (3α,5α)-3-hydroxypregnan-20-one (3α,5α-THP, allopregnanolone)-positive cells in the VTA, but did not increase 3α,5α-THP immunoreactivity in NAc. These results suggest that P450scc overexpression and the resultant increase of 3α,5α-THP-positive cells in the VTA reduces ethanol reinforcement. 3α,5α-THP is localized to neurons in the VTA, including tyrosine hydroxylase neurons, but not astrocytes. Overall, the results demonstrate that using gene delivery to modulate neuroactive steroids shows promise for examining the neuronal mechanisms of moderate ethanol drinking, which could be extended to other behavioral paradigms and neuropsychiatric pathology. PMID:24760842

  11. Overexpression of the steroidogenic enzyme cytochrome P450 side chain cleavage in the ventral tegmental area increases 3α,5α-THP and reduces long-term operant ethanol self-administration.

    PubMed

    Cook, Jason B; Werner, David F; Maldonado-Devincci, Antoniette M; Leonard, Maggie N; Fisher, Kristen R; O'Buckley, Todd K; Porcu, Patrizia; McCown, Thomas J; Besheer, Joyce; Hodge, Clyde W; Morrow, A Leslie

    2014-04-23

    Neuroactive steroids are endogenous neuromodulators capable of altering neuronal activity and behavior. In rodents, systemic administration of endogenous or synthetic neuroactive steroids reduces ethanol self-administration. We hypothesized this effect arises from actions within mesolimbic brain regions that we targeted by viral gene delivery. Cytochrome P450 side chain cleavage (P450scc) converts cholesterol to pregnenolone, the rate-limiting enzymatic reaction in neurosteroidogenesis. Therefore, we constructed a recombinant adeno-associated serotype 2 viral vector (rAAV2), which drives P450scc expression and neuroactive steroid synthesis. The P450scc-expressing vector (rAAV2-P450scc) or control GFP-expressing vector (rAAV2-GFP) were injected bilaterally into the ventral tegmental area (VTA) or nucleus accumbens (NAc) of alcohol preferring (P) rats trained to self-administer ethanol. P450scc overexpression in the VTA significantly reduced ethanol self-administration by 20% over the 3 week test period. P450scc overexpression in the NAc, however, did not alter ethanol self-administration. Locomotor activity was unaltered by vector administration to either region. P450scc overexpression produced a 36% increase in (3α,5α)-3-hydroxypregnan-20-one (3α,5α-THP, allopregnanolone)-positive cells in the VTA, but did not increase 3α,5α-THP immunoreactivity in NAc. These results suggest that P450scc overexpression and the resultant increase of 3α,5α-THP-positive cells in the VTA reduces ethanol reinforcement. 3α,5α-THP is localized to neurons in the VTA, including tyrosine hydroxylase neurons, but not astrocytes. Overall, the results demonstrate that using gene delivery to modulate neuroactive steroids shows promise for examining the neuronal mechanisms of moderate ethanol drinking, which could be extended to other behavioral paradigms and neuropsychiatric pathology.

  12. High-resolution chromosomal microarrays in prenatal diagnosis significantly increase diagnostic power.

    PubMed

    Oneda, Beatrice; Baldinger, Rosa; Reissmann, Regina; Reshetnikova, Irina; Krejci, Pavel; Masood, Rahim; Ochsenbein-Kölble, Nicole; Bartholdi, Deborah; Steindl, Katharina; Morotti, Denise; Faranda, Marzia; Baumer, Alessandra; Asadollahi, Reza; Joset, Pascal; Niedrist, Dunja; Breymann, Christian; Hebisch, Gundula; Hüsler, Margaret; Mueller, René; Prentl, Elke; Wisser, Josef; Zimmermann, Roland; Rauch, Anita

    2014-06-01

    The objective of this study was to determine for the first time the reliability and the diagnostic power of high-resolution microarray testing in routine prenatal diagnostics. We applied high-resolution chromosomal microarray testing in 464 cytogenetically normal prenatal samples with any indication for invasive testing. High-resolution testing revealed a diagnostic yield of 6.9% and 1.6% in cases of fetal ultrasound anomalies and cases of advanced maternal age (AMA), respectively, which is similar to previous studies using low-resolution microarrays. In three (0.6%) additional cases with an indication of AMA, an aberration in susceptibility risk loci was detected. Moreover, one case (0.2%) showed an X-linked aberration in a female fetus, a finding relevant for future family planning. We found the rate of cases, in which the parents had to be tested for interpretation of unreported copy number variants (3.7%), and the rate of remaining variants of unknown significance (0.4%) acceptably low. Of note, these findings did not cause termination of pregnancy after expert genetic counseling. The 0.4% rate of confined placental mosaicism was similar to that observed by conventional karyotyping and notably involved a case of placental microdeletion. High-resolution prenatal microarray testing is a reliable technique that increases diagnostic yield by at least 17.3% when compared with conventional karyotyping, without an increase in the frequency of variants of uncertain significance. © 2014 John Wiley & Sons, Ltd.

  13. Significantly Increasing the Ductility of High Performance Polymer Semiconductors through Polymer Blending.

    PubMed

    Scott, Joshua I; Xue, Xiao; Wang, Ming; Kline, R Joseph; Hoffman, Benjamin C; Dougherty, Daniel; Zhou, Chuanzhen; Bazan, Guillermo; O'Connor, Brendan T

    2016-06-08

    Polymer semiconductors based on donor-acceptor monomers have recently resulted in significant gains in field effect mobility in organic thin film transistors (OTFTs). These polymers incorporate fused aromatic rings and have been designed to have stiff planar backbones, resulting in strong intermolecular interactions, which subsequently result in stiff and brittle films. The complex synthesis typically required for these materials may also result in increased production costs. Thus, the development of methods to improve mechanical plasticity while lowering material consumption during fabrication will significantly improve opportunities for adoption in flexible and stretchable electronics. To achieve these goals, we consider blending a brittle donor-acceptor polymer, poly[4-(4,4-dihexadecyl-4H-cyclopenta[1,2-b:5,4-b']dithiophen-2-yl)-alt-[1,2,5]thiadiazolo[3,4-c]pyridine] (PCDTPT), with ductile poly(3-hexylthiophene). We found that the ductility of the blend films is significantly improved compared to that of neat PCDTPT films, and when the blend film is employed in an OTFT, the performance is largely maintained. The ability to maintain charge transport character is due to vertical segregation within the blend, while the improved ductility is due to intermixing of the polymers throughout the film thickness. Importantly, the application of large strains to the ductile films is shown to orient both polymers, which further increases charge carrier mobility. These results highlight a processing approach to achieve high performance polymer OTFTs that are electrically and mechanically optimized.

  14. Tassel Removal Positively Affects Biomass Production Coupled with Significantly Increasing Stem Digestibility in Switchgrass

    PubMed Central

    Zhao, Chunqiao; Fan, Xifeng; Hou, Xincun; Zhu, Yi; Yue, Yuesen; Zhang, Shuang; Wu, Juying

    2015-01-01

    In this study, tassels of Cave-in-Rock (upland) and Alamo (lowland) were removed at or near tassel emergence to explore its effects on biomass production and quality. Tassel-removed (TR) Cave-in-Rock and Alamo both exhibited a significant (P<0.05) increase in plant heights (not including tassel length), tiller number, and aboveground biomass dry weight (10% and 12%, 30% and 13%, 13% and 18%, respectively by variety) compared to a control (CK) treatment. Notably, total sugar yields of TR Cave-in-Rock and Alamo stems increased significantly (P<0.05 or 0.01) by 19% and 19%, 21% and 14%, 52% and 18%, respectively by variety, compared to those of control switchgrass under 3 treatments by direct enzymatic hydrolysis (DEH), enzymatic hydrolysis after 1% NaOH pretreatment (EHAL) and enzymatic hydrolysis after 1% H2SO4 pretreatment (EHAC). These differences were mainly due to significantly (P<0.05 or 0.01) higher cellulose content, lower cellulose crystallinity indexes (CrI) caused by higher arabinose (Ara) substitution in xylans, and lower S/G ratio in lignin. However, the increases of nitrogen (N) and sulphur (S) concentration negatively affects the combustion quality of switchgrass aboveground biomass. This work provides information for increasing biomass production and quality in switchgrass and also facilitates the inhibition of gene dispersal of switchgrass in China. PMID:25849123

  15. Alteration in metabolism and toxicity of acetaminophen upon repeated administration in rats.

    PubMed

    Kim, Sun J; Lee, Min Y; Kwon, Do Y; Kim, Sung Y; Kim, Young C

    2009-10-01

    Our previous studies showed that administration of a subtoxic dose of acetaminophen (APAP) to female rats increased generation of carbon monoxide from dichloromethane, a metabolic reaction catalyzed mainly by cytochrome P450 (CYP) 2E1. In this study we examined the changes in metabolism and toxicity of APAP upon repeated administration. An intraperitoneal dose of APAP (500 mg/kg) alone did not increase aspartate aminotransferase, alanine aminotransferase, or sorbitol dehydrogenase activity in serum, but was significantly hepatotoxic when the rats had been pretreated with an identical dose of APAP 18 h earlier. The concentrations and disappearance of APAP and its metabolites in plasma were monitored for 8 h after the treatment. APAP pretreatment reduced the elevation of APAP-sulfate, but increased APAP-cysteine concentrations in plasma. APAP or APAP-glucuronide concentrations were not altered. Administration of a single dose of APAP 18 h before sacrifice increased microsomal CYP activities measured with p-nitrophenol, p-nitroanisole, and aminopyrine as probes. Expression of CYP2E1, CYP3A, and CYP1A proteins in the liver was also elevated significantly. The results suggest that administration of APAP at a subtoxic dose may result in an induction of hepatic CYP enzymes, thereby altering metabolism and toxicological consequences of various chemical substances that are substrates for the same enzyme system.

  16. Effects of chronic administration of nicotine on storage and synthesis of noradrenaline in rat brain

    PubMed Central

    Bhagat, B.

    1970-01-01

    1. Chronic administration of nicotine (0·5 mg/kg, subcutaneously four times a day, 5 days a week, for 6 weeks) did not affect the growth rate and water intake in rats. In these animals food intake was normal for the first 5 weeks, but was significantly increased during the sixth week of treatment. 2. Nicotine administration increased the blood pressure of rats from 120 mm Hg to 151 mm Hg. 3. The concentrations of endogenous noradrenaline, dopamine, 5-hydroxytryptamine and acetylcholine in the brain remained unaltered. However, chronic treatment with nicotine increased the turnover rate of noradrenaline. Initial accumulation of 3H-noradrenaline was also significantly increased. 4. It is concluded from these studies that changes in the turnover of cerebral noradrenaline caused by chronic administration rather than changes in the concentration of noradrenaline may be an important factor in nicotine-induced behavioural changes. PMID:5413293

  17. Administrators' Perceptions of Motives to Offer Online Academic Degree Programs in Universities

    ERIC Educational Resources Information Center

    Özcan, Hakan; Yildirim, Soner

    2018-01-01

    Although the number of online academic degree programs offered by universities in Turkey has become increasingly significant in recent years, the current lack of understanding of administrators' motives that contribute to initiating these programs suggests there is much to be learned in this field. This study aimed to investigate administrators'…

  18. [Preparation and administration of cytotoxic drugs: prickly innovation].

    PubMed

    Mullot, H; Simon, L; Payen, C; Gentes, P

    2005-06-01

    The requirement for safe and optimal administration of cytotoxic drugs led us to test a new product manufactured by Codan. The transfer set (CONNECT SET) and the administration set (CYTO-AD-SET) were assessed successively by pharmacist assistance within a centralized unit for cytotoxic drug preparation and by the nursing staff in an ambulatory unit. Transfer sets can be handled in the centralized units without using needles, but with an increased sterilization load and production cost. Assessment of the administration sets demonstrated time saving for the nursing staff. These materials require significant expenditures, careful training, and a change in treatment routine, but provide important time savings for the nursing staff and considerable improvement in the safety of handling cytotoxic drugs.

  19. Prolonged withdrawal following cocaine self-administration increases resistance to punishment in a cocaine binge.

    PubMed

    Gancarz-Kausch, Amy M; Adank, Danielle N; Dietz, David M

    2014-11-03

    Drug addiction is characterized by compulsive drug-taking behaviors and a high propensity to relapse following drug cessation. Drug craving and seeking can increase during a period of abstinence, but this phenomenon is not observed in drug-induced reinstatement models. To investigate the effect of withdrawal on cocaine relapse, rats were exposed to extended-access cocaine self-administration and subjected to either 1 or 30 d of withdrawal. When tested during 12 h unlimited access to cocaine (binge), the duration of the withdrawal did not influence cocaine intake. However, using a histamine punishment procedure that greatly suppresses drug-taking behavior, we demonstrate that longer periods of abstinence from cocaine induce a greater persistence in responding for drug in the face of negative consequences.

  20. Short-term administration of rhGH increases markers of cellular proliferation but not milk protein gene expression in normal lactating women

    PubMed Central

    Maningat, Patricia D.; Sen, Partha; Rijnkels, Monique; Hadsell, Darryl L.; Bray, Molly S.

    2011-01-01

    Growth hormone is one of few pharmacologic agents known to augment milk production in humans. We hypothesized that recombinant human GH (rhGH) increases the expression of cell proliferation and milk protein synthesis genes. Sequential milk and blood samples collected over four days were obtained from five normal lactating women. Following 24 h of baseline milk and blood sampling, rhGH (0.1 mg/kg/day) was administered subcutaneously once daily for 3 days. Gene expression changes were determined by microarray studies utilizing milk fat globule RNA isolated from each milk sample. Following rhGH administration, DNA synthesis and cell cycle genes were induced, while no significant changes were observed in the expression of milk synthesis genes. Expression of glycolysis and citric acid cycle genes were increased by day 4 compared with day 1, while lipid synthesis genes displayed a circadian-like pattern. Cell cycle gene upregulation occurred after a lag of ∼2 days, likely explaining the failure to increase milk production after only 3 days of rhGH treatment. We conclude that rhGH induces expression of cellular proliferation and metabolism genes but does not induce milk protein gene expression, as potential mechanisms for increasing milk production and could account for the known effect of rhGH to increase milk production following 7–10 days. PMID:21205870

  1. Changes in oral ethanol self-administration patterns resulting from ethanol concentration manipulations.

    PubMed

    Slawecki, C J; Samson, H H

    1997-09-01

    A variety of initiation procedures have been used to develop oral ethanol consumption. Using the sucrose-substitution procedure, oral self-administration of ethanol-water solutions with ethanol concentrations as high as 40% can be initiated in food- and fluid-sated rats. An important question for these models is the relationship between ethanol concentration and self-administration patterns after initiation. This study examined the differential patterns of ethanol self-administration maintained by a range of ethanol solutions (10 to 30%) over a 5-week period, compared with rats maintained on 10% ethanol for 5 weeks. In 43 male Long Evans rats, the sucrose-substitution procedure was used to initiate responding maintained by 10% ethanol on a Fixed Ratio 4 schedule of reinforcement. The ethanol concentration presented was then increased to 30% in stepwise fashion and then returned to 10% [Ethanol Concentration Manipulation (ECM) group, n = 32], or 10% ethanol was maintained as the reinforcer for 5 weeks [Control (Con) group, n = 11]. Significant increases in ethanol intake and decreases in responding were associated with increased ethanol concentration. Although no overall differences in total session responding were observed in either group between week 1 and week 5 (10E vs. 10E), examination of changes in initial low responders of the ECM group revealed significant increases in responding that were not observed in the initial low responders of the Con group. Significant increases in momentary response rates were observed on both the ECM and Con groups, independent of the ethanol concentration presented. Increases in response rate in the ECM group were the result of increases in initial low rate and high rate responders; however, the increased response rates in the Con group were the result of increases only in the initial low rate responders. These data suggest that the ECM procedure can aid in the initiation of ethanol self-administration and may be particularly

  2. Progressive increase in brain glucose metabolism after intrathecal administration of autologous mesenchymal stromal cells in patients with diffuse axonal injury.

    PubMed

    Vaquero, Jesús; Zurita, Mercedes; Bonilla, Celia; Fernández, Cecilia; Rubio, Juan J; Mucientes, Jorge; Rodriguez, Begoña; Blanco, Edelio; Donis, Luis

    2017-01-01

    Cell therapy in neurological disability after traumatic brain injury (TBI) is in its initial clinical stage. We describe our preliminary clinical experience with three patients with diffuse axonal injury (DAI) who were treated with intrathecal administration of autologous mesenchymal stromal cells (MSCs). Three patients with established neurological sequelae due to DAI received intrathecally autologous MSCs. The total number of MSCs administered was 60 × 10 6 (one patient), 100 × 10 6 (one patient) and 300 × 10 6 (one patient). All three patients showed improvement after cell therapy, and subsequent studies with 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) showed a diffuse and progressive increase in brain glucose metabolism. Our present results suggest benefit of intrathecal administration of MSCs in patients with DAI, as well as a relationship between this type of treatment and increase in brain glucose metabolism. These preliminary findings raise the question of convenience of assessing the potential benefit of intrathecal administration of MSCs for brain diseases in which a decrease in glucose metabolism represents a crucial pathophysiological finding, such as Alzheimer's disease (AD) and other dementias. Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  3. Laboratory alcohol self-administration experiments do not increase subsequent real-life drinking in young adult social drinkers

    PubMed Central

    Sommer, Christian; Seipt, Christian; Spreer, Maik; Blümke, Toni; Markovic, Alexandra; Jünger, Elisabeth; Plawecki, Martin H.; Zimmermann, Ulrich S.

    2015-01-01

    Background While the utility of experimental free-access alcohol self-administration paradigms is well-established, little data exist addressing the question of whether study participation influences subsequent natural alcohol consumption. We here present drinking reports of young adults before and after participation in intravenous alcohol self-administration studies. Methods Timeline Follow-back (TLFB) drinking reports for the 6 weeks immediately preceding the first, and the 6 weeks after the last experimental alcohol challenge were examined from subjects completing one of two similar alcohol self-administration paradigms. In study 1, eighteen social drinkers (9 females, mean age 24.1 years) participated in 3 alcohol self-infusion sessions up to a maximum blood alcohol concentration (BAC) of 160 mg%. Study 2 involved 60 participants (30 females, mean age 18.3 years) of the Dresden Longitudinal Study on Alcohol Use in Young Adults (D-LAYA), who participated in 2 sessions of alcohol self-infusion up to a maximum BAC of 120 mg%, and a non-exposed age- matched control group of 42 (28 females, mean age 18.4 years) subjects. Results In study 1, participants reported (3.7%) fewer heavy drinking days as well as a decrease of 2.5 drinks per drinking day after study participation compared to pre-study levels (p<.05 respectively).. In study 2, alcohol-exposed participants reported 7.1% and non- alcohol-exposed controls 6.5% fewer drinking days at post-study measurement (p<.001), while percent heavy drinking days and drinks per drinking day did not differ. Conclusion These data suggest that participation in intravenous alcohol self-administration experiments does not increase subsequent real-life drinking of young adults. PMID:25903217

  4. Test Administration Models

    ERIC Educational Resources Information Center

    Becker, Kirk A.; Bergstrom, Betty A.

    2013-01-01

    The need for increased exam security, improved test formats, more flexible scheduling, better measurement, and more efficient administrative processes has caused testing agencies to consider converting the administration of their exams from paper-and-pencil to computer-based testing (CBT). Many decisions must be made in order to provide an optimal…

  5. Repeated administration of aripiprazole produces a sensitization effect in the suppression of avoidance responding and phencyclidine-induced hyperlocomotion and increases D2 receptor-mediated behavioral function.

    PubMed

    Gao, Jun; Qin, Rongyin; Li, Ming

    2015-04-01

    The present study investigated how repeated administration of aripiprazole (a novel antipsychotic drug) alters its behavioral effects in two behavioral tests of antipsychotic activity and whether this alteration is correlated with an increase in dopamine D2 receptor function. Male adult Sprague-Dawley rats were first repeatedly tested with aripiprazole (3, 10 and 30 mg/kg, subcutaneously (sc)) or vehicle in a conditioned avoidance response (CAR) test or a phencyclidine (PCP) (3.20 mg/kg, sc)-induced hyperlocomotion test daily for five consecutive days. After 2-3 days of drug-free retraining or resting, all rats were then challenged with aripiprazole (1.5 or 3.0 mg/kg, sc). Repeated administration of aripiprazole progressively increased its inhibition of avoidance responding and PCP-induced hyperlocomotion. More importantly, rats previously treated with aripiprazole showed significantly lower avoidance response and lower PCP-induced hyperlocomotion than those previously treated with vehicle in the challenge tests. An increased sensitivity to quinpirole (a selective D2/3 agonist) in prior aripiprazole-treated rats was also found in the quinpirole-induced hyperlocomotion test, suggesting an enhanced D2/3-mediated function. These findings suggest that aripiprazole, despite its distinct receptor mechanisms of action, induces a sensitization effect similar to those induced by other antipsychotic drugs and this effect may be partially mediated by brain plasticity involving D2/3 receptor systems. © The Author(s) 2014.

  6. Repeated administration of aripiprazole produces a sensitization effect in the suppression of avoidance responding and phencyclidine-induced hyperlocomotion and increases D2 receptor-mediated behavioral function

    PubMed Central

    Gao, Jun; Qin, Rongyin; Li, Ming

    2016-01-01

    The present study investigated how repeated administration of aripiprazole (a novel antipsychotic drug) alters its behavioral effects in two behavioral tests of antipsychotic activity and whether this alteration is correlated with an increase in dopamine D2 receptor function. Male adult Sprague-Dawley rats were first repeatedly tested with aripiprazole (3, 10 and 30 mg/kg, subcutaneously (sc)) or vehicle in a conditioned avoidance response (CAR) test or a phencyclidine (PCP) (3.20 mg/kg, sc)-induced hyperlocomotion test daily for five consecutive days. After 2–3 days of drug-free retraining or resting, all rats were then challenged with aripiprazole (1.5 or 3.0 mg/kg, sc). Repeated administration of aripiprazole progressively increased its inhibition of avoidance responding and PCP-induced hyperlocomotion. More importantly, rats previously treated with aripiprazole showed significantly lower avoidance response and lower PCP-induced hyperlocomotion than those previously treated with vehicle in the challenge tests. An increased sensitivity to quinpirole (a selective D2/3 agonist) in prior aripiprazole-treated rats was also found in the quinpirole-induced hyperlocomotion test, suggesting an enhanced D2/3-mediated function. These findings suggest that aripiprazole, despite its distinct receptor mechanisms of action, induces a sensitization effect similar to those induced by other antipsychotic drugs and this effect may be partially mediated by brain plasticity involving D2/3 receptor systems. PMID:25586399

  7. Caffeine Induces a Stimulant Effect and Increases Dopamine Release in the Nucleus Accumbens Shell Through the Pulmonary Inhalation Route of Administration in Rats.

    PubMed

    Galvalisi, Martín; Prieto, José Pedro; Martínez, Marcela; Abin-Carriquiry, Juan Andrés; Scorza, Cecilia

    2017-01-01

    Oral, intraperitoneal, or intravenous have been the common routes of administration used to study the behavioral and neurochemical pharmacology of caffeine, one of the most widely used psychoactive substances worldwide. We have reported that caffeine is an active adulterant frequently found in coca-paste (CP)-seized samples, a highly addictive form of smokable cocaine. The role of caffeine in the psychostimulant and neurochemical effects induced by CP remains under study. No preclinical animal studies have been performed so far to characterize the effects of caffeine when it is administered through the pulmonary inhalation route. Caffeine (10, 25, and 50 mg) was volatilized and rats were exposed to one inhalation session of its vapor. The stimulant effect was automatically recorded and plasmatic levels of caffeine were measured. Caffeine capability (50 mg) to increase extracellular dopamine (DA) levels in nucleus accumbens shell was also studied by in vivo microdialysis in non-anesthetized animals. A dose-dependent stimulant effect induced by volatilized caffeine was observed and this effect was directly related with caffeine plasmatic levels. A significant increase in the extracellular DA was achieved after 50 mg of volatilized caffeine exposure. This is the first report showing pharmacological acute effects of caffeine through the pulmonary inhalation route of administration and suggests that this could be a condition under which caffeine can elevate its weak reinforcing effect and even enhance the psychostimulant effect and abuse liability of smokable adulterated psychostimulant drugs.

  8. Trends and Indicators: Pension Money in the Stock Market; One-Year Percentage Increases in Median Salaries of College Administrators.

    ERIC Educational Resources Information Center

    Chronicle of Higher Education, 1992

    1992-01-01

    Trends in Teachers Insurance and Annuities Association (TIAA) and College Retirement Equities Fund (CREF) investments as compared with Standard and Poor's 500 stocks are graphed for 1989-92; and increases in college administrator salaries, by institution type and job type, are tabulated for each academic year, 1988-89 through 1991-92. (MSE)

  9. Subacute Zinc Administration and L-NAME Caused an Increase of NO, Zinc, Lipoperoxidation, and Caspase-3 during a Cerebral Hypoxia-Ischemia Process in the Rat

    PubMed Central

    Blanco-Alvarez, Victor Manuel; Lopez-Moreno, Patricia; Soto-Rodriguez, Guadalupe; Martinez-Fong, Daniel; Rubio, Hector; Gonzalez-Barrios, Juan Antonio; Piña-Leyva, Celia; Torres-Soto, Maricela; Gomez-Villalobos, María de Jesus; Hernandez-Baltazar, Daniel; Eguibar, José Ramon; Ugarte, Araceli; Cebada, Jorge

    2013-01-01

    Zinc or L-NAME administration has been shown to be protector agents, decreasing oxidative stress and cell death. However, the treatment with zinc and L-NAME by intraperitoneal injection has not been studied. The aim of our work was to study the effect of zinc and L-NAME administration on nitrosative stress and cell death. Male Wistar rats were treated with ZnCl2 (2.5 mg/kg each 24 h, for 4 days) and N-ω-nitro-L-arginine-methyl ester (L-NAME, 10 mg/kg) on the day 5 (1 hour before a common carotid-artery occlusion (CCAO)). The temporoparietal cortex and hippocampus were dissected, and zinc, nitrites, and lipoperoxidation were assayed at different times. Cell death was assayed by histopathology using hematoxylin-eosin staining and caspase-3 active by immunostaining. The subacute administration of zinc before CCAO decreases the levels of zinc, nitrites, lipoperoxidation, and cell death in the late phase of the ischemia. L-NAME administration in the rats treated with zinc showed an increase of zinc levels in the early phase and increase of zinc, nitrites, and lipoperoxidation levels, cell death by necrosis, and the apoptosis in the late phase. These results suggest that the use of these two therapeutic strategies increased the injury caused by the CCAO, unlike the alone administration of zinc. PMID:23997853

  10. Iontophoresis significantly increases the trans-dentinal delivery of osteoprotegerin, alendronate, and calcitonin.

    PubMed

    Kitchens, James A; Schwartz, Scott A; Schindler, William G; Hargreaves, Kenneth M

    2007-10-01

    The purpose of this study was to evaluate the delivery of alendronate, calcitonin, and osteoprotegerin (OPG) through human dentin by both diffusion and iontophoresis for the potential treatment of invasive cervical resorption. Radiolabeled alendronate, calcitonin, and OPG were added to the top of a split chamber device that contained 1-mm thick dentin disks devoid of a smear layer. Transdentinal movement of medicaments by either random diffusion or application of an iontophoretic current was measured by analysis of gamma emission of effluent fractions. In addition, calcitonin delivery was evaluated at differing magnitudes of current (0-4 mA) by using the aforementioned chamber. Diffusion of all 3 medicaments was minimal. In contrast, the application of a 3-mA iontophoretic gradient significantly increased delivery for all 3 compounds at 10-, 20-, and 30-minute intervals. In addition, a linear increase in permeability was seen for calcitonin as milliamperes were increased from 0 to 4 (r = 0.947), with more than a 100-fold increase in delivery observed with iontophoresis. Delivery of the tested medicaments by using iontophoresis might prove to be a useful technique for treatment of invasive cervical resorption.

  11. Administrators' Perceptions of Factors Related to Student Retention at Colleges with a Significant Black Student Enrollment Affiliated with the Association for Biblical Higher Education

    ERIC Educational Resources Information Center

    Wilson, Wesley B.

    2013-01-01

    This study described and explored the factors perceived as relevant to student retention by administrators at colleges and universities with significant Black student populations. The sample was 31 institutions affiliated with the Association for Biblical Higher Education (ABHE) that had Black student enrollment of 20% or more. The study sought to…

  12. Modernizing Administration.

    ERIC Educational Resources Information Center

    Lombardi, Vincent L.; Hildebrand, Verna

    1981-01-01

    Suggests assignment of research duties and rotation of teaching and management roles for college administrators, to increase their effectiveness and diminish the negative effects of declining enrollments. (JD)

  13. Electroporation-delivered transdermal neostigmine in rats: equivalent action to intravenous administration

    PubMed Central

    Berkó, Szilvia; Szűcs, Kálmán F; Balázs, Boglárka; Csányi, Erzsébet; Varju, Gábor; Sztojkov-Ivanov, Anita; Budai-Szűcs, Mária; Bóta, Judit; Gáspár, Róbert

    2016-01-01

    Purpose Transdermal electroporation has become one of the most promising noninvasive methods for drug administration, with greatly increased transport of macromolecules through the skin. The cecal-contracting effects of repeated transdermal electroporation delivery and intravenous administration of neostigmine were compared in anesthetized rats. Methods The cecal contractions were detected with implantable strain gauge sensors, and the plasma levels of neostigmine were followed by high-performance liquid chromatography. Results Both intravenously and EP-administered neostigmine (0.2–66.7 μg/kg) increased the cecal contractions in a dose-dependent manner. For both the low doses and the highest dose, the neostigmine plasma concentrations were the same after the two modes of administration, while an insignificantly higher level was observed at a dose of 20 μg/kg after intravenous administration as compared with the electroporation route. The contractile responses did not differ significantly after the two administration routes. Conclusion The results suggest that electroporation-delivered neostigmine elicits action equivalent to that observed after intravenous administration as concerning both time and intensity. Electroporation permits the delivery of even lower doses of water-soluble compounds through the skin, which is very promising for clinical practice. PMID:27274203

  14. Substantially increased sildenafil bioavailability after sublingual administration in children with congenital heart disease: two case reports

    PubMed Central

    2014-01-01

    Introduction Pulmonary hypertension is a progressive disease of diverse origin with devastating consequences in adults as well as in children. The phosphodiesterase 5 inhibitor sildenafil successfully lowers pulmonary vascular resistance. However, because of its poor enteral absorption, resulting in ineffective plasma concentrations, responses in infants and children are often erratic. Case presentations We report the cases of two Caucasian boys, one born at term (case 1) and one aged 2.5 years (case 2), who had structural cardiac and pulmonary defects accompanied by symptomatic pulmonary hypertension. They received sildenafil enterally and sublingually and also intravenously in one of them. Plasma samples were taken at various time points to determine the plasma concentrations of sildenafil and its partially active metabolite. Sildenafil and N-desmethyl sildenafil were quantified using a validated liquid chromatography/mass spectrometry method. Oxygen partial pressure was determined from routine arterial blood gas samples. Conclusion In agreement with previous observations in adults, we found that sublingual sildenafil was more extensively absorbed in our two pediatric patients. After sublingual administration, sildenafil plasma concentrations increased by 314% to 361% compared to enteral dosing. Concurrently, the metabolic ratio increased, suggesting not only that the overall absorption was enhanced but also that first-pass metabolism was partially bypassed. In case 2, the free fraction of sildenafil was 0.9%, which is considerably less than in adults (4%), suggesting that, in case 2, higher plasma concentration would have been needed to achieve effects similar to those in adults. Sublingual sildenafil appears to be a promising alternative route of administration in children with poor enteral absorption. PMID:24885923

  15. Effects of daily delta-9-tetrahydrocannabinol treatment on heroin self-administration in rhesus monkeys

    PubMed Central

    Maguire, David R.; France, Charles P.

    2015-01-01

    Opioid abuse remains a significant public health problem; together with the greater availability of marijuana in some regions there is an increasing likelihood that opioids and marijuana will be used together. Poly-drug abuse is associated with increased toxicity and poorer treatment outcome; thus, a better understanding of the consequences of repeated co-administration of these drugs will facilitate the development of better prevention and treatment strategies. This study examined the effects of daily treatment with the cannabinoid receptor agonist delta-9-tetrahydrocannabinol (Δ9-THC) and its discontinuation on self-administration of heroin in rhesus monkeys (n=4) lever-pressing under a fixed-ratio 30 schedule. Heroin self-administration (0.32–32 μg/kg/infusion, i.v.) generated an inverted U-shaped dose–effect curve. Administered acutely, Δ9-THC (0.01–0.32 mg/kg, s.c.) dose dependently decreased responding for heroin and flattened the self-administration dose-effect curve. Daily treatment with Δ9-THC (0.01–0.1 mg/kg/12hr, s.c.) either had no effect on or decreased responding for heroin. In addition, daily treatment did not significantly impact extinction of heroin self-administration or resumption of responding for heroin after extinction. Discontinuation of daily Δ9-THC treatment did not systematically impact rates of heroin self-administration. These data suggest that repeated administration of a cannabinoid receptor agonist likely does not increase, and possibly decreases, the positive reinforcing effects of a mu opioid receptor agonist. PMID:26397756

  16. Effects of daily delta-9-tetrahydrocannabinol treatment on heroin self-administration in rhesus monkeys.

    PubMed

    Maguire, David R; France, Charles P

    2016-04-01

    Opioid abuse remains a significant public health problem; together with the greater availability of marijuana in some regions there is an increasing likelihood that opioids and marijuana will be used together. Polydrug abuse is associated with increased toxicity and poorer treatment outcome; thus, a better understanding of the consequences of repeated coadministration of these drugs will facilitate the development of better prevention and treatment strategies. This study examined the effects of daily treatment with the cannabinoid receptor agonist delta-9-tetrahydrocannabinol (Δ-THC) and its discontinuation on self-administration of heroin in rhesus monkeys (n=4) lever-pressing under a fixed-ratio 30 schedule. Heroin self-administration (0.32-32 μg/kg/infusion, intravenously) generated an inverted U-shaped dose-effect curve. Administered acutely, Δ-THC (0.01-0.32 mg/kg, subcutaneously) dose dependently decreased responding for heroin and flattened the self-administration dose-effect curve. Daily treatment with Δ-THC (0.01-0.1 mg/kg/12 h, subcutaneously) either had no effect on or decreased responding for heroin. In addition, daily treatment did not significantly impact extinction of heroin self-administration or resumption of responding for heroin after extinction. Discontinuation of daily Δ-THC treatment did not systematically impact rates of heroin self-administration. These data suggest that repeated administration of a cannabinoid receptor agonist likely does not increase, and possibly decreases, the positive reinforcing effects of a mu opioid receptor agonist.

  17. 75 FR 18014 - Federal Highway Administration

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-08

    ... DEPARTMENT OF TRANSPORTATION Federal Highway Administration AGENCY: Federal Highway Administration (FHWA), DOT. ACTION: Notice of Availability regarding a Finding of No Significant Impact (FONSI): U.S.... FOR FURTHER INFORMATION CONTACT: Federal Highway Administration, Kentucky Division: Mr. Greg Rawlings...

  18. Repeated Lentivirus-Mediated Granulocyte Colony-Stimulating Factor Administration to Treat Canine Cyclic Neutropenia

    PubMed Central

    Yanay, Ofer; Dale, David C.

    2012-01-01

    Abstract Cyclic neutropenia occurs in humans and gray collie dogs, is characterized by recurrent neutropenia, and is treated by repeated injections of recombinant granulocyte colony-stimulating factor (rG-CSF). As dose escalation of lentivirus may be clinically necessary, we monitored the outcome of four sequential intramuscular injections of G-CSF-lentivirus (3×107 IU/kg body weight) to a normal dog and a gray collie. In the normal dog absolute neutrophil counts were significantly increased after each dose of virus, with mean levels of 27.75±3.00, 31.50±1.40, 35.05±1.68, and 43.88±2.94×103 cells/μl, respectively (p<0.001), and elevated neutrophil counts of 31.18±7.81×103 cells/μl were maintained for more than 6 years with no adverse effects. A gray collie dog with a mean count of 1.94±1.48×103 cells/μl received G-CSF-lentivirus and we observed sustained elevations in neutrophil levels for more than 5 months with a mean of 26.00±11.00×103 cells/μl, significantly increased over the pretreatment level (p<0.001). After the second and third virus administrations mean neutrophil counts of 15.80±6.14 and 11.52±4.90×103 cells/μl were significantly reduced compared with cell counts after the first virus administration (p<0.001). However, after the fourth virus administration mean neutrophil counts of 15.21±4.50×103 cells/μl were significantly increased compared with the previous administration (p<0.05). Throughout the nearly 3 years of virus administrations the dog gained weight, was healthy, and showed neutrophil counts significantly higher than pretreatment levels (p<0.001). These studies suggest that patients with cyclic and other neutropenias may be treated with escalating doses of G-CSF-lentivirus to obtain a desired therapeutic neutrophil count. PMID:22845776

  19. Rapid Bolus Administration Does not Increase The Extravasation Rate of Albumin: A Randomized Controlled Trial in The Endotoxemic Pig.

    PubMed

    von Seth, Magnus; Lipcsey, Miklós; Engström, Peter; Larsson, Anders; Hillered, Lars; Maripuu, Enn; Widström, Charles; Sjölin, Jan

    2017-04-01

    Some experimental data suggest that rapid bolus administration of albumin causes less plasma-expanding effects than slow, continuous infusion. To determine whether rapid bolus administration, in comparison with slow infusion, results in greater extravasation of albumin in experimental septic shock we performed a randomized controlled trial with 32 endotoxemic pigs. The animals were monitored and ventilated with standard intensive care equipment and given 10 mL × kg 5% albumin labeled with Technetium-99m, either as a rapid 15-min bolus (Bolus group, n = 16) or as a 2-h infusion (Infusion group, n = 16). Radioactivity was monitored in plasma, extracellular microdialysate, and urine for 6 h. Physiological parameters were monitored hourly. Radioactivity in the liver, spleen, kidney, and lung was analyzed post mortem.The plasma area under the curve activity0-6 h was 4.4 ± 0.9 × 10 in the Bolus group and 4.4 ± 1.1 × 10 counts × min × mL × h in the Infusion group. Blood hemoglobin levels increased in both groups, suggesting severe capillary leakage. Yet, there were no group differences in albumin radioactivity in plasma, muscle tissue, urine, or in the post-mortem analysis of the organs. Following albumin administration, circulatory and respiratory parameters were similar in the two groups.In conclusion, the present results suggest that albumin might be given as a bolus without leading to increased extravasation of albumin, in contrast to previous animal experiments in rodents.

  20. Estriol administration modulates luteinizing hormone secretion in women with functional hypothalamic amenorrhea.

    PubMed

    Genazzani, Alessandro D; Meczekalski, Blazej; Podfigurna-Stopa, Agnieszka; Santagni, Susanna; Rattighieri, Erica; Ricchieri, Federica; Chierchia, Elisa; Simoncini, Tommaso

    2012-02-01

    To evaluate the influence of estriol administration on the hypothalamus-pituitary function and gonadotropins secretion in patients affected by functional hypothalamic amenorrhea (FHA). Controlled clinical study. Patients with FHA in a clinical research environment. Twelve hypogonadotropic patients affected by FHA. Pulsatility study of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), and a gonadotropin-releasing hormone (GnRH) test (10 μg in bolus) at baseline condition and after 8 weeks of therapy with 2 mg/day of estriol. Measurements of plasma LH, FSH, estradiol (E(2)), androstenedione (A), 17α-hydroxyprogesterone (17-OHP), cortisol, androstenedione (A), testosterone (T), thyroid-stimulating hormone (TSH), free triiodothyronine (fT(3)), free thyroxine (fT(4)), and insulin, and pulse detection. After treatment, the FHA patients showed a statistically significant increase of LH plasma levels (from 0.7 ± 0.1 mIU/mL to 3.5 ± 0.3 mIU/mL) and a statistically significant increase of LH pulse amplitude with no changes in LH pulse frequency. In addition, the LH response to the GnRH bolus was a statistically significant increase. Estriol administration induced the increase of LH plasma levels in FHA and improved GnRH-induced LH secretion. These findings suggest that estriol administration modulates the neuroendocrine control of the hypothalamus-pituitary unit and induces the recovery of LH synthesis and secretion in hypogonadotropic patients with FHA. Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  1. Urinary and plasma oxytocin changes in response to MDMA or intranasal oxytocin administration.

    PubMed

    Francis, Sunday M; Kirkpatrick, Matthew G; de Wit, Harriet; Jacob, Suma

    2016-12-01

    The neuropeptide oxytocin (OT) has received increased experimental attention for its putative role in both normal social functioning and several psychiatric disorders that are partially characterized by social dysfunction (e.g., autism spectrum disorders: ASD). Many human experimental studies measure circulating plasma levels of OT in order to examine the relationship between the hormone and behavior. Urinary OT (uOT) assays offer a simple, easy, and non-invasive method to measure peripheral hormone levels, but the correspondence between uOT and plasma OT (pOT) levels is unclear. Here, we conducted two within-subjects, double-blind studies exploring changes in uOT and pOT levels following administration of two drugs: MDMA, an oxytocin-releasing drug (Study 1), and intranasal oxytocin (INOT: Study 1 and 2). In Study 1, 14 adult participants (2 females) were each administered either oral 1.5mg/kg MDMA or 40IU INOT across two different study sessions. In Study 2, 10 male participants (adolescents and young adults) diagnosed with ASD received either 40IU INOT or placebo across two different sessions. In both studies, blood and urine samples were collected before and after drug administration at each study session. For Study 1, 10 participants provided valid plasma and urine samples for the MDMA session, and 8 provided valid samples for the INOT session. For Study 2, all 10 participants provided valid samples for both INOT and placebo sessions. Pre- and post-administration levels of pOT and uOT were compared. Additionally, correlations between percent change from baseline uOT and pOT levels were examined. Study 1: Plasma OT and uOT levels significantly increased after administration of MDMA and INOT. Furthermore, uOT levels were positively correlated with pOT levels following administration of MDMA (r=0.57, p=0.042) but not INOT (r=0.51, p=0.097). Study 2: There was a significant increase in uOT levels after administration of INOT, but not after administration of

  2. Enalapril and diltiazem co-administration and respiratory side effects of enalapril.

    PubMed

    Franová, S; Nosál'ová, G; Antosová, M; Nosál', S

    2005-01-01

    A persistent, chronic dry cough is the most common adverse effect of angiotensin converting enzyme (ACE) inhibitors therapy. The mechanism of this respiratory adverse effect is related to the inhibition of ACE and the accumulation of bradykinin, substance P, prostanoids and other inflammatory neuropeptides in the airways. The aim of this study was to follow the relationship between 15-day administration of enalapril and the defense reflexes (cough and bronchoconstriction) of the airways in experimental animals, as well as the possibility of their pharmacological restriction with simultaneous diltiazem administration. Cough reflex was investigated by the method of mechanical irritation of laryngopharyngeal and tracheobronchial area in non-anesthetized cats. The reactivity of tracheal smooth muscles of the airways to bronchoconstrictor mediators (histamine 10 nM - 1 mM, acetylcholine 10 nM - 1 mM and KCl 1 mM - 100 mM) was evaluated by an in vitro method in guinea pigs. Enalapril 5 mg/kg/day and diltiazem 30 mg/kg/day were administered perorally for 15 days. The results showed that long-lasting administration of enalapril resulted in a significant increase of measured cough parameters and increased reactivity of tracheal smooth muscle to histamine and KCl. Simultaneous administration of enalapril together with diltiazem significantly decreased the enalapril induced cough, and decreased enalapril induced hyperreactivity of tracheal smooth muscles to KCl. The results showed a partially protective effect of diltiazem and enalapril co-administration on the respiratory adverse effects induced by enalapril therapy.

  3. Serotonergic disturbances in autistic disorder: L-5-hydroxytryptophan administration to autistic youngsters increases the blood concentrations of serotonin in patients but not in controls.

    PubMed

    Croonenberghs, Jan; Verkerk, Robert; Scharpe, Simon; Deboutte, Dirk; Maes, Michael

    2005-03-25

    Some studies have suggested that disorders in the peripheral and central metabolism of serotonin (5-HT) may play a role in the pathophysiology of autistic disorder. This study examines the whole blood concentrations of 5-HT and 5-hydroxy-indoleacetic acid (5-HIAA) in baseline conditions and during a challenge with L-5-OH-tryptophane (5-HTP; 4 mg/kg in non enteric-coated tablets), the precursor of 5-HT, in a study group of 18 male, post-pubertal, Caucasian autistic patients (age 13-19 y.; I.Q.>55) and 20 matched healthy volunteers. In baseline conditions, no significant differences in 5-HT or 5-HIAA levels could be found between autistic youngsters and normal controls. 5-HTP administration significantly increased the levels of 5-HT in autistic youngsters but not in normal controls. Following 5-HTP challenge the 5-HT levels were significantly higher in autistic patients than in healthy volunteers. After challenge with 5-HTP, no significant differences were found in the concentrations of 5-HIAA or the test substance between autistic youngsters and normal controls. Differences in the peripheral metabolism of 5-HT which may not be observed in baseline conditions but which became clear after loading with 5-HTP, suggest that an increased synthesis of 5-HT from its precursor 5-HTP might be a one factor responsible for differences in the serotonergic system between autistic post-pubertal youngsters and normal controls.

  4. Cardiorespiratory effects of epidural administration of morphine and fentanyl in dogs anesthetized with sevoflurane.

    PubMed

    Naganobu, Kiyokazu; Maeda, Noriaki; Miyamoto, Toru; Hagio, Mitsuyoshi; Nakamura, Tadashi; Takasaki, Mayumi

    2004-01-01

    To determine the cardiorespiratory effects of epidural administration of morphine alone and in combination with fentanyl in dogs anesthetized with sevoflurane. Prospective study. 6 dogs. Dogs were anesthetized with sevoflurane and allowed to breathe spontaneously. After a stable plane of anesthesia was achieved, morphine (0.1 mg/kg [0.045 mg/lb]) or a combination of morphine and fentanyl (10 microg/kg [4.5 microg/lb]) was administered through an epidural catheter, the tip of which was positioned at the level of L6 or L7. Cardiorespiratory variables were measured for 90 minutes. Epidural administration of morphine alone did not cause any significant changes in cardiorespiratory measurements. However, epidural administration of morphine and fentanyl induced significant decreases in diastolic and mean arterial blood pressures and total peripheral resistance. Stroke volume was unchanged, PaCO2 was significantly increased, and arterial pH and base excess were significantly decreased. Heart rate was significantly lower after epidural administration of morphine and fentanyl than after administration of morphine alone. None of the dogs had any evidence of urine retention, vomiting, or pruritus after recovery from anesthesia. Results suggest that epidural administration of morphine at a dose of 0.1 mg/kg in combination with fentanyl at a dose of 10 microg/kg can cause cardiorespiratory depression in dogs anesthetized with sevoflurane.

  5. Chronic clenbuterol administration negatively alters cardiac function.

    PubMed

    Sleeper, Margaret M; Kearns, Charles F; McKeever, Kenneth H

    2002-04-01

    Chronic administration of pharmacological levels of beta2-agonists have been shown to have toxic effects on the heart; however, no data exist on cardiac function after chronic clenbuterol administration. The purpose of this study was to examine the effect of therapeutic levels of clenbuterol on cardiac performance. Twenty unfit Standardbred mares were divided into four experimental groups: clenbuterol (2.4 microg.kg(-1) twice daily 5 d.wk(-1)) plus exercise (20 min at 50% .VO(2max)) (CLENEX; N = 6), clenbuterol (CLEN; N = 6), exercise (EX; N = 4), and control (CON; N = 4). M-mode and two-dimensional echocardiography (2.5-MHz sector scanner transducer) were used to measure cardiac size and function before and immediately after an incremental exercise test, before and after 8 wk of drug and/or exercise treatments. After treatment, CLENEX and CLEN demonstrated significantly higher left ventricular internal dimension (LVD) at end diastole (+23.7 +/- 4.8%; +25.6 +/- 4.1%), LVD at end systole (+29.2 +/- 8.7%; +40.1 +/- 7.9%), interventricular septal wall thickness (IVS) at end diastole (+28.9 +/- 11.0%; +30.7 +/- 7.0%), IVS at end systole (+29.2 +/- 8.7%; +40.1 +/- 7.9%), and left ventricular posterior wall systolic thickness (+43.1 +/- 14.%; +45.8 +/- 14.1%). CLENEX and CLEN had significantly increased aortic root dimensions (+29.9 +/- 6.1%; +24.0 +/- 1.7%), suggesting increased risk of aortic rupture. Taken together, these data indicate that chronic clenbuterol administration may negatively alter cardiac function.

  6. Intranasal administration of oxytocin increases compassion toward women

    PubMed Central

    Palgi, Sharon; Klein, Ehud

    2015-01-01

    It has been suggested that the degree of compassion—the feeling of warmth, understanding and kindness that motivates the desire to help others, is modulated by observers’ views regarding the target’s vulnerability and suffering. This study tested the hypothesis that as compassion developed to protect vulnerable kinships, hormones such as oxytocin, which have been suggested as playing a key role in ‘tend-and-befriend’ behaviors among women, will enhance compassion toward women but not toward men. Thirty subjects participated in a double-blind, placebo-controlled, within-subject study. Following administration of oxytocin/placebo, participants listened to recordings of different female/male protagonists describing distressful emotional conflicts and were then asked to provide compassionate advice to the protagonist. The participants’ responses were coded according to various components of compassion by two clinical psychologists who were blind to the treatment. The results showed that in women and men participants oxytocin enhanced compassion toward women, but did not affect compassion toward men. These findings indicate that the oxytocinergic system differentially mediates compassion toward women and toward men, emphasizing an evolutionary perspective that views compassion as a caregiving behavior designed to help vulnerable individuals. PMID:24711542

  7. Fulfilment of administrative and professional organisational obligations and nurses' customer-oriented behaviours.

    PubMed

    Trybou, Jeroen; Gemmel, Paul

    2016-07-01

    The aim of the study was to examine the relationship between the perceived quality of organisational exchange and nurses' customer-oriented behaviours. Hospitals face increasing competitive market conditions. Registered nurses interact closely with patients and therefore play an important front-office role towards patients. A cross-sectional study was conducted. Registered nurses (n = 151) of a Belgian hospital received a questionnaire to assess the fulfilment of administrative and professional organisational obligations and their customer-oriented behaviours. We found a positive relationship between psychological contract fulfilment and nurses' customer-oriented behaviours. More precisely administrative and professional psychological contract fulfilment relates significantly to nurses' service delivery and external representation. In case of internal influence only administrative psychological contract fulfilment was significantly related. Nurses' perceptions of the fulfilment of administrative and professional obligations are important to their customer-oriented behaviours. Nurse managers must be aware of the impact of fulfilling both administrative and professional obligations of registered nurses in order to optimise their customer-oriented behaviours. © 2016 John Wiley & Sons Ltd.

  8. Increased ventilatory response to carbon dioxide in COPD patients following vitamin C administration

    PubMed Central

    Hartmann, Sara E.; Kissel, Christine K.; Szabo, Lian; Walker, Brandie L.; Leigh, Richard; Anderson, Todd J.

    2015-01-01

    Patients with chronic obstructive pulmonary disease (COPD) have decreased ventilatory and cerebrovascular responses to hypercapnia. Antioxidants increase the ventilatory response to hypercapnia in healthy humans. Cerebral blood flow is an important determinant of carbon dioxide/hydrogen ion concentration at the central chemoreceptors and may be affected by antioxidants. It is unknown whether antioxidants can improve the ventilatory and cerebral blood flow response in individuals in whom these are diminished. Thus, we aimed to determine the effect of vitamin C administration on the ventilatory and cerebrovascular responses to hypercapnia during healthy ageing and in COPD. Using transcranial Doppler ultrasound, we measured the ventilatory and cerebral blood flow responses to hyperoxic hypercapnia before and after an intravenous vitamin C infusion in healthy young (Younger) and older (Older) subjects and in moderate COPD. Vitamin C increased the ventilatory response in COPD patients (mean (95% CI) 1.1 (0.9–1.1) versus 1.5 (1.1–2.0) L·min−1·mmHg−1, p<0.05) but not in Younger (2.5 (1.9–3.1) versus 2.4 (1.9–2.9) L·min−1·mmHg−1, p>0.05) or Older (1.3 (1.0–1.7) versus 1.3 (1.0–1.7) L·min−1·mmHg−1, p>0.05) healthy subjects. Vitamin C did not affect the cerebral blood flow response in the young or older healthy subjects or COPD subjects (p>0.05). Vitamin C increases the ventilatory but not cerebrovascular response to hyperoxic hypercapnia in patients with moderate COPD. PMID:27730137

  9. Short-term administration of uridine increases brain membrane phospholipids precursors in healthy adults: a 31-phosphorus magnetic resonance spectroscopy study at 4T

    PubMed Central

    Agarwal, Nivedita; Sung, Young-Hoon; Jensen, J Eric; daCunha, Grace; Harper, David; Olson, David; Renshaw, Perry F

    2010-01-01

    Objectives Altered metabolism of membrane phospholipids has been implicated in bipolar disorder. In humans, uridine is an important precursor of cytidine diphosphate (CDP)-choline, which plays a critical role in phospholipid synthesis and is currently being evaluated as a potential treatment for bipolar depression. Methods A total of 17 healthy males (mean age ± SD: 32.73 ± 7.2 years; range: 21.8- 46.4 years) were enrolled in this study. Subjects underwent a 31-phosphorus magnetic resonance spectroscopy (31P-MRS) acquisition at baseline and then again after seven days of either 2 g of uridine or placebo administration. A two-dimensional chemical shift imaging 31P-MRS acquisition collected spectral data from a 4 × 4 cluster of voxels acquired in the axial plane encompassing the subcortical structures as well as frontaltemporal cortical gray and white matter. The slab thickness was 3 cm and the approximate total volume of brain sampled was 432 cm3. The spectra obtained were analyzed using a fully automated in-house fitting algorithm. A population-averaged generalized estimating equation was used to evaluate changes both in phosphomonoesters (PME) [phosphocholine (PCho) and phosphoethanolamine (PEtn)] and phosphodiesters (PDE) [glycerophosphocholine (GPCho) and glycerophosphethanolamine (GPEtn)]. Metabolite ratios were reported with respect to the total integrated 31P resonance area. Results The uridine group had significantly increased total PME and PEtn levels over the one-week period [6.32% and 7.17% for PME and PEtn, respectively (p < 0.001)]. Other metabolite levels such as PCho, PDE, GPEtn and GPCho showed no significant changes following either uridine or placebo (all p > 0.05). Conclusions This is the first study to report a direct effect of uridine on membrane phospholipid precursors in healthy adults using 31P-MRS. Sustained administration of uridine appears to increase PME in healthy subjects. Further investigation is required to clarify the effects of

  10. Valproic acid triggers increased mitochondrial biogenesis in POLG-deficient fibroblasts

    PubMed Central

    Sitarz, Kamil S.; Elliott, Hannah R.; Karaman, Betül S.; Relton, Caroline; Chinnery, Patrick F.; Horvath, Rita

    2014-01-01

    Valproic acid (VPA) is a widely used antiepileptic drug and also prescribed to treat migraine, chronic headache and bipolar disorder. Although it is usually well tolerated, a severe hepatotoxic reaction has been repeatedly reported after VPA administration. A profound toxic reaction on administration of VPA has been observed in several patients carrying POLG mutations, and heterozygous genetic variation in POLG has been strongly associated with VPA-induced liver toxicity. Here we studied the effect of VPA in fibroblasts of five patients carrying pathogenic mutations in the POLG gene. VPA administration caused a significant increase in the expression of POLG and several regulators of mitochondrial biogenesis. It was further supported by elevated mtDNA copy numbers. The effect of VPA on mitochondrial biogenesis was observed in both control and patient cell lines, but the capacity of mutant POLG to increase the expression of mitochondrial genes and to increase mtDNA copy numbers was less effective. No evidence of substantive differences in DNA methylation across the genome was observed between POLG mutated patients and controls. Given the marked perturbation of gene expression observed in the cell lines studied, we conclude that altered DNA methylation is unlikely to make a major contribution to POLG-mediated VPA toxicity. Our data provide experimental evidence that VPA triggers increased mitochondrial biogenesis by altering the expression of several mitochondrial genes; however, the capacity of POLG-deficient liver cells to address the increased metabolic rate caused by VPA administration is significantly impaired. PMID:24725338

  11. Intracerebroventricular oxytocin administration in rats enhances object recognition and increases expression of neurotrophins, microtubule-associated protein 2, and synapsin I.

    PubMed

    Havranek, Tomas; Zatkova, Martina; Lestanova, Zuzana; Bacova, Zuzana; Mravec, Boris; Hodosy, Julius; Strbak, Vladimir; Bakos, Jan

    2015-06-01

    Brain oxytocin regulates a variety of social and affiliative behaviors and affects also learning and memory. However, mechanisms of its action at the level of neuronal circuits are not fully understood. The present study tests the hypothesis that molecular factors required for memory formation and synaptic plasticity, including brain-derived neurotrophic factor, neural growth factor, nestin, microtubule-associated protein 2 (MAP2), and synapsin I, are enhanced by central administration of oxytocin. We also investigated whether oxytocin enhances object recognition and acts as anxiolytic agent. Therefore, male Wistar rats were infused continuously with oxytocin (20 ng/µl) via an osmotic minipump into the lateral cerebral ventricle for 7 days; controls were infused with vehicle. The object recognition test, open field test, and elevated plus maze test were performed on the sixth, seventh, and eighth days from starting the infusion. No significant effects of oxytocin on anxious-like behavior were observed. The object recognition test showed that oxytocin-treated rats significantly preferred unknown objects. Oxytocin treatment significantly increased gene expression and protein levels of neurotrophins, MAP2, and synapsin I in the hippocampus. No changes were observed in nestin expression. Our results provide the first direct evidence implicating oxytocin as a regulator of brain plasticity at the level of changes of neuronal growth factors, cytoskeletal proteins, and behavior. The data support assumption that oxytocin is important for short-term hippocampus-dependent memory. © 2015 Wiley Periodicals, Inc.

  12. Extended nicotine self-administration increases sensitivity to nicotine, motivation to seek nicotine and the reinforcing properties of nicotine-paired cues.

    PubMed

    Clemens, Kelly J; Lay, Belinda P P; Holmes, Nathan M

    2017-03-01

    An array of pharmacological and environmental factors influence the development and maintenance of tobacco addiction. The nature of these influences likely changes across the course of an extended smoking history, during which time drug seeking can become involuntary and uncontrolled. The present study used an animal model to examine the factors that drive nicotine-seeking behavior after either brief (10 days) or extended (40 days) self-administration training. In Experiment 1, extended training increased rats' sensitivity to nicotine, indicated by a leftward shift in the dose-response curve, and their motivation to work for nicotine, indicated by an increase in the break point achieved under a progressive ratio schedule. In Experiment 2, extended training imbued the nicotine-paired cue with the capacity to maintain responding to the same high level as nicotine itself. However, Experiment 3 showed that the mechanisms involved in responding for nicotine or a nicotine-paired cue are dissociable, as treatment with the partial nicotine receptor agonist, varenicline, suppressed responding for nicotine but potentiated responding for the nicotine-paired cue. Hence, across extended nicotine self-administration, pharmacological and environmental influences over nicotine seeking increase such that nicotine seeking is controlled by multiple sources, and therefore highly resistant to change. © 2015 Society for the Study of Addiction.

