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

Social stimuli enhance phencyclidine (PCP) self-administration in rhesus monkeys

PubMed Central

Newman, Jennifer L.; Perry, Jennifer L.; Carroll, Marilyn E.

2007-01-01

Environmental factors, including social interaction, can alter the effects of drugs of abuse on behavior. The present study was conducted to examine the effects of social stimuli on oral phencyclidine (PCP) self-administration by rhesus monkeys. Ten adult rhesus monkeys (M. mulatta) were housed side by side in modular cages that could be configured to provide visual, auditory, and olfactory stimuli provided by another monkey located in the other side of the paired unit. During the first experiment, monkeys self-administered PCP (0.25 mg/ml) and water under concurrent fixed ratio (FR) 16 schedules of reinforcement with either a solid or a grid (social) partition separating each pair of monkeys. In the second experiment, a PCP concentration-response relationship was determined under concurrent progressive ratio (PR) schedules of reinforcement under the solid and grid partition conditions. Under the concurrent FR 16 schedules, PCP and water self-administration was significantly higher during exposure to a cage mate through a grid partition than when a solid partition separated the monkeys. The relative reinforcing strength of PCP, as measured by PR break points, was greater during the grid partition condition compared to the solid partition condition indicated by an upward shift in the concentration-response curve. To determine whether the social stimuli provided by another monkey led to activation of the hypothalamic-pituitary-adrenal (HPA) axis, which may have evoked the increase of PCP self-administration during the grid partition condition, a third experiment was conducted to examine cortisol levels under the two housing conditions. A modest, but nonsignificant increase in cortisol levels was found upon switching from the solid to the grid partition condition. The results suggest that social stimulation among monkeys in adjoining cages leads to enhanced reinforcing strength of PCP. PMID:17560636

Glucose administration prior to a divided attention task improves tracking performance but not word recognition: evidence against differential memory enhancement?

PubMed

Scholey, Andrew B; Sünram-Lea, Sandra I; Greer, Joanna; Elliott, Jade; Kennedy, David O

2009-01-01

The cognition-enhancing effects of glucose administration to humans have been well-documented; however, it remains unclear whether this effect preferentially targets episodic memory or other cognitive domains. The effect of glucose on the allocation of attentional resources during memory encoding was assessed using a sensitive dual-attention paradigm. One hundred and twenty volunteers (mean age 21.60, SD 4.89, 77 females) took part in this randomised, double-blind, placebo-controlled, parallel groups study where each consumed a 25-g glucose drink or a placebo. Half of the participants in each drink condition attempted to track a moving on-screen target during auditory word presentation. The distance between the cursor and the tracking target was used as an index of attentional cost during encoding. Effects of drink and tracking on recognition memory and drink on tracking performance were assessed. Self-rated appetite and mood were co-monitored. Co-performing the tracking task significantly impaired memory performance irrespective of drink condition. In the placebo-tracking condition, there was a cost to tracking manifest as greater deviation from target during and immediately following word presentation. Compared with placebo, the glucose drink significantly improved tracking performance during encoding. There were significant time-related changes in thirst and alertness ratings but these were not differentially affected by drink or tracking conditions. Tracking but not memory was enhanced by glucose. This finding suggests that, under certain task conditions, glucose administrations does not preferentially enhance memory performance. One mechanism through which glucose acts as a cognition enhancer is through allowing greater allocation of attentional resources.

Systemic Administration of Interleukin 2 Enhances the Therapeutic Efficacy of Dendritic Cell-Based Tumor Vaccines

NASA Astrophysics Data System (ADS)

Shimizu, K.; Fields, R. C.; Giedlin, M.; Mule, J. J.

1999-03-01

We have reported previously that murine bone marrow-derived dendritic cells (DC) pulsed with whole tumor lysates can mediate potent antitumor immune responses both in vitro and in vivo. Because successful therapy was dependent on host immune T cells, we have now evaluated whether the systemic administration of the T cell stimulatory/growth promoting cytokine interleukin-2 (IL-2) could enhance tumor lysate-pulsed DC-based immunizations to further promote protective immunity toward, and therapeutic rejection of, syngeneic murine tumors. In three separate approaches using a weakly immunogenic sarcoma (MCA-207), the systemic administration of non-toxic doses of recombinant IL-2 (20,000 and 40,000 IU/dose) was capable of mediating significant increases in the potency of DC-based immunizations. IL-2 could augment the efficacy of tumor lysate-pulsed DC to induce protective immunity to lethal tumor challenge as well as enhance splenic cytotoxic T lymphocyte activity and interferon-γ production in these treated mice. Moreover, treatment with the combination of tumor lysate-pulsed DC and IL-2 could also mediate regressions of established pulmonary 3-day micrometastases and 7-day macrometastases as well as established 14- and 28-day s.c. tumors, leading to either significant cure rates or prolongation in overall survival. Collectively, these findings show that nontoxic doses of recombinant IL-2 can potentiate the antitumor effects of tumor lysate-pulsed DC in vivo and provide preclinical rationale for the use of IL-2 in DC-based vaccine strategies in patients with advanced cancer.

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.

Enhancing topical analgesic administration: review and prospect for transdermal and transbuccal drug delivery systems.

PubMed

Sanz, Roser; Calpena, Ana C; Mallandrich, Mireia; Clares, Beatriz

2015-01-01

Topical administration is an appealing method for drug delivery due to its non-invasiveness, self-controlled application, avoidance of first-pass metabolism in the liver and reduction of systemic side effects compared to other conventional routes such as oral and parenteral. However, topical administration must overcome the permeable barriers that skin and mucosa represent for the drug to achieve its desired therapeutic effect. Penetration of drugs through human skin is mainly impaired by the stratum corneum- the uppermost keratinized skin layer. In contrast, the stratified squamous epithelium (a nonkeratinized tissue) represents the major physical barrier for transbuccal drug administration in humans. Different technologies have been studied to enhance the bioavailability or local effects of drugs administered through skin and buccal mucosa. Those technologies involve the use of physical or chemical enhancers and new dosage forms such as vesicles, cyclodextrins, nanoparticles and other complex systems. Combinations of these technologies may further increase drug delivery in some cases. As analgesia is one of the main therapeutic effects sought through topical administration, this paper focuses on the review of drug delivery systems to improve the topical and transdermal/transbuccal drug delivery of substances with known analgesic action. A discussion of their possibilities and limitations is also included.

Previous Exposure to Δ9-Tetrahydrocannibinol Enhances Locomotor Responding to but Not Self-Administration of AmphetamineS⃞

PubMed Central

Cortright, James J.; Lorrain, Daniel S.; Beeler, Jeff A.; Tang, Wei-Jen

2011-01-01

Previous exposure to amphetamine leads to enhanced locomotor and nucleus accumbens (NAcc) dopamine (DA) responding to the drug as well as enhanced amphetamine self-administration. Here, we investigated the effects of exposure to Δ9-tetrahydrocannibinol (Δ9-THC) on behavioral and biochemical responding to amphetamine. Rats in different groups received five exposure injections of vehicle or one of five doses of Δ9-THC (0.4, 0.75, 1.5, 3.0, and 6.0 mg/kg i.p.) and were tested 2 days and 2 weeks later. Exposure to all but the lowest and highest doses of Δ9-THC enhanced the locomotor response to amphetamine (0.75 mg/kg i.p.), but all failed to enhance NAcc DA overflow in response to the drug. Moreover, exposure to 3.0 mg/kg i.p. Δ9-THC increased forskolin-evoked adenylyl cyclase activity in the NAcc and rats' locomotor response to the direct DA receptor agonist apomorphine (1.0 mg/kg s.c.), suggesting that Δ9-THC sensitized locomotor responding to amphetamine by up-regulating postsynaptic DA receptor signaling in the NAcc. Finally, amphetamine self-administration (200 μg/kg/infusion i.v.) was enhanced in amphetamine (5 × 1.5 mg/kg i.p.)-exposed rats, but not in rats exposed to Δ9-THC (5 × 3.0 mg/kg i.p.). Previous exposure to this dose of Δ9-THC modestly increased apomorphine SA (0.5 mg/kg/infusion i.v.). Thus, unlike amphetamine exposure, exposure to Δ9-THC does not enhance the subsequent NAcc DA response to amphetamine or promote amphetamine self-administration. Although Δ9-THC leads to alterations in postsynaptic DA receptor signaling in the NAcc and these can affect the generation of locomotion, these neuroadaptations do not seem to be linked to the expression of enhanced amphetamine self-administration. PMID:21389094

Enhanced Systemic Bioavailability of Curcumin Through Transmucosal Administration of a Novel Microgranular Formulation.

PubMed

Latimer, Brian; Ekshyyan, Oleksandr; Nathan, Neil; Moore-Medlin, Tara; Rong, Xiaohua; Ma, Xiaohui; Khandelwal, Alok; Christy, Hunter T; Abreo, Fleurette; McClure, Gloria; Vanchiere, John A; Caldito, Gloria; Dugas, Tammy; McMartin, Kenneth; Lian, Timothy; Mehta, Vikas; Nathan, Cherie-Ann O

2015-12-01

Curcumin is a promising nutraceutical for chemoprevention of head and neck squamous cell carcinoma (HNSCC). Capsular formulations of curcumin demonstrate low systemic bioavailability. We aimed to determine if curcumin levels were higher in healthy volunteers and cancer patients with microgranular curcumin that allows for transmucosal absorption and identify a consistent biomarker. Eight healthy volunteers and 15 HNSCC patients completed the trials. Serum levels of curcumin were measured by HPLC. Biological activity of curcumin was assessed with Multiplex Immunoassay and immunohistochemistry. We achieved higher serum levels of curcumin compared to trials using capsular formulation. In cancer patients a significant decrease in expression of fibroblast growth factor-2 (FGF-2) in post-biopsy samples and decreased serum levels of FGF-2, granulocyte macrophage colony-stimulating factor (GM-CSF) and interleukin-17 (IL-17) (p<0.05) was observed. Transmucosal administration of microgranular curcumin leads to enhanced curcumin bioavailability that is associated with significant biological effects. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

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.

Oral administration of arginine enhances the growth hormone response to growth hormone releasing hormone in short children.

PubMed

Loche, S; Carta, D; Muntoni, A C; Corda, R; Pintor, C

1993-10-01

We have evaluated the effect of oral administration of arginine chlorhydrate on the growth hormone response to growth hormone releasing hormone in a group of nine short prepubertal children (six boys and four girls). Arginine chlorhydrate 10 g, administered orally 60 min before an i.v. bolus injection of growth hormone releasing hormone 1-29, 1 microgram/kg, significantly enhanced the growth hormone response to the neuropeptide, confirming the results of previous studies which used the i.v. route. Furthermore, our data strengthen the view that the effects of arginine chlorhydrate on growth hormone secretion are mediated by inhibition of endogenous somatostatin release.

Oxytocin administration enhances controlled social cognition in patients with schizophrenia

PubMed Central

Woolley, J.D.; Chuang, B.; Lam, O.; Lai, W.; O’Donovan, A.; Rankin, K.P.; Mathalon, D.H.; Vinogradov, S.

2014-01-01

Summary Background Individuals with schizophrenia have functionally significant deficits in automatic and controlled social cognition, but no currently available pharmacologic treatments reduce these deficits. The neuropeptide oxytocin has multiple prosocial effects when administered intranasally in humans and there is growing interest in its therapeutic potential in schizophrenia. Methods We administered 40 IU of oxytocin and saline placebo intranasally to 29 male subjects with schizophrenia and 31 age-matched, healthy controls in a randomized, double-blind, placebo-controlled, cross-over study. Social cognition was assessed with The Awareness of Social Inference Test (TASIT) and the Reading the Mind in the Eyes Test (RMET). We examined the effects of oxytocin administration on automatic social cognition (the ability to rapidly interpret and understand emotional cues from the voice, face, and body); controlled social cognition (the ability to comprehend indirectly expressed emotions, thoughts, and intentions through complex deliberations over longer time periods); and a control task (the ability to comprehend truthful dialog and perform general task procedures) in individuals with and without schizophrenia using mixed factorial analysis of variance models. Results Patients with schizophrenia showed significant impairments in automatic and controlled social cognition compared to healthy controls, and administration of oxytocin significantly improved their controlled, but not automatic, social cognition, F(1, 58) = 8.75; p = 0.004. Conversely, oxytocin administration had limited effects on social cognition in healthy participants. Patients and controls performed equally well and there were no effects of oxytocin administration on the control task. Discussion Intact social cognitive abilities are associated with better functional outcomes in individuals with schizophrenia. Our data highlight the potentially complex effects of oxytocin on some but not all aspects of

Glucose Administration Enhances fMRI Brain Activation and Connectivity Related to Episodic Memory Encoding for Neutral and Emotional Stimuli

ERIC Educational Resources Information Center

Parent, Marise B.; Krebs-Kraft, Desiree L.; Ryan, John P.; Wilson, Jennifer S.; Harenski, Carla; Hamann, Stephan

2011-01-01

Glucose enhances memory in a variety of species. In humans, glucose administration enhances episodic memory encoding, although little is known regarding the neural mechanisms underlying these effects. Here we examined whether elevating blood glucose would enhance functional MRI (fMRI) activation and connectivity in brain regions associated with…

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

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.

Delayed Enhancement of Ascites After IV Contrast Material Administration at CT: Time Course and Clinical Correlation

PubMed Central

Benedetti, Nancy; Aslam, Rizwan; Wang, Zhen J.; Joe, Bonnie N.; Fu, Yanjun; Yee, Judy; Yeh, Benjamin M.

2010-01-01

OBJECTIVE The objective of our study was to determine the prevalence and clinical predictors of delayed contrast enhancement of ascites. MATERIALS AND METHODS In this retrospective study, 132 consecutive patients with ascites who underwent repeated abdominopelvic CT examinations performed within 7 days of each other were identified. These patients included 112 patients who received and 20 who did not receive IV contrast material at the initial CT examination. For each examination, we recorded the CT attenuation of the ascites. For the follow-up scan, the presence of delayed enhancement of ascites was defined as an increase in CT attenuation > 10 HU over baseline. The Fisher’s exact test, unpaired Student’s t test, and logistic regression were used to determine predictors of delayed enhancement of ascites. RESULTS A threshold increase in the attenuation of ascites by > 10 HU or more between the initial and follow-up CT examinations occurred only when IV contrast material was given with the initial examination. The increased attenuation was due to delayed contrast enhancement of ascites and occurred in 15 of the 112 patients (13%). Of the 16 patients scanned less than 1 day apart, 10 (63%) showed delayed enhancement of ascites. Delayed enhancement was not observed 3 or more days after IV contrast material administration. For each 1 mg/dL increase in serum creatinine level, the likelihood of delayed enhancement of ascites increased (odds ratio, 2.02; 95% CI, 1.11–3.69). Multivariate logistic regression showed that a short time interval between examinations (p < 0.001), increased serum creatinine level (p < 0.001), and presence of loculated ascites (p = < 0.01) were independent predictors of the magnitude of delayed enhancement of ascites. CONCLUSION Delayed contrast enhancement of ascites occurs commonly after recent prior IV contrast material administration and should not be mistaken for hemoperitoneum or proteinaceous fluid such as pus. PMID:19696286

Enhanced actions of insulin-like growth factor-I and interferon-alpha co-administration in experimental cirrhosis.

PubMed

Tutau, Federico; Rodríguez-Ortigosa, Carlos; Puche, Juan Enrique; Juanarena, Nerea; Monreal, Iñigo; García Fernández, María; Clavijo, Encarna; Castilla, Alberto; Castilla-Cortázar, Inma

2009-01-01

Cirrhosis is a diffuse process of hepatic fibrosis and regenerative nodule formation. The liver is the major source of circulating insulin-like growth factor-I (IGF-I) whose plasma levels are diminished in cirrhosis. IGF-I supplementation has been shown to induce beneficial effects in cirrhosis, including antifibrogenic and hepatoprotective effects. On other hand, interferon-alpha (IFN-alpha) therapy seems to suppress the progression of hepatic fibrosis. The aim of this study was to investigate the effect of the co-administration of IGF-I+IFN-alpha to Wistar rats with CCl(4)-induced cirrhosis, exploring liver function tests, hepatic lipid peroxidation and histopathology. The mechanisms underlying the effects of these agents were studied by reverse transcription-polymerase chain reaction, determining the expression of some factors [hepatocyte growth factor (HGF), transforming growth factor-beta (TGF-beta), alpha-smooth muscle actin, collagen, tissular inhibitor of metalloproteinases-1 and pregnane X receptor (PXR)] involved in fibrogenesis, fibrolysis and/or hepatoprotection. Both IGF-I and IFN-alpha exerted significant effects on fibrogenesis. IGF-I significantly increased serum albumin and HGF whereas IFN-alpha-therapy did not. The inhibition of TGF-beta expression was only observed by the effect of IFN-alpha-therapy. In addition, only the co-administration of IGF-I and IFN-alpha was able to increase the PXR. The combined therapy with both factors improved liver function tests, hepatic lipid peroxidation and reduced fibrosis, inducing a relevant histological improvement, reducing fibrosis and recovering hepatic architecture. The co-administration IGF-I+IFN enhanced all the beneficial effects observed with each factor separately, showing an additive action on histopathology and PXR expression, which is involved in the inhibition of fibrogenesis.

Design of experiments confirms optimization of lithium administration parameters for enhanced fracture healing.

PubMed

Vachhani, Kathak; Pagotto, Andrea; Wang, Yufa; Whyne, Cari; Nam, Diane

2018-01-03

Fracture healing is a lengthy process which fails in 5-10% of cases. Lithium, a low-cost therapeutic used in psychiatric medicine, up-regulates the canonical Wingless pathway crucial for osteoblastic mineralization in fracture healing. A design-of-experiments (DOE) methodology was used to optimize lithium administration parameters (dose, onset time and treatment duration) to enhance healing in a rat femoral fracture model. In the previously completed first stage (screening), onset time was found to significantly impact healing, with later (day 7 vs. day 3 post-fracture) treatment yielding improved maximum yield torque. The greatest strength was found in healing femurs treated at day 7 post fracture, with a low lithium dose (20 mg/kg) for 2 weeks duration. This paper describes the findings of the second (optimization) and third (verification) stages of the DOE investigation. Closed traumatic diaphyseal femur fractures were induced in 3-month old rats. Healing was evaluated on day 28 post fracture by CT-based morphometry and torsional loading. In optimization, later onset times of day 10 and 14 did not perform as well as day 7 onset. As such, efficacy of the best regimen (20 mg/kg dose given at day 7 onset for 2 weeks duration) was reassessed in a distinct cohort of animals to complete the DOE verification. A significant 44% higher maximum yield torque (primary outcome) was seen with optimized lithium treatment vs. controls, which paralleled the 46% improvement seen in the screening stage. Successful completion of this robustly designed preclinical DOE study delineates the optimal lithium regimen for enhancing preclinical long-bone fracture healing. Copyright © 2017 Elsevier Ltd. All rights reserved.

Significantly enhanced thermal conductivity of indium arsenide nanowires via sulfur passivation.

PubMed

Xiong, Yucheng; Tang, Hao; Wang, Xiaomeng; Zhao, Yang; Fu, Qiang; Yang, Juekuan; Xu, Dongyan

2017-10-16

In this work, we experimentally investigated the effect of sulfur passivation on thermal transport in indium arsenide (InAs) nanowires. Our measurement results show that thermal conductivity can be enhanced by a ratio up to 159% by sulfur passivation. Current-voltage (I-V) measurements were performed on both unpassivated and S-passivated InAs nanowires to understand the mechanism of thermal conductivity enhancement. We observed a remarkable improvement in electrical conductivity upon sulfur passivation and a significant contribution of electrons to thermal conductivity, which account for the enhanced thermal conductivity of the S-passivated InAs nanowires.

Administration of interleukin-12 enhances the therapeutic efficacy of dendritic cell-based tumor vaccines in mouse hepatocellular carcinoma.

PubMed

Tatsumi, T; Takehara, T; Kanto, T; Miyagi, T; Kuzushita, N; Sugimoto, Y; Jinushi, M; Kasahara, A; Sasaki, Y; Hori, M; Hayashi, N

2001-10-15

Dendritic cells (DCs) are potent antigen-presenting cells that are capable of priming systemic antitumor immune response. Here, we evaluated the combined effectiveness of tumor lysate-pulsed DC immunization and interleukin (IL)-12 administration on the induction of antitumor immunity in a mouse hepatocellular carcinoma (HCC) model. Mouse DCs were pulsed with lysate of BNL 1ME A.7R.1 (BNL), a BALB/c-derived HCC cell line, and then injected into syngeneic mice in combination with systemic administration of IL-12. Lymphocytes from mice treated with BNL lysate-pulsed DCs and IL-12 showed stronger cytolytic activity and produced higher amounts of IFN-gamma than those from mice treated with BNL lysate-pulsed DCs alone. Although immunization with BNL lysate-pulsed DCs alone did not lead to complete regression of established tumors, it significantly inhibited tumor growth compared with vehicle injection. Importantly, the combined therapy of BNL lysate-pulsed DCs and IL-12 resulted in tumor rejection or significant inhibition of tumor growth compared with mice treated with BNL lysate-pulsed DCs alone. In vivo lymphocyte depletion experiments demonstrated that this combination was dependent on both CD8+ and CD4+ T cells, but not natural killer cells. These results demonstrated that IL-12 administration enhanced the therapeutic effect of immunization of tumor lysate-pulsed DCs against HCC in mice. This combination of IL-12 and DCs may be useful for suppressing the growth of residual tumor after primary therapy of human HCC.

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

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.

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.

Clinical significance of quantitative analysis of facial nerve enhancement on MRI in Bell's palsy.

PubMed

Song, Mee Hyun; Kim, Jinna; Jeon, Ju Hyun; Cho, Chang Il; Yoo, Eun Hye; Lee, Won-Sang; Lee, Ho-Ki

2008-11-01

Quantitative analysis of the facial nerve on the lesion side as well as the normal side, which allowed for more accurate measurement of facial nerve enhancement in patients with facial palsy, showed statistically significant correlation with the initial severity of facial nerve inflammation, although little prognostic significance was shown. This study investigated the clinical significance of quantitative measurement of facial nerve enhancement in patients with Bell's palsy by analyzing the enhancement pattern and correlating MRI findings with initial severity of facial palsy and clinical outcome. Facial nerve enhancement was measured quantitatively by using the region of interest on pre- and postcontrast T1-weighted images in 44 patients diagnosed with Bell's palsy. The signal intensity increase on the lesion side was first compared with that of the contralateral side and then correlated with the initial degree of facial palsy and prognosis. The lesion side showed significantly higher signal intensity increase compared with the normal side in all of the segments except for the mastoid segment. Signal intensity increase at the internal auditory canal and labyrinthine segments showed correlation with the initial degree of facial palsy but no significant difference was found between different prognostic groups.

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

Short-term repeated corticosterone administration enhances glutamatergic but not GABAergic transmission in the rat motor cortex.

PubMed

Kula, Joanna; Blasiak, Anna; Czerw, Anna; Tylko, Grzegorz; Sowa, Joanna; Hess, Grzegorz

2016-04-01

It has been demonstrated that stress impairs performance of skilled reaching and walking tasks in rats due to the action of glucocorticoids involved in the stress response. Skilled reaching and walking are controlled by the primary motor cortex (M1); however, it is not known whether stress-related impairments in skilled motor tasks are related to functional and/or structural alterations within the M1. We studied the effects of single and repeated injections of corticosterone (twice daily for 7 days) on spontaneous excitatory and inhibitory postsynaptic currents (sEPSCs and sIPSCs) recorded from layer II/III pyramidal neurons in ex vivo slices of the M1, prepared 2 days after the last administration of the hormone. We also measured the density of dendritic spines on pyramidal cells and the protein levels of selected subunits of AMPA, NMDA, and GABAA receptors after repeated corticosterone administration. Repeatedly administered corticosterone induced an increase in the frequency but not in the amplitude of sEPSCs, while a single administration had no effect on the recorded excitatory currents. The frequency and amplitude of sIPSCs as well as the excitability of pyramidal cells were changed neither after single nor after repeated corticosterone administration. Treatment with corticosterone for 7 days did not modify the density of dendritic spines on pyramidal neurons. Corticosterone influenced neither the protein levels of GluA1, GluA2, GluN1, GluN2A, and GluN2B subunits of glutamate receptors nor those of α1, β2, and γ2 subunits of the GABAA receptor. The increase in sEPSCs frequency induced by repeated corticosterone administration faded out within 7 days. These data indicate that prolonged administration of exogenous corticosterone selectively and reversibly enhances glutamatergic, but not GABAergic transmission in the rat motor cortex. Our results suggest that corticosterone treatment results in an enhancement of spontaneous glutamate release from presynaptic

Focused ultrasound-enhanced intranasal brain delivery of brain-derived neurotrophic factor

NASA Astrophysics Data System (ADS)

Chen, Hong; Yang, Georgiana Zong Xin; Getachew, Hoheteberhan; Acosta, Camilo; Sierra Sánchez, Carlos; Konofagou, Elisa E.

2016-06-01

The objective of this study was to unveil the potential mechanism of focused ultrasound (FUS)-enhanced intranasal (IN) brain drug delivery and assess its feasibility in the delivery of therapeutic molecules. Delivery outcomes of fluorescently-labeled dextrans to mouse brains by IN administration either before or after FUS sonication were compared to evaluate whether FUS enhances IN delivery by active pumping or passive diffusion. Fluorescence imaging of brain slices found that IN administration followed by FUS sonication achieved significantly higher delivery than IN administration only, while pre-treatment by FUS sonication followed by IN administration was not significantly different from IN administration only. Brain-derived neurotrophic factor (BDNF), a promising neurotrophic factor for the treatment of many central nervous system diseases, was delivered by IN followed by FUS to demonstrate the feasibility of this technique and compared with the established FUS technique where drugs are injected intravenously. Immunohistochemistry staining of BDNF revealed that FUS-enhanced IN delivery achieved similar locally enhanced delivery as the established FUS technique. This study suggested that FUS enhances IN brain drug delivery by FUS-induced active pumping of the drug and demonstrated that FUS-enhanced IN delivery is a promising technique for noninvasive and localized delivery of therapeutic molecules to the brain.

Photoexcited Graphene Metasurfaces: Significantly Enhanced and Tunable Magnetic Resonances

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

Fan, Yuancheng; Shen, Nian -Hai; Zhang, Fuli

Artificially constructed metamaterials or metasurfaces with tailored resonant elements provide a revolutionary platform for controlling light at the subwavelength scale. Switchable or frequency-agile meta-devices are highly desirable in achieving more flexible functionalities and have been explored extensively by incorporating various materials, which respond to external stimuli. Graphene, a two-dimensional material showing extraordinary physical properties, has been found very promising for tunable meta-devices. However, the high intrinsic loss of graphene severely obstructs us from achieving high-quality resonance in various graphene metamaterials and metasurfaces, and the loss compensation can be considered as a straightforward strategy to take further advantages of enhanced light–graphenemore » interactions. Here, we demonstrate that the photoexcited graphene, in which the quasi-Fermi energy of graphene changes corresponding to optical pumping, can boost the originally extremely weak magnetic resonance in a graphene split-ring metasurface, showing remarkable modulations in the transmission. In conclusion, our work pioneers the possibilities of optically pumped graphene metasurfaces for significant enhancement of resonances and feasible modulations.« less

Photoexcited Graphene Metasurfaces: Significantly Enhanced and Tunable Magnetic Resonances

DOE PAGES

Fan, Yuancheng; Shen, Nian -Hai; Zhang, Fuli; ...

2018-02-27

Artificially constructed metamaterials or metasurfaces with tailored resonant elements provide a revolutionary platform for controlling light at the subwavelength scale. Switchable or frequency-agile meta-devices are highly desirable in achieving more flexible functionalities and have been explored extensively by incorporating various materials, which respond to external stimuli. Graphene, a two-dimensional material showing extraordinary physical properties, has been found very promising for tunable meta-devices. However, the high intrinsic loss of graphene severely obstructs us from achieving high-quality resonance in various graphene metamaterials and metasurfaces, and the loss compensation can be considered as a straightforward strategy to take further advantages of enhanced light–graphenemore » interactions. Here, we demonstrate that the photoexcited graphene, in which the quasi-Fermi energy of graphene changes corresponding to optical pumping, can boost the originally extremely weak magnetic resonance in a graphene split-ring metasurface, showing remarkable modulations in the transmission. In conclusion, our work pioneers the possibilities of optically pumped graphene metasurfaces for significant enhancement of resonances and feasible modulations.« less

Administrative Technology and the School Executive: Applying the Systems Approach to Educational Administration.

ERIC Educational Resources Information Center

Knezevich, Stephen J., Ed.

In this era of rapid social change, educational administrators have discovered that new approaches to problem solving and decision making are needed. Systems analysis could afford a promising approach to administrative problems by providing a number of systematic techniques designed to sharpen administrative decision making, enhance efficiency,…

A novel core-shell lipid nanoparticle for improving oral administration of water soluble chemotherapeutic agents: inhibited intestinal hydrolysis and enhanced lymphatic absorption.

PubMed

Wang, Tao; Shen, Liao; Zhang, Zhen; Li, Haiyan; Huang, Ri; Zhang, Yadan; Quan, Dongqin

2017-11-01

The oral administration of water-soluble chemotherapeutical agents is limited by their serious gastrointestinal side effects, instability at intestinal pH, and poor absorption. Aiming to solve these problems, we chose topotecan (TPT) as a model drug and developed a novel lipid formulation containing core-shell lipid nanoparticle (CLN) that makes the water-soluble drug to 'dissolve' in oil. TPT molecules can be encapsulated into nanoparticles surrounded by oil barrier while avoiding the direct contact with intestinal environment, thus easing the intestinal hydrolytic degradation and gastrointestinal (GI) irritation. Microstructure and mean particle size of TPT-CLN were characterized by Transmission Electron Microscope (TEM) and Dynamic Light Scattering (DLS), respectively. The average size of nanoparticles was approximately 60 nm with a homogeneous distribution in shapes of spheres or ellipsoid. According to in vitro stability studies, more initial form of TPT was observed in presence of lipid nanoparticle compared with free topotecan solution in artificial intestinal juice (pH 6.5). After oral administration of TPT-CLN in rats, AUC and C max of TPT were all increased compared with free TPT, indicating significant enhancement of oral absorption. Intestinal lymphatic transport was confirmed as the major way for CLN to enhance oral absorption of TPT by the treatment of blocking chylomicron flow. Lower GI irritation of TPT-CLN was observed in the gastrointestinal damage studies. The in vivo antitumor activity of TPT-CLN showed an improved antitumor efficacy by oral treatment of TPT-CLN compared to free TPT. From the obtained data, the systems appear an attractive progress in oral administration of topotecan.

Direct Administration of Nerve-Specific Contrast to Improve Nerve Sparing Radical Prostatectomy

PubMed Central

Barth, Connor W.; Gibbs, Summer L.

2017-01-01

Nerve damage remains a major morbidity following nerve sparing radical prostatectomy, significantly affecting quality of life post-surgery. Nerve-specific fluorescence guided surgery offers a potential solution by enhancing nerve visualization intraoperatively. However, the prostate is highly innervated and only the cavernous nerve structures require preservation to maintain continence and potency. Systemic administration of a nerve-specific fluorophore would lower nerve signal to background ratio (SBR) in vital nerve structures, making them difficult to distinguish from all nervous tissue in the pelvic region. A direct administration methodology to enable selective nerve highlighting for enhanced nerve SBR in a specific nerve structure has been developed herein. The direct administration methodology demonstrated equivalent nerve-specific contrast to systemic administration at optimal exposure times. However, the direct administration methodology provided a brighter fluorescent nerve signal, facilitating nerve-specific fluorescence imaging at video rate, which was not possible following systemic administration. Additionally, the direct administration methodology required a significantly lower fluorophore dose than systemic administration, that when scaled to a human dose falls within the microdosing range. Furthermore, a dual fluorophore tissue staining method was developed that alleviates fluorescence background signal from adipose tissue accumulation using a spectrally distinct adipose tissue specific fluorophore. These results validate the use of the direct administration methodology for specific nerve visualization with fluorescence image-guided surgery, which would improve vital nerve structure identification and visualization during nerve sparing radical prostatectomy. PMID:28255352

Direct Administration of Nerve-Specific Contrast to Improve Nerve Sparing Radical Prostatectomy.

PubMed

Barth, Connor W; Gibbs, Summer L

2017-01-01

Nerve damage remains a major morbidity following nerve sparing radical prostatectomy, significantly affecting quality of life post-surgery. Nerve-specific fluorescence guided surgery offers a potential solution by enhancing nerve visualization intraoperatively. However, the prostate is highly innervated and only the cavernous nerve structures require preservation to maintain continence and potency. Systemic administration of a nerve-specific fluorophore would lower nerve signal to background ratio (SBR) in vital nerve structures, making them difficult to distinguish from all nervous tissue in the pelvic region. A direct administration methodology to enable selective nerve highlighting for enhanced nerve SBR in a specific nerve structure has been developed herein. The direct administration methodology demonstrated equivalent nerve-specific contrast to systemic administration at optimal exposure times. However, the direct administration methodology provided a brighter fluorescent nerve signal, facilitating nerve-specific fluorescence imaging at video rate, which was not possible following systemic administration. Additionally, the direct administration methodology required a significantly lower fluorophore dose than systemic administration, that when scaled to a human dose falls within the microdosing range. Furthermore, a dual fluorophore tissue staining method was developed that alleviates fluorescence background signal from adipose tissue accumulation using a spectrally distinct adipose tissue specific fluorophore. These results validate the use of the direct administration methodology for specific nerve visualization with fluorescence image-guided surgery, which would improve vital nerve structure identification and visualization during nerve sparing radical prostatectomy.

Enhancement of the fibrinolytic activity in plasma by oral administration of nattokinase.

PubMed

Sumi, H; Hamada, H; Nakanishi, K; Hiratani, H

1990-01-01

The existence of a potent fibrinolytic enzyme (nattokinase, NK) in the traditional fermented food called 'natto', was reported by us previously. It was confirmed that oral administration of NK (or natto) produced a mild and frequent enhancement of the fibrinolytic activity in the plasma, as indicated by the fibrinolytic parameters, and the production of tissue plasminogen activator. NK capsules were also administered orally to dogs with experimentally induced thrombosis, and lysis of the thrombi was observed by angiography. The results obtained suggest that NK represents a possible drug for use not only in the treatment of embolism but also in the prevention of the disease, since NK has a proven safety and can be massproduced.

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.

Self-administration of the synthetic cathinone MPDV enhances reward function via a nicotinic receptor dependent mechanism.

PubMed

Geste, Jean R; Pompilus, Marjory; Febo, Marcelo; Bruijnzeel, Adriaan W

2018-05-09

Methylenedioxypyrovalerone (MDPV) is an addictive synthetic drug with severe side effects. Previous studies have shown that MDPV has positive reinforcing properties. However, little is known about the effect of MDPV self-administration on the state of the brain reward system and the neuronal mechanisms by which MDPV mediates its effects. The goal of the present studies was to determine the effect of MDPV self-administration on reward function and the role of cholinergic neurotransmission in the reinforcing effects of MDPV. To study the effect of MDPV self-administration on the brain reward system, rats were prepared with intravenous catheters and intracranial self-stimulation electrodes (ICSS). For 10 days, the reward thresholds were assessed immediately before (23 h post prior session) and after 1 h of MDPV self-administration. The reward thresholds were decreased immediately after MDPV self-administration, which is indicative of a potentiation of brain reward function. The reward thresholds 23 h after MDPV intake gradually increased over time, which is indicative of anhedonia. Pretreatment with the nicotinic acetylcholine receptor (nAChR) antagonist mecamylamine decreased the self-administration of MDPV and completely prevented the decrease in reward thresholds. A control study with palatable chocolate pellets showed that responding for a natural reinforcer does not affect the state of the brain reward system. Furthermore, mecamylamine did not affect responding for food pellets. In conclusion, the self-administration of MDPV potentiates reward function and nAChR blockade prevents the reward enhancing effects of MDPV self-administration. Preventing the MDPV-induced increase in cholinergic neurotransmission might be a safe approach to diminish MDPV abuse. Copyright © 2018. Published by Elsevier Ltd.

The National Aeronautics and Space Administration's Earth Science Applications Program: Exploring Partnerships to Enhance Decision Making in Public Health Practice

NASA Technical Reports Server (NTRS)

Vann, Timi S.; Venezia, Robert A.

2002-01-01

The National Aeronautics and Space Administration (NASA), Earth Science Enterprise is engaged in applications of NASA Earth science and remote sensing technologies for public health. Efforts are focused on establishing partnerships with those agencies and organizations that have responsibility for protecting the Nation's Health. The program's goal is the integration of NASA's advanced data and technology for enhanced decision support in the areas of disease surveillance and environmental health. A focused applications program, based on understanding partner issues and requirements, has the potential to significantly contribute to more informed decision making in public health practice. This paper intends to provide background information on NASA's investment in public health and is a call for partnership with the larger practice community.

Exploring the Phase Behavior of Monoolein/Oleic Acid/Water Systems for Enhanced Donezepil Administration for Alzheimer Disease Treatment.

PubMed

Ruela, André Luís Morais; Carvalho, Flávia Chiva; Pereira, Gislaine Ribeiro

2016-01-01

Donepezil is a drug usually administered by oral route for Alzheimer disease treatment, but several gastric side effects have been reported as diarrhea, nausea, and anorexia. We explored the phase behavior of lyotropic liquid crystalline (LLC) mesophases composed by monoolein/oleic acid/water for enhanced administration of donepezil. Polarized light microscopy suggested that these systems ranged from isotropic inverse micellar solutions (L2) to viscous and birefringent reverse hexagonal (HII) mesophases according to the amount of water in the ternary systems. Phase transition was observed from a L2 phase to HII mesophase after swelling studies, an interesting property to be explored as a precursor of LLC mesophases for mucosal administration that increases its viscosity in situ. Mucoadhesive properties of LLC mesophases were characterized using a texture analyzer indicating that these systems can have an increased residence time in the site of absorption. Donepezil-free base was incorporated in the evaluated formulations, and their in vitro release was controlled up to 24 h. The phase behavior of the systems demonstrated a great potential for enhanced donepezil administration once these mucoadhesive-controlled release formulations can incorporate the drug and prolong its release, possibly reducing its side effects. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Phase-Defined van der Waals Schottky Junctions with Significantly Enhanced Thermoelectric Properties.

PubMed

Wang, Qiaoming; Yang, Liangliang; Zhou, Shengwen; Ye, Xianjun; Wang, Zhe; Zhu, Wenguang; McCluskey, Matthew D; Gu, Yi

2017-07-06

We demonstrate a van der Waals Schottky junction defined by crystalline phases of multilayer In 2 Se 3 . Besides ideal diode behaviors and the gate-tunable current rectification, the thermoelectric power is significantly enhanced in these junctions by more than three orders of magnitude compared with single-phase multilayer In 2 Se 3 , with the thermoelectric figure-of-merit approaching ∼1 at room temperature. Our results suggest that these significantly improved thermoelectric properties are not due to the 2D quantum confinement effects but instead are a consequence of the Schottky barrier at the junction interface, which leads to hot carrier transport and shifts the balance between thermally and field-driven currents. This "bulk" effect extends the advantages of van der Waals materials beyond the few-layer limit. Adopting such an approach of using energy barriers between van der Waals materials, where the interface states are minimal, is expected to enhance the thermoelectric performance in other 2D materials as well.