  13. Medication administration error: magnitude and associated factors among nurses in Ethiopia.

    PubMed

    Feleke, Senafikish Amsalu; Mulatu, Muluadam Abebe; Yesmaw, Yeshaneh Seyoum

    2015-01-01

    The significant impact of medication administration errors affect patients in terms of morbidity, mortality, adverse drug events, and increased length of hospital stay. It also increases costs for clinicians and healthcare systems. Due to this, assessing the magnitude and associated factors of medication administration error has a significant contribution for improving the quality of patient care. The aim of this study was to assess the magnitude and associated factors of medication administration errors among nurses at the Felege Hiwot Referral Hospital inpatient department. A prospective, observation-based, cross-sectional study was conducted from March 24-April 7, 2014 at the Felege Hiwot Referral Hospital inpatient department. A total of 82 nurses were interviewed using a pre-tested structured questionnaire, and observed while administering 360 medications by using a checklist supplemented with a review of medication charts. Data were analyzed by using SPSS version 20 software package and logistic regression was done to identify possible factors associated with medication administration error. The incidence of medication administration error was 199 (56.4 %). The majority (87.5 %) of the medications have documentation error, followed by technique error 263 (73.1 %) and time error 193 (53.6 %). Variables which were significantly associated with medication administration error include nurses between the ages of 18-25 years [Adjusted Odds Ratio (AOR) = 2.9, 95 % CI (1.65,6.38)], 26-30 years [AOR = 2.3, 95 % CI (1.55, 7.26)] and 31-40 years [AOR = 2.1, 95 % CI (1.07, 4.12)], work experience of less than or equal to 10 years [AOR = 1.7, 95 % CI (1.33, 4.99)], nurse to patient ratio of 7-10 [AOR = 1.6, 95 % CI (1.44, 3.19)] and greater than 10 [AOR = 1.5, 95 % CI (1.38, 3.89)], interruption of the respondent at the time of medication administration [AOR = 1.5, 95 % CI (1.14, 3.21)], night shift of medication administration

  14. Rebound increase in seizure susceptibility but not isolation-induced calls after single administration of clonazepam and Ro 19-8022 in infant rats.

    PubMed

    Mikulecká, A; Mareš, P; Kubová, H

    2011-01-01

    The purpose of our study was to determine whether a single administration of anticonvulsant doses of two ligands of benzodiazepine receptors, clonazepam and Ro 19-8022, leads to development of rebound phenomena in immature 12-day-old rats. Three tests were used: pentylenetetrazole (PTZ)-induced seizures, isolation-induced ultrasonic vocalizations, and motor performance. Susceptibility to the convulsant effects of PTZ decreased 24 hours, but increased 48 hours, after clonazepam administration. Ultrasonic vocalizations were completely suppressed 30 minutes and 3 hours after clonazepam; a moderate inhibitory effect persisted even at 48 hours. Motor abilities were slightly compromised up to 3 hours. Similar effects of Ro 19-8022 on PTZ-induced seizures and ultrasonic vocalizations were observed 24 and 48 hours after administration; motor performance was not affected. Rebound proconvulsant effects followed different time courses after administration of the two benzodiazepine receptor ligands in developing animals. Anxiolytic-like effects of these drugs were still present at the time when animals exhibited rebound proconvulsant effects. Copyright © 2010 Elsevier Inc. All rights reserved.

  15. The Administrator's Use of Microcomputer Systems.

    ERIC Educational Resources Information Center

    Brown, Kenneth C.

    1983-01-01

    The use of microcomputers by college administrators to increase productivity is discussed. Microcomputers can help increase productivity in the following administrative office tasks: decision support, communication, personal assistance, and task management. One of the most promising developments to emerge from the decision sciences over the past…

  16. Effect of Hypnosis During Administration of Local Anesthesia in Six- to 16-year-old Children.

    PubMed

    Oberoi, Jyoti; Panda, Anup; Garg, Iti

    2016-01-01

    Hypnosis is a tool that can help pediatric dentists allay fear or increase patient cooperation while administering local anesthesia. The purpose of this study was to determine whether hypnosis altered a patient's physical and/or verbal resistance and oxygen saturation or heart rate during administration of local anesthesia. Two hundred six- to 16-year-olds were randomly allocated to either a control group or an experimental group that received hypnotic induction prior to the delivery of local anesthesia. Subjects were monitored for signs of physical or verbal resistance and changes in pulse rate and oxygen saturation at baseline and upon administration of local anesthetic. Children under hypnosis exhibited significantly less resistance to administration of local anesthesia (P<0.05). A bi-serial correlation for age and resistance showed a significant positive correlation (0.337) in the experimental group, indicating that resistance in children increases with age, but none was shown between gender and hypnotic suggestibility. There was a significant difference in pulse rate, attributable to the hypnotic condition (P=.000), but not in oxygen saturation level. Using hypnosis may increase patient cooperation, decrease resistance during painful procedures, and lead to a lower heart rate.

  17. The usefulness of administrative databases for identifying disease cohorts is increased with a multivariate model.

    PubMed

    van Walraven, Carl; Austin, Peter C; Manuel, Douglas; Knoll, Greg; Jennings, Allison; Forster, Alan J

    2010-12-01

    Administrative databases commonly use codes to indicate diagnoses. These codes alone are often inadequate to accurately identify patients with particular conditions. In this study, we determined whether we could quantify the probability that a person has a particular disease-in this case renal failure-using other routinely collected information available in an administrative data set. This would allow the accurate identification of a disease cohort in an administrative database. We determined whether patients in a randomly selected 100,000 hospitalizations had kidney disease (defined as two or more sequential serum creatinines or the single admission creatinine indicating a calculated glomerular filtration rate less than 60 mL/min/1.73 m²). The independent association of patient- and hospitalization-level variables with renal failure was measured using a multivariate logistic regression model in a random 50% sample of the patients. The model was validated in the remaining patients. Twenty thousand seven hundred thirteen patients had kidney disease (20.7%). A diagnostic code of kidney disease was strongly associated with kidney disease (relative risk: 34.4), but the accuracy of the code was poor (sensitivity: 37.9%; specificity: 98.9%). Twenty-nine patient- and hospitalization-level variables entered the kidney disease model. This model had excellent discrimination (c-statistic: 90.1%) and accurately predicted the probability of true renal failure. The probability threshold that maximized sensitivity and specificity for the identification of true kidney disease was 21.3% (sensitivity: 80.0%; specificity: 82.2%). Multiple variables available in administrative databases can be combined to quantify the probability that a person has a particular disease. This process permits accurate identification of a disease cohort in an administrative database. These methods may be extended to other diagnoses or procedures and could both facilitate and clarify the use of

  18. Long-term aldosterone administration increases renal Na+-Cl- cotransporter abundance in late distal convoluted tubule.

    PubMed

    Poulsen, Søren Brandt; Christensen, Birgitte Mønster

    2017-09-01

    Renal Na + -Cl - cotransporter (NCC) is expressed in early distal convoluted tubule (DCT) 1 and late DCT (DCT2). NCC activity can be stimulated by aldosterone administration, and the mechanism is assumed to depend on the enzyme 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2), which inactivates glucocorticoids that would otherwise occupy aldosterone receptors. Because 11β-HSD2 in rat may only be abundantly expressed in DCT2 cells and not in DCT1 cells, it has been speculated that aldosterone specifically stimulates NCC activity in DCT2 cells. In mice, however, it is debated if 11β-HSD2 is expressed in DCT2 cells. The present study examined whether aldosterone administration in mice stimulates NCC abundance and phosphorylation in DCT2 cells but not in DCT1 cells. B6/C57 male mice were administered 100 µg aldosterone·kg body weight -1 ·24 h -1 for 6 days and euthanized during isoflurane inhalation. Western blotting of whole kidney homogenate showed that aldosterone administration stimulated NCC and pT58-NCC abundances ( P < 0.001). In DCT1 cells, confocal microscopy detected no effect of the aldosterone administration on NCC and pT58-NCC abundances. By contrast, NCC and pT58-NCC abundances were stimulated by aldosterone administration in the middle of DCT2 ( P < 0.001 and <0.01, respectively) and at the junction between DCT2 and CNT ( P < 0.001 and <0.05, respectively). In contrast to rat, immunohistochemistry in mouse showed no/very weak 11β-HSD2 expression in DCT2 cells. Collectively, long-term aldosterone administration stimulates mouse NCC and pT58-NCC abundances in DCT2 cells and presumably not in DCT1 cells. Copyright © 2017 the American Physiological Society.

  19. Nephrotoxicity in rabbits after long-term nandrolone decanoate administration.

    PubMed

    Tsitsimpikou, Christina; Vasilaki, Fotini; Tsarouhas, Konstantinos; Fragkiadaki, Persefoni; Tzardi, Maria; Goutzourelas, Nikolaos; Nepka, Charitini; Kalogeraki, Alexandra; Heretis, Ioannis; Epitropaki, Zoi; Kouretas, Dimitrios; Tsatsakis, Aristidis M

    2016-09-30

    Among the various side effects of supra-physiological dose of anabolic androgenic steroids that are described, renal toxicity remains the least evaluated. The present study provides evidence that long-term administration of nandrolone decanoate could lead to alterations of renal function and structure in the experimental rabbit model. A pronounced increase in serum urea, creatinine, SGOT and SGPT is observed in the treated animals, with intramuscular administration being more detrimental. Histopathological evaluation of kidneys indicated hyperaemia, fibrosis and focal inflammation. Furthermore, the significantly increased telomerase activity found in the kidneys of the intramuscularly treated animals could possibly represent a counteracting survival mechanism. Oxidative stress markers that were influenced the most were TBARS, indicating lipid peroxidation, and GSH. An interesting finding in our study though, was that while intramuscular administration showed the highest biochemical derangement, oxidative stress markers provided mixed results between intramuscularly and subcutaneously treated rabbits. In conclusion, nephrotoxicity of nandrolone decanoate remains a multi-factorial, partly irreversible effect that involves augmented tissue oxidative status. Copyright © 2016. Published by Elsevier Ireland Ltd.

  20. Amphiphysin I but not dynamin I nor synaptojanin mRNA expression increased after repeated methamphetamine administration in the rat cerebrum and cerebellum.

    PubMed

    Hamamura, Mitsuko; Okouchi, Jiro; Ozawa, Hidetoshi; Kimuro, Yoshihiko; Iwaki, Akiko; Fukumaki, Yasuyuki

    2013-07-01

    Dopamine increases/decreases synaptic vesicle recycling and in schizophrenia the proteins/mRNA is decreased. We isolated cDNA clone, similar to amphiphysin 1 (vesicle protein) mRNA from the neocortex of rats injected repeatedly with methamphetamine using polymerase chain reaction (PCR) differential display. This clone is highly homologous to the 3' region of the human amphiphysin gene. PCR extension study using a primer specific for the rat amphiphysin 1 gene and a primer located within the clone revealed that it is the 3' UTR region of the rat amphiphysin 1 gene. Furthermore, in situ hybridization revealed that amphiphysin 1 mRNA is expressed in the cerebrum, medial thalamus, hippocampus and cerebellum. In the cerebellum, amphiphysin mRNA expression was confined to upper granule cell layer. Repeated methamphetamine administration increased amphiphysin I mRNA expression in both anterior part of the cerebrum, and the cerebellum. However, the repeated administration did not alter mRNA expression of the other vesicle proteins, synaptotagmin I, synapsin I, synaptojanin and dynamin I, we conclude that the repeated administration selectively increased amphiphysin 1 mRNA expression. Thus, amphiphysin 1 does not work as synaptic recycling, but it is suggested, as a part of pathogenesis of brain tissue injury (under Ca²⁺ and Mg²⁺ devoid environment) in repeated methamphetamine-injected states, the gene regulate actin-asssembly, learning, cell stress signaling and cell polarity.

  1. Metabolomic Analysis of Blood Plasma after Oral Administration of N-acetyl-d-Glucosamine in Dogs

    PubMed Central

    Osaki, Tomohiro; Kurozumi, Seiji; Sato, Kimihiko; Terashi, Taro; Azuma, Kazuo; Murahata, Yusuke; Tsuka, Takeshi; Ito, Norihiko; Imagawa, Tomohiro; Minami, Saburo; Okamoto, Yoshiharu

    2015-01-01

    N-acetyl-d-glucosamine (GlcNAc) is a monosaccharide that polymerizes linearly through (1,4)-β-linkages. GlcNAc is the monomeric unit of the polymer chitin. GlcNAc is a basic component of hyaluronic acid and keratin sulfate found on the cell surface. The aim of this study was to examine amino acid metabolism after oral GlcNAc administration in dogs. Results showed that plasma levels of ectoine were significantly higher after oral administration of GlcNAc than prior to administration (p < 0.001). To our knowledge, there have been no reports of increased ectoine concentrations in the plasma. The mechanism by which GlcNAc administration leads to increased ectoine plasma concentration remains unclear; future studies are required to clarify this mechanism. PMID:26262626

  2. Oxidative stress and myocardial dysfunction in young rabbits after short term anabolic steroids administration.

    PubMed

    Germanakis, Ioannis; Tsarouhas, Konstantinos; Fragkiadaki, Persefoni; Tsitsimpikou, Christina; Goutzourelas, Nikolaos; Champsas, Maria Christakis; Stagos, Demetrios; Rentoukas, Elias; Tsatsakis, Aristidis M

    2013-11-01

    The present study focuses on the short term effects of repeated low level administration of turinabol and methanabol on cardiac function in young rabbits (4 months-old). The experimental scheme consisted of two oral administration periods, lasting 1 month each, interrupted by 1-month wash-out period. Serial echocardiographic evaluation at the end of all three experimental periods was performed in all animals. Oxidative stress markers have also been monitored at the end of each administration period. Treated animals originally showed significantly increased myocardial mass and systolic cardiac output, which normalized at the end of the wash out period. Re-administration led to increased cardiac output, at the cost though of a progressive myocardial mass reduction. A dose-dependent trend towards impaired longitudinal systolic, diastolic and global myocardial function was also observed. The adverse effects were more pronounced in the methanabol group. For both anabolic steroids studied, the low dose had no significant effects on oxidative stress markers monitored, while the high dose created a hostile oxidative environment. In conclusion, anabolic administration has been found to create a possible deleterious long term effect on the growth of the immature heart and should be strongly discouraged especially in young human subjects. Copyright © 2013 Elsevier Ltd. All rights reserved.

  3. Is pre-emptive administration of ketamine a significant adjunction to intravenous morphine analgesia for controlling postoperative pain? A randomized, double-blind, placebo-controlled clinical trial.

    PubMed

    Fiorelli, Alfonso; Mazzella, Antonio; Passavanti, Beatrice; Sansone, Pasquale; Chiodini, Paolo; Iannotti, Mario; Aurilio, Caterina; Santini, Mario; Pace, Maria Caterina

    2015-09-01

    To evaluate if the pre-emptive administration of ketamine would potentiate the effect of intravenous morphine analgesia in the management of post-thoracotomy pain. This was a unicentre, double-blind, placebo-controlled, parallel-group, prospective study. Patients were randomly assigned to receive 1 mg/kg ketamine (ketamine group) or an equivalent dose of normal saline (placebo group) before thoracotomy in 1:1 ratio. All patients received postoperatively intravenous morphine administration as additional analgesic regimen. Primary end-point was the pain relief measured with Visual Analogue Scale at rest. The secondary end-points were the reduction of inflammatory response expressed by plasma C-reactive protein levels, the morphine consumption and the rate of side effects. The measurements were carried out 6, 12, 24, 36 and 48 hours postoperatively. A total of 75 patients were randomized of whom 38 were allocated to ketamine group and 37 to placebo group. Baseline characteristics were comparable. Ketamine compared with placebo group showed a significant reduction of pain scores (P = 0.01), C-reactive protein (P < 0.001) and morphine consumption (P < 0.001). No acute psychological side effects related to the use of ketamine were registered. The administration of ketamine before surgery may be an effective adjunct to intravenous morphine analgesia in acute post-thoracotomy pain management. In ketamine group, satisfaction of pain relief was significantly higher with a significant reduction of inflammatory response and morphine consumption compared with placebo group. Our results, if confirmed by larger studies, may be of clinical relevance in situations where epidural analgesia or other analgesic procedures different from systemic opioid analgesia are unavailable or contraindicated. © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

  4. Effect of morphine, methadone, hydromorphone or oxymorphone on the thermal threshold, following intravenous or buccal administration to cats.

    PubMed

    Pypendop, Bruno H; Shilo-Benjamini, Yael; Ilkiw, Jan E

    2016-11-01

    To determine the effects of morphine, methadone, hydromorphone or oxymorphone on the thermal threshold in cats, following buccal and intravenous (IV) administration. Randomized crossover study. Six healthy adult female ovariohysterectomized cats weighing 4.5 ± 0.4 kg. Morphine sulfate (0.2 mg kg -1 IV or 0.5 mg kg -1 buccal), methadone hydrochloride (0.3 mg kg -1 IV or 0.75 mg kg -1 buccal), hydromorphone hydrochloride (0.1 mg kg -1 IV or 0.25 mg kg -1 buccal) or oxymorphone hydrochloride (0.1 mg kg -1 IV or 0.25 mg kg -1 buccal) were administered. All cats were administered all treatments. Skin temperature and thermal threshold were measured in duplicate prior to drug administration, and at various times up to 8 hours after drug administration. The difference between thermal threshold and skin temperature (ΔT) was analyzed. Administration of methadone and hydromorphone IV resulted in significant increases in ΔT at 40 minutes after drug administration. Buccal administration of methadone resulted in significant increases in thermal threshold, although no significant difference from baseline measurement was detected at any time point. IV administration of morphine and oxymorphone, and buccal administration of morphine, hydromorphone and oxymorphone did not cause significant thermal antinociception. At the doses used in this study, IV administration of methadone and hydromorphone, and buccal administration of methadone resulted in transient thermal antinociception. The results of this study do not allow us to predict the usefulness of these drugs for providing analgesia in clinical patients. © 2016 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.

  5. Acute administration of capsaicin increases resting energy expenditure in young obese subjects without affecting energy intake, appetite, and circulating levels of orexigenic/anorexigenic peptides.

    PubMed

    Rigamonti, Antonello E; Casnici, Claudia; Marelli, Ornella; De Col, Alessandra; Tamini, Sofia; Lucchetti, Elisa; Tringali, Gabriella; De Micheli, Roberta; Abbruzzese, Laura; Bortolotti, Mauro; Cella, Silvano G; Sartorio, Alessandro

    2018-04-01

    Although capsaicin has been reported to reduce energy intake and increase energy expenditure in an adult (normal weight or overweight) population, thus resulting in a net negative energy balance and weight loss, these beneficial effects have not been investigated in young obese subjects. We hypothesize that capsaicin acutely administered in young obese subjects exerts the same effects on energy balance and that these effects are mediated by changes in gastrointestinal peptides regulating appetite. Thus, the aim of the present study was to evaluate the acute effects of capsaicin (2 mg) or placebo on energy intake, hunger, and satiety in obese adolescents and young adults (female-male ratio: 4:6, age: 21.0 ± 5.8 years; body mass index: 41.5 ± 4.3 kg/m 2 ) provided an ad libitum dinner. Furthermore, circulating levels of some orexigenic (ghrelin) and anorexigenic (glucagon-like peptide 1 and peptide YY) peptides were measured after a meal completely consumed (lunch), together with the evaluation of hunger and satiety and assessment of resting energy expenditure (REE) through indirect computerized calorimetry. When compared to placebo, capsaicin did not significantly change either energy intake or hunger/satiety 6 hours after its administration (dinner). No differences in circulating levels of ghrelin, glucagon-like peptide 1, and peptide YY and in hunger/satiety were found in the 3 hours immediately after food ingestion among obese subjects treated with capsaicin or placebo (lunch). By contrast, the meal significantly increased REE in the capsaicin- but not placebo-treated group (capsaicin: from 1957.2 ± 455.1 kcal/d up to 2342.3 ± 562.1 kcal/d, P < .05; placebo: from 2060.1 ± 483.4 kcal/d up to 2296.0 ± 484.5 kcal/d). The pre-post meal difference in REE after capsaicin administration was significantly higher than that observed after placebo (385.1 ± 164.4 kcal/d vs 235.9 ± 166.1 kcal/d, P < .05). In conclusion, although capsaicin does not exert hypophagic

  6. A significant increase in both basal and maximal calcineurin activity following fluid percussion injury in the rat.

    PubMed

    Kurz, Jonathan E; Parsons, J Travis; Rana, Aniruddha; Gibson, Cynthia J; Hamm, Robert J; Churn, Severn B

    2005-04-01

    Calcineurin, a neuronally enriched, calcium-stimulated phosphatase, is an important modulator of many neuronal processes, including several that are physiologically related to the pathology of traumatic brain injury. This study examined the effects of moderate, central fluid percussion injury on the activity of this important neuronal enzyme. Animals were sacrificed at several time-points postinjury and cortical, hippocampal, and cerebellar homogenates were assayed for calcineurin activity by dephosphorylation of p-nitrophenol phosphate. A significant brain injury-dependent increase was observed in both hippocampal and cortical homogenates under both basal and maximally-stimulated reaction conditions. This increase persisted 2-3 weeks post-injury. Brain injury did not alter substrate affinity, but did induce a significant increase in the apparent maximal dephosphorylation rate. Unlike the other brain regions, no change in calcineurin activity was observed in the cerebellum following brain injury. No brain region tested displayed a significant change in calcineurin enzyme levels as determined by Western blot, demonstrating that increased enzyme synthesis was not responsible for the observed increase in activity. The data support the conclusion that fluid percussion injury results in increased calcineurin activity in the rat forebrain. This increased activity has broad physiological implications, possibly resulting in altered cellular excitability or a greater likelihood of neuronal cell death.

  7. [Serum non-esterified fatty acids to albumin ratio increased significantly in children with nephrotic syndrome].

    PubMed

    Fan, Chun-Li; Wu, Jia; Bu, Xiao-Min; Wan, Shu-Jun; Guo, Peng-Tao; Ma, Yan-Juan; Wang, Jun-Jun

    2016-10-20

    To analyze serum levels of non-esterified fatty acids (NEFA) and albumin (ALB) in children with nephrotic syndrome (NS) and investigate the clinical significance of altered serum NEFA to ALB ratio in children with NS in acute and remission phases. Serum levels of NEFA and ALB were measured in 55 NS children in acute phase, in 33 NS children in remission and in 122 healthy control children, and the ratio of NEFA to ALB was calculated. The other lipid/lipoprotein and renal function parameters were also analyzed in these children. Compared with the healthy control children, children with NS had a significantly decreased serum ALB level (t=11.152, P<0.001) and a significantly increased NEFA to ALB ratio (t=4.991, P<0.001). Compared with NS children in remission, those in acute phase showed a significantly decreased ALB (Z=7.822, P<0.001) and an increased NEFA to ALB ratio (t=4.991, P<0.001). In all the NS children, NEFA to ALB ratio was positively correlated with the levels of TC (r=0.564, P<0.001), TG (r=0.444, P<0.001), LDL-C (r=0.625, P<0.001), urea (r=0.437, P<0.001), creatinine (r=0.278, P=0.013), and uric acid (r=0.397, P<0.001), while negatively correlated with the level of total protein (r=-0.461, P<0.001). Multiple linear regression analyses showed that NEFA to ALB ratio was independently associated with serum urea levels (β=0.703, P=0.001; adjusted R 2 =0.494) after adjustment of other related factors. Serum NEFA to ALB ratio is significantly increased in NS children in close association with impaired kidney function, and may function as a novel parameter for assessing the development of NS.

  8. Increasing Comprehension of Students with Significant Intellectual Disabilities and Visual Impairments during Shared Stories

    ERIC Educational Resources Information Center

    Mims, Pamela J.; Browder, Diane M.; Baker, Joshua N.; Lee, Angel; Spooner, Fred

    2009-01-01

    Shared stories have been shown to help increase emerging literacy skills in students with significant intellectual disabilities. One important literacy skill is the development of listening comprehension. In this study, least-to-most prompt system was used to promote listening comprehension during shared stories for two students with significant…

  9. Unexpected significant increase in bulk conductivity of a dielectric arising from charge injection

    NASA Astrophysics Data System (ADS)

    Wang, Jian-Jun; Bayer, Thorsten J. M.; Wang, Rui; Carter, Jared J.; Randall, Clive A.; Chen, Long-Qing

    2017-06-01

    Charge injection is a common phenomenon in heterostructures or devices containing metal-insulator interfaces under a voltage bias ranging from dielectric capacitors to electroluminescent and lasing devices. It is generally believed that charge injection only significantly increases the conductivity near the interfacial region or in capacitors with very thin dielectric layers. In this work, the impact of charge injection on bulk conductivity of a 0.5 mm thick Fe-doped SrTiO3 single crystal is investigated with a combination of experimental impedance measurements and computational modelling. It is found that the interfacial charge injection may increase the predicted bulk conductivity of a dielectric by more than one order of magnitude as a consequence of Schottky barrier height lowering.

  10. Issues in Educational Administration.

    ERIC Educational Resources Information Center

    Ediger, Marlow

    School administrators need to study and analyze the pros and cons of issues before making decisions. Ultimately, decisions need to be made by administrators as to which philosophies of education to implement in resolving conflicting points of view. More research studies would lead to an increased number of syntheses of the pros and cons of certain…

  11. Faculty Involvement in Administration of Schools.

    ERIC Educational Resources Information Center

    Ogletree, Earl J.; Schmidt, Linda J.

    1992-01-01

    Contrasts the faculty-led administration of the Waldorf Schools founded by R. Steiner with the administration by local school councils established in the Chicago (Illinois) Public Schools through the School Reform Act. In Chicago, morale and status of teachers can be improved by increasing their administrative partnership. (SLD)

  12. Comparison of buprenorphine and methadone effects on opiate self-administration in primates.

    PubMed

    Mello, N K; Bree, M P; Mendelson, J H

    1983-05-01

    The effects of ascending and descending doses of buprenorphine (0.014-0.789 mg/kg/day) and methadone (0.179-11.86 mg/kg/day) on opiate and food intake were studied in Macaque monkeys over 195 to 245 days. Food (1-g banana pellets) and i.v. drug self-administration (heroin 0.01 or 0.02 mg/kg/injection or Dilaudid 0.02 mg/kg/injection) were maintained on a second-order schedule of reinforcement [FR 4 (VR 16:S)]. Buprenorphine (0.282-0.789 mg/kg/day) produced a significant suppression of opiate self-administration at 2.5 to 7 times the dose shown to be effective in human opiate abusers (P less than .05-.001). Methadone (1.43-11.86 mg/kg/day) did not suppress opiate self-administration in four of five monkeys across a dose range equivalent to 100 to 800 mg/day in man. The distribution of opiate self-administration across drug sessions did not account for the absence of methadone suppression as monkeys took 43% of the total daily opiate injections during the first daily drug session, 2.5 hr after methadone administration. During buprenorphine maintenance, food intake remained stable or increased significantly above base-line levels. Methadone maintenance was associated with significant decrements in food intake in four of five monkeys. Buprenorphine appeared to be significantly more effective in suppressing opiate self-administration than methadone across the dose range studied. Buprenorphine had none of the toxic side effects (seizures, respiratory depression, profound psychomotor retardation) associated with high doses of methadone over 6 to 8 months of daily drug treatment. These data are consistent with clinical studies of buprenorphine effects on heroin self-administration in human opiate addicts.

  13. 23 CFR 771.121 - Findings of no significant impact.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 23 Highways 1 2011-04-01 2011-04-01 false Findings of no significant impact. 771.121 Section 771.121 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RIGHT-OF-WAY AND ENVIRONMENT ENVIRONMENTAL IMPACT AND RELATED PROCEDURES § 771.121 Findings of no significant impact. (a) The Administration...

  14. 23 CFR 771.121 - Findings of no significant impact.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 23 Highways 1 2010-04-01 2010-04-01 false Findings of no significant impact. 771.121 Section 771.121 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RIGHT-OF-WAY AND ENVIRONMENT ENVIRONMENTAL IMPACT AND RELATED PROCEDURES § 771.121 Findings of no significant impact. (a) The Administration...

  15. Increased diffuse radiation fraction does not significantly accelerate plant growth

    NASA Astrophysics Data System (ADS)

    Angert, Alon; Krakauer, Nir

    2010-05-01

    ), will result in a measurable decrease (~0.6ppm) in the seasonal CO2 minimum. This holds regardless of whether the sink is the result of 1) An increase in NPP, or 2) The combined effect of a temperature-driven decrease in heterotrophic respiration (Rh) and no change in NPP. This is since both NPP and Rh peak in summer. By contrast, observations from the NOAA global CO2 monitoring network show the opposite change in the seasonal minimum in 1992 and 1993 (~0.2ppm increase) both at Mauna Loa, and in the Marine Boundary Layer mean (>20° N), which is hard to reconcile with increased NPP in northern summer. Another indicator of annual NPP is tree wood increment. Previous work (Krakauer et al., 2003) showed that the average response in tree ring series after past Pinatubo-size volcanic eruptions implied lower NPP north of 45° N, presumably as a result of shorter growing season and lower total irradiance induced by scattering aerosols, and no significant change in NPP at lower latitudes. Here we show that In 1992, after the Pinatubo eruption, ring width in the 25° N-45° N band was 99.3±2.9% of average (n=351 sites), similar to the average of 100.4±2.2% over past eruptions (n=15 eruptions) (Uncertainty is given as 2 SE.). These results are also inconsistent with substantial NPP enhancement, although a limitation of the tree-ring approach is that available measurements do not uniformly sample the latitude band. The combined evidence of tree rings and the CO2 seasonal cycle shows that the enhancement of NPP by scattering aerosols on annual timescales is weak. This result suggests that reducing aerosols through stricter pollution controls may strengthen the land carbon sink, while geo-engineering schemes which aim to mitigate global warming by spreading scattering aerosols in the stratosphere may weaken it.

  16. Effects of intranasal and peripheral oxytocin or gastrin-releasing peptide administration on social interaction and corticosterone levels in rats.

    PubMed

    Kent, Pamela; Awadia, Alisha; Zhao, Leah; Ensan, Donna; Silva, Dinuka; Cayer, Christian; James, Jonathan S; Anisman, Hymie; Merali, Zul

    2016-02-01

    The intranasal route of drug administration has gained increased popularity as it is thought to allow large molecules, such as peptide hormones, more direct access to the brain, while limiting systemic exposure. Several studies have investigated the effects of intranasal oxytocin administration in humans as this peptide is associated with prosocial behavior. There are, however, few preclinical studies investigating the effects of intranasal oxytocin administration in rodents. Oxytocin modulates hypothalamic-pituitary-adrenal (HPA) axis functioning and it has been suggested that oxytocin's ability to increase sociability may occur through a reduction in stress reactivity. Another peptide that appears to influence both social behavior and HPA axis activity is gastrin-releasing peptide (GRP), but it is not known if these GRP-induced effects are related. With this in mind, in the present study, we assessed the effects of intranasal and intraperitoneal oxytocin and GRP administration on social interaction and release of corticosterone in rats. Intranasal and intraperitoneal administration of 20, but not 5 μg, of oxytocin significantly increased social interaction, whereas intranasal and peripheral administration of GRP (20 but not 5 μg) significantly decreased levels of social interaction. In addition, while intranasal oxytocin (20 μg) had no effect on blood corticosterone levels, a marked increase in blood corticosterone levels was observed following intraperitoneal oxytocin administration. With GRP, intranasal (20 μg) but not peripheral administration increased corticosterone levels. These findings provide further evidence that intranasal peptide delivery can induce behavioral alterations in rodents which is consistent with findings from human studies. In addition, the peptide-induced changes in social interaction were not linked to fluctuations in corticosterone levels. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Intranasal administration of live Lactobacillus species facilitates protection against influenza virus infection in mice.

    PubMed

    Youn, Ha-Na; Lee, Dong-Hun; Lee, Yu-Na; Park, Jae-Keun; Yuk, Seong-Su; Yang, Si-Yong; Lee, Hyun-Jeong; Woo, Seo-Hyung; Kim, Hyoung-Moon; Lee, Joong-Bok; Park, Seung-Yong; Choi, In-Soo; Song, Chang-Seon

    2012-01-01

    Influenza virus infections continue to be a significant public health problem. For improved therapies and preventive measures against influenza, there has been an increased tendency in modern medicine involving the use of probiotics. In this study, we compared the protective efficacy of various live and dead Lactobacillus species against challenge with influenza virus in mice according to the administration route and dose. In addition, to understand the underlying mechanism behind this clinical protective effect, we performed immunologic assays including examination of IgA levels and cytokine profiles in the lung. The survival rate of mice receiving intranasal administration of Lactobacillus was higher than after oral administration, and administration of live bacteria was more protective than of dead bacteria. The lung levels of interleukin (IL)-12 and IgA were significantly increased (P<0.05). Conversely, the levels of the pro-inflammatory cytokines tumor necrosis factor-alpha and IL-6 were decreased. Interestingly, there were huge differences in protective effects of various Lactobacillus strains on influenza virus infection. Therefore, for clinical applications, selection of effective strains could be critical and individually optimized application regimens of the selected strains are required. Copyright © 2011 Elsevier B.V. All rights reserved.

  18. Perceived Stress Among Nursing and Administration Staff Related to Accreditation

    PubMed Central

    Elkins, Gary; Cook, Teresa; Dove, Jacqueline; Markova, Denka; Marcus, Joel D.; Meyer, Tricia; Rajab, M. Hassan; Perfect, Michelle

    2014-01-01

    Background Nurses in hospital administration and management positions may experience workplace stress, which can have important consequences on the health and well-being. Purpose The aim of this study was to examine the effects of perceived stress on nursing hospital management and administrative employees of a large health care organization before and after a review by The Joint Commission on the Accreditation of Healthcare Organizations. Methods A total of 100 hospital employees were randomly selected to complete questionnaires assessing their perception of stress and its effect on their well-being before and after the site review. They were also asked to rate their subjective experience of sleep, anxiety, depression, and job satisfaction. Results Perceived stress was significantly related to employees’ increased health concerns, symptoms of depression and anxiety, interpersonal relationships, and job satisfaction (p = .003). Conclusions Hospital accreditation reviews may increase perceived stress and appears to be related to emotional and physical well-being. Application The implications include evidence there is a need for organizations to initiate corrective action to help nurses in administrative roles to cope with increased levels of job strain, minimize potential psychological and physiological consequences, and preserve job satisfaction. PMID:20601637

  19. Targeting of Repeated Sequences Unique to a Gene Results in Significant Increases in Antisense Oligonucleotide Potency

    PubMed Central

    Vickers, Timothy A.; Freier, Susan M.; Bui, Huynh-Hoa; Watt, Andrew; Crooke, Stanley T.

    2014-01-01

    A new strategy for identifying potent RNase H-dependent antisense oligonucleotides (ASOs) is presented. Our analysis of the human transcriptome revealed that a significant proportion of genes contain unique repeated sequences of 16 or more nucleotides in length. Activities of ASOs targeting these repeated sites in several representative genes were compared to those of ASOs targeting unique single sites in the same transcript. Antisense activity at repeated sites was also evaluated in a highly controlled minigene system. Targeting both native and minigene repeat sites resulted in significant increases in potency as compared to targeting of non-repeated sites. The increased potency at these sites is a result of increased frequency of ASO/RNA interactions which, in turn, increases the probability of a productive interaction between the ASO/RNA heteroduplex and human RNase H1 in the cell. These results suggest a new, highly efficient strategy for rapid identification of highly potent ASOs. PMID:25334092

  20. Experimentally-induced immune activation in natural hosts of SIV induces significant increases in viral replication and CD4+ T cell depletion

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ribeiro, Ruy M

    2008-01-01

    Chronically SIVagm-infected African green monkeys (AGMs) have a remarkably stable non-pathogenic disease course, with levels of immune activation in chronic SIVagm infection similar to those observed in uninfected monkeys and stable viral loads (VLs) for long periods of time. In vivo administration of lipopolysaccharide (LPS) or an IL-2/diphtheria toxin fusion protein (Ontak) to chronically SIVagm-infected AGMs triggered increases in immune activation and subsequently of viral replication and depletion of intestinal CD4{sup +} T cells. Our study indicates that circulating microbial products can increase viral replication by inducing immune activation and increasing the number of viral target cells, thus demonstrating thatmore » immune activation and T cell prolifeation are key factors in AIDS pathogenesis.« less

  1. An Analyses of Federal Initiatives To Support Women's Upward Mobility in Educational Administration.

    ERIC Educational Resources Information Center

    Gupton, Sandra Lee; Del Rosario, Rose Marie

    The most significant role played by the federal government in advancing the state of sex equity in educational administration, as well as in most other issues involving social change, has been through legislation. This paper describes a few of the more significant federally funded initiatives related to increasing sex equity (with particular…

  2. Increase of fecundity by probiotic administration in zebrafish (Danio rerio).

    PubMed

    Gioacchini, Giorgia; Maradonna, Francesca; Lombardo, Francesco; Bizzaro, Davide; Olivotto, Ike; Carnevali, Oliana

    2010-12-01

    It is well known established that reproduction is sensitive to the state of energy reserves, and that there is a balance between energy homeostasis and fertility. In this view, this study examined the effects of the probiotic Lactobacillus rhamnosus, as a feed additive, on zebrafish (Danio rerio) fecundity. Ten days of probiotic treatment modulate the gene expression of neuropeptide hormones and metabolic signals, such as kiss1, kiss2 and leptin both at the CNS level and at the peripheral level. The increase in fecundity brought about by the probiotic was demonstrated by the higher number of ovulated eggs in vivo and by the higher germinal vesicle breakdown rate obtained with the in vitro maturation assay. The increase in oocyte maturation was associated with increased transcription of genes coding for signals which induce the maturation phase, such as lhcgr, cbr1l, and paqr8 genes, concomitant with a decreased transcription of genes coding for local factors which prevent oocyte maturation, such as tgfb1, gdf9, and bmp15. In conclusion, all these findings highlight the action of L. rhamnosus both on the endocrine system and at the local level by inducing oocyte maturation. The significance of the results herein obtained underlined the importance of diet in the reproductive process, supporting the hypothesis that feed additives can improve fecundity. Considering that the zebrafish has been clearly established as a vertebrate model for biomedical research, these results support the potentiality of feed additives such as probiotics, frequently used in the human diet, as a new technology to improve reproduction in all vertebrates, including humans.

  3. Microdialysis pharmacokinetic study of scopolamine in plasma, olfactory bulb and vestibule after intranasal administration.

    PubMed

    Wei, Yan; Ying, Mingzhen; Xu, Shuai; Wang, Feng; Zou, Aifeng; Cao, Shilei; Jiang, Xinguo; Wang, Yajie

    2016-01-01

    The purpose of this study was to investigate the microdialysis pharmacokinetic of scopolamine in plasma, olfactory bulb and vestibule after intranasal administration. The pharmacokinetic study of subcutaneous and oral administration was also performed in rats. From the in vivo results, scopolamine intranasal administration can avoid hepatic first-pass effect. Tmax plasma samples after intranasal administration were significantly faster than oral administration and subcutaneous injection. The relative bioavailability of intranasal administrations was 51.8-70% when compared with subcutaneous injection. Moreover, one can see that in comparison with scopolamine subcutaneous administration, scopolamine intranasal gel and solutions can increased drug target index (DTI) with olfactory bulb 1.69 and 2.05, vestibule 1.80 and 2.15, respectively. The results indicated that scopolamine can be absorbed directly through the olfactory mucosa into the olfactory bulb, and then transported to various brain tissue after intranasal administration, with the characteristics of brain drug delivery.

  4. Type 2 diabetes mellitus is associated with increased risk of pancreatic cancer: A veteran administration registry study.

    PubMed

    Makhoul, Issam; Yacoub, Abdulraheem; Siegel, Eric

    2016-01-01

    The etiology of pancreatic cancer remains elusive. Several studies have suggested a role for diabetes mellitus, but the magnitude of its contribution remains controversial. Utilizing a large administrative database, this retrospective cohort study was designed to investigate the relationship between type 2 diabetes mellitus and pancreatic cancer. Using the Veterans Integrated Services Network 16 database, 322,614 subjects were enrolled in the study, including 110,919 with type 2 diabetes mellitus and 211,695 diabetes-free controls matched by gender, year of birth and healthcare facility. A significantly higher incidence of pancreatic cancer was observed in patients with type 2 diabetes mellitus, with an adjusted hazard ratio (95% confidence interval) of 2.17 (1.70-2.77) for type 2 diabetes mellitus compared to controls (p < 10 -9 ) after controlling for the matching factors. The association between type 2 diabetes mellitus and pancreatic cancer was statistically significant and may, in part, explain the rising incidence of pancreatic cancer.

  5. Increased sexual desire with exogenous testosterone administration in men with obstructive sleep apnea: a randomized placebo-controlled study.

    PubMed

    Melehan, K L; Hoyos, C M; Yee, B J; Wong, K K; Buchanan, P R; Grunstein, R R; Liu, P Y

    2016-01-01

    Testosterone (T) deficiency, sexual dysfunction, obesity and obstructive sleep apnea (OSA) are common and often coexist. T prescriptions have increased worldwide during the last decade, including to those with undiagnosed or untreated OSA. The effect of T administration on sexual function, neurocognitive performance and quality of life in these men is poorly defined. The aim of this study was to examine the impact of T administration on sexual function, quality of life and neurocognitive performance in obese men with OSA. We also secondarily examined whether baseline T might modify the effects of T treatment by dichotomizing on baseline T levels pre-specified at 8, 11 and 13 nmol/L. This was a randomized placebo-controlled study in which 67 obese men with OSA (mean age 49 ± 1.3 years) were randomized to receive intramuscular injections of either 1000 mg T undecanoate or placebo at baseline, week 6 and week 12. All participants were concurrently enrolled in a weight loss program. General and sleep-related quality of life, neurocognitive performance and subjective sexual function were assessed before and 6, 12 and 18 weeks after therapy. T compared to placebo increased sexual desire (p = 0.004) in all men, irrespective of baseline T levels. There were no differences in erectile function, frequency of sexual attempts, orgasmic ability, general or sleep-related quality of life or neurocognitive function (all p = NS). In those with baseline T levels below 8 nmol/L, T increased vitality (p = 0.004), and reduced reports of feeling down (p = 0.002) and nervousness (p = 0.03). Our findings show that 18 weeks of T therapy increased sexual desire in obese men with OSA independently of baseline T levels whereas improvements in quality of life were evident only in those with T levels below 8 nmol/L. These small improvements would need to be balanced against potentially more serious adverse effects of T therapy on breathing. © 2015 American Society of Andrology and European

  6. The Wildland-Urban Interface: Increasing Significance, Complexity and Contribution

    Treesearch

    John F. Dwyer; Sarah M. McCaffrey

    2002-01-01

    During the past two decades, presentations at International Symposia on Society and Resource Management (ISSRM) have covered an increasingly broad scope of topics on natural resource issues. The wildland-urban interface (WUI) was a key topic of discussion at the ninth ISSRM in 2002: a reflection of the response by social scientists to increasing residential development...

  7. Determinants of cocaine self-administration by laboratory animals.

    PubMed

    Woolverton, W L

    1992-01-01

    The reinforcing effect of a drug is that effect that increases the probability that the drug will be self-administered again. Like other drug effects, a reinforcing effect is the result of an interaction between organism, drug and environment. Laboratory research using animal subjects has helped elucidate the contribution of each of these factors to the self-administration of cocaine. A substantial amount of research indicates that increased dopamine neurotransmission in the brain, particularly in mesolimbic and mesocortical regions, plays a major role in cocaine self-administration. Both indirect and direct dopamine agonists can function as positive reinforcers in animals, whereas noradrenergic and serotonergic (5-HT, 5-hydroxytryptamine) agonists have not been found to do so. In addition, evidence suggests that dopamine but not noradrenaline (norepinephrine) or serotonin antagonists can attenuate the reinforcing effect of cocaine. Environmental factors have also been shown to be critical determinants of the reinforcing effect of cocaine. The schedule of reinforcement essentially determines the rate and pattern of drug-maintained behaviour. In addition, punishing self-administration, increasing the value of alternative reinforcers that are available, and increasing the cost of cocaine have all been shown to decrease the reinforcing effect of cocaine. With regard to organismic factors, recent research has suggested that there are significant genetic determinants of cocaine consumption. Taken together these research findings in animals imply that certain individuals may be more sensitive to the reinforcing effect of cocaine but that cocaine abuse can be decreased by pharmacological or behavioural means or by a combination of the two.

  8. How to Control Administrative Cost.

    ERIC Educational Resources Information Center

    Halfond, Jay A.

    1991-01-01

    Growth in college administration has increased costs and bureaucracy. Rather than wait for fiscal crisis or consumer revolt, academic leaders, including faculty and administrators, should initiate change by simplifying activities and procedures and rewarding consolidation. The challenge is to use resources more effectively and efficiently in a…

  9. The regulation of pituitary-thyroid abnormalities by peripheral administration of levothyroxine increased brain-derived neurotrophic factor and reelin protein expression in an animal model of Alzheimer's disease.

    PubMed

    Shabani, Sahreh; Farbood, Yaghoob; Mard, Seyyed Ali; Sarkaki, Alireza; Ahangarpour, Akram; Khorsandi, Layasadat

    2018-03-01

    Alzheimer's disease (AD) is associated with decreased serum levels of thyroid hormones (THs), increased levels of thyroid-stimulating hormone (TSH), and decreased protein expression of brain-derived neurotrophic factor (BDNF) and reelin in the hippocampus. In this study, we have evaluated the effect of subcutaneous administration of levothyroxine (L-T 4 ) on levels of THs and TSH as well as protein expression of BDNF and reelin in AD rats. To make an animal model of AD, amyloid-beta peptide (Aβ) plus ibotenic acid were infused intrahippocampally, and rats were treated with L-T 4 and (or) saline for 10 days. The levels of THs and TSH were measured by ELISA kits. Protein synthesis was detected by Western blotting method. Results have been shown that serum level of THs, BDNF, and reelin protein expression in the hippocampus were significantly decreased (P < 0.001) in AD animals and elevated significantly in AD rats treated with L-T 4 (P < 0.01). Data showed that TSH level significantly decreased in AD rats treated with L-T 4 (P < 0.05). These findings indicated that L-T 4 increased BDNF and reelin protein expression by regulation of serum THs and TSH level in Aβ-induced AD rats.

  10. The effects of nicotine administration on the pathophysiology of rat aortic wall.

    PubMed

    Kugo, H; Zaima, N; Tanaka, H; Urano, T; Unno, N; Moriyama, T

    2017-01-01

    Abdominal aortic aneurysm (AAA) is the progressive dilation of the abdominal aorta. Nicotine is reported to be associated with the development and rupture of AAA, but the pathological effects of nicotine on normal rat aorta have not been determined. We investigated pathological changes in the aortic wall of rats caused by the administration of nicotine. Nicotine administration weakened the vascular wall, increased gelatinolytic activity and promoted the destruction of elastin and collagen in the rat abdominal aorta. There were no differences in the areas positive for matrix metalloproteinase (MMP)-2 and MMP-9 between the control and nicotine treated groups. The areas positive for MMP-12 in the nicotine group were significantly greater than for the control group. Gelatinolytic activity in the aortic wall was increased significantly in the nicotine group. Our findings suggest that MMP-12 is sensitive to nicotine exposure in rats.

  11. Fermented soymilk increases voluntary wheel running activity and sexual behavior in male rats.

    PubMed

    Sato, Takuya; Shinohara, Yasutomo; Kaneko, Daisuke; Nishimura, Ikuko; Matsuyama, Asahi

    2010-12-01

    Wheel running by rodents is thought to reflect voluntary exercise in humans. The present study examined the effect of fermented soymilk (FSM) on voluntary wheel running in rats. FSM was prepared from soymilk (SM) using the bacteria Leuconostoc pseudomesenteroides. The rats were fed a normal diet for 3 weeks followed by a 3-week administration of diet containing FSM or SM (5% w/w), and then the diets were switched back to a normal diet for 3 weeks. The voluntary wheel running activity was increased by FSM administration, although no changes were observed by SM administration. This effect was observed 2 weeks after FSM administration and lasted 1 week after deprivation of FSM. Then we evaluated the effect of FSM on sexual behavior in male rats. FSM administration for 10 days significantly increased the number of mounts. The protein expression of tyrosine hydroxylase (TH) increased in the hippocampus by FSM administration and it is suggested that FSM may change norepinephrine or dopamine signaling in the brain. Our study provides the first evidence that FSM increases voluntary wheel running activity and sexual behavior and suggests that TH may be involved in these effects.

  12. A significant increase in both basal and maximal calcineurin activity in the rat pilocarpine model of status epilepticus.

    PubMed

    Kurz, J E; Sheets, D; Parsons, J T; Rana, A; Delorenzo, R J; Churn, S B

    2001-07-01

    This study focused on the effects of status epilepticus on the activity of calcineurin, a neuronally enriched, calcium-dependent phosphatase. Calcineurin is an important modulator of many neuronal processes, including learning and memory, induction of apoptosis, receptor function and neuronal excitability. Therefore, a status epilepticus-induced alteration of the activity of this important phosphatase would have significant physiological implications. Status epilepticus was induced by pilocarpine injection and allowed to continue for 60 min. Brain region homogenates were then assayed for calcineurin activity by dephosphorylation of p-nitrophenol phosphate. A significant status epilepticus-dependent increase in both basal and Mn(2+)-dependent calcineurin activity was observed in homogenates isolated from the cortex and hippocampus, but not the cerebellum. This increase was resistant to 150 nM okadaic acid, but sensitive to 50 microM okadaic acid. The increase in basal activity was also resistant to 100 microM sodium orthovanadate. Both maximal dephosphorylation rate and substrate affinity were increased following status epilepticus. However, the increase in calcineurin activity was not found to be due to an increase in calcineurin enzyme levels. Finally, increase in calcineurin activity was found to be NMDA-receptor activation dependent. The data demonstrate that status epilepticus resulted in a significant increase in both basal and maximal calcineurin activity.

  13. Antinociceptive effects of tramadol hydrochloride after intravenous administration to Hispaniolan Amazon parrots (Amazona ventralis).

    PubMed

    Geelen, Saskia; Sanchez-Migallon Guzman, David; Souza, Marcy J; Cox, Sherry; Keuler, Nicholas S; Paul-Murphy, Joanne R

    2013-02-01

    To determine the antinociceptive and sedative effects of tramadol in Hispaniolan Amazon parrots (Amazona ventralis) following IV administration. 11 healthy Hispaniolan Amazon parrots of unknown sex. Tramadol hydrochloride (5 mg/kg, IV) and an equivalent volume (≤ 0.34 mL) of saline (0.9% NaCl) solution were administered to parrots in a complete crossover study design. Foot withdrawal response to a thermal stimulus was determined 30 to 60 minutes before (baseline) and 15, 30, 60, 120, and 240 minutes after treatment administration; agitation-sedation scores were determined for parrots at each of those times. The estimated mean changes in temperature from the baseline value that elicited a foot withdrawal response were 1.65° and -1.08°C after administration of tramadol and saline solution, respectively. Temperatures at which a foot withdrawal response was elicited were significantly higher than baseline values at all 5 evaluation times after administration of tramadol and were significantly lower than baseline values at 30, 120, and 240 minutes after administration of saline solution. No sedation, agitation, or other adverse effects were observed in any of the parrots after administration of tramadol. Tramadol hydrochloride (5 mg/kg, IV) significantly increased the thermal nociception threshold for Hispaniolan Amazon parrots in the present study. Sedation and adverse effects were not observed. These results are consistent with results of other studies in which the antinociceptive effects of tramadol after oral administration to parrots were determined.

  14. Women in Higher Education Administration.

    ERIC Educational Resources Information Center

    Association of American Colleges, Washington, DC. Project on the Status and Education of Women.

    Two papers are presented that examine the barriers to women in academic decision making and identify a variety of effective strategies for improving the status of women in higher education administration. "Strategies for Advancing Women in Higher Education Administration," by Garry D. Hays, proposes that commitment to increasing the…

  15. Thermal antinociception after dexmedetomidine administration in cats: a comparison between intramuscular and oral transmucosal administration.

    PubMed

    Slingsby, Louisa S; Taylor, Polly M; Monroe, Taylor

    2009-10-01

    Dexmedetomidine 40microg/kg was administered either intramuscularly (IM) or oral transmucosally (OTM) to 12 cats in a randomised cross-over study. Thermal nociceptive thresholds and visual analogue scale (VAS) sedation scores were obtained before and at regular intervals up to 24h after test drug administration. The summary measures of overall mean threshold, overall mean VAS sedation plus onset, offset and duration of analgesia were investigated using a univariate general linear model. There were no significant differences between treatment groups. Data are presented as mean+/-standard deviation: delta T mean increase over time (IM 6 degrees C+/-3 degrees C, OTM 6 degrees C+/-2 degrees C); overall mean VAS (IM 43+/-9 OTM 39+/-1); onset (IM 35+/-32 and OTM 30+/-40min); offset (IM 96+/-56 and OTM 138+/-135min); duration (IM 61+/-47 OTM 99+/-124min). Dexmedetomidine is well absorbed through the oral mucosa in cats since OTM and IM administration of dexmedetomidine 40microg/kg produced similar overall sedative and antinociceptive effects.

  16. Does Neostigmine Administration Produce a Clinically Important Increase in Postoperative Nausea and Vomiting?

    PubMed Central

    Cheng, Ching-Rong; Sessler, Daniel I.; Apfel, Christian C.

    2005-01-01

    Neostigmine is used to antagonize neoromuscluar blocker-induced residual neuromuscular paralysis. Despite a previous meta-analysis, the effect of neostigmine on postoperative nausea and vomiting (PONV) remains unresolved. We reevaluated the effect of neostigmine on PONV while considering the different anticholinergics as potentially confounding factors. We performed a systematic literature search using Medline, Embase, Cochrane library, reference listings, and hand searching with no language restriction through December 2004 and identified 10 clinical, randomized, controlled trials evaluating neostigmine's effect on PONV. Data on nausea or vomiting from 933 patients were extracted for the early (0-6 h), delayed (6-24 h), and overall postoperative periods (0-24 h) and analyzed with RevMan 4.2 (Cochrane Collaboration, Oxford, UK) and multiple logistic regression analysis. The combination of neostigmine with either atropine or glycopyrrolate did not significantly increase the incidence of overall (0-24 h) vomiting (relative risk (RR) 0.91 [0.70-1.18], P=0.48) or nausea (RR 1.24 [95% CI: 0.98-1.59], P=0.08). Multiple logistic regression analysis indicated that that there was not a significant increase in the risk of vomiting with large compared with small doses of neostigmine. In contrast to a previous analysis, we conclude that there is insufficient evidence to conclude that neostigmine increases the risk of PONV. PMID:16243993

  17. Probiotic administration effect on fecal mutagenicity and microflora in the goat's gut.

    PubMed

    Apás, Ana Lidia; Dupraz, Javier; Ross, Romina; González, Silvia Nelina; Arena, Mario Eduardo

    2010-11-01

    The application of potentially beneficial microorganisms to increase host defense is a new trend to increase health benefits. In this paper the first specific host probiotics for goats from a mixture isolated from healthy animals (Lactobacillus reuteri DDL 19, Lactobacillus alimentarius DDL 48, Enterococcus faecium DDE 39 and Bifidobacterium bifidum DDBA) was assayed. The effect of probiotic oral administration on goats' weight, gut microbiota, as well as on the production of mutagen compounds and their indicator (putrescine), were evaluated. The probiotic supplement was able to modify microflora balance by reducing Enterobacteria like Salmonella/Shigella (1.09 and 1.21 log CFU/g feces, respectively) and increasing lactic acid bacteria and Bifidobacteria (1.67 and 2.34 log CFU/g feces, respectively). The probiotics administration was correlated with a ten time diminution of fecal putrescine (cancer and bacterial disease marker) and a decrease of 60% mutagen fecal concentration, indicating the protective effect of the treatment. Additionally, a significant increase in ruminant weight was observed after probiotic administration. These results are encouraging towards the use of probiotic mixtures as functional food for goats. Copyright © 2010 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  18. Locomotor activity: A distinctive index in morphine self-administration in rats

    PubMed Central

    Kong, Qingyao

    2017-01-01

    Self-administration of addictive drugs is a widely used tool for studying behavioral, neurobiological, and genetic factors in addiction. However, how locomotor activity is affected during self-administration of addictive drugs has not been extensively studied. In our present study, we tested the locomotor activity levels during acquisition, extinction and reinstatement of morphine self-administration in rats. We found that compared with saline self-administration (SA), rats that trained with morphine SA had higher locomotor activity. Rats that successfully acquired SA also showed higher locomotor activity than rats that failed in acquiring SA. Moreover, locomotor activity was correlated with the number of drug infusions but not with the number of inactive pokes. We also tested the locomotor activity in the extinction and the morphine-primed reinstatement session. Interestingly, we found that in the first extinction session, although the number of active pokes did not change, the locomotor activity was significantly lower than in the last acquisition session, and this decrease can be maintained for at least six days. Finally, morphine priming enhanced the locomotor activity during the reinstatement test, regardless of if the active pokes were significantly increased or not. Our results clearly suggest that locomotor activity, which may reflect the pharmacological effects of morphine, is different from drug seeking behavior and is a distinctive index in drug self-administration. PMID:28380023

  19. Locomotor activity: A distinctive index in morphine self-administration in rats.

    PubMed

    Zhang, Jian-Jun; Kong, Qingyao

    2017-01-01

    Self-administration of addictive drugs is a widely used tool for studying behavioral, neurobiological, and genetic factors in addiction. However, how locomotor activity is affected during self-administration of addictive drugs has not been extensively studied. In our present study, we tested the locomotor activity levels during acquisition, extinction and reinstatement of morphine self-administration in rats. We found that compared with saline self-administration (SA), rats that trained with morphine SA had higher locomotor activity. Rats that successfully acquired SA also showed higher locomotor activity than rats that failed in acquiring SA. Moreover, locomotor activity was correlated with the number of drug infusions but not with the number of inactive pokes. We also tested the locomotor activity in the extinction and the morphine-primed reinstatement session. Interestingly, we found that in the first extinction session, although the number of active pokes did not change, the locomotor activity was significantly lower than in the last acquisition session, and this decrease can be maintained for at least six days. Finally, morphine priming enhanced the locomotor activity during the reinstatement test, regardless of if the active pokes were significantly increased or not. Our results clearly suggest that locomotor activity, which may reflect the pharmacological effects of morphine, is different from drug seeking behavior and is a distinctive index in drug self-administration.

  20. Hydrologic effects of large southwestern USA wildfires significantly increase regional water supply: fact or fiction?

    NASA Astrophysics Data System (ADS)

    Wine, M. L.; Cadol, D.