Conjugation of 10 kDa Linear PEG onto Trastuzumab Fab' Is Sufficient to Significantly Enhance Lymphatic Exposure while Preserving in Vitro Biological Activity.

PubMed

Chan, Linda J; Ascher, David B; Yadav, Rajbharan; Bulitta, Jürgen B; Williams, Charlotte C; Porter, Christopher J H; Landersdorfer, Cornelia B; Kaminskas, Lisa M

2016-04-04

The lymphatic system is a major conduit by which many diseases spread and proliferate. There is therefore increasing interest in promoting better lymphatic drug targeting. Further, antibody fragments such as Fabs have several advantages over full length monoclonal antibodies but are subject to rapid plasma clearance, which can limit the lymphatic exposure and activity of Fabs against lymph-resident diseases. This study therefore explored ideal PEGylation strategies to maximize biological activity and lymphatic exposure using trastuzumab Fab' as a model. Specifically, the Fab' was conjugated with single linear 10 or 40 kDa PEG chains at the hinge region. PEGylation led to a 3-4-fold reduction in binding affinity to HER2, but antiproliferative activity against HER2-expressing BT474 cells was preserved. Lymphatic pharmacokinetics were then examined in thoracic lymph duct cannulated rats after intravenous and subcutaneous dosing at 2 mg/kg, and the data were evaluated via population pharmacokinetic modeling. The Fab' displayed limited lymphatic exposure, but conjugation of 10 kDa PEG improved exposure by approximately 11- and 5-fold after intravenous (15% dose collected in thoracic lymph over 30 h) and subcutaneous (9%) administration, respectively. Increasing the molecular weight of the PEG to 40 kDa, however, had no significant impact on lymphatic exposure after intravenous (14%) administration and only doubled lymphatic exposure after subcutaneous administration (18%) when compared to 10 kDa PEG-Fab'. The data therefore suggests that minimal PEGylation has the potential to enhance the exposure and activity of Fab's against lymph-resident diseases, while no significant benefit is achieved with very large PEGs.

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.

50 CFR 401.1 - Administration.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 50 Wildlife and Fisheries 7 2010-10-01 2010-10-01 false Administration. 401.1 Section 401.1... INTERIOR AND NATIONAL MARINE FISHERIES SERVICE, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT..., DEVELOPMENT AND ENHANCEMENT § 401.1 Administration. The Director of the U.S. Fish and Wildlife Service and the...

50 CFR 401.1 - Administration.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 50 Wildlife and Fisheries 11 2013-10-01 2013-10-01 false Administration. 401.1 Section 401.1... INTERIOR AND NATIONAL MARINE FISHERIES SERVICE, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT..., DEVELOPMENT AND ENHANCEMENT § 401.1 Administration. The Director of the U.S. Fish and Wildlife Service and the...

50 CFR 401.1 - Administration.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 50 Wildlife and Fisheries 11 2012-10-01 2012-10-01 false Administration. 401.1 Section 401.1... INTERIOR AND NATIONAL MARINE FISHERIES SERVICE, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT..., DEVELOPMENT AND ENHANCEMENT § 401.1 Administration. The Director of the U.S. Fish and Wildlife Service and the...

50 CFR 401.1 - Administration.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 50 Wildlife and Fisheries 9 2011-10-01 2011-10-01 false Administration. 401.1 Section 401.1... INTERIOR AND NATIONAL MARINE FISHERIES SERVICE, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT..., DEVELOPMENT AND ENHANCEMENT § 401.1 Administration. The Director of the U.S. Fish and Wildlife Service and the...

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.

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

Significant enhancement by biochar of caproate production via chain elongation.

PubMed

Liu, Yuhao; He, Pinjing; Shao, Liming; Zhang, Hua; Lü, Fan

2017-08-01

In this study, biochar was introduced into a chain elongation system to enhance the bioproduction of caproate and caprylate. The concentration of caproate increased to 21.1 g/L upon the addition of biochar, which is the highest level of caproate reported for such a system to date when ethanol was used as electron donor. The addition of biochar created a tougher system with more stable microorganism community structure for chain elongation, in which no obvious inhibition by products or substrates was observed, moreover, the lag phase was reduced 2.3-fold compared to the system without biochar. These reinforcement effect of biochar are attributed to the enhanced conductivity due to the significant enrichment of functional microorganisms via the microbial network surrounding smaller biochar particles, and via the adsorption on the rough surfaces or pores of larger particles, which facilitated electron transfer. Higher amounts of extracellular polymer substances and higher conductivity induced by biochar could contribute to the reinforcement effect in chain elongation. Copyright © 2017 Elsevier Ltd. All rights reserved.

THE ROLE OF OBSERVATION AND FEEDBACK IN ENHANCING PERFORMANCE WITH MEDICATION ADMINISTRATION.

PubMed

Davies, Karen; Mitchell, Charles; Coombes, Ian

2015-12-01

Legislation in Queensland such as the Health (Drugs and Poisons) Regulation 1996, the national registration competency standards set by the Nursing and Midwifery Board of Australia, and the Continuing Professional Development Registration Standards made pursuant to the Health Practitioner Regulation National Law define expected standards of practice for nurses. The Framework for Assessing Standards for Practice for Registered Nurses, Enrolled Nurses and Midwives, released in July 2015, includes the principles for assessing standards but not the methods. Local policies and procedures offer specific requirements founded on evidence-based practice. Observation of clinical practice with the provision of immediate descriptive feedback to individual practitioners has been associated with improved performance. This column describes the role of regular observation and individual feedback on medication administration as a strategy to enhance performance and patient care.

Corticosterone administration and high-energy feed results in enhanced fat accumulation and insulin resistance in broiler chickens.

PubMed

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

2008-07-01

1. Two experiments were conducted to investigate the effects of exogenous corticosterone administration (30 mg/kg diet) and dietary energy level on feed or energy intake and fat deposition in broiler chickens of 1 and 4 weeks of age. 2. Corticosterone treatment significantly suppressed body weight (BW) gain and reduced feed and caloric efficiencies. The retarded growth may conceal the stimulatory effect of corticosterone on feed consumption or metabolisable energy (ME) intake. A high-energy diet may increase energy intake and partially alleviate the suppressing effect of corticosterone on growth of broilers. 3. Corticosterone administration promoted the conservation of energy stores as fat at both abdominal and subcutaneous sites and this process occurred regardless of dietary energy level in ad libitum feeding status. A high-energy diet increased fat accumulation and showed no significant interaction with corticosterone treatment. 4. The suppressed development of breast and thigh muscles by corticosterone treatment was observed only in 1-week-old chickens fed on the low-energy diet. In contrast, the yield of breast muscle but not thigh muscle was significantly decreased by corticosterone in 4-week-old chickens, suggesting that the tissue specificity to corticosterone challenge is age dependent. 5. Plasma concentrations of glucose, insulin, triglyceride, non-esterified fatty acids (NEFA) and very low density lipoprotein were increased by corticosterone treatment regardless of diet treatment. A high-energy diet increased plasma levels of NEFA and resulted in hyperinsulinism in 4-week-old chickens but not in 1-week-old chickens. 6. Lipoprotein lipase (LPL) activities in adipose tissues may have been up-regulated by corticosterone treatment and showed tissue specificity. The increased LPL activities at ad libitum feeding status were not necessarily linked with the increased fat accumulation in corticosterone challenged chickens. 7. Corticosterone resulted in augmented

Glucose administration enhances fMRI brain activation and connectivity related to episodic memory encoding for neutral and emotional stimuli.

PubMed

Parent, Marise B; Krebs-Kraft, Desiree L; Ryan, John P; Wilson, Jennifer S; Harenski, Carla; Hamann, Stephan

2011-04-01

Glucose enhances memory in a variety of species. In humans, glucose administration enhances episodic memory encoding, although little is known regarding the neural mechanisms underlying these effects. Here we examined whether elevating blood glucose would enhance functional MRI (fMRI) activation and connectivity in brain regions associated with episodic memory encoding and whether these effects would differ depending on the emotional valence of the material. We used a double-blind, within-participants, crossover design in which either glucose (50g) or a saccharin placebo were administered before scanning, on days approximately 1 week apart. We scanned healthy young male participants with fMRI as they viewed emotionally arousing negative pictures and emotionally neutral pictures, intermixed with baseline fixation. Free recall was tested at 5 min after scanning and again after 1 day. Glucose administration increased activation in brain regions associated with successful episodic memory encoding. Glucose also enhanced activation in regions whose activity was correlated with subsequent successful recall, including the hippocampus, prefrontal cortex, and other regions, and these effects differed for negative vs. neutral stimuli. Finally, glucose substantially increased functional connectivity between the hippocampus and amygdala and a network of regions previously implicated in successful episodic memory encoding. These findings fit with evidence from nonhuman animals indicating glucose modulates memory by selectively enhancing neural activity in brain regions engaged during memory tasks. Our results highlight the modulatory effects of glucose and the importance of examining both regional changes in activity and functional connectivity to fully characterize the effects of glucose on brain function and memory. Copyright © 2011 Elsevier Ltd. All rights reserved.

Enhanced protective immune response to PCV2 subunit vaccine by co-administration of recombinant porcine IFN-γ in mice.

PubMed

Wang, Yi-Ping; Liu, Dan; Guo, Long-Jun; Tang, Qing-Hai; Wei, Yan-Wu; Wu, Hong-Li; Liu, Jian-Bo; Li, Sheng-Bin; Huang, Li-Ping; Liu, Chang-Ming

2013-01-21

The capsid (Cap) protein of PCV2 is the major immunogenic protein that is crucial to induce PCV2-specific neutralizing antibodies and protective immunity; thus, it is a suitable target antigen for the research and development of genetically engineered vaccines against PCV2 infection. IFN-γ has exhibited potential efficacy as an immune adjuvant that enhances the immunogenicity of certain vaccines in experimental animal models. In this study, three recombinant proteins: PCV2-Cap protein, porcine IFN-γ (PoIFN-γ), and the fusion protein (Cap-PoIFN-γ) of PCV2-Cap protein and PoIFN-γ were respectively expressed in the baculovirus system, and analyzed by Western blot and indirect ELISA. Additionally, we evaluated the enhancement of the protective immune response to the Cap protein-based PCV2 subunit vaccine elicited by co-administration of PoIFN-γ in mice. Vaccination of mice with the PCV2-Cap+PoIFN-γ vaccine elicited significantly higher levels of PCV2-specific IPMA antibodies, neutralizing antibodies, and lymphocyte proliferative responses compared to the Cap-PoIFN-γ vaccine, the PCV2-Cap vaccine, and LG-strain. Following virulent PCV2 challenge, no viraemia was detected in all immunized groups, and the viral loads in lungs of the PCV2-Cap+PoIFN-γ group were significantly lower compared to the Cap-PoIFN-γ group, the LG-strain group, and the mock group, but slightly lower compared to the PCV2-Cap group. These findings suggested that PoIFN-γ substantially enhanced the protective immune response to the Cap protein-based PCV2 subunit vaccine, and that the PCV2-Cap+PoIFN-γ subunit vaccine potentially serves as an attractive candidate vaccine for the prevention and control of PCV2-associated diseases. Copyright © 2012 Elsevier Ltd. All rights reserved.

[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.

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.

A Hybrid Actuation System Demonstrating Significantly Enhanced Electromechanical Performance

NASA Technical Reports Server (NTRS)

Su, Ji; Xu, Tian-Bing; Zhang, Shujun; Shrout, Thomas R.; Zhang, Qiming

2004-01-01

A hybrid actuation system (HYBAS) utilizing advantages of a combination of electromechanical responses of an electroactive polymer (EAP), an electrostrictive copolymer, and an electroactive ceramic single crystal, PZN-PT single crystal, has been developed. The system employs the contribution of the actuation elements cooperatively and exhibits a significantly enhanced electromechanical performance compared to the performances of the device made of each constituting material, the electroactive polymer or the ceramic single crystal, individually. The theoretical modeling of the performances of the HYBAS is in good agreement with experimental observation. The consistence between the theoretical modeling and experimental test make the design concept an effective route for the development of high performance actuating devices for many applications. The theoretical modeling, fabrication of the HYBAS and the initial experimental results will be presented and discussed.

Bupropion-varenicline interactions and nicotine self-administration behavior in rats.

PubMed

Hall, Brandon J; Slade, Susan; Wells, Corinne; Rose, Jed E; Levin, Edward D

2015-03-01

Varenicline and bupropion each have been shown to significantly improve cessation of tobacco addiction in humans. They act through different mechanisms and the question about the potential added efficacy with their combined used has arisen. Preclinical animal models of nicotine addiction can help with the evaluation of this combined approach and what dose combinations of varenicline and bupropion may be useful for enhancing tobacco cessation. In this study, we investigated the interacting dose-effect functions of varenicline and bupropion in a rat model of nicotine self-administration. Young adult female Sprague-Dawley rats were allowed to self-administer nicotine in 1-h sessions under an FR1 reinforcement schedule. Varenicline (0.3, 1. 3 mg/kg) and bupropion (8.33, 25, 75 mg/kg) were administered alone or together 15 min before each session. The vehicle saline was the control. Higher doses of each drug alone reduced nicotine self-administration compared to control with reductions of 62% and 75% with 3 mg/kg varenicline and 75 mg/kg bupropion respectively. Lower dose varenicline which does not by itself reduce nicotine self-administration, significantly augmented bupropion effects. The 0.3 mg/kg varenicline dose combined with the 25 and 75 mg/kg bupropion doses caused greater reductions of nicotine self-administration than either dose of bupropion given alone. However, higher dose varenicline did not have this effect. Lower dose bupropion did not augment varenicline effects. Only the high bupropion dose significantly enhanced the varenicline effect. Likewise, combining 1 mg/kg varenicline with 75 mg/kg bupropion reduced self-administration to a greater extent than either dose alone. These results demonstrate that combination therapy with varenicline and bupropion may be more beneficial than monotherapy with either drug alone. Copyright © 2015 Elsevier Inc. All rights reserved.

Co-administration of a charge-conversional dendrimer enhances antitumor efficacy of conventional chemotherapy.

PubMed

Cao, Jun; Wang, Chenhong; Guo, Leijia; Xiao, Zhiyong; Liu, Keliang; Yan, Husheng

2018-06-01

Despite extensive investigations, the clinical translation of nanocarrier-based drug delivery systems (NDDS) for cancer therapy is hindered by inefficient delivery and poor tumor penetration. Conventional chemotherapy by administration of free small molecule anticancer drugs remains the standard of care for many cancers. Herein, other than for carrying and releasing drugs, small nanoparticles were used as a potentiator of conventional chemotherapy by co-administration with free chemotherapeutic agents. This strategy avoided the problems associated with drug loading and controlled release encountered in NDDS, and was also much simpler than NDDS. Negatively charged poly(amido amine)-2,3-dimethylmaleic monoamide (PAMAM-DMA) dendrimers were prepared, which possessed low toxicity and can be converted to positively charged PAMAM dendrimers responsive to tumor acidic pH. The in situ formed PAMAM in tumor tissue promoted cellular uptake of co-administered doxorubicin by increasing the cell membrane permeability, and subsequently enhanced the cytotoxicity of doxorubicin. The small size of the dendrimers was favorable for deep penetration in tumor. Co-injection of PAMAM-DMA with doxorubicin into nude mice bearing human tumors almost completely inhibited tumor growth, with a mean tumor weight reducing by 55.9% after the treatment compared with the treatment with doxorubicin alone. Copyright © 2018 Elsevier B.V. All rights reserved.

Cognitive enhancement effects of Bacopa monnieri (Brahmi) on novel object recognition and neuronal density in the prefrontal cortex, striatum and hippocampus in sub-chronic phencyclidine administration rat model of schizophrenia.

PubMed

Wetchateng, Thanitsara; Piyabhan, Pritsana

2015-03-01

Cognitive deficit is a significant problem, which finally occurs in all schizophrenic patients. It can not be attenuated by any antipsychotic drugs. It is well known that changes of neuronal density are correlated with learning and memory deficits. Bacopa monnieri (Brahmi), popularly known as a cognitive enhancer; might be a novel therapeutic agentfor cognitive deficit in schizophrenia by changing cerebral neuronal density. The objective of this study was to determine the effects of Brahmi on attenuation at cognitive deficit and on the neuronal density in the prefrontal cortex, striatum and cornu ammonis subfield 1 (CA1) and 2/3 (CA2/3) of hippocampus in sub-chronic phencyclidine (PCP) rat model of schizophrenia. Rats were assigned to three groups; Group-1: Control, Group-2: PCP administration and Group-3: PCP + Brahmi. Rats were testedfor cognitive ability by using the novel object recognition test. Neuronal density from a serial Nissl stain sections ofthe prefrontal cortex, striatum and hippocampus ofrat model ofschizophrenia were measured by using Image ProPlus software and manual counting. Sub-chronic administration of PCP results in cognitive deficits in novel object recognition task. This occurred alongside significantly increased neuronal density in CA1. The cognitive deficit was recovery to normal in PCP + Brahmi group and it occurred alongside significantly decreased neuronal density in CA1. On the other hand, significantly increased neuronal density was observed in CA2/3 of PCP + Brahmi group compared with PCP alone. Brahmi is a potential cognitive enhancer against schizophrenia. It reduces neuronal density, most likely glutamatergic neuron, which results in neuronal toxicity and cognitive deficit. Therefore, Brahmi has cognitive enhancement effect by reducing glutamatergic neuron in CAI. Moreover, it also has neurogenesis effect in CA2/3, which is needed to be investigated in the further study.

Comparison of the enhancement of plasma glucose levels in type 2 diabetes Otsuka Long-Evans Tokushima Fatty rats by oral administration of sucrose or maple syrup.

PubMed

Nagai, Noriaki; Ito, Yoshimasa; Taga, Atsushi

2013-01-01

Maple syrup is used as a premium natural sweeter, and is known for being good for human health. In the present study, we investigate whether maple syrup is suitable as a sweetener in the management of type 2 diabetes using Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model of type 2 diabetes mellitus. OLETF rats develop type 2 diabetes mellitus by 30 weeks of age, and 60-week-old OLETF rats show hyperglycemia and hypoinsulinemia via pancreatic β-cell dysfunction. The administration of sucrose or maple syrup following an OGT test increased plasma glucose (PG) levels in OLETF rats, but the enhancement in PG following the oral administration of maple syrup was lower than in the case of sucrose administration in both 30- and 60-week-old OLETF rats. Although, the insulin levels in 30-week-old OLETF rats also increased following the oral administration of sucrose or maple syrup, no increase in insulin levels was seen in 60-week-old OLETF rats following the oral administration of either sucrose or maple syrup. No significant differences were observed in insulin levels between sucrose- and maple syrup-administered OLETF rats at either 30 or 60 weeks of age. The present study strongly suggests that the maple syrup may have a lower glycemic index than sucrose, which may help in the prevention of type 2 diabetes.

Transdermal absorption of memantin--effect of chemical enhancers, iontophoresis, and role of enhancer lipophilicity.

PubMed

del Rio-Sancho, S; Serna-Jiménez, C E; Calatayud-Pascual, M A; Balaguer-Fernández, C; Femenía-Font, A; Merino, V; López-Castellano, A

2012-09-01

The transdermal administration of memantine may have advantages with respect to oral therapy when treating advanced stages of Alzheimer's disease. With the ultimate objective of administrating memantine through a transdermal patch, the absorption of the drug across skin was evaluated by means of in vitro permeation studies. The effect of several chemical enhancers was studied in order to enhance percutaneous absorption of the memantine. The iontophoretic transdermal transport of memantine hydrochloride using a current density of 0.5 mA/cm(2) was also investigated. Results demonstrated that pre-treatment of the skin with R-(+)-limonene, laurocapram, decenoic acid, or oleic acid produced a statistically significant increment in the transdermal flux of memantine hydrochloride with respect to the control. Iontophoresis exhibited the greatest ability to enhance the flux of drug with respect to the control; nevertheless, the results obtained with R-(+)-limonene indicate that this compound could be of great use as a percutaneous enhancer in a memantine transdermal delivery system. In this study, the relationship between enhancement activity and lipophilicity was also studied. Satisfactory correlations have been obtained between the optimum lipophilicity of the enhancer and n-octanol/water partition coefficients of drugs. This relationship is a very useful tool that could allow to reduce time and to optimize the selection of appropriate enhancers for transdermal formulations. Copyright © 2012 Elsevier B.V. All rights reserved.

Significance of excipients to enhance the bioavailability of poorly water-soluble drugs in oral solid dosage forms: A Review

NASA Astrophysics Data System (ADS)

Vadlamudi, Manoj Kumar; Dhanaraj, Sangeetha

2017-11-01

Nowadays most of the drug substances are coming into the innovation pipeline with poor water solubility. Here, the influence of excipients will play a significant role to improve the dissolution of poorly aqueous soluble compounds. The drug substance needs to be dissolved in gastric fluids to get the better absorption and bioavailability of an orally administered drug. Dissolution is the rate-controlling stage for drugs which controls the rate and degree of absorption. Usually, poorly soluble oral administrated drugs show a slower dissolution rate, inconsistent and incomplete absorption which can lead to lower bioavailability. The low aqueous solubility of BCS class II and IV drugs is a major challenge in the drug development and delivery process. Several technologies have been used in an attempt to progress the bioavailability of poorly water-soluble drug compounds which include solid dispersions, lipid-based formulations, micronization, solvent evaporation, co-precipitation, ordered mixing, liquid-solid compacts, solvent deposition inclusion complexation, and steam aided granulation. In fact, most of the technologies require excipient as a carrier which plays a significant role in improving the bioavailability using Hypromellose acetate succinate, Cyclodextrin, Povidone, Copovidone, Hydroxypropyl cellulose, Hydroxypropyl methylcellulose, Crospovidone, Starch, Dimethylacetamide, Polyethylene glycol, Sodium lauryl sulfate, Polysorbate, Poloxamer. Mesoporous silica and so on. This review deliberates about the excipients significance on bioavailability enhancement of drug products in a single platform along with pragmatically proved applications so that user can able to select the right excipients as per the molecule.

Glucocorticoids enhance extinction-based psychotherapy

PubMed Central

de Quervain, Dominique J.-F.; Bentz, Dorothée; Michael, Tanja; Bolt, Olivia C.; Wiederhold, Brenda K.; Margraf, Jürgen; Wilhelm, Frank H.

2011-01-01

Behavioral exposure therapy of anxiety disorders is believed to rely on fear extinction. Because preclinical studies have shown that glucocorticoids can promote extinction processes, we aimed at investigating whether the administration of these hormones might be useful in enhancing exposure therapy. In a randomized, double-blind, placebo-controlled study, 40 patients with specific phobia for heights were treated with three sessions of exposure therapy using virtual reality exposure to heights. Cortisol (20 mg) or placebo was administered orally 1 h before each of the treatment sessions. Subjects returned for a posttreatment assessment 3–5 d after the last treatment session and for a follow-up assessment after 1 mo. Adding cortisol to exposure therapy resulted in a significantly greater reduction in fear of heights as measured with the acrophobia questionnaire (AQ) both at posttreatment and at follow-up, compared with placebo. Furthermore, subjects receiving cortisol showed a significantly greater reduction in acute anxiety during virtual exposure to a phobic situation at posttreatment and a significantly smaller exposure-induced increase in skin conductance level at follow-up. The present findings indicate that the administration of cortisol can enhance extinction-based psychotherapy. PMID:21444799

Repeated administration of almonds increases brain acetylcholine levels and enhances memory function in healthy rats while attenuates memory deficits in animal model of amnesia.

PubMed

Batool, Zehra; Sadir, Sadia; Liaquat, Laraib; Tabassum, Saiqa; Madiha, Syeda; Rafiq, Sahar; Tariq, Sumayya; Batool, Tuba Sharf; Saleem, Sadia; Naqvi, Fizza; Perveen, Tahira; Haider, Saida

2016-01-01

Dietary nutrients may play a vital role in protecting the brain from age-related memory dysfunction and neurodegenerative diseases. Tree nuts including almonds have shown potential to combat age-associated brain dysfunction. These nuts are an important source of essential nutrients, such as tocopherol, folate, mono- and poly-unsaturated fatty acids, and polyphenols. These components have shown promise as possible dietary supplements to prevent or delay the onset of age-associated cognitive dysfunction. This study investigated possible protective potential of almond against scopolamine induced amnesia in rats. The present study also investigated a role of acetylcholine in almond induced memory enhancement. Rats in test group were orally administrated with almond suspension (400 mg/kg/day) for four weeks. Both control and almond-treated rats were then divided into saline and scopolamine injected groups. Rats in the scopolamine group were injected with scopolamine (0.5 mg/kg) five minutes before the start of each memory test. Memory was assessed by elevated plus maze (EPM), Morris water maze (MWM) and novel object recognition (NOR) task. Cholinergic function was determined in terms of hippocampal and frontal cortical acetylcholine content and acetylcholinesterase activity. Results of the present study suggest that almond administration for 28 days significantly improved memory retention. This memory enhancing effect of almond was also observed in scopolamine induced amnesia model. Present study also suggests a role of acetylcholine in the attenuation of scopolamine induced amnesia by almond. Copyright © 2015 Elsevier Inc. All rights reserved.

Attenuation by all-trans-retinoic acid of sodium chloride-enhanced gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats.

PubMed

Tatsuta, M; Iishi, H; Baba, M; Hirasawa, R; Yano, H; Sakai, N; Nakaizumi, A

1999-02-01

The effect of prolonged administration of all-trans-retinoic acid (RA) on sodium chloride-enhanced gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine, and the labelling and apoptotic indices and immunoreactivity of transforming growth factor (TGF) alpha in the gastric cancers was investigated in Wistar rats. After 25 weeks of carcinogen treatment, the rats were given chow pellets containing 10% sodium chloride and subcutaneous injections of RA at doses of 0.75 or 1.5 mg kg(-1) body weight every other day. In week 52, oral supplementation with sodium chloride significantly increased the incidence of gastric cancers compared with the untreated controls. Long-term administration of RA at both doses significantly reduced the incidence of gastric cancers, which was enhanced by oral administration of sodium chloride. RA at both doses significantly decreased the labelling index and TGF-alpha immunoreactivity of gastric cancers, which were enhanced by administration of sodium chloride, and significantly increased the apoptotic index of cancers, which was lowered by administration of sodium chloride. These findings suggest that RA attenuates gastric carcinogenesis, enhanced by sodium chloride, by increasing apoptosis, decreasing DNA synthesis, and reducing TGF-alpha expression in gastric cancers.

Bioavailability of Lumefantrine Is Significantly Enhanced with a Novel Formulation Approach, an Outcome from a Randomized, Open-Label Pharmacokinetic Study in Healthy Volunteers.

PubMed

Jain, Jay Prakash; Leong, F Joel; Chen, Lan; Kalluri, Sampath; Koradia, Vishal; Stein, Daniel S; Wolf, Marie-Christine; Sunkara, Gangadhar; Kota, Jagannath

2017-09-01

The artemether-lumefantrine combination requires food intake for the optimal absorption of lumefantrine. In an attempt to enhance the bioavailability of lumefantrine, new solid dispersion formulations (SDF) were developed, and the pharmacokinetics of two SDF variants were assessed in a randomized, open-label, sequential two-part study in healthy volunteers. In part 1, the relative bioavailability of the two SDF variants was compared with that of the conventional formulation after administration of a single dose of 480 mg under fasted conditions in three parallel cohorts. In part 2, the pharmacokinetics of lumefantrine from both SDF variants were evaluated after a single dose of 480 mg under fed conditions and a single dose of 960 mg under fasted conditions. The bioavailability of lumefantrine from SDF variant 1 and variant 2 increased up to ∼48-fold and ∼24-fold, respectively, relative to that of the conventional formulation. Both variants demonstrated a positive food effect and a less than proportional increase in exposure between the 480-mg and 960-mg doses. Most adverse events (AEs) were mild to moderate in severity and not suspected to be related to the study drug. All five drug-related AEs occurred in subjects taking SDF variant 2. No clinically significant treatment-emergent changes in vital signs, electrocardiograms, or laboratory blood assessments were noted. The solid dispersion formulation enhances the lumefantrine bioavailability to a significant extent, and SDF variant 1 is superior to SDF variant 2. Copyright © 2017 Jain et al.

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.

Implementation of the Enhanced Flight Termination System at National Aeronautics and Space Administration Dryden Flight Research Center

NASA Technical Reports Server (NTRS)

Tow, David

2010-01-01

This paper discusses the methodology, requirements, tests, and results of the implementation of the current operating capability for the Enhanced Flight Termination System (EFTS) at the National Aeronautics and Space Administration (NASA) Dryden Flight Research Center (DFRC). The implementation involves the development of the EFTS at NASA DFRC starting from the requirements to system safety review to full end to end system testing, and concluding with the acceptance of the system as an operational system. The paper discusses the first operational usage and subsequent flight utilizing EFTS successfully.

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.

Cobalt-doping-induced synthesis of ceria nanodisks and their significantly enhanced catalytic activity.

PubMed

Guo, Xiao-Hui; Mao, Chao-Chao; Zhang, Ji; Huang, Jun; Wang, Wa-Nv; Deng, Yong-Hui; Wang, Yao-Yu; Cao, Yong; Huang, Wei-Xin; Yu, Shu-Hong

2012-05-21

High-quality cobalt-doped ceria nanostructures with triangular column, triangular slab, and disklike shapes are synthesized by tuning the doping amount of cobalt nitrate in a facile hydrothermal reaction. The cobalt-doped ceria nanodisks display significantly enhanced catalytic activity in CO oxidation due to exposed highly active crystal planes and the presence of numerous surface defects. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Structural Modification of (-)-Epigallocatechin Gallate (EGCG) Shows Significant Enhancement in Mitochondrial Biogenesis.

PubMed

Ha, Taewoong; Kim, Mi Kyoung; Park, Kwang-Su; Jung, Woong; Choo, Hyunah; Chong, Youhoon

2018-04-18

(-)-Epigallocatechin-3-gallate (EGCG) is known as a mitochondria-targeted molecule that can prevent mitochondrial deterioration and induce mitochondrial biogenesis by modulating key regulators of mitochondrial metabolism. In this study, we tackled whether derivatization of EGCG could result in enhancement of its effects on mitochondrial biogenesis. EGCG, EGCG peracetate (AcEGCG), and its 4″- O-alkyl substituted congeners prepared by previously reported procedures were biologically evaluated. Interestingly, EGCG and AcEGCG were only marginally effective in inducing mitochondrial biogenesis, while AcEGCG congeners with an alkyl group at the 4″- O position showed significantly increased biological activity compared to their parent compound. Among these series, 3f with a methyl-branched carbonate chain at the 4″- O position of the AcEGCG scaffold showed the most enhancement in inducing mitochondrial biogenesis. Hepa1-6 cells treated with 3f exhibited increases in both mitochondrial mass (1.5 times) and relative mtDNA content to nDNA (1.5 times). As a mitochondrial biogenesis enhancer, 3f also increased expression levels of regulators for mitochondrial function, including PGC-1α (4.0 fold), p-AMPK (2.5 fold), SIRT1 (4.2 fold), ERRα (1.8 fold), NRF-1 (1.6 fold), NRF-2 (1.7 fold), and mtTFA (1.6 folds). Investigation of oxidative phosphorylation by mitochondria in the presence of 3f revealed that 3f increased the NAD + /NADH ratio, the amount of cytochrome c, ATP synthesis, and oxygen consumption in Hepa1-6 cells by 2.2, 1.4, 1.5, and 2.1 fold, respectively. Taken together, these results warrant an extensive structure-activity relationship study for EGCG derivatives to develop novel mitochondrial biogenesis enhancers.

Changes in plasma glucose in Otsuka Long-Evans Tokushima Fatty rats after oral administration of maple syrup.

PubMed

Nagai, Noriaki; Yamamoto, Tetsushi; Tanabe, Wataru; Ito, Yoshimasa; Kurabuchi, Satoshi; Mitamura, Kuniko; Taga, Atsushi

2015-01-01

We investigate whether maple syrup is a suitable sweetener in the management of type 2 diabetes using the Otsuka Long-Evans Tokushima Fatty (OLETF) rat. The enhancement in plasma glucose (PG) and glucose absorption in the small intestine were lower after the oral administration of maple syrup than after sucrose administration in OLETF rats, and no significant differences were observed in insulin levels. These data suggested that maple syrup might inhibit the absorption of glucose from the small intestine and preventing the enhancement of PG in OLETF rats. Therefore, maple syrup might help in the prevention of type 2 diabetes.

Enhancement of bioavailability of cinnarizine from its beta-cyclodextrin complex on oral administration with DL-phenylalanine as a competing agent.

PubMed

Tokumura, T; Nanba, M; Tsushima, Y; Tatsuishi, K; Kayano, M; Machida, Y; Nagai, T

1986-04-01

The present investigation is concerned with an improvement of the bioavailability of cinnarizine by administering its beta-cyclodextrin complex together with another compound which competes with the beta-cyclodextrin molecule in complex formation in aqueous solution (competing agent). The bioavailability of cinnarizine on oral administration of the cinnarizine-beta-cyclodextrin inclusion complex was enhanced by the simultaneous administration of DL-phenylalanine as a competing agent, e.g., the AUC was 1.9 and 2.7 times as large as those of the cinnarizine-beta-cyclodextrin complex alone and cinnarizine alone, respectively. The enhancement of AUC and Cmax completely depended on the dose of DL-phenylalanine. It was found from these results that DL-phenylalanine acted as a competing agent in the GI tract and the minimum effective dose required of DL-phenylalanine might be 1 g for 50 mg of cinnarizine in the cinnarizine-beta-cyclodextrin complex. Evaluating the competing effect of DL-phenylalanine in vitro using an absorption simulator, it was found that the decreased penetration rate of cinnarizine through the artificial lipid barrier with addition of beta-cyclodextrin was restored with the addition of DL-phenylalanine.

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.

Rebamipide promotes healing of colonic ulceration through enhanced epithelial restitution.

PubMed

Takagi, Tomohisa; Naito, Yuji; Uchiyama, Kazuhiko; Okuda, Toshimitsu; Mizushima, Katsura; Suzuki, Takahiro; Handa, Osamu; Ishikawa, Takeshi; Yagi, Nobuaki; Kokura, Satoshi; Ichikawa, Hiroshi; Yoshikawa, Toshikazu

2011-09-07

To investigate the efficacy of rebamipide in a rat model of colitis and restitution of intestinal epithelial cells in vitro. Acute colitis was induced with trinitrobenzene sulfonic acid (TNBS) in male Wistar rats. Rats received intrarectal rebamipide treatment daily starting on day 7 and were sacrificed on day 14 after TNBS administration. The distal colon was removed to evaluate the various parameters of inflammation. Moreover, wound healing assays were used to determine the enhanced restitution of rat intestinal epithelial (RIE) cells treated with rebamipide. Intracolonic administration of rebamipide accelerated TNBS-induced ulcer healing. Increases in the wet weight of the colon after TNBS administration were significantly inhibited by rebamipide. The wound assay revealed that rebamipide enhanced the migration of RIE cells through phosphorylation of extracellular signal-regulated kinase (ERK) and activation of Rho kinase. Rebamipide enema healed intestinal injury by enhancing restitution of RIE cells, via ERK activation. Rebamipide might be a novel therapeutic approach for inflammatory bowel disease.

Rebamipide promotes healing of colonic ulceration through enhanced epithelial restitution

PubMed Central

Takagi, Tomohisa; Naito, Yuji; Uchiyama, Kazuhiko; Okuda, Toshimitsu; Mizushima, Katsura; Suzuki, Takahiro; Handa, Osamu; Ishikawa, Takeshi; Yagi, Nobuaki; Kokura, Satoshi; Ichikawa, Hiroshi; Yoshikawa, Toshikazu

2011-01-01

AIM: To investigate the efficacy of rebamipide in a rat model of colitis and restitution of intestinal epithelial cells in vitro. METHODS: Acute colitis was induced with trinitrobenzene sulfonic acid (TNBS) in male Wistar rats. Rats received intrarectal rebamipide treatment daily starting on day 7 and were sacrificed on day 14 after TNBS administration. The distal colon was removed to evaluate the various parameters of inflammation. Moreover, wound healing assays were used to determine the enhanced restitution of rat intestinal epithelial (RIE) cells treated with rebamipide. RESULTS: Intracolonic administration of rebamipide accelerated TNBS-induced ulcer healing. Increases in the wet weight of the colon after TNBS administration were significantly inhibited by rebamipide. The wound assay revealed that rebamipide enhanced the migration of RIE cells through phosphorylation of extracellular signal-regulated kinase (ERK) and activation of Rho kinase. CONCLUSION: Rebamipide enema healed intestinal injury by enhancing restitution of RIE cells, via ERK activation. Rebamipide might be a novel therapeutic approach for inflammatory bowel disease. PMID:21987622

Enhanced effects of cortisol administration on episodic and working memory in aging veterans with PTSD.

PubMed

Yehuda, Rachel; Harvey, Philip D; Buchsbaum, Monte; Tischler, Lisa; Schmeidler, James

2007-12-01

Though both glucocorticoid alterations and memory impairments have been noted in posttraumatic stress disorder (PTSD), it is not clear if these phenomena are causally linked. As there is emerging evidence that these domains become further altered in PTSD with increasing age, it is of interest to examine these relationships in an older cohort. Aging (mean age, 62.7+/-8.9; range, 52-81) combat veterans with (n=13) and without (n=17) PTSD received an intravenous bolus of 17.5 mg hydrocortisone (cortisol), a naturally occurring glucocorticoid, or placebo in a randomized, double-blind manner, on two mornings approximately 1-2 weeks apart. Neuropsychological testing to evaluate episodic and working memory performance was performed 75 min later. Cortisol enhanced episodic memory performance in both groups of subjects, but enhanced elements of working memory performance only in the PTSD+ group. The preferential effect of cortisol administration on working memory in PTSD may be related to the superimposition of PTSD and age, as cortisol had impairing effects on this task in a previously studied, younger cohort. The findings suggest that there may be opportunities for developing therapeutic strategies using glucocorticoids in the treatment of aging combat veterans.

Complete Au@ZnO core-shell nanoparticles with enhanced plasmonic absorption enabling significantly improved photocatalysis

NASA Astrophysics Data System (ADS)

Sun, Yiqiang; Sun, Yugang; Zhang, Tao; Chen, Guozhu; Zhang, Fengshou; Liu, Dilong; Cai, Weiping; Li, Yue; Yang, Xianfeng; Li, Cuncheng

2016-05-01

Nanostructured ZnO exhibits high chemical stability and unique optical properties, representing a promising candidate among photocatalysts in the field of environmental remediation and solar energy conversion. However, ZnO only absorbs the UV light, which accounts for less than 5% of total solar irradiation, significantly limiting its applications. In this article, we report a facile and efficient approach to overcome the poor wettability between ZnO and Au by carefully modulating the surface charge density on Au nanoparticles (NPs), enabling rapid synthesis of Au@ZnO core-shell NPs at room temperature. The resulting Au@ZnO core-shell NPs exhibit a significantly enhanced plasmonic absorption in the visible range due to the Au NP cores. They also show a significantly improved photocatalytic performance in comparison with their single-component counterparts, i.e., the Au NPs and ZnO NPs. Moreover, the high catalytic activity of the as-synthesized Au@ZnO core-shell NPs can be maintained even after many cycles of photocatalytic reaction. Our results shed light on the fact that the Au@ZnO core-shell NPs represent a promising class of candidates for applications in plasmonics, surface-enhanced spectroscopy, light harvest devices, solar energy conversion, and degradation of organic pollutants.Nanostructured ZnO exhibits high chemical stability and unique optical properties, representing a promising candidate among photocatalysts in the field of environmental remediation and solar energy conversion. However, ZnO only absorbs the UV light, which accounts for less than 5% of total solar irradiation, significantly limiting its applications. In this article, we report a facile and efficient approach to overcome the poor wettability between ZnO and Au by carefully modulating the surface charge density on Au nanoparticles (NPs), enabling rapid synthesis of Au@ZnO core-shell NPs at room temperature. The resulting Au@ZnO core-shell NPs exhibit a significantly enhanced plasmonic

Black silicon significantly enhances phosphorus diffusion gettering.