    2016-08-01

    In recent years climate change and historic fire suppression have increased the frequency of large wildfires in the southwestern USA, motivating study of the hydrological consequences of these wildfires at point and watershed scales, typically over short periods of time. These studies have revealed that reduced soil infiltration capacity and reduced transpiration due to tree canopy combustion increase streamflow at the watershed scale. However, the degree to which these local increases in runoff propagate to larger scales—relevant to urban and agricultural water supply—remains largely unknown, particularly in semi-arid mountainous watersheds co-dominated by winter snowmelt and the North American monsoon. To address this question, we selected three New Mexico watersheds—the Jemez (1223 km2), Mogollon (191 km2), and Gila (4807 km2)—that together have been affected by over 100 wildfires since 1982. We then applied climate-driven linear models to test for effects of fire on streamflow metrics after controlling for climatic variability. Here we show that, after controlling for climatic and snowpack variability, significantly more streamflow discharged from the Gila watershed for three to five years following wildfires, consistent with increased regional water yield due to enhanced infiltration-excess overland flow and groundwater recharge at the large watershed scale. In contrast, we observed no such increase in discharge from the Jemez watershed following wildfires. Fire regimes represent a key difference between the contrasting responses of the Jemez and Gila watersheds with the latter experiencing more frequent wildfires, many caused by lightning strikes. While hydrologic dynamics at the scale of large watersheds were previously thought to be climatically dominated, these results suggest that if one fifth or more of a large watershed has been burned in the previous three to five years, significant increases in water yield can be expected.

  1. Effects of ambroxol hydrochloride on concentrations of paclitaxel and carboplatin in lung cancer patients at different administration times.

    PubMed

    Li, J; Yi, W; Jiang, P; Sun, R; Li, T

    2016-11-30

    Our previous preliminary study revealed a synergistic effect of ambroxol hydrochloride with chemotherapeutic agents such as paclitaxel and carboplatin in lung cancer. However, the optimal conditions such as administration time and drug concentration of ambroxol hydrochloride to achieve the maximum synergistic effect remained unclear. Therefore, concentration changes of the chemotherapy drugs paclitaxel and carboplatin in the sputum were observed after ambroxol hydrochloride administration at different times in order to determine the most effective time frame of ambroxol hydrochloride administration. In this study, 470 cases of non-small cell lung cancer (NSCLC) were divided into different groups with ambroxol hydrochloride administered at different time points prior to chemotherapy, while another 171 cases received no ambroxol hydrochloride prior to chemotherapy. The results showed the concentrations of paclitaxel and carboplatin in sputum of patients treated with ambroxol hydrochloride were significantly higher than those of the control group, suggesting that ambroxol hydrochloride significantly increased the local concentrations of chemotherapeutic agents in lung tissues of NSCLC. Furthermore, the intravenous administration of ambroxol hydrochloride more than 48 hours before chemotherapy showed an optimized schedule and much greater efficacy in increasing drug concentrations than that of the control group. No statistical differences were found in the rates of grade 2 or above myelosuppression between the ambroxol intervention and control groups. Taken together, these results demonstrate that ambroxol hydrochloride administered intravenously more than 48 hours prior to chemotherapy optimally increased the concentrations of paclitaxel and carboplatin in lung tissue without significantly increasing hematologic toxicity.

  2. Oral chronic ethanol administration to rodents by agar gel diet.

    PubMed

    Bykov, I; Palmén, M; Piirainen, L; Lindros, K O

    2004-01-01

    Chronic ethanol administration to rodents requires specially designed equipment and is labor intensive. Here we report a new procedure. A commercial liquid diet preparation was made into a gel by addition of 0.5% agar. The gel, containing 5.3% ethanol, was offered in Falcon tubes equipped with a feeding opening. The gel consumption by C57/Bl mice resulted in high blood ethanol levels (average 43 mM). After 6 weeks, marked liver steatosis and significantly increased serum alanine aminotransferase levels had developed. Administration of ethanol in a nutritionally adequate gel provides a simple method for studies on chronic ethanol effects in rodents.

  3. [11C]choline uptake in regenerating liver after partial hepatectomy or CCl4-administration.

    PubMed

    Sasaki, Toru

    2004-02-01

    To characterize [methyl-(11)C]choline ([(11)C]choline) as an oncologic PET radiopharmaceutical, [(11)C]choline uptake in regenerating livers after partial hepatectomy as a model of typical proliferating tissue and after CCl(4) insult as that of proliferating tissue with inflammation, was studied in rats. [(11)C]Choline, [(18)F]2-fluoro-2-deoxy-D-glucose ([(18)F]FDG) and [2-(14)C]thymidine ([(14)C]TdR) uptake was studied in regenerating rat liver after 70% partial hepatectomy or CCl(4)-administration. [(11)C]Choline uptake in regenerating liver after partial hepatectomy was significantly increased with [(14)C]TdR uptake as a marker of DNA synthesis at 18 hours after surgery. On the other hand, the uptake was not accelerated by CCl(4)-administration, though it significantly increased [(14)C]TdR uptake. There were no differences of [(11)C]choline uptake acceleration following partial hepatectomy among the three parts of the regenerating liver. [(18)F]FDG uptake was accelerated in the regenerating liver on either partial hepatectomy or CCl(4)-administration. The magnitude of the increase in [(18)F]FDG uptake in the regenerating liver induced by partial hepatectomy was greater than that for [(11)C]choline. [(11)C]Choline uptake in the liver was accelerated by partial hepatectomy, but not by CCl(4)-administration. This might be expected given that the differentiation between proliferating tissues such as tumor and inflammatory tissue was possible by [(11)C]choline-PET.

  4. Administration of Antibiotics to Children Before Age 2 Years Increases Risk for Childhood Obesity

    PubMed Central

    Scott, Frank I; Horton, Daniel B.; Mamtani, Ronac; Haynes, Kevin; Goldberg, David S; Lee, Dale Y.; Lewis, James D

    2016-01-01

    Background & Aims Childhood obesity is increasing and is associated with adult obesity. Antibiotics have been used to promote weight gain in livestock for several decades. Antibiotics are commonly prescribed for children, but it is not clear how exposure to antibiotics early in life affects risk for obesity. We performed a population-based cohort study to assess the association between antibiotic exposure before age 2 years and obesity at age 4 years. Methods We performed a retrospective cohort study of 21,714 children in The Health Improvement Network —a population-representative dataset of more than 10 million individuals derived from electronic medical records from 1995 through 2013 in the United Kingdom. Eligible subjects were registered within 3 months of birth with complete follow-up and height and weight were recorded within 12 months of their 4th birthday. Antibiotic exposure was assessed before age 2 years, and classified based on anti-anaerobic activity. The primary outcome was obesity at age 4 years. We performed logistic regression analyses, adjusting for maternal and sibling obesity, maternal diabetes, mode of delivery, socioeconomic status, year and country of birth, and urban dwelling. Results In the cohort, 1306 of the children (6.4%) were obese at 4 years of age. Antibiotic exposure was associated with an increased risk of obesity at 4 years (odds ratio [OR]=1.21; 95% confidence interval [CI], 1.07–1.38). Odds ratios increased with repeated exposures: for 1–2 prescriptions, OR=1.07 (95% CI, 0.91–1.23); for 3–5 prescriptions, OR=1.41 (95% CI, 1.20–1.65); for 6 or more prescriptions, OR=1.47 (95% CI, 1.19–1.82). Antifungal agents were not associated with obesity (OR=0.81; 95% CI, 0.59–1.11). Conclusions Administration of 3 or more courses of antibiotics before children reach an age of 2 years is associated with an increased risk of early childhood obesity. PMID:27003602

  5. Administration of Antibiotics to Children Before Age 2 Years Increases Risk for Childhood Obesity.

    PubMed

    Scott, Frank I; Horton, Daniel B; Mamtani, Ronac; Haynes, Kevin; Goldberg, David S; Lee, Dale Y; Lewis, James D

    2016-07-01

    Childhood obesity is increasing and is associated with adult obesity. Antibiotics have been used to promote weight gain in livestock for several decades. Antibiotics are commonly prescribed for children, but it is not clear how exposure to antibiotics early in life affects risk for obesity. We performed a population-based cohort study to assess the association between antibiotic exposure before age 2 years and obesity at age 4 years. We performed a retrospective cohort study of 21,714 children in The Health Improvement Network-a population-representative dataset of >10 million individuals derived from electronic medical records from 1995 through 2013 in the United Kingdom. Eligible subjects were registered within 3 months of birth with complete follow-up and height and weight were recorded within 12 months of their 4th birthday. Antibiotic exposure was assessed before age 2 years, and classified based on anti-anaerobic activity. The primary outcome was obesity at age 4 years. We performed logistic regression analyses, adjusting for maternal and sibling obesity, maternal diabetes, mode of delivery, socioeconomic status, year and country of birth, and urban dwelling. In the cohort, 1306 of the children (6.4%) were obese at 4 years of age. Antibiotic exposure was associated with an increased risk of obesity at 4 years (odds ratio [OR] = 1.21; 95% confidence interval [CI]: 1.07-1.38). ORs increased with repeated exposures: for 1-2 prescriptions, OR = 1.07 (95% CI, 0.91-1.23); for 3-5 prescriptions, OR = 1.41 (95% CI, 1.20-1.65); and for 6 or more prescriptions, OR = 1.47 (95% CI, 1.19-1.82). Antifungal agents were not associated with obesity (OR = 0.81; 95% CI, 0.59-1.11). Administration of 3 or more courses of antibiotics before children reach an age of 2 years is associated with an increased risk of early childhood obesity. Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.

  6. Expansion of extracellular volume and suppression of atrial natriuretic peptide after growth hormone administration in normal man.

    PubMed

    Møller, J; Jørgensen, J O; Møller, N; Hansen, K W; Pedersen, E B; Christiansen, J S

    1991-04-01

    Sodium retention and symptoms and signs of fluid retention are commonly recorded during GH administration in both GH-deficient patients and normal subjects. Most reports have however, been casuistic or uncontrolled. In a randomized double blind placebo-controlled cross-over study we therefore examined the effect of 14-day GH administration (12 IU sc at 2000 h) on plasma volume, extracellular volume (ECV), atrial natriuretic peptide (ANP), arginine vasopressin, and the renin angiotensin system in eight healthy adult men. A significant GH induced increase in serum insulin growth factor I was observed. GH caused a significant increase in ECV (L): 20.45 +/- 0.45 (GH), 19.53 +/- 0.48 (placebo) (P less than 0.01), whereas plasma volume (L) remained unchanged 3.92 +/- 0.16 (GH), 4.02 +/- 0.13 (placebo). A significant decrease in plasma ANP (pmol/L) after GH administration was observed: 2.28 +/- 0.54 (GH), 3.16 +/- 0.53 (placebo) P less than 0.01. Plasma aldosterone (pmol/L): 129 +/- 14 (GH), 89 +/- 17 (placebo), P = 0.08, and plasma angiotensin II (pmol/L) levels: 18 +/- 12 (GH), 14 +/- 7 (placebo), P = 0.21, were not significantly elevated. No changes in plasma arginine vasopressin occurred (1.86 +/- 0.05 pmol/L vs. 1.90 +/- 0.05, P = 0.33). Serum sodium and blood pressure remained unaffected. Moderate complaints, which could be ascribed to water retention, were recorded in four subjects [periorbital edema (n = 3), acral paraesthesia (n = 2) and light articular pain (n = 1)]. The symptoms were most pronounced after 2-3 days of treatment and diminished at the end of the period. In summary, 14 days of high dose GH administration caused a significant increase in ECV and a significant suppression of ANP.

  7. Significant and Sustained Reduction in Chemotherapy Errors Through Improvement Science.

    PubMed

    Weiss, Brian D; Scott, Melissa; Demmel, Kathleen; Kotagal, Uma R; Perentesis, John P; Walsh, Kathleen E

    2017-04-01

    A majority of children with cancer are now cured with highly complex chemotherapy regimens incorporating multiple drugs and demanding monitoring schedules. The risk for error is high, and errors can occur at any stage in the process, from order generation to pharmacy formulation to bedside drug administration. Our objective was to describe a program to eliminate errors in chemotherapy use among children. To increase reporting of chemotherapy errors, we supplemented the hospital reporting system with a new chemotherapy near-miss reporting system. After the model for improvement, we then implemented several interventions, including a daily chemotherapy huddle, improvements to the preparation and delivery of intravenous therapy, headphones for clinicians ordering chemotherapy, and standards for chemotherapy administration throughout the hospital. Twenty-two months into the project, we saw a centerline shift in our U chart of chemotherapy errors that reached the patient from a baseline rate of 3.8 to 1.9 per 1,000 doses. This shift has been sustained for > 4 years. In Poisson regression analyses, we found an initial increase in error rates, followed by a significant decline in errors after 16 months of improvement work ( P < .001). After the model for improvement, our improvement efforts were associated with significant reductions in chemotherapy errors that reached the patient. Key drivers for our success included error vigilance through a huddle, standardization, and minimization of interruptions during ordering.

  8. Ethosomes as delivery system for transdermal administration of vinpocetine.

    PubMed

    Mao, Yan-Ting; Hua, Hai-Ying; Zhang, Xiang-Guo; Zhu, Dong-Xue; Li, Feng; Gui, Zhen-Hua; Zhao, Yong-Xing

    2013-05-01

    The purpose of the present study was to develop a novel transdermal vinpocetine patch containing a stable formulation and with good entrapment efficiency, and percutaneous absorption which via ethosome. Ethosome was found to be a more efficient delivery carrier with high encapsulation capacities (79.5% +/- 1.8%) and nanometric size (180.7 +/- 1.5 nm). In vitro percutaneous permeation experiments demonstrated that the permeation of vinpocetine through abdominal skin of Sprague Dawley was significantly increased when ethosome was used. The vinpocetine transdermal fluxes from ethosome gel (3.56 +/- 0.13 microg/cm2/h) were 6.72 and 3.10 times higher than that of vinpocetine gel solution and vinpocetine aueous solution, respectively. Furthermore, the AUC(0 --> infinity), and eliminiation half-life by the transdermal administration were significantly higher than those by the intragastric administration (P < 0.01). The study demonstrated that ethosome is a promising vesicular carrier for enhancing percutaneous absorption of vinpocetine.

  9. Chronic nicotine administration differentially affects neurotransmitter release from rat striatal slices.

    PubMed

    Yu, Z J; Wecker, L

    1994-07-01

    The objective of these experiments was to determine whether the chronic administration of nicotine, at a dose regimen that increases the density of nicotine binding sites, alters the nicotine-induced release of [3H]-dopamine ([3H]DA), [3H]norepinephrine ([3H]NE), [3H]-serotonin ([3H]5-HT), or [3H]acetylcholine ([3H]ACh) from rat striatal slices. For these experiments, rats received subcutaneous injections of either saline or nicotine bitartrate [1.76 mg (3.6 mumol)/kg, dissolved in saline] twice daily for 10 days, and neurotransmitter release was measured following preloading of the tissues with [3H]DA, [3H]NE, [3H]5-HT, or [3H]choline. Chronic nicotine administration did not affect the accumulation of tritium by striatal slices, the basal release of radioactivity, or the 25 mM KCl-evoked release of neurotransmitter. Superfusion of striatal slices with 1, 10, and 100 microM nicotine increased [3H]DA release in a concentration-dependent manner, and release from slices from nicotine-injected animals was significantly (p < 0.05) greater than release from saline-injected controls; release from the former increased to 132, 191, and 172% of release from the controls following superfusion with 1, 10, and 100 microM nicotine, respectively. Similarly, [3H]5-HT release increased in a concentration-related manner following superfusion with nicotine, and release from slices from nicotine-injected rats was significantly (p < 0.05) greater than that from controls. [3H]5-HT release from slices from nicotine-injected rats evoked by superfusion with 1 and 10 microM nicotine increased to 453 and 217%, respectively, of release from slices from saline-injected animals. The nicotine-induced release of [3H]NE from striatal slices was also concentration dependent but was unaffected by chronic nicotine administration.(ABSTRACT TRUNCATED AT 250 WORDS)

  10. Reporting ethics committee approval in public administration research.

    PubMed

    Jordan, Sara R; Gray, Phillip W

    2014-03-01

    While public administration research is thriving because of increased attention to social scientific rigor, lingering problems of methods and ethics remain. This article investigates the reporting of ethics approval within public administration publications. Beginning with an overview of ethics requirements regarding research with human participants, I turn to an examination of human participants protections for public administration research. Next, I present the findings of my analysis of articles published in the top five public administration journals over the period from 2000 to 2012, noting the incidences of ethics approval reporting as well as funding reporting. In explicating the importance of ethics reporting for public administration research, as it relates to replication, reputation, and vulnerable populations, I conclude with recommendations for increasing ethics approval reporting in public administration research.

  11. Establishment of a schizophrenic animal model through chronic administration of MK-801 in infancy and social isolation in childhood.

    PubMed

    Liu, Weiqing; Wang, Xiuyan; Hong, Wenjuan; Wang, Dong; Chen, Xiaogang

    2017-02-01

    Although an increasing amount of evidence supports a "two-hit" hypothesis for the neurodevelopmental model of schizophrenia, there has been no development in animal models to test this hypothesis. An animal model was established by chronic administration of 0.1, 0.3, and 0.5mg/kg MK-801 in P7-P21 rats followed by four weeks of social isolation in childhood and then five days of social housing. Animal behaviors were measured by the open field (OF) test, the novel object recognition (NOR) test, the prepulse inhibition (PPI) test, and the elevated plus maze (EPM) test. We found a significant decrease in the NOR index in adolescent rats compared to saline control rats when administering 0.5mg/kg of MK-801 (P=0.02). We found that social isolation had no significant effect on NOR index, though social isolation significantly increased the total distance traveled and significantly decreased the resting time in adolescent rats in the OF test (P<0.001 and P=0.003, respectively). In contrast, we observed that MK-801 administration showed no significant effects on either total distance traveled or resting time. Both MK-801 administration and social isolation had no significant effect on the percent of PPI and startle amplitudes in adolescent rats. Social isolation significantly reduced the open arm entries in adolescent rats in the EPM test (P=0.023), but it did not reduce the ratio to enter the open arms and the stay time in open arm. Administration of MK-801 showed no significant effect on the indexes of entering the open arms in the EPM test on adolescent rats. MK-801 intervention in infancy is associated with the damage of long-term visual memory, whereas social isolation in childhood is associated with the increased spontaneous activity and anxiety levels. Administration of MK-801 in infancy and social isolation in childhood are two independent factors on the neurodevelopmental defects. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Increasing the statistical significance of entanglement detection in experiments.

    PubMed

    Jungnitsch, Bastian; Niekamp, Sönke; Kleinmann, Matthias; Gühne, Otfried; Lu, He; Gao, Wei-Bo; Chen, Yu-Ao; Chen, Zeng-Bing; Pan, Jian-Wei

    2010-05-28

    Entanglement is often verified by a violation of an inequality like a Bell inequality or an entanglement witness. Considerable effort has been devoted to the optimization of such inequalities in order to obtain a high violation. We demonstrate theoretically and experimentally that such an optimization does not necessarily lead to a better entanglement test, if the statistical error is taken into account. Theoretically, we show for different error models that reducing the violation of an inequality can improve the significance. Experimentally, we observe this phenomenon in a four-photon experiment, testing the Mermin and Ardehali inequality for different levels of noise. Furthermore, we provide a way to develop entanglement tests with high statistical significance.

  13. Actigraphy-based sleep parameters during the reinstatement of methamphetamine self-administration in rhesus monkeys.

    PubMed

    Berro, Laís F; Andersen, Monica L; Tufik, Sergio; Howell, Leonard L

    2016-04-01

    The objective of this study was to investigate nighttime activity of nonhuman primates during extinction and cue- and drug-primed reinstatement of methamphetamine self-administration. Adult rhesus monkeys (Macaca mulatta; n = 5) self-administered methamphetamine (0.01 mg/kg/injection, i.v.) under a fixed-ratio 20 schedule of reinforcement. Saline infusions were then substituted for methamphetamine and stimulus light (drug-conditioned stimulus presented during drug self-administration) withheld until subjects reached extinction criteria. Drug- and cue-induced reinstatement effects were evaluated after i.v. noncontingent priming injections of methamphetamine (0.03, 0.1, or 0.3 mg/kg). Activity-based sleep measures were evaluated with Actiwatch monitors a week before (baseline nighttime activity parameters) and throughout the protocol. Although methamphetamine self-administration did not significantly affect nighttime activity compared to baseline, sleeplike parameters were improved during extinction compared to self-administration maintenance. Priming injection of 0.1 mg/kg methamphetamine, but not 0.03 or 0.3 mg/kg, induced significant reinstatement effects. These behavioral responses were accompanied by nighttime outcomes, with increased sleep fragmentation and decreased sleep efficiency in the night following 0.1 mg/kg methamphetamine-induced reinstatement. In the absence of both drug and drug-paired cues (extinction conditions), nighttime activity decreased compared to self-administration maintenance. Additionally, effective reinstatement conditions impaired sleeplike measures. Our data indicate that the reintroduction of the stimulus light as a drug-paired cue increased nighttime activity. (c) 2016 APA, all rights reserved).

  14. Processes involved in assisted reproduction technologies significantly increase sperm DNA fragmentation and phosphatidylserine translocation.

    PubMed

    Balasuriya, A; Serhal, P; Doshi, A; Harper, J C

    2014-03-01

    Sperm preparation techniques in assisted reproduction technologies (ART) are potential generators of exogenous stresses that cause additional DNA damage. DNA fragmentation tests, such as the sperm chromatin structure assay, involve freezing sperm samples in the absence of cryoprotectant. Thermal, oxidative stress (OS) and freezing are detrimental to sperm DNA fragmentation and phosphatidylserine (PS) translocation. The primary aim of this study was to subject mature sperm to environmental insults that normally occur during ART. We tested the hypotheses that OS, thermal stress and freeze-thawing caused sperm nuclear and membrane damage and that a positive correlation exists between PS translocation and DNA fragmentation. Sperm DNA integrity deteriorates in semen samples from men with advancing age and a sperm concentration of <15 m ml(-1) . The significant increase in sperm DNA fragmentation at 37 °C after merely 1 h is important clinically as semen liquefaction and short-term sperm storage in an ART cycle involve incubating samples at this temperature. Freezing without a cryoprotectant significantly increases the level of sperm nuclear damage, so it is important not to freeze neat semen prior to DNA fragmentation testing. This study highlights the importance of minimising the production of exogenous stresses during sperm preparation in ART. © 2012 Blackwell Verlag GmbH.

  15. Attitudes toward Women School Administrators in Turkey

    ERIC Educational Resources Information Center

    Celikten, Mustafa

    2010-01-01

    There is a shortage of women in educational administration. Women represent a majority of teachers, yet men occupy most administrative positions. Although the numbers of women in administrative positions have been increasing during the last two decades, women are still reported as facing barriers and being discriminated against while reaching…

  16. Sleeping Pill Administration Time and Patient Subjective Satisfaction.

    PubMed

    Chung, Seockhoon; Youn, Soyoung; Yi, Kikyoung; Park, Boram; Lee, Suyeon

    2016-01-01

    Taking hypnotic agents 30 min before bedtime is the usual suggested administration time, but some patients report dissatisfaction with their sleeping pills. We investigated whether the timing of sleeping pill administration influences patient subjective satisfaction with these drugs. One hundred twelve patients with primary insomnia currently taking benzodiazepine or nonbenzodiazepine gamma-aminobutyric acid (GABA) agonists as sleeping pills were selected. The time of administration for their sleeping pills, bedtime, sleep onset time, and wake up time were obtained from their medical records. Subjects were also categorized into satisfied or dissatisfied groups. Hypnotic agents administration time (p < 0.001) and bedtime (p < 0.001), but not sleep onset or wake up time, occurred later in the night in the satisfied group. The durations from administration of pills to sleep onset (33.6 ± 20.7 min) and to wake up time (7.2 ± 1.2 h) were significantly shorter in the satisfied group when compared to the dissatisfied group (135.9 ± 73.4 min and 9.3 ± 1.5 h for time to sleep onset and wake up, respectively). Logistic regression analysis revealed that patient subjective satisfaction with hypnotic agents could be predicted by a short duration from administration of pills to sleep onset (odds ratio = 0.01; 95% confidence interval [0.001-0.09]) and a short duration from administration of pills to wake up time (0.53; [0.31-0.89], F = 49.9, p < 0.001). Taking sleeping pills at a later time and a shorter interval between pill administration and wake up time may increase patient subjective satisfaction with hypnotic agents. We propose that physicians advise patients to take sleeping pills approximately 7 h before their usual getting-out-of-bed time instead of the current standard of 30 min before bedtime. © 2016 American Academy of Sleep Medicine.

  17. The differential effects of alprazolam and oxazepam on methamphetamine self-administration in rats.

    PubMed

    Spence, Allyson L; Guerin, Glenn F; Goeders, Nicholas E

    2016-09-01

    Methamphetamine is the second most commonly used illicit drug in the world, and despite recent attempts by the Drug Enforcement Administration to combat this epidemic, methamphetamine use is still on the rise. As methamphetamine use increases so does polydrug use, particularly that involving methamphetamine and benzodiazepines. The present study was designed to examine the effects of two benzodiazepines on methamphetamine self-administration. Five doses of methamphetamine (0.0075, 0.015, 0.03, 0.09, and 0.12mg/kg/infusion) were tested, producing an inverted U-shaped dose-response curve. Rats were then pretreated with oxazepam, alprazolam, or vehicle prior to methamphetamine self-administration. To determine if the effects of these drugs were due to the GABAA receptor and/or translocator protein (TSPO), we also pretreated rats with an antagonist for the benzodiazepine-binding site on the GABAA receptor (i.e., flumazenil) and a TSPO antagonist (i.e., PK11195) prior to alprazolam or oxazepam administration. Oxazepam significantly reduced methamphetamine self-administration as demonstrated by a downward shift of the dose-response curve. In contrast, alprazolam significantly enhanced methamphetamine self-administration as evidenced by a leftward shift of the dose-response curve. Flumazenil completely blocked the effects of alprazolam on methamphetamine self-administration. When administered individually, both flumazenil and PK11195 partially reversed the effects of oxazepam on methamphetamine self-administration. However, when these two antagonists were combined, the effects of oxazepam were completely reversed. The GABAA receptor is responsible for the alprazolam-induced enhancement of methamphetamine self-administration, while the activation of both the GABAA receptor and TSPO are responsible for the oxazepam-induced reduction of methamphetamine self-administration. Published by Elsevier Ireland Ltd.

  18. Effect of iodinated low-osmolar contrast media on the hemostatic system after intraarterial and intravenous contrast administration.

    PubMed

    Lukasiewicz, A; Lebkowska, U; Galar, M

    2012-01-01

    Some of the adverse clinical effects of intravascular radiological contrast agents include the interference of these contrast media with normal hemostatic processes. The aim of this report was to investigate in vivo whether a non-ionic iodinated contrast agent possess prothrombotic or anticoagulant properties. Hemostatic parameters: vWF (von Willebrand factor), F1+2 (prothrombin fragments 1+2), TAT (thrombin-antithrombin complexes), D-Dimer, β-TG (beta-thromboglobulin) were measured in a group of 35 patients. Blood samples for laboratory investigations were collected before and 30 min after the administration of a iodine contrast agent. There was observed statistically highly significant contrast-induced increase in TAT and F1+2 (p = 0.005 and p = 0.008, respectively). D-Dimer increase and decrease of β-TG and vWF after contrast medium administration were non significant. The volume of contrast medium has no influence on the assessed hemostatic parameters, while the type of contrast medium and/or the route of the contrast administration may significantly affect hemostatic parameters. We found significant effects of non-ionic agents on hemostatic activation. These effects may be important for adverse reactions and for thromboembolic complications.

  19. Effect of hCG administration during corpus luteum establishment on subsequent corpus luteum development and circulating progesterone concentrations in beef heifers.

    PubMed

    Maillo, V; Duffy, P; O'Hara, L; de Frutos, C; Kelly, A K; Lonergan, P; Rizos, D

    2014-03-01

    This study examined the effect of a single administration of human chorionic gonadotrophin (hCG) on Day 1 to 4 after oestrus on corpus luteum (CL) development and circulating progesterone (P4). Oestrus-synchronized heifers (n=43) were administered a single intramuscular injection of saline on Day 1 (control) or 3000IU hCG on Day 1, 2, 3 or 4 after oestrus. Administration of hCG on Day 1 had no effect on CL area, on Day 2 increased CL area from Day 6 to 12 (P<0.05), on Day 3 increased CL area from Day 9 to 11, while on Day 4 increased CL size on Days 9 and 10 (P<0.05). Administration of hCG on Day 4 induced the formation of an accessory CL in 89% of heifers, resulting in a significant increase in total luteal tissue area on the ovaries compared with all other groups. Consistent with the effects on the CL, hCG on Day 1 did not affect P4 concentrations, on Day 2 significantly increased P4 compared with the control from Day 6 to 11 (P<0.05), on Day 3 resulted in a non-significant increase in P4 while hCG on Day 4 increased P4 from Day 8 to 13 compared with the control (P<0.05). In conclusion, administration of hCG as early as Day 2 after oestrus results in increased P4 in circulation from Day 6, which should have beneficial downstream effects in terms of uterine receptivity and conceptus elongation.

  20. Antidepressant-like effects of the acute and chronic administration of nicotine in the rat forced swimming test and its interaction with fluoxetine [correction of flouxetine].

    PubMed

    Vázquez-Palacios, G; Bonilla-Jaime, H; Velázquez-Moctezuma, J

    2004-05-01

    An antidepressant action of nicotine (NIC) has recently been suggested. Flouxetine, a selective serotonin reuptake inhibitor, is currently the most widely used antidepressant. In the present study, we analyzed the effects of the administration of NIC, fluoxetine (FLX), and the combination of both drugs given acutely, subchronically, and chronically as well as 7 days after chronic administration of these drugs on the forced swim test. Results showed that NIC induced a significant reduction of the time in immobility during the forced swim test (antidepressant effect), with a concomitant increase in swimming activity (serotonergic activation), after acute administration. These effects remain the same after subchronic and chronic administration. FLX failed to induce any effect after acute administration but did induce a significant decrease of immobility and an increase of swimming after subchronic administration. The effect of the chronic administration was significantly larger compared to subchronic administration. The combination of both drugs induced a larger effect than that observed after a single administration but only after subchronic treatment. No effect was observed after the end of the 7-day treatments. Data suggest that NIC has an antidepressant action that is expressed faster than FLX but remains the same later. Thus, cholinergic-serotonergic interactions could play an important role in the treatment of depression.

  1. Chronic administration of ethanol leaf extract of Moringa oleifera Lam. (Moringaceae) may compromise glycaemic efficacy of Sitagliptin with no significant effect in retinopathy in a diabetic rat model.

    PubMed

    Olurishe, Comfort; Kwanashie, Helen; Zezi, Abdulkadiri; Danjuma, Nuhu; Mohammed, Bisalla

    2016-12-24

    Moringa oleifera Lam. (Moringaceae) has gained awareness for its antidiabetic effect, and is used as alternative therapy or concurrently with orthodox medicines such as sitagliptin in diabetes mellitus. This is without ascertaining the possibility of drug-herb interactions, which could either lead to enhanced antidiabetic efficacy, increased toxicity, or compromised glycaemic control with negative consequence in diabetic retinopathy. To investigate the effect, of sitagliptin (50mg/kg), Moringa oleifera (300mg/kg) leaf extract, and a combination of both on glycaemic control parameters, lenticular opacity and changes in retinal microvasculature in alloxan (150mg/kg i.p) induced diabetic rat model. Seven groups of eight rats per group were used, with groups I, II and VII as normal (NC), diabetic (DC) and post-prandial controls (PPC). Groups III to VI were diabetic rats on sitagliptin (III), M. oleifera (IV), sitagliptin and M. oleifera (SM) (V), for 42 days with 2 weeks delayed treatment in a post-prandial hyperglycaemic group (PPSM) (VI). Glycaemic control parameters, insulin levels, body weights, and effects of retinal microvasculature on lenticular opacity/morphology were investigated. A significant decrease in fasting blood glucose (FBG) levels was displayed in SM group from day 14(60%) (p<0.01) to day 28 (38%) (p<0.01) of treatment, compared to day 1. Thereafter, a steady increase of up to 57% on day 42 compared to day 28 was observed. A significant decrease in random blood glucose (RBG) levels, were demonstrated on day 42 (24%) (p<0.001), compared to day 1. No significant difference was seen in mean serum levels of insulin across groups. No significant changes in body weights. Evidence of mild lenticular opacity was observed, with no significant effect in pathologic lesions in the retina. The chronic co-administration of sitagliptin and M. oleifera showed a progressive decrease in anti-hyperglycaemic effect of sitagliptin, and although it delayed the onset of

  2. Combined administration of taurine and monoisoamyl DMSA protects arsenic induced oxidative injury in rats

    PubMed Central

    Chouhan, Swapnila; Kannan, Gurusamy M; Mittal, Megha; Swarnkar, Harimohan

    2008-01-01

    Arsenic is a naturally occurring element that is ubiquitously present in the environment. High concentration of naturally occurring arsenic in drinking water is a major health problem in different parts of the world. Despite arsenic being a health hazard and a well documented carcinogen, no safe, effective and specific preventive or therapeutic measures are available. Among various recent strategies adopted, administration of an antioxidant has been reported to be the most effective. The present study was designed to evaluate the therapeutic efficacy of monoisoamyl dimercaptosuccinic acid (MiADMSA), administered either individually or in combination with taurine post chronic arsenic exposure in rats. Arsenic exposed male rats (25 ppm, sodium arsenite in drinking water for 24 weeks) were treated with taurine (100 mg/kg, i.p., once daily), monoisoamyl dimercaptosuccinic acid (MiADMSA) (50 mg/kg, oral, once daily) either individually or in combination for 5 consecutive days. Biochemical variables indicative of oxidative stress along-with arsenic concentration in blood, liver and kidney were measured. Arsenic exposure significantly reduced blood δ-aminolevulinic acid dehydratase (ALAD) activity, a key enzyme involved in the heme biosynthesis and enhanced zinc protoporphyrin (ZPP) level. Clinical hematological variables like white blood cells (WBC), mean cell hemoglobin (MCH), and mean cell hemoglobin concentration (MCHC) showed significant decrease with a significant elevation in platelet (PLT) count. These changes were accompanied by significant decrease in superoxide dismutase (SOD) activity and increased catalase activity. Arsenic exposure caused a significant decrease in hepatic and renal glutathione (GSH) level and an increase in oxidized glutathione (GSSG). These biochemical changes were correlated with an increased uptake of arsenic in blood, liver and kidney. Administration of taurine significantly reduced hepatic oxidative stress however co-administration of

  3. Does Gender of Administrator Matter? National Study Explores U.S. University Administrators' Attitudes About Retaining Women Professors in STEM

    PubMed Central

    Williams, Wendy M.; Mahajan, Agrima; Thoemmes, Felix; Barnett, Susan M.; Vermeylen, Francoise; Cash, Brian M.; Ceci, Stephen J.

    2017-01-01

    Omnipresent calls for more women in university administration presume women will prioritize using resources and power to increase female representation, especially in STEM fields where women are most underrepresented. However, empirical evidence is lacking for systematic differences in female vs. male administrators' attitudes. Do female administrators agree on which strategies are best, and do men see things differently? We explored United States college and university administrators' opinions regarding strategies, policies, and structural changes in their organizations designed to increase women professors' representation and retention in STEM fields. A comprehensive review of past research yielded a database of potentially-effective, recommended policies. A survey based on these policies was sent to provosts, deans, associate deans, and department chairs of STEM fields at 96 public and private research universities across the U.S. These administrators were asked to rate the quality and feasibility of each strategy; 474 provided data, of which 334 contained complete numerical data used in the analyses. Our data revealed that female (vs. male) administrators believed the 44 strategies were higher in quality overall—but not higher in feasibility—with 9 strategies perceived differently by women and men, after imposing conservative statistical controls. There was broad general agreement on the relative-quality rankings of the 44 strategies. Women (vs. men) gave higher quality ratings to increasing the value of teaching, service, and administrative experience in tenure/promotion decisions, increasing flexibility of federal-grant funding to accommodate mothers, conducting gender-equity research, and supporting shared tenure lines enabling work-life balance. Women (vs. men) believed it was more feasible for men to stop the tenure clock for 1 year for childrearing and for universities to support requests for shared tenure lines, but less feasible for women to chair

  4. Does Gender of Administrator Matter? National Study Explores U.S. University Administrators' Attitudes About Retaining Women Professors in STEM.

    PubMed

    Williams, Wendy M; Mahajan, Agrima; Thoemmes, Felix; Barnett, Susan M; Vermeylen, Francoise; Cash, Brian M; Ceci, Stephen J

    2017-01-01

    Omnipresent calls for more women in university administration presume women will prioritize using resources and power to increase female representation, especially in STEM fields where women are most underrepresented. However, empirical evidence is lacking for systematic differences in female vs. male administratorsŠ attitudes. Do female administrators agree on which strategies are best, and do men see things differently? We explored United States college and university administratorsŠ opinions regarding strategies, policies, and structural changes in their organizations designed to increase women professorsŠ representation and retention in STEM fields. A comprehensive review of past research yielded a database of potentially-effective, recommended policies. A survey based on these policies was sent to provosts, deans, associate deans, and department chairs of STEM fields at 96 public and private research universities across the U.S. These administrators were asked to rate the quality and feasibility of each strategy; 474 provided data, of which 334 contained complete numerical data used in the analyses. Our data revealed that female (vs. male) administrators believed the 44 strategies were higher in quality overall-but not higher in feasibility -with 9 strategies perceived differently by women and men, after imposing conservative statistical controls. There was broad general agreement on the relative-quality rankings of the 44 strategies. Women (vs. men) gave higher quality ratings to increasing the value of teaching, service, and administrative experience in tenure/promotion decisions, increasing flexibility of federal-grant funding to accommodate mothers, conducting gender-equity research, and supporting shared tenure lines enabling work-life balance. Women (vs. men) believed it was more feasible for men to stop the tenure clock for 1 year for childrearing and for universities to support requests for shared tenure lines, but less feasible for women to

  5. Thrombopoietic effects of interleukin-6 in long-term administration in mice.

    PubMed

    Ishibashi, T; Shikama, Y; Kimura, H; Kawaguchi, M; Uchida, T; Yamamoto, T; Okano, A; Akiyama, Y; Hirano, T; Kishimoto, T

    1993-05-01

    To further investigate the thrombopoietic and adverse effects of interleukin-6 (IL-6), 2 or 10 micrograms/day of recombinant human (rh) IL-6 was administered intraperitoneally (i.p.) to mice for up to 30 days. IL-6 increased platelet count, which plateaued at a level 30 to 40% higher than control after 5 days of treatment. This cytokine also maintained the high platelet count for the duration of treatment. The count exceeded normal levels 7 days after cessation of the 30-day treatment. IL-6 also induced a remarkable increase in the size but not the frequency of megakaryocytes in bone marrow sections. The number of bone marrow colony-forming units megakaryocyte (CFU-MK) and colony-forming units granulocyte-macrophage (CFU-GM) was not augmented by the administration of IL-6 in this protocol, while spleen progenitors were significantly stimulated. Small but significant increases did occur in the number of bone marrow megakaryocytes and CFU-MK, and in the proportion of CFU-MK in the DNA synthetic phase in mice treated with 10 micrograms/day of IL-6 for 30 days. Electron microscopic examination of bone marrow demonstrated that IL-6 remarkably developed the distribution of the demarcation membrane system (DMS) in mice treated for 30 days, with little change in mice treated for 5 days. The administration of 2 micrograms/day for 30 days induced a 2.2-fold increase in fibrinogen. No changes were observed in the hepatic or renal functions. Histologic and immunofluorescence studies on the kidneys revealed no significant changes compared with controls, indicating that proliferation of the glomerular mesangium did not occur. No neutralizing antibodies were detected in mice treated for 30 days. We conclude that the long-term administration of IL-6 in mice stimulates megakaryocyte maturation and platelet production with few adverse effects, and that this cytokine may be a candidate for the treatment of thrombocytopenia in humans.

  6. Administration of antibiotics to ewes at the beginning of the dry-period.

    PubMed

    Petridis, Ioannis G; Fthenakis, George C

    2014-02-01

    The objective of the present paper is to review the significance of administration of antibiotics at the end of a lactation period/beginning of the dry-period in ewes. During the stage of active involution, there is an increased risk of new mastitis cases and recrudescence of subclinical infections that had occurred during the previous lactation period. The main pathogens involved in the so-called 'dry-period mastitis' are coagulase-negative staphylococci. The principle of antibiotic administration at the end of a lactation period involves the intramammary infusion of a preparation to both mammary glands of ewes in the flock. Although a variety of products is licensed for administration in ewes, preferably the product for administration should be selected on the results of susceptibility testing of bacteria to be isolated from samples from ewes in the flock. In many clinical studies from around the world, performed in dairy- or mutton-production flocks, administration of antimicrobial agents at the end of a lactation period has been found beneficial in curing intramammary infections present at cessation of a lactation period, as well as in minimising the risk for intramammary infections during the dry-period. In dairy flocks, there are also benefits from increase in milk yield and decrease flock bulk milk mean somatic cell counts during the subsequent lactation period. Antibiotic administration at drying-off may be performed to all animals in a flock ('complete') or only to those considered to be infected ('selective'). In all cases, after administration of the antibiotic, definite and complete cessation of the lactation period is essential for success of the procedure. Moreover, maintenance of the prescribed withdrawal periods is essential to safeguard public health. The procedure should always be applied as part of a strategic udder health management plan in a flock; implementation improves the welfare of animals and affords significant financial benefits to the

  7. Black Administrators and Administrative Law

    ERIC Educational Resources Information Center

    Harper, Robert

    1975-01-01

    The stated objective of this paper is to keep the Black administrator out of court by creating an awareness of legal pitfalls: the discussion is divided into four sections--a brief overview of some of the functions of administrators and administrative agencies, sharing information with the public, the use of discretion, and limitations of the…

  8. Phytohormone supplementation significantly increases growth of Chlamydomonas reinhardtii cultivated for biodiesel production.

    PubMed

    Park, Won-Kun; Yoo, Gursong; Moon, Myounghoon; Kim, Chul Woong; Choi, Yoon-E; Yang, Ji-Won

    2013-11-01

    Cultivation is the most expensive step in the production of biodiesel from microalgae, and substantial research has been devoted to developing more cost-effective cultivation methods. Plant hormones (phytohormones) are chemical messengers that regulate various aspects of growth and development and are typically active at very low concentrations. In this study, we investigated the effect of different phytohormones on microalgal growth and biodiesel production in Chlamydomonas reinhardtii and their potential to lower the overall cost of commercial biofuel production. The results indicated that all five of the tested phytohormones (indole-3-acetic acid, gibberellic acid, kinetin, 1-triacontanol, and abscisic acid) promoted microalgal growth. In particular, hormone treatment increased biomass production by 54 to 69 % relative to the control growth medium (Tris-acetate-phosphate, TAP). Phytohormone treatments also affected microalgal cell morphology but had no effect on the yields of fatty acid methyl esters (FAMEs) as a percent of biomass. We also tested the effect of these phytohormones on microalgal growth in nitrogen-limited media by supplementation in the early stationary phase. Maximum cell densities after addition of phytohormones were higher than in TAP medium, even when the nitrogen source was reduced to 40 % of that in TAP medium. Taken together, our results indicate that phytohormones significantly increased microalgal growth, particularly in nitrogen-limited media, and have potential for use in the development of efficient microalgal cultivation for biofuel production.

  9. Strategic plan modelling by hospital senior administration to integrate diversity management.

    PubMed

    Newhouse, John J

    2010-11-01

    Limited research suggests that some hospital senior administrators and chief executive officers (CEOs) have employed a strategic planning function to achieve diversity management practices. As the hospital industry struggles with how to integrate diversity practices to improve patient satisfaction, increase the quality of care and enhance clinical outcomes for minority populations, understanding the planning process involved in this endeavour becomes significant for senior hospital administrators. What is not well understood is what this strategic planning process represents and how it is applied to integrate diversity management. Scant research exists about the type of strategic models that hospital CEOs employ when they wish to reposition their organizations through diversity management. This study examines the strategic planning models used by senior administrators to integrate diversity management for an institutional-wide agenda. A qualitative survey process was used for CEOs in the states of New York, Pennsylvania, New Jersey and Delaware. The key research questions dealt with what type of strategic plan approach senior administrators used for integrating diversity management and what rationale they used to pursue this. Significant differences were reported between three types of strategic plan modelling used by CEOs. Also, when comparing past and current practices over time, such differences existed. The need to integrate diversity management is underscored by this study. How senior hospital administrators apply strategic plan models and what impact these approaches have represent the major implications that this study offers.

  10. Wheel-running attenuates intravenous cocaine self-administration in rats: sex differences.

    PubMed

    Cosgrove, Kelly P; Hunter, Robb G; Carroll, Marilyn E

    2002-10-01

    This experiment examines the effect of access to a running-wheel on intravenous cocaine self-administration in male and female rats. Rats maintained at 85% of their free-feeding body weight were first exposed to the running-wheel alone during the 6-h sessions until behavior stabilized for 14 days. Intravenous cannulae were then implanted, and the rats were trained to self-administer a low dose of cocaine (0.2 mg/kg) under a fixed-ratio (FR 1) schedule during the 6-h sessions, while the wheel remained inactive and cocaine self-administration stabilized (cocaine-only condition). Next, the wheel access and cocaine self-administration were concurrently available followed by a period of cocaine-only. Behavior was allowed to stabilize for 10 days at each phase. During wheel access, cocaine infusions decreased by 21.9% in males and 70.6% in females compared to the cocaine-only condition; the effect was statistically significant in females. Infusions increased to baseline levels when wheel access was terminated. When cocaine infusions were concurrently available, wheel revolutions were reduced by 63.7% and 61.5% in males and females, respectively, compared to the wheel-only condition. This result did not differ due to sex, but it was statistically significant when data from males and females were combined. These results indicate that wheel-running activity had a greater suppressant effect on cocaine self-administration in females than in males, and in females, wheel-running and cocaine self-administration are substitutable as reinforcers.

  11. Co-administration of water containing magnesium ion prevents loxoprofen-induced lesions in gastric mucosa of adjuvant-induced arthritis rat.

    PubMed

    Nagai, Noriaki; Takeda, Atsushi; Itanami, Yuri; Ito, Yoshimasa

    2012-01-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) comprise one of the most frequently used classes of medicines in the world; however, NSAIDs have significant side effects, such as gastroenteropathy, and rheumatoid arthritis patients taking NSAIDs are more susceptible to NSAID-induced gastric lesions as compared to patients with other diseases. In Asian countries, loxoprofen has been used clinically for many years as a standard NSAID. We demonstrate the preventive effect of the co-administration of water containing magnesium ion (magnesium water, 1-200 µg/kg) on the ulcerogenic response to loxoprofen in adjuvant-induced arthritis (AA) rats. Oral administration of loxoprofen (100 mg/kg) caused hemorrhagic lesions in the gastric mucosa of AA rats 14 d after adjuvant injection, and, following loxoprofen administration, the lesion score of AA rats was significantly higher than that of normal rats. The expression of inducible nitric oxide synthase (iNOS) mRNA and nitric oxide (NO) production in the gastric mucosa of AA rats were also increased by the administration of loxoprofen, and the increase in lesions and NO were prevented by the administration of aminoguanidine, an iNOS inhibitor. The co-administration of magnesium water decreased the ulcerogenic response to loxoprofen in AA rats. In addition, the co-administration of magnesium water attenuated the increase in iNOS mRNA expression and NO production in AA rats receiving loxoprofen. These results suggest that the oral co-administration of magnesium water to AA rats has a potent preventive effect on the ulcerogenic response to loxoprofen, probably by inhibiting the rise in iNOS and NO levels in the gastric mucosa.

  12. Chronic corticosterone administration facilitates aversive memory retrieval and increases GR/NOS immunoreactivity.

    PubMed

    Santos, Thays B; Céspedes, Isabel C; Viana, Milena B

    2014-07-01

    Glucocorticoids are stress hormones that mediate the organism's reaction to stress. It has been previously proposed that the facilitation of emotional aversive conditioning induced by these hormones may involve nitric oxide-pathways. The purpose of the present study was to address this question. For that, male Wistar rats were surgically implanted with slow-release corticosterone (CORT) pellets (21 days) and tested in a step-down inhibitory avoidance task. Additional groups of animals were also submitted to the same treatment conditions and on the 21st day of treatment assayed for GR (glucocorticoid receptors)-nNOS (neuronal nitric oxide synthase) immunoreactivity (GRi-nNOSi) or measurements of plasma CORT. Results showed that CORT treatment induced facilitation of step-down inhibitory avoidance. This same treatment also significantly increased CORT plasma levels and GRi in the medial, basolateral and basomedial amygdala, in the paraventricular hypothalamic nucleus (PVN), in the ventral and dorsal dentate gyrus, in the ventral CA1 region and in the dorsal CA1 and CA3 regions. Furthermore, nNOSi and GRi-nNOSi were significantly increased by CORT treatment in the medial amygdala and basolateral amygdaloid complex, in the PVN, subiculum, in the dorsal CA3 region and in the ventral CA1 and CA3 regions. These results indicate that the facilitation of aversive conditioning induced by CORT involves GR-nNOS pathways activation, what may be of relevance for a better understanding of stress-related psychiatric conditions. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Pharmacokinetics of escin Ia in rats after intravenous administration.

    PubMed

    Wu, Xiu-Jun; Cui, Xiang-Yong; Tian, Lian-tian; Gao, Feng; Guan, Xin; Gu, Jing-Kai

    2014-10-28

    Escin, a natural mixture of triterpene saponins, is commonly utilized for the treatment of chronic venous insufficiency, hemorrhoids, inflammation and edema. Escin Ia is the chief active ingredient in escin and plays key role in mediating its pharmacological effects. Adequate pharmacokinetic data are essential for proper application of escin agent in clinical practice. However, pharmacokinetic properties of escin Ia are still poorly understood and this conflicts with the growing use of escin agent over the years. The goal of this study is to investigate the pharmacokinetic behavior of escin Ia in rats after low, medium and high-dose intravenous administration. Wistar rats were divided into 3 groups (n=6 per group) and escin Ia was administered via the caudal vein at doses of 0.5, 1.0 and 2.0 mg/kg, respectively. Subsequently, the concentrations of escin Ia and its metabolite isoescin Ia, a positional isomer of escin Ia, in rats׳ plasma were measured by an established liquid chromatography tandem mass spectrometry (LC-MS/MS) method at various time points following the administration of the drug. Main pharmacokinetic parameters were calculated by non-compartmental analysis using the TopFit 2.0 software package (Thomae GmbH, Germany). After intravenous administration, the Cmax and AUC of escin Ia increased in a dose-proportional manner at the dose of 0.5 mg/kg and 1.0 mg/kg, while increased in a more than dose-proportional manner at the doses of 1.0 mg/kg and 2.0 mg/kg. The t₁/₂ was significantly longer with increased intravenous doses, while other parameters such as CL and Vd also exhibit disagreement among three doses. Taken together, our data showed dose-dependent pharmacokinetic profile of escin Ia in rats after intravenous administration at the doses of 0.5-2.0 mg/kg. After intravenous administration, escin Ia was rapidly and extensively converted to isoescin Ia. The results suggested dose-dependent pharmacokinetics of escin Ia at the doses of 0.5-2.0 mg

  14. Increased oral AUC of baicalin in streptozotocin-induced diabetic rats due to the increased activity of intestinal beta-glucuronidase.

    PubMed

    Liu, Li; Deng, Yuan-Xiong; Liang, Yan; Pang, Xiao-Yan; Liu, Xiao-Dong; Liu, Yao-Wu; Yang, Jian-Song; Xie, Lin; Wang, Guang-Ji

    2010-01-01

    The purpose of the study was to investigate the pharmacokinetics of baicalin, a major bioactive component of Scutellariae radix, in diabetic conditions. The 4-week diabetic rats were induced by intraperitoneal administration of streptozotocin. Plasma concentrations of baicalin were measured following oral (200 mg/kg) or intravenous (12 mg/kg) administration. Everted intestinal transport, intestinal mucosal metabolism of baicalin and intestinal beta-glucuronidase activity were also investigated. It was found that the diabetic condition significantly increased the exposure of baicalin following oral doses (AUC 100.77 +/- 4.16 microg x h/mL in diabetic rats vs. 48.48 +/- 7.94 microg x h/mL in normal rats). In contrast, the diabetic condition significantly decreased the exposure of baicalin following intravenous doses (AUC 11.20 +/- 2.28 microg x h/mL in diabetic rats vs. 18.02 +/- 3.45 microg x h/mL in normal rats). We also found lower apparent permeability coefficients of baicalin in the ileum of diabetic rats (8.43 x 10 (-6) +/- 2.40 x 10 (-6) cm/s in diabetic rats vs. 5.21 x 10 (-5) +/- 1.55 x 10 (-5) cm/s in normal rats). Further studies showed that the diabetic condition enhanced the hydrolysis of baicalin to baicalein in intestinal mucosal, accompanied by an increase of beta-glucuronidase activity. All these results suggested that the higher oral exposure of baicalin in diabetic rats did not result from the decreased hepatic metabolism or increased intestinal absorption of baicalin. The enhancement of intestinal beta-glucuronidase activity may partly account for the higher exposure of baicalin in diabetic rats after oral administration. Copyright Georg Thieme Verlag KG Stuttgart . New York.

  15. Sleeping Pill Administration Time and Patient Subjective Satisfaction

    PubMed Central

    Chung, Seockhoon; Youn, Soyoung; Yi, Kikyoung; Park, Boram; Lee, Suyeon

    2016-01-01

    Study Objectives: Taking hypnotic agents 30 min before bedtime is the usual suggested administration time, but some patients report dissatisfaction with their sleeping pills. We investigated whether the timing of sleeping pill administration influences patient subjective satisfaction with these drugs. Methods: One hundred twelve patients with primary insomnia currently taking benzodiazepine or nonbenzodiazepine gamma-aminobutyric acid (GABA) agonists as sleeping pills were selected. The time of administration for their sleeping pills, bedtime, sleep onset time, and wake up time were obtained from their medical records. Subjects were also categorized into satisfied or dissatisfied groups. Results: Hypnotic agents administration time (p < 0.001) and bedtime (p < 0.001), but not sleep onset or wake up time, occurred later in the night in the satisfied group. The durations from administration of pills to sleep onset (33.6 ± 20.7 min) and to wake up time (7.2 ± 1.2 h) were significantly shorter in the satisfied group when compared to the dissatisfied group (135.9 ± 73.4 min and 9.3 ± 1.5 h for time to sleep onset and wake up, respectively). Logistic regression analysis revealed that patient subjective satisfaction with hypnotic agents could be predicted by a short duration from administration of pills to sleep onset (odds ratio = 0.01; 95% confidence interval [0.001–0.09]) and a short duration from administration of pills to wake up time (0.53; [0.31–0.89], F = 49.9, p < 0.001). Conclusions: Taking sleeping pills at a later time and a shorter interval between pill administration and wake up time may increase patient subjective satisfaction with hypnotic agents. We propose that physicians advise patients to take sleeping pills approximately 7 h before their usual getting-out-of-bed time instead of the current standard of 30 min before bedtime. Citation: Chung S, Youn S, Yi K, Park B, Lee S. Sleeping pill administration time and patient subjective satisfaction. J

  16. 48-hours administration of fenoterol in spontaneous preterm labor - does it affect fetal preload?

    PubMed

    Grzesiak, Mariusz; Forys, Sebastian; Sobczak, Malgorzata; Ahmed, Rehana B; Wilczynski, Jan

    2013-01-01

    to investigate whether any changes in the preload index (PLI) occur within the first 48 hours of fenoterol intravenous tocolysis. Doppler evaluation of placental and fetal circulation was performed in 36 pregnant women prior to fenoterol administration and after 24/48 hours. Measurements were obtained from a longitudinal section of the inferior vena cava (IVC) and preload index was calculated. To determine changes over time, an all study variable analysis of variance (ANOVA) for repeated measurements, followed by Tukey-Kramer's multiple comparison test was used. The effects of additional clinical covariates were checked. The maternal heart rate values were significantly increased after 24 hours and 48 hours in comparison to pre-treatment values. No significant changes in fetal heart rate were observed during treatment. The fetal IVC PLI values were significantly reduced after 24 hours and 48 hours of treatment. The increase in PLI values when comparing 24 and 48 hours results were not statistically significant. These observations were consistent with ANOVA post-hoc analysis. 48 hours intravenous administration of fenoterol appears not to alter inferior vena cava blood flow by itself. The reduction in PLI values may reflect lower fetal preload conditions during the course of successful tocolytic treatment. Therefore, Doppler IVC PLI measurement should be considered as a possible additional assessment method of effectiveness of treatment. However, other Doppler venous blood flow parameters should be assessed to confirm the results and clarify whether maternal corticosteroids administration may be interfering with the results.

  17. Does administering a comprehensive examination affect pass rates on the Registered Health Information Administrator certification examination?

    PubMed

    McNeill, Marjorie H

    2009-01-01

    The purpose of this research study was to determine whether the administration of a comprehensive examination before graduation increases the percentage of students passing the Registered Health Information Administrator certification examination. A t-test for independent means yielded a statistically significant difference between the Registered Health Information Administrator certification examination pass rates of health information administration programs that administer a comprehensive examination and programs that do not administer a comprehensive examination. Programs with a high certification examination pass rate do not require a comprehensive examination when compared with those programs with a lower pass rate. It is concluded that health information administration faculty at the local level should perform program self-analysis to improve student progress toward achievement of learning outcomes and entry-level competencies.

  18. Chronic Ethanol Administration Prevents Compensatory Cardiac Hypertrophy in Pressure Overload.

    PubMed

    Ninh, Van K; El Hajj, Elia C; Mouton, Alan J; El Hajj, Milad C; Gilpin, Nicholas W; Gardner, Jason D

    2018-05-30

    Alcohol is among the most commonly abused drugs worldwide and affects many organ systems, including the heart. Alcoholic cardiomyopathy is characterized by a dilated cardiac phenotype with extensive hypertrophy and extracellular matrix (ECM) remodeling. We have previously shown that chronic ethanol (EtOH) administration accelerates the progression to heart failure in a rat model of volume overload. However, the mechanism by which this decompensation occurs is unknown. For this study, we hypothesized that chronic EtOH administration would prevent compensatory hypertrophy and cardiac remodeling in a rodent model of pressure overload (PO). Abdominal aortic constriction was used to create PO in 8-week-old male Wistar rats. Alcohol administration was performed via chronic intermittent EtOH vapor inhalation for 2 weeks prior to surgery and for the duration of the 8-week study. Echocardiography measurements were taken to assess ventricular functional and structural changes. PO increased posterior wall thickness and the hypertrophic markers, atrial and B-type natriuretic peptides (ANP and BNP). With the added stressor of EtOH, wall thickness, ANP, and BNP decreased in PO animals. The combination of PO and EtOH resulted in increased wall stress compared to PO alone. PO also caused increased expression of collagen I and III, whereas EtOH alone only increased collagen III. The combined stresses of PO and EtOH led to an increase in collagen I expression, but collagen III did not change, resulting in an increased collagen I/III ratio in the PO rats treated with EtOH. Lastly, Notch1 expression was significantly increased only in the PO rats treated with EtOH. Our data indicate that chronic EtOH may limit the cardiac hypertrophy induced by PO which may be associated with a Notch1 mechanism, resulting in increased wall stress and altered ECM profile. Copyright © 2018 by the Research Society on Alcoholism.