PubMed

Pasanen, Toni P; Laine, Hannu S; Vähänissi, Ville; Schön, Jonas; Savin, Hele

2018-01-31

Black silicon (b-Si) is currently being adopted by several fields of technology, and its potential has already been demonstrated in various applications. We show here that the increased surface area of b-Si, which has generally been considered as a drawback e.g. in applications that require efficient surface passivation, can be used as an advantage: it enhances gettering of deleterious metal impurities. We demonstrate experimentally that interstitial iron concentration in intentionally contaminated silicon wafers reduces from 1.7 × 10 13  cm -3 to less than 10 10  cm -3 via b-Si gettering coupled with phosphorus diffusion from a POCl 3 source. Simultaneously, the minority carrier lifetime increases from less than 2 μs of a contaminated wafer to more than 1.5 ms. A series of different low temperature anneals suggests segregation into the phosphorus-doped layer to be the main gettering mechanism, a notion which paves the way of adopting these results into predictive process simulators. This conclusion is supported by simulations which show that the b-Si needles are entirely heavily-doped with phosphorus after a typical POCl 3 diffusion process, promoting iron segregation. Potential benefits of enhanced gettering by b-Si include the possibility to use lower quality silicon in high-efficiency photovoltaic devices.

Transepithelial Transport of Curcumin in Caco-2 Cells Is significantly Enhanced by Micellar Solubilisation.

PubMed

Frank, Jan; Schiborr, Christina; Kocher, Alexa; Meins, Jürgen; Behnam, Dariush; Schubert-Zsilavecz, Manfred; Abdel-Tawab, Mona

2017-03-01

Curcumin, the active constituent of Curcuma longa L. (family Zingiberaceae), has gained increasing interest because of its anti-cancer, anti-inflammatory, anti-diabetic, and anti-rheumatic properties associated with good tolerability and safety up to very high doses of 12 g. Nanoscaled micellar formulations on the base of Tween 80 represent a promising strategy to overcome its low oral bioavailability. We therefore aimed to investigate the uptake and transepithelial transport of native curcumin (CUR) vs. a nanoscaled micellar formulation (Sol-CUR) in a Caco-2 cell model. Sol-CUR afforded a higher flux than CUR (39.23 vs. 4.98 μg min -1  cm -2 , respectively). This resulted in a higher P app value of 2.11 × 10 -6  cm/s for Sol-CUR compared to a P app value of 0.56 × 10 -6  cm/s for CUR. Accordingly a nearly 9.5 fold higher amount of curcumin was detected on the basolateral side at the end of the transport experiments after 180 min with Sol-CUR compared to CUR. The determined 3.8-fold improvement in the permeability of curcumin is in agreement with an up to 185-fold increase in the AUC of curcumin observed in humans following the oral administration of the nanoscaled micellar formulation compared to native curcumin. The present study demonstrates that the enhanced oral bioavailability of micellar curcumin formulations is likely a result of enhanced absorption into and increased transport through small intestinal epithelial cells.

Quantitative evaluation of contrast-enhanced ultrasound after intravenous administration of a microbubble contrast agent for differentiation of benign and malignant thyroid nodules: assessment of diagnostic accuracy.

PubMed

Nemec, Ursula; Nemec, Stefan F; Novotny, Clemens; Weber, Michael; Czerny, Christian; Krestan, Christian R

2012-06-01

To investigate the diagnostic accuracy, through quantitative analysis, of contrast-enhanced ultrasound (CEUS), using a microbubble contrast agent, in the differentiation of thyroid nodules. This prospective study enrolled 46 patients with solitary, scintigraphically non-functional thyroid nodules. These patients were scheduled for surgery and underwent preoperative CEUS with pulse-inversion harmonic imaging after intravenous microbubble contrast medium administration. Using histology as a standard of reference, time-intensity curves of benign and malignant nodules were compared by means of peak enhancement and wash-out enhancement relative to the baseline intensity using a mixed model ANOVA. ROC analysis was performed to assess the diagnostic accuracy in the differentiation of benign and malignant nodules on CEUS. The complete CEUS data of 42 patients (31/42 [73.8%] benign and 11/42 [26.2%] malignant nodules) revealed a significant difference (P < 0.001) in enhancement between benign and malignant nodules. Furthermore, based on ROC analysis, CEUS demonstrated sensitivity of 76.9%, specificity of 84.8% and accuracy of 82.6%. Quantitative analysis of CEUS using a microbubble contrast agent allows the differentiation of benign and malignant thyroid nodules and may potentially serve, in addition to grey-scale and Doppler ultrasound, as an adjunctive tool in the assessment of patients with thyroid nodules. • Contrast-enhanced ultrasound (CEUS) helps differentiate between benign and malignant thyroid nodules. • Quantitative CEUS analysis yields sensitivity of 76.9% and specificity of 84.8%. • CEUS may be a potentially useful adjunct in assessing thyroid nodules.

Significantly enhanced memory effect in metallic glass by multistep training

NASA Astrophysics Data System (ADS)

Li, M. X.; Luo, P.; Sun, Y. T.; Wen, P.; Bai, H. Y.; Liu, Y. H.; Wang, W. H.

2017-11-01

The state of metastable equilibrium glass can carry an imprint of the past and exhibit memory effect. As a hallmark of glassy dynamics, memory effect can affect glassy behavior as it evolves further upon time. Even though the physical picture of the memory effect has been well studied, it is unclear whether a glass can recall as many pieces of information as possible, and if so, how the glass will accordingly behave. We report that by fractionizing temperature interval, inserting multistep aging protocols, and optimizing the time of each temperature step, i.e., by imposing a multistep "training" on a prototypical P d40N i10C u30P20 metallic glass, the memory of the trained glass can be significantly strengthened, marked by a pronounced augment in potential energy. These findings provide a new guide for regulating the energy state of glass by enhancing the nonequilibrium behaviors of the memory effect and offer an opportunity to develop a clearer physical picture of glassy dynamics.

Does adding clinical data to administrative data improve agreement among hospital quality measures?

PubMed

Hanchate, Amresh D; Stolzmann, Kelly L; Rosen, Amy K; Fink, Aaron S; Shwartz, Michael; Ash, Arlene S; Abdulkerim, Hassen; Pugh, Mary Jo V; Shokeen, Priti; Borzecki, Ann

2017-09-01

Hospital performance measures based on patient mortality and readmission have indicated modest rates of agreement. We examined if combining clinical data on laboratory tests and vital signs with administrative data leads to improved agreement with each other, and with other measures of hospital performance in the nation's largest integrated health care system. We used patient-level administrative and clinical data, and hospital-level data on quality indicators, for 2007-2010 from the Veterans Health Administration (VA). For patients admitted for acute myocardial infarction (AMI), heart failure (HF) and pneumonia we examined changes in hospital performance on 30-d mortality and 30-d readmission rates as a result of adding clinical data to administrative data. We evaluated whether this enhancement yielded improved measures of hospital quality, based on concordance with other hospital quality indicators. For 30-d mortality, data enhancement improved model performance, and significantly changed hospital performance profiles; for 30-d readmission, the impact was modest. Concordance between enhanced measures of both outcomes, and with other hospital quality measures - including Joint Commission process measures, VA Surgical Quality Improvement Program (VASQIP) mortality and morbidity, and case volume - remained poor. Adding laboratory tests and vital signs to measure hospital performance on mortality and readmission did not improve the poor rates of agreement across hospital quality indicators in the VA. Efforts to improve risk adjustment models should continue; however, evidence of validation should precede their use as reliable measures of quality. Published by Elsevier Inc.

Administration of exogenous acylated ghrelin or rikkunshito, an endogenous ghrelin enhancer, improves the decrease in postprandial gastric motility in an acute restraint stress mouse model

PubMed Central

Nahata, M; Saegusa, Y; Sadakane, C; Yamada, C; Nakagawa, K; Okubo, N; Ohnishi, S; Hattori, T; Sakamoto, N; Takeda, H

2014-01-01

Background Physical or psychological stress causes functional disorders in the upper gastrointestinal tract. This study aims to elucidate the ameliorating effect of exogenous acylated ghrelin or rikkunshito, a Kampo medicine which acts as a ghrelin enhancer, on gastric dysfunction during acute restraint stress in mice. Methods Fasted and postprandial motor function of the gastric antrum was wirelessly measured using a strain gauge force transducer and solid gastric emptying was detected in mice exposed to restraint stress. Plasma corticosterone and ghrelin levels were also measured. To clarify the role of ghrelin on gastrointestinal dysfunction in mice exposed to stress, exogenous acylated ghrelin or rikkunshito was administered, then the mice were subjected to restraint stress. Key Results Mice exposed to restraint stress for 60 min exhibited delayed gastric emptying and increased plasma corticosterone levels. Gastric motility was decreased in mice exposed to restraint stress in both fasting and postprandial states. Restraint stress did not cause any change in plasma acylated ghrelin levels, but it significantly increased the plasma des-acyl ghrelin levels. Administration of acylated ghrelin or rikkunshito improved the restraint stress-induced delayed gastric emptying and decreased antral motility. Ameliorating effects of rikkunshito on stress-induced gastric dysfunction were abolished by simultaneous administration of a ghrelin receptor antagonist. Conclusions & Inferences Plasma acylated/des-acyl ghrelin imbalance was observed in acute restraint stress. Supplementation of exogenous acylated ghrelin or enhancement of endogenous ghrelin signaling may be useful in the treatment of decreased gastric function caused by stress. PMID:24684160

Administration of CD34+ cells after stroke enhances neurogenesis via angiogenesisin a mouse model

PubMed Central

Taguchi, Akihiko; Soma, Toshihiro; Tanaka, Hidekazu; Kanda, Takayoshi; Nishimura, Hiroyuki; Yoshikawa, Hiroo; Tsukamoto, Yoshitane; Iso, Hiroyuki; Fujimori, Yoshihiro; Stern, David M.; Naritomi, Hiroaki; Matsuyama, Tomohiro

2004-01-01

Thrombo-occlusive cerebrovascular disease resulting in stroke and permanent neuronal loss is an important cause of morbidity and mortality. Because of the unique properties of cerebral vasculature and the limited reparative capability of neuronal tissue, it has been difficult to devise effective neuroprotective therapies in cerebral ischemia. Our results demonstrate that systemic administration of human cord blood–derived CD34+ cells to immunocompromised mice subjected to stroke 48 hours earlier induces neovascularization in the ischemic zone and provides a favorable environment for neuronal regeneration. Endogenous neurogenesis, suppressed by an antiangiogenic agent, is accelerated as a result of enhanced migration of neuronal progenitor cells to the damaged area, followed by their maturation and functional recovery. Our data suggest an essential role for CD34+ cells in promoting directly or indirectly an environment conducive to neovascularization of ischemic brain so that neuronal regeneration can proceed. PMID:15286799

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.

Cognitive Enhancement and Education

ERIC Educational Resources Information Center

Buchanan, Allen

2011-01-01

Cognitive enhancement--augmenting normal cognitive capacities--is not new. Literacy, numeracy, computers, and the practices of science are all cognitive enhancements. Science is now making new cognitive enhancements possible. Biomedical cognitive enhancements (BCEs) include the administration of drugs, implants of genetically engineered or…

Chronic administration of parecoxib exerts anxiolytic-like and memory enhancing effects and modulates synaptophysin expression in mice.

PubMed

Wang, Bo; Jin, Xin; Kuang, Xin; Tian, Shaowen

2017-11-13

Previous studies have shown that cyclooxygenase-2, a key enzyme that converts arachidonic acid to prostaglandins, is involved in anxiety and cognitive processes, but few studies have investigated the effects of chronic administration of cyclooxygenase-2 inhibitors on anxiety, learning and memory under normal physiological conditions. The aim of the study was to investigate the effects of chronic administration of parecoxib, a cyclooxygenase-2 inhibitor, on anxiety behavior and memory performance under normal physiological conditions and to explore the possible neural mechanism underlying parecoxib-mediated effects. Adult male ICR mice were randomly divided into four groups: the control group and three parecoxib groups. Mice received normal saline or parecoxib (2.5, 5.0 or 10 mg/kg) intraperitoneal injection once a day for 21 days, respectively. Elevated plus-maze, novel object recognition and Y maze tests were conducted on day 23, 24 and 26, respectively. Four additional groups that received same drug treatment were used to measure synaptophysin protein levels by western blot and prostaglandin E2 (PGE2) levels by ELISA in the amygdala and hippocampus on day 26. Chronic parecoxib exerted an anxiolytic-like effect in the plus-maze test test, and enhanced memory performance in the novel object recognition and Y maze tests. Western blot analysis showed that chronic parecoxib down-regulated synaptophysin levels in the amygdala and up-regulated synaptophysin levels in the hippocampus. ELISA assay showed that chronic parecoxib inhibited PGE2 in the hippocampus but not amygdala. Chronic parecoxib exerts anxiolytic-like and memory enhancing effects, which might be mediated through differential modulation of synaptophysin and PGE2 in the amygdala and hippocampus.

Practice enhancement strengthens hospital-physician ties.

PubMed

Pivnicny, V

1992-12-01

In the increasingly competitive U.S. healthcare environment, hospitals must be concerned with maintaining and increasing the number of patients admitted. A key strategy for hospitals is to fortify relationships with physicians who admit and refer patients. Practice enhancement services designed to improve the strategic, financial, and administrative operation of physicians' practices can contribute significantly to the development of positive hospital-physician relationships.

The Impact of Injector-Based Contrast Agent Administration on Bolus Shape and Magnetic Resonance Angiography Image Quality.

PubMed

Jost, Gregor; Endrikat, Jan; Pietsch, Hubertus

2017-01-01

To compare injector-based contrast agent (CA) administration with hand injection in magnetic resonance angiography (MRA). Gadobutrol was administered in 6 minipigs with 3 protocols: (a) hand injection (one senior technician), (b) hand injection (6 less-experienced technicians), and (c) power injector administration. The arterial bolus shape was quantified by test bolus measurements. A head and neck MRA was performed for quantitative and qualitative comparison of signal enhancement. A significantly shorter time to peak was observed for protocol C, whereas no significant differences between protocols were found for peak height and bolus width. However, for protocol C, these parameters showed a much lower variation. The MRA revealed a significantly higher signal-to-noise ratio for injector-based administration. A superimposed strong contrast of the jugular vein was found in 50% of the hand injections. Injector-based CA administration results in a more standardized bolus shape, a higher vascular contrast, and a more robust visualization of target vessels.

Enhanced reporting of deaths among Aboriginal and Torres Strait Islander peoples using linked administrative health datasets.

PubMed

Taylor, Lee K; Bentley, Jason; Hunt, Jennifer; Madden, Richard; McKeown, Sybille; Brandt, Peter; Baker, Deborah

2012-07-02

Aboriginal and Torres Strait Islander peoples are under-reported in administrative health datasets in NSW, Australia. Correct reporting of Aboriginal and Torres Strait Islander peoples is essential to measure the effectiveness of policies and programmes aimed at reducing the health disadvantage experienced by Aboriginal and Torres Strait Islander peoples. This study investigates the potential of record linkage to enhance reporting of deaths among Aboriginal and Torres Strait Islander peoples in NSW, Australia. Australian Bureau of Statistics death registration data for 2007 were linked with four population health datasets relating to hospitalisations, emergency department attendances and births. Reporting of deaths was enhanced from linked records using two methods, and effects on patterns of demographic characteristics and mortality indicators were examined. Reporting of deaths increased by 34.5% using an algorithm based on a weight of evidence of a person being Aboriginal or Torres Strait Islander, and by 56.6% using an approach based on 'at least one report' of a person being Aboriginal or Torres Strait Islander. The increase was relatively greater in older persons and those living in less geographically remote areas. Enhancement resulted in a reduction in the urban-remote differential in median age at death and increases in standardised mortality ratios particularly for chronic conditions. Record linkage creates a statistical construct that helps to correct under-reporting of deaths and potential bias in mortality statistics for Aboriginal and Torres Strait Islander peoples.

Diagnostic significance of gadolinium-DTPA (diethylenetriamine penta-acetic acid) enhanced magnetic resonance imaging in thrombolytic treatment for acute myocardial infarction: its potential in assessing reperfusion.

PubMed Central

van der Wall, E E; van Dijkman, P R; de Roos, A; Doornbos, J; van der Laarse, A; Manger Cats, V; van Voorthuisen, A E; Matheijssen, N A; Bruschke, A V

1990-01-01

The diagnostic value of gadolinium-DTPA (diethylenetriamine penta-acetic acid) enhanced magnetic resonance imaging in patients treated by thrombolysis for acute myocardial infarction was assessed in 27 consecutive patients who had a first acute myocardial infarction (14 anterior, 13 inferior) and who underwent thrombolytic treatment and coronary arteriography within 4 hours of the onset of symptoms. Magnetic resonance imaging was performed 93 hours (range 15-241) after the onset of symptoms. A Philips Gyroscan (0.5 T) was used, and spin echo measurements (echo time 30 ms) were made before and 20 minutes after intravenous injection of 0.1 mmol/kg gadolinium-DTPA. In all patients contrast enhancement of the infarcted areas was seen after Gd-DTPA. The signal intensities of the infarcted and normal values were used to calculate the intensity ratios. Mean (SD) intensity ratios after Gd-DTPA were significantly increased (1.15 (0.17) v 1.52 (0.29). Intensity ratios were higher in the 17 patients who underwent magnetic resonance imaging more than 72 hours after the onset of symptoms than in the 10 who underwent magnetic resonance imaging earlier, the difference being significantly greater after administration of Gd-DTPA (1.38 (0.12) v 1.61 (0.34). When patients were classified according to the site and size of the infarcted areas, or to reperfusion (n = 19) versus non-reperfusion (n = 8), the intensity ratios both before and after Gd-DTPA did not show significant differences. Magnetic resonance imaging with Gd-DTPA improved the identification of acutely infarcted areas, but with current techniques did not identify patients in whom thrombolytic treatment was successful. Images PMID:2310640

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.

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

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.

Tyrosine administration enhances dopamine synthesis and release in light-activated rat retina

NASA Technical Reports Server (NTRS)

Gibson, C. J.; Watkins, C. J.; Wurtman, R. J.

1983-01-01

Exposure of dark-adapted albino rats to light (350 lux) significantly elevated retinal levels of the dopamine metabolite dihydroxyphenyl acetic acid during the next hour; their return to a dark environment caused dihydroxyphenyl acetic acid levels to fall. Retinal dopamine levels were increased slightly by light exposure, suggesting that the increase in dihydroxyphenyl acetic acid reflected accelerated dopamine synthesis. Administration of tyrosine (100 mg/kg, i.p.) further elevated retinal dihydroxyphenyl acetic acid among light-exposed animals, but failed to affect dopamine release among animals in the dark. These observations show that a physiological stimulus - light exposure - can cause catecholaminergic neurons to become tyrosine-dependent; they also suggest that food consumption may affect neurotransmitter release within the retina.

Enhanced electrical responsiveness in the cerebral cortex with oral melatonin administration after a small hemorrhage near the internal capsule in rats.