  19. Testosterone Administration Reduces Lying in Men

    PubMed Central

    Wibral, Matthias; Dohmen, Thomas; Klingmüller, Dietrich; Weber, Bernd; Falk, Armin

    2012-01-01

    Lying is a pervasive phenomenon with important social and economic implications. However, despite substantial interest in the prevalence and determinants of lying, little is known about its biological foundations. Here we study a potential hormonal influence, focusing on the steroid hormone testosterone, which has been shown to play an important role in social behavior. In a double-blind placebo-controlled study, 91 healthy men (24.32±2.73 years) received a transdermal administration of 50 mg of testosterone (n = 46) or a placebo (n = 45). Subsequently, subjects participated in a simple task, in which their payoff depended on the self-reported outcome of a die-roll. Subjects could increase their payoff by lying without fear of being caught. Our results show that testosterone administration substantially decreases lying in men. Self-serving lying occurred in both groups, however, reported payoffs were significantly lower in the testosterone group (p<0.01). Our results contribute to the recent debate on the effect of testosterone on prosocial behavior and its underlying channels. PMID:23071635

  20. Long-term parenteral administration of 2-hydroxypropyl-β-cyclodextrin causes bone loss.

    PubMed

    Kantner, Ingrid; Erben, Reinhold G

    2012-07-01

    Cyclodextrins are oligosaccharides which are used in the pharmaceutical industry and research as vehicles for application of apolar substances such as steroids. The aim of this study was to examine the long-term effects of parenteral administration of 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) on bone. Sham-operated (SHAM) or ovariectomized (OVX) adult rats were subcutaneously injected with physiological saline, 50, or 200 mg/kg HP-β-CD daily. After 4 months, body weight in OVX rats and uterine weight in SHAM rats were significantly lower after administration of 200 mg/kg HP-β-CD, relative to vehicle controls. At 200 mg/kg, HP-β-CD was hepatotoxic as measured by increased serum transaminases, and reduced serum albumin. Moreover, 200 mg/kg HP-β-CD led to decreased vertebral and tibial bone mineral density (BMD), and to cortical thinning at the tibial shaft. Bone loss in HP-β-CD-treated rats was associated with increased bone resorption as measured by increased renal deoxypyridinoline excretion. Although 50 mg/kg HP-β-CD was devoid of overt signs of organ toxicity and did not impair BMD, bone resorption was already increased. In summary, subcutaneous long-term administration of HP-β-CD at a daily dose of 200 mg/kg led to increased bone resorption and subsequent bone loss. Minor alterations in bone metabolism were also seen at 50 mg/kg.

  1. Administration's Proposed NSF Budget Includes a 5.5% Increase for Geosciences

    NASA Astrophysics Data System (ADS)

    Showstack, Randy

    2013-04-01

    The fiscal year (FY) 2014 proposed federal budget for the U.S. National Science Foundation (NSF) is $7.63 billion, 7.3% above the FY 2012 actual amount. NSF acting director Cora Marrett said the budget reflects the administration's recognition of NSF and the importance of funding basic research. "We are pleased about where we stand and hope that Congress will be just as pleased with the budget proposal and will help move things forward," she said during a meeting of the NSF Advisory Committee for Geosciences on 11 April. Budget comparisons are to FY 2012 because the 2013 appropriations were enacted at the end of March, less than 2 weeks before President Barack Obama sent the proposed budget to Congress.

  2. The Veterans Administration Library Network: VALNET.

    PubMed Central

    van Vuren, D D

    1982-01-01

    Given substantial federal budget cuts and ever-increasing quantities of print and nonprint material, Veterans Administration (VA) Library Services have pooled their resources in a network to improve the scope and efficiency of the services they provide. The VA Library Network, VALNET, composed of 176 libraries, serves health care facilities throughout the continental United States and Puerto Rico. This paper outlines VALNET's organization and the range of individual VA Library Services. It also describes centrally provided services and resource-sharing tools being developed by the VA, as well as significant sharing arrangement among VA Library Services and between the VA and non-VA libraries. PMID:7052164

  3. Effect of local administration of simvastatin on postorthodontic relapse in a rabbit model.

    PubMed

    AlSwafeeri, Hani; ElKenany, Walid; Mowafy, Mohamed; Karam, Sahar

    2018-06-01

    Posttreatment relapse is a major challenging clinical issue. The objective of this study was to evaluate the effect of local administration of simvastatin on posttreatment relapse. Orthodontic tooth movement was induced in 10 white New Zealand rabbits. After 21 days of active tooth movement, the orthodontic appliances were removed, and the experimental teeth were allowed to relapse for 21 days. During the relapse phase, 1 mandibular quadrant received local simvastatin administration, and the other received the control vehicle solution on a weekly basis. Three-dimensional models of the experimental teeth were created to allow the measurement of experimental tooth movement and posttreatment relapse. The animals were killed at the end of the relapse phase for histomorphometric analysis of alveolar bone remodeling. The mean relapse percentages were 75.83% in the quadrant receiving the control vehicle solution and 62.01% in the quadrant receiving simvastatin. Neither the relapse magnitude nor the relapse percentage showed a significant difference between the 2 quadrants. Histomorphometric analyses showed that local simvastatin administration yielded a significant reduction in the area of active bone-resorptive lacunae and a significant increase in newly formed bone area. Although local administration of simvastatin aids in bone remodeling associated with posttreatment relapse by reducing the area of active bone resorption and upregulating bone formation, it did not significantly minimize posttreatment relapse. Copyright © 2018 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.

  4. Applying airline safety practices to medication administration.

    PubMed

    Pape, Theresa M

    2003-04-01

    Medication administration errors (MAE) continue as major problems for health care institutions, nurses, and patients. However, MAEs are often the result of system failures leading to patient injury, increased hospital costs, and blaming. Costs include those related to increased hospital length of stay and legal expenses. Contributing factors include distractions, lack of focus, poor communication, and failure to follow standard protocols during medication administration.

  5. Challenges to Women's Participation in Senior Administrative Positions in Iranian Higher Education

    ERIC Educational Resources Information Center

    Mohajeri, Bahieh; Mousavi, Farah

    2017-01-01

    In the last three decades, growth in the education of women in Iran has led to a significant increase in demand for women professionals and administrators in Iranian universities. However, the path to the top is not easy and numerous challenges must still be overcome. This study explored the challenges of women's participation in senior…

  6. Effectiveness of administration of gonadotropin-releasing hormone at Days 11, 14 or 15 after anticipated ovulation for increasing fertility of lactating dairy cows and non-lactating heifers.

    PubMed

    Franco, M; Thompson, P M; Brad, A M; Hansen, P J

    2006-09-01

    One strategy for improving fertility in cattle is mid-cycle administration of GnRH to increase progesterone secretion and delay luteolysis. This strategy might be especially useful during hot weather because heat stress increases uterine prostaglandin release and reduces development of the elongating embryo. A series of experiments was conducted to test the efficacy of GnRH for increasing fertility. There was no effect of administration of 100 microg GnRH at Day 11 after anticipated ovulation on pregnancy rates in virgin heifers subjected to timed artificial insemination (TAI) during the summer. Similarly, there was no beneficial effect of administration of GnRH at Day 11 after anticipated ovulation on pregnancy rates of lactating cows subjected to TAI in summer and winter. Three experiments tested effects of injection of GnRH at Days 14 or 15 after anticipated ovulation on pregnancy rates of lactating cows. The first experiment used 477 lactating cows subjected to TAI. Cows receiving GnRH at Day 14 had higher pregnancy rates in both summer and winter than cows receiving vehicle (20.3 versus 12.7%, P<0.02). When this experiment was repeated during summer with 137 cows, there was a negative effect of GnRH treatment at Day 14 on pregnancy rate. In the third experiment, lactating cows during summer were inseminated at detected estrus and cows were assigned to treatment with either GnRH or vehicle at Days 14 or 15 after insemination. Pregnancy rates were 25.6% (32/125) for cows receiving vehicle, 20.7% (19/92) for cows receiving GnRH at Day 14, and 20.3% (16/79) for cows receiving GnRH at Day 15. In conclusion, GnRH administration at Days 11-15 after anticipated ovulation or estrus did not consistently increase pregnancy rates in either cool or warm seasons.

  7. Effects of vasopressin administration on diuresis of water immersion in normal humans

    NASA Technical Reports Server (NTRS)

    Epstein, M.; Denunzio, A. G.; Loutzenhiser, R. D.

    1981-01-01

    The influence of vasopressin suppression on the diuresis encountered during water immersion is investigated in studies on normal humans immersed to the neck. Six hydrated male subjects were studied on two occasions while undergoing 6 h of immersion without or during the administration of aqueous vasopressin for the initial 4 h. Neck immersion is found to result in a significant increase in urinary flow rate beginning in the first hour and persisting throughout the immersion. The administration of vasopressin markedly attenuated the diuretic response throughout the period of infusion, while cessation of vasopressin administration during the final 2 h of immersion resulted in a marked offset of the antidiuresis. Results thus support the view that the suppression of antidiuretic hormone contributes to the immersion diuresis of hydrated subjects.

  8. Significant increase of Curie temperature in nano-scale BaTiO{sub 3}

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Li, Yueliang; Liao, Zhenyu; Fang, Fang

    2014-11-03

    The low Curie temperature (T{sub c} = 130 °C) of bulk BaTiO{sub 3} greatly limits its applications. In this work, the phase structures of BaTiO{sub 3} nanoparticles with sizes ranging from 2.5 nm to 10 nm were studied at various temperatures by using aberration-corrected transmission electron microscopy (TEM) equipped with an in-situ heating holder. The results implied that each BaTiO{sub 3} nanoparticle was composed of different phases, and the ferroelectric ones were observed in the shells due to the complicated surface structure. The ferroelectric phases in BaTiO{sub 3} nanoparticles remained at 600 °C, suggesting a significant increase of T{sub c}. Based on the in-situ TEM resultsmore » and the data reported by others, temperature-size phase diagrams for BaTiO{sub 3} particles and ceramics were proposed, showing that the phase transition became diffused and the T{sub c} obviously increased with decreasing size. The present work sheds light on the design and fabrication of advanced devices for high temperature applications.« less

  9. School Choice and Administrators: Will Principals Become Marketers?

    ERIC Educational Resources Information Center

    Robenstine, Clark

    2000-01-01

    Argues that school choice, with its reliance on market forces, has serious implications for what goes on inside the school and the principal's role. Looks at changes in administrative focus and management style; at administrators and school marketing, with image management increasingly preoccupying school administrators; and the almost exclusive…

  10. Enhanced absorption of indomethacin after oral or rectal administration of a self-emulsifying system containing indomethacin to rats.

    PubMed

    Kim, J Y; Ku, Y S

    2000-01-20

    A self-emulsifying system (SES), a mixture of an oil and a surfactant which forms an oil-in-water emulsion, is expected to improve the in vitro drug dissolution and enhance the in vivo drug absorption. In this study, a poorly water-soluble drug, indomethacin (IDM) was incorporated into the SES to increase bioavailability. The SES with 30% of Tween 85 and 70% of ethyl oleate, EO (w/w) was selected as an optimized formulation (high drug loading, low surfactant concentration, and small particle size). After an oral administration of the SES containing IDM and IDM suspension, (IDM was suspended in methyl cellulose), 22.5 mg/kg as IDM, to rats, the area under the plasma concentration-time curve from time zero to the last measured time in plasma, 12 h (AUC(0-12 h)) was significantly greater (57% increase) in the SES, suggesting that oral absorption of IDM increased significantly by the SES. After a rectal administration of gelatin hollow type suppositories, filled with the SES containing IDM and IDM powder physically mixed with the SES, 22. 5 mg/kg, to rats, the AUC(0-12 h) also increased significantly (41% increase) by the SES, suggesting that rectal absorption of IDM also increased significantly by the SES.

  11. Endocrinological effects of single daily ketoconazole administration in male beagle dogs.

    PubMed

    De Coster, R; Beerens, D; Dom, J; Willemsens, G

    1984-10-01

    Some endocrinological effects of single daily oral administration of 150 mg ketoconazole for 15 days were investigated in 4 male beagle dogs. Plasma testosterone fell markedly within 3-4 h and then progressively returned to control concentrations by 10 h after drug administration. On the other hand, plasma 17 alpha-hydroxyprogesterone, progesterone and 17 alpha, 20 alpha-dihydroxyprogesterone increased within 3-10 h before returning to basal values after 24 h. Plasma LH did not rise significantly though some high individual levels were noted. Plasma cortisol and oestradiol-17 alpha levels were not significantly modified by the treatment. These results confirm that a high therapeutic dose of ketoconazole, given orally once a day, transiently inhibits in vivo the 17-20 lyase enzyme of the testis, without modifying basal cortisol and oestradiol-17 beta plasma concentrations and that enzymatic inhibition still occurs after daily treatment for up to 2 weeks but remains transient and parallels the resorption profile of the drug so that normal plasma testosterone levels are observed from 10 to 24 h after drug intake. However, permanent inhibition of androgen biosynthesis might be obtained by the administration of high doses of ketoconazole given several times a day.

  12. Cerebrospinal fluid and behavioral changes after methyltestosterone administration: preliminary findings.

    PubMed

    Daly, R C; Su, T P; Schmidt, P J; Pickar, D; Murphy, D L; Rubinow, D R

    2001-02-01

    Anabolic androgen steroid abuse is associated with multiple psychiatric symptoms and is a significant public health problem. The biological mechanisms underlying behavioral symptom development are poorly understood. We examined levels of monoamine metabolites, neurohormones, and neuropeptides in the cerebrospinal fluid (CSF) of 17 healthy men, at baseline and following 6 days of methyltestosterone (MT) administration (3 days of 40 mg/d, then 3 days of 240 mg/d). Subjects received MT or placebo in a fixed sequence, with neither subjects nor raters aware of the order. Potential relationships were examined between CSF measures, CSF MT levels, and behavioral changes measured on a visual analog scale. Following MT administration, levels of 3-methoxy-4-hydroxyphenylglycol (MHPG) were significantly lower (mean +/- SD, 103.8 +/- 47 vs 122.0 +/- 50.7 pmol/mL; P<.01), and 5-hydroxyindoleacetic acid (5-HIAA) levels were significantly higher (mean +/- SD, 104.7 +/- 31.3 vs 86.9 +/- 23.6 pmol/mL; P<.01). No significant MT-related changes were observed in CSF levels of corticotropin, norepinephrine, cortisol, arginine vasopressin, prolactin, corticotropin-releasing hormone, beta-endorphin, and somatotropin release-inhibiting factor. Changes in CSF 5-HIAA significantly correlated with increases in "activation" symptoms (energy, sexual arousal, and diminished sleep) (r = 0.55; P =.02). No significant correlation was observed between changes in CSF and plasma MT, CSF MHPG, and behavioral symptoms. Short-term anabolic androgenic steroid use affects brain neurochemistry, increasing CSF 5-HIAA and decreasing MHPG. Changes in 5-HIAA levels caused by anabolic androgenic steroids are related to the behavioral changes we observed. In this small sample, we did not observe a significant relationship between behavioral measures and either dose of MT or CSF and plasma levels of MT.

  13. Increase in swimming endurance capacity of mice by capsaicin-induced adrenal catecholamine secretion.

    PubMed

    Kim, K M; Kawada, T; Ishihara, K; Inoue, K; Fushiki, T

    1997-10-01

    Increase in endurance swimming capacity caused by capsaicin (CAP), a pungent component of red pepper, -induced increase of fat metabolism in mice was investigated using an adjustable-current water pool. The mice administered CAP via a stomach tube, showed longer swimming time until exhaustion than the control group of mice, in a dose-dependent manner. The maximal effect was observed at a dose of 10 mg/kg while more than 15 mg/kg had no effect. The increase of endurance was observed only when CAP was administered two hours before swimming. After the administration of CAP, the serum glucose concentration rapidly increased and then decreased within 60 min, while the concentration of serum-free fatty acids gradually increased through 3 hours. The residual glycogen concentration of the gastrocnemius muscle after 30 min of swimming was significantly higher in the CAP-administered mice than in control mice, suggesting that use of the serum free fatty acids spared muscle glycogen consumption. The serum adrenaline concentration significantly increased with twin peaks at 30 min and two hours after administration of CAP. An experiment using adrenalectomized mice was done to confirm that the effect of CAP is due to increased energy metabolism through the secretion of adrenaline from the adrenal gland. The swimming endurance capacity of the adrenalectomized mice was not increased by CAP administration, although adrenaline injection induced a 58% increase in the endurance time. These results suggest that the increase of swimming endurance induced by CAP in mice is caused by an increase in fatty acid utilization due to CAP-induced adrenal catecholamine secretion.

  14. Hierarchical pulmonary target nanoparticles via inhaled administration for anticancer drug delivery.

    PubMed

    Chen, Rui; Xu, Liu; Fan, Qin; Li, Man; Wang, Jingjing; Wu, Li; Li, Weidong; Duan, Jinao; Chen, Zhipeng

    2017-11-01

    Inhalation administration, compared with intravenous administration, significantly enhances chemotherapeutic drug exposure to the lung tissue and may increase the therapeutic effect for pulmonary anticancer. However, further identification of cancer cells after lung deposition of inhaled drugs is necessary to avoid side effects on normal lung tissue and to maximize drug efficacy. Moreover, as the action site of the major drug was intracellular organelles, drug target to the specific organelle is the final key for accurate drug delivery. Here, we designed a novel multifunctional nanoparticles (MNPs) for pulmonary antitumor and the material was well-designed for hierarchical target involved lung tissue target, cancer cell target, and mitochondrial target. The biodistribution in vivo determined by UHPLC-MS/MS method was employed to verify the drug concentration overwhelmingly increasing in lung tissue through inhaled administration compared with intravenous administration. Cellular uptake assay using A549 cells proved the efficient receptor-mediated cell endocytosis. Confocal laser scanning microscopy observation showed the location of MNPs in cells was mitochondria. All results confirmed the intelligent material can progressively play hierarchical target functions, which could induce more cell apoptosis related to mitochondrial damage. It provides a smart and efficient nanocarrier platform for hierarchical targeting of pulmonary anticancer drug. So far, this kind of material for pulmonary mitochondrial-target has not been seen in other reports.

  15. Effects of Oral Glucosamine Hydrochloride Administration on Plasma Free Amino Acid Concentrations in Dogs

    PubMed Central

    Azuma, Kazuo; Osaki, Tomohiro; Tsuka, Takeshi; Imagawa, Tomohiro; Okamoto, Yoshiharu; Takamori, Yoshimori; Minami, Saburo

    2011-01-01

    We examined the effects of oral glucosamine hydrochloride (GlcN), N-acetyl-d-glucosamine (GlcNAc) and d-glucose (Glc) administration on plasma total free amino acid (PFAA) concentrations in dogs. The PFAA concentrations increased in the control group and the GlcNAc group at one hour after feeding, and each amino acid concentration increased. On the other hand, in the GlcN group and the Glc group PFAA concentrations decreased at one hour after feeding. A significant decrease in amino acid concentration was observed for glutamate, glycine and alanine. Our results suggest the existence of differences in PFAA dynamics after oral administration of GlcN and GlcNAc in dogs. PMID:21673884

  16. [Case report: a recurrent gastric cancer in the terminal stage, associated with obstructive jaundice which responded significantly to oral administration of TS-1].

    PubMed

    Tasaka, K; Tomofuzi, Y; Sugihara, Z; Fukuda, H

    2001-10-01

    TS-1, a novel oral formation of 5-fluorouracil that consists of 1M tegafur (5-FU), 0.4M CDHP and 1M Oxo, is reported to achieve a higher response rate of 49% in patients with advanced gastric cancer in a late phase II study. We report a case of recurrent gastric cancer that responded significantly to the short-term administration of TS-1. A 73-year-old man, who had undergone a curative distal gastrectomy with D2 lymphadenectomy 2 years earlier, had presented with obstructive jaundice resulting from cancerous lymphadenopathy. PTCD was performed for drainage, but cholestasis disappeared completely through the two courses of oral administration of TS-1. The serum level of transaminase and bilirubin remained within normal limits, even with PTCD unequipped, until the patient died of the original disease. The adverse effects observed with the drug were anemia (grade 1) and skin pigmentation (grade 2), both of which improved soon after discontinuing the medication. In conclusion, TS-1 may be well-tolerable and effective in some cases of terminal-stage and/or recurrent gastric cancer, especially those associated with obstructive jaundice arising from the cancerous lymphadenopathy, in that patient QOL can be maintained to a much greater extent.

  17. Lidocaine Administration Controls MicroRNAs Alterations Observed After Lung Ischemia-Reperfusion Injury.

    PubMed

    Rancan, Lisa; Simón, Carlos; Marchal-Duval, Emmeline; Casanova, Javier; Paredes, Sergio Damian; Calvo, Alberto; García, Cruz; Rincón, David; Turrero, Agustín; Garutti, Ignacio; Vara, Elena

    2016-12-01

    Ischemia-reperfusion injury (IRI) is associated with morbidity and mortality. MicroRNAs (miRNAs) have emerged as regulators of IRI, and they are involved in the pathogenesis of organ rejection. Lidocaine has proven anti-inflammatory activity in several tissues but its modulation of miRNAs has not been investigated. This work aims to investigate the involvement of miRNAs in lung IRI in a lung auto-transplantation model and to investigate the effect of lidocaine. Three groups (sham, control, and Lidocaine), each comprising 6 pigs, underwent a lung autotransplantation. All groups received the same anesthesia. In addition, animals of lidocaine group received a continuous intravenous administration of lidocaine (1.5 mg/kg/h) during surgery. Lung biopsies were taken before pulmonary artery clamp, before reperfusion, 30 minutes postreperfusion (Rp-30), and 60 minutes postreperfusion (Rp-60). Samples were analyzed for different miRNAs (miR-122, miR-145, miR-146a, miR-182, miR-107, miR-192, miR-16, miR-21, miR-126, miR-127, miR142-5p, miR152, miR155, miR-223, and let7) via the use of reverse-transcription quantitative polymerase chain reaction. Results were normalized with miR-103. The expression of miR-127 and miR-16 did not increase after IRI. Let-7d, miR-21, miR-107, miR-126, miR-145, miR-146a, miR-182, and miR-192 significantly increased at the Rp-60 (control versus sham P < .001). miR-142-5p, miR-152, miR-155, and miR 223 significantly increased at the Rp-30 (control versus sham P < .001) and at the Rp-60 (control versus. sham P < .001). The administration of lidocaine was able to attenuate these alterations in a significant way (control versus Lidocaine P < .001). Lung IRI caused dysregulation miRNA. The administration of lidocaine reduced significantly miRNAs alterations.

  18. Intraintestinal administration of ulinastatin protects against sepsis by relieving intestinal damage.

    PubMed

    Yang, Bingchang; Gao, Min; Wang, Kangkai; Jiang, Yu; Peng, Yue; Zhang, Huali; Yang, Mingshi; Xiao, Xianzhong

    2017-05-01

    Intravenous administration of ulinastatin (UTI), a broad spectral protease inhibitor, has been used on an experimental basis with severe sepsis patients in Asia. However, the effects of intraintestinal administration of UTI on intestinal and multiple organ damage in sepsis have not been reported. In this study, we established a sepsis model in rats using cecal ligation and puncture and compared the effects of intraintestinal administration of UTI through an artificial fistula of duodenum and intraperitoneal administration of UTI on the pathophysiological changes of sepsis. It was found that intraintestinal administration of UTI (1) significantly improved the survival of septic rats, (2) significantly reduced the serum levels of tumor necrosis factor-α, interleukin-1β, interleukin-6 as well as intestinal injury biomarkers diamine oxidase, D-lactic acid, and fluorescein isothiocyanate-dextran 4, and (3) significantly reduced intestinal microscopic and ultrastructural damage of septic rats. In addition, the protective effects of intraintestinal administration of UTI were significantly better than those of intraperitoneal administration of UTI. Overall, the present study for the first time revealed that intraintestinal administration of protease inhibitor UTI could reduce systemic inflammatory responses and multiple organ dysfunction in rats with sepsis by inhibiting autodigestion of intestinal wall due to proteases and provided new research ideas and experimental evidences for treatment of sepsis by intraintestinal administration of UTI. Copyright © 2016. Published by Elsevier Inc.

  19. Effect of poloxamer 407 administration on the serum lipids profile, anxiety level and protease activity in the heart and liver of mice

    PubMed Central

    Johnston, Thomas P.; Dubrovina, Nina I.; Kisarova, Yana A.; Zhanaeva, Svetlana Ya.; Cherkanova, Marina S.; Filjushina, Elena E.; Alexeenko, Tatyana V.; Machova, Eva; Zhukova, Natalya A.

    2013-01-01

    Chronic administration of the poloxamer 407 (P-407), a block copolymer, to elevate serum lipids in mice is a well-established mouse model of hyperlipidemia and atherosclerosis. We tested the hypothesis that the activity of several types of proteases in heart and liver tissue is changed in the early stages of atherosclerosis development. Additionally, we evaluated whether increased serum lipids would induce anxiety in mice, as determined by using a ‘plus-maze’ test. The mice were administered P-407 by intraperitoneal injection twice a week for one month. P-407 administration to mice resulted in a marked increase in total serum cholesterol, atherogenic non-HDL-cholesterol, and especially in total triglycerides, and it also increased anxiety. Morphological changes observed in P-407-treated mice included contractile type changes in cardiomyocytes and foamy macrophages in liver. A significant increase of cysteine proteases cathepsin B and cathepsin L (at 24 h) and aspartate protease cathepsin D (at both 24 h and 5 days) was determined in heart tissue following P-407 administration. However, no changes were noted in heart matrix metalloproteinase activity. The activity of cysteine and aspartate proteases was significantly increased in liver at both 24 hours and 5 days after P-407 administration. In conclusion, administration of P-407 to mice for one month resulted in increased anxiety, and more importantly, there was an increase in the activity of heart and liver proteases secondary to sustained dyslipidemia. It is suggested that heart and liver cysteine and aspartate proteases may represent potential therapeutic targets in the early stages of atherosclerosis. PMID:24170975

  20. A study of the prevalence of significant increases in serum creatinine following angiotension-converting enzyme inhibitor administration.

    PubMed

    Thorp, M L; Ditmer, D G; Nash, M K; Wise, R; Jaderholm, P L; Smith, J D; Chan, W

    2005-05-01

    Angiontension-converting enzyme inhibitors (ACEIs) are beneficial in the treatment of diabetic and nondiabetic kidney disease, coronary artery disease and congestive heart failure. One adverse effect of ACEIs use is a rise in serum creatinine and potential renal failure. This paper attempts to quantify this risk and assess the need for pre- and post-ACEI serum creatinine measurements. A computerized search of Kaiser Permanente Northwest's electronic medical record was conducted to find patients over the age of 40 years taking lisinopril between July 1, 2000 and June 30, 2002. Patient demographic information and presence in diabetes and coronary artery disease registries was collected. A subsequent search for pre- and postlisinopril serum creatinine levels within 6 months of initial lisinopril prescription was conducted. Patients with prelisinopril creatinine < or = 1.2 mg/dl and postlisinopril creatinine > 2.5 mg/dl underwent chart review to discern adverse events associated with the rise in serum creatinine. A total of 18,977 patients were prescribed lisinopril between July 1, 2000 and June 30, 2002. In all 13 166 patients had a pre- and postlisinopril creatinine checked. In all, 31 patients had a rise in creatinine from < or = 1.2 mg/dl to > 2.5 mg/dl (0.2%). Possible contributors to rise in creatinine included congestive heart failure, dehydration and infection. No patients developed end-stage renal disease, although three died. In conclusion, end-stage renal disease is an unlikely outcome among patients prescribed lisinopril and is most likely associated with other events.

  1. Arsenic Speciation and Accumulation in Selected Organs after Oral Administration of Rice Extracts in Wistar Rats.

    PubMed

    Lewchalermvong, Kittima; Rangkadilok, Nuchanart; Nookabkaew, Sumontha; Suriyo, Tawit; Satayavivad, Jutamaad

    2018-03-28

    Despite its nutritional values, rice also contains arsenic. There has been increasing concern about health implications associated with exposure to arsenic through rice consumption. The present study evaluated arsenic accumulation and its speciation in selected organs of Wistar rats after 28 day repeated oral administrations of polished or unpolished rice and their control arsenic compounds (sodium arsenite or dimethylarsinic acid; DMA). Only the treatment of sodium arsenite (2 μg/kg body weight), significantly increased total arsenic concentrations in blood when compared to the distilled water control group. In all groups, total arsenic concentrations were highest in kidney (1.54-1.90 mg/kg) followed by liver (0.85-1.52 mg/kg), and the predominant arsenic form in these organs was DMA. However, there was no significant difference in arsenic accumulation in the measured organs among the control and rice-treated groups. Therefore, the repeated 28 day administration of arsenic-contaminated rice did not cause significant arsenic accumulation in the animal organs.

  2. Interdisciplinary Systems-Based Intervention to Improve IV Hydration during Parenteral Administration of Acyclovir.

    PubMed

    Dubrofsky, Lisa; Kerzner, Ryan S; Delaunay, Chloë; Kolenda, Camille; Pepin, Jocelyne; Schwartz, Blair C

    2016-01-01

    Intravenous (IV) hydration is considered a protective factor in reducing the incidence of acyclovir-induced nephrotoxicity. A systems-based review of cases of acyclovir-associated acute kidney injury can be used to examine institution-, care provider-, and task-related factors involved in administering the drug and can serve as a basis for developing a quality improvement intervention to achieve safer administration of acyclovir. To explore the effectiveness of the study institution's inter-disciplinary quality improvement intervention in increasing the dilution of acyclovir before IV administration. After conducting a systems-based review for intervention development, a retrospective analysis was undertaken to compare IV administration of acyclovir in the 6-month periods before and after implementation of the intervention. The study population was a sequential sample of all patients over 18 years of age who were seen in the emergency department or admitted to a ward and who received at least one IV dose of acyclovir at the study institution. The primary outcome was the volume in which each acyclovir dose was delivered. The secondary outcomes were the hourly rate of fluid administration, the frequency of an increase in hourly hydration rate, and the incidence of acute kidney injury. Eighty-four patients (44 in the pre-intervention period and 40 in the post-intervention period) received IV acyclovir and had evaluable data for the primary outcome. The median volume in which the acyclovir dose was administered was significantly higher in the post-intervention group (250 mL versus 100 mL, p < 0.001). In this study, an easily implemented intervention significantly increased the volume of IV fluid administered to patients receiving acyclovir. Adequately powered prospective studies are suggested to investigate the effectiveness of this intervention on the clinically relevant incidence of acyclovir-induced nephrotoxicity.

  3. Operant self-administration of alcohol and nicotine in a preclinical model of co-abuse

    PubMed Central

    Lê, A.D.; Funk, Douglas; Lo, Steven; Coen, Kathleen

    2017-01-01

    Rationale and objectives Alcohol and nicotine are often taken together. In humans, intake of nicotine, via smoked tobacco, increases alcohol drinking, and alcohol increases smoking. Chronic nicotine treatment increases alcohol self-administration (SA) in laboratory animals; the reverse relationship is less clear. Most animal work modeling this has used passive administration, which lacks relevance to human co-abuse. Here, we describe a model based on sequential operant SA of alcohol and nicotine. Methods Animals are first trained on alcohol SA (0.19 ml of 12% w/v/delivery) and then receive separate alcohol (8% w/v) and nicotine (15 μg/kg/infusion) SA sessions on the same day (“daily dual access”). Animals then receive access to alcohol and then to nicotine (or in the reverse order) in alternating 5 min periods in 2h sessions (“alternating access”). We then determine if alternating access modifies the effects of naltrexone on responding for alcohol and nicotine. Results We found that with daily dual access, nicotine significantly increased alcohol SA when alcohol access occurred prior to nicotine access, and that nicotine SA significantly decreased when the alcohol SA session preceded it. During alternating access, nicotine also significantly increased alcohol intake. Naltrexone (0.3 or 1 mg/kg) significantly reduced alcohol SA during these alternating access sessions in animals that also received nicotine SA, but had minimal effects on animals receiving alcohol SA alone. Naltrexone did not affect nicotine SA under any condition. Conclusions This sequential access procedure effectively models the effects of nicotine on alcohol intake noted in humans. PMID:24696081

  4. Stromal p16 expression is significantly increased in endometrial carcinoma

    PubMed Central

    Yoon, Nara; Kim, Ji-Ye; Kim, Hyun-Soo

    2017-01-01

    p16 is a negative regulator of cell proliferation and is considered a tumor suppressor protein. Alterations in p16 protein expression are associated with tumor development and progression. However, the p16 expression status in the peritumoral stroma has not been investigated in the endometrium. Therefore, we evaluated stromal p16 expression in different types of endometrial lesions using immunohistochemistry. Differences in the p16 expression status according to the degree of malignancy and histological type were analyzed. This study included 62, 26, and 36 cases of benign, precancerous, and malignant endometrial lesions, respectively. Most benign lesions showed negative or weak expression, whereas precancerous lesions showed a variable degree of staining proportion and intensity. Atypical hyperplasia/endometrial intraepithelial neoplasia (AH/EIN) and serous endometrial intraepithelial carcinoma (SEIC) had significantly higher stromal p16 expression levels than benign lesions. Endometrioid carcinoma (EC), serous carcinoma (SC), and carcinosarcoma showed significantly elevated stromal p16 expression levels compared with benign and precancerous lesions. In addition, there were significant differences in stromal p16 expression between AH/EIN and SEIC and between EC and SC. In contrast, differences in stromal p16 expression among nonpathological endometrium, atrophic endometrium, endometrial polyp, and hyperplasia without atypia were not statistically significant. Our observations suggest that stromal p16 expression is involved in the development and progression of endometrial carcinoma, and raise the possibility that p16 overexpression in the peritumoral stroma is associated with aggressive oncogenic behavior of endometrial SC. PMID:27902476

  5. Creatine metabolism and safety profiles after six-week oral guanidinoacetic acid administration in healthy humans.

    PubMed

    Ostojic, Sergej M; Niess, Barbara; Stojanovic, Marko; Obrenovic, Milos

    2013-01-01

    Guanidinoacetic acid (GAA) is a natural precursor of creatine, yet the potential use of GAA as a nutritional additive for restoring creatine availability in humans has been limited by unclear efficacy and safety after exogenous GAA administration. The present study evaluated the effects of orally administered GAA on serum and urinary GAA, creatine and creatinine concentration, and on the occurrence of adverse events in healthy humans. Twenty-four healthy volunteers were randomized in a double-blind design to receive either GAA (2.4 grams daily) or placebo (PLA) by oral administration for 6 weeks. www.clinicaltrials.gov, identification number NCT01133899. Serum creatine and creatinine increased significantly from before to after administration in GAA-supplemented participants (P < 0.05). The proportion of participants who reported minor side effects was 58.3% in the GAA group and 45.5% in the placebo group (P = 0.68). A few participants experienced serum creatine levels above 70 µmol/L. Exogenous GAA is metabolized to creatine, resulting in a significant increase of fasting serum creatine after intervention. GAA had an acceptable side-effects profile with a low incidence of biochemical abnormalities.

  6. Creatine Metabolism and Safety Profiles after Six-Week Oral Guanidinoacetic Acid Administration in Healthy Humans

    PubMed Central

    Ostojic, Sergej M.; Niess, Barbara; Stojanovic, Marko; Obrenovic, Milos

    2013-01-01

    Objectives; Guanidinoacetic acid (GAA) is a natural precursor of creatine, yet the potential use of GAA as a nutritional additive for restoring creatine availability in humans has been limited by unclear efficacy and safety after exogenous GAA administration. The present study evaluated the effects of orally administered GAA on serum and urinary GAA, creatine and creatinine concentration, and on the occurrence of adverse events in healthy humans. Methods and Results; Twenty-four healthy volunteers were randomized in a double-blind design to receive either GAA (2.4 grams daily) or placebo (PLA) by oral administration for 6 weeks. Clinical trial registration: www.clinicaltrials.gov, identification number NCT01133899. Serum creatine and creatinine increased significantly from before to after administration in GAA-supplemented participants (P < 0.05). The proportion of participants who reported minor side effects was 58.3% in the GAA group and 45.5% in the placebo group (P = 0.68). A few participants experienced serum creatine levels above 70 µmol/L. Conclusion; Exogenous GAA is metabolized to creatine, resulting in a significant increase of fasting serum creatine after intervention. GAA had an acceptable side-effects profile with a low incidence of biochemical abnormalities. PMID:23329885

  7. Blunted insula activation reflects increased risk and reward seeking as an interaction of testosterone administration and the MAOA polymorphism.

    PubMed

    Wagels, Lisa; Votinov, Mikhail; Radke, Sina; Clemens, Benjamin; Montag, Christian; Jung, Sonja; Habel, Ute

    2017-09-01

    Testosterone, a male sex hormone, has been suggested to partly explain mixed findings in males and females when investigating behavioral tendencies associated with the MAOA polymorphism. Prior studies indicated that the MAOA polymorphism represents a vulnerability factor for financial risk-taking and harm avoidance and that testosterone increases human risk-taking. We therefore assumed an interactive influence of the MAOA polymorphism and testosterone application on decision making and corresponding neural correlates in a risk and reward context. Stratified for the MAOA polymorphism (S =short, L =long), 103 healthy males were assigned to a placebo or testosterone group (double blind, randomized) receiving a topical gel containing 50 mg testosterone. During a functional MRI scan, the participants performed a sequential decision making task. Our results indicate that testosterone and the MAOA polymorphism jointly influence sequential decision making. The MAOA-S variant was associated with less automatic harm avoidance as reflected in response times on safe decisions. Moreover, after testosterone administration, MAOA-S carriers were more risk-taking. Overall activity in the anterior cingulate cortex, anterior insula and inferior frontal gyrus increased with growing risk for losses. In the anterior insula, testosterone administration mitigated this effect solely in MAOA-S carriers. This might be a reflection of an improved coping during risk-reward conflicts subsequently modulating risky decision making. While the molecular basis is not well defined so far, our results support the assumption of testosterone as a modulatory factor for previously reported sex differences of behavioral associations with the MAOA-S variant. Hum Brain Mapp 38:4574-4593, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  8. Sink or swim: the Titanic medication administration fair.

    PubMed

    Ward, Kathleen R; Koerner, Dianna K

    2008-04-01

    The Peer Review Committee at a Midwest hospital identified a knowledge deficit relative to medication administration. A continuing increase in the number of medication errors helped the committee to address the issue in a creative and educational way that reinforced knowledge of medication administration. Under the guidance of the Director of Education, employees who recently made medication errors developed and implemented a creative medication administration learning opportunity for hospital employees. The employees chose a project theme, developed educational workstations, and used creative approaches to increase awareness of medication administration pitfalls. This article explains the process of implementing and delivering this fun and exciting learning activity. Theme-based educational experiences are effective teaching strategies that can be used to trigger participants' learning in almost any setting.

  9. Multiple oral dosing of ketoconazole influences pharmacokinetics of quinidine after intravenous and oral administration in beagle dogs.

    PubMed

    Kuroha, M; Shirai, Y; Shimoda, M

    2004-10-01

    In this study, we investigated the effect of multiple oral dosing of ketoconazole (KTZ) on pharmacokinetics of quinidine (QN), a CYP3A substrate with low hepatic clearance, after i.v. and oral administration in beagle dogs. Four dogs were given p.o. KTZ for 20 days (200 mg, b.i.d.). QN was administered either i.v. (1 mg/kg) or p.o. (100 mg) 10 and 20 days before the KTZ treatment and 10 and 20 days after start of KTZ treatment. Multiple oral dosing of KTZ decreased significantly alpha and beta, whereas increased t(1/2beta), V(1), and k(a). The KTZ treatment also decreased significantly both total body clearance (Cl(tot)) and oral clearance (Cl(oral)). No significant change in bioavailability was observed in the presence of KTZ. Co-administration of KTZ increased C(max) of QN to about 1.5-fold. Mean resident time after i.v. administration (MRT(i.v.)), and after oral administration (MRT(p.o.)) of QN were prolonged to about twofold, whereas mean absorption time (MAT) was decreased to 50%. Volume of distribution at steady state (V(d(ss))) of QN was unchanged in the presence of KTZ. These alterations may be because of a decrease in metabolism of QN by inhibition of KTZ on hepatic CYP3A activity. In conclusion, multiple oral dosing of KTZ affected largely pharmacokinetics of QN after i.v. and oral administration in beagle dogs. Therefore, KTZ at a clinical dosing regimen may markedly change the pharmacokinetics of drugs primarily metabolized by CYP3A with low hepatic clearance in dogs. In clinical use, much attention should be paid to concomitant administration of KTZ with the drug when given either p.o. or i.v.

  10. Clinton Administration announces FY 2001 budget request

    NASA Astrophysics Data System (ADS)

    Showstack, Randy

    Blessed with a strong US. economy the Clinton Administration on February 7 released a fiscal year 2001 federal budget request totaling a whopping $1,835 billion. Most of the funding request is slated for big ticket items including Social Security defense spending, Medicaid, Medicare, and paying down the federal debt. However, within the 19% of the budget that funds non-defense discretionary programs,science agencies receive fairly healthy increases.The National Science Foundation (NSF) budget request would increase NSF funding by 17.3% $675 million and bring the total budget request to $4.6 billion. This includes significant increases for several initiatives: biocomplexity in the environment, information technology research, nanoscale science and engineering, and 21st century workforce. Among the major Earth science projects are launching the Earthscope initiative which includes the US Array and San Andreas Fault Observatory at Depth (SAFOD) and the National Ecological Observatory Network (NEON).

  11. A conscious rat model involving bradycardia and hypotension after oral administration: a toxicokinetical study of aconitine.

    PubMed

    Zhang, Panpan; Kong, Dezhi; Du, Qian; Zhao, Jing; Li, Qing; Zhang, Jianghua; Li, Tonghui; Ren, Leiming

    2017-06-01

    1. A model of aconitine-induced bradycardia and hypotension, which is similar to aconitine poisoning in humans, was constructed in conscious rats by oral administration. 2. Blood pressure (BP) and heart rate (HR) of Sprague-Dawley rats were measured using a volume pressure recording (VPR) system. The pharmacokinetics of toxic doses of aconitine and its metabolites were analyzed using UPLC-MS/MS. 3. The HR was significantly decreased by 29% at 2 h after oral administration of 200 μg/kg aconitine. When the dose was increased to 400 μg/kg, systolic BP and diastolic BP were significantly decreased by 11% and 12% at 2 h after the administration, except when bradycardia occurred at 2 h and 4 h. The drug concentration-time curve showed a double-peak phenomenon in rats administered a 400 μg/kg dose. The AUC 0-12 h value in the 400 μg/kg group significantly increased 0.8-fold compared to the 200 μg/kg group. Moreover, a high plasma concentration of 16-O-demethyaconitine was found in the rats that received two toxic doses. 4. In conclusion, bradycardia and hypotension are induced in conscious rats by a toxic dose of aconitine (400 μg/kg), and there was no significant difference in dose-normalized AUC 0-12 h values between oral administrations of 200 μg/kg and that of 400 μg/kg. However, the dose-normalized C max and AUC 0-12 h values in 200 μg/kg and 400 μg/kg groups were significantly smaller than those in 100 μg/kg group. The metabolites of aconitine, 16-O-demethyaconitine, and benzoylaconitine may also contribute to the hypotensive response.

  12. Anti-obesity effect of intranasal administration of galanin-like peptide (GALP) in obese mice

    PubMed Central

    Kageyama, Haruaki; Shiba, Kanako; Hirako, Satoshi; Wada, Nobuhiro; Yamanaka, Satoru; Nogi, Yukinori; Takenoya, Fumiko; Nonaka, Naoko; Hirano, Tsutomu; Inoue, Shuji; Shioda, Seiji

    2016-01-01

    Galanin-like peptide (GALP) has an anti-obesity effect in rats and mice. It has been reported that the uptake of GALP by the brain is higher after intranasal administration than with intravenous injection. This study therefore aimed to clarify the effect of intranasal administration of GALP on the feeding behavior of lean and obese mice. Autoradiography revealed the presence of 125I-GALP in the olfactory bulb and the brain microcirculation. The body weights of ob/ob mice gradually increased during vehicle treatment, but remained unchanged in response to repeated intranasal administration of GALP, with both ob/ob and diet-induced obese mice displaying significantly decreased food intake, water intake and locomotor activity when treated with GALP. These results suggest that intranasal administration is an effective route whereby GALP can exert its effect as an anti-obesity drug. PMID:27323911

  13. Analysis of computed tomography density of liver before and after amiodarone administration.

    PubMed

    Matsuda, Masazumi; Otaka, Aoi; Tozawa, Tomoki; Asano, Tomoyuki; Ishiyama, Koichi; Hashimoto, Manabu

    2018-05-01

    To evaluate CT density of liver changes between before and after amiodarone administration. Twenty-five patients underwent non-enhanced CT including the liver before and after amiodarone administration. We set regions of interest (ROIs) at liver S8, spleen, paraspinal muscle, and calculated average CT density in these ROIs, then compared CT density between liver and other organs. Statistical differences between CT density of liver and various ratios before and after administration were determined, along with correlations between cumulative dose of amiodarone and liver density after administration, density change of liver, and various ratios after administration. Liver density, liver-to-spleen ratio, and liver-to-paraspinal muscle ratio differed significantly between before and after amiodarone administration. No significant correlations were found between cumulative doses of amiodarone and any of liver density after administration, density change of liver, or various ratios after administration. CT density of liver after amiodarone administration was significantly higher than that before administration. No correlations were identified between cumulative dose of amiodarone and either liver density after administration or density change of liver. Amiodarone usage should be checked when radiologists identify high density of the liver on CT.

  14. ApoA-I mimetic administration, but not increased apoA-I-containing HDL, inhibits tumour growth in a mouse model of inherited breast cancer.

    PubMed

    Cedó, Lídia; García-León, Annabel; Baila-Rueda, Lucía; Santos, David; Grijalva, Victor; Martínez-Cignoni, Melanie Raquel; Carbó, José M; Metso, Jari; López-Vilaró, Laura; Zorzano, Antonio; Valledor, Annabel F; Cenarro, Ana; Jauhiainen, Matti; Lerma, Enrique; Fogelman, Alan M; Reddy, Srinivasa T; Escolà-Gil, Joan Carles; Blanco-Vaca, Francisco

    2016-11-03

    Low levels of high-density lipoprotein cholesterol (HDLc) have been associated with breast cancer risk, but several epidemiologic studies have reported contradictory results with regard to the relationship between apolipoprotein (apo) A-I and breast cancer. We aimed to determine the effects of human apoA-I overexpression and administration of specific apoA-I mimetic peptide (D-4F) on tumour progression by using mammary tumour virus-polyoma middle T-antigen transgenic (PyMT) mice as a model of inherited breast cancer. Expression of human apoA-I in the mice did not affect tumour onset and growth in PyMT transgenic mice, despite an increase in the HDLc level. In contrast, D-4F treatment significantly increased tumour latency and inhibited the development of tumours. The effects of D-4F on tumour development were independent of 27-hydroxycholesterol. However, D-4F treatment reduced the plasma oxidized low-density lipoprotein (oxLDL) levels in mice and prevented oxLDL-mediated proliferative response in human breast adenocarcinoma MCF-7 cells. In conclusion, our study shows that D-4F, but not apoA-I-containing HDL, hinders tumour growth in mice with inherited breast cancer in association with a higher protection against LDL oxidative modification.

  15. ApoA-I mimetic administration, but not increased apoA-I-containing HDL, inhibits tumour growth in a mouse model of inherited breast cancer

    PubMed Central

    Cedó, Lídia; García-León, Annabel; Baila-Rueda, Lucía; Santos, David; Grijalva, Victor; Martínez-Cignoni, Melanie Raquel; Carbó, José M.; Metso, Jari; López-Vilaró, Laura; Zorzano, Antonio; Valledor, Annabel F.; Cenarro, Ana; Jauhiainen, Matti; Lerma, Enrique; Fogelman, Alan M.; Reddy, Srinivasa T.; Escolà-Gil, Joan Carles; Blanco-Vaca, Francisco

    2016-01-01

    Low levels of high-density lipoprotein cholesterol (HDLc) have been associated with breast cancer risk, but several epidemiologic studies have reported contradictory results with regard to the relationship between apolipoprotein (apo) A-I and breast cancer. We aimed to determine the effects of human apoA-I overexpression and administration of specific apoA-I mimetic peptide (D-4F) on tumour progression by using mammary tumour virus-polyoma middle T-antigen transgenic (PyMT) mice as a model of inherited breast cancer. Expression of human apoA-I in the mice did not affect tumour onset and growth in PyMT transgenic mice, despite an increase in the HDLc level. In contrast, D-4F treatment significantly increased tumour latency and inhibited the development of tumours. The effects of D-4F on tumour development were independent of 27-hydroxycholesterol. However, D-4F treatment reduced the plasma oxidized low-density lipoprotein (oxLDL) levels in mice and prevented oxLDL-mediated proliferative response in human breast adenocarcinoma MCF-7 cells. In conclusion, our study shows that D-4F, but not apoA-I-containing HDL, hinders tumour growth in mice with inherited breast cancer in association with a higher protection against LDL oxidative modification. PMID:27808249

  16. Accelerated skeletal muscle recovery after in vivo polyphenol administration.

    PubMed

    Myburgh, Kathryn H; Kruger, Maria J; Smith, Carine

    2012-09-01

    Acute skeletal muscle damage results in fiber disruption, oxidative stress and inflammation. We investigated cell-specific contributions to the regeneration process after contusion-induced damage (rat gastrocnemius muscle) with or without chronic grape seed-derived proanthocyanidolic oligomer (PCO) administration. In this placebo-controlled study, male Wistar rats were subjected to PCO administration for 2 weeks, after which they were subjected to a standardised contusion injury. Supplementation was continued after injury. Immune and satellite cell responses were assessed, as well as oxygen radical absorption capacity and muscle regeneration. PCO administration resulted in a rapid satellite cell response with an earlier peak in activation (Pax7⁺, CD56⁺, at 4 h post-contusion) vs. placebo groups (PLA) (P<.001: CD56⁺ on Day 5 and Pax7⁺ on Day 7). Specific immune-cell responses in PLA followed expected time courses (neutrophil elevation on Day 1; sustained macrophage elevation from Days 3 to 5). PCO dramatically decreased neutrophil elevation to nonsignificant, while macrophage responses were normal in extent, but significantly earlier (peak between Days 1 and 3) and completely resolved by Day 5. Anti-inflammatory cytokine, IL-10, increased significantly only in PCO (Day 3). Muscle fiber regeneration (MHC(f) content and central nuclei) started earlier and was complete by Day 14 in PCO, but not in PLA. Thus, responses by three crucial cell types involved in muscle recovery were affected by in vivo administration of a specific purified polyphenol in magnitude (neutrophil), time course (macrophages), or time course and activation state (satellite cell), explaining faster effective regeneration in the presence of proanthocyanidolic oligomers. Copyright © 2012 Elsevier Inc. All rights reserved.

  17. Improving health care strategy planning through assessment of perceptions of consumers, providers and administrators.

    PubMed

    Scammon, D; Kennard, L

    1983-01-01

    Perceptions of consumers, health care administrators, and physicians regarding health care providers are analyzed. Ratings on 26 dimensions of health care services were obtained from members of the three participant groups using measures of image and satisfaction of both physicians in general, and of specific physicians. Discriminant analysis reveals significantly different perceptions of the health care system among the three groups of respondents. These differences suggest some changes in health care administration which could lead to increased consumer satisfaction and competitive advantages for physicians and health care institutions.

  18. Increased 1-year continuation of DMPA among women randomized to self-administration: results from a randomized controlled trial at Planned Parenthood.

    PubMed

    Kohn, Julia E; Simons, Hannah R; Della Badia, Lisa; Draper, Elissa; Morfesis, Johanna; Talmont, Elizabeth; Beasley, Anitra; McDonald, Melanie; Westhoff, Carolyn L

    2018-03-01

    Self-administration of subcutaneous depot medroxyprogesterone acetate (DMPA-sc) is feasible, acceptable, and effective. Our objective was to compare one-year continuation of DMPA-sc between women randomized to self-administration versus clinic administration. We randomized 401 females ages 15-44 requesting DMPA at clinics in Texas and New Jersey to self-administration or clinic administration in a 1:1 allocation. Clinic staff taught participants randomized to self-administration to self-inject and observed the first injection; participants received instructions, a sharps container, and three doses for home use. Participants randomized to clinic administration received usual care. All participants received DMPA-sc at no cost and injection reminders via text message or email. We conducted follow-up surveys at six and 12 months. Three hundred thirty-six participants (84%) completed the 12-month survey; 316 completed both follow-up surveys (an 80% response rate excluding eight withdrawals). Participants ranged in age from 16-44. One-year DMPA continuous use was 69% in the self-administration group and 54% in the clinic group (p=.005). There were three self-reported pregnancies during the study period, all occurred in the clinic group; all three women had discontinued DMPA and one reported her pregnancy as intended. Among the self-administration group, 97% reported that self-administration was very or somewhat easy; 87% would recommend self-administration of DMPA-sc to a friend. Among the clinic group, 52% reported interest in self-administration in the future. Satisfaction was similar between groups. No serious adverse events were reported. DMPA self-administration improves contraceptive continuation and is a feasible and acceptable option for women and adolescents. Self-administration of subcutaneous DMPA can improve contraceptive access, autonomy, and continuation, and is a feasible and acceptable option for women and adolescents. It should be made widely available

  19. Evidence of thyroxine formation following iodine administration in Sprague-Dawley rats

    NASA Technical Reports Server (NTRS)

    Thrall, K. D.; Sauer, R. L.; Bull, R. J.

    1992-01-01

    Iodine (I2) has been proposed to be used as a water disinfectant on the manned space station. Previous work has shown that subchronic administration of I2 to Sprague-Dawley rats in drinking water significantly increases plasma thyroxine/triiodothyronine (T4/T3) levels. This is not observed with iodide (I-) treatment. The present study addresses the possibility that I2 reacts with deiodinated T4 metabolites in the gastrointestinal tract to resynthesize T4. Incubation of diiodothyronine (T2), T3, or reverse T3 with I2 in phosphate-buffered saline resulted in the formation of T4 as measured by radioimmunoassay. Washes from the initial segments of the small intestine of the rat show that substrates are present that react with I2 to produce T4. Single oral doses of I2 to rats produced significant dose-related increases in serum T4 and decreases in T3 concentrations after 2 h. Administration of an equivalent dose of I- did not alter significantly plasma T4 concentrations. Higher concentrations of a radioactive substance that bound a T4-specific antibody are present in plasma of animals treated with 125I2 compared to 125I-. These data support the hypothesis that I2 reacts with metabolites of thyroid hormone in the gastrointestinal tract to resynthesize T4 and elevate its levels in blood.

  20. Effect of formulation- and administration-related variables on deposition pattern of nasal spray pumps evaluated using a nasal cast.

    PubMed

    Kundoor, Vipra; Dalby, Richard N

    2011-08-01

    To systematically evaluate the effect of formulation- and administration-related variables on nasal spray deposition using a nasal cast. Deposition pattern was assessed by uniformly coating a transparent nose model with Sar-Gel®, which changes from white to purple on contact with water. Sprays were subsequently discharged into the cast, which was then digitally photographed. Images were quantified using Adobe® Photoshop. The effects of formulation viscosity (which influences droplet size), simulated administration techniques (head orientation, spray administration angle, spray nozzle insertion depth), spray pump design and metering volume on nasal deposition pattern were investigated. There was a significant decrease in the deposition area associated with sprays of increasing viscosity. This appeared to be mediated by an increase in droplet size and a narrowing of the spray plume. Administration techniques and nasal spray pump design also had a significant effect on the deposition pattern. This simple color-based method provides quantitative estimates of the effects that different formulation and administration variables may have on the nasal deposition area, and provides a rational basis on which manufacturers of nasal sprays can base their patient instructions or post approval changes when it is impractical to optimize these using a clinical study.

  1. Co-administration of trientine and flaxseed oil on oxidative stress, serum lipids and heart structure in diabetic rats.

    PubMed

    Rezaei, Ali; Heidarian, Esfandiar

    2013-08-01

    The administration of flaxseed oil or flaxseed oil plus trientine in diabetic rats reduced triglyceride, very low density lipoprotein, and total cholesterol. Furthermore, the combined treatment significantly increased superoxide dismutase activity and attenuated serum Cu2+. The results suggest that the administration of flaxseed oil plus trientine is useful in controlling serum lipid abnormalities, oxidative stress, restoring heart structure, and reducing serum Cu2+ in diabetic rats.

  2. Quantifying nursing workflow in medication administration.

    PubMed

    Keohane, Carol A; Bane, Anne D; Featherstone, Erica; Hayes, Judy; Woolf, Seth; Hurley, Ann; Bates, David W; Gandhi, Tejal K; Poon, Eric G

    2008-01-01

    New medication administration systems are showing promise in improving patient safety at the point of care, but adoption of these systems requires significant changes in nursing workflow. To prepare for these changes, the authors report on a time-motion study that measured the proportion of time that nurses spend on various patient care activities, focusing on medication administration-related activities. Implications of their findings are discussed.

  3. Lubiprostone increases spontaneous bowel movement frequency and quality of life in patients with chronic idiopathic constipation.

    PubMed

    Fukudo, Shin; Hongo, Michio; Kaneko, Hiroshi; Takano, Masahiro; Ueno, Ryuji

    2015-02-01

    Lubiprostone is an activator of the type 2 chloride channel that facilitates spontaneous bowel movement (SBM). We performed phase 3 studies to determine whether lubiprostone increases the frequency of SBM in patients with chronic idiopathic constipation (CIC) in Japan, and whether long-term administration of lubiprostone increases the quality of life of patients with CIC. We performed a randomized, double-blind, placebo-controlled, phase 3 trial of lubiprostone. Patients with CIC (n = 124) were assigned randomly to groups given placebo (n = 62) or lubiprostone (48 μg/day; n = 62) for 4 weeks. The primary efficacy end point was the change from baseline in the weekly average number of SBMs after 1 week of administration. In a long-term study of efficacy and safety, 209 patients with CIC were given lubiprostone (24 μg twice daily) for 48 weeks. Daily administration of lubiprostone induced a significantly greater change, from baseline, in the weekly average number of SBMs at week 1 (increase of 3.7 ± 2.8), compared with placebo (increase of 1.3 ± 1.8; P < .001). The frequency of SBMs during each week of the study period was significantly higher after subjects began receiving lubiprostone than at baseline (P < .0001 at all weeks). Long-term administration of lubiprostone significantly increased scores from the Short-Form health survey and irritable bowel syndrome quality-of-life questionnaire, compared with baseline. We did not observe any severe adverse reactions to lubiprostone. In phase 3 studies in Japan, lubiprostone increased the weekly average number of SBMs and increased the quality of life of patients with CIC. Clinical Trial Notification of the Japanese Regulatory Authorities: 20-3296 and 20-3300. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

  4. Leukocyte and platelet changes following low-dose lipopolysaccharide administration in five dogs.

    PubMed

    Flatland, B; Fry, M M; LeBlanc, C J; Rohrbach, B W

    2011-02-01

    Effects of low-dose LPS (0.1 μg/kg i.v.) on leukocyte and platelet parameters measured using an Advia 120 hematology analyzer were investigated. Five dogs received a saline sham treatment prior to LPS, and blood was collected before and 3, 6, and 24 h post-treatment. LPS-treated dogs had mild neutrophil toxic change and increased neutrophil bands at 3 and 6 h. Compared to saline-treated controls, total leukocyte, neutrophil, and monocyte counts of LPS-treated dogs were significantly decreased at 3 h and increased at 24 h. Compared to baseline, total leukocyte counts of LPS-treated dogs were significantly decreased at 3 h and increased at 24 h. Mean platelet volume was significantly increased and mean platelet component concentration was decreased at 3 h compared to baseline. Platelet count was significantly decreased at 3 and 6 h; plateletcrit did not change significantly. High dosage is not required in order to detect LPS-mediated hematologic effects in dogs. Low-dose LPS administration causes significant changes in leukocyte and platelet indices in dogs without causing severe clinical signs or death. Copyright © 2010 Elsevier Ltd. All rights reserved.

  5. Provider risk factors for medication administration error alerts: analyses of a large-scale closed-loop medication administration system using RFID and barcode.

    PubMed

    Hwang, Yeonsoo; Yoon, Dukyong; Ahn, Eun Kyoung; Hwang, Hee; Park, Rae Woong

    2016-12-01

    To determine the risk factors and rate of medication administration error (MAE) alerts by analyzing large-scale medication administration data and related error logs automatically recorded in a closed-loop medication administration system using radio-frequency identification and barcodes. The subject hospital adopted a closed-loop medication administration system. All medication administrations in the general wards were automatically recorded in real-time using radio-frequency identification, barcodes, and hand-held point-of-care devices. MAE alert logs recorded during a full 1 year of 2012. We evaluated risk factors for MAE alerts including administration time, order type, medication route, the number of medication doses administered, and factors associated with nurse practices by logistic regression analysis. A total of 2 874 539 medication dose records from 30 232 patients (882.6 patient-years) were included in 2012. We identified 35 082 MAE alerts (1.22% of total medication doses). The MAE alerts were significantly related to administration at non-standard time [odds ratio (OR) 1.559, 95% confidence interval (CI) 1.515-1.604], emergency order (OR 1.527, 95%CI 1.464-1.594), and the number of medication doses administered (OR 0.993, 95%CI 0.992-0.993). Medication route, nurse's employment duration, and working schedule were also significantly related. The MAE alert rate was 1.22% over the 1-year observation period in the hospital examined in this study. The MAE alerts were significantly related to administration time, order type, medication route, the number of medication doses administered, nurse's employment duration, and working schedule. The real-time closed-loop medication administration system contributed to improving patient safety by preventing potential MAEs. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  6. Increase in migraine diagnoses and guideline-concordant treatment in veterans, 2004-2012.

    PubMed

    Altalib, H H; Fenton, B T; Sico, J; Goulet, J L; Bathulapalli, H; Mohammad, A; Kulas, J; Driscoll, M; Dziura, J; Mattocks, K; Kerns, R; Brandt, C; Haskell, S

    2017-01-01

    Background and aim Health administrators, policy makers, and educators have attempted to increase guideline adherence of migraine medications while reducing inappropriate use of opioid- and barbiturate-containing medications. We evaluated the burden of migraine and proportion of guideline-concordant care in a large, national health care system over time. Methods We conducted a time-series study using data from the Veterans Health Administration (VHA) electronic health record. Veterans with migraines were identified by ICD-9 code (346.X). Prescriptions and comorbid conditions were evaluated before and after migraine diagnosis. Chi-square tests and logistic regression were performed. Results A total of 57,064 veterans were diagnosed with migraine headache (5.3%), with women significantly more likely diagnosed (11.6% vs. 4.4%, p < 0.0001). The number of veterans diagnosed with migraine has significantly increased over the years. By 2012, triptans were prescribed to 43% of people with migraine, with no difference by gender. However, triptan prescriptions increased from 2004 to 2012 in men, but not women, veterans. Preventive medicines showed a significant increase with the year of migraine diagnosis, after controlling for age, sex, race, and for comorbidities treated with medications used for migraine prevention. Conclusions The burden of migraines is increasing within the VHA, with a corresponding increase in the delivery of guideline-concordant acute and prophylactic migraine-specific medication.

  7. Increasing Neuroplasticity to Bolster Chronic Pain Treatment: A Role for Intermittent Fasting and Glucose Administration?

    PubMed

    Sibille, Kimberly T; Bartsch, Felix; Reddy, Divya; Fillingim, Roger B; Keil, Andreas

    2016-03-01

    Neuroplastic changes in brain structure and function are not only a consequence of chronic pain but are involved in the maintenance of pain symptoms. Thus, promotion of adaptive, treatment-responsive neuroplasticity represents a promising clinical target. Emerging evidence about the human brain's response to an array of behavioral and environmental interventions may assist in identifying targets to facilitate increased neurobiological receptivity, promoting healthy neuroplastic changes. Specifically, strategies to maximize neuroplastic responsiveness to chronic pain treatment could enhance treatment gains by optimization of learning and positive central nervous system adaptation. Periods of heightened plasticity have been traditionally identified with the early years of development. More recent research, however, has identified a wide spectrum of methods that can be used to "reopen" and enhance plasticity and learning in adults. In addition to transcranial direct current stimulation and transcranial magnetic stimulation, behavioral and pharmacological interventions have been investigated. Intermittent fasting and glucose administration are two propitious strategies, that are noninvasive, inexpensive to administer, implementable in numerous settings, and might be applicable across differing chronic pain treatments. Key findings and neurophysiological mechanisms are summarized, and evidence for the potential clinical contributions of these two strategies toward ameliorating chronic pain is presented. Neuroplastic changes are a defining feature of chronic pain and a complicating factor in treatment. Noninvasive strategies to optimize the brain's response to treatment interventions might improve learning and memory, increase the positive adaptability of the central nervous system, and enhance treatment outcomes. Copyright © 2016 American Pain Society. Published by Elsevier Inc. All rights reserved.

  8. Intracarotid administration of short-chain alkylglycerols for increased delivery of methotrexate to the rat brain

    PubMed Central

    Erdlenbruch, Bernhard; Schinkhof, Claudia; Kugler, Wilfried; Heinemann, Dagmar E H; Herms, Jochen; Eibl, Hansjörg; Lakomek, Max

    2003-01-01

    The intracarotid administration of alkylglycerols has been reported previously by us to be a novel strategy for increased delivery of various chemotherapeutic drugs to the normal brain and brain tumors in rats. Effectiveness and structure–activity relations of the most promising pentyl- and hexylglycerol derivatives have been elucidated in vivo by analyzing the transfer of methotrexate (MTX) across the blood–brain barrier (BBB) in normal rats. The effects were compared with BBB disruption using hypertonic mannitol or intracarotid infusion of bradykinin. Furthermore, toxicity of the alkylglycerols has been studied in long-term experiments. Apart from 1-O-pentyldiglycerol, all alkylglycerols induced a concentration-dependent increase in MTX delivery to the brain varying from 1.1 to more than 300-fold compared to intra-arterial MTX alone. Enhanced barrier permeability rapidly approached baseline values within 5 and 120 min at the latest. Chemical structure, concentration, time schedule of injections and combination of different alkylglycerols were identified as instruments suited to regulate the MTX accumulation within a wide range. Mannitol 1.4 M resulted in very high MTX levels in the brain as observed using the highest concentrations of alkylglycerols. Intracarotid infusion of bradykinin had only a minor effect on the BBB. Using 1-O-pentylglycerol or 2-O-hexyldiglycerol, both cell culture experiments and long-term in vivo analyses including clinical, laboratory and histopathological evaluations revealed no signs of toxicity. In summary, intracarotid short-chain alkylglycerols constitute a very effective and low toxic strategy for transient opening of the BBB to overcome the limited access of cytotoxic drugs to the brain. PMID:12812991

  9. Assessment of human 4-hydroxynonenal, 8-isoprostane concentrations and glutathione reductase activity after synbiotics administration.

    PubMed

    Kleniewska, Paulina; Pawliczak, Rafał

    2018-05-30

    Probiotics and prebiotics have become an object of intense research, to identify methods of mitigating oxidative stress. Over the past few years, the number of in vitro and in vivo studies, related to antioxidant properties of probiotics/prebiotics has significantly increased. The aim of the present study was to assess whether probiotic in combination with prebiotic influences the level of human 4-hydroxynonenal, 8-isoprostane and glutathione reductase activity. Experiments were carried out on healthy volunteers (male and female). All oxidative stress markers were measured in blood plasma pre- and post-administration of synbiotic. The administration of synbiotic resulted in a significant decrease in 4-hydroxynonenal in the female-synbiotic group (p < 0.05), 8-isoprostanes in the female-synbiotic group and male-synbiotic group (p < 0.05) and non-significant increase in the activity of glutathione reductase (p > 0.05) vs. control. The present results show that supplementation of synbiotics contributed to the decrease in oxidative stress parameters in the female patients. Copyright © 2018 Medical University of Bialystok. Published by Elsevier B.V. All rights reserved.

  10. An observational study of drug administration errors in a Malaysian hospital (study of drug administration errors).

    PubMed

    Chua, S S; Tea, M H; Rahman, M H A

    2009-04-01

    Drug administration errors were the second most frequent type of medication errors, after prescribing errors but the latter were often intercepted hence, administration errors were more probably to reach the patients. Therefore, this study was conducted to determine the frequency and types of drug administration errors in a Malaysian hospital ward. This is a prospective study that involved direct, undisguised observations of drug administrations in a hospital ward. A researcher was stationed in the ward under study for 15 days to observe all drug administrations which were recorded in a data collection form and then compared with the drugs prescribed for the patient. A total of 1118 opportunities for errors were observed and 127 administrations had errors. This gave an error rate of 11.4 % [95% confidence interval (CI) 9.5-13.3]. If incorrect time errors were excluded, the error rate reduced to 8.7% (95% CI 7.1-10.4). The most common types of drug administration errors were incorrect time (25.2%), followed by incorrect technique of administration (16.3%) and unauthorized drug errors (14.1%). In terms of clinical significance, 10.4% of the administration errors were considered as potentially life-threatening. Intravenous routes were more likely to be associated with an administration error than oral routes (21.3% vs. 7.9%, P < 0.001). The study indicates that the frequency of drug administration errors in developing countries such as Malaysia is similar to that in the developed countries. Incorrect time errors were also the most common type of drug administration errors. A non-punitive system of reporting medication errors should be established to encourage more information to be documented so that risk management protocol could be developed and implemented.

  11. Comparison of the efficacy and safety profile of morning administration of controlled-release simvastatin versus evening administration of immediate-release simvastatin in chronic kidney disease patients with dyslipidemia.

    PubMed

    Yi, Yong Jin; Kim, Hyo Jin; Jo, Sang Kyung; Kim, Sung Gyun; Song, Young Rim; Chung, Wookyung; Han, Kum Hyun; Lee, Chang Hwa; Hwang, Young-Hwan; Oh, Kook-Hwan

    2014-08-01

    Evening administration of the conventional immediate-release (IR) formulation of simvastatin is recommended because of its short half-life (1.9 hours). In a healthy population, morning administration of a controlled-release (CR) formulation of simvastatin was shown to have equivalent lipid-lowering efficacy and a safety profile similar to that of evening doses of IR simvastatin. The present study aimed to verify noninferiority and to compare the safety of morning administration of CR simvastatin with that of evening administration of IR simvastatin in patients with chronic kidney disease (CKD) who have dyslipidemia. The present study was a prospective, multicenter, double-blind, Phase IV trial with an active comparator. We randomly assigned 122 patients with CKD and dyslipidemia to 1 of 2 drug administration groups: morning administration of CR simvastatin 20 mg (test group) and evening administration of IR simvastatin 20 mg (control group). After 8 weeks, the treatment outcomes and adverse effects of the 2 treatments were compared. The mean (SD) percentage of change in serum LDL-C at the end of treatment was -35.1% (15.7%) for the test group and -35.6% (14.6%) for the control group. The difference between the 2 groups was not significant (P = 0.858). The 95% CI of the difference in the percentage of change of LDL-C between the test and control groups was -6.0 to 5.0. There was no difference in the percentage of change of total cholesterol (-24.3% [12.5%] vs -26.5% [12.0%], P = 0.317), triglyceride (-10.6% [35.1%] vs -12.4% [33.2%], P = 0.575) and HDL-C (10.2% [20.7%] vs 4.5% [11.4%], P = 0.064). Treatment-related adverse events were similar in both groups (10 events in the test group vs 8 events in the control group, P = 0.691). The efficacy of morning administration of CR simvastatin was noninferior to evening administration of IR simvastatin in patients with CKD. Furthermore, the safety profile analysis showed no significant difference between the 2 treatments

  12. Induction of testicular damage by daily methamphetamine administration in rats.

    PubMed

    Lin, Ji-Fan; Lin, Yi-Hsuan; Liao, Po-Cheng; Lin, Yi-Chia; Tsai, Te-Fu; Chou, Kuang-Yu; Chen, Hung-En; Tsai, Shiow-Chwen; Hwang, Thomas I-Sheng

    2014-02-28

    Methamphetamine (METH)-induced brain damage and apoptosis within the central nervous system are well documented. This study was conducted to investigate the toxic effects of daily METH administration on the testes in a rat model. Male Sprague-Dawley rats (5 weeks old, ~100 g, n = 64) were divided into two groups and treated with vehicle (saline, control) or METH (10 mg/kg) for 15, 30, 60 and 90 days. The results showed that daily administration of METH decreased the body, testicular and epididymis weights as well as the serum levels of total testosterone. The increased apoptotic index (Bad/Bcl2 expression ratio) and levels of cleaved caspase-3 indicated that apoptosis had occurred in the testes of the METH-treated rats. The oxidative stress levels increased as the reduced and oxidized glutathione (GSH/GSSG) ratio decreased. The overall sperm counts decreased at 15 and 90 days, where- as morphologically abnormal sperm counts increased at 30, 60 and 90 days in the METH-treated rats. This study demonstrates that daily exposure to METH significantly reduced the number and quality of sperm in rats. The underlying pathophysiological mechanisms likely include the reduction of serum testosterone levels and the increase of oxidative stress and apoptosis in the rat testes.

  13. Effect of acute administration of hypericum perforatum-CO2 extract on dopamine and serotonin release in the rat central nervous system.

    PubMed

    Di Matteo, V; Di Giovanni, G; Di Mascio, M; Esposito, E

    2000-01-01

    The hydromethanolic extract of Hypericum perforatum has been shown to be an effective antidepressant, although its mechanism of action is still unclear. In this study, in vivo microdialysis was used to investigate the effects of Hypericum perforatum-CO2 extract on dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), serotonin (5-HT), and 5-hydroxyindoleacetic acid (5-HIAA) release in various areas of brain. Administration of Hypericum perforatum extract (1 mg/kg, p.o.) caused a slight, but significant increase of DA outflow both in the nucleus accumbens and the striatum. The maximal increase of DA efflux (+19.22+/-1.93%, relative to the control group) in the nucleus accumbens occurred 100 min after administration of Hypericum perforatum. In the striatum, the extract maximally enhanced DA outflow (+24.83+/-7.49 %, relative to the control group) 80 min after administration. Extraneuronal DOPAC levels were not significantly affected by Hypericum perforatum treatment. Moreover, Hypericum perforatum (1 mg/kg, p.o.) did not produce any significant effect on either 5-HT or 5-HIAA efflux in the ventral hippocampus. This study shows for the first time that Hypericum perforatum extract is capable of increasing in vivo DA release.

  14. Increased Protection against Pneumococcal Disease by Mucosal Administration of Conjugate Vaccine plus Interleukin-12

    PubMed Central

    Lynch, Joyce M.; Briles, David E.; Metzger, Dennis W.

    2003-01-01

    Streptococcus pneumoniae is a common cause of respiratory tract infections, its main entry route being the nasal mucosa. The recent development of pneumococcal polysaccharide conjugate vaccines has led to a dramatic improvement in protection against invasive disease in infants and children, but these vaccines have been found to be only 50 to 60% protective against bacterial carriage. In this study, we investigated the efficacy of intranasal (i.n.) conjugate vaccine delivery using interleukin-12 (IL-12) as a mucosal adjuvant. Immunized mice treated with IL-12 demonstrated increased expression of lung and splenic gamma interferon and IL-10 mRNAs; high levels of antibody, particularly serum immunoglobulin G2a (IgG2a) and respiratory IgA; and significantly increased opsonic activity. After intraperitoneal challenge with type 3 pneumococci, there was 75% survival of i.n. vaccinated mice compared to 0% survival of unvaccinated mice. In addition, after i.n. challenge with type 14 pneumococci, vaccinated mice possessed fewer bacterial colonies in the upper respiratory tract than unvaccinated mice. However, no significant difference in type 14 carriage was observed between vaccinated and unvaccinated groups following intramuscular vaccination, the typical route of vaccination in humans. Using mice with a genetic disruption in IgA expression, it was found that pneumococcus-specific IgA played a significant role in the clearance of bacteria from the upper respiratory tract. We conclude that i.n vaccination in the presence of IL-12 is able to enhance systemic and mucosal immune responses to pneumococci and efficiently protect against both invasive infection and bacterial carriage. PMID:12874361

  15. Disruption of frontal-parietal connectivity during conscious sedation by propofol administration.

    PubMed

    Kim, Pil-Jong; Kim, Hong-Gee; Noh, Gyu-Jeong; Koo, Yong-Seo; Shin, Teo Jeon

    2017-09-27

    The sedative state is a transitional state from wakefulness to general anesthesia. However, little is understood regarding the mechanism of conscious sedation, different from general anesthesia while maintaining wakefulness. In this study, we aimed to investigate changes in functional connectivity of the parietal-frontal network, implicated in wakefulness during conscious sedation induced by propofol infusion. The electroencephalography was obtained at the frontal and parietal areas of adult volunteers who maintain wakefulness during low-dose propofol infusion (1.5 mg/kg/h) over 1 h. Spectral Granger causality (GC) (δ, θ, α, β, and γ frequency bands) and time-domain GC were calculated during each stage of awake (before propofol administration), sedation, and recovery (after discontinuation of propofol). We also calculated the phase-locking index and compared it with GC during each stage. A decrease in GC from the frontal to parietal areas was observed particularly in the low-frequency bands during propofol administration. Contrary to the GC changes in the frontoparietal direction, GC from the parietal to frontal areas was increased in the high-frequency bands during propofol administration and significantly decreased after discontinuation of propofol. In summary, we showed that frontal-parietal neural networks were significantly changed differently by the frequency of the brain rhythm and the directions of connections during sedation by propofol administration. Our result suggests that the alteration of brain interaction may induce sedative state lying between awake and general anesthesia.

  16. Improved memory for reward cues following acute buprenorphine administration in humans.

    PubMed

    Syal, Supriya; Ipser, Jonathan; Terburg, David; Solms, Mark; Panksepp, Jaak; Malcolm-Smith, Susan; Bos, Peter A; Montoya, Estrella R; Stein, Dan J; van Honk, Jack

    2015-03-01

    In rodents, there is abundant evidence for the involvement of the opioid system in the processing of reward cues, but this system has remained understudied in humans. In humans, the happy facial expression is a pivotal reward cue. Happy facial expressions activate the brain's reward system and are disregarded by subjects scoring high on depressive mood who are low in reward drive. We investigated whether a single 0.2mg administration of the mixed mu-opioid agonist/kappa-antagonist, buprenorphine, would influence short-term memory for happy, angry or fearful expressions relative to neutral faces. Healthy human subjects (n38) participated in a randomized placebo-controlled within-subject design, and performed an emotional face relocation task after administration of buprenorphine and placebo. We show that, compared to placebo, buprenorphine administration results in a significant improvement of memory for happy faces. Our data demonstrate that acute manipulation of the opioid system by buprenorphine increases short-term memory for social reward cues. Copyright © 2015. Published by Elsevier Ltd.

  17. Administrative review process for adjudicating initial disability claims. Final rule.

    PubMed

    2006-03-31

    The Social Security Administration is committed to providing the high quality of service the American people expect and deserve. In light of the significant growth in the number of disability claims and the increased complexity of those claims, the need to make substantial changes in our disability determination process has become urgent. We are publishing a final rule that amends our administrative review process for applications for benefits that are based on whether you are disabled under title II of the Social Security Act (the Act), or applications for supplemental security income (SSI) payments that are based on whether you are disabled or blind under title XVI of the Act. We expect that this final rule will improve the accuracy, consistency, and timeliness of decision-making throughout the disability determination process.

  18. The Legal Implications of Administrative Decision-Making.

    ERIC Educational Resources Information Center

    Bender, Louis W.

    Administrative decision-making encompasses three levels on which increasing legal challenges and liability and their implications need to be considered. At the local level, this may involve violations of procedural due process. A second level concerns state laws and regulations. Line administrators, who frequently make decisions on programs,…

  19. Amphetamine enhances endurance by increasing heat dissipation.

    PubMed

    Morozova, Ekaterina; Yoo, Yeonjoo; Behrouzvaziri, Abolhassan; Zaretskaia, Maria; Rusyniak, Daniel; Zaretsky, Dmitry; Molkov, Yaroslav

    2016-09-01

    Athletes use amphetamines to improve their performance through largely unknown mechanisms. Considering that body temperature is one of the major determinants of exhaustion during exercise, we investigated the influence of amphetamine on the thermoregulation. To explore this, we measured core body temperature and oxygen consumption of control and amphetamine-trea ted rats running on a treadmill with an incrementally increasing load (both speed and incline). Experimental results showed that rats treated with amphetamine (2 mg/kg) were able to run significantly longer than control rats. Due to a progressively increasing workload, which was matched by oxygen consumption, the control group exhibited a steady increase in the body temperature. The administration of amphetamine slowed down the temperature rise (thus decreasing core body temperature) in the beginning of the run without affecting oxygen consumption. In contrast, a lower dose of amphetamine (1 mg/kg) had no effect on measured parameters. Using a mathematical model describing temperature dynamics in two compartments (the core and the muscles), we were able to infer what physiological parameters were affected by amphetamine. Modeling revealed that amphetamine administration increases heat dissipation in the core. Furthermore, the model predicted that the muscle temperature at the end of the run in the amphetamine-treated group was significantly higher than in the control group. Therefore, we conclude that amphetamine may mask or delay fatigue by slowing down exercise-induced core body temperature growth by increasing heat dissipation. However, this affects the integrity of thermoregulatory system and may result in potentially dangerous overheating of the muscles. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

  20. Antinociceptive effects of long-acting nalbuphine decanoate after intramuscular administration to Hispaniolan Amazon parrots (Amazona ventralis).

    PubMed

    Sanchez-Migallon Guzman, David; Braun, Jana M; Steagall, Paulo V M; Keuler, Nicholas S; Heath, Timothy D; Krugner-Higby, Lisa A; Brown, Carolyn S; Paul-Murphy, Joanne R

    2013-02-01

    To evaluate the thermal antinociceptive effects and duration of action of nalbuphine decanoate after IM administration to Hispaniolan Amazon parrots (Amazona ventralis). 10 healthy adult Hispaniolan Amazon parrots of unknown sex. Nalbuphine decanoate (33.7 mg/kg) or saline (0.9% NaCl) solution was administered IM in a randomized complete crossover experimental design (periods 1 and 2). Foot withdrawal threshold to a noxious thermal stimulus was used to evaluate responses. Baseline thermal withdrawal threshold was recorded 1 hour before drug or saline solution administration, and thermal foot withdrawal threshold measurements were repeated 1, 2, 3, 6, 12, 24, 48, and 72 hours after drug administration. Nalbuphine decanoate administered IM at a dose of 33.7 mg/kg significantly increased thermal foot withdrawal threshold, compared with results after administration of saline solution during period 2, and also caused a significant change in withdrawal threshold for up to 12 hours, compared with baseline values. Nalbuphine decanoate increased the foot withdrawal threshold to a noxious thermal stimulus in Hispaniolan Amazon parrots for up to 12 hours and provided a longer duration of action than has been reported for other nalbuphine formulations. Further studies with other types of nociceptive stimulation, dosages, and dosing intervals as well as clinical trials are needed to fully evaluate the analgesic effects of nalbuphine decanoate in psittacine birds.

  1. Kinematic and Microphysical Significance of Lightning Jumps versus Non-Jump Increases in Total Flash Rate

    PubMed Central

    Schultz, Christopher J.; Carey, Lawrence D.; Schultz, Elise V.; Blakeslee, Richard J.

    2017-01-01

    Thirty-nine thunderstorms are examined using multiple-Doppler, polarimetric and total lightning observations to understand the role of mixed phase kinematics and microphysics in the development of lightning jumps. This sample size is larger than those of previous studies on this topic. The principal result of this study is that lightning jumps are a result of mixed phase updraft intensification. Larger increases in intense updraft volume (≥ 10 m s−1) and larger changes in peak updraft speed are observed prior to lightning jump occurrence when compared to other non-jump increases in total flash rate. Wilcoxon-Mann-Whitney Rank Sum testing yields p-values ≤0.05, indicating statistical independence between lightning jump and non-jump distributions for these two parameters. Similar changes in mixed phase graupel mass magnitude are observed prior to lightning jumps and non-jump increases in total flash rate. The p-value for graupel mass change is p=0.096, so jump and non-jump distributions for graupel mass change are not found statistically independent using the p=0.05 significance level. Timing of updraft volume, speed and graupel mass increases are found to be 4 to 13 minutes in advance of lightning jump occurrence. Also, severe storms without lightning jumps lack robust mixed phase updrafts, demonstrating that mixed phase updrafts are not always a requirement for severe weather occurrence. Therefore, the results of this study show that lightning jump occurrences are coincident with larger increases in intense mixed phase updraft volume and peak updraft speed than smaller non-jump increases in total flash rate. PMID:29158622

  2. Kinematic and Microphysical Significance of Lightning Jumps versus Non-Jump Increases in Total Flash Rate.

    PubMed

    Schultz, Christopher J; Carey, Lawrence D; Schultz, Elise V; Blakeslee, Richard J

    2017-02-01

    Thirty-nine thunderstorms are examined using multiple-Doppler, polarimetric and total lightning observations to understand the role of mixed phase kinematics and microphysics in the development of lightning jumps. This sample size is larger than those of previous studies on this topic. The principal result of this study is that lightning jumps are a result of mixed phase updraft intensification. Larger increases in intense updraft volume (≥ 10 m s -1 ) and larger changes in peak updraft speed are observed prior to lightning jump occurrence when compared to other non-jump increases in total flash rate. Wilcoxon-Mann-Whitney Rank Sum testing yields p-values ≤0.05, indicating statistical independence between lightning jump and non-jump distributions for these two parameters. Similar changes in mixed phase graupel mass magnitude are observed prior to lightning jumps and non-jump increases in total flash rate. The p-value for graupel mass change is p=0.096, so jump and non-jump distributions for graupel mass change are not found statistically independent using the p=0.05 significance level. Timing of updraft volume, speed and graupel mass increases are found to be 4 to 13 minutes in advance of lightning jump occurrence. Also, severe storms without lightning jumps lack robust mixed phase updrafts, demonstrating that mixed phase updrafts are not always a requirement for severe weather occurrence. Therefore, the results of this study show that lightning jump occurrences are coincident with larger increases in intense mixed phase updraft volume and peak updraft speed than smaller non-jump increases in total flash rate.

  3. Kinematic and Microphysical Significance of Lightning Jumps Versus Non-Jump Increases in Total Flash Rate

    NASA Technical Reports Server (NTRS)

    Schultz, Christopher J.; Carey, Lawrence D.; Schultz, Elise V.; Blakeslee, Richard J.

    2017-01-01

    Thirty-nine thunderstorms are examined using multiple-Doppler, polarimetric and total lightning observations to understand the role of mixed phase kinematics and microphysics in the development of lightning jumps. This sample size is larger than those of previous studies on this topic. The principal result of this study is that lightning jumps are a result of mixed phase updraft intensification. Larger increases in intense updraft volume greater than or equal to 10 m(sup -1) and larger changes in peak updraft speed are observed prior to lightning jump occurrence when compared to other non-jump increases in total ash rate. Wilcoxon-Mann-Whitney Rank Sum testing yields p-values 0.05, indicating statistical independence between lightning jump and non-jump distributions for these two parameters. Similar changes in mixed phase graupel mass magnitude are observed prior to lightning jumps and non-jump increases in total ash rate. The p-value for graupel mass change is p=0.096, so jump and non-jump distributions for graupel mass change are not found statistically independent using the p=0.05 significance level. Timing of updraft volume, speed and graupel mass increases are found to be 4 to 13 minutes in advance of lightning jump occurrence. Also, severe storms without lightning jumps lack robust mixed phase updrafts, demonstrating that mixed phase updrafts are not always a requirement for severe weather occurrence. Therefore, the results of this study show that lightning jump occurrences are coincident with larger increases in intense mixed phase updraft volume and peak updraft speed than smaller non-jump increases in total ash rate.

  4. Accelerated blood clearance phenomenon upon cross-administration of PEGylated nanocarriers in beagle dogs

    PubMed Central

    Wang, Chunling; Cheng, Xiaobo; Su, Yuqing; Pei, Ying; Song, Yanzhi; Jiao, Jiao; Huang, Zhenjun; Ma, Yanfei; Dong, Yinming; Yao, Ying; Fan, Jingjing; Ta, Han; Liu, Xinrong; Xu, Hui; Deng, Yihui

    2015-01-01

    The cross-administration of nanocarriers modified by poly(ethylene glycol) (PEG), named PEGylated nanocarriers, a type of combination therapy, is becoming an increasingly important method of long-term drug delivery, to decrease side effects, avoid multidrug resistance, and increase therapeutic efficacy. However, repeated injections of PEGylated nanocarriers induces the accelerated blood clearance (ABC) phenomenon, prevents long circulation, and can cause adverse effects owing to alterations in the biodistribution of the drug. Although the nature of the ABC phenomenon that is induced by repeated injections of PEGylated nanocarriers has already been studied in detail, there are few reports on the immune response elicited by the cross-administration of PEGylated nanocarriers. In this study, we investigated the ABC phenomenon induced by the intravenous cross-administration of various PEGylated nanocarriers, including PEGylated liposomes (PL), PEG micelles (PM), PEGylated solid lipid nanoparticles (PSLN), and PEGylated emulsions (PE), in beagle dogs. The results indicated that the magnitude of the immune response elicited by the cross-administration was in the following order (from the strongest to the weakest): PL, PE, PSLN, PM. It is specifically PEG in the brush structure that elicits a significant immune response, in both the induction phase and the effectuation phase. Furthermore, the present study suggests that there is a considerable difference between the effect of repeated injections and cross-administration, depending on the colloidal structure. This work is a preliminary investigation into the cross-administration of PEGylated nanocarriers, and our observations can have serious implications for the design of combination therapies that use PEGylated vectors. PMID:25999716

  5. Co-administration of furosemide with albumin for overcoming diuretic resistance in patients with hypoalbuminemia: a meta-analysis.

    PubMed

    Kitsios, Georgios D; Mascari, Paolo; Ettunsi, Riad; Gray, Anthony W

    2014-04-01

    To systematically review clinical studies of co-administration of albumin and loop diuretics in hypoalbuminemic patients as a strategy to overcome diuretic resistance. Systematic search of electronic databases up to October 2012. We included randomized clinical trials of adults with hypoalbuminemia, comparing co-administration of loop diuretics and albumin versus loop diuretics alone. Quantitative data were synthesized with meta-analytic techniques for clinical, surrogate (urinary volume and urinary sodium excretion) and intermediate (pharmacokinetic and hemodynamic parameters) outcomes. Ten studies were included, of which 8 trials with crossover design were synthesized with meta-analysis. A statistically significant increase in the amount of urine volume (increment of 231 mL [95% confidence interval 135.5-326.5]) and sodium excreted (15.9 mEq [4.9-26.8]) at 8 hours were found in favor of co-administration of albumin and furosemide. These differences were no longer statistically significant at 24 hours. Meta-analyses for intermediate outcomes (ie, furosemide excretion, distribution volume etc.) did not reveal statistically significant differences. Synthesis of a heterogeneous body of evidence shows transient effects of modest clinical significance for co-administration of albumin with furosemide in hypoalbuminemic patients. Pragmatic, large-scale randomized studies are needed to delineate the role of this strategy. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Renal Effects of Long Term Administration of Triamcinolone Acetonide in Normal Dogs

    PubMed Central

    Osbaldiston, G. W.

    1971-01-01

    Triamcinolone acetonide was administered in excessive dosage to dogs to study the renal mechanism responsible for polyuria which is a clinically undesirable side effect of long term glucocorticoid therapy. Polyuria occurred coincident with a significant increase in urinary solute output. Although continuous administration of triamcinolone acetonide at 0.1 or 0.2 mg/lb/day caused a small but significant increase in creatinine output, the primary mechanism for the polyuria was increased solute excretion. Associated with the polyuria was pronounced hyperphagia and polydipsia. The cause of the hyperphagia was not established. The increase in electrolyte excretion caused by this synthetic steroid was probably compensated for by the hyperphagia. Because all the dogs showed muscle weakness and loss of body condition, it is likely that alteration in protein and amino acid metabolism was responsible for the hyperphagia. PMID:4251411

  7. Peri-OVLT E-series prostaglandins and core temperature do not increase after intravenous IL-1beta in pregnant rats.

    PubMed

    Fewell, James E; Eliason, Heather L; Auer, Roland N

    2002-08-01

    Rats have an attenuated febrile response to endogenous pyrogen near the term of pregnancy. Given the fundamental role of E-series prostaglandins (PGEs) in mediating the febrile response to blood-borne endogenous pyrogen, the present experiments were carried out to determine whether PGEs increase in the area surrounding the organum vasculosum laminae terminalis (peri-OVLT) of near-term pregnant (P) rats as in nonpregnant (NP) rats after intravenous (iv) administration of recombinant rat interleukin-1beta (rrIL-1beta). Core temperature was measured by telemetry and peri-OVLT interstitial fluid was sampled in 12 NP and 12 P chronically instrumented, Sprague-Dawley rats by microdialysis for determination of total PGEs by radioimmunoassay. Basal core temperatures were higher in NP compared with P rats (NP 37.9 degrees C +/- 0.5, P 36.9 degrees C +/- 0.4; P < 0.05), but basal peri-OVLT PGEs were similar in both groups (NP 260 +/- 153 pg/ml, P 278 +/- 177 pg/ml; P =not significant). Intravenous administration of rrIL-1beta to NP rats produced a significant increase in core temperature with a latency, magnitude, and duration of 10 min, 0.87 degrees C, and at least 170 min, respectively; peri-OVLT PGEs were increased significantly by 30 min and averaged 270% above basal levels throughout the experiment. In P rats, however, neither core temperature nor peri-OVLT PGEs increased significantly after iv administration of rrIL-1beta. Intravenous administration of vehicle did not significantly alter core temperature or peri-OVLT PGEs in either group of rats. Thus peri-OVLT PGEs do not increase in P rats as they do in NP rats after iv administration of rrIL-1beta. The mechanism of this interesting component of the maternal adaptation to pregnancy, which likely plays a major role in mediating the attenuated febrile response to endogenous pyrogen near the term of pregnancy, warrants further investigation.

  8. Enhanced serotonergic neurotransmission in the hippocampus following tryptophan administration improves learning acquisition and memory consolidation in rats.

    PubMed

    Haider, Saida; Khaliq, Saima; Haleem, Darakhshan J

    2007-01-01

    Increasing evidence shows that serotonin (5-hydroxytryptamine - 5-HT) plays a modulatory role in memory functions. 5-HT transmission has been implicated in learning and memory. Both 5-HT depletion and specific 5-HT agonists lower memory performance. Hippocampus is thought to be the key region involved in long-term memory. It is the major limbic target of the brainstem serotonergic neurons that modulate learning. In the present study, we examined the effects of increased hippocampal 5-HT metabolism following tryptophan (TRP) administration on short-term memory (STM) and long-term memory (LTM) in rats. Learning acquisition (LA) and memory consolidation (MC) in rats was also evaluated. TRP at 50 mg/kg and 100 mg/kg body weight was used. Assessment of memory in rats was done using the water maze test (WM) after 6 weeks of daily administration of TRP. The results showed that administration of TRP enhanced both STM and LTM. However, the effect on STM was significant only at the higher dose. Rats administered the higher dose of TRP also exhibited a significant enhancement in LA. A significant effect on MC was also observed in tryptophan-treated rats. The results suggest that serotonergic system in the hippocampus is important in LA and MC in rats.

  9. Age and body composition influence TSH concentrations after administration of rhTSH.

    PubMed

    Holthausen, F F; von Müller, F; Happel, C; Kranert, W T; Grünwald, F

    2015-01-01

    Previous studies listed body surface area (BSA), lean body mass (LBM), and age as modifying factors on the TSH concentrations after administration of recombinant human thyrotropin (rhTSH). The purpose of this study was to identify the main modifying factors on serum TSH levels and to compare the stimulation via single rhTSH injection after a short thyroid hormone withdrawal (THW) with that of the standard stimulating protocol. 106 patients with differentiated thyroid cancer (DTC) undergoing radioiodine therapy (RIT) after rhTSH administration were obtained through chart review. Two groups were evaluated: Group I was treated with a single rhTSH administration after two weeks of T3 therapy followed by one week of THW. Group II was stimulated according to the international standard protocol via rhTSH injections for two consecutive days. Serum TSH concentrations were documented prior to rhTSH administration (day 1 TSH), one day after (day 3 TSH) and 3-6 days after (mean 4.2 days, day 6 TSH) the last rhTSH injection. The following data was collected: age, gender, weight, height, BMI, LBM, BSA, residual thyroid tissue, CRP, creatinine, GFR, liver enzymes, alkaline phosphatase, cholesterol, and triglycerides. Group I: Age combined with anthropometric factors like BMI (TSH increase and day 6 TSH), BSA (TSH decrease), and gender (day 6 TSH) are the main modifying factors on serum TSH concentrations after rhTSH administration. Group II: Age and lean body mass (LBM) showed a significant impact on day 3 TSH, TSH increase (day 3-day 1), and TSH decrease (day 6-day 3). Day 6 TSH was found to be influenced by GFR (group II). Age and anthropometric parameters have significant independent influence on TSH concentrations after rhTSH injection in both groups. Anthropometric parameters (BSA, LBM) and demographic parameters (female gender) show strong influence on TSH concentrations. Further research should be conducted to examine the influence of body compartments on TSH levels

  10. Will health fund rationalisation lead to significant premium reductions?

    PubMed

    Hanning, Brian

    2003-01-01

    It has been suggested that rationalisation of health funds will generate significant albeit unquantified cost savings and thus hold or reduce health fund premiums. 2001-2 Private Health Industry Administration Council (PHIAC) data has been used to analyse these suggestions. Payments by funds for clinical services will not vary after fund rationalisation. The savings after rationalisation will arise from reductions in management expenses, which form 10.9% of total fund expenditure. A number of rationalisation scenarios are considered. The highest theoretical industry wide saving found in any plausible scenario is 2.5%, and it is uncertain whether this level of saving could be achieved in practice. If a one off saving of this order were achieved, it would have no medium and long term impact on fund premiums increases given funds are facing cost increases of 4% to 5% per annum due to demographic changes and age standardised utilization increases. It is suggested discussions on fund amalgamation divert attention from the major factors increasing fund costs, which are substantially beyond fund control.

  11. The effects of chronic intraperitoneal administration of the GABA B receptor agonist baclofen on food intake in rats.

    PubMed

    Patel, Sunit M; Ebenezer, Ivor S

    2008-09-28

    This study was undertaken to examine the effects of repeated administration of the GABA(B) receptor agonist baclofen on food intake in male Wistar rats. In the 1st Experiment, the effects of daily administration of physiological saline and baclofen (2 mg/kg, i.p.) for 27 days were investigated on food intake and body weight in non-deprived rats (n=6 in each group). Baclofen significantly (P<0.05) increased cumulative food intake each day over the treatment period during the 60 min measurement period following administration. Tolerance did not develop to the short-term hyperphagic effect of baclofen over the course of the experiment. In addition, treatment with baclofen did not alter body weight of the animals over the 27 day treatment period when compared with the saline control rats. In the 2nd Experiment, the effects of acute and chronic administration of baclofen (2 mg/kg) were investigated on 24 h food intake in rats. The rats were injected daily for 21 days with either saline (n=6) or baclofen (n=6). Food intake was measured in 30 min time bins for 24 h on treatment Days 1, 12 and 21 following injection. The results showed that while baclofen produced short-term increases in food consumption following injection on treatment Days 1, 12 and 21, the daily (24 h) food intake of the animals was not significantly different from those of control rats. Thus, these data reveal that while chronic administration of baclofen (2 mg/kg) produces short-term increases in feeding without the development of tolerance, daily (24 h) food consumption is not affected. These findings are consistent with the observation that chronic administration of baclofen (2 mg/kg) had no effect on the body weight of these animals.

  12. Comparison of the effects of acute fluvoxamine and desipramine administration on melatonin and cortisol production in humans.

    PubMed Central

    Skene, D J; Bojkowski, C J; Arendt, J

    1994-01-01

    1. Acute administration of the specific serotonin uptake inhibitor, fluvoxamine (100 mg at 16.00 h), markedly increased nocturnal plasma melatonin concentrations, with high levels extending into the morning hours. 2. Acute administration of the noradrenaline uptake inhibitor, desipramine (DMI) (100 mg at 16.00 h), increased evening plasma melatonin concentrations. 3. Both drug treatments increased the duration of melatonin secretion, fluvoxamine significantly delaying the offset time and DMI significantly advancing the onset time. 4. The stimulatory effect of DMI on plasma melatonin was mirrored by increased urinary 6-sulphatoxymelatonin (aMT6s) excretion. 5. On the contrary, there was no correlation between plasma melatonin and urinary aMT6s concentrations following fluvoxamine treatment, suggesting that fluvoxamine may inhibit the metabolism of melatonin. 6. Treatment with DMI increased plasma cortisol concentrations in the evening and early morning, treatment with fluvoxamine increased plasma cortisol at 03.00 h, 10.00 h and 11.00 h. 7. The drug treatments affected different aspects of the nocturnal plasma melatonin profile suggesting that the amplitude of the melatonin rhythm may depend upon serotonin availability and/or melatonin metabolism whilst the onset of melatonin production depends upon noradrenaline availability. PMID:8186063

  13. The effects of perphenazine on self-administration behavior.

    PubMed

    Johanson, C E; Kandel, D A; Bonese, K

    1976-04-01

    In Experiment 1.6 rhesus monkeys prepared with intravenous catheters responded on a fixed-ratio 10 schedule for either an injection of 0.2 mg/kg of cocaine or 0.5 mg/kg of pentobarbital during a daily 3 hr session. The substitution of saline or various doses of perphenazine resulted in very low rates of responding. These results indicate that perphenazine is not a positive reinforcer. Pretreating animals maintained on 0.1 mg/kg or 0.2 mg/kg of cocaine with perphenazine resulted in increases in rate of self-administration at some doses and a decrease in rate at higher doses. The dose of perphenazine which resulted in the maximal increase in cocaine self-administration was directly related to the dose of cocaine maintaining responding. Pretreating animals maintained on 0.5 mg/kg of pentobarbital with perphenazine had no effect at doses which increased cocaine self-administration but decreased rate of pentobarbital self-administration at higher doses. These results indicate that perphenazine is capable of antagonizing some of the effects of cocaine.

  14. Pharmacokinetics and pharmacodynamics of detomidine following sublingual administration to horses.

    PubMed

    Dimaio Knych, Heather K; Stanley, Scott D

    2011-10-01

    To characterize pharmacokinetics and pharmacodynamics of detomidine gel administered sublingually in accordance with label instructions to establish appropriate withdrawal guidelines for horses before competition. 12 adult racehorses. Horses received a single sublingual administration of 0.04 mg of detomidine/kg. Blood samples were collected before and up to 72 hours after drug administration. Urine samples were collected for 5 days after detomidine administration. Plasma and urine samples were analyzed via liquid chromatography-mass spectrometry, and resulting data were analyzed by use of noncompartmental analysis. Chin-to-ground distance, heart rate and rhythm, glucose concentration, PCV, and plasma protein concentration were also assessed following detomidine administration. Mean ± SD terminal elimination half-life of detomidine was 1.5 ± 1 hours. Metabolite concentrations were below the limit of detection (0.02, 0.1, and 0.5 ng/mL for detomidine, carboxydetomidine, and hydroxydetomidine, respectively) in plasma by 24 hours. Concentrations of detomidine and its metabolites were below the limit of detection (0.05 ng/mL for detomidine and 0.10 ng/mL for carboxydetomidine and hydroxydetomidine) in urine by 3 days. All horses had various degrees of sedation after detomidine administration. Time of onset was ≤ 40 minutes, and duration of sedation was approximately 2 hours. Significant decreases, relative to values at time 0, were detected for chin-to-ground distance and heart rate. There was an increased incidence and exacerbation of preexisting atrioventricular blocks after detomidine administration. A 48-hour and 3-day withdrawal period for detection in plasma and urine samples, respectively, should be adopted for sublingual administration of detomidine gel.

  15. Short-term estriol administration modulates hypothalamo-pituitary function in patients with functional hypothalamic amenorrhea (FHA).

    PubMed

    Genazzani, Alessandro D; Podfigurna-Stopa, Agnieszka; Czyzyk, Adam; Katulski, Krzysztof; Prati, Alessia; Despini, Giulia; Angioni, Stefano; Simoncini, Tommaso; Meczekalski, Blazej

    2016-01-01

    To evaluate the influence of short-term estriol administration (10 d) on the hypothalamus-pituitary function and gonadotropins secretion in patients affected by functional hypothalamic amenorrhea (FHA). Controlled clinical study on patients with FHA (n = 12) in a clinical research environment. Hormonal determinations and gonadotropin (luteinizing hormone [LH] and FSH) response to a gonadotropin-releasing hormone (GnRH) bolus (10 μg) at baseline condition and after 10 d of therapy with 2 mg/d of estriol per os. Measurements of plasma LH, FSH, prolactin, estradiol, androstenedione, 17α-hydroxyprogesterone, insulin, cortisol, thyroid-stimulating hormone, free triiodothyronine, and free thyroxine. After treatment, the FHA patients showed a statistically significant increase of both LH and FSH plasma levels and the significant increase of their responses to the GnRH bolus. Estriol short-term therapy modulates within 10 d of administration the neuroendocrine control of the hypothalamus-pituitary unit and induces the recovery of both gonadotropins synthesis and secretion in hypogonadotropic patients with FHA.

  16. U.S. Public Administration Programs: Increasing Academic Achievement by Identifying and Utilizing Student Learning Styles

    ERIC Educational Resources Information Center

    Naylor, Lorenda A; Wooldridge, Blue; Lyles, Alan

    2014-01-01

    Global economic shifts are forcing universities to become more competitive and operationally efficient. As a result, universities emphasize access, affordability, and achievement. More specifically, U.S. universities have responded by emphasizing course assessment, retention rates, and graduation rates. Both university administrators and faculty…

  17. Free ammonia pre-treatment of secondary sludge significantly increases anaerobic methane production.

    PubMed

    Wei, Wei; Zhou, Xu; Wang, Dongbo; Sun, Jing; Wang, Qilin

    2017-07-01

    Energy recovery in the form of methane from sludge/wastewater is restricted by the poor and slow biodegradability of secondary sludge. An innovative pre-treatment technology using free ammonia (FA, i.e. NH 3 ) was proposed in this study to increase anaerobic methane production. The solubilisation of secondary sludge was significantly increased after FA pre-treatment at up to 680 mg NH 3 -N/L for 1 day, under which the solubilisation (i.e. 0.4 mg SCOD/mg VS; SCOD: soluble chemical oxygen demand; VS: volatile solids) was >10 times higher than that without FA pre-treatment (i.e. 0.03 mg SCOD/mg VS). Biochemical methane potential assays showed that FA pre-treatment at above 250 mg NH 3 -N/L is effective in improving anaerobic methane production. The highest improvement in biochemical methane potential (B 0 ) and hydrolysis rate (k) was achieved at FA concentrations of 420-680 mg NH 3 -N/L, and was determined as approximately 22% (from 160 to 195 L CH 4 /kg VS added) and 140% (from 0.22 to 0.53 d -1 ) compared to the secondary sludge without pre-treatment. More analysis revealed that the FA induced improvement in B 0 and k could be attributed to the rapidly biodegradable substances rather than the slowly biodegradable substances. Economic and environmental analyses showed that the FA-based technology is economically favourable and environmentally friendly. Since this FA technology aims to use the wastewater treatment plants (WWTPs) waste (i.e. anaerobic digestion liquor) to enhance methane production from the WWTPs, it will set an example for the paradigm shift of the WWTPs from 'linear economy' to 'circular economy'. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Pedi-cap color change precedes a significant increase in heart rate during neonatal resuscitation.

    PubMed

    Blank, Doug; Rich, Wade; Leone, Tina; Garey, Donna; Finer, Neil

    2014-11-01

    Heart rate is the most important indicator of infant well-being during neonatal resuscitation. The Nellcor Pedi-Cap turns gold when exposed to exhaled gas with CO₂>15 mmHg. The aim of this study was to determine if Pedi-Cap gold color change during neonatal resuscitation precedes an increase in heart rate in babies with bradycardia receiving mask ventilation. This was a single-center retrospective review of video recordings and physiologic data of newborns with bradycardia receiving mask positive pressure ventilation during neonatal resuscitation. Subjects were included if the baby's HR<100 BPM within the first 90 s of resuscitation. The primary outcome was the change in HR prior to Pedi-Cap gold color change compared to the HR after Pedi-Cap gold color change. Forty-one newborns during the study period had HR<100 BPM and received mask positive pressure ventilation with a Pedi-Cap. The median heart rate 10s prior to Pedi-Cap gold color change was 75 BPM (IQR 62-85) and increased to 136 BPM (IQR 113-158) 30 s after gold color change (p<0.001). SpO₂ increased from 45 ± 17% prior to Pedi-Cap gold color change to 52 ± 17% 30s after gold color change (p=0.001). Colorimetric CO₂ detection during mask positive pressure ventilation in neonatal resuscitation precedes a significant increase in heart rate and SpO₂. The Pedi-Cap can be easily applied during resuscitation, requires no electricity, provides immediate feedback and may be a useful, simple tool early in resuscitation and may be especially useful in resource limited settings. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  19. Effects of maropitant, acepromazine, and electroacupuncture on vomiting associated with administration of morphine in dogs.

    PubMed

    Koh, Ronald B; Isaza, Natalie; Xie, Huisheng; Cooke, Kirsten; Robertson, Sheilah A

    2014-04-01

    To evaluate effects of maropitant, acepromazine, and electroacupuncture on morphine-related signs of nausea and vomiting in dogs and assess sedative effects of the treatments. Randomized controlled clinical trial. 222 dogs. Dogs received 1 of 6 treatments: injection of saline (0.9% NaCl) solution, maropitant citrate, or acepromazine maleate or electroacupuncture treatment at 1 acupoint, 5 acupoints, or a sham acupoint. Morphine was administered after 20 minutes of electroacupuncture treatment or 20 minutes after injectable treatment. Vomiting and retching events and signs of nausea and sedation were recorded. Incidence of vomiting and retching was significantly lower in the maropitant (14/37 [37.8%]) group than in the saline solution (28/37 [75.7%]) and sham-acupoint electroacupuncture (32/37 [86.5%]) groups. The number of vomiting and retching events in the maropitant (21), acepromazine (38), 1-acupoint (35), and 5-acupoint (34) groups was significantly lower than in the saline solution (88) and sham-acupoint electroacupuncture (109) groups. Incidence of signs of nausea was significantly lower in the acepromazine group (3/37 [8.1%]) than in the sham-acupoint group (15/37 [40.5%]). Mean nausea scores for the saline solution, maropitant, and sham-acupoint electroacupuncture groups increased significantly after morphine administration, whereas those for the acepromazine, 1-acupoint electroacupuncture, and 5-acupoint electroacupuncture groups did not. Mean sedation scores after morphine administration were significantly higher in dogs that received acepromazine than in dogs that received saline solution, maropitant, and sham-acupoint electroacupuncture treatment. Maropitant treatment was associated with a lower incidence of vomiting and retching, compared with control treatments, and acepromazine and electroacupuncture appeared to prevent an increase in severity of nausea following morphine administration in dogs.

  20. Effects of intravenous, sternal, and humerus intraosseous administration of Hextend on time of administration and hemodynamics in a hypovolemic swine model.

    PubMed

    Blouin, Dawn; Gegel, Brian T; Johnson, Don; Garcia-Blanco, Jose C

    2016-01-01

    To determine if there were significant differences among humerus intraosseous (HIO), sternal intraosseous (SIO), and intravenous (IV) administration of 500 mL Hextend in hemodynamics or administration time in a hypovolemic swine model. Vivarium. Yorkshire swine; sample size was based on a large effect size of 0.5, an α of 0.05, and a power of 80 percent Swine were randomly assigned to one of four groups: HIO (n = 9), SIO (n = 9), IV (n = 9), and control (n = 9). Swine were exsanguinated 30 percent of their blood volume. Hextend (500 mL) was administered by either the HIO, SIO, or IV route; the control group received none. Time of administration of Hextend; systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), heart rate (HR), cardiac output (CO), and stroke volume (SV) data were collected every 2 minutes and compared by group over 8 minutes. A repeated analysis of variance found that there were no significant differences in SBP, DBP, MAP, HR, CO, and SV among HIO, SIO, and IV groups over 8 minutes (p > 0.05). An analyses of variance determined that there was no significant difference between groups relative to time of administration (p = 0.521). When IV access is difficult, both HIO and SIO are effective techniques for rapid vascular access and the administration of Hextend for patients in hypovolemic shock.

  1. Initiation and maintenance of oral ethanol self-administration in female Sprague-Dawley rats.

    PubMed

    Neill, J C; Domeney, A M; Costall, B

    1994-01-01

    Group-housed female Sprague-Dawley rats were trained to self-administer 5% ethanol (v/v) in a large self-administration chamber (100 x 40 x 40 cm) following three different initiation methods. The procedures were 1) an ethanol injection procedure, 2) a sucrose substitution procedure, and 3) a prandial drinking technique. Only the prandial drinking method served to maintain responding for ethanol in the absence of water deprivation or sweetening of the alcohol solution. Rats trained using this technique showed a large preference for 5% ethanol over water and a significant increase in locomotor activity while responding for 5% ethanol but not while responding for water. When the concentration of ethanol was increased from 1% to 32%, the amount of ethanol ingested increased up to a maximum of 1.233 +/- 0.3 g/kg of 32% ethanol, and response rates and number of ethanol deliveries followed an inverted U-shaped curve. Appreciable blood ethanol levels were detected immediately following self-administration of 8% ethanol. These results show that, in female Sprague-Dawley rats under the experimental conditions described, the prandial drinking technique was the most effective in inducing stable oral ethanol self-administration and suggest that under these conditions and in these subjects ethanol was acting as a positive reinforcer.

  2. Oral administration of live- or heat-killed Candida albicans worsened cecal ligation and puncture sepsis in a murine model possibly due to an increased serum (1→3)-β-D-glucan.

    PubMed

    Panpetch, Wimonrat; Somboonna, Naraporn; Bulan, Dewi Embong; Issara-Amphorn, Jiraphorn; Finkelman, Malcolm; Worasilchai, Navaporn; Chindamporn, Ariya; Palaga, Tanapat; Tumwasorn, Somying; Leelahavanichkul, Asada

    2017-01-01

    Candida albicans is the most common fungus in the human intestinal microbiota but not in mice. To make a murine sepsis model more closely resemble human sepsis and to explore the role of intestinal C. albicans, in the absence of candidemia, in bacterial sepsis, live- or heat-killed C. albicans was orally administered to mice at 3h prior to cecal ligation and puncture (CLP). A higher mortality rate of CLP was demonstrated with Candida-administration (live- or heat-killed) prior to CLP. Fecal Candida presented only in experiments with live-Candida administration. Despite the absence of candidemia, serum (1→3)-β-D-glucan (BG) was higher in CLP with Candida-administration than CLP-controls (normal saline administration) at 6h and/or 18h post-CLP. Interestingly, fluconazole attenuated the fecal Candida burden and improved survival in mice with live-Candida administration, but not CLP-control. Microbiota analysis revealed increased Bacteroides spp. and reduced Lactobacillus spp. in feces after Candida administration. Additionally, synergy in the elicitation of cytokine production from bone marrow-derived macrophages, in vitro, was demonstrated by co-exposure to heat-killed E. coli and BG. In conclusion, intestinal abundance of fungi and/or fungal-molecules was associated with increased bacterial sepsis-severity, perhaps through enhanced cytokine elicitation induced by synergistic responses to molecules from gut-derived bacteria and fungi. Conversely, reducing intestinal fungal burdens decreased serum BG and attenuated sepsis in our model.

  3. Hospital administrator's perspectives regarding the health care industry.

    PubMed

    McDermott, D R; Little, M W

    1988-01-01

    , followed by product/service development and finally, market penetration strategies. Clearly, the role of marketing will increase as new targets and new offerings dominate future, strategic decision-making. Specific hospital services having the highest future priority include out-patient services, in-patient care, cardiology, cancer/oncology, obstetrics, and services geared specifically to women and the elderly. Finally, when asked to identify the three most significant challenges facing the health care/hospital industry over the next five years, 12 challenges emerged, with five being mentioned by the majority of the administrators and seven by the minority.(ABSTRACT TRUNCATED AT 400 WORDS)

  4. Intracarotid administration of short-chain alkylglycerols for increased delivery of methotrexate to the rat brain.

    PubMed

    Erdlenbruch, Bernhard; Schinkhof, Claudia; Kugler, Wilfried; Heinemann, Dagmar E H; Herms, Jochen; Eibl, Hansjörg; Lakomek, Max

    2003-06-01

    1 The intracarotid administration of alkylglycerols has been reported previously by us to be a novel strategy for increased delivery of various chemotherapeutic drugs to the normal brain and brain tumors in rats. 2 Effectiveness and structure-activity relations of the most promising pentyl- and hexylglycerol derivatives have been elucidated in vivo by analyzing the transfer of methotrexate (MTX) across the blood-brain barrier (BBB) in normal rats. The effects were compared with BBB disruption using hypertonic mannitol or intracarotid infusion of bradykinin. Furthermore, toxicity of the alkylglycerols has been studied in long-term experiments. 3 Apart from 1-O-pentyldiglycerol, all alkylglycerols induced a concentration-dependent increase in MTX delivery to the brain varying from 1.1 to more than 300-fold compared to intra-arterial MTX alone. Enhanced barrier permeability rapidly approached baseline values within 5 and 120 min at the latest. Chemical structure, concentration, time schedule of injections and combination of different alkylglycerols were identified as instruments suited to regulate the MTX accumulation within a wide range. Mannitol 1.4 M resulted in very high MTX levels in the brain as observed using the highest concentrations of alkylglycerols. Intracarotid infusion of bradykinin had only a minor effect on the BBB. Using 1-O-pentylglycerol or 2-O-hexyldiglycerol, both cell culture experiments and long-term in vivo analyses including clinical, laboratory and histopathological evaluations revealed no signs of toxicity. 4 In summary, intracarotid short-chain alkylglycerols constitute a very effective and low toxic strategy for transient opening of the BBB to overcome the limited access of cytotoxic drugs to the brain.

  5. Isoflurane administration before ischemia and during reperfusion attenuates ischemia/reperfusion-induced injury of isolated rabbit lungs.

    PubMed

    Liu, R; Ishibe, Y; Ueda, M; Hang, Y

    1999-09-01

    To investigate the effects of isoflurane on ischemia/ reperfusion (IR)-induced lung injury, we administered isoflurane before ischemia or during reperfusion. Isolated rabbit lungs were divided into the following groups: control (n = 6), perfused and ventilated for 120 min without ischemia; ISO-control (n = 6), 1 minimum alveolar anesthetic concentration (MAC) isoflurane was administered for 30 min before 120 min continuous perfusion; IR (n = 6), ischemia for 60 min, followed by 60 min reperfusion; IR-ISO1 and IR-ISO2, ischemia followed by reperfusion and 1 MAC (n = 6) or 2 MAC (n = 6) isoflurane for 60 min; ISO-IR (n = 6), 1 MAC isoflurane was administered for 30 min before ischemia, followed by IR. During these maneuvers, we measured total pulmonary vascular resistance (Rt), coefficient of filtration (Kfc), and lung wet to dry ratio (W/D). The results indicated that administration of isoflurane during reperfusion inhibited an IR-induced increase in Kfc and W/D ratio. Furthermore, isoflurane at 2 MAC, but not 1 MAC, significantly inhibited an IR-induced increase in Rt. The administration of isoflurane before ischemia significantly attenuated the increase in IR-induced Kfc, W/D, and Rt. Our results suggest that the administration of isoflurane before ischemia and during reperfusion protects against ischemia-reperfusion-induced injury in isolated rabbit lungs.