PubMed

Ueda, Yoshitomo; Masuda, Tadashi; Ishida, Akimasa; Misumi, Sachiyo; Shimizu, Yuko; Jung, Cha-Gyun; Hida, Hideki

2014-11-01

Intracerebral hemorrhage (ICH) can cause direct brain injury at the insult site and indirect damage in remote brain areas. Although a protective effect of melatonin (ML) has been reported for ICH, its detailed mechanisms and effects on remote brain injury remain unclear. To clarify the mechanism of indirect neuroprotection after ICH, we first investigated whether ML improved motor function after ICH and then examined the underlying mechanisms. The ICH model rat was made by collagenase injection into the left globus pallidus, adjacent to the internal capsule. ML oral administration (15 mg/kg) for 7 days after ICH resulted in significant recovery of motor function. Retrograde labeling of the corticospinal tract by Fluoro-Gold revealed a significant increase in numbers of positive neurons in the cerebral cortex. Immunohistological analysis showed that ML treatment induced no difference in OX41-positive activated microglia/macrophage at day 1 (D1) but a significant reduction in 8-hydroxydeoxyguanosin-positive cells at D7. Neutral red assay revealed that ML significantly prevented H2 O2 -induced cell death in cultured oligodendrocytes and astrocytes but not in neurons. Electrophysiological response in the cerebral cortex area where the number of Fluoro-Gold-positive cells was increased was significantly improved in ML-treated rats. These data suggest that ML improves motor abilities after ICH by protecting oligodendrocytes and astrocytes in the vicinity of the lesion in the corticospinal tract from oxidative stress and causes enhanced electrical responsiveness in the cerebral cortex remote to the ICH pathology. Copyright © 2014 Wiley Periodicals, Inc.

Caffeine potentiates the enhancement by choline of striatal acetylcholine release

NASA Technical Reports Server (NTRS)

Johnson, D. A.; Ulus, I. H.; Wurtman, R. J.

1992-01-01

We investigated the effect of peripherally administered caffeine (50 mg/kg), choline (30, 60, or 120 mg/kg) or combinations of both drugs on the spontaneous release of acetylcholine (ACh) from the corpus striatum of anesthetized rats using in vivo microdialysis. Caffeine alone or choline in the 30 or 60 mg/kg dose failed to increase ACh in microdialysis samples; the 120 mg/kg choline dose significantly enhanced ACh during the 80 min following drug administration. Coadministration of caffeine with choline significantly increased ACh release after each of the choline doses tested. Peak microdialysate levels with the 120 mg/kg dose were increased 112% when caffeine was additionally administered, as compared with 54% without caffeine. These results indicate that choline administration can enhance spontaneous ACh release from neurons, and that caffeine, a drug known to block adenosine receptors on these neurons, can amplify the choline effect.

Microperforations significantly enhance diffusion across round window membrane.

PubMed

Kelso, Catherine M; Watanabe, Hirobumi; Wazen, Joseph M; Bucher, Tizian; Qian, Zhen J; Olson, Elizabeth S; Kysar, Jeffrey W; Lalwani, Anil K

2015-04-01

Introduction of microperforations in round window membrane (RWM) will allow reliable and predictable intracochlear delivery of pharmaceutical, molecular, or cellular therapeutic agents. Reliable delivery of medications into the inner ear remains a formidable challenge. The RWM is an attractive target for intracochlear delivery. However, simple diffusion across intact RWM is limited by what material can be delivered, size of material to be delivered, difficulty with precise dosing, timing, and precision of delivery over time. Further, absence of reliable methods for measuring diffusion across RWM in vitro is a significant experimental impediment. A novel model for measuring diffusion across guinea pig RWM, with and without microperforation, was developed and tested: cochleae, sparing the RWM, were embedded in 3D-printed acrylic holders using hybrid dental composite and light cured to adapt the round window niche to 3 ml Franz diffusion cells. Perforations were created with 12.5-μm-diameter needles and examined with light microscopy. Diffusion of 1 mM Rhodamine B across RWM in static diffusion cells was measured via fluorescence microscopy. The diffusion cell apparatus provided reliable and replicable measurements of diffusion across RWM. The permeability of Rhodamine B across intact RWM was 5.1 × 10(9-) m/s. Manual application of microperforation with a 12.5-μm-diameter tip produced an elliptical tear removing 0.22 ± 0.07% of the membrane and was associated with a 35× enhancement in diffusion (P < 0.05). Diffusion cells can be applied to the study of RWM permeability in vitro. Microperforation in RWM is an effective means of increasing diffusion across the RWM.

Adrenergic enhancement of consolidation of object recognition memory.

PubMed

Dornelles, Arethuza; de Lima, Maria Noemia Martins; Grazziotin, Manoela; Presti-Torres, Juliana; Garcia, Vanessa Athaide; Scalco, Felipe Siciliani; Roesler, Rafael; Schröder, Nadja

2007-07-01

Extensive evidence indicates that epinephrine (EPI) modulates memory consolidation for emotionally arousing tasks in animals and human subjects. However, previous studies have not examined the effects of EPI on consolidation of recognition memory. Here we report that systemic administration of EPI enhances consolidation of memory for a novel object recognition (NOR) task under different training conditions. Control male rats given a systemic injection of saline (0.9% NaCl) immediately after NOR training showed significant memory retention when tested at 1.5 or 24, but not 96h after training. In contrast, rats given a post-training injection of EPI showed significant retention of NOR at all delays. In a second experiment using a different training condition, rats treated with EPI, but not SAL-treated animals, showed significant NOR retention at both 1.5 and 24-h delays. We next showed that the EPI-induced enhancement of retention tested at 96h after training was prevented by pretraining systemic administration of the beta-adrenoceptor antagonist propranolol. The findings suggest that, as previously observed in experiments using aversively motivated tasks, epinephrine modulates consolidation of recognition memory and that the effects require activation of beta-adrenoceptors.

Monitoring Items in Real Time to Enhance CAT Security

ERIC Educational Resources Information Center

Zhang, Jinming; Li, Jie

2016-01-01

An IRT-based sequential procedure is developed to monitor items for enhancing test security. The procedure uses a series of statistical hypothesis tests to examine whether the statistical characteristics of each item under inspection have changed significantly during CAT administration. This procedure is compared with a previously developed…

Co-administration of liposomal l-OHP and PEGylated TS shRNA-lipoplex: A novel approach to enhance anti-tumor efficacy and reduce the immunogenic response to RNAi molecules.

PubMed

Alaaeldin, Eman; Abu Lila, Amr S; Ando, Hidenori; Fukushima, Masakazu; Huang, Cheng-Long; Wada, Hiromi; Sarhan, Hatem A; Khaled, Khaled A; Ishida, Tatsuhiro

2017-06-10

Many therapeutic strategies have been applied in efforts to conquer the development and/or progression of cancer. The combination of chemotherapy and an RNAi-based approach has proven to be an efficient anticancer therapy. However, the feasibility of such a therapeutic strategy has been substantially restricted either by the failure to achieve the efficient delivery of RNAi molecules to tumor tissue or by the immunostimulatory response triggered by RNAi molecules. In this study, therefore, we intended to investigate the efficacy of using liposomal oxaliplatin (liposomal l-OHP) to guarantee the efficient delivery of RNAi molecules, namely shRNA against thymidylate synthase (TS shRNA) complexed with cationic liposome (TS shRNA-lipoplex), to solid tumors, and to suppress the immunostimulatory effect of RNAi molecules, TS shRNA, following intravenous administration. Herein, we describe how liposomal l-OHP enhanced the intra-tumor accumulation of TS shRNA-lipoplex and significantly reduced the immunostimulatory response triggered by TS shRNA. Consequently, such enhanced accumulation of TS shRNA-lipoplex along with the cytotoxic effect of liposomal l-OHP led to a remarkable tumor growth suppression (compared to mono-therapy) following systemic administration. Our results, therefore, may have important implications for the provision of a safer and more applicable combination therapy of RNAi molecules and anti-cancer agents that can produce a more reliable anti-tumor effect. Copyright © 2017 Elsevier B.V. All rights reserved.

Strengthening Collaborative Leadership for Thai Primary School Administrators

ERIC Educational Resources Information Center

Samriangjit, Prapaporn; Tesaputa, Kowat; Somprach, Kanokorn

2016-01-01

The objectives of this research were: 1) to investigate the elements and indicators of collaborative leadership of primary school administrators, 2) to explore the existing situation and required situation of collaborative leadership of primary school administrators, 3) to develop a program to enhance collaborative leadership of primary school…

Gender Profiles and Career Aspiration of Administrators in Higher Education.

ERIC Educational Resources Information Center

Hubbard, Susan S.; Robinson, Jacquelyn P.

A study surveyed 370 administrators in four-year institutions in the mid-southern United States to identify factors that enhance administrative placement with regard to gender. By administrative position, the sample included the following: 20 presidents/chancellors/provosts; 50 vice-presidents/vice-chancellors; 100 deans; and 200 department or…

Potential of Essential Oils as Penetration Enhancers for Transdermal Administration of Ibuprofen to Treat Dysmenorrhoea.

PubMed

Chen, Jun; Jiang, Qiu-Dong; Wu, Ye-Ming; Liu, Pei; Yao, Jun-Hong; Lu, Qing; Zhang, Hui; Duan, Jin-Ao

2015-10-07

The present study was conducted to evaluate and compare five essential oils (EOs) as penetration enhancers (PEs) to improve the transdermal drug delivery (TDD) of ibuprofen to treat dysmenorrhoea. The EOs were prepared using the steam distillation method and their chemical compositions were identified by GC-MS. The corresponding cytotoxicities were evaluated in epidermal keartinocyte HaCaT cell lines by an MTT assay. Furthermore, the percutaneous permeation studies were carried out to compare the permeation enhancement effect of EOs. Then the therapeutic efficacy of ibuprofen with EOs was evaluated using dysmenorrheal model mice. The data supports a decreasing trend of skin cell viability in which Clove oil >Angelica oil > Chuanxiong oil > Cyperus oil > Cinnamon oil > Azone. Chuanxiong oil and Angelica oil had been proved to possess a significant permeation enhancement for TDD of ibuprofen. More importantly, the pain inhibitory intensity of ibuprofen hydrogel was demonstrated to be greater with Chuanxiong oil when compared to ibuprofen without EOs (p < 0.05). The contents of calcium ion and nitric oxide (NO) were also significantly changed after the addition of Chuanxiong oil (p < 0.05). In summary, we suggest that Chuanxiong oil should be viewed as the best PE for TDD of ibuprofen to treat dysmenorrhea.

Dentate gyrus neurogenesis ablation via cranial irradiation enhances morphine self-administration and locomotor sensitization.

PubMed

Bulin, Sarah E; Mendoza, Matthew L; Richardson, Devon R; Song, Kwang H; Solberg, Timothy D; Yun, Sanghee; Eisch, Amelia J

2018-03-01

Adult dentate gyrus (DG) neurogenesis is important for hippocampal-dependent learning and memory, but the role of new neurons in addiction-relevant learning and memory is unclear. To test the hypothesis that neurogenesis is involved in the vulnerability to morphine addiction, we ablated adult DG neurogenesis and examined morphine self-administration (MSA) and locomotor sensitization. Male Sprague-Dawley rats underwent hippocampal-focused, image-guided X-ray irradiation (IRR) to eliminate new DG neurons or sham treatment (Sham). Six weeks later, rats underwent either MSA (Sham = 16, IRR = 15) or locomotor sensitization (Sham = 12, IRR = 12). Over 21 days of MSA, IRR rats self-administered ~70 percent more morphine than Sham rats. After 28 days of withdrawal, IRR rats pressed the active lever 40 percent more than Sham during extinction. This was not a general enhancement of learning or locomotion, as IRR and Sham groups had similar operant learning and inactive lever presses. For locomotor sensitization, both IRR and Sham rats sensitized, but IRR rats sensitized faster and to a greater extent. Furthermore, dose-response revealed that IRR rats were more sensitive at a lower dose. Importantly, these increases in locomotor activity were not apparent after acute morphine administration and were not a byproduct of irradiation or post-irradiation recovery time. Therefore, these data, along with other previously published data, indicate that reduced hippocampal neurogenesis confers vulnerability for multiple classes of drugs. Thus, therapeutics to specifically increase or stabilize hippocampal neurogenesis could aid in preventing initial addiction as well as future relapse. © 2017 Society for the Study of Addiction.

Enhanced oral bioavailability of docetaxel in rats combined with myricetin: In situ and in vivo evidences.

PubMed

Hao, Tianyun; Ling, Yunni; Wu, Meijuan; Shen, Yajing; Gao, Yu; Liang, Shujun; Gao, Yuan; Qian, Shuai

2017-04-01

The purpose of this study was to investigate the effect of myricetin on the pharmacokinetics of docetaxel in rats. In comparison to oral docetaxel alone (40mg/kg), the bioavailability of docetaxel could be significantly enhanced by 1.6-2.4-fold via oral co-administration with various flavonoids (apigenin, naringenin, baicalein, quercetin and myricetin) at a dosage of 10mg/kg, and myricetin showed the highest bioavailability improvement. Further pharmacokinetic studies demonstrated that the presence of myricetin (5-20mg/kg) enhanced both C max and AUC of docetaxel with the highest C max (162ng/mL, 2.3-fold) and relative bioavailability (244%) achieved at 10mg/kg of myricetin, while t 1/2 was not influenced. In order to explore the reasons for such bioavailability enhancement of docetaxel, rat in situ single-pass intestinal perfusion model and intravenous docetaxel co-administrated with oral myricetin were carried out. After combining with myricetin, the permeability coefficient (P blood ) of docetaxel based on its appearance in mesenteric blood was significantly increased up to 3.5-fold in comparison to that of docetaxel alone. Different from oral docetaxel, the intravenous pharmacokinetics of docetaxel was not affected by co-administration of myricetin, indicating the limited effect of myricetin on the elimination of docetaxel. The above findings suggested that the oral bioavailability enhancement of docetaxel via co-administration with myricetin might be mainly attributed to the enhanced absorption in gastrointestinal tract rather than modulating the elimination of docetaxel. Copyright © 2017 Elsevier B.V. All rights reserved.

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.

Enhancing Effective Administration at Faculty Level through Shared Leadership

ERIC Educational Resources Information Center

Afful, Deborah

2015-01-01

We live in the world of knowledge, and knowledge keeps increasing in shape and complexity. As a result, no single individual has the repository of knowledge required to effectively manage an organisation all alone to affect organisational performance positively. This explains why administration is explained as doing things through the efforts of…

Fluorescence contrast-enhanced proliferative lesion imaging by enema administration of indocyanine green in a rat model of colon carcinogenesis

PubMed Central

Onda, Nobuhiko; Mizutani-Morita, Reiko; Yamashita, Susumu; Nagahara, Rei; Matsumoto, Shinya; Yoshida, Toshinori; Shibutani, Makoto

2017-01-01

The fluorescent contrast agent indocyanine green (ICG) is approved by the Food and Drug Administration for clinical applications. We previously reported that cultured human colon tumor cells preferentially take up ICG by endocytic activity in association with disruption of their tight junctions. The present study explored ICG availability in fluorescence imaging of the colon to identify proliferative lesions during colonoscopy. The cellular uptake of ICG in cultured rat colon tumor cells was examined using live-cell imaging. Colon lesions in rats administered an ICG-containing enema were further assessed in rats with azoxymethane-induced colon carcinogenesis, using in vivo endoscopy, ex vivo microscopy, and immunofluorescence microscopy. The uptake of ICG by the cultured cells was temperature-dependent. The intracellular retention of the dye in the membrane trafficking system suggested endocytosis as the uptake mechanism. ICG administered via enema accumulated in colon proliferative lesions ranging from tiny aberrant crypt foci to adenomas and localized in proliferating cells. Fluorescence endoscopy detected these ICG-positive colonic proliferative lesions in vivo. The immunoreactivity of the tight-junction molecule occludin was altered in the proliferative lesions, suggesting the disruption of the integrity of tight junctions. These results suggest that fluorescence contrast-enhanced imaging following the administration of an ICG-containing enema can enhance the detection of mucosal proliferative lesions of the colon during colonoscopy. The tissue preference of ICG in the rat model evaluated in this study can be attributed to the disruption of tight junctions, which in turn promotes endocytosis by proliferative cells and the cellular uptake of ICG. PMID:29163827

The Effect and Mechanism of Transdermal Penetration Enhancement of Fu's Cupping Therapy: New Physical Penetration Technology for Transdermal Administration with Traditional Chinese Medicine (TCM) Characteristics.

PubMed

Xie, Wei-Jie; Zhang, Yong-Ping; Xu, Jian; Sun, Xiao-Bo; Yang, Fang-Fang

2017-03-27

In this paper, a new type of physical penetration technology for transdermal administration with traditional Chinese medicine (TCM) characteristics is presented. Fu's cupping therapy (FCT), was established and studied using in vitro and in vivo experiments and the penetration effect and mechanism of FCT physical penetration technology was preliminarily discussed. With 1-(4-chlorobenzoyl)-5-methoxy-2-methylindole-3-ylacetic acid (indomethacin, IM) as a model drug, the establishment of high, medium, and low references was completed for the chemical permeation system via in vitro transdermal tests. Furthermore, using chemical penetration enhancers (CPEs) and iontophoresis as references, the percutaneous penetration effect of FCT for IM patches was evaluated using seven species of in vitro diffusion kinetics models and in vitro drug distribution; the IM quantitative analysis method in vivo was established using ultra-performance liquid chromatography-tandem mass spectrometry technology (UPLC-MS/MS), and pharmacokinetic parameters: area under the zero and first moment curves from 0 to last time t (AUC 0-t , AUMC 0-t ), area under the zero and first moment curves from 0 to infinity (AUC 0-∞ , AUMC 0-∞ ), maximum plasma concentration (C max ) and mean residence time (MRT), were used as indicators to evaluate the percutaneous penetration effect of FCT in vivo. Additionally, we used the 3 K factorial design to study the joint synergistic penetration effect on FCT and chemical penetration enhancers. Through scanning electron microscopy (SEM) and transmission electron microscope (TEM) imaging, micro- and ultrastructural changes on the surface of the stratum corneum (SC) were observed to explore the FCT penetration mechanism. In vitro and in vivo skin permeation experiments revealed that both the total cumulative percutaneous amount and in vivo percutaneous absorption amount of IM using FCT were greater than the amount using CPEs and iontophoresis. Firstly, compared with

Progressive augmentation and ventilatory long-term facilitation are enhanced in sleep apnoea patients and are mitigated by antioxidant administration

PubMed Central

Lee, Dorothy S; Badr, M Safwan; Mateika, Jason H

2009-01-01

Progressive augmentation (PA) and ventilatory long-term facilitation (vLTF) of respiratory motor output are forms of respiratory plasticity that are initiated during exposure to intermittent hypoxia. The present study was designed to determine whether PA and vLTF are enhanced in obstructive sleep apnoea (OSA) participants compared to matched healthy controls. The study was also designed to determine whether administration of an antioxidant cocktail mitigates PA and vLTF. Thirteen participants with sleep apnoea and 13 controls completed two trials. During both trials participants were exposed to intermittent hypoxia which included twelve 4-min episodes of hypoxia (, 50 mmHg; , 4 mmHg above baseline) followed by 30 min of recovery. Prior to exposure to intermittent hypoxia, participants were administered, in a randomized fashion, either an antioxidant or a placebo cocktail. Baseline measures of minute ventilation during the placebo and antioxidant trials were not different between or within groups. During the placebo trial, PA was evident in both groups; however it was enhanced in the OSA group compared to control (last hypoxic episode 36.9 ± 2.8 vs. 27.7 ± 2.2 l min−1; P≤ 0.01). Likewise, vLTF was evident during the recovery period in both groups; on the other hand vLTF was greater in the OSA group compared to control (29.3 ± 2.8 vs. 20.4 ± 1.3 l min−1; P≤ 0.01). PA and vLTF were reduced in the OSA group following antioxidant administration compared to the placebo (PA 30.6 ± 2.0 vs. 36.9 ± 2.8 l min−1, P≤ 0.01; vLTF 23.3 ± 1.4 vs. 29.3 ± 2.8 l min−1, P≤ 0.05). We conclude that PA and vLTF are enhanced in participants with OSA and that these forms of respiratory plasticity are mitigated after treatment with an antioxidant cocktail. PMID:19805747

Professional Development to Enhance Instructional Leadership and Practice of Central Office Administrators

ERIC Educational Resources Information Center

McCue, Cheryl A. R.