  6. [Effect of Radix euphorbiae pekinensis extract on bioavailability of paclitaxel after their oral co-administration].

    PubMed

    Li, Minghua; Peng, Li; Yang, Fuheng; Liu, Sijia; Wang, Shengqi

    2015-06-01

    To evaluate the effect of Radix euphorbiae pekinensis extract on the permeability and bioavailability of paclitaxel co-administered orally. Based on Ussing Chamber and in vivo experiment, the permeability and bioavailability of paclitaxel were evaluated after oral co-administration with radix euphorbiae pekinensis in rats. The contents of paclitaxel in the permeates and the blood samples were determined using HPLC and LC-MS/MS method, respectively. In Radix euphorbiae pekinensis co-administration group, the Papp of the mucosal-to-serosal (M-S) transport or serosal-to-mucosal transport (S-M) of paclitaxel in the jejunum or ileum segment differed significantly from those in verapamil co-administration group and blank control group (P<0.05), but the Papp of S-M transport in the colon showed no significant difference from that in the blank control group. In the blank group, the average absolute bioavailability (AB%) of orally administered paclitaxel was only 2.81%, compared to that of 7.63% in radix euphorbiae pekinensis group. The average AB% in verapamil group was about 1.5 times that of the blank group. Co-administration of Radix euphorbiae pekinensis extract can increase the bioavailability of orally administered paclitaxel.

  7. Short-term increase of serum troponin I and serum heart-type fatty acid-binding protein (H-FABP) in dogs following administration of formoterol.

    PubMed

    Strauss, Volker; Wöhrmann, Thomas; Frank, Ilona; Hübel, Ulrich; Luft, Jörg; Bode, Gerd; Germann, Paul-Georg

    2010-07-01

    In this paper, changes in serum levels of the cardiac biomarkers troponin I and the heart-type fatty acid-binding protein (H-FABP) following administration of a long-acting beta(2)-sympathicomimeticum (long-acting beta-agonist, LABA) to dogs were measured. We measured troponin I in dogs in a 4-week repeated-dose study with inhalative administration of formoterol (13microg/kgd) and a glucocorticoid/formoterol combination (143/16microg/kgd). The medians of troponin I increased within 3 days in both groups, far beyond the cut-off level (0.1microg/L), but returned to baseline levels on study day 9. The increase was more pronounced in the formoterol-only group (3.29microg/L) compared to the glucocorticoid/formoterol combination group (1.32microg/L). In a second study, we measured serum troponin I as well as serum H-FABP levels in several samples over 7 days in dogs, receiving a single inhalative dose of a glucocorticoid/formoterol combination (120/12mug/kgd). The median of the troponin I concentration increased above the cut-off level within 2h and that of H-FABP within 4h. The medians of both parameters were temporarily above the cut-off levels even on study day 7. Both studies were conducted according to national animal welfare guidelines. To our knowledge, this is the first report that shows a corresponding increase of troponin I and H-FABP in dogs treated with formoterol. Both parameters are more sensitive in detecting a drug-induced cardiac injury compared to total LDH, total CK as well as CK MB activity. However, it is recommended to take at least three blood samples per day to assess a temporary increase of troponin I.

  8. [Effects of perioperative administration of celecoxib on pain management and recovery of function after total knee replacement].

    PubMed

    Shen, Bin; Tang, Xin; Yang, Jing; Li, Yong; Zhou, Zong-ke; Kang, Peng-de; Pei, Fu-xing

    2009-01-15

    To assess the effect of perioperative administration of a selective cyclooxygenase 2 inhibitor (celecoxib) on pain management and recovery of function after total knee arthroplasty (TKA). Randomized, controlled trial conducted from January 2005 through February 2006, 60 patients underwent TKA for osteoarthritis or rheumatoid arthritis were randomly divided into group of perioperative, administration of celecoxib (Study group, n = 30) and postoperative administration of celecoxib (Control group, n = 30). Patients in Study group were given oral celecoxib 3 d before TKA, 200 mg twice daily, and extended to 5 d postoperatively; patients in Control group were given oral celecoxib 2 h after TKA, 200 mg twice daily, and extended to 5 d postoperatively. All operations were finished by the same surgeon group. The postoperative patient-controlled analgesia (PCA) consumption was significantly less in Study group than in Control group [(43 +/- 12) ml vs. (53 +/- 12) ml, P < 0.05]. The pain scores of postoperative 4, 8, 12 h, 1, 2 d in Study group were 6.1 +/- 1.2, 5.0 +/- 1.3, 4.3 +/- 1.1, 3.4 +/- 1.2, significantly less than in Control group (P < 0.05); There were no intergroup significant differences in the pain scores of postoperative 3, 4, 5 d (P > 0.05). There were no intergroup significant differences in respect to the side-effect occurrence, operation time and postoperative drainage, postoperative analgesic consumption (P > 0.05). The time to achieve 90 degrees knee flexion was significantly shorter in Study group than in Control group [(6.2 +/- 1.7) d vs. (8.6 +/- 1.8) d, P < 0.05]. Perioperative administration of the selective Celecoxib holds the effect of preemptive analgesia. Compared with postoperative administration, perioperative administration of celecoxib can alleviate the early postoperative pain score, reduce the consumption of postoperative analgesic, accelerate the recovery of joint motion and thus increase the patient satisfaction.

  9. Co-administration of α-lipoic acid and glutathione is associated with no significant changes in serum bilirubin, alkaline phosphatase or γ-glutamyltranspeptidase levels during the treatment of neuroborreliosis with intravenous ceftriaxone.

    PubMed

    Puri, Basant K; Hakkarainen-Smith, Jaana S; Derham, Anne; Monro, Jean A

    2015-09-01

    While pharmacotherapy with intravenous ceftriaxone, a third-generation cephalosporin, is a potential treatment of Lyme neuroborreliosis, there is concern that it can cause the formation of biliary sludge, leading to hepatobiliary complications such as biliary colic, jaundice and cholelithiasis, which are reflected in changes in serum levels of bilirubin and markers of cholestatic liver injury (alkaline phosphatase and γ-glutamyltranspeptidase). It has been suggested that the naturally occurring substances α-lipoic acid and glutathione may be helpful in preventing hepatic disease. α-Lipoic acid exhibits antioxidant, anti-inflammatory and anti-apoptotic activities in the liver, while glutathione serves as a sulfhydryl buffer. The aim of this study was to determine whether co-administration of α-lipoic acid and glutathione is associated with significant changes in serum levels of bilirubin, alkaline phosphatase and γ-glutamyltranspeptidase during the treatment of Lyme neuroborreliosis with long-term intravenous ceftriaxone. Serum levels of bilirubin, alkaline phosphatase and γ-glutamyltranspeptidase were measured in 42 serologically positive Lyme neuroborreliosis patients before and after long-term treatment with intravenous ceftriaxone (2-4 g daily) with co-administration of oral/intravenous α-lipoic acid (600 mg daily) and glutathione (100 mg orally or 0.6-2.4 g intravenously daily). None of the patients developed biliary colic and there were no significant changes in serum bilirubin, alkaline phosphatase or γ-glutamyltranspeptidase levels over the course of the intravenous ceftriaxone treatment (mean length 75.0 days). Co-administration of α-lipoic acid and glutathione is associated with no significant changes in serum bilirubin, alkaline phosphatase or γ-glutamyltranspeptidase levels during the treatment of neuroborreliosis with intravenous ceftriaxone.

  10. Local administration of a cannabinoid agonist alters norepinephrine efflux in the rat frontal cortex.

    PubMed

    Page, M E; Oropeza, V C; Van Bockstaele, E J

    2008-01-24

    Delta(9)-tetrahydrocannabinol, the main psychoactive ingredient in marijuana, activates specific cannabinoid (CB) receptors to exert complex actions on modulatory neurotransmitters involved in attention and cognition. Previous research has demonstrated that systemic administration of the synthetic cannabinoid agonist, WIN 55,212-2, increases norepinephrine efflux in the frontal cortex. The distribution of CB1 receptors on noradrenergic fibers in the frontal cortex suggests this may be one potential site for the regulation of norepinephrine release. In the present study, we first examined the ability of a CB1 antagonist, applied locally in the frontal cortex of adult male Sprague-Dawley rats, to block the actions of systemic WIN 55,212-2. Pretreatment with SR 141716A (300 microM) significantly attenuated the excitatory effects of WIN 55,212-2 (15 mg/kg, i.p.). Next, the impact of direct perfusion of WIN 55,212-2 into the frontal cortex on extracellular norepinephrine efflux was measured. Direct application of WIN 55,212-2 (100 microM) into the frontal cortex elicited a significant increase in extracellular norepinephrine efflux suggesting that activation of cortical cannabinoid receptors contributes to alterations in norepinephrine levels in this brain region. Finally, local administration of SR 141716A followed by local administration of WIN 55,212-2 revealed a paradoxical inhibition of norepinephrine efflux.

  11. Increasing Neuroplasticity to Bolster Chronic Pain Treatment: A Role for Intermittent Fasting and Glucose Administration?

    PubMed Central

    Sibille, KT; Bartsch, F; Reddy, D; Fillingim, RB; Keil, A

    2016-01-01

    Neuroplastic changes in brain structure and function are not only a consequence of chronic pain but are involved in the maintenance of pain symptoms. Thus, promoting adaptive, treatment responsive neuroplasticity represents a promising clinical target. Emerging evidence about the human brain’s response to an array of behavioral and environmental interventions may assist in identifying targets to facilitate increased neurobiological receptivity, promoting healthy neuroplastic changes. Specifically, strategies to maximize neuroplastic responsiveness to chronic pain treatment could enhance treatment gains by optimizing learning and positive central nervous system (CNS) adaptation. Periods of heightened plasticity have been traditionally identified with the early years of development. More recent research however has identified a wide spectrum of methods that can be used to “re-open” and enhance plasticity and learning in adults. In addition to transcranial direct current stimulation and transcranial magnetic stimulation, behavioral and pharmacological interventions have been investigated. Intermittent fasting and glucose administration are two propitious strategies, which are non-invasive, inexpensive to administer, implementable in numerous settings, and may be applicable across differing chronic pain treatments. Key findings and neurophysiological mechanisms are summarized, providing evidence for the potential clinical contributions of these two strategies toward ameliorating chronic pain. PMID:26848123

  12. School Business Administration: A Planning Approach. Third Edition.

    ERIC Educational Resources Information Center

    Candoli, I. Carl; And Others

    The school business administration function in the operation of American schools has undergone dramatic changes during the past several years. Changing demographics, high technology, the movement to professionalize school administration, and changes by the legislative and judicial systems have all had significant impact on the character of school…

  13. Hypotensive effect of alpha-lipoic acid after a single administration in rats.

    PubMed

    Dudek, Magdalena; Razny, Katarzyna; Bilska-Wilkosz, Anna; Iciek, Malgorzata; Sapa, Jacek; Wlodek, Lidia; Filipek, Barbara

    2016-05-01

    The effect of alpha-lipoic acid on blood pressure was investigated many times in chronic studies, but there are no studies on the effect of this compound after a single administration. Alpha-lipoic acid is a drug used in diabetic neuropathy, often in obese patients, to treat hypertension. Therefore, knowledge of the potential antihypertensive effect of alpha-lipoic acid even after a single dose and possibly too much pressure reduction is interesting and useful. The mechanism of the hypotensive effect of alpha-lipoic acid was examined in normotensive rats in vivo after a single intraperitoneal administration, blood pressure in the left carotid artery of the rats was measured prior to the administration of the compounds (alpha- lipoic acid and/or glibenclamide) and 80 min thereafter. Alpha-lipoic acid at a dosage of 50 mg/kg b.w. i.p. significantly decreased the blood pressure from the 50th min after drug administration. This cardiovascular effect of this compound was reversed by glibenclamide, a selective KATP blocker. Glibenclamide alone at this dose did not significantly affect the blood pressure. Statistical significance was evaluated using two-way ANOVA. This suggests that alpha-lipoic acid affects ATP-dependent potassium channels. It is possible that this is an indirect effect of hydrogen sulfide because alpha-lipoic acid can increase its concentration. The results obtained in this study are very important because the patients taking alpha-lipoic acid may be treated for co-existing hypertension. Therefore, the possibility of blood pressure lowering by alpha-lipoic acid should be taken into account, although it does not lead to excessive orthostatic hypotension.

  14. A mechanistic study to increase understanding of titanium dioxide nanoparticles-increased plasma glucose in mice.

    PubMed

    Hu, Hailong; Li, Li; Guo, Qian; Jin, Sanli; Zhou, Ying; Oh, Yuri; Feng, Yujie; Wu, Qiong; Gu, Ning

    2016-09-01

    Titanium dioxide nanoparticle (TiO2 NP) is an authorized food additive. Previous studies determined oral administration of TiO2 NPs increases plasma glucose in mice via inducing insulin resistance. An increase in reactive oxygen species (ROS) has been considered the possible mechanism of increasing plasma glucose. However, persistently high plasma glucose is also a mechanism of increasing ROS. This study aims to explore whether TiO2 NPs increase plasma glucose via ROS. We found after oral administration of TiO2 NPs, an increase in ROS preceded an increase in plasma glucose. Subsequently, mice were treated with two antioxidants (resveratrol and vitamin E) at the same time as oral administration of TiO2 NPs. Results showed resveratrol and vitamin E reduced TiO2 NPs-increased ROS. An increase in plasma glucose was also inhibited. Further research showed resveratrol and vitamin E inhibited the secretion of TNF-α and IL-6, and the phosphorylation of JNK and p38 MAPK, resulting in improved insulin resistance. These results suggest TiO2 NPs increased ROS levels, and then ROS activated inflammatory cytokines and phosphokinases, and thus induced insulin resistance, resulting in an increase in plasma glucose. Resveratrol and vitamin E can reduce TiO2 NPs-increased ROS and thereby inhibit an increase in plasma glucose in mice. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. The role of reactive oxygen species in methamphetamine self-administration and dopamine release in the nucleus accumbens.

    PubMed

    Jang, Eun Young; Yang, Chae Ha; Hedges, David M; Kim, Soo Phil; Lee, Jun Yeon; Ekins, Tyler G; Garcia, Brandon T; Kim, Hee Young; Nelson, Ashley C; Kim, Nam Jun; Steffensen, Scott C

    2017-09-01

    Methamphetamine (METH) markedly increases dopamine (DA) release in the mesolimbic DA system, which plays an important role in mediating the reinforcing effects of METH. METH-induced DA release results in the formation of reactive oxygen species (ROS), leading to oxidative damage. We have recently reported that ROS are implicated in behavior changes and DA release in the nucleus accumbens (NAc) following cocaine administration. The aim of this study was to evaluate the involvement of ROS in METH-induced locomotor activity, self-administration and enhancement of DA release in the NAc. Systemic administration of a non-specific ROS scavenger, N-tert-butyl-α-phenylnitrone (PBN; 0, 50 and 75 mg/kg, IP) or a superoxide-selective scavenger, 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPOL; 0, 50 and 100 mg/kg, IP), attenuated METH-induced locomotor activity without affecting generalized behavior in METH-naïve rats. PBN and TEMPOL significantly attenuated METH self-administration without affecting food intake. Increased oxidative stress was found in neurons, but not astrocytes, microglia or oligodendrocytes, in the NAc of METH self-administering rats. In addition, TEMPOL significantly decreased METH enhancement of DA release in the NAc. Taken together, these results suggest that enhancement of ROS in the NAc contributes to the reinforcing effect of METH. © 2016 Society for the Study of Addiction.

  16. Levels of Stress among Secondary School Administrators and Its Implication in Education Management in Kenya

    ERIC Educational Resources Information Center

    Ngari, S. M.; Ndungu, A.; Mwonya, R.; Ngumi, O.; Mumiukha, C.; Chepchieng, M.; Kariuki, M.

    2013-01-01

    Stress significantly affects performance and service delivery of workers. Given the important role that education plays in the society, coupled with the dynamic nature of the education sector there has been an increased social pressure on the education system in general and school administrators in particular. This influences their levels of…

  17. Co-treatment with grapefruit juice inhibits while chronic administration activates intestinal P-glycoprotein-mediated drug efflux.

    PubMed

    Panchagnula, R; Bansal, T; Varma, M V S; Kaul, C L

    2005-12-01

    P-Glycoprotein (P-gp) mediated efflux is recognized as a significant biochemical barrier affecting oral absorption for a number of drugs. Various conflicting reports have been published regarding the effects of grapefruit juice (GFJ) on P-gp-mediated drug efflux, in which GFJ has been shown both to inhibit and activate it. Hence, the present study adopted a two-way approach, involving both co-treatment and chronic administration. Bi-directional transport of paclitaxel (PCL) was carried out in the absence and presence of GFJ extract, in rat everted ileum sac. Further, the effect of chronic administration of GFJ to rats was characterized by permeability studies with indinavir (INDI). Co-treatment of GFJ extract at 100% concentration reduced the asymmetric transport of PCL (efflux ratio = 20.8) by increasing absorptive (A --> B) transport by 921% and reducing secretory (B --> A) transport by 41%. Further, GFJ showed a concentration dependent effect on PCL permeability. Imipramine, a passive permeability marker with absorptive permeability of 15.33 +/- 4.26 x 10(-6) cm/s showed no asymmetric transport and also no significant (P < 0.05) change in permeability in the presence of GFJ. Chronic administration of GFJ resulted in a significant decrease in absorptive transport of indinavir, which was even greater than that produced by rifampicin pretreatment. No change in permeability of propranolol, a passive permeability marker, was observed. Further, the decrease in absorptive transport of INDI was reversed by the P-gp inhibitor verapamil. In conclusion, GFJ extract inhibited P-gp-mediated efflux in co-treatment, whereas chronic administration led to increased levels of P-gp expression, thus having a profound effect on intestinal absorption and GFJ-drug interactions in vivo.

  18. Web course on medication administration strengthens nursing students' competence prior to graduation.

    PubMed

    Mettiäinen, Sari; Luojus, Katja; Salminen, Satu; Koivula, Meeri

    2014-08-01

    Nursing students' competence has been found inadequate in mastering of pharmacotherapy regulations and prescriptions, pharmacology, medical calculations, fractional and decimal numbers, and mathematics on the whole. The study investigated the efficacy of an additional medication administration web course in increasing nursing students' self-evaluated competence on medication administration. Finnish nursing students self-evaluated their medication administration competence before and after the web-based medication course. Design was quasi-experimental. 244 students answered the questionnaire before and 192 after the web course. An online self-evaluation questionnaire was developed to measure students' competence on basic pharmacotherapy, intravenous medication and infusion, blood transfusion and epidural medication. The data was analysed with SPSS 18.0 software using descriptive analyses and comparing sum variables with Man-Whitney U-test. The medication administration web course, which took 8 h on average, significantly improved self-evaluated competence of nursing students in all the fields. Prior to the education most defects were found in matters concerning compatibility and adverse effects of pharmaceuticals and solutions and in epidural medication competency. The education strengthened all these competencies. It is necessary to revise medication administration before graduation and web-based learning can be used in it. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Overexpression of CREB in the nucleus accumbens shell increases cocaine reinforcement in self-administering rats.

    PubMed

    Larson, Erin B; Graham, Danielle L; Arzaga, Rose R; Buzin, Nicole; Webb, Joseph; Green, Thomas A; Bass, Caroline E; Neve, Rachael L; Terwilliger, Ernest F; Nestler, Eric J; Self, David W

    2011-11-09

    Chronic exposure to addictive drugs enhances cAMP response element binding protein (CREB)-regulated gene expression in nucleus accumbens (NAc), and these effects are thought to reduce the positive hedonic effects of passive cocaine administration. Here, we used viral-mediated gene transfer to produce short- and long-term regulation of CREB activity in NAc shell of rats engaging in volitional cocaine self-administration. Increasing CREB expression in NAc shell markedly enhanced cocaine reinforcement of self-administration behavior, as indicated by leftward (long-term) and upward (short-term) shifts in fixed ratio dose-response curves. CREB also increased the effort exerted by rats to obtain cocaine on more demanding progressive ratio schedules, an effect highly correlated with viral-induced modulation of BDNF protein in the NAc shell. CREB enhanced cocaine reinforcement when expressed either throughout acquisition of self-administration or when expression was limited to postacquisition tests, indicating a direct effect of CREB independent of reinforcement-related learning. Downregulating endogenous CREB in NAc shell by expressing a short hairpin RNA reduced cocaine reinforcement in similar tests, while overexpression of a dominant-negative CREB(S133A) mutant had no significant effect on cocaine self-administration. Finally, increasing CREB expression after withdrawal from self-administration enhanced cocaine-primed relapse, while reducing CREB levels facilitated extinction of cocaine seeking, but neither altered relapse induced by cocaine cues or footshock stress. Together, these findings indicate that CREB activity in NAc shell increases the motivation for cocaine during active self-administration or after withdrawal from cocaine. Our results also highlight that volitional and passive drug administration can lead to substantially different behavioral outcomes.

  20. Caffeine enhances the speed of the recovery of the hypothalamo-pituitary-adrenocortical axis after chronic prednisolone administration in the rat.

    PubMed

    Marzouk, H F; Zuyderwijk, J; Uitterlinden, P; van Koetsveld, P; Blijd, J J; Abou-Hashim, E M; el-Kannishy, M H; de Jong, F H; Lamberts, S W

    1991-11-01

    Chronic administration of corticosteroids results in a suppression of the hypothalamo-pituitary-adrenocortical (HPA) axis. The time course of the recovery of the HPA axis depends on the dose and duration of corticosteroid administration. We investigated the recovery of the HPA axis after 14 days of prednisolone administration to rats at a dose of 2.0 mg/rat/day via the drinking water (188 mumol/l). The in vitro corticosterone production by dispersed adrenal cells in response to increasing concentrations of ACTH had recovered 3 days after stopping prednisolone administration. In parallel the initially suppressed plasma corticosterone concentrations had recovered after 3 days, while the pituitary ACTH content had recovered after 5 days. We investigated the possibility to enhance the speed of the recovery of the HPA axis by the simultaneous administration of two drugs with known CRF-stimulating activity via the drinking water. Caffeine in a dose of 100 mg/kg body weight enhanced the recovery of the prednisolone-suppressed HPA axis significantly. One day after the end of prednisolone administration a significant increase in the adrenal weight, in the corticosterone production by dispersed adrenal cells, as well as in the plasma corticosterone concentrations, and in the pituitary ACTH content was observed in the caffeine-treated rats. Chlorimipramine (20 mg/kg body weight), on the other hand, did not influence the prednisolone-mediated suppression of the HPA axis.(ABSTRACT TRUNCATED AT 250 WORDS)

  1. Chronic administration of dietary grape seed extract increases colonic expression of gut tight junction protein occludin and reduces fecal calprotectin: a secondary analysis of healthy Wistar Furth rats.

    PubMed

    Goodrich, Katheryn M; Fundaro, Gabrielle; Griffin, Laura E; Grant, Ar'quette; Hulver, Matthew W; Ponder, Monica A; Neilson, Andrew P

    2012-10-01

    Animal studies have demonstrated the potential of grape seed extract (GSE) to prevent metabolic syndrome, obesity, and type 2 diabetes. Recently, metabolic endotoxemia induced by bacterial endotoxins produced in the colon has emerged as a possible factor in the etiology of metabolic syndrome. Improving colonic barrier function may control endotoxemia by reducing endotoxin uptake. However, the impact of GSE on colonic barrier integrity and endotoxin uptake has not been evaluated. We performed a secondary analysis of samples collected from a chronic GSE feeding study with pharmacokinetic end points to examine potential modulation of biomarkers of colonic integrity and endotoxin uptake. We hypothesized that a secondary analysis would indicate that chronic GSE administration increases colonic expression of intestinal tight junction proteins and reduces circulating endotoxin levels, even in the absence of an obesity-promoting stimulus. Wistar Furth rats were administered drinking water containing 0.1% GSE for 21 days. Grape seed extract significantly increased the expression of gut junction protein occludin in the proximal colon and reduced fecal levels of the neutrophil protein calprotectin, compared with control. Grape seed extract did not significantly reduce serum or fecal endotoxin levels compared with control, although the variability in serum levels was widely increased by GSE. These data suggest that the improvement of gut barrier integrity and potential modulation of endotoxemia warrant investigation as a possible mechanism by which GSE prevents metabolic syndrome and associated diseases. Further investigation of this mechanism in high-fat feeding metabolic syndrome and obesity models is therefore justified. Copyright © 2012 Elsevier Inc. All rights reserved.

  2. Effects of MAO inhibition and a combination of minor alkaloids, β-carbolines, and acetaldehyde on nicotine self-administration in adult male rats*

    PubMed Central

    Smith, Tracy T.; Schaff, Matthew B.; Rupprecht, Laura E.; Schassburger, Rachel L.; Buffalari, Deanne M.; Murphy, Sharon E.; Sved, Alan F.; Donny, Eric C.

    2015-01-01

    Introduction Although nicotine is the primary reinforcing constituent in cigarettes, there is evidence that other constituents in cigarette smoke may interact with nicotine to reinforce smoking behavior. Methods The present experiments investigated whether a novel combination of these cigarette smoke constituents would increase nicotine self-administration in adult male rats. The constituents included five minor alkaloids (anabasine, nornicotine, cotinine, myosmine, and anatabine), two β-carbolines (harman and norharman), and acetaldehyde. All doses were indexed to be proportional to concentrations in cigarette smoke given a standard dose of nicotine used in rodent self-administration, or ten times higher than this standard. To model MAO inhibition seen in chronic smokers, some groups received separate injections of tranylcypromine prior to each self-administration session. Results Tranylcypromine increased low-dose nicotine self-administration independent of other smoke constituents, which had no effect on self-administration behavior. The effect of tranylcypromine was confirmed across a large range of reinforcement schedules. The effect of tranylcypromine on low-dose nicotine self-administration was observed regardless of whether the injection was delivered 1-hr or 23-hrs prior to the self-administration session, consistent with the interpretation that MAO inhibition was responsible for the increase in self-administration, instead of acute off-target effects. Conclusions These data suggest that this cocktail of constituents does not significantly alter the primary reinforcing effects of nicotine, but constituents that inhibit MAO may increase the primary reinforcing effects of nicotine, especially at low doses. PMID:26257022

  3. Self-Administration of Cocaine Induces Dopamine-Independent Self-Administration of Sigma Agonists

    PubMed Central

    Hiranita, Takato; Mereu, Maddalena; Soto, Paul L; Tanda, Gianluigi; Katz, Jonathan L

    2013-01-01

    Sigma1 receptors (σ1Rs) are intracellularly mobile chaperone proteins implicated in several disease processes, as well as psychiatric disorders and substance abuse. Here we report that although selective σ1R agonists (PRE-084, (+)-pentazocine) lacked reinforcing effects in drug-naive rats, over the course of 28 experimental sessions, which was more than sufficient for acquisition of cocaine self-administration, responding was not maintained by either σ1R agonist. In contrast, after subjects self-administered cocaine σ1R agonists were readily self-administered. The induced reinforcing effects were long lasting; a response for which subjects had no history of reinforcement was newly conditioned with both σ1R agonists, extinguished when injections were discontinued, and reconditioned when σ1R agonists again followed responses. Experience with food reinforcement was ineffective as an inducer of σ1R agonist reinforcement. Although a variety of dopamine receptor antagonists blocked cocaine self-administration, consistent with its dopaminergic mechanism, PRE-084 self-administration was entirely insensitive to these drugs. Conversely, the σR antagonist, BD1063, blocked PRE-084 self-administration but was inactive against cocaine. In microdialysis studies i.v. PRE-084 did not significantly stimulate dopamine at doses that were self-administered in rats either with or without a cocaine self-administration experience. The results indicate that cocaine experience induces reinforcing effects of previously inactive σ1R agonists, and that the mechanism underlying these reinforcing effects is dopamine independent. It is further suggested that induced σ1R mechanisms may have an essential role in treatment-resistant stimulant abuse, suggesting new approaches for the development of effective medications for stimulant abuse. PMID:23187725

  4. Self-administration of cocaine induces dopamine-independent self-administration of sigma agonists.

    PubMed

    Hiranita, Takato; Mereu, Maddalena; Soto, Paul L; Tanda, Gianluigi; Katz, Jonathan L

    2013-03-01

    Sigma(1) receptors (σ(1)Rs) are intracellularly mobile chaperone proteins implicated in several disease processes, as well as psychiatric disorders and substance abuse. Here we report that although selective σ(1)R agonists (PRE-084, (+)-pentazocine) lacked reinforcing effects in drug-naive rats, over the course of 28 experimental sessions, which was more than sufficient for acquisition of cocaine self-administration, responding was not maintained by either σ(1)R agonist. In contrast, after subjects self-administered cocaine σ(1)R agonists were readily self-administered. The induced reinforcing effects were long lasting; a response for which subjects had no history of reinforcement was newly conditioned with both σ(1)R agonists, extinguished when injections were discontinued, and reconditioned when σ(1)R agonists again followed responses. Experience with food reinforcement was ineffective as an inducer of σ(1)R agonist reinforcement. Although a variety of dopamine receptor antagonists blocked cocaine self-administration, consistent with its dopaminergic mechanism, PRE-084 self-administration was entirely insensitive to these drugs. Conversely, the σR antagonist, BD1063, blocked PRE-084 self-administration but was inactive against cocaine. In microdialysis studies i.v. PRE-084 did not significantly stimulate dopamine at doses that were self-administered in rats either with or without a cocaine self-administration experience. The results indicate that cocaine experience induces reinforcing effects of previously inactive σ(1)R agonists, and that the mechanism underlying these reinforcing effects is dopamine independent. It is further suggested that induced σ(1)R mechanisms may have an essential role in treatment-resistant stimulant abuse, suggesting new approaches for the development of effective medications for stimulant abuse.

  5. Saliva oxytocin measures do not reflect peripheral plasma concentrations after intranasal oxytocin administration in men.

    PubMed

    Quintana, Daniel S; Westlye, Lars T; Smerud, Knut T; Mahmoud, Ramy A; Andreassen, Ole A; Djupesland, Per G

    2018-05-16

    Oxytocin plays an important role in social behavior. Thus, there has been significant research interest for the role of the oxytocin system in several psychiatric disorders, and the potential of intranasal oxytocin administration to treat social dysfunction. Measurement of oxytocin concentrations in saliva are sometimes used to approximate peripheral levels of oxytocin; however, the validity of this approach is unclear. In this study, saliva and plasma oxytocin was assessed after two doses of Exhalation Delivery System delivered intranasal oxytocin (8 IU and 24 IU), intravenous oxytocin (1 IU) and placebo in a double-dummy, within-subjects design with men. We found that intranasal oxytocin (8 IU and 24 IU) administration increased saliva oxytocin concentrations in comparison to saliva oxytocin concentration levels after intravenous and placebo administration. Additionally, we found that saliva oxytocin concentrations were not significantly associated with plasma oxytocin concentrations after either intranasal or intravenous oxytocin administration. Altogether, we suggest that saliva oxytocin concentrations do not accurately index peripheral oxytocin after intranasal or intravenous oxytocin administration, at least in men. The data indicates that elevated oxytocin saliva levels after nasal delivery primarily reflect exogenous administered oxytocin that is cleared from the nasal cavity to the oropharynx, and is therefore a weak surrogate for peripheral blood measurements. Copyright © 2018 Elsevier Inc. All rights reserved.

  6. Anti-cancer activity of bromelain nanoparticles by oral administration.

    PubMed

    Bhatnagar, Priyanka; Patnaik, Soma; Srivastava, Amit K; Mudiam, Mohan K R; Shukla, Yogeshwer; Panda, Amulya K; Pant, Aditya B; Kumar, Pradeep; Gupta, Kailash C

    2014-12-01

    Oral administration of anti-cancer drugs is an effective alternative to improve their efficacy and reduce undesired toxicity. Bromelain (BL) is known as an effective anti-cancer phyto-therapeutic agent, however, its activity is reduced upon oral administration. In addressing the issue, BL was encapsulated in Poly(lactic-co-glycolic acid) (PLGA) to formulate nanoparticles (NPs). Further, the NPs were coated with Eudragit L30D polymer to introduce stability against the gastric acidic conditions. The resultant coated NPs were characterized for BL entrapment, proteolytic activity and mean particle size. The stability and release pattern of NPs were evaluated under simulated gastrointestinal tract (GIT) pH conditions. Cytotoxicity studies carried out in human cell lines of diverse origin have shown significant dose advantage (-7-10 folds) with NPs in reducing the IC50 values compared with free BL. The cellular uptake of NPs in MCF-7, HeLa and Caco-2 cells monolayer was significantly enhanced several folds as compared to free BL. Altered expression of marker proteins associated with apoptosis and cell death (P53, P21, Bcl2, Bax) also confirmed the enhanced anti-carcinogenic potential of formulated NPs. Oral administration of NPs reduced the tumor burden of Ehrlich ascites carcinoma (EAC) in Swiss albino mice and also increased their life-span (160.0 ± 5.8%) when compared with free BL (24 ± 3.2%). The generation of reactive oxygen species, induction of apoptosis and impaired mitochondrial membrane potential in EAC cells treated with NPs confirmed the suitability of Eudragit coated BL-NPs as a promising candidate for oral chemotherapy.

  7. Use of radiotelemetry to evaluate respiratory depression produced by chronic methadone administration.

    PubMed

    Lewanowitsch, Tanya; White, Jason M; Irvine, Rodney J

    2004-01-26

    Illicit and therapeutic opioid administration can result in overdose due to opioid-induced respiratory depression. Research investigating the respiratory depressant effects of opioids has been limited due to difficulties associated with acquiring long-term respiratory data. This study examined the novel use of radiotelemetry to measure respiratory rate, heart rate, locomotor activity and blood pressure in rats treated chronically with methadone. Over 4 days of treatment, respiratory rate decreased, but partial tolerance appeared to develop during active (night) periods. Decreased heart rate was observed during the night periods and tolerance appeared to develop to this effect. Activity and blood pressure did not change with treatment. The effects of naloxone hydrochloride and naloxone methiodide administration on the methadone-treated rats were also examined and both antagonists increased respiratory rate and heart rate, with only naloxone hydrochloride producing significant increases in activity. Radiotelemetry offers a means of evaluating drug effects on respiratory rate continually in ambulatory, unstressed animals.

  8. Avoiding Assessment Anarchy. Quality Test Administration Strategies: Communicate Expectations, Reduce Variation, Increase Quality, Improve Relationships, Reward Excellence, Recognize Success.

    ERIC Educational Resources Information Center

    Matter, M. Kevin

    This paper presents strategies that address the needs of the school district assessment office for standardized procedures to support reliable and efficient test processing and reporting and that meet the needs of school staff for test administration guidelines. The key to test administration and processing quality is a knowledgeable test…

  9. Increased Mortality in Diabetic Foot Ulcer Patients: The Significance of Ulcer Type

    PubMed Central

    Chammas, N. K.; Hill, R. L. R.; Edmonds, M. E.

    2016-01-01

    Diabetic foot ulcer (DFU) patients have a greater than twofold increase in mortality compared with nonulcerated diabetic patients. We investigated (a) cause of death in DFU patients, (b) age at death, and (c) relationship between cause of death and ulcer type. This was an eleven-year retrospective study on DFU patients who attended King's College Hospital Foot Clinic and subsequently died. A control group of nonulcerated diabetic patients was matched for age and type of diabetes mellitus. The cause of death was identified from death certificates (DC) and postmortem (PM) examinations. There were 243 DFU patient deaths during this period. Ischaemic heart disease (IHD) was the major cause of death in 62.5% on PM compared to 45.7% on DC. Mean age at death from IHD on PM was 5 years lower in DFU patients compared to controls (68.2 ± 8.7 years versus 73.1 ± 8.0 years, P = 0.015). IHD as a cause of death at PM was significantly linked to neuropathic foot ulcers (OR 3.064, 95% CI 1.003–9.366, and P = 0.049). Conclusions. IHD is the major cause of premature mortality in DFU patients with the neuropathic foot ulcer patients being at a greater risk. PMID:27213157

  10. Penguins significantly increased phosphine formation and phosphorus contribution in maritime Antarctic soils.

    PubMed

    Zhu, Renbin; Wang, Qing; Ding, Wei; Wang, Can; Hou, Lijun; Ma, Dawei

    2014-11-14

    Most studies on phosphorus cycle in the natural environment focused on phosphates, with limited data available for the reduced phosphine (PH3). In this paper, matrix-bound phosphine (MBP), gaseous phosphine fluxes and phosphorus fractions in the soils were investigated from a penguin colony, a seal colony and the adjacent animal-lacking tundra and background sites. The MBP levels (mean 200.3 ng kg(-1)) in penguin colony soils were much higher than those in seal colony soils, animal-lacking tundra soils and the background soils. Field PH3 flux observation and laboratory incubation experiments confirmed that penguin colony soils produced much higher PH3 emissions than seal colony soils and animal-lacking tundra soils. Overall high MBP levels and PH3 emissions were modulated by soil biogeochemical processes associated with penguin activities: sufficient supply of the nutrients phosphorus, nitrogen, and organic carbon from penguin guano, high soil bacterial abundance and phosphatase activity. It was proposed that organic or inorganic phosphorus compounds from penguin guano or seal excreta could be reduced to PH3 in the Antarctic soils through the bacterial activity. Our results indicated that penguin activity significantly increased soil phosphine formation and phosphorus contribution, thus played an important role in phosphorus cycle in terrestrial ecosystems of maritime Antarctica.

  11. Penguins significantly increased phosphine formation and phosphorus contribution in maritime Antarctic soils

    PubMed Central

    Zhu, Renbin; Wang, Qing; Ding, Wei; Wang, Can; Hou, Lijun; Ma, Dawei

    2014-01-01

    Most studies on phosphorus cycle in the natural environment focused on phosphates, with limited data available for the reduced phosphine (PH3). In this paper, matrix-bound phosphine (MBP), gaseous phosphine fluxes and phosphorus fractions in the soils were investigated from a penguin colony, a seal colony and the adjacent animal-lacking tundra and background sites. The MBP levels (mean 200.3 ng kg−1) in penguin colony soils were much higher than those in seal colony soils, animal-lacking tundra soils and the background soils. Field PH3 flux observation and laboratory incubation experiments confirmed that penguin colony soils produced much higher PH3 emissions than seal colony soils and animal-lacking tundra soils. Overall high MBP levels and PH3 emissions were modulated by soil biogeochemical processes associated with penguin activities: sufficient supply of the nutrients phosphorus, nitrogen, and organic carbon from penguin guano, high soil bacterial abundance and phosphatase activity. It was proposed that organic or inorganic phosphorus compounds from penguin guano or seal excreta could be reduced to PH3 in the Antarctic soils through the bacterial activity. Our results indicated that penguin activity significantly increased soil phosphine formation and phosphorus contribution, thus played an important role in phosphorus cycle in terrestrial ecosystems of maritime Antarctica. PMID:25394572

  12. Managerial Techniques in Educational Administration.

    ERIC Educational Resources Information Center

    Lane, John J.

    1983-01-01

    Management techniques developed during the past 20 years assume the rational bureaucratic model. School administration requires contingent techniques. Quality Circle, Theory Z, and the McKenzie 7-Framework are discussed as techniques to increase school productivity. (MD)

  13. [Expectations of hospital administrators about administrative functions of nurses].

    PubMed

    Melo, M R; Fávero, N; Trevizan, M A; Hayashida, M

    1996-01-01

    The objective of the present study was to investigate hospital administrator's expectations about the administrative role played by nurses, utilizing functions proposed by the Neoclassical Theory of Administration: planning, organization, direction, and control as theoretical references. An instrument established in TREVIZAN (1989) was applied to 11 hospital administrators. The results showed they expect the four functions to be done by nurses. Therefore, the interaction between nurses and hospital administrators is critical to improve the patient's assistance.

  14. Biphasic alterations in serotonin-1B (5-HT1B) receptor function during abstinence from extended cocaine self-administration.

    PubMed

    O'Dell, Laura E; Manzardo, Ann M; Polis, Ilham; Stouffer, David G; Parsons, Loren H

    2006-12-01

    Alterations in 5-HT1B receptor function during cocaine abstinence were evaluated in rats given either limited- or extended access (LA and EA, respectively) to cocaine self-administration. The locomotor response to the 5-HT1B/1A agonist RU24969 was significantly reduced in cocaine-experienced animals relative to cocaine-naïve controls following 6 h of abstinence but became sensitized over the subsequent 14 days of abstinence. Both the early phase subsensitivity and later phase supersensivity to RU 24969-induced activity were greater in EA versus LA animals. Intra-nucleus accumbens administration of the 5-HT1B agonist CP 93, 129 produced significantly greater increases in dialysate dopamine levels in EA versus control animals following 14 days of abstinence. However, there was no difference between EA and cocaine-naïve control animals in the augmentation of cocaine-induced increases in nucleus accumbens DA produced by intra-VTA CP 93, 129. Collectively these findings demonstrate that 5-HT1B receptor function is persistently altered by cocaine self-administration.

  15. The effects of intraperitoneal administration of the GABA(B) receptor agonist baclofen on food intake in CFLP and C57BL/6 mice.

    PubMed

    Ebenezer, Ivor S; Prabhaker, Monika

    2007-08-13

    The effects of the GABA(B) receptor agonist baclofen were investigated on food intake in non-deprived CFLP and C57BL/6 mice. In Experiment 1, baclofen (1-8 mg /kg) administered i.p. to CFLP mice, produced a dose-related increase in food intake. The 4 and 8 mg/kg doses produced significant increases in cumulative feeding when measure 120 min after administration (at least P < 0.05, in each case). In Experiment 2, baclofen (1-10 mg/kg), administered intraperitoneally (i.p.) to C57BL/6 mice, also produced a dose-related increase in food intake. The 4 mg/kg dose of baclofen significantly increased cumulative food intake at 60 min (P < 0.05), while the 2 and 4 mg/kg doses significantly increased cumulative food intake at 120 min (P < 0.01, in each case). The 10mg/kg dose was without effect. These data show that systemic administration of the GABA(B) agonist baclofen produces an increase in food consumption in two different strains of mice and extend previous observations made in rat to another rodent species.

  16. Recruiting and Retaining Rural School Administrators. ERIC Digest.

    ERIC Educational Resources Information Center

    Howley, Aimee; Pendarvis, Edwina

    School districts nationwide, but especially rural districts, are finding it hard to recruit and retain administrators. In the past 25 years, administrators have had to address increasing demands for special programs, collaborative decision making, and accountability. In addition, potential for conflict with school boards and various constituencies…

  17. The influence of timing of administration on the analgesic efficacy of parecoxib in orthopedic surgery.

    PubMed

    Martinez, Valéria; Belbachir, Anissa; Jaber, Aithem; Cherif, Kamel; Jamal, Adel; Ozier, Yves; Sessler, Daniel I; Chauvin, Marcel; Fletcher, Dominique

    2007-06-01

    Parecoxib, a selective cyclooxygenase-2 inhibitor, may reduce postoperative pain without increasing bleeding when administered before surgery. We randomly assigned 62 patients scheduled for total hip arthroplasty to the following IV dosing schedule: 1) placebo at induction, at wound closure, and 12 h after induction (control); 2) parecoxib 40 mg at induction, placebo at wound closure, and parecoxib 40 mg 12 h after induction (pre); or, 3) placebo at induction, parecoxib 40 mg at wound closure, and parecoxib 40 mg 12 h after induction (post). Pain scores at rest and with movement were recorded every 4 h for 24 h using a visual analog scale. Treatment side effects were recorded every 4 h. Red cell loss for 5 days after surgery was calculated. Postoperative pain scores were less in the pre and post groups than in the control group. Postoperative bleeding was similar in the three groups. There were no significant differences between the pre and post groups, nor was their any trend suggesting a preemptive analgesic efficacy from preincision administration of parecoxib. Morphine use in the Postanesthesia Care Unit was reduced in the pre and post groups compared with the control group (14.2 +/- 2.0, and 15.7 +/- 2.0, vs 20.4 +/- 2.3 mg), although the trend was only significant (P < 0.05) in the pre group. The first pain score was also reduced in the pre and post groups compared to the control group (56.1 +/- 7.5 and 64.2 +/- 7.0 vs 78.3 +/- 5), but this was also only significant for the pre group (P = 0.001). The delay for first analgesic demand was increased for both the pre and post group compared to the control group (38 +/- 9 and 28.2 +/- 6.6 vs 18 +/- 6 min) but, again, this was only significant for the pre group (P = 0.05). Twenty-four hour consumption of morphine was similar in the pre (26 +/- 12 mg) and post groups (25 +/- 13 mg); both were significantly less than in the control group (47 +/- 27 mg, P < 0.001). Administration of parecoxib before hip arthroplasty

  18. Changes in the concentrations of vitamin E analogs and their metabolites in rat liver and kidney after oral administration

    PubMed Central

    Kiyose, Chikako; Saito, Kazuki; Yachi, Rieko; Muto, Chie; Igarashi, Osamu

    2015-01-01

    Vitamin E analog, such as α- and γ-tocopherol, can undergo ω-oxidation without cleavage of the chroman ring, and this pathway is responsible for generation of the major urinary vitamin E metabolite, carboxyethyl hydroxychroman. However, it is still unclear how carboxyethyl hydroxychroman is changed in various tissues after vitamin E intake. We therefore investigated changes in the concentrations of α- and γ-tocopherol and their metabolites in rat liver and kidney. The concentration of α-tocopherol in rat liver increased until 6 h after oral administration, and then decreased. The change in the concentration of α-carboxyethyl hydroxychroman in rat liver in the α-Toc group slowly increased until 12 h after oral administration. Cytochrome P450 3A1 mRNA expression significantly increased from 12 h after the start of α-tocopherol administration. The change in the concentration of γ-carboxyethyl hydroxychroman in rat liver in the γ-Toc group markedly increased until 12 h after oral administration. On the other hand, γ-carboxyethyl hydroxychroman in rat kidney showed greater accumulation than α-carboxyethyl hydroxychroman from 3 h to 24 h after oral administration. From these results, we considered that γ-carboxyethyl hydroxychroman formed in the liver continues to be released into the bloodstream and is transported to the kidney rapidly. PMID:25759520

  19. Effect of Timing of Proton Pump Inhibitor Administration on Acid Suppression.

    PubMed

    Furuta, Kenji; Adachi, Kyoichi; Aimi, Masahito; Shimura, Shino; Mikami, Hironobu; Nishimura, Nobuhiro; Ishimura, Norihisa; Ishihara, Shunji; Naora, Kohji; Kinoshita, Yoshikazu

    2016-01-01

    Esomeprazole has been reported to show a strong acid suppression following preprandial as compared to postprandial administration, though no known study has compared the acid suppressing effects of other proton pump inhibitors between those administrations. The aim of this study was to compare intragastric pH levels following pre- and postprandial administrations of rabeprazole and esomeprazole. In 15 Helicobacter pylori-negative healthy volunteers, we measured intragastric pH after 7 days of pre- and postprandial administrations of rabeprazole (10 mg) or esomeprazole (20 mg) using a 5-way crossover design. Preprandial administration of esomeprazole showed stronger acid suppression than postprandial administration. The values for percent time at pH >4.0 over a 24-hour period increased from 45.3% with postprandial administration of esomeprazole to 54.4% with preprandial administration, while the percent time at pH >4.0 during daytime was increased to a greater extent from 51.4 to 66.5% with preprandial administration (p = 0.05). On the other hand, the acid suppressing effect of rabeprazole was not influenced by the timing of administration. The acid suppressing effect of esomeprazole is influenced by administration timing. In contrast, the acid suppressing effect of rabeprazole is not augmented by preprandial administration. © 2015 S. Karger AG, Basel.

  20. Equal Opportunity: Women in Administration in the California Community Colleges.

    ERIC Educational Resources Information Center

    Kistler, Kathleen M.

    This paper examines the extent to which women have attained administrative positions in California community colleges, highlights barriers to women's advancement and methods of overcoming them, and profiles the female college administrator. After citing the low incidence of female community college administrators and the increasing visibility of…

  1. The Intracranial Volume Pressure Response in Increased Intracranial Pressure Patients: Clinical Significance of the Volume Pressure Indicator.

    PubMed

    Lai, Hung-Yi; Lee, Ching-Hsin; Lee, Ching-Yi

    2016-01-01

    For patients suffering from primary brain injury, monitoring intracranial pressure alone is not enough to reflect the dynamic intracranial condition. In our previous study, a segment of the pressure-volume curve can be expressed by the parabolic regression model with single indicator "a". The aim of this study is to evaluate if the indicator "a" can reflect intracranial conditions. Patients with traumatic brain injury, spontaneous intracranial hemorrhage, and/or hydrocephalus who had external ventricular drainage from January 2009 to February 2010 were included. The successive volume pressure response values were obtained by successive drainage of cerebral spinal fluid from intracranial pressure 20-25 mm Hg to 10 mm Hg. The relationship between withdrawn cerebral spinal fluid volume and intracranial pressure was analyzed by the parabolic regression model with single parameter "a". The overall mean for indicator "a" was 0.422 ± 0.046. The mean of "a" in hydrocephalus was 0.173 ± 0.024 and in severe intracranial mass with slender ventricle, it was 0.663 ± 0.062. The two extreme intracranial conditions had a statistical significant difference (p<0.001). The indicator "a" of a pressure-volume curve can reflect the dynamic intracranial condition and is comparable in different situations. A significantly larger indicator "a" with increased intracranial pressure is always observed in severe intracranial mass lesions with cerebral edema. A significantly smaller indicator "a" with increased intracranial pressure is observed in hydrocephalus. Brain computed tomography should be performed early if a rapid elevation of indicator "a" is detected, as it can reveal some ongoing intracranial pathology prior to clinical deterioration. Increased intracranial pressure was frequently observed in patients with intracranial pathology. The progression can be differentiated using the pattern of the volume pressure indicator.

  2. The Intracranial Volume Pressure Response in Increased Intracranial Pressure Patients: Clinical Significance of the Volume Pressure Indicator

    PubMed Central

    2016-01-01

    Background For patients suffering from primary brain injury, monitoring intracranial pressure alone is not enough to reflect the dynamic intracranial condition. In our previous study, a segment of the pressure-volume curve can be expressed by the parabolic regression model with single indicator “a”. The aim of this study is to evaluate if the indicator “a” can reflect intracranial conditions. Methods Patients with traumatic brain injury, spontaneous intracranial hemorrhage, and/or hydrocephalus who had external ventricular drainage from January 2009 to February 2010 were included. The successive volume pressure response values were obtained by successive drainage of cerebral spinal fluid from intracranial pressure 20–25 mm Hg to 10 mm Hg. The relationship between withdrawn cerebral spinal fluid volume and intracranial pressure was analyzed by the parabolic regression model with single parameter “a”. Results The overall mean for indicator “a” was 0.422 ± 0.046. The mean of “a” in hydrocephalus was 0.173 ± 0.024 and in severe intracranial mass with slender ventricle, it was 0.663 ± 0.062. The two extreme intracranial conditions had a statistical significant difference (p<0.001). Conclusion The indicator “a” of a pressure-volume curve can reflect the dynamic intracranial condition and is comparable in different situations. A significantly larger indicator “a” with increased intracranial pressure is always observed in severe intracranial mass lesions with cerebral edema. A significantly smaller indicator “a” with increased intracranial pressure is observed in hydrocephalus. Brain computed tomography should be performed early if a rapid elevation of indicator “a” is detected, as it can reveal some ongoing intracranial pathology prior to clinical deterioration. Increased intracranial pressure was frequently observed in patients with intracranial pathology. The progression can be differentiated using the pattern of the volume

  3. Reversal of the toxic effects of cachectin by concurrent insulin administration.

    PubMed

    Fraker, D L; Merino, M J; Norton, J A

    1989-06-01

    Rats treated with recombinant human tumor necrosis factor-cachectin, 100 micrograms/kg ip twice daily for 5 consecutive days, had a 56% decrease in food intake, a 54% decrease in nitrogen balance, and a 23-g decrease in body weight gain vs. saline-treated controls. Concurrent neutral protamine hagedorn insulin administration of 2 U/100 g sc twice daily reversed all of these changes to control levels without causing any treatment deaths. The improvement seen with insulin was dose independent. Five days of cachectin treatment caused a severe interstitial pneumonitis, periportal inflammation in the liver, and an increase in wet organ weight in the heart, lungs, kidney, and spleen. Concurrent insulin treatment led to near total reversal of these histopathologic changes. Cachectin treatment did not significantly change blood glucose levels from control values of 130-140 mg/dl, but insulin plus cachectin caused a significant decrease in blood glucose from 1 through 12 h after injection. Administration of high-dose insulin can near totally reverse the nutritional and histopathologic toxicity of sublethal doses of cachectin in rats.

  4. Therapeutic effects of N-acetyl-L-cysteine on liver damage induced by long-term CCl4 administration.

    PubMed

    Otrubová, Oľga; Turecký, Ladislav; Uličná, Oľga; Janega, Pavol; Luha, Ján; Muchová, Jana

    2018-01-01

    N-acetyl-L-cysteine (NAC) is a drug routinely used in several health problems, e.g. liver damage. There is some information emerged on its negative effects in certain situations. The aim of our study was to examine its ability to influence liver damage induced by long-term burden. We induced liver damage by CCl4 (10 weeks) and monitored the impact of parallel NAC administration (daily 150 mg/kg of b.w.) on liver morphology and some biochemical parameters (triacylglycerols, cholesterol, alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, bile acids, proteins, albumins and cholinesterase). NAC significantly decreased levels of bile acids and bilirubin in plasma and triacylglycerols in liver, all of them elevated by impairment with CCl4. Reduction of cholesterol induced by CCl4 was completely recovered in the presence of NAC as indicated by its elevation to control levels. NAC administration did not improve the histological parameters. Together with protective effects of NAC, we found also its deleterious properties: parallel administration of CCl4 and NAC increased triacylglycerols, ALT and AST activity and significantly increased plasma cholinesterase activity. We have observed nonsignificantly increased percentage of liver tissue fibrosis. Our results have shown that NAC administered simultaneously with liver damaging agent CCl4, exhibits not only protective, but also deleterious effects as indicated by several biochemical parameters.

  5. 5 CFR 9701.342 - Performance pay increases.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 5 Administrative Personnel 3 2010-01-01 2010-01-01 false Performance pay increases. 9701.342 Section 9701.342 Administrative Personnel DEPARTMENT OF HOMELAND SECURITY HUMAN RESOURCES MANAGEMENT... HUMAN RESOURCES MANAGEMENT SYSTEM Pay and Pay Administration Performance-Based Pay § 9701.342...

  6. Administration of different Lactobacillus strains in fermented oatmeal soup: in vivo colonization of human intestinal mucosa and effect on the indigenous flora.

    PubMed Central

    Johansson, M L; Molin, G; Jeppsson, B; Nobaek, S; Ahrné, S; Bengmark, S

    1993-01-01

    In vivo colonization by different Lactobacillus strains on human intestinal mucosa of healthy volunteers was studied together with the effect of Lactobacillus administration on different groups of indigenous bacteria. A total of 19 test strains were administered in fermented oatmeal soup containing 5 x 10(6) CFU of each strain per ml by using a dose of 100 ml of soup per day for 10 days. Biopsies were taken from both the upper jejunum and the rectum 1 day before administration was started and 1 and 11 days after administration was terminated. The administration significantly increased the Lactobacillus counts on the jejunum mucosa, and high levels remained 11 days after administration was terminated. The levels of streptococci increased by 10- to 100-fold in two persons, and the levels of sulfite-reducing clostridia in the jejunum decreased by 10- to 100-fold in three of the volunteers 1 day after administration was terminated. In recta, the anaerobic bacterium counts and the gram-negative anaerobic bacterium counts decreased significantly by the end of administration. Furthermore, a decrease in the number of members of the Enterobacteriaceae by 1,000-fold was observed on the rectal mucosa of two persons. Randomly picked Lactobacillus isolates were identified phenotypically by API 50CH tests and genotypically by the plasmid profiles of strains and by restriction endonuclease analysis of chromosomal DNAs.(ABSTRACT TRUNCATED AT 250 WORDS) Images PMID:8439146

  7. The Control of Environment Management Through Administrative Court

    NASA Astrophysics Data System (ADS)

    Putrijanti, Aju

    2018-02-01

    Environment is important in human life. Conflict of interest comes between development of economy sector, citizenship needs and Governance, as it becomes completely difficult to analyze. The environment's lawsuit is increase from the beginning of the Court established. The duty of Administrative Court are to investigate, decide and settle administrative disputes. The Governance has to pay attention before issuing the Government's decree by put principle of good governance as priority. The issue in this paper is strengthening the role of Administrative Court to maintain the environment reuse by settle environment disputes based on the importance of environment. The administrative decisions in environment field may cause a loss or damage for the people. When the public officer did not put the appreciation to the reuse of environment and principle of good governance, it will become problems. The decision should be environmentally friendly. There should be certified judge to settle the dispute. The method of this research by examines the Judge's verdict in environment disputes, and its relation with regulations and the newest issues. The conclusion is increase the role of the Administrative Court to maintain the environment by law enforcement through settle environment disputes.

  8. Cortisol in saliva and plasma of cattle after ACTH administration and milking.

    PubMed

    Negrão, J A; Porcionato, M A; de Passillé, A M; Rushen, J

    2004-06-01

    Interest in the measurement of salivary cortisol has increased recently because saliva can be easily collected before and after an imposed stress. This study evaluated the relationship between plasma and salivary concentrations of cortisol following ACTH administration in calves (experiment 1) and machine milking of adult cows (experiment 2). A catheter was inserted into the jugular vein of all animals 72 h before the beginning of experiments. Blood and saliva samples were collected before and after ACTH administration (0.6 IU/kg BW) in calves or before and after machine milking of cows. Using a cotton swab, each saliva sample was taken immediately following the blood sample. In general, cortisol profiles were similar in plasma and saliva and correlated in both experiments; however, plasma concentrations were significantly higher than salivary concentrations. In addition, the differences between cortisol concentrations measured in saliva and plasma within each experiment varied substantially between animals and samples. Furthermore, in experiment 2, nearly 10% of salivary samples were below limits of detection. The sharp peaks in cortisol after ACTH administration in both the plasma and saliva were reflected adrenal stimulation. In addition, increases in cortisol in response to milking in both the plasma and saliva suggest that salivary sampling is a reliable option when studying cortisol responses to normal physiological events.