2016-01-01

Decades of research and practice suggest that educational administrators need to experience opportunities for professional development and continuous learning. This project study addressed the problem regarding the lack of a formal or systemic plan for professional development of central office administrators in a large suburban school district in…

RCRA, Superfund and EPCRA hotline training module. Introduction to: Superfund administrative improvements/reforms (update February 1998); Directive

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

NONE

1998-06-01

This module includes the following: Administrative Improvements (Round 1) (Enhance Enforcement Fairness and Reduce Transaction Costs; Enhance Cleanup Effectiveness and Consistency; Enhance Public Involvement; Enhance State Role; and On-going Initiatives); Administration Reforms (February 1995 Reforms (Round 2); and October 1995 Reforms (Round 3)); and Summary.

Developing Psychic Income in School Administration: The Unique Role School Administrators Can Play

ERIC Educational Resources Information Center

Guramatunhu-Mudiwa, Precious; Scherz, Susan Day

2013-01-01

This concept article discusses the importance of developing psychic income as an administrative strategy to enhance the context of school environments and to curb high teacher turnover. The hope is to promote further debate and research in order to establish the extent to which psychic income influences retention rates in hard-to-staff schools.…

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.

A single low-dose of hydrocortisone enhances cognitive functioning in HIV-infected women.

PubMed

Rubin, Leah H; Phan, K Luan; Keating, Sheila M; Maki, Pauline M

2018-06-14

Low-dose hydrocortisone (LDH) enhances aspects of learning and memory in select populations including patients with PTSD and HIV-infected men. HIV-infected women show impairments in learning and memory, but the cognitive effects of LDH in HIV-infected women are unknown. Double-blind, placebo-controlled, cross-over study examining the time-dependent effects of a single low-dose administration of hydrocortisone (10 mg oral) on cognition in 36 HIV-infected women. Participants were first randomized to LDH or placebo and then received the opposite treatment one month later. Cognitive performance was assessed 30 minutes and 4 hours after pill administration to assess, respectively nongenomic and genomic effects. Self-reported stress/anxiety and salivary cortisol were assessed throughout sessions. LDH significantly increased salivary cortisol levels versus placebo; levels returned to baseline 4-hours post-administration. At the 30-minute assessment, LDH enhanced verbal learning and delayed memory, working memory, behavioral inhibition, and visuospatial abilities. At the 4-hour assessment, LDH enhanced verbal learning and delayed memory compared to placebo. LDH-induced cognitive benefits related to reductions in cytokines and to a lesser extent to increases in cortisol. The extended benefits from 30 minutes to 4 hours of a single administration of LDH on learning and delayed memory suggest that targeting the HPA axis may have potential clinical utility in HIV-infected women. These findings contrast with our findings in HIV-infected men who showed improved learning only at the 30-minute assessment. Larger, longer-term studies are underway to verify possible cognitive enhancing effects of LDH and the clinical significance of these effects in HIV.

Cyclase inhibitor tripropylamine significantly enhanced lycopene accumulation in Blakeslea trispora.

PubMed

Wang, Yanlong; Chen, Xiwen; Hong, Xiao; Du, Shipeng; Liu, Chunxiao; Gong, Wenfang; Chen, Defu

2016-11-01

Lycopene is a member of carotenoids that exhibits strong antioxidant activity. In this study, on the basis of screening suitable strain combination [ATCC 14271(+) and ATCC 14272(-)] and establishing the optimal inoculation proportion of mated culture (1/2, +/-, w/w) for carotenoid production, the efficiency of compounds, mainly tertiary amines, on enhancing the lycopene content of Blakeslea trispora was systematically assessed. Of these compounds, tripropylamine showed the best enhancing effect, and then sequentially followed by triethylamine, tributylamine, trimethylamine, diisopropylamine, and isopropylamine. After treated with 1.8 g/L tripropylamine for two days, the lycopene proportion was increased from 1.7% to 90.1%, while the β-carotene proportion was decreased from 91.1% to 6.4% of the total carotenoids. In this case, the lycopene and total carotenoid contents were increased to 83.2 and 92.4 mg/gDW, which were 315.8- and 5.9-fold of that of the untreated control, respectively; while the growth of mycelia was only decreased at 6.0 g/L tripropylamine. Gene expression analysis showed that all the tested genes, especially genes encoding 3-hydroxy-3-methylglutaryl coenzyme A reductase (hmgr) and isopentenyl pyrophosphate isomerase (ipi) in mevalonate pathway, as well as phytoene desaturase (carB) in carotenoid biosynthesis process were upregulated. Therefore, tripropylamine enhanced lycopene content of B. trispora by inhibiting the cyclase activity, and by upregulating the expression of genes associated with terpenoid biosynthesis. Besides, a possible association between the structure and the lycopene-enhancing capability of these compounds was also discussed. Copyright © 2016 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Significant enhancement of yellow-green light emission of ZnO nanorod arrays using Ag island films

NASA Astrophysics Data System (ADS)

Lin, Chin-An; Tsai, Dung-Sheng; Chen, Cheng-Ying; He-Hau, Jr.

2011-03-01

Surface plasmon (SP) mediated emission from ZnO nanorod arrays (NRAs)/Ag/Si structures has been investigated. The ratio of visible emission to UV emission can be increased by over 30 times via coupling with SP without deterioration of the crystal quality. The fact that the effect of SP crucially depends on the size of Ag island films provides the feasibility to significantly enhance the yellow-green emission of the ZnO nanostructures without sacrificing the crystallinity of ZnO.Surface plasmon (SP) mediated emission from ZnO nanorod arrays (NRAs)/Ag/Si structures has been investigated. The ratio of visible emission to UV emission can be increased by over 30 times via coupling with SP without deterioration of the crystal quality. The fact that the effect of SP crucially depends on the size of Ag island films provides the feasibility to significantly enhance the yellow-green emission of the ZnO nanostructures without sacrificing the crystallinity of ZnO. Electronic supplementary information (ESI) available. See DOI: 10.1039/c0nr00732c

Vertically Aligned and Interconnected SiC Nanowire Networks Leading to Significantly Enhanced Thermal Conductivity of Polymer Composites.

PubMed

Yao, Yimin; Zhu, Xiaodong; Zeng, Xiaoliang; Sun, Rong; Xu, Jian-Bin; Wong, Ching-Ping

2018-03-21

Efficient heat removal via thermal management materials has become one of the most critical challenges in the development of modern microelectronic devices. However, previously reported polymer composites exhibit limited enhancement of thermal conductivity, even when highly loaded with thermally conductive fillers, because of the lack of efficient heat transfer pathways. Herein, we report vertically aligned and interconnected SiC nanowire (SiCNW) networks as efficient fillers for polymer composites, achieving significantly enhanced thermal conductivity. The SiCNW networks are produced by freeze-casting nanowire aqueous suspensions followed by thermal sintering to consolidate the nanowire junctions, exhibiting a hierarchical architecture in which honeycomb-like SiCNW layers are aligned. The composite obtained by infiltrating SiCNW networks with epoxy resin, at a relatively low SiCNW loading of 2.17 vol %, represents a high through-plane thermal conductivity (1.67 W m -1 K -1 ) compared to the pure matrix, which is equivalent to a significant enhancement of 406.6% per 1 vol % loading. The orderly SiCNW network which can act as a macroscopic expressway for phonon transport is believed to be the main contributor for the excellent thermal performance. This strategy provides insights for the design of high-performance composites with potential to be used in advanced thermal management materials.

Effects of Oxytocin Administration on Receiving Help.

PubMed

Human, Lauren J; Woolley, Joshua D; Mendes, Wendy Berry

2017-11-27

Receiving help can be a "mixed blessing." Despite the many psychosocial benefits it can carry, it sometimes has negative psychological consequences, such as loss in self-esteem or enhanced guilt. It is, therefore, important to understand the factors that modify responses to receiving help from others. We explored the role of the hormone oxytocin (OT) on affective and social responses to receiving help, given the putative role of OT in social bonding and attunement. To this end, we manipulated whether help was received from a same-sex interaction partner (confederate) versus a control condition, crossed with a double-blind administration of intranasal OT (vs. placebo), and examined subjective and observer-rated participant responses to help. We observed significant interactions between OT and the help manipulation. In the placebo condition, receiving help from the interaction partner compared with the control condition had negative consequences, such that participants reported greater negative affect and came to view themselves and their interaction partners more negatively after interacting together on several tasks. What is important, however, is that OT administration buffered against these negative subjective responses to receiving help. Further, outside observers rated participants who received OT administration as expressing greater happiness and gratitude in response to help, relative to those who received placebo. In sum, in the context of receiving help from a stranger, oxytocin administration fostered more positive affective and social responses. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

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…

Significant enhancement of magnetoresistance with the reduction of particle size in nanometer scale

PubMed Central

Das, Kalipada; Dasgupta, P.; Poddar, A.; Das, I.

2016-01-01

The Physics of materials with large magnetoresistance (MR), defined as the percentage change of electrical resistance with the application of external magnetic field, has been an active field of research for quite some times. In addition to the fundamental interest, large MR has widespread application that includes the field of magnetic field sensor technology. New materials with large MR is interesting. However it is more appealing to vast scientific community if a method describe to achieve many fold enhancement of MR of already known materials. Our study on several manganite samples [La1−xCaxMnO3 (x = 0.52, 0.54, 0.55)] illustrates the method of significant enhancement of MR with the reduction of the particle size in nanometer scale. Our experimentally observed results are explained by considering model consisted of a charge ordered antiferromagnetic core and a shell having short range ferromagnetic correlation between the uncompensated surface spins in nanoscale regime. The ferromagnetic fractions obtained theoretically in the nanoparticles has been shown to be in the good agreement with the experimental results. The method of several orders of magnitude improvement of the magnetoresistive property will have enormous potential for magnetic field sensor technology. PMID:26837285

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

Quality of abdominal computed tomography angiography: hand versus mechanical intravenous contrast administration in children.

PubMed

Ayyala, Rama S; Zurakowski, David; Lee, Edward Y

2015-11-01

administration of IV contrast agent and 30 (65%; 10.2 ± 4.2 years; range 4-18 years) had mechanical administration of IV contrast agent. All 46 abdominal CT angiography studies were of diagnostic quality based on qualitative evaluation (all ≥3). All abdominal CT angiography studies from both groups showed diagnostic quality of contrast enhancement (>150 HU) at both the celiac axis and the inferior mesenteric artery (IMA) levels. The contrast enhancement of the abdominal aorta was not significantly different between the IV contrast administration methods at either the celiac axis level (360 ± 158 vs. 353 ± 116, P = 0.24) or the IMA level (340 ± 140 vs. 351 ± 90, P = 0.27), adjusting for age. Diagnostic-quality abdominal CT angiography can be achieved using hand administration of IV contrast agent in infants and young children (≤5 years).

Redox system and phospholipid metabolism in the kidney of hypertensive rats after FAAH inhibitor URB597 administration.

PubMed

Biernacki, Michał; Ambrożewicz, Ewa; Gęgotek, Agnieszka; Toczek, Marek; Bielawska, Katarzyna; Skrzydlewska, Elżbieta

2018-05-01

Primary and secondary hypertension is associated with kidney redox imbalance resulting in enhanced reactive oxygen species (ROS) and enzymes dependent phospholipid metabolism. The fatty acid amide hydrolase inhibitor, URB597, modulates the levels of endocannabinoids, particularly of anandamide, which is responsible for controlling blood pressure and regulating redox balance. Therefore, this study aimed to compare the effects of chronic URB597 administration to spontaneously hypertensive rats (SHR) and rats with secondary hypertension (DOCA-salt rats) on the kidney metabolism associated with the redox and endocannabinoid systems. It was shown fatty acid amide hydrolase (FAAH) inhibitor decreased the activity of ROS-generated enzymes what resulted in a reduction of ROS level. Moreover varied changes in antioxidant parameters were observed with tendency to improve antioxidant defense in SHR kidney. Moreover, URB597 administration to hypertensive rats decreased pro-inflammatory response, particularly in the kidneys of DOCA-salt hypertensive rats. URB597 had tendency to enhance ROS-dependent phospholipid oxidation, estimated by changes in neuroprostanes in the kidney of SHR and reactive aldehydes (4-hydroxynonenal and malondialdehyde) in DOCA-salt rats, in particular. The administration of FAAH inhibitor resulted in increased level of endocannabinoids in kidney of both groups of hypertensive rats led to enhanced expression of the cannabinoid receptors type 1 and 2 in SHR as well as vanilloid receptor 1 receptors in DOCA-salt rats. URB597 given to normotensive rats also affected kidney oxidative metabolism, resulting in enhanced level of neuroprostanes in Wistar Kyoto rats and reactive aldehydes in Wistar rats. Moreover, the level of endocannabinoids and cannabinoid receptors were significantly higher in both control groups of rats after URB597 administration. In conclusion, because URB597 disturbed the kidney redox system and phospholipid ROS-dependent and enzymatic

Intranasal administration of Lactobacillus rhamnosus GG protects mice from H1N1 influenza virus infection by regulating respiratory immune responses.

PubMed

Harata, G; He, F; Hiruta, N; Kawase, M; Kubota, A; Hiramatsu, M; Yausi, H

2010-06-01

To investigate whether intranasal Lactobacillus administration protects host animals from influenza virus (IFV) infection by enhancing respiratory immune responses in a mouse model. After 3 days of intranasal exposure to Lactobacillus rhamnosus GG (LGG), BALB/c mice were infected with IFV A/PR/8/34 (H1N1). Mice treated with LGG showed a lower frequency of accumulated symptoms and a higher survival rate than control mice (P < 0.05). The YAC-1 cell-killing activity of lung cells isolated from mice treated with LGG was significantly greater than those isolated from control mice (P < 0.01). Intranasal administration of LGG significantly increased mRNA expression of interleukin (IL)-1 beta, tumour necrosis factor (TNF) and monocyte chemotactic protein (MCP)-1 (P < 0.01). These results suggest that intranasal administration of LGG protects the host animal from IFV infection by enhancing respiratory cell-mediated immune responses following up-regulation of lung natural killer (NK) cell activation. We have demonstrated that probiotics might protect host animals from viral infection by stimulating immune responses in the respiratory tract.

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…

Geospatial Data for Computerisation of Public Administration in the Czech Republic

NASA Astrophysics Data System (ADS)

Cada, V.; Mildorf, T.

2011-08-01

The main aim of the eGovernment programme in the Czech Republic is to enhance the efficiency of public administration. The Digital Map of Public Administration (DMVS) should be composed of digital orthophotographs of the Czech Republic, digital and digitised cadastral maps, digital purpose cadastral map (ÚKM) and a technical map of municipality, if available. The DMVS project is a part of computerisation of public administration in the Czech Republic. The project enhances the productivity of government administration and also simplifies the processes between citizens and public administration. The DMVS project, that should be compliant with the INSPIRE (Infrastructure for Spatial Information in the European Community) initiative, generates definite demand for geodata on the level of detail of land data model. The user needs that are clearly specified and required are not met due to inconsistencies in terminology, data management and level of detail.

Affective significance enhances covert attention: roles of anxiety and word familiarity.

PubMed

Calvo, Manuel G; Eysenck, Michael W

2008-11-01

To investigate the processing of emotional words by covert attention, threat-related, positive, and neutral word primes were presented parafoveally (2.2 degrees away from fixation) for 150 ms, under gaze-contingent foveal masking, to prevent eye fixations. The primes were followed by a probe word in a lexical-decision task. In Experiment 1, results showed a parafoveal threat-anxiety superiority: Parafoveal prime threat words facilitated responses to probe threat words for high-anxiety individuals, in comparison with neutral and positive words, and relative to low-anxiety individuals. This reveals an advantage in threat processing by covert attention, without differences in overt attention. However, anxiety was also associated with greater familiarity with threat words, and the parafoveal priming effects were significantly reduced when familiarity was covaried out. To further examine the role of word knowledge, in Experiment 2, vocabulary and word familiarity were equated for low- and high-anxiety groups. In these conditions, the parafoveal threat-anxiety advantage disappeared. This suggests that the enhanced covert-attention effect depends on familiarity with words.

Single prolonged stress effects on sensitization to cocaine and cocaine self-administration in rats

PubMed Central

Eagle, Andrew L.; Singh, Robby; Kohler, Robert J.; Friedman, Amy L.; Liebowitz, Chelsea P.; Galloway, Matthew P.; Enman, Nicole M.; Jutkiewicz, Emily M.; Perrine, Shane A.

2017-01-01

Posttraumatic stress disorder (PTSD) is often comorbid with substance use disorders (SUD). Single prolonged stress (SPS) is a well-validated rat model of PTSD that provides a framework to investigate drug-induced behaviors as a preclinical model of the comorbidity. We hypothesized that cocaine sensitization and self-administration would be increased following exposure to SPS. Male Sprague–Dawley rats were exposed to SPS or control treatment. After SPS, cocaine (0,10 or 20mg/kg, i.p.) was administered for 5 consecutive days and locomotor activity was measured. Another cohort was assessed for cocaine self-administration (0.1 or 0.32 mg/kg/i.v.) after SPS. Rats were tested for acquisition, extinction and cue-induced reinstatement behaviors. Control animals showed a dose-dependent increase in cocaine-induced locomotor activity after acute cocaine whereas SPS rats did not. Using a sub-threshold sensitization paradigm, control rats did not exhibit enhanced locomotor activity at Day 5 and therefore did not develop behavioral sensitization, asexpected. However, compared to control ratson Day 5 the locomotor response to 20mg/kg repeated cocaine was greatly enhanced in SPS-treated rats, which exhibited enhanced cocaine locomotor sensitization. The effect of SPS on locomotor activity was unique in that SPS did not modify cocaine self-administration behaviors under a simple schedule of reinforcement. These data show that SPS differentially affects cocaine-mediated behaviors causing no effect to cocaine self-administration, under a simple schedule of reinforcement, but significantly augmenting cocaine locomotor sensitization. These results suggest that SPS shares common neurocircuitry with stimulant-induced plasticity, but dissociable from that underlying psychostimulant-induced reinforcement. PMID:25712697

Single prolonged stress effects on sensitization to cocaine and cocaine self-administration in rats.

PubMed

Eagle, Andrew L; Singh, Robby; Kohler, Robert J; Friedman, Amy L; Liebowitz, Chelsea P; Galloway, Matthew P; Enman, Nicole M; Jutkiewicz, Emily M; Perrine, Shane A

2015-05-01

Posttraumatic stress disorder (PTSD) is often comorbid with substance use disorders (SUD). Single prolonged stress (SPS) is a well-validated rat model of PTSD that provides a framework to investigate drug-induced behaviors as a preclinical model of the comorbidity. We hypothesized that cocaine sensitization and self-administration would be increased following exposure to SPS. Male Sprague-Dawley rats were exposed to SPS or control treatment. After SPS, cocaine (0, 10 or 20 mg/kg, i.p.) was administered for 5 consecutive days and locomotor activity was measured. Another cohort was assessed for cocaine self-administration (0.1 or 0.32 mg/kg/i.v.) after SPS. Rats were tested for acquisition, extinction and cue-induced reinstatement behaviors. Control animals showed a dose-dependent increase in cocaine-induced locomotor activity after acute cocaine whereas SPS rats did not. Using a sub-threshold sensitization paradigm, control rats did not exhibit enhanced locomotor activity at Day 5 and therefore did not develop behavioral sensitization, as expected. However, compared to control rats on Day 5 the locomotor response to 20mg/kg repeated cocaine was greatly enhanced in SPS-treated rats, which exhibited enhanced cocaine locomotor sensitization. The effect of SPS on locomotor activity was unique in that SPS did not modify cocaine self-administration behaviors under a simple schedule of reinforcement. These data show that SPS differentially affects cocaine-mediated behaviors causing no effect to cocaine self-administration, under a simple schedule of reinforcement, but significantly augmenting cocaine locomotor sensitization. These results suggest that SPS shares common neurocircuitry with stimulant-induced plasticity, but dissociable from that underlying psychostimulant-induced reinforcement. Copyright © 2015. Published by Elsevier B.V.