  9. Nandrolone decanoate increases satellite cell numbers in the chicken pectoralis muscle.

    PubMed

    Allouh, Mohammed Z; Rosser, Benjamin W C

    2010-02-01

    The anabolic androgenic steroid nandrolone decanoate has minimal androgenic effects and, thus, is widely used to induce muscle hypertrophy in both patients and athletes. Although increases in satellite cell numbers and satellite cells giving rise to new myonuclei are associated with hypertrophy in many experimental models, the relationship between nandrolone and satellite cells is poorly understood. Here we test the hypothesis that nandrolone administration is associated with an increase in satellite cell numbers in muscle. Nandrolone was injected at weekly intervals for four weeks into the right pectoralis muscle of female white leghorn chickens aged 63 days post hatch. Age/size/sex matched control birds received saline injections. The contralateral pectoralis was excised for study from each control and nandrolone treated bird. An antibody against Pax7 and immunocytochemical techniques were used to identify satellite cells. Nandrolone significantly increased mean pectoralis mass by approximately 22%, and mean fiber diameter by about 24%. All satellite cell indices that were quantified increased significantly in chicken pectoralis with administration of nandrolone. Nandrolone injected birds had on average higher satellite cell frequencies (#SC nuclei/all nuclei within basal lamina), number of satellite cells per millimeter of fiber, and satellite cell concentrations (closer together). Myonuclei were further apart (less concentrated) in nandrolone injected muscle. However, an overall increase in myonuclear numbers was revealed by a significantly greater mean number of myonuclei per millimeter of fiber in nandrolone injected muscle. Our results suggest that satellite cells may be key cellular vectors for nandrolone induced muscle fiber hypertrophy.

  10. Effects of intraperitoneal administration of the GABA B receptor agonist baclofen on food intake in rats measured under different feeding conditions.

    PubMed

    Ebenezer, Ivor S; Patel, Sunit M

    2011-02-25

    The effects of intraperitoneal (i.p.) administration of the GABA(B) receptor agonist baclofen were assessed in rats under different feeding conditions. In Experiment 1, it was observed that baclofen (1-4 mg/kg) significantly (at least, P<0.05) increased cumulative food intake in non-deprived rats during the 120 min measurement period during the early light phase of the light-dark cycle. By contrast, during the early dark phase of the light-dark cycle in non-deprived rats, the 1mg/kg doses of baclofen significantly increased cumulative feeding at 30, 60 and 120 min (at least P<0.05), the 2mg/kg dose significantly increased feeding at 30 and 60 min (at least P<0.05) and the 4 mg/kg dose had no effects on feeding. In Experiment 2, baclofen (1-4 mg/kg) was found to produce no significant effects on food intake in rats that were food-deprived for 22 h. In Experiment 3, the effects of baclofen were investigated on food intake in 16 h food-deprived rats that had received an oral preload for 2h prior to drug administration. Baclofen (1-4 mg/kg) significantly increased cumulative food consumption (at least, P<0.05) only during the first 30 min after administration in these animals. The results of this study indicate that the effects of baclofen on food intake may be related to the state of hunger or satiety of the animals and the time during the light-dark cycle when the drug is administered. Copyright © 2010 Elsevier B.V. All rights reserved.

  11. Effects of tibial intraosseous and intravenous administration of Hextend on time of administration and hemodynamics in a hypovolemic swine model.

    PubMed

    Wilson, James; Passmore, Alex; Leger, Sephra; Lannan, Johnathon; Bentley, Michael; Johnson, Don

    2016-01-01

    To determine if there were significant differences between the tibial intraosseous (TIO) and intravenous (IV) administration of Hextend relative to time and in hemodynamics in a hypovolemic model. Vivarium. Yorkshire swine; sample size was based on a power of 80 percent, α of 0.05, and a large effect size of 0.6. Swine were randomly assigned to one of three groups: TIO (n = 7), IV (n = 7), and control (n = 7). Swine were exsanguinated 30 percent of their blood volume. Hextend (500 mL) was administered either by the TIO or IV route; the control group received none. Time of administration of Hextend; systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), heart rate (HR), cardiac output (CO), and stroke volume (SV) data were collected every 2 minutes and compared by group over 8 minutes. An independent t test determined that there was no significant difference between groups relative to time of administration (p = 0.001). A repeated analysis of variance found that there were no significant differences in SBP, DBP, MAP, HR, CO, and SV between the TIO and IV groups over 8 minutes (p > 0.05) but significant differences between both TIO and IV compared to the control group (p < 0.05). TIO is an effective and easily used method to administer Hextend for patients in hypovolemic shock. Based upon the findings of this study, the TIO route might be considered the first choice for rapid vascular access and the administration of Hextend.

  12. Effects of oral administration of a commercial activated charcoal suspension on serum osmolality and lactate concentration in the dog.

    PubMed

    Burkitt, Jamie M; Haskins, Steve C; Aldrich, Janet; Jandrey, Karl E; Rezende, Marlis L; Boyle, Jennifer E

    2005-01-01

    The purpose of this investigation was to determine the effects of an activated charcoal (AC) suspension containing propylene glycol and glycerol on serum osmolality, osmolal gap, and lactate concentration in dogs. Six healthy adult dogs were administered 4 g/kg AC in a commercially available suspension that contained propylene glycol and glycerol as vehicles. Blood samples were taken before and 1, 4, 6, 8, 12, and 24 hours after the administration of the test suspension. Samples were analyzed for osmolality, blood gases, and concentrations of lactate, sodium, potassium, serum urea nitrogen, and glucose. Osmolal gaps were calculated for each time point. Mean serum osmolality, osmolal gap, and lactate concentration were significantly increased after suspension administration compared to baseline. Serum osmolality increased from 311 mOsm/kg at baseline to 353 mOsm/kg, osmolal gap increased from 5 to 52 mOsm/kg, and lactate concentration increased from 1.9 to 4.5 mmol/L after suspension administration (all P < .01). Three of the 6 dogs vomited between 1 and 3 hours after the administration of the test suspension, and 4 of 6 dogs were lethargic. All dogs drank frequently after AC administration. Commercial AC suspension administered at a clinically relevant dose increases serum osmolality, osmolal gap, and lactate concentration in dogs. These laboratory measures and the clinical signs of vomiting, lethargy, and increased frequency of drinking might complicate the diagnosis or monitoring of some intoxications (such as ethylene glycol) in dogs that have previously received AC suspension containing propylene glycol, glycerol, or both as vehicles.

  13. Effects of caffeine on alcohol reinforcement: beverage choice, self-administration, and subjective ratings.

    PubMed

    Sweeney, Mary M; Meredith, Steven E; Evatt, Daniel P; Griffiths, Roland R

    2017-03-01

    Combining alcohol and caffeine is associated with increased alcohol consumption, but no prospective experimental studies have examined whether added caffeine increases alcohol consumption. This study examined how caffeine alters alcohol self-administration and subjective reinforcing effects in healthy adults. Thirty-one participants completed six double-blind alcohol self-administration sessions: three sessions with alcohol only (e.g., beverage A) and three sessions with alcohol and caffeine (e.g., beverage B). Participants chose which beverage to consume on a subsequent session (e.g., beverage A or B). The effects of caffeine on overall beverage choice, number of self-administered drinks, subjective ratings (e.g., Biphasic Alcohol Effects Scale), and psychomotor performance were examined. A majority of participants (65%) chose to drink the alcohol beverage containing caffeine on their final self-administration session. Caffeine did not increase the number of self-administered drinks. Caffeine significantly increased stimulant effects, decreased sedative effects, and attenuated decreases in psychomotor performance attributable to alcohol. Relative to nonchoosers, caffeine choosers reported overall lower stimulant ratings and reported greater drinking behavior prior to the study. Although caffeine did not increase the number of self-administered drinks, most participants chose the alcohol beverage containing caffeine. Given the differences in subjective ratings and pre-existing differences in self-reported alcohol consumption for caffeine choosers and nonchoosers, these data suggest that decreased stimulant effects of alcohol and heavier self-reported drinking may predict subsequent choice of combined caffeine and alcohol beverages. These predictors may identify individuals who would benefit from efforts to reduce risk behaviors associated with combining alcohol and caffeine.

  14. Superovulation Using the Combined Administration of Inhibin Antiserum and Equine Chorionic Gonadotropin Increases the Number of Ovulated Oocytes in C57BL/6 Female Mice

    PubMed Central

    Takeo, Toru; Nakagata, Naomi

    2015-01-01

    Superovulation is a reproductive technique generally used to produce genetically engineered mice. Superovulation in mice involves the administration of equine chorionic gonadotropin (eCG) to promote follicle growth and then that of human chorionic gonadotropin (hCG) to induce ovulation. Previously, some published studies reported that inhibin antiserum (IAS) increased the number of ovulated oocytes in ddY and wild-derived strains of mice. However, the effect of IAS on the C57BL/6 strain, which is the most widely used inbred strain for the production of genetically engineered mice, has not been investigated. In addition, the combined effect of IAS and eCG (IASe) on the number of ovulated oocytes in superovulation treatment has not been examined. In this study, we examined the effect of IAS and eCG on the number of ovulated oocytes in immature female mice of the C57BL/6 strain in superovulation treatment. Furthermore, we evaluated the quality of obtained oocytes produced by superovulation using IASe by in vitro fertilization (IVF) with sperm from C57BL/6 or genetically engineered mice. The developmental ability of fresh or cryopreserved embryos was examined by embryo transfer. The administration of IAS or eCG had a similar effect on the number of ovulated oocytes in C57BL/6 female mice. The number of ovulated oocytes increased to about 3-fold by the administration of IASe than by the administration of IAS or eCG alone. Oocytes derived from superovulation using IASe normally developed into 2-cell embryos by IVF using sperm from C57BL/6 mice. Fresh or cryopreserved 2-cell embryos produced by IVF between oocytes of C57BL/6 mice and sperm from genetically engineered mice normally developed into live pups following embryo transfer. In summary, a novel technique of superovulation using IASe is extremely useful for producing a great number of oocytes and offspring from genetically engineered mice. PMID:26024317

  15. Cardiotoxicity in rabbits after long-term nandrolone decanoate administration.

    PubMed

    Vasilaki, Fotini; Tsitsimpikou, Christina; Tsarouhas, Konstantinos; Germanakis, Ioannis; Tzardi, Marias; Kavvalakis, Matthaios; Ozcagli, Eren; Kouretas, Dimitrios; Tsatsakis, Aristidis M

    2016-01-22

    Abuse of anabolic androgenic steroids is linked to a variety of cardiovascular complications. The aim of our study was to investigate the possible cardiovascular effects of nandrolone decanoate on young rabbits using echocardiography, histology and monitoring of telomerase activity, oxidative stress and biochemical markers. Fourteen rabbits were divided into three administration groups and the control group. Doses of 4mg/kg and 10mg/kg of nandrolone decanoate, given intramuscularly and subcutaneously, two days per week for six months were applied. A 4-months wash-out period followed. Focal fibrosis and inflammatory infiltrations of cardiac tissue were observed in the high dose groups. Thiobarbituric acid-reactive species (TBARS) levels were significantly increased in the high dose groups, while catalase activity decreased. Myocardial Performance Index (MPI) is the main echocardiographic index primarily affected by nandrolone administration in rabbits. Despite the preserved systolic performance, histological lesions observed associated with distorted MPI values, point to diastolic impairment of the thickened myocardium due to nandrolone treatment. Oxidative stress accumulates and telomerase activity in cardiac tissue rises. Subcutaneous administration seems to be more deleterious to the cardiovascular system, as oxidative stress, telomerase activity and biochemical markers do not appear to return into normal values in the wash-out period. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  16. Tibial Tray Thickness Significantly Increases Medial Tibial Bone Resorption in Cobalt-Chromium Total Knee Arthroplasty Implants.

    PubMed

    Martin, J Ryan; Watts, Chad D; Levy, Daniel L; Miner, Todd M; Springer, Bryan D; Kim, Raymond H

    2017-01-01

    Stress shielding is an uncommon complication associated with primary total knee arthroplasty. Patients are frequently identified radiographically with minimal clinical symptoms. Very few studies have evaluated risk factors for postoperative medial tibial bone loss. We hypothesized that thicker cobalt-chromium tibial trays are associated with increased bone loss. We performed a retrospective review of 100 posterior stabilized, fixed-bearing total knee arthroplasty where 50 patients had a 4-mm-thick tibial tray (thick tray cohort) and 50 patients had a 2.7-mm-thick tibial tray (thin tray cohort). A clinical evaluation and a radiographic assessment of medial tibial bone loss were performed on both cohorts at a minimum of 2 years postoperatively. Mean medial tibial bone loss was significantly higher in the thick tray cohort (1.07 vs 0.16 mm; P = .0001). In addition, there were significantly more patients with medial tibial bone loss in the thick tray group compared with the thin tray group (44% vs 10%, P = .0002). Despite these differences, there were no statistically significant differences in range of motion, knee society score, complications, or revision surgeries performed. A thicker cobalt-chromium tray was associated with significantly more medial tibial bone loss. Despite these radiographic findings, we found no discernable differences in clinical outcomes in our patient cohort. Further study and longer follow-up are needed to understand the effects and clinical significance of medial tibial bone loss. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. The influence of repeated administration of poloxamer 407 on serum lipoproteins and protease activity in mouse liver and heart.

    PubMed

    Korolenko, Tatyana A; Tuzikov, Fedor V; Johnston, Thomas P; Tuzikova, Natalia A; Kisarova, Yana A; Zhanaeva, Svetlana Ya; Alexeenko, Tatyana V; Zhukova, Natalia A; Brak, Ivan V; Spiridonov, Victor K; Filjushina, Elena E; Cherkanova, Marina S; Monoszon, Anna A

    2012-11-01

    The effects of repeated administration of poloxamer 407 (P-407) on lipoprotein-cholesterol (LP-C) and lipoprotein-triglyceride (LP-TG) fractions and subfractions, as well as the effect on liver and heart proteases, were studied. Repeated administration of P-407 to male CBA mice resulted in a model of atherosclerosis with increased diastolic blood pressure; there was a drastic increase in total serum cholesterol and especially TG. A novel small-angle X-ray scattering method for the determination of the fractional and subfractional composition of LP-C and LP-TG was used. In chronically P-407-treated mice, P-407 significantly increased atherogenic low-density lipoprotein C (LDL-C) fractions, as well as intermediate-density lipoprotein C (IDL-C), and LDL₁₋₃-C subfractions, and very-low-density lipoprotein-C (VLDL-C) fractions, as well as VLDL₁₋₂-C and VLDL₃₋₅-C subfractions), to a lesser extent, the total anti-atherogenic high-density lipoprotein C (HDL-C) fraction, as well as HDL₂-C and HDL₃-C subfractions. Additionally, we demonstrated an increase in the serum chitotriosidase activity, without significant changes in serum matrix metalloprotease (MMP) activity. Morphological changes observed in P-407-treated mice included atherosclerosis in the heart and storage syndrome in the liver macrophages. P-407 significantly increased the activity of cysteine, aspartate proteases, and MMPs in the heart, and only the activity of cathepsin B and MMPs in the liver of mice. Thus, repeated administration of P-407 to mice induced atherosclerosis secondary to sustained dyslipidemia and formation of foamy macrophages in liver, and also modulated the activity of heart and liver proteases.

  18. Repeated seizures induce long-term increase in hippocampal benzodiazepine receptors.

    PubMed Central

    McNamara, J O; Peper, A M; Patrone, V

    1980-01-01

    Repeated seizures, whether induced by kindling or electroshock, caused a long-lasting (at least 24 hr) increase of [3H]diazepam binding in hippocampal membranes of Sprague-Dawley rats. Scatchard analyses demonstrated that increased numbers of binding sites accounted for the increase. Neither repeated hypoxia nor repeated administration of electrical current without inducing seizures caused an increase of [3H]diazepam binding. Regardless of the method used for seizure induction, the response was graded in that large numbers of seizures were required to induce significant increases, whereas fewer seizures induced only slight increases. We suggest that the receptor increases imply a heightened response to benzodiazepines and more powerful hippocampal recurrent inhibition. PMID:6930682

  19. Oral administration of a medium containing both D-aspartate-producing live bacteria and D-aspartate reduces rectal temperature in chicks.

    PubMed

    Do, P H; Tran, P V; Bahry, M A; Yang, H; Han, G; Tsuchiya, A; Asami, Y; Furuse, M; Chowdhury, V S

    2017-10-01

    1. The aim of this study was to investigate the effects on the rectal temperature of young chicks of the oral administration of a medium that contained both live bacteria that produce D-aspartate (D-Asp) and D-Asp. 2. In Experiment 1, chicks were subjected to chronic oral administration of either the medium (containing live bacteria and 2.46 μmol D-Asp) or water from 7 to 14 d of age. Plasma-free amino acids as well as mitochondrial biogenic gene expression in the breast muscle were analysed. In Experiment 2, 7-d-old chicks were subjected to acute oral administration of the above medium or of an equimolar amount of D-Asp to examine their effect on changes in rectal temperature. In Experiment 3, after 1 week of chronic oral administration of the medium, 14-d-old chicks were exposed to either high ambient temperature (HT; 40 ± 1°C, 3 h) or control thermoneutral temperature (CT; 30 ± 1°C, 3 h) to monitor the changes in rectal temperature. 3. Chronic, but not acute, oral administration of the medium significantly reduced rectal temperature in chicks, and a chronic effect also appeared under HT conditions. 4. Chronic oral administration of the medium significantly reduced the mRNA abundance of the avian uncoupling protein (avUCP) in the breast muscle, but led to a significant increase in avian adenine nucleotide translocator (avANT) mRNA in the same muscle. 5. (a) These results indicate that the medium can reduce body temperature through the decline in avUCP mRNA expression in the breast muscle that may be involved in reduced mitochondrial proton leaks and heat production. (b) The increase in avANT further suggests a possible enhancement of adenosine triphosphate (ATP) synthesis.

  20. Full-Day Kindergarten Results in Significant Achievement Gains

    ERIC Educational Resources Information Center

    Raskin, Candace F.; Haar, Jean M.

    2009-01-01

    In 2004, after an in-depth review of student achievement data for over 4,000 students, the administration of a school district in southern Minnesota identified the following challenges: (1) above-state-average number of special education students; (2) increasing number of English as Second Language (ESL) students; (3) increasing number of students…

  1. Evaluation of tibolone administration in bone architectural by MicroCT

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Carvalho, A. C. B.; Henriques, H. N.; Granjeiro, J. M.

    Elderly women are at higher risk for hip fracture because of additional and relatively rapid bone loss due to estrogen deficiency by loss of the ovarian function and a longer average life span than men. The early application of agents that suppress the increase in bone turnover due to estrogen deficiency is essential to prevent bone loss and reduce the risk of osteoporosis. Some advanced imaging techniques may be required to investigate osteoporosis. X-ray micro-computed tomography has been used to generate high-resolution 3D images of cancellous and cortical bone morphology from normal and pathologic human and animal specimens. The aimmore » of this study is to verify the effects of tibolone administration by evaluating the trabecular bone region. The experiment was performed on two groups of rats previously ovariectomized in which one received tibolone while the other did not. Tibolone administration (1 mg/day) began thirty days after the ovariectomy and the treatment remained for five months. At last, the animals were euthanized and femurs were collected. The scan was obtained using a Hamamatsu 10 Mp camera with a pixel size of 11.59 {mu}m and trabecular region in the right femoral head were quantified. All results were statistically evaluated with significance set at P<0.05%. Tibolone administration was shown to be beneficial in some analysis of the femoral head, performing higher bone volume and reducing the porosity when compared to ovariectomized. It can be concluded that tibolone administered to ovariectomized rats significantly preserved bone mass in the femoral head and microtomography was an efficient method to identify bone loss process and to evaluate potential therapies, as tibolone administration. (authors)« less

  2. Male and Female Administrative Potential--Is There a Difference?

    ERIC Educational Resources Information Center

    Arons, Elizabeth Levin

    1980-01-01

    A diagnostic administrative style test administered to 98 candidates for administrative positions revealed no significant differences between men and women; the most frequent style for both was the "separated" style characterized by low task orientation, low relationship orientation, attention to rules, conscientiousness, and desire for…

  3. Sublingual administration of detomidine in horses: sedative effect, analgesia and detection time.

    PubMed

    L'Ami, Jiske J; Vermunt, Lian E; van Loon, Johannes P A M; Sloet van Oldruitenborgh-Oosterbaan, Marianne M

    2013-05-01

    A single dose of 40 μg/kg bodyweight (BW) of oromucosal detomidine gel was administered sublingually to 10 healthy Dutch Warmblood mares aged 7 ± 4 years (mean ± SD) and BW 580 ± 69 kg. Blood and urine samples were collected before and for 8 days following administration and evaluated qualitatively in an FEI Reference Laboratory and quantitatively in a research laboratory. Clinical effects were evaluated at baseline and for 24 h after administration. Sedation was determined using head height and scores of reaction to auditory and mixed auditory/sensory stimuli. Mechanical nociceptive thresholds (MNTs) were assessed using pressure algometry to evaluate analgesia. Heart rate (HR) was measured and ataxia scored. All horses were considered negative for detomidine in blood samples by 48 h post-administration and in urine by 60 h. These results indicated that a safe withdrawal time for detomidine oromucosal gel may be 72 h following a single sublingual administration of 40 μg/kgBW. Decreases in HR and head height were maximal at 40 and 60 min post-administration, respectively. The maximal decrease in response to stimuli was observed at 100 min. Ataxia was maximal at 60 min. At 40 and 80 min MNTs were significantly increased compared to baseline. All parameters, except the MNTs of two locations, which were decreased, returned to baseline values within 24 h post-administration. Copyright © 2012 Elsevier Ltd. All rights reserved.

  4. CDP-choline liposomes provide significant reduction in infarction over free CDP-choline in stroke

    PubMed Central

    Adibhatla, Rao Muralikrishna; Hatcher, J.F.; Tureyen, K.

    2007-01-01

    Cytidine-5′-diphosphocholine (CDP-choline, Citicoline, Somazina) is in clinical use (intravenous administration) for stroke treatment in Europe and Japan, while USA phase III stroke clinical trials (oral administration) were disappointing. Others showed that CDP-choline liposomes significantly increased brain uptake over the free drug in cerebral ischemia models. Liposomes were formulated as DPPC, DPPS, cholesterol, GM1 ganglioside; 7/4/7/1.57 molar ratio or 35.8/20.4/35.8/8.0 mol%. GM1 ganglioside confers long-circulating properties to the liposomes by suppressing phagocytosis. CDP-choline liposomes deliver the agent intact to the brain, circumventing the rate-limiting, cytidine triphosphate:phosphocholine cytidylyltransferase in phosphatidylcholine synthesis. Our data show that CDP-choline liposomes significantly ( P < 0.01) decreased cerebral infarction (by 62%) compared to the equivalent dose of free CDP-choline (by 26%) after 1 h focal cerebral ischemia and 24 h reperfusion in spontaneously hypertensive rats. Beneficial effects of CDP-choline liposomes in stroke may derive from a synergistic effect between the phospholipid components of the liposomes and the encapsulated CDP-choline. PMID:16153613

  5. 21 CFR 201.18 - Drugs; significance of control numbers.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 4 2012-04-01 2012-04-01 false Drugs; significance of control numbers. 201.18 Section 201.18 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL LABELING General Labeling Provisions § 201.18 Drugs; significance of control...

  6. 21 CFR 201.18 - Drugs; significance of control numbers.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 4 2014-04-01 2014-04-01 false Drugs; significance of control numbers. 201.18 Section 201.18 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL LABELING General Labeling Provisions § 201.18 Drugs; significance of control...

  7. 21 CFR 201.18 - Drugs; significance of control numbers.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 4 2011-04-01 2011-04-01 false Drugs; significance of control numbers. 201.18 Section 201.18 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL LABELING General Labeling Provisions § 201.18 Drugs; significance of control...

  8. 21 CFR 201.18 - Drugs; significance of control numbers.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 4 2013-04-01 2013-04-01 false Drugs; significance of control numbers. 201.18 Section 201.18 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL LABELING General Labeling Provisions § 201.18 Drugs; significance of control...

  9. 21 CFR 201.18 - Drugs; significance of control numbers.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 4 2010-04-01 2010-04-01 false Drugs; significance of control numbers. 201.18 Section 201.18 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL LABELING General Labeling Provisions § 201.18 Drugs; significance of control...

  10. Interest in Long-Term Care among Health Services Administration Students

    ERIC Educational Resources Information Center

    Temple, April; Thompson, Jon M.

    2011-01-01

    The aging of the population has created increased opportunities for health administrators in long-term care. This study consisted of a cross-sectional survey of 68 undergraduate health services administration students to explore factors related to interest in a career in long-term care administration. One third expressed interest working in the…

  11. Calm to chaos: Engaging undergraduate nursing students with the complex nature of interruptions during medication administration.

    PubMed

    Hayes, Carolyn; Jackson, Debra; Davidson, Patricia M; Daly, John; Power, Tamara

    2017-12-01

    To describe undergraduate student nurse responses to a simulated role-play experience focussing on managing interruptions during medication administration. Improving patient safety requires that we find creative and innovative methods of teaching medication administration to undergraduate nurses in real-world conditions. Nurses are responsible for the majority of medication administrations in health care. Incidents and errors associated with medications are a significant patient safety issue and often occur as a result of interruptions. Undergraduate nursing students are generally taught medication administration skills in a calm and uninterrupted simulated environment. However, in the clinical environment medication administration is challenged by multiple interruptions. A qualitative study using convenience sampling was used to examine student perceptions of a simulated role-play experience. Data were collected from 451 of a possible 528 student written reflective responses and subject to thematic analysis. Students reported an increased understanding of the impacts of interruptions while administering medications and an improved awareness of how to manage disruptions. This study reports on one of three emergent themes: "Calm to chaos: engaging with the complex nature of clinical practice." Interrupting medication administration in realistic and safe settings facilitates awareness, allows for students to begin to develop management strategies in relation to interruption and increases their confidence. Students were given the opportunity to consolidate and integrate prior and new knowledge and skills through this role-play simulation. © 2017 John Wiley & Sons Ltd.

  12. Immunological changes in the intestines and skin after senna administration.

    PubMed

    Yamate, Yurika; Hiramoto, Keiichi; Yokoyama, Satoshi; Ooi, Kazuya

    2015-06-01

    It has been reported that chronic sennoside use is associated with the development of melanosis coli, colonic adenoma, and/or carcinomas. In this study, we investigated the immunological changes in the colon and skin after the administration of senna. In this study, we investigated the colon and epidermis of C57/BL6j mice after a single administration of 10 mg/kg of senna [Cassia angustifolia (Caesalpiniaceae); 3, 6, 12, and 24 h after administration] and after repeated once per week administrations (on days 3, 5, 7, 14, and 21 of administration). The LD50 and ED50 of senna used in this experiment were 165 mg/kg and 13 g/kg, respectively. We demonstrated that the DOPA-positive cells in the colon increased at 12 h after single administration and were further increased from at 5-28 d after repeated administration. We also studied the physiological changes of the small intestine using the charcoal meal test. We found that there was a tendency for peristalsis to be inhibited after repeated senna administration. In the epidermis, we investigated the number of Langerhans cells, because they are important immune cells of the skin. The number of these cells decreased, especially after repeated administration. The present findings suggested that it is necessary to pay attention to not only the intestine but also the skin, during long-term senna treatment.

  13. Castration and pregnancy of rural pigs significantly increase the prevalence of naturally acquired Taenia solium cysticercosis.

    PubMed

    Morales, J; Velasco, T; Tovar, V; Fragoso, G; Fleury, A; Beltrán, C; Villalobos, N; Aluja, A; Rodarte, L F; Sciutto, E; Larralde, C

    2002-08-30

    Cuentepec is a rural village of central Mexico, where 1300 pigs were bred at the time of the study in conditions that favor Taenia solium transmission. The tongues of 1087 (84%) of these pigs were visually examined and 33% were found to be cysticercotic. Castration of male pigs increased prevalence from 23 to 50% (P < 0.001) and pregnancy in sows also increased their prevalence from 28 to 59% (P < 0.001). Thus, endocrinological conditions characterized by low levels of androgens or high levels of female hormones probably influence the susceptibility of pigs to T. solium cysticercosis as observed in mice infected with Taenia crassiceps. Delaying castration of male pigs and confinement of sows during pregnancy might significantly decrease the prevalence of pig-cysticercosis and help curb transmission without much cost or difficulty. Copyright 2002 Elsevier Science B.V.

  14. Improved accuracy of co-morbidity coding over time after the introduction of ICD-10 administrative data

    PubMed Central

    2011-01-01

    Background Co-morbidity information derived from administrative data needs to be validated to allow its regular use. We assessed evolution in the accuracy of coding for Charlson and Elixhauser co-morbidities at three time points over a 5-year period, following the introduction of the International Classification of Diseases, 10th Revision (ICD-10), coding of hospital discharges. Methods Cross-sectional time trend evaluation study of coding accuracy using hospital chart data of 3'499 randomly selected patients who were discharged in 1999, 2001 and 2003, from two teaching and one non-teaching hospital in Switzerland. We measured sensitivity, positive predictive and Kappa values for agreement between administrative data coded with ICD-10 and chart data as the 'reference standard' for recording 36 co-morbidities. Results For the 17 the Charlson co-morbidities, the sensitivity - median (min-max) - was 36.5% (17.4-64.1) in 1999, 42.5% (22.2-64.6) in 2001 and 42.8% (8.4-75.6) in 2003. For the 29 Elixhauser co-morbidities, the sensitivity was 34.2% (1.9-64.1) in 1999, 38.6% (10.5-66.5) in 2001 and 41.6% (5.1-76.5) in 2003. Between 1999 and 2003, sensitivity estimates increased for 30 co-morbidities and decreased for 6 co-morbidities. The increase in sensitivities was statistically significant for six conditions and the decrease significant for one. Kappa values were increased for 29 co-morbidities and decreased for seven. Conclusions Accuracy of administrative data in recording clinical conditions improved slightly between 1999 and 2003. These findings are of relevance to all jurisdictions introducing new coding systems, because they demonstrate a phenomenon of improved administrative data accuracy that may relate to a coding 'learning curve' with the new coding system. PMID:21849089

  15. Improved accuracy of co-morbidity coding over time after the introduction of ICD-10 administrative data.

    PubMed

    Januel, Jean-Marie; Luthi, Jean-Christophe; Quan, Hude; Borst, François; Taffé, Patrick; Ghali, William A; Burnand, Bernard

    2011-08-18

    Co-morbidity information derived from administrative data needs to be validated to allow its regular use. We assessed evolution in the accuracy of coding for Charlson and Elixhauser co-morbidities at three time points over a 5-year period, following the introduction of the International Classification of Diseases, 10th Revision (ICD-10), coding of hospital discharges. Cross-sectional time trend evaluation study of coding accuracy using hospital chart data of 3'499 randomly selected patients who were discharged in 1999, 2001 and 2003, from two teaching and one non-teaching hospital in Switzerland. We measured sensitivity, positive predictive and Kappa values for agreement between administrative data coded with ICD-10 and chart data as the 'reference standard' for recording 36 co-morbidities. For the 17 the Charlson co-morbidities, the sensitivity - median (min-max) - was 36.5% (17.4-64.1) in 1999, 42.5% (22.2-64.6) in 2001 and 42.8% (8.4-75.6) in 2003. For the 29 Elixhauser co-morbidities, the sensitivity was 34.2% (1.9-64.1) in 1999, 38.6% (10.5-66.5) in 2001 and 41.6% (5.1-76.5) in 2003. Between 1999 and 2003, sensitivity estimates increased for 30 co-morbidities and decreased for 6 co-morbidities. The increase in sensitivities was statistically significant for six conditions and the decrease significant for one. Kappa values were increased for 29 co-morbidities and decreased for seven. Accuracy of administrative data in recording clinical conditions improved slightly between 1999 and 2003. These findings are of relevance to all jurisdictions introducing new coding systems, because they demonstrate a phenomenon of improved administrative data accuracy that may relate to a coding 'learning curve' with the new coding system.

  16. Using administrative data to track fall-related ambulatory care services in the Veterans Administration Healthcare system.

    PubMed

    Luther, Stephen L; French, Dustin D; Powell-Cope, Gail; Rubenstein, Laurence Z; Campbell, Robert

    2005-10-01

    The Veterans Administration (VA) Healthcare system, containing hospital and community-based outpatient clinics, provides the setting for the study. Summary data was obtained from the VA Ambulatory Events Database for fiscal years (FY) 1997-2001 and in-depth data for FY 2001. In FY 2001, the database included approximately 4 million unique patients with 60 million encounters. The purpose of this study was: 1) to quantify injuries and use of services associated with falls among the elderly treated in Veterans Administration (VA) ambulatory care settings using administrative data; 2) to compare fall-related services provided to elderly veterans with those provided to younger veterans. Retrospective analysis of administrative data. This study describes the trends (FY 1997-2001) and patterns of fall-related ambulatory care encounters (FY 2001) in the VA Healthcare System. An approximately four-fold increase in both encounters and patients seen was observed in FY 1997-2001, largely paralleling the growth of VA ambulatory care services. More than two-thirds of the patients treated were found to be over the age of 65. Veterans over the age of 65 were found to be more likely to receive care in the non-urgent setting and had higher numbers of co-morbid conditions than younger veterans. While nearly half of the encounters occurred in the Emergency/Urgent Care setting, fall-related injuries led to services across a wide spectrum of medical and surgical providers/departments. This study represents the first attempt to use the VA Ambulatory Events Database to study fall-related services provided to elderly veterans. In view of the aging population served by the VA and the movement to provide increased services in the outpatient setting, this database provides an important resource for researchers and administrators interested in the prevention and treatment of fall-related injuries.

  17. Severe hypophosphataemia after intravenous iron administration.

    PubMed

    Blazevic, A; Hunze, J; Boots, J M M

    2014-01-01

    Currently, in many centres, intravenous administration of iron is becoming increasingly popular because of higher efficacy and decreased side effects, mainly gastrointestinal, compared with oral iron therapy. Studies of intravenous ferric carboxymaltose administration in the postpartum setting and in patients with non-dialysis-dependent chronic kidney disease revealed a decrease in serum phosphate levels that was generally asymptomatic and transient. Here, we report four cases of severe and symptomatic hypophosphataemia after intravenous iron administration. All patients received this as therapy for iron deficiency anaemia due to heavy menstrual bleeding. In most cases, a pre-existent disorder in the phosphate homeostasis existed, such as a secondary (cases 3 and 4) or tertiary hyperparathyroidism (case 1). However, in the second case there were no risk factors for a dysregulation of the phosphate homeostasis. Based on these findings, we conclude that severe and symptomatic hypophosphatemia can occur as a side effect of intravenous iron administration and can persist for months after administration. Especially patients with low phosphate levels prior to therapy due to concomitant disorders in phosphate homeostasis (e.g. hyperparathyroidism, vitamin D deficiency) are at risk.

  18. Oral administration of a recombinant cholera toxin B subunit promotes mucosal healing in the colon.

    PubMed

    Baldauf, K J; Royal, J M; Kouokam, J C; Haribabu, B; Jala, V R; Yaddanapudi, K; Hamorsky, K T; Dryden, G W; Matoba, N

    2017-07-01

    Cholera toxin B subunit (CTB) is a component of a licensed oral cholera vaccine. However, CTB has pleiotropic immunomodulatory effects whose impacts on the gut are not fully understood. Here, we found that oral administration in mice of a plant-made recombinant CTB (CTBp) significantly increased several immune cell populations in the colon lamina propria. Global gene expression analysis revealed that CTBp had more pronounced impacts on the colon than the small intestine, with significant activation of TGFβ-mediated pathways in the colon epithelium. The clinical relevance of CTBp-induced impacts on colonic mucosa was examined. In a human colon epithelial model using Caco2 cells, CTBp, but not the non-GM1-binding mutant G33D-CTBp, induced TGFβ-mediated wound healing. In a dextran sodium sulfate (DSS) acute colitis mouse model, oral administration of CTBp protected against colon mucosal damage as manifested by mitigated body weight loss, decreased histopathological scores, and blunted escalation of inflammatory cytokine levels while inducing wound healing-related genes. Furthermore, biweekly oral administration of CTBp significantly reduced disease severity and tumorigenesis in the azoxymethane/DSS model of ulcerative colitis and colon cancer. Altogether, these results demonstrate CTBp's ability to enhance mucosal healing in the colon, highlighting its potential application in ulcerative colitis therapy besides cholera vaccination.

  19. Oxidative stress in blood and testicle of rat following intraperitoneal administration of aluminum and indium.

    PubMed

    Maghraoui, S; Clichici, Simona; Ayadi, A; Login, C; Moldovan, R; Daicoviciu, D; Decea, N; Mureşan, A; Tekaya, L

    2014-03-01

    Aluminum (Al) and indium (In) have embryotoxic, neurotoxic and genotoxic effects, oxidative stress being one of the possible mechanisms involved in their cytotoxicity. We have recently demonstrated that indium intraperitoneal (ip) administration induced histological disorganization of testicular tissue. In the present research we aimed at investigating the effect of Al and In ip administration on systemic and testicular oxidative stress status. Studies were performed on Wistar rats ip injected with Al, In or physiological solution for two weeks. Our results showed that In significantly decreased the absolute weight of testicles. Measurements of lactate dehydrogenase (LDH) and paraoxonase (PON) activities showed that In induced a significant augmentation in the first parameter but no changes were observed in the second. Both Al and In caused oxidative stress in testicles by increasing malondialdehyde (MDA) and protein carbonyls (PC) production. Concomitantly, thiol group (-SH) and glutathione (GSH) level were enhanced in the testicles. In the blood, while concentrations of MDA was not changed, those of GSH was significantly decreased in the Al and In groups. Our results indicated that Al and In cause oxidative stress both in blood and testicles but In has cytotoxic effect as well as negative impact on testicle weights. These findings could explain the testicular histological alterations previously described after In ip administration.

  20. Administration of a non-NMDA antagonist, GYKI 52466, increases excitotoxic Purkinje cell degeneration caused by ibogaine.

    PubMed

    O'Hearn, E; Molliver, M E

    2004-01-01

    Ibogaine is a tremorigenic hallucinogen that has been proposed for clinical use in treating addiction. We previously reported that ibogaine, administered systemically, produces degeneration of a subset of Purkinje cells in the cerebellum, primarily within the vermis. Ablation of the inferior olive affords protection against ibogaine-induced neurotoxicity leading to the interpretation that ibogaine itself is not directly toxic to Purkinje cells. We postulated that ibogaine produces sustained excitation of inferior olivary neurons that leads to excessive glutamate release at climbing fiber terminals, causing subsequent excitotoxic injury to Purkinje cells. The neuronal degeneration induced by ibogaine provides an animal model for studying excitotoxic injury in order to analyze the contribution of glutamate receptors to this injury and to evaluate neuroprotective strategies. Since non-N-methyl-D-aspartate (NMDA) receptors mediate Purkinje cell excitation by climbing fibers, we hypothesized that 1-4-aminophenyl-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine (GYKI-52466), which antagonizes non-NMDA receptors, may have a neuroprotective effect by blocking glutamatergic excitation at climbing fiber synapses. To test this hypothesis, rats were administered systemic ibogaine plus GYKI-52466 and the degree of neuronal injury was analyzed in cerebellar sections. The results indicate that the AMPA antagonist GYKI-52466 (10 mg/kg i.p. x 3) does not protect against Purkinje cell injury at the doses used. Rather, co-administration of GYKI-52466 with ibogaine produces increased toxicity evidenced by more extensive Purkinje cell degeneration. Several hypotheses that may underlie this result are discussed. Although the reason for the increased toxicity found in this study is not fully explained, the present results show that a non-NMDA antagonist can produce increased excitotoxic injury under some conditions. Therefore, caution should be exercised before employing glutamate

  1. School-based administration of ADHD drugs decline, along with diversion, theft, and misuse.

    PubMed

    Dupont, Robert L; Bucher, Richard H; Wilford, Bonnie B; Coleman, John J

    2007-12-01

    Since 2000 researchers have reported a decline in the administration of attention-deficit/hyperactivity disorder (ADHD) medications given by school nurses, although no decline has been noted in the incidence of ADHD in school-age populations. Government data for the same period show reduced levels of methylphenidate abuse as measured by its involvement in hospital emergency department (ED) admissions. Offsetting this, however, is an increase in the involvement of amphetamine-dextroamphetamine in hospital ED admissions for the same period. Because ADHD medications are often administered in the school setting, a survey of school nurses was undertaken to identify factors related to the administration as well as to the diversion, theft, and misuse of ADHD medications. Of 311 school nurses responding, 295 (95%) reported a significant or moderate decline between 2002 and 2004 in the need for school-based administration of ADHD medications. Respondents also reported reductions in diversion, theft, and misuse of ADHD drugs.

  2. Effect of age increase on metabolism and toxicity of ethanol in female rats.

    PubMed

    Kim, Young C; Kim, Sung Y; Sohn, Young R

    2003-12-12

    Age-dependent change in the effects of acute ethanol administration on female rat liver was investigated. Female Sprague-Dawley rats, each aged 4, 12, or 50 weeks, received ethanol (2 g/kg) via a catheter inserted into a jugular vein. Ethanol elimination rate (EER), most rapid in the 4 weeks old rats, was decreased as the age advanced. Hepatic alcohol dehydrogenase activity was not altered by age, but microsomal p-nitrophenol hydroxylase activity was significantly greater in the 4 weeks old rats. Relative liver weight decreased with age increase in proportion to reduction of EER. Hepatic triglyceride and malondialdehyde concentrations increased spontaneously in the 50 weeks old nai;ve rats. Ethanol administration (3 g/kg, ip) elevated malondialdehyde and triglyceride contents only in the 4 and the 12 weeks old rats. Hepatic glutathione concentration was increasingly reduced by ethanol with age increase. Ethanol decreased cysteine concentration in the 4 weeks old rats, but elevated it significantly in the older rats. Inhibition of gamma-glutamylcysteine synthetase activity by ethanol was greater with age increase, which appeared to be responsible for the increase in hepatic cysteine. The results indicate that age does not affect the ethanol metabolizing capacity of female rat liver, but the overall ethanol metabolism is decreased in accordance with the reduction of relative liver size. Accordingly induction of acute alcoholic fatty liver is less significant in the old rats. However, progressively greater depletion of glutathione by ethanol in older rats suggests that susceptibility of liver to oxidative damage would be increased as animals grow old.

  3. Subjective and physiological effects, and expired carbon monoxide concentrations in frequent and occasional cannabis smokers following smoked, vaporized, and oral cannabis administration.

    PubMed

    Newmeyer, Matthew N; Swortwood, Madeleine J; Abulseoud, Osama A; Huestis, Marilyn A

    2017-06-01

    Although smoking is the most common cannabis administration route, vaporization and consumption of cannabis edibles are common. Few studies directly compare cannabis' subjective and physiological effects following multiple administration routes. Subjective and physiological effects, and expired carbon monoxide (CO) were evaluated in frequent and occasional cannabis users following placebo (0.001% Δ 9 -tetrahydrocannabinol [THC]), smoked, vaporized, and oral cannabis (6.9% THC, ∼54mg). Participants' subjective ratings were significantly elevated compared to placebo after smoking and vaporization, while only occasional smokers' ratings were significantly elevated compared to placebo after oral dosing. Frequent smokers' maximum ratings were significantly different between inhaled and oral routes, while no differences in occasional smokers' maximum ratings between active routes were observed. Additionally, heart rate increases above baseline 0.5h after smoking (mean 12.2bpm) and vaporization (10.7bpm), and at 1.5h (13.0bpm) and 3h (10.2bpm) after oral dosing were significantly greater than changes after placebo, with no differences between frequent and occasional smokers. Finally, smoking produced significantly increased expired CO concentrations 0.25-6h post-dose compared to vaporization. All participants had significant elevations in subjective effects after smoking and vaporization, but only occasional smokers after oral cannabis, indicating partial tolerance to subjective effects with frequent exposure. There were no differences in occasional smokers' maximum subjective ratings across the three active administration routes. Vaporized cannabis is an attractive alternative for medicinal administrations over smoking or oral routes; effects occur quickly and doses can be titrated with minimal CO exposure. These results have strong implications for safety and abuse liability assessments. Published by Elsevier B.V.

  4. Methylphenidate and Cocaine Self-Administration Produce Distinct Dopamine Terminal Alterations

    PubMed Central

    Calipari, Erin S.; Ferris, Mark J.; Melchior, James R.; Bermejo, Kristel; Salahpour, Ali; Roberts, David C. S.; Jones, Sara R.

    2012-01-01

    Methylphenidate (MPH) is a commonly abused psychostimulant prescribed for the treatment of attention deficit hyperactivity disorder. MPH has a mechanism of action similar to cocaine (COC) and is commonly characterized as a dopamine transporter (DAT) blocker. While there has been extensive work aimed at understanding dopamine (DA) nerve terminal changes following COC self-administration, very little is known about the effects of MPH self-administration on the DA system. We used fast scan cyclic voltammetry in nucleus accumbens core slices from animals with a five-day self-administration history of 40 injections/day of either MPH (0.56 mg/kg) or COC (1.5 mg/kg) to explore alterations in baseline DA release and uptake kinetics as well as alterations in the interaction of each compound with the DAT. Although MPH and COC have similar behavioral effects, the consequences of self-administration on DA system parameters were found to be divergent. We show that COC self-administration reduced DAT levels and maximal rates of DA uptake, as well as reducing electrically stimulated release, suggesting decreased DA terminal function. In contrast, MPH self-administration increased DAT levels, DA uptake rates, and DA release, suggesting enhanced terminal function, which was supported by findings of increased metabolite/DA tissue content ratios. Tyrosine hydroxylase mRNA, protein and phosphorylation levels were also assessed in both groups. Additionally, COC self-administration reduced COC-induced DAT inhibition, while MPH self-administration increased MPH-induced DAT inhibition, suggesting opposite pharmacodynamic effects of these two drugs. These findings suggest that the factors governing DA system adaptations are more complicated than simple DA uptake blockade. PMID:22458761

  5. Reinforcing effectiveness of nicotine in nonhuman primates: effects of nicotine dose and history of nicotine self-administration.

    PubMed

    Kohut, Stephen J; Bergman, Jack

    2016-07-01

    Despite the high prevalence of nicotine use in humans, robust nicotine self-administration has been difficult to demonstrate in laboratory animals. A parametric analysis of nicotine self-administration was conducted to study its reinforcing effects in nonhuman primates. Adult rhesus macaques (N = 6) self-administered intravenous (IV) nicotine (0.001-0.1 mg/kg) under a fixed-ratio (FR)1 schedule of reinforcement during daily 90-min sessions. Next, the demand function relating drug intake and response cost was determined by increasing the FR across sessions during the availability of each of several unit doses of nicotine (0.0032-0.032 mg/kg/inj). The reinforcing effects of 0.01 mg/kg/inj cocaine and 1 g banana-flavored food pellets were also determined under similar testing conditions. Finally, the nicotine demand function was re-determined after approximately 8 months of daily IV nicotine self-administration. IV nicotine self-administration followed an inverted U-shaped pattern, with the peak number of injections maintained by 0.0032 mg/kg/inj. Self-administration of each reinforcer (food pellets, IV cocaine, and IV nicotine) decreased as FR size increased. Application of the exponential model of demand showed that demand elasticity for nicotine was (1) dose-dependent and lowest for 0.0032 mg/kg/inj; (2) for 0.0032 mg/kg/inj, similar to that of food pellets and significantly higher than cocaine; and (3) decreased after 8 months of daily nicotine self-administration. These data show that, though high levels of nicotine self-administration can be achieved under simple FR schedules in nonhuman primates, its reinforcing effectiveness is dose-related but limited and may increase over time.

  6. Nucleus accumbens shell excitability is decreased by methamphetamine self-administration and increased by 5-HT2C receptor inverse agonism and agonism

    PubMed Central

    Graves, Steven M.; Clark, Mary J.; Traynor, John R.; Hu, Xiu-Ti; Napier, T. Celeste

    2014-01-01

    Methamphetamine profoundly increases brain monoamines and is a widely abused psychostimulant. The effects of methamphetamine self-administration on neuron function are not known for the nucleus accumbens, a brain region involved in addictive behaviors, including drug-seeking. One therapeutic target showing preclinical promise at attenuating psychostimulant-seeking is 5-HT2C receptors; however, the effects of 5-HT2C receptor ligands on neuronal physiology are unclear. 5-HT2C receptor agonism decreases psychostimulant-mediated behaviors, and the putative 5-HT2C receptor inverse agonist, SB 206553, attenuates methamphetamine-seeking in rats. To ascertain the effects of methamphetamine, and 5-HT2C receptor inverse agonism and agonism, on neuronal function in the nucleus accumbens, we evaluated methamphetamine, SB 206553, and the 5-HT2C receptor agonist and Ro 60-0175, on neuronal excitability within the accumbens shell subregion using whole-cell current-clamp recordings in forebrain slices ex vivo. We reveal that methamphetamine self-administration decreased generation of evoked action potentials. In contrast, SB 206553 and Ro 60-0175 increased evoked spiking, effects that were prevented by the 5-HT2C receptor antagonist, SB 242084. We also assessed signaling mechanisms engaged by 5-HT2C receptors, and determined that accumbal 5-HT2C receptors stimulated Gq, but not Gi/o. These findings demonstrate that methamphetamine-induced decreases in excitability of neurons within the nucleus accumbens shell were abrogated by both 5-HT2C inverse agonism and agonism, and this effect likely involved activation of Gq–mediated signaling pathways. PMID:25229719

  7. Metabolic syndrome is a significant and independent risk factor for increased arterial stiffness in Japanese subjects.

    PubMed

    Satoh, Hiroki; Kishi, Reiko; Tsutsui, Hiroyuki

    2009-12-01

    Metabolic syndrome (MetS) has been recognized as a risk factor for cardiovascular disease; however, the impact of MetS on arterial stiffness has not been fully established in the general Japanese population. We analyzed the relationship between MetS and the severity of arterial stiffness using brachial-ankle pulse wave velocity (baPWV) in 2744 male and 358 female subjects aged 38-62 years, adjusted for conventional risk factors and C-reactive protein. The prevalence rates of MetS identified by Japanese criteria were 22.7% (n=624) and 7.8% (n=28) in male and female subjects, respectively. The subjects with MetS had significantly greater mean values of baPWV than those without MetS among both male and female subjects (1444+/-209 vs. 1294+/-165 cm/s in male subjects, P<0.001; 1379+/-151 vs. 1220+/-171 cm/s in female subjects, P<0.001). After adjustment for atherosclerotic variables such as age, smoking habits, total cholesterol and C-reactive protein, the odds ratio (OR) of MetS for increased baPWV was 3.65 in male subjects (95% confidence interval (CI): 2.99-4.47, P<0.001) and 8.02 in female subjects (95% CI: 3.18-20.25 P<0.001). In conclusion, MetS was identified as a significant and independent risk factor for increased arterial stiffness in both the male and female general population in Japan.

  8. Contemplative Administration: Transforming the Workplace Culture of Higher Education

    ERIC Educational Resources Information Center

    Beer, Laura E.

    2010-01-01

    A contemplative approach to higher education is receiving increased attention and application in the classroom. Applying contemplative practices to administration, however, has received little attention in the literature. This case study offers a unique look at Naropa University and its implementation of contemplative administration. Findings…

  9. Ethanol self-administration and nicotine treatment increase brain levels of CYP2D in African green monkeys

    PubMed Central

    Miller, R T; Miksys, S; Hoffmann, E; Tyndale, R F

    2014-01-01

    BACKGROUND AND PURPOSE CYP2D6 metabolizes many centrally acting drugs, neurotoxins and endogenous neurochemicals, and differences in brain levels of CYP2D have been associated with brain function and drug response. Alcohol consumers and smokers have higher levels of CYP2D6 in brain, but not liver, suggesting ethanol and/or nicotine may induce human brain CYP2D6. We investigated the independent and combined effects of chronic ethanol self-administration and nicotine treatment on CYP2D expression in African green monkeys. EXPERIMENTAL APPROACH Forty monkeys were randomized into control, ethanol-only, nicotine-only and ethanol + nicotine groups. Two groups voluntarily self-administered 10% ethanol in sucrose solution for 4 h·day−1, whereas two groups consumed sucrose solution on the same schedule. Two groups received daily s.c. injections of 0.5 mg·kg−1 nicotine in saline bid, whereas two groups were injected with saline on the same schedule. KEY RESULTS Both nicotine and ethanol dose-dependently increased CYP2D in brain; brain mRNA was unaffected, and neither drug altered hepatic CYP2D protein or mRNA. The combination of ethanol and nicotine increased brain CYP2D protein levels to a greater extent than either drug alone (1.2–2.2-fold, P < 0.05 among the eight brain regions assessed). Immunohistochemistry revealed the induction of brain CYP2D protein within specific cell types and regions in the treatment groups. CONCLUSIONS AND IMPLICATIONS Ethanol and nicotine increase brain CYP2D protein levels in monkeys, in a region and treatment-specific manner, suggesting that CNS drug responses, neurodegeneration and personality may be affected among people who consume alcohol and/or nicotine. PMID:24611668

  10. Biochemical changes in the kidney and liver of rats following administration of ethanolic extract of Psidium guajava leaves.

    PubMed

    Adeyemi, O S; Akanji, M A

    2011-09-01

    Furtherance to a previous report on the anti-trypanosomal properties of Psidium guajava aqueous leaf extract in rats experimentally infected with Trypanosoma brucei brucei, we have evaluated the effects of the daily intraperitoneal administration of P. guajava leaf extract to rats on the activities of alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT) and acid phosphatase (ACP) in the kidney, liver and serum. The results obtained revealed that the administration of the extract produced significant increase in the serum activities of AST, ALT, ALP and ACP when compared with the control (p < 0.05). Also AST, ALT and ALP and ACP activities in the tissues of animals administered the extract revealed inconsistent changes (p < 0.05) relative to control. The increase in the serum activity of ALP may be an indicator that there was a likely compromise to the integrity of the plasma membrane as a result of the ethanolic extract administration. This could have caused leakages of the other enzymes investigated, which may explain the corresponding increases in the serum activities of AST, ALT and ACP observed.

  11. Physicians and administrators can work together.

    PubMed

    Fuller, G W; Beaupre, E M

    1979-10-01

    This article describes the working relationship between the administration and medical staff of the Mid-Maine Medical Center which is comprised of two separate modern hospitals. The authors advocate the philosophy that "a hospital which harnesses the medical staff's considerable talent and expertise through sound organizational input will be a stronger institution." They explain that patient care is becoming increasingly complex and that management decisions impact heavily on the care provided. In 1973, the Medical Center changed from its traditional organizational form of having a full-time medical director and an administrator report to the board of directors, to a modified corporate model designed to increase physician involvement. In the new organization, the vice president of finance and a part-time chief of staff (acting as vice president for medical affairs) report to the president (former medical director) who, in turn, is responsible to the board of trustees. The authors attribute the success of the reorganization to the CEO's willingness to delegate and share authority, not to the CEO's physician background. Planning at the institution involves a committee of six physicians, four administrators, and one full-time planner. A budgeting committee of three physicians and three administrators is responsible for the review of the budget as well as for making recommendations for the executive board for the expected volume of services. It is concluded that there is no perfect way to run a hospital, but the involvement of doctors in hospital decisions is necessary.

  12. Co-administration of dexamethasone increases severity and accelerates onset day of neutropenia in bladder cancer patients on methotrexate, vinblastine, adriamycin and cisplatin chemotherapy: a retrospective cohort study.

    PubMed

    Itai, Shingo; Suga, Yukio; Hara, Yusuke; Izumi, Kouji; Maeda, Yuji; Kitagawa, Yasuhide; Ishizaki, Junko; Shimada, Tsutomu; Mizokami, Atsushi; Sai, Yoshimichi

    2017-01-01

    Bladder cancer patients receiving methotrexate, vinblastine, adriamycin and cisplatin (MVAC) chemotherapy are co-administered with dexamethasone as an anti-emetic. We examined whether or not dexamethasone affects the severity and onset day of MVAC-induced severe neutropenia. This was a retrospective study of bladder cancer patients treated with MVAC chemotherapy with or without dexamethasone as an antiemetic at Kanazawa University Hospital during January 2005 - December 2009. Patients were categorized into three groups; no dexamethasone use (Dex (-)), dexamethasone on day 2 (Dex 1 day), and dexamethasone on days 2, 3 and 4 (Dex multiday). We evaluated the incidence of grade 3/4 neutropenia and the day of onset of first severe neutropenic episode during the first course of MVAC chemotherapy. Logistic regression was used to investigate whether co-administration of dexamethasone was a risk factor for severe neutropenia. Episodes of grade 3/4 neutropenia occurred in 3 out of 6 (50.0%), 11 out of 12 (91.7%) and 6 out of 6 (100%) patients in the Dex (-), Dex 1 day, and Dex multiday groups, respectively. The appearance day of first severe neutropenia in the Dex multiday group (13.2 ± 1.0) was significantly accelerated compared to the Dex (-) group (17.7 ± 2.1). Univariate logistic regression analysis revealed that dexamethasone is a risk factor for severe neutropenia (OR 17.0; 95%CI: 1.3-223.1). Co-administration of dexamethasone for anti-emesis brings forward the first appearance of neutropenia, and increases the severity of neutropenia, in bladder cancer patients receiving MVAC chemotherapy.

  13. Impact of chronic administration of anabolic androgenic steroids and taurine on blood pressure in rats

    PubMed Central

    Roşca, A.E.; Stoian, I.; Badiu, C.; Gaman, L.; Popescu, B.O.; Iosif, L.; Mirica, R.; Tivig, I.C.; Stancu, C.S.; Căruntu, C.; Voiculescu, S.E.; Zăgrean, L.

    2016-01-01

    Supraphysiological administration of anabolic androgenic steroids has been linked to increased blood pressure. The widely distributed amino acid taurine seems to be an effective depressor agent in drug-induced hypertension. The purpose of this study was to assess the impact of chronic high dose administration of nandrolone decanoate (DECA) and taurine on blood pressure in rats and to verify the potentially involved mechanisms. The study was conducted in 4 groups of 8 adult male Wistar rats, aged 14 weeks, treated for 12 weeks with: DECA (A group); vehicle (C group); taurine (T group), or with both drugs (AT group). Systolic blood pressure (SBP) was measured at the beginning of the study (SBP1), 2 (SBP2) and 3 months (SBP3) later. Plasma angiotensin-converting enzyme (ACE) activity and plasma end products of nitric oxide metabolism (NOx) were also determined. SBP3 and SBP2 were significantly increased compared to SBP1 only in the A group (P<0.002 for both). SBP2, SBP3 and ACE activity showed a statistically significant increase in the A vs C (P<0.005), andvs AT groups (P<0.05), while NOx was significantly decreased in the A and AT groups vs controls (P=0.01). ACE activity was strongly correlated with SBP3 in the A group (r=0.71, P=0.04). These findings suggest that oral supplementation of taurine may prevent the increase in SBP induced by DECA, an effect potentially mediated by angiotensin-converting enzyme. PMID:27254659

  14. Evaluation of knowledge and confidence following opioid overdose prevention training: A comparison of types of training participants and naloxone administration methods.

    PubMed

    Ashrafioun, Lisham; Gamble, Stephanie; Herrmann, Michele; Baciewicz, Gloria

    2016-01-01

    The purpose of the current study was to assess the effect of opioid overdose prevention training on participants' knowledge about opioid overdose and confidence to recognize and respond to opioid overdose situations as a function of naloxone administration (i.e., injection vs. intranasal spray) and participant type (friend/family, provider, "other"). Opioid overdose prevention trainings were offered throughout a mid-sized metropolitan area in the northeast. Participants (n = 428) were trained to administer naloxone via intramuscular injection (n = 154) or intranasal spray (n = 274). All training participants were given pre-post assessments of knowledge about opioid overdose and confidence to recognize and respond to opioid overdose situations. Participants' overall knowledge and confidence increased significantly from pre- to post-training (ps < .001). There was no significant association between knowledge and route of administration or participant type. Knowledge significantly increased from pre- to post-training in all participant types (ps < .001). Confidence improved significantly from pre- to post-training across both routes of administration (ps < .001). However, confidence was higher among those who were trained using the intranasal naloxone compared to those who were trained using the intramuscular injection naloxone at pre- (p = .011) and post-training (p < .001). Confidence increased from pre- to post-training in each of the participant types (ps < .001). Post-hoc tests revealed that confidence was higher among providers and friends/family members compared to "other" participants, such as first responders, only at post-training (p < .05). Opioid overdose trainings are effective in increasing knowledge and confidence related to opioid overdose situations. Findings suggest that trainees are more confident administering naloxone via intranasal spray compared to injection. Future research should attempt to identify other factors that may increase the

  15. Effect of acute and chronic MK-801 administration on extracellular glutamate and ascorbic acid release in the prefrontal cortex of freely moving mice on line with open-field behavior.

    PubMed

    Zuo, Dai-Ying; Zhang, Ya-Hong; Cao, Yue; Wu, Chun-Fu; Tanaka, Masatoshi; Wu, Ying-Liang

    2006-04-04

    The present study was designed to investigate the effects of acute and chronic administration of MK-801 (0.6 mg/kg), a noncompetitive NMDA-receptor antagonist on extracellular glutamate (Glu) and ascorbic acid (AA) release in the prefrontal cortex (PFC) of freely moving mice using in vivo microdialysis with open-field behavior. In line with earlier studies, acute administration of MK-801 induced an increase of Glu in the PFC. We also observed single MK-801 treatment increased AA release in the PFC. In addition, our results indicated that the basal AA levels in the PFC after MK-801 administration for 7 consecutive days were significantly decreased, and basal Glu levels also had a decreased tendency. After chronic administration (0.6 mg/kg, 7 days), MK-801 (0.6 mg/kg) challenge significantly decreased dialysate levels of AA and Glu. Our study also found that both acute and chronic administration of MK-801 induced hyperactivity in mice, but the intensity of acute administration was more than that of chronic administration. Furthermore, in all acute treatment mice, individual changes in Glu dialysate concentrations and the numbers of locomotion were positively correlated. In conclusion, this study may provide new evidence that a single MK-801 administration induces increases of dialysate AA and Glu concentrations in the PFC of freely moving mice, which are opposite to those induced by repeated MK-801 administration, with an unknown mechanism. Our results suggested that redox-response might play an important role in the model of schizophrenic symptoms induced by MK-801.

  16. Effects of caffeine on alcohol reinforcement: Beverage choice, self-administration, and subjective ratings

    PubMed Central

    Sweeney, Mary M.; Meredith, Steven E.; Evatt, Daniel P.; Griffiths, Roland R.

    2017-01-01

    Rationale Combining alcohol and caffeine is associated with increased alcohol consumption, but no prospective experimental studies have examined whether added caffeine increases alcohol consumption. Objectives This study examined how caffeine alters alcohol self-administration and subjective reinforcing effects in healthy adults. Methods Thirty-one participants completed six double-blind alcohol self-administration sessions: three sessions with alcohol only (e.g., Beverage A) and three sessions with alcohol and caffeine (e.g., Beverage B). Participants chose which beverage to consume on a subsequent session (e.g., Beverage A or B). Effects of caffeine on overall beverage choice, number of self-administered drinks, subjective ratings (e.g., Biphasic Alcohol Effects Scale), and psychomotor performance were examined. Results A majority of participants (65%) chose to drink the alcohol beverage containing caffeine on their final self-administration session. Caffeine did not increase the number of self-administered drinks. Caffeine significantly increased stimulant effects, decreased sedative effects, and attenuated decreases in psychomotor performance attributable to alcohol. Relative to nonchoosers, caffeine choosers reported overall lower stimulant ratings, and reported greater drinking behavior prior to the study. Conclusions Although caffeine did not increase the number of self-administered drinks, most participants chose the alcohol beverage containing caffeine. Given the differences in subjective ratings and pre-existing differences in self-reported alcohol consumption for caffeine choosers and nonchoosers, these data suggest decreased stimulant effects of alcohol and heavier self-reported drinking may predict subsequent choice of combined caffeine and alcohol beverages. These predictors may identify individuals who would benefit from efforts to reduce risk behaviors associated with combining alcohol and caffeine. PMID:28108773

  17. 5 CFR 9901.323 - Eligibility for general salary increase.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 5 Administrative Personnel 3 2010-01-01 2010-01-01 false Eligibility for general salary increase... NATIONAL SECURITY PERSONNEL SYSTEM (NSPS) Pay and Pay Administration Rate Ranges and General Salary Increases § 9901.323 Eligibility for general salary increase. (a) Employees with a current rating of record...

  18. The significance of task significance: Job performance effects, relational mechanisms, and boundary conditions.

    PubMed

    Grant, Adam M

    2008-01-01

    Does task significance increase job performance? Correlational designs and confounded manipulations have prevented researchers from assessing the causal impact of task significance on job performance. To address this gap, 3 field experiments examined the performance effects, relational mechanisms, and boundary conditions of task significance. In Experiment 1, fundraising callers who received a task significance intervention increased their levels of job performance relative to callers in 2 other conditions and to their own prior performance. In Experiment 2, task significance increased the job dedication and helping behavior of lifeguards, and these effects were mediated by increases in perceptions of social impact and social worth. In Experiment 3, conscientiousness and prosocial values moderated the effects of task significance on the performance of new fundraising callers. The results provide fresh insights into the effects, relational mechanisms, and boundary conditions of task significance, offering noteworthy implications for theory, research, and practice on job design, social information processing, and work motivation and performance. 2008 APA

  19. Administrative Training: What Really Prepares Administrators for the Job?

    ERIC Educational Resources Information Center

    Kraus, Christine M.

    This paper describes part of a study (Kraus 1996) involving 25 school administrators who attended one of five administrator preparation programs at four New England universities. The study addressed research questions regarding perceptions of administrators' job preparedness and how components of formal training programs (i.e., internships,…

  20. The Need for Administrative Know-How in Libraries *

    PubMed Central

    Simon, Beatrice V.

    1969-01-01

    The need for administrative know-how in libraries is great. Problems of administration in libraries do not differ significantly from those in other types of organizations. It behooves librarians to be aware of modern management theory, as developed and tested in the environment of business, and to adopt such useful tools as operations analysis and the systems approach to problems in the library environment. PMID:5778724

  1. Defibrotide in combination with granulocyte colony-stimulating factor significantly enhances the mobilization of primitive and committed peripheral blood progenitor cells in mice.

    PubMed

    Carlo-Stella, Carmelo; Di Nicola, Massimo; Magni, Michele; Longoni, Paolo; Milanesi, Marco; Stucchi, Claudio; Cleris, Loredana; Formelli, Franca; Gianni, Massimo A

    2002-11-01

    Defibrotide is a polydeoxyribonucleotide, which significantly reduces the expression of adhesion molecules on endothelial cells. We investigated the activity of Defibrotide alone or in combination with recombinant human granulocyte colony-stimulating factor (rhG-CSF) to mobilize peripheral blood progenitor cells (PBPCs) in BALB/c mice. A 5-day treatment with Defibrotide alone (1-15 mg/mouse/day) had no effect on WBC counts, frequencies and absolute numbers of total circulating colony-forming cells (CFCs), i.e., granulocyte-macrophage colony-forming units, erythroid burst-forming units, and multilineage colony-forming units. As compared with mock-injected mice, administration of rhG-CSF alone (5 micro g/mouse/day) for 5 days significantly (P < or = 0.0001) increased WBC counts, CFC frequencies, and CFC absolute numbers by 2-, 13-, and 27-fold, respectively. As compared with control mice, the combined administration of Defibrotide (15 mg/mouse/day) and rhG-CSF significantly (P < or = 0.0001) increased WBC counts, frequencies and absolute numbers of CFCs by 4-, 38-, and 119-fold, respectively. As compared with rhG-CSF alone, administration of Defibrotide plus rhG-CSF resulted in a significant increase (P < or = 0.001) of the frequency of circulating long-term culture-initiating cells. In addition, transplantation of 2 x 10(5) rhG-CSF- or Defibrotide/rhG-CSF-mobilized mononuclear cells rescued 43% and 71% of recipient mice, respectively. Experiments of CFC homing performed in lethally irradiated or nonirradiated recipients showed that marrow homing of transplanted PBPCs was reduced by 3-fold in Defibrotide-treated animals as compared with mock-injected mice (P < or = 0.001), suggesting that the mobilizing effect of Defibrotide might be because of an effect on PBPC trafficking. In conclusion, our data demonstrate that Defibrotide synergizes with rhG-CSF and significantly increases the mobilization of a broad spectrum of PBPCs, including primitive and committed

  2. Chapter 3 : from agency to administration.

    DOT National Transportation Integrated Search

    2008-01-01

    On March 3, 1961, NAJEEB HALABY [TERM: 03/03/61 : 07/01/65] became the second FAA Administrator. A : lawyer with significant experience as a military and civilian : pilot, and a Kennedy family friend, Halaby took over an agency : reputed, after :...

  3. Significant social events and increasing use of life-sustaining treatment: trend analysis using extracorporeal membrane oxygenation as an example.

    PubMed

    Chen, Yen-Yuan; Chen, Likwang; Huang, Tien-Shang; Ko, Wen-Je; Chu, Tzong-Shinn; Ni, Yen-Hsuan; Chang, Shan-Chwen

    2014-03-04

    Most studies have examined the outcomes of patients supported by extracorporeal membrane oxygenation as a life-sustaining treatment. It is unclear whether significant social events are associated with the use of life-sustaining treatment. This study aimed to compare the trend of extracorporeal membrane oxygenation use in Taiwan with that in the world, and to examine the influence of significant social events on the trend of extracorporeal membrane oxygenation use in Taiwan. Taiwan's extracorporeal membrane oxygenation uses from 2000 to 2009 were collected from National Health Insurance Research Dataset. The number of the worldwide extracorporeal membrane oxygenation cases was mainly estimated using Extracorporeal Life Support Registry Report International Summary July 2012. The trend of Taiwan's crude annual incidence rate of extracorporeal membrane oxygenation use was compared with that of the rest of the world. Each trend of extracorporeal membrane oxygenation use was examined using joinpoint regression. The measurement was the crude annual incidence rate of extracorporeal membrane oxygenation use. Each of the Taiwan's crude annual incidence rates was much higher than the worldwide one in the same year. Both the trends of Taiwan's and worldwide crude annual incidence rates have significantly increased since 2000. Joinpoint regression selected the model of the Taiwan's trend with one joinpoint in 2006 as the best-fitted model, implying that the significant social events in 2006 were significantly associated with the trend change of extracorporeal membrane oxygenation use following 2006. In addition, significantly social events highlighted by the media are more likely to be associated with the increase of extracorporeal membrane oxygenation use than being fully covered by National Health Insurance. Significant social events, such as a well-known person's successful extracorporeal membrane oxygenation use highlighted by the mass media, are associated with the use of

  4. Sublingual Nitroglycerin Administration in Coronary Computed Tomography Angiography: a Systematic Review.

    PubMed

    Takx, Richard A P; Suchá, Dominika; Park, Jakob; Leiner, Tim; Hoffmann, Udo

    2015-12-01

    To systematically investigate the literature for the influence of sublingual nitroglycerin administration on coronary diameter, the number of evaluable segments, image quality, heart rate and blood pressure, and diagnostic accuracy of coronary computed tomography (CT) angiography. A systematic search was performed in PubMed, EMBASE and Web of Science. The studies were evaluated for the effect of sublingual nitroglycerin on coronary artery diameter, evaluable segments, objective and subjective image quality, systemic physiological effects and diagnostic accuracy. Due to the heterogeneous reporting of outcome measures, a narrative synthesis was applied. Of the 217 studies identified, nine met the inclusion criteria: seven reported on the effect of nitroglycerin on coronary artery diameter, six on evaluable segments, four on image quality, five on systemic physiological effects and two on diagnostic accuracy. Sublingual nitroglycerin administration resulted in an improved evaluation of more coronary segments, in particular, in smaller coronary branches, better image quality and improved diagnostic accuracy. Side effects were mild and were alleviated without medical intervention. Sublingual nitroglycerin improves the coronary diameter, the number of assessable segments, image quality and diagnostic accuracy of coronary CT angiography without major side effects or systemic physiological changes. • Sublingual nitroglycerin administration results in significant coronary artery dilatation. • Nitroglycerin increases the number of evaluable coronary branches. • Image quality is improved the most in smaller coronary branches. • Nitroglycerin increases the diagnostic accuracy of coronary CT angiography. • Most side effects are mild and do not require medical intervention.

  5. The influence of timing of administration on the analgesic efficacy of parecoxib in orthopedic surgery

    PubMed Central

    Martinez, Valéria; Belbachir, Anissa; Jaber, Aithem; Cherif, Kamel; Jamal, Adel; Ozier, Yves; Sessler, Daniel I.; Chauvin, Marcel; Fletcher, Dominique

    2007-01-01

    Background Parecoxib, a selective cyclooxygenase-2 inhibitor, may reduce postoperative pain when administered before surgery without increasing bleeding. Methods We randomly assigned 62 patients scheduled for total hip arthroplasty to the following intravenous dosing schedule: 1) placebo at induction, at wound closure, and 12 hours after induction (control); 2) parecoxib 40 mg at induction, placebo at wound closure, and parecoxib 40 mg 12 hours after induction (pre); or, 3) placebo at induction, parecoxib 40 mg at wound closure, and parecoxib 40 mg 12 hours after induction (post). Pain scores at rest and with movement recorded every 4 hours for 24 hours using a visual analog scale. Treatment side effects were recorded every 4 hours. Red cell loss for 5 days after surgery was calculated. Results Postoperative pain scores were less in pre and post groups than in the control group. Postoperative bleeding was similar in the three groups. There were no significant differences between pre and post groups, nor was their any trend suggesting a pre-emptive analgesic efficacy from preincision administration of parecoxib. Morphine use in the Post Anesthesia Care Unit was reduced in the pre and post groups compared with the control group (14.2±2.0, and 15.7±2.0, versus 20.4±2.3 mg), although the trend was only significant (p < 0.05) in the pre group. The first pain score was also reduced in the pre and post groups compared to the control group (56.1±7.5 and 64.2 ± 7.0 versus 78.3±5), but this was also only significant for the pre group (p=0.001). The delay for first analgesic demand was increased for both the pre and post group compared to the control group (38±9 and 28.2 ± 6.6 versus 18±6 min), but again this was only significant for the pre group (P=0.05). Twenty-four hour consumption of morphine was similar in the pre (26±12 mg) and post groups (25±13 mg); both of which were significantly less than control group (47±27 mg, P<0.001). Conclusions Administration of

  6. Medication administration through enteral feeding tubes.

    PubMed

    Williams, Nancy Toedter

    2008-12-15

    An overview of enteral feeding tubes, drug administration techniques, considerations for dosage form selection, common drug interactions with enteral formulas, and methods to minimize tube occlusion is given. Enteral nutrition through a feeding tube is the preferred method of nutrition support in patients who have a functioning gastrointestinal tract but who are unable to be fed orally. This method of delivering nutrition is also commonly used for administering medications when patients cannot swallow safely. However, several issues must be considered with concurrent administration of oral medications and enteral formulas. Incorrect administration methods may result in clogged feeding tubes, decreased drug efficacy, increased adverse effects, or drug-formula incompatibilities. Various enteral feeding tubes are available and are typically classified by site of insertion and location of the distal tip of the feeding tube. Liquid medications, particularly elixirs and suspensions, are preferred for enteral administration; however, these formulations may be hypertonic or contain large amounts of sorbitol, and these properties increase the potential for adverse effects. Before solid dosage forms are administered through the feeding tube, it should be determined if the medications are suitable for manipulation, such as crushing a tablet or opening a capsule. Medications should not be added directly to the enteral formula, and feeding tubes should be properly flushed with water before and after each medication is administered. To minimize drug-nutrient interactions, special considerations should be taken when administering phenytoin, carbamazepine, warfarin, fluoroquinolones, and proton pump inhibitors via feeding tubes. Precautions should be implemented to prevent tube occlusions, and immediate intervention is required when blockages occur. Successful drug delivery through enteral feeding tubes requires consideration of the tube size and placement as well as careful

  7. Administrator Leadership Styles and Their Impact on School Nursing Part II. A High-Performance School Nurse-Building Administrator Relationship Model.

    PubMed

    Davis, Charles R; Lynch, Erik J

    2018-06-01

    There is a significant disparity in roles, responsibilities, education, training, and expertise between the school nurse and building administrator. Because of this disparity, a natural chasm must be bridged to optimize student health, safety, well-being, and achievement in the classroom while meeting the individual needs of both professionals. This article constructs and presents a new school nurse-building administrator relationship model, the foundation of which is formed from the pioneering and seminal work on high-performance professional relationships and outcomes of Lewin and Drucker. The authors posit that this new model provides the framework for successful school nurse-building administrator interactions that will lead to optimal student outcomes.

  8. Oral administration of heat-killed Lactobacillus gasseri OLL2809 reduces cedar pollen antigen-induced peritoneal eosinophilia in Mice.

    PubMed

    Sashihara, Toshihiro; Ikegami, Shuji; Sueki, Natsuko; Yamaji, Taketo; Kino, Kohsuke; Taketomo, Naoki; Gotoh, Minoru; Okubo, Kimihiro

    2008-12-01

    Lactobacillus gasseri OLL2809 strongly stimulates the production of interleukin (IL)-12 (p70) by innate immune cells. Thus, it is expected to ameliorate allergic diseases. We investigated whether the oral administration of heat-killed L. gasseri OLL2809 suppressed eosinophilia in cedar pollen antigen-challenged mice. BALB/c mice sensitized with Japanese cedar pollen extract were intraperitoneally challenged with the same extract. The mice were orally given heat-killed L. gasseri OLL2809 at doses of 0.5, 1, or 2mg/day throughout the experimental period (21 d). After 24 hours of the challenge, the eosinophil number and cytokine levels in the peritoneal lavage fluid and the serum antigen-specific IgG levels were determined. On administering varying amounts of heat-killed L. gasseri OLL2809, the number of eosinophils among the total number of cells was significantly reduced in all groups. In addition, the eosinophil number significantly decreased, and the eosinophil-suppression rate significantly increased by 44% in the 2-mg group. Although the serum immunoglobulin (Ig) G2a and IgG1 levels were not affected, the IgG2a/IgG1 ratio increased significantly in the 2-mg group compared with that of the control group. Furthermore, the administration of heat-killed L. gasseri OLL2809 resulted in the induction of IL-2 and reduction in granulocyte-macrophage colony-stimulating factor levels in peritoneal lavage fluid. We demonstrated that the oral administration of heat-killed L. gasseri OLL2809 suppresses eosinophilia via the modulation of Th1/Th2 balance. These observations suggested that heat-killed L. gasseri OLL2809 might potentially ameliorate the increased number of eosinophils in patients with Japanese cedar pollinosis.

  9. Administrative Woman and Administrative Man: Teaching Public Administration from a Gender Inclusive Perspective.

    ERIC Educational Resources Information Center

    Burnier, DeLysa

    1992-01-01

    Asserts that courses in public administration provide special challenges for feminist instructors because men and women do not always have the same career opportunities or experiences. Describes the content and teaching procedures of a Principles of Public Administration course designed to consider women's issues. (CFR)

  10. Administrative Synergy

    ERIC Educational Resources Information Center

    Hewitt, Kimberly Kappler; Weckstein, Daniel K.

    2012-01-01

    One of the biggest obstacles to overcome in creating and sustaining an administrative professional learning community (PLC) is time. Administrators are constantly deluged by the tyranny of the urgent. It is a Herculean task to carve out time for PLCs, but it is imperative to do so. In this article, the authors describe how an administrative PLC…

  11. Mutagenesis of a bacteriophage lytic enzyme PlyGBS significantly increases its antibacterial activity against group B streptococci.

    PubMed

    Cheng, Qi; Fischetti, Vincent A

    2007-04-01

    Group B streptococci (GBS) are the leading cause of neonatal meningitis and sepsis worldwide. Intrapartum antibiotic prophylaxis (IAP) is the current prevention strategy given to pregnant women with confirmed vaginal GBS colonization. Due to antibiotic resistance identified in GBS, we previously developed another strategy using a bacteriophage lytic enzyme, PlyGBS, to reduce vaginal GBS colonization. In this study, various DNA mutagenesis methods were explored to produce PlyGBS mutants with increased lytic activity against GBS. Several hyperactive mutants were identified that contain only the endopeptidase domain found in the N-terminal region of PlyGBS and represent only about one-third of the wild-type PlyGBS in length. Significantly, these mutants not only have 18-28-fold increases in specific activities compared to PlyGBS, but they also have a similar activity spectrum against several streptococcal species. One of the hyperactive mutants, PlyGBS90-1, reduced the GBS colonization from >5 logs of growth per mouse to <50 colony-forming units (cfu) 4 h post treatment ( approximately 4-log reduction) using a single dose in a mouse vaginal model. A reduction in GBS colonization before delivery should significantly reduce neonatal GBS infection providing a safe alternative to IAP.

  12. Financial Management in School Administration.

    ERIC Educational Resources Information Center

    Tronc, Keith, Ed.

    Because Australian school principals are being given increasing autonomy, knowledge of basic accounting principles and skill in elementary financial management are becoming more necessary. This book attempts to supply school administrators with information needed to handle new accounting duties and to lay a foundation for future fuller involvement…

  13. Modulation of gut microbiota and increase in fecal water content in mice induced by administration of Lactobacillus kefiranofaciens DN1.

    PubMed

    Jeong, Dana; Kim, Dong-Hyeon; Kang, Il-Byeong; Kim, Hyunsook; Song, Kwang-Young; Kim, Hong-Seok; Seo, Kun-Ho

    2017-02-22

    Lactobacillus kefiranofaciens is the key probiotic bacterium in kefir. In this study, we investigated the effects of oral consumption of L. kefiranofaciens on the fecal quality and intestinal microbiota of mice. Four-week-old Balb/c mice were divided into two groups (n = 8 each) and administered 0.2 mL of saline (control group) or saline containing 2 × 10 8 cfu L. kefiranofaciens DN1 (LKF_DN1 group) for two weeks. At the end of the experiment, their fecal samples were collected and the fecal quality and microbiota were assessed. The LKF_DN1 group exhibited higher total fecal weight and fecal weight per stool sample than the control group (p < 0.05). Interestingly, the fecal water content was significantly higher in the fecal samples of the LKF_DN1 group than in those of the control group (p < 0.05). The numbers of total bacteria, Firmicutes, Bacteroidetes, Lactobacillus, and Prevotella were significantly higher in the LKF_DN1 group than in the control group (p < 0.05). In contrast, the number of opportunistic pathogens, including Proteobacteria and Enterobacteriaceae, and the percentage of genus Clostridium among the total bacteria were significantly reduced in the LKF_DN1 group (p < 0.05). Our data suggest that regular L. kefiranofaciens DN1 administration could alleviate constipation and improve gut microbiota.

  14. A conceptual framework contributing to nursing administration and research.

    PubMed

    Biron, Alain D; Richer, Marie-Claire; Ezer, Hélène

    2007-03-01

    The health care system has undergone major changes in the last decade. With greater acuity and complexity of illness, the adoption of innovative technologies and the shortage of health care personnel, the coordination and integration of health care services has become increasingly demanding for administrators. Growing dissatisfaction and concerns about safety issues are being expressed by the users of care who need to navigate through an increasingly complex system and by health care personnel who feel less efficient within the organization. Nursing administrators have a responsibility to address these issues but there is little scientific evidence to guide their actions. There are also few comprehensive models highlighting the main components of nursing administration - models that could guide nursing administration research. This paper presents a conceptual framework for nursing administration and research that links patient health care needs, nursing resources and the nursing care processes to the context of the health care system, and the social, political and cultural environments of care. A selected review of the oncology and cancer care literature is presented to demonstrate how this framework can organize existing knowledge about these concepts in the context of cancer care.

  15. Administration of magnesium sulphate before rocuronium: effects on speed of onset and duration of neuromuscular block.

    PubMed

    Kussman, B; Shorten, G; Uppington, J; Comunale, M E

    1997-07-01

    The speeds of onset of pancuronium, atracurium and vecuronium are increased by prior administration of magnesium sulphate. A prospective, randomized, double-blind, controlled, clinical study was performed to examine the effects of prior i.v. administration of magnesium sulphate 60 mg kg-1 on the neuromuscular blocking effects of rocuronium 0.6 mg kg-1 during isoflurane anaesthesia. Neuromuscular function was measured electromyographically (Relaxograph) in 30 patients who received either magnesium sulphate 60 mg kg-1 or normal saline, 1-min before rocuronium 0.6 mg kg-1. Mean onset times were similar in the two groups (magnesium sulphate 71 (SD 20) s; normal saline 75 (23) s), but times to initial, 10% and 25% recovery from neuromuscular block were significantly longer in the magnesium sulphate group (42.1 (16.3), 49.0 (12.4) and 56.5 (13.2) min, respectively) than in the saline group (25.1 (9.1), 33.0 (11.1) and 35.6 (13.2) min, respectively) (P < 0.05 in all three cases). Administration of magnesium sulphate was not associated with adverse haemodynamic effects. Prior administration of magnesium sulphate, under the study conditions described, prolonged rocuronium-induced neuromuscular block but did not increase speed of onset.

  16. Increased Severe Trauma Patient Volume is Associated With Survival Benefit and Reduced Total Health Care Costs: A Retrospective Observational Study Using a Japanese Nationwide Administrative Database.

    PubMed

    Endo, Akira; Shiraishi, Atsushi; Fushimi, Kiyohide; Murata, Kiyoshi; Otomo, Yasuhiro

    2017-06-07

    The aim of this study was to evaluate the associations of severe trauma patient volume with survival benefit and health care costs. The effect of trauma patient volume on survival benefit is inconclusive, and reports on its effects on health care costs are scarce. We conducted a retrospective observational study, including trauma patients who were transferred to government-approved tertiary emergency hospitals, or hospitals with an intensive care unit that provided an equivalent quality of care, using a Japanese nationwide administrative database. We categorized hospitals according to their annual severe trauma patient volumes [1 to 50 (reference), 51 to 100, 101 to 150, 151 to 200, and ≥201]. We evaluated the associations of volume categories with in-hospital survival and total cost per admission using a mixed-effects model adjusting for patient severity and hospital characteristics. A total of 116,329 patients from 559 hospitals were analyzed. Significantly increased in-hospital survival rates were observed in the second, third, fourth, and highest volume categories compared with the reference category [94.2% in the highest volume category vs 88.8% in the reference category, adjusted odds ratio (95% confidence interval, 95% CI) = 1.75 (1.49-2.07)]. Furthermore, significantly lower costs (in US dollars) were observed in the second and fourth categories [mean (standard deviation) for fourth vs reference = $17,800 ($17,378) vs $20,540 ($32,412), adjusted difference (95% CI) = -$2559 (-$3896 to -$1221)]. Hospitals with high volumes of severe trauma patients were significantly associated with a survival benefit and lower total cost per admission.

  17. Learning mechanisms to limit medication administration errors.

    PubMed

    Drach-Zahavy, Anat; Pud, Dorit

    2010-04-01

    This paper is a report of a study conducted to identify and test the effectiveness of learning mechanisms applied by the nursing staff of hospital wards as a means of limiting medication administration errors. Since the influential report ;To Err Is Human', research has emphasized the role of team learning in reducing medication administration errors. Nevertheless, little is known about the mechanisms underlying team learning. Thirty-two hospital wards were randomly recruited. Data were collected during 2006 in Israel by a multi-method (observations, interviews and administrative data), multi-source (head nurses, bedside nurses) approach. Medication administration error was defined as any deviation from procedures, policies and/or best practices for medication administration, and was identified using semi-structured observations of nurses administering medication. Organizational learning was measured using semi-structured interviews with head nurses, and the previous year's reported medication administration errors were assessed using administrative data. The interview data revealed four learning mechanism patterns employed in an attempt to learn from medication administration errors: integrated, non-integrated, supervisory and patchy learning. Regression analysis results demonstrated that whereas the integrated pattern of learning mechanisms was associated with decreased errors, the non-integrated pattern was associated with increased errors. Supervisory and patchy learning mechanisms were not associated with errors. Superior learning mechanisms are those that represent the whole cycle of team learning, are enacted by nurses who administer medications to patients, and emphasize a system approach to data analysis instead of analysis of individual cases.

  18. Oral administration of L-arginine in patients with angina or following myocardial infarction may be protective by increasing plasma superoxide dismutase and total thiols with reduction in serum cholesterol and xanthine oxidase

    PubMed Central

    Tripathi, Pratima; Chandra, M

    2009-01-01

    Administration of L-arginine has been shown to control ischemic injury by producing nitric oxide which dilates the vessels and thus maintains proper blood flow to the myocardium. In the present study attempt has been made to determine whether oral administration of L-arginine has any effect on oxidant/antioxidant homeostasis in ischemic myocardial patients [represented by the patients of acute angina (AA) and acute myocardial infarction (MI)]. L-arginine has antioxidant and antiapoptotic properties, decreases endothelin-1 expression and improves endothelial function, thereby controlling oxidative injury caused during myocardial ischemic syndrome. Effect of L-arginine administration on the status of free radical scavenging enzymes, pro-oxidant enzyme and antioxidants viz. total thiols, carbonyl content and plasma ascorbic acid levels in the patients has been evaluated. We have observed that L-arginine administration (three grams per day for 15 days) resulted in increased activity of free radical scavenging enzyme superoxide dismutase (SOD) and increase in the levels of total thiols (T-SH) and ascorbic acid with concomitant decrease in lipid per-oxidation, carbonyl content, serum cholesterol and the activity of proxidant enzyme, xanthine oxidase (XO). These findings suggest that the supplementation of L-arginine along with regular therapy may be beneficial to the patients of ischemic myocardial syndromes. PMID:20716909

  19. Intestinal microbiota and oral administration of Enterococcus faecium associated with the growth performance of new-born piglets.

    PubMed

    Wang, Y B; Du, W; Fu, A K; Zhang, X P; Huang, Y; Lee, K H; Yu, K; Li, W F; Li, Y L

    2016-09-01

    The oral administration of Enterococcus faecium EF1 to new-born suckling and weaning piglets along with their growth performances and intestinal microbiota was investigated in this study. Twenty-four new-born piglets were initially divided into 2 groups. The probiotics group received 2 ml of 10% sterilised skimmed milk by oral gavage supplemented with 6×10(8) cfu/ml viable E. faecium EF1 at the first, the third and the fifth day after birth, while the control group received 2 ml of 10% sterilised skimmed milk without probiotics at the same time. Results showed that oral administration of E. faecium EF1 was associated with a remarkable increase on the body weight of piglets for both suckling and weaning periods, by 30.73% (P<0.01) and 320.84% (P<0.01), and also decreased the diarrhoea rate, by 43.21% (P<0.05) and 71.42% (P<0.05), respectively. In addition, 454-pyrosequencing analysis revealed that there was no significant difference in the intestinal microbial diversity of the suckling piglets between the two groups; nevertheless, when compared to the control group, the relative abundance of Firmicutes in the probiotics group was substantially augmented, while the relative abundance of Proteobacteria, Bacteroidetes and Fusobacteria diminished. However, results indicated that oral administration of E. faecium EF1 did not have any influence on the relative abundance of Firmicutes in weaning piglets rather than increasing the relative abundance of Bacteroidetes and decreasing the relative abundance of Proteobacteria. Furthermore, at the level of the Firmicutes phylum, the relative abundance of Lactobacillales in the probiotic group increased significantly. These findings suggest that oral administration of E. faecium EF1 to new-born piglets could improve the growth performance and intestinal microbiota of piglets for both suckling and weaning periods.

  20. Prevention of hypoxic brain oedema by the administration of vasopressin receptor antagonist OPC-31260.

    PubMed

    Molnár, Andor H; Varga, Csaba; Berkó, Anikó; Rojik, Imre; Párducz, Arpád; László, Ferenc; László, Ferenc A

    2008-01-01

    The numerous situations which can result in cerebral hypoxic damage occur in newborn infants and in the elderly. In research aimed at more effective therapeutic intervention in ischaemic disorders of the brain, the animal model used and the principles of the causal therapy should be better outlined. The effects of the non-peptide AVPR (V2) antagonist 5-dimethylamino-1-[4-(2-methylbenzoylamino) benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine hydrochloride (OPC-31260) on the cerebral oedema induced by general cerebral hypoxia were studied in rats. The general cerebral hypoxia was produced by bilateral common carotid ligation in Sprague-Dawley rats of the CFY strain. By 6h after the ligation, half of the rats had died, but the survival rate was significantly higher following OPC-31260 administration. Electron microscopic examinations revealed typical ischaemic changes after the carotid ligation, and OPC-31260 treatment did not significantly reduce the hypoxic signs in the brain cortex; only a certain decrease in the pericapillary oedema was observed. The carotid ligation increased the brain contents of water and Na(+) and enhanced the plasma AVP level. The increased brain water and Na(+) accumulation was prevented by OPC-31260 administration, but the plasma AVP level was further enhanced by OPC-31260. These results demonstrate the important role of AVP in the development of the disturbances in brain water and electrolyte balance in response to general cerebral hypoxia. The carotid ligation-induced cerebral oedema was significantly reduced following oral OPC-31260 administration. The protective mechanism exerted by OPC-31260 stems from its influence on the renal AVPR (V2). These observations might suggest an effective approach to the treatment of global hypoxia-induced cerebral oedema in humans.

  1. Correlation of ABO and Rh blood groups with transfusion administration and fever onset after hip surgery in children.

    PubMed

    Brdar, Radivoj; Petronic, Ivana; Nikolic, Dejan; Golubovic, Zoran; Bukva, Bojan; Radlovic, Vladimir; Abramovic, Dusan; Ducic, Sinisa; Colovic, Hristina

    2012-01-01

    Aim of our study was to evaluate distribution of ABO and Rh blood type groups in children after hip surgery regarding transfusion administration and fever presence. Four types of ABO blood groups (A; B; AB; O) and 2 types of Rh blood groups (Rh+; Rh-) were evaluated in group with administered transfusion (tr+) and without given transfusion (tr-); and in group with fever (fev+) and without fever (fev-), in 146 children after hip surgery. Tr+ and fev+ groups were divided into 3 groups (0-24h; 25-48h; 49-72h): for tr+ group (Group 1, Group 2, Group 3), and for fev+ group (Group A, Group B, Group C). AB blood group significantly decreased in Group 1 (χ2= 6.44; p<0.05) and A blood group in Group 3 in tr+ group (χ2= 7.68; p<0.01). O blood group significantly increased in Group 3 in tr+ group (χ2= 9.96; p<0.01). AB blood group significantly decreased in Groups B (χ2= 12.2; p<0.01) and C (χ2= 4.2; p<0.05) in fev+ versus fevgroup. B blood group significantly increased in Group C (χ2= 34.4; p<0.01) in fev+group. Administration of transfusion and fever onset in pediatric patients undergoing surgical correction of the hip is not influenced by the ABO and Rh blood groups system in humans. There is correlation between distribution of ABO blood groups with the time of transfusion administration and fever onset in children after hip surgery.

  2. Global Comparative Public Administration: Are Graduate Programs Responding to the Call?

    ERIC Educational Resources Information Center

    Manoharan, Aroon P.; Mirbel, Wendel; Carrizales, Tony J.

    2018-01-01

    Within the past two decades, globalization has led to increased literature on comparative public administration (CPA) research, and it has enhanced analyses of administrative systems in various societies. Our paper examines CPA education among Master of Public Administration and Master of Public Policy programs in the United States. The findings…

  3. The impact of high progesterone levels on the day of HCG administration in assisted human reproduction treatments.

    PubMed

    Tanada, Michelli S; Yoshida, Ivan H; Santos, Monise; Berton, Caroline Z; Souto, Elen; Carvalho, Waldemar P de; Cordts, Emerson B; Barbosa, Caio P

    2018-06-01

    Progesterone is a steroid hormone that acts on the endometrium. It is known for producing physical and mood-related side effects. Few studies have looked into how progesterone levels affect embryo development and quality. This study aimed to find a cutoff level for serum progesterone on the day of HCG administration from which embryo quality is impaired. The study included 145 cycles, from which 885 oocytes and 613 embryos were obtained. All patients had their serum progesterone levels measured on the day of HCG administration. Data sets were collected from patient medical records. The chi-square test was used to assess qualitative variables and the Mann-Whitney test to evaluate quantitative variables. Statistical analysis revealed that serum progesterone levels and reproductive variables were not significantly associated. In regards to oocyte maturity, however, when progesterone levels were greater than 1.3 ng/mL the probability of oocytes being immature increased by 12.7%. The fragmentation rate of embryos categorized as "top quality" in D3 increased proportionately to increases in progesterone levels (12.23%). High progesterone levels appeared to be correlated with increased embryo fragmentation rates, but high serum levels of the hormone on the day of HCG administration had no impact on reproductive variables and were not associated with impaired embryo development.

  4. Transparency and the Food and Drug Administration--a quantitative study.

    PubMed

    Lofstedt, Ragnar; Bouder, Frederic; Chakraborty, Sweta

    2013-01-01

    In Europe and North America, there is increasing political pressure being put on health regulatory agencies to become more transparent. To date, however, there has been little academic evaluation--let alone analysis--of these transparency initiatives from a risk communication perspective. This review examines whether the U.S. Food and Drug Administration's Adverse Event Reporting System quarterly signal postings, put in place after the passage of the Food and Drug Administration Amendments Act 2007, will assist patients and doctors in their decision-making processes, on the basis of results of a quantitative Internet survey of 433 physicians and 1,000 American adults. The results indicate that there is significant disagreement between physicians and the public about when medical safety issues should be communicated in the first place, with physicians opposed to early signal postings while the public in general is in favor. In addition the findings show that if the public were to find their drugs listed on the Adverse Event Reporting System signals web postings, more than a quarter would stop taking their medicine. Going forward, the Food and Drug Administration needs to work to a greater degree with social scientists in developing scientific-based communication strategies, rather than developing transparency initiatives on the basis of stakeholder consultations.

  5. 5 CFR 9701.344 - Special within-band increases.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 5 Administrative Personnel 3 2010-01-01 2010-01-01 false Special within-band increases. 9701.344 Section 9701.344 Administrative Personnel DEPARTMENT OF HOMELAND SECURITY HUMAN RESOURCES MANAGEMENT... HUMAN RESOURCES MANAGEMENT SYSTEM Pay and Pay Administration Performance-Based Pay § 9701.344 Special...

  6. Momordica charantia Administration Improves Insulin Secretion in Type 2 Diabetes Mellitus.

    PubMed

    Cortez-Navarrete, Marisol; Martínez-Abundis, Esperanza; Pérez-Rubio, Karina G; González-Ortiz, Manuel; Villar, Miriam Méndez-Del

    2018-02-12

    An improvement in parameters of glycemic control has been observed with Momordica charantia in patients with type 2 diabetes mellitus (T2DM). It is unknown whether this improvement is through a modification of insulin secretion, insulin sensitivity, or both. We hypothesized that M. charantia administration can improve insulin secretion and/or insulin sensitivity in patients with T2DM, without pharmacological treatment. The objective of the study was to evaluate the effect of M. charantia administration on insulin secretion and sensitivity. A randomized, double-blinded, placebo-controlled, clinical trial was carried out in 24 patients who received M. charantia (2000 mg/day) or placebo for 3 months. A 2-h oral glucose tolerance test (OGTT) was done before and after the intervention to calculate areas under the curve (AUC) of glucose and insulin, total insulin secretion (insulinogenic index), first phase of insulin secretion (Stumvoll index), and insulin sensitivity (Matsuda index). In the M. charantia group, there were significant decreases in weight, body mass index (BMI), fat percentage, waist circumference (WC), glycated hemoglobin A1c (A1C), 2-h glucose in OGTT, and AUC of glucose. A significant increase in insulin AUC (56,562 ± 36,078 vs. 65,256 ± 42,720 pmol/L/min, P = .043), in total insulin secretion (0.29 ± 0.18 vs. 0.41 ± 0.29, P = .028), and during the first phase of insulin secretion (557.8 ± 645.6 vs. 1135.7 ± 725.0, P = .043) was observed after M. charantia administration. Insulin sensitivity was not modified with any intervention. In conclusion, M. charantia administration reduced A1C, 2-h glucose, glucose AUC, weight, BMI, fat percentage, and WC, with an increment of insulin AUC, first phase and total insulin secretion.

  7. The impact of a closed-loop electronic prescribing and administration system on prescribing errors, administration errors and staff time: a before-and-after study.

    PubMed

    Franklin, Bryony Dean; O'Grady, Kara; Donyai, Parastou; Jacklin, Ann; Barber, Nick

    2007-08-01

    To assess the impact of a closed-loop electronic prescribing, automated dispensing, barcode patient identification and electronic medication administration record (EMAR) system on prescribing and administration errors, confirmation of patient identity before administration, and staff time. Before-and-after study in a surgical ward of a teaching hospital, involving patients and staff of that ward. Closed-loop electronic prescribing, automated dispensing, barcode patient identification and EMAR system. Percentage of new medication orders with a prescribing error, percentage of doses with medication administration errors (MAEs) and percentage given without checking patient identity. Time spent prescribing and providing a ward pharmacy service. Nursing time on medication tasks. Prescribing errors were identified in 3.8% of 2450 medication orders pre-intervention and 2.0% of 2353 orders afterwards (p<0.001; chi(2) test). MAEs occurred in 7.0% of 1473 non-intravenous doses pre-intervention and 4.3% of 1139 afterwards (p = 0.005; chi(2) test). Patient identity was not checked for 82.6% of 1344 doses pre-intervention and 18.9% of 1291 afterwards (p<0.001; chi(2) test). Medical staff required 15 s to prescribe a regular inpatient drug pre-intervention and 39 s afterwards (p = 0.03; t test). Time spent providing a ward pharmacy service increased from 68 min to 98 min each weekday (p = 0.001; t test); 22% of drug charts were unavailable pre-intervention. Time per drug administration round decreased from 50 min to 40 min (p = 0.006; t test); nursing time on medication tasks outside of drug rounds increased from 21.1% to 28.7% (p = 0.006; chi(2) test). A closed-loop electronic prescribing, dispensing and barcode patient identification system reduced prescribing errors and MAEs, and increased confirmation of patient identity before administration. Time spent on medication-related tasks increased.

  8. Templated assembly of photoswitches significantly increases the energy-storage capacity of solar thermal fuels.

    PubMed

    Kucharski, Timothy J; Ferralis, Nicola; Kolpak, Alexie M; Zheng, Jennie O; Nocera, Daniel G; Grossman, Jeffrey C

    2014-05-01

    Large-scale utilization of solar-energy resources will require considerable advances in energy-storage technologies to meet ever-increasing global energy demands. Other than liquid fuels, existing energy-storage materials do not provide the requisite combination of high energy density, high stability, easy handling, transportability and low cost. New hybrid solar thermal fuels, composed of photoswitchable molecules on rigid, low-mass nanostructures, transcend the physical limitations of molecular solar thermal fuels by introducing local sterically constrained environments in which interactions between chromophores can be tuned. We demonstrate this principle of a hybrid solar thermal fuel using azobenzene-functionalized carbon nanotubes. We show that, on composite bundling, the amount of energy stored per azobenzene more than doubles from 58 to 120 kJ mol(-1), and the material also maintains robust cyclability and stability. Our results demonstrate that solar thermal fuels composed of molecule-nanostructure hybrids can exhibit significantly enhanced energy-storage capabilities through the generation of template-enforced steric strain.

  9. [Vasovagal syncope and increased baroreceptor activity: evidence for increased sensibility of the baroreflex and its rapid reversal with acute administration of metoprolol].

    PubMed

    Pucciarelli, G; De Vecchis, R; Ebraio, F; Corigliano, G G

    1997-07-01

    In 17 patients suffering from recurrent episodes of vasovagal syncope as well as in 21 healthy subjects without clinical episodes of presyncope or syncope, we evaluated the reflex decrease in heart rate evoked by the phenilephrine test. In the syncopal patients, the measurements were taken 4-12 hours after the clinical appearance of syncope. We divided the syncopal patients as follows: 9 patients, undergoing pharmacological treatment, and 8 untreated patients (drug free arm). In the pharmacological arm of the study, an alternate, randomized administration of metoprolol (150 mg twice daily for 2 days) and verapamil (80 mg every 6 hours for 2 days) was provided. Therefore, in the pharmacological arm as well as in drug free patients, we tested again the baroreflex sensitivity, by means of iv phenilephrine bolus, 3 and 7 days after the clinical appearance of the syncopal event. The baroreflex sensitivity values were significantly higher in the syncopal group compared to the control group (21 +/- 5 vs 13 +/- 4.5 ms/mm Hg; p < 0.01). Of the two tested drugs, only the metoprolol produced a fast (day 3) decrease in baroreflex sensitivity. On the basis of measurements taken after 7 days, we noted a pattern of widespread reduction in baroreflex sensitivity values, found in both treated and untreated patients. In conclusion, patients with vasovagal syncope exhibited a more pronounced maximal parasympathetic activation compared to the control group. The high baroreflex sensitivity values were soon (day 3) reduced by metoprolol, but not by verapamil therapy; a spontaneous normalization in baroreflex sensitivity values was found 7 days after the clinical episode, regardless of therapy.

  10. Oral L-glutamine administration attenuated cutaneous wound healing in Wistar rats.

    PubMed

    Goswami, Saurabh; Kandhare, Amit; Zanwar, Anand A; Hegde, Mahabaleshwar V; Bodhankar, Subhash L; Shinde, Sudhir; Deshmukh, Shahaji; Kharat, Ravindran

    2016-02-01

    The objective of this study was to evaluate the wound healing potential of L-glutamine in laboratory rats using excision and incision wound models. Excision wounds of size 500 mm(2) and depth 2 mm were made on the dorsal portion of male Wistar rats (230-250 g) and were used for the study of oral L-glutamine (1 g/kg) treatment on the rate of contraction of wound and epithelisation. Histological evaluation of wound tissue was also performed. Six-centimetre-long two linear-paravertebral incisions in male Wistar rats (230-250 g) were used to study the effect of L-glutamine (1 g/kg, p.o.) treatment on tensile strength, total protein and hydroxyproline content in the incision model. Oral administration of L-glutamine (1 g/kg) significantly decreased wound area, epithelisation period and wound index, whereas the rate of wound contraction significantly increased (P < 0·001) when compared with vehicle control rats in the excision wound model. Tensile strength, hydroxyproline content and protein level were significantly increased (P < 0·001) in L-glutamine (1 g/kg, p.o.)-treated rats when compared with vehicle control rats in the incision wound model. Histological evaluation of wound tissue from L-glutamine (1 g/kg, p.o.)-treated rats showed complete epithelialisation with new blood vessel formation and high fibrous tissues in the excision wound model. In conclusion, oral administration of l-glutamine (1 g/kg) promotes wound healing by acting on various stages of wound healing such as collagen synthesis, wound contraction and epithelialisation. © 2014 The Authors. International Wound Journal © 2014 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

  11. Increased ethanol self-administration after a period of imposed ethanol deprivation in rats trained in a limited access paradigm.

    PubMed

    Heyser, C J; Schulteis, G; Koob, G F

    1997-08-01

    A predominant feature in human alcohol abuse is the reported desire or "craving" to consume ethanol along with frequent episodes of drinking after periods of abstinence. These and other factors may be responsible for relapse to uncontrolled ethanol drinking. When relapse occurs after a period of abstinence, ethanol drinking has been shown to be temporarily increased. Two aspects of drug dependence could contribute to these increases. One may be the development of a need state; the other may involve changes in the perception of the positive reinforcing effects of ethanol when reinforcer access is limited. To investigate this phenomenon further, the present study was conducted to examine in nondependent rats the effect of forced time-off on oral ethanol self-administration in a limited access paradigm (30 min/day). Male Wistar rats were trained to respond for ethanol (10% w/v) or water in a two-lever, free-choice condition using a saccharin fading procedure. After the establishment of stable baseline responding for ethanol, various ethanol deprivation periods (3, 5, 7, 14, or 28 days) were imposed, during which no ethanol was available. Responding for ethanol increased as a function of the duration of the deprivation period when compared with baseline levels. This increase was temporary and returned to baseline levels within 2 to 3 days. Given that the shortest time-off period was 5 days and the rats showed no signs of withdrawal, this transient increase in ethanol responding does not seem to be related to the manifestation of dependence and withdrawal, and may be related to changes in ethanol's reinforcement properties. These results with rats may provide a useful tool to elucidate mechanisms underlying human alcohol seeking behavior and relapse.

  12. Effects of Testosterone Administration on Strategic Gambling in Poker Play

    PubMed Central

    van Honk, Jack; Will, Geert-Jan; Terburg, David; Raub, Werner; Eisenegger, Christoph; Buskens, Vincent

    2016-01-01

    Testosterone has been associated with economically egoistic and materialistic behaviors, but -defensibly driven by reputable status seeking- also with economically fair, generous and cooperative behaviors. Problematically, social status and economic resources are inextricably intertwined in humans, thus testosterone’s primal motives are concealed. We critically addressed this issue by performing a placebo-controlled single-dose testosterone administration in young women, who played a game of bluff poker wherein concerns for status and resources collide. The profit-maximizing strategy in this game is to mislead the other players by bluffing randomly (independent of strength of the hand), thus also when holding very poor cards (cold bluffing). The profit-maximizing strategy also dictates the players in this poker game to never call the other players’ bluffs. For reputable-status seeking these materialistic strategies are disadvantageous; firstly, being caught cold bluffing damages one’s reputation by revealing deceptive intent, and secondly, not calling the other players’ bluffs signals submission in blindly tolerating deception. Here we show that testosterone administration in this game of bluff poker significantly reduces random bluffing, as well as cold bluffing, while significantly increasing calling. Our data suggest that testosterone in humans primarily motivates for reputable-status seeking, even when this elicits behaviors that are economically disadvantageous. PMID:26727636

  13. Effects of Testosterone Administration on Strategic Gambling in Poker Play.

    PubMed

    van Honk, Jack; Will, Geert-Jan; Terburg, David; Raub, Werner; Eisenegger, Christoph; Buskens, Vincent

    2016-01-04

    Testosterone has been associated with economically egoistic and materialistic behaviors, but -defensibly driven by reputable status seeking- also with economically fair, generous and cooperative behaviors. Problematically, social status and economic resources are inextricably intertwined in humans, thus testosterone's primal motives are concealed. We critically addressed this issue by performing a placebo-controlled single-dose testosterone administration in young women, who played a game of bluff poker wherein concerns for status and resources collide. The profit-maximizing strategy in this game is to mislead the other players by bluffing randomly (independent of strength of the hand), thus also when holding very poor cards (cold bluffing). The profit-maximizing strategy also dictates the players in this poker game to never call the other players' bluffs. For reputable-status seeking these materialistic strategies are disadvantageous; firstly, being caught cold bluffing damages one's reputation by revealing deceptive intent, and secondly, not calling the other players' bluffs signals submission in blindly tolerating deception. Here we show that testosterone administration in this game of bluff poker significantly reduces random bluffing, as well as cold bluffing, while significantly increasing calling. Our data suggest that testosterone in humans primarily motivates for reputable-status seeking, even when this elicits behaviors that are economically disadvantageous.

  14. Single oral administration of flavan 3-ols induces stress responses monitored with stress hormone elevations in the plasma and paraventricular nucleus.

    PubMed

    Fujii, Yasuyuki; Suzuki, Kenta; Hasegawa, Yahiro; Nanba, Fumio; Toda, Toshiya; Adachi, Takahiro; Taira, Shu; Osakabe, Naomi

    2018-06-11

    We previously confirmed that postprandial alterations in the circulation and metabolism after a single oral dose of flavan 3-ols (mixture of catechin and catechin oligomers) were involved in an increase in sympathetic nervous activity. However, it is well known that, in response to various stresses, activation of the hypothalamic-pituitary-adrenal (HPA) axis occurs together with sympathetic nerve activity, which is associated with activation of the sympathetic-adrenal-medullary (SAM) axis. In this study, we examined whether the HPA axis was activated after a single dose of flavan 3-ols. We administered an oral dose of 10 or 50 mg/kg flavan 3-ols to male ICR mice, removed the brains, and fixed them in paraformaldehyde-phosphate buffer. Other animals that were treated similarly were decapitated, and blood was collected. In the paraventricular nucleus (PVN), c-fos mRNA expression increased significantly at 15 min after administration of either 10 or 50 mg/kg flavan 3-ols. Corticotropin-releasing hormone (CRH) mRNA expression levels significantly increased at 240 min after administration of 10 mg/kg flavan 3-ols, and at 60 min after administration of 50 mg/kg flavan 3-ols. Plasma corticosterone levels were also significantly increased at 240 min after ingestion of 50 mg/kg flavan 3-ols. In this experiment, we confirmed that the ingestion of flavan 3-ols acted as a stressor in mammals with activation both the SAM and HPA axes. Copyright © 2018 Elsevier B.V. All rights reserved.

  15. Emerging Characteristics of Women Administrators in Texas Community/Junior Colleges.

    ERIC Educational Resources Information Center

    Durnovo, Maya

    A study was conducted to examine the characteristics of women administrators in Texas public community colleges. Specifically, the study examined what positions women administrators occupied at what institutions; their educational, professional, and personal background; career mobility issues; the significance of mentoring; the differences among…

  16. The Effect of Using Item Parameters Calibrated from Paper Administrations in Computer Adaptive Test Administrations

    ERIC Educational Resources Information Center

    Pommerich, Mary

    2007-01-01

    Computer administered tests are becoming increasingly prevalent as computer technology becomes more readily available on a large scale. For testing programs that utilize both computer and paper administrations, mode effects are problematic in that they can result in examinee scores that are artificially inflated or deflated. As such, researchers…

  17. Increased presynaptic regulation of dopamine neurotransmission in the nucleus accumbens core following chronic ethanol self-administration in female macaques

    PubMed Central

    Siciliano, Cody A.; Calipari, Erin S.; Yorgason, Jordan T.; Lovinger, David M.; Mateo, Yolanda; Jimenez, Vanessa A.; Helms, Christa M.; Grant, Kathleen A.; Jones, Sara R.

    2016-01-01

    Rationale Hypofunction of striatal dopamine neurotransmission, or hypodopaminergia, is a consequence of excessive ethanol use, and is hypothesized to be a critical component of alcoholism, driving alcohol intake in an attempt to restore dopamine levels; however, the neurochemical mechanisms involved in these dopaminergic deficiencies are unknown. Objective Here we examined the specific dopaminergic adaptations that produce hypodopaminergia and contribute to alcohol use disorders using direct, sub-second measurements of dopamine signaling in nonhuman primates following chronic ethanol self-administration. Methods Female rhesus macaques completed one year of daily (22 hr/day) ethanol self-administration. Subsequently, fast-scan cyclic voltammetry was used in nucleus accumbens core brain slices to determine alterations in dopamine terminal function, including release and uptake kinetics, and sensitivity to quinpirole (D2/D3 dopamine receptor agonist) and U50,488 (kappa-opioid receptor agonist) induced inhibition of dopamine release. Results Ethanol drinking greatly increased uptake rates, which were positively correlated with lifetime ethanol intake. Furthermore, the sensitivity of dopamine D2/D3 autoreceptors and kappa-opioid receptors, which both act as negative regulators of presynaptic dopamine release, were moderately and robustly enhanced in ethanol drinkers. Conclusions Greater uptake rates and sensitivity to D2-type autoreceptor and kappa-opioid receptor agonists could converge to drive a hypodopaminergic state, characterized by reduced basal dopamine and an inability to mount appropriate dopaminergic responses to salient stimuli. Together, we outline the specific alterations to dopamine signaling that may drive ethanol-induced hypofunction of the dopamine system, and suggest that the dopamine and dynorphin/kappa-opioid receptor systems may be efficacious pharmcotherapeutic targets in the treatment of alcohol use disorders. PMID:26892380

  18. Increased presynaptic regulation of dopamine neurotransmission in the nucleus accumbens core following chronic ethanol self-administration in female macaques.

    PubMed

    Siciliano, Cody A; Calipari, Erin S; Yorgason, Jordan T; Lovinger, David M; Mateo, Yolanda; Jimenez, Vanessa A; Helms, Christa M; Grant, Kathleen A; Jones, Sara R

    2016-04-01

    Hypofunction of striatal dopamine neurotransmission, or hypodopaminergia, is a consequence of excessive ethanol use and is hypothesized to be a critical component of alcoholism, driving alcohol intake in an attempt to restore dopamine levels; however, the neurochemical mechanisms involved in these dopaminergic deficiencies are not fully understood. Here we examined the specific dopaminergic adaptations that produce hypodopaminergia and contribute to alcohol use disorders using direct, sub-second measurements of dopamine signaling in nonhuman primates following chronic ethanol self-administration. Female rhesus macaques completed 1 year of daily (22 h/day) ethanol self-administration. Subsequently, fast-scan cyclic voltammetry was used in nucleus accumbens core brain slices to determine alterations in dopamine terminal function, including release and uptake kinetics, and sensitivity to quinpirole (D2/D3 dopamine receptor agonist) and U50,488 (kappa opioid receptor agonist) induced inhibition of dopamine release. Ethanol drinking greatly increased uptake rates, which were positively correlated with lifetime ethanol intake. Furthermore, the sensitivity of dopamine D2/D3 autoreceptors and kappa opioid receptors, which both act as negative regulators of presynaptic dopamine release, was moderately and robustly enhanced in ethanol drinkers. Greater uptake rates and sensitivity to D2-type autoreceptor and kappa opioid receptor agonists could converge to drive a hypodopaminergic state, characterized by reduced basal dopamine and an inability to mount appropriate dopaminergic responses to salient stimuli. Together, we outline the specific alterations to dopamine signaling that may drive ethanol-induced hypofunction of the dopamine system and suggest that the dopamine and dynorphin/kappa opioid receptor systems may be efficacious pharmacotherapeutic targets in the treatment of alcohol use disorders.

  19. Pre-electroconvulsive shock administration of calcium channel blockers reduces retrograde amnesia induced by ECS.

    PubMed

    Sushma, M; Sudha, S; Guido, S

    2004-11-01

    Effect of pre-electroconvulsive shock (ECS) administration of calcium channel blockers (CCBs) like verapamil, diltiazem, nifedipine, nimodipine, flunarizine and cinnarizine on retrograde amnesia induced by ECS was examined using passive avoidance paradigm in rats. The groups (Gr 1-7) of adult, male Wistar rats received true ECS with CCBs (5mg/kg; i.p) or vehicle (10 ml/kg; ip) and other groups (Gr 8-14) received sham ECS with CCBs (5mg/kg; i.p) or vehicle (10 ml/kg; i.p). The anti-amnestic activity of CCBs were evaluated using the passive avoidance paradigm in rats. Results showed that, the baseline latencies for all the groups did not differ significantly. Rats receiving true ECS produced significantly lower latencies. There was increase in the post ECS step through latencies of the rats administered CCBs before ECS. Therefore, pre-ECS administration of calcium channel blockers might reduce retrograde amnesia produced by ECS without altering seizure duration.

  20. Software Solutions for Better Administration.

    ERIC Educational Resources Information Center

    Kazanjian, Edward

    1997-01-01

    The CO/OP (founded in 1973 as the Massachusetts Association of School Business Officials Cooperative Corporation) has created and produced administrative software for schools. Describes two areas in which software can increase revenue and provide protection for personnel: (1) invoice/accounts receivable for the rental of school space; and (2) an…