Acute caffeine administration effect on brain activation patterns in mild cognitive impairment.

PubMed

Haller, Sven; Montandon, Marie-Louise; Rodriguez, Cristelle; Moser, Dominik; Toma, Simona; Hofmeister, Jeremy; Sinanaj, Indrit; Lovblad, Karl-Olof; Giannakopoulos, Panteleimon

2014-01-01

Previous studies showed that acute caffeine administration enhances task-related brain activation in elderly individuals with preserved cognition. To explore the effects of this widely used agent on cognition and brain activation in early phases of cognitive decline, we performed a double-blinded, placebo-controlled functional magnetic resonance imaging (fMRI) study during an n-back working memory task in 17 individuals with mild cognitive impairment (MCI) compared to 17 age-matched healthy controls (HC). All individuals were regular caffeine consumers with an overnight abstinence and given 200 mg caffeine versus placebo tablets 30 minutes before testing. Analyses included assessment of task-related activation (general linear model), functional connectivity (tensorial-independent component analysis, TICA), baseline perfusion (arterial spin labeling, ASL), grey matter density (voxel-based morphometry, VBM), and white matter microstructure (tract-based spatial statistics, TBSS). Acute caffeine administration induced a focal activation of the prefrontal areas in HC with a more diffuse and posteromedial activation pattern in MCI individuals. In MCI, TICA documented a significant caffeine-related enhancement in the prefrontal cortex, supplementary motor area, ventral premotor and parietal cortex as well as the basal ganglia and cerebellum. The absence of significant group differences in baseline ASL perfusion patterns supports a neuronal rather than a purely vascular origin of these differences. The VBM and TBSS analyses excluded potentially confounding differences in grey matter density and white matter microstructure between MCI and HC. The present findings suggest a posterior displacement of working memory-related brain activation patterns after caffeine administration in MCI that may represent a compensatory mechanism to counterbalance a frontal lobe dysfunction.

Heavy Atom Effect of Bromine Significantly Enhances Exciton Utilization of Delayed Fluorescence Luminogens.

PubMed

Gan, Shifeng; Hu, Shimin; Li, Xiang-Long; Zeng, Jiajie; Zhang, Dongdong; Huang, Tianyu; Luo, Wenwen; Zhao, Zujin; Duan, Lian; Su, Shi-Jian; Tang, Ben Zhong

2018-05-23

Raising triplet exciton utilization of pure organic luminescent materials is of significant importance for efficiency advancement of organic light-emitting diodes (OLEDs). Herein, by introducing bromine atom(s) onto a typical molecule (bis(carbazol-9-yl)-4,5-dicyanobenzene) with thermally activated delayed fluorescence, we demonstrate that the heavy atom effect of bromine can increase spin-orbit coupling and promote the reverse intersystem crossing, which endow the molecules with more distinct delayed fluorescence. In consequence, the triplet exciton utilization is improved greatly with the increase of bromine atoms, affording apparently advanced external quantum efficiencies of OLEDs. Utilizing the enhancement effect of bromine atoms on delayed fluorescence should be a simple and promising design concept for efficient organic luminogens with high exciton utilization.

Prognostic significance of contrast-enhanced CT attenuation value in extrahepatic cholangiocarcinoma.

PubMed

Asayama, Yoshiki; Nishie, Akihiro; Ishigami, Kousei; Ushijima, Yasuhiro; Takayama, Yukihisa; Okamoto, Daisuke; Fujita, Nobuhiro; Ohtsuka, Takao; Yoshizumi, Tomoharu; Aishima, Shinichi; Oda, Yoshinao; Honda, Hiroshi

2017-06-01

To determine whether washout characteristics of dynamic contrast-enhanced computed tomography (CT) could predict survival in patients with extrahepatic cholangiocarcinoma (EHC). This study collected 46 resected cases. All cases were examined by dynamic contrast study on multidetector-row CT. Region-of-interest measurements were obtained at the non-enhanced, portal venous phase and delayed phase in the tumour and were used to calculate the washout ratio as follows: [(attenuation value at portal venous phase CT - attenuation value at delayed enhanced CT)/(attenuation value at portal venous phase CT - attenuation value at unenhanced CT)] × 100. On the basis of the median washout ratio, we classified the cases into two groups, a high-washout group and low-washout group. Associations between overall survival and various factors including washout rates were analysed. The median washout ratio was 29.4 %. Univariate analysis revealed that a lower washout ratio, venous invasion, lymphatic permeation and lymph node metastasis were associated with shorter survival. Multivariate analysis identified the lower washout ratio as an independent prognostic factor (hazard ratio, 3.768; p value, 0.027). The washout ratio obtained from the contrast-enhanced CT may be a useful imaging biomarker for the prediction of survival of patients with EHC. • Dynamic contrast study can evaluate the aggressiveness of extrahepatic cholangiocarcinoma. • A lower washout ratio was an independent prognostic factor for overall survival. • CT can predict survival and inform decisions on surgical options or chemotherapy.

Significant enhancement in thermoelectric performance of nanostructured higher manganese silicides synthesized employing a melt spinning technique.

PubMed

Muthiah, Saravanan; Singh, R C; Pathak, B D; Avasthi, Piyush Kumar; Kumar, Rishikesh; Kumar, Anil; Srivastava, A K; Dhar, Ajay

2018-01-25

The limited thermoelectric performance of p-type Higher Manganese Silicides (HMS) in terms of their low figure-of-merit (ZT), which is far below unity, is the main bottle-neck for realising an efficient HMS based thermoelectric generator, which has been recognized as the most promising material for harnessing waste-heat in the mid-temperature range, owing to its thermal stability, earth-abundant and environmentally friendly nature of its constituent elements. We report a significant enhancement in the thermoelectric performance of nanostructured HMS synthesized using rapid solidification by optimizing the cooling rates during melt-spinning followed by spark plasma sintering of the resulting melt-spun ribbons. By employing this experimental strategy, an unprecedented ZT ∼ 0.82 at 800 K was realized in spark plasma sintered 5 at% Al-doped MnSi 1.73 HMS, melt spun at an optimized high cooling rate of ∼2 × 10 7 K s -1 . This enhancement in ZT represents a ∼25% increase over the best reported values thus far for HMS and primarily originates from a nano-crystalline microstructure consisting of a HMS matrix (20-40 nm) with excess Si (3-9 nm) uniformly distributed in it. This nanostructure, resulting from the high cooling rates employed during the melt-spinning of HMS, introduces a high density of nano-crystallite boundaries in a wide spectrum of nano-scale dimensions, which scatter the low-to-mid-wavelength heat-carrying phonons. This abundant phonon scattering results in a significantly reduced thermal conductivity of ∼1.5 W m -1 K -1 at 800 K, which primarily contributes to the enhancement in ZT.

Progressing Toward a Cohesive Pediatric 18F-FDG PET/MR Protocol: Is Administration of Gadolinium Chelates Necessary?

PubMed

Klenk, Christopher; Gawande, Rakhee; Tran, Vy Thao; Leung, Jennifer Trinh; Chi, Kevin; Owen, Daniel; Luna-Fineman, Sandra; Sakamoto, Kathleen M; McMillan, Alex; Quon, Andy; Daldrup-Link, Heike E

2016-01-01

With the increasing availability of integrated PET/MR scanners, the utility and need for MR contrast agents for combined scans is questioned. The purpose of our study was to evaluate whether administration of gadolinium chelates is necessary for evaluation of pediatric tumors on (18)F-FDG PET/MR images. First, in 119 pediatric patients with primary and secondary tumors, we used 14 diagnostic criteria to compare the accuracy of several MR sequences: unenhanced T2-weighted fast spin-echo imaging; unenhanced diffusion-weighted imaging; and-before and after gadolinium chelate contrast enhancement-T1-weighted 3-dimensional spoiled gradient echo LAVA (liver acquisition with volume acquisition) imaging. Next, in a subset of 36 patients who had undergone (18)F-FDG PET within 3 wk of MRI, we fused the PET images with the unenhanced T2-weighted MR images (unenhanced (18)F-FDG PET/MRI) and the enhanced T1-weighted MR images (enhanced (18)F-FDG PET/MRI). Using the McNemar test, we compared the accuracy of the two types of fused images using the 14 diagnostic criteria. We also evaluated the concordance between (18)F-FDG avidity and gadolinium chelate enhancement. The standard of reference was histopathologic results, surgical notes, and follow-up imaging. There was no significant difference in diagnostic accuracy between the unenhanced and enhanced MR images. Accordingly, there was no significant difference in diagnostic accuracy between the unenhanced and enhanced (18)F-FDG PET/MR images. (18)F-FDG avidity and gadolinium chelate enhancement were concordant in 30 of the 36 patients and 106 of their 123 tumors. Gadolinium chelate administration is not necessary for accurate diagnostic characterization of most solid pediatric malignancies on (18)F-FDG PET/MR images, with the possible exception of focal liver lesions. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Co-administration of Bacillus subtilis RJGP16 and Lactobacillus salivarius B1 strongly enhances the intestinal mucosal immunity of piglets.

PubMed

Deng, Jun; Li, Yunfeng; Zhang, Jinhua; Yang, Qian

2013-02-01

Probiotics, including Bacillus spp. and Lactobacillus, are potential replacements for low dose in-feed antibiotics for pig. This study aimed to evaluate the effect of the co-administration of Bacillus subtilis RJGP16 and Lactobacillus salivarius B1 as potential probiotics to stimulate local immune responses. Thirty two newborn piglets were divided into four groups and orally administrated with different combination of probiotics (none; RJGP16; B1; RJGP16 and B1) at the age of 0, 7 and 11 days. We analysed the parameters of the mucosal immunity of piglets a week after weaning. Our results showed that the gene expression of interleukin (IL)-6 in the duodenum and ileum, porcine beta-defensins (pBD)-2 in the duodenum were significantly increased (p<0.01) with co-administration of the RJGP16 and B1. Also the expression and release of TLR-2 and the number of immunoglobulin (Ig) A producing cells were increased (p<0.01). The results demonstrate that the co-administration of the two bacteria stimulate a more intense mucosal immunity than the administration of each bacterium alone. Copyright © 2012 Elsevier Ltd. All rights reserved.

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

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…

Preclinical Evaluation of Riluzole: Assessments of Ethanol Self-Administration and Ethanol Withdrawal Symptoms

PubMed Central

Besheer, Joyce; Lepoutre, Veronique; Hodge, Clyde W.

2010-01-01

Background Many of the neurobehavioral effects of ethanol are mediated by inhibition of excitatory N-methyl-d-aspartate (NMDA) and enhancement of inhibitory γ-amino-butyric-acid (GABA) receptor systems. There is growing interest in drugs that alter these systems as potential medications for problems associated with alcoholism. The drug riluzole, approved for treatment of amyotrophic lateral sclerosis (ALS), inhibits NMDA and enhances GABAA receptor system activity. This study was designed to determine the preclinical efficacy of riluzole to modulate ethanol self-administration and withdrawal. Methods Male C57BL/6J mice were trained to lever press on a concurrent fixed-ratio 1 schedule of ethanol (10% v/v) versus water reinforcement during daily 16-hour sessions. Riluzole (1 to 40 mg/kg, IP) was evaluated on ethanol self-administration after acute and chronic (2 week) treatment. To determine if riluzole influences ethanol withdrawal-associated seizures, mice were fed an ethanol-containing or control liquid diet for 18 days. The effects of a single injection of riluzole (30 mg/kg) were examined on handling-induced convulsions after ethanol withdrawal. Results Acute riluzole (30 and 40 mg/kg) reduced ethanol self-administration during the first 4 hours of the session, which corresponds to the known pharmacokinetics of this drug. Ethanol self-administration was also reduced by riluzole after chronic treatment. Riluzole (30 mg/kg) significantly decreased the severity of ethanol-induced convulsions 2 hours after ethanol withdrawal. Conclusions These results demonstrate that riluzole decreases ethanol self-administration and may reduce ethanol withdrawal severity in mice. Thus, riluzole may have utility in the treatment of problems associated with alcoholism. PMID:19426166

Glucocorticoids enhance in vivo exposure-based therapy of spider phobia.

PubMed

Soravia, Leila M; Heinrichs, Markus; Winzeler, Livia; Fisler, Melanie; Schmitt, Wolfgang; Horn, Helge; Dierks, Thomas; Strik, Werner; Hofmann, Stefan G; de Quervain, Dominique J-F

2014-05-01

Preclinical and clinical studies indicate that the administration of glucocorticoids may promote fear extinction processes. In particular, it has been shown that glucocorticoids enhance virtual reality based exposure therapy of fear of heights. Here, we investigate whether glucocorticoids enhance the outcome of in vivo exposure-based group therapy of spider phobia. In a double blind, block-randomized, placebo-controlled, between-subject study design, 22 patients with specific phobia of spiders were treated with two sessions of in vivo exposure-based group therapy. Cortisol (20 mg) or placebo was orally administered 1 hr before each therapy session. Patients returned for a follow-up assessment one month after therapy. Exposure-based group therapy led to a significant decrease in phobic symptoms as assessed with the Fear of Spiders Questionnaire (FSQ) from pretreatment to immediate posttreatment and to follow-up. The administration of cortisol to exposure therapy resulted in increased salivary cortisol concentrations and a significantly greater reduction in fear of spiders (FSQ) as compared to placebo at follow-up, but not immediately posttreatment. Furthermore, cortisol-treated patients reported significantly less anxiety during standardized exposure to living spiders at follow-up than placebo-treated subjects. Notably, groups did not differ in phobia-unrelated state-anxiety before and after the exposure sessions and at follow-up. These findings indicate that adding cortisol to in vivo exposure-based group therapy of spider phobia enhances treatment outcome. © 2013 Wiley Periodicals, Inc.

Significant performance enhancement in photoconductive terahertz optoelectronics by incorporating plasmonic contact electrodes.

PubMed

Berry, C W; Wang, N; Hashemi, M R; Unlu, M; Jarrahi, M

2013-01-01

Even though the terahertz spectrum is well suited for chemical identification, material characterization, biological sensing and medical imaging, practical development of these applications has been hindered by attributes of existing terahertz optoelectronics. Here we demonstrate that the use of plasmonic contact electrodes can significantly mitigate the low-quantum efficiency performance of photoconductive terahertz optoelectronics. The use of plasmonic contact electrodes offers nanoscale carrier transport path lengths for the majority of photocarriers, increasing the number of collected photocarriers in a subpicosecond timescale and, thus, enhancing the optical-to-terahertz conversion efficiency of photoconductive terahertz emitters and the detection sensitivity of photoconductive terahertz detectors. We experimentally demonstrate 50 times higher terahertz radiation powers from a plasmonic photoconductive emitter in comparison with a similar photoconductive emitter with non-plasmonic contact electrodes, as well as 30 times higher terahertz detection sensitivities from a plasmonic photoconductive detector in comparison with a similar photoconductive detector with non-plasmonic contact electrodes.

Development of Program to Enhance Team Building Leadership Skills of Primary School Administrators

ERIC Educational Resources Information Center

Sairam, Boonchauy; Sirisuthi, Chaiyuth; Wisetrinthong, Kanjana

2017-01-01

Team building leadership skills are important to understandings of how the primary school administrators might work towards creating more effective teamwork in the school. This research aimed 1) to study the components of team building leadership skills needed for primary school administrators, 2) to examine the current states and desirable…

Structure-activity relationship of chemical penetration enhancers in transdermal drug delivery.

PubMed

Kanikkannan, N; Kandimalla, K; Lamba, S S; Singh, M

2000-06-01

Transdermal drug delivery (TDD) is the administration of therapeutic agents through intact skin for systemic effect. TDD offers several advantages over the conventional dosage forms such as tablets, capsules and injections. Currently there are about eight drugs marketed as transdermal patches. Examples of such products include nitroglycerin (angina pectoris), clonidine (hypertension), scopolamine (motion sickness), nicotine (smoking cessation), fentanil (pain) and estradiol (estrogen deficiency). Since skin is an excellent barrier for drug transport, only potent drugs with appropriate physicochemical properties (low molecular weight, adequate solubility in aqueous and non-aqueous solvents, etc) are suitable candidates for transdermal delivery. Penetration enhancement technology is a challenging development that would increase significantly the number of drugs available for transdermal administration. The permeation of drugs through skin can be enhanced by physical methods such as iontophoresis (application of low level electric current) and phonophoresis (use of ultra sound energy) and by chemical penetration enhancers (CPE). In this review, we have discussed about the CPE which have been investigated for TDD. CPE are compounds that enhance the permeation of drugs across the skin. The CPE increase skin permeability by reversibly altering the physicochemical nature of the stratum corneum, the outer most layer of skin, to reduce its diffusional resistance. These compounds increase skin permeability also by increasing the partition coefficient of the drug into the skin and by increasing the thermodynamic activity of the drug in the vehicle. This review compiles the various CPE used for the enhancement of TDD, the mechanism of action of different chemical enhancers and the structure-activity relationship of selected and extensively studied enhancers such as fatty acids, fatty alcohols and terpenes. Based on the chemical structure of penetration enhancers (such as chain

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...

Cocaine Administration and Its Withdrawal Enhance the Expression of Genes Encoding Histone-Modifying Enzymes and Histone Acetylation in the Rat Prefrontal Cortex.

PubMed

Sadakierska-Chudy, Anna; Frankowska, Małgorzata; Jastrzębska, Joanna; Wydra, Karolina; Miszkiel, Joanna; Sanak, Marek; Filip, Małgorzata

2017-07-01

Chronic exposure to cocaine, craving, and relapse are attributed to long-lasting changes in gene expression arising through epigenetic and transcriptional mechanisms. Although several brain regions are involved in these processes, the prefrontal cortex seems to play a crucial role not only in motivation and decision-making but also in extinction and seeking behavior. In this study, we applied cocaine self-administration and extinction training procedures in rats with a yoked triad to determine differentially expressed genes in prefrontal cortex. Microarray analysis showed significant upregulation of several genes encoding histone modification enzymes during early extinction training. Subsequent real-time PCR testing of these genes following cocaine self-administration or early (third day) and late (tenth day) extinction revealed elevated levels of their transcripts. Interestingly, we found the enrichment of Brd1 messenger RNA in rats self-administering cocaine that lasted until extinction training during cocaine withdrawal with concomitant increased acetylation of H3K9 and H4K8. However, despite elevated levels of methyl- and demethyltransferase-encoded transcripts, no changes in global di- and tri-methylation of histone H3 at lysine 4, 9, 27, and 79 were observed. Surprisingly, at the end of extinction training (10 days of cocaine withdrawal), most of the analyzed genes in the rats actively and passively administering cocaine returned to the control level. Together, the alterations identified in the rat prefrontal cortex may suggest enhanced chromatin remodeling and transcriptional activity induced by early cocaine abstinence; however, to know whether they are beneficial or not for the extinction of drug-seeking behavior, further in vivo evaluation is required.

Significantly enhanced high-frequency permeability for composites with amorphous-membrane-fillers prepared using an infiltration method

NASA Astrophysics Data System (ADS)

Li, Z. W.; Yang, Z. H.

2016-03-01

Amorphous-membrane-filler composites have been fabricated using an infiltration method. The composites are able to significantly increase the permeability by 200%, as compared to general amorphous flake composites. SEM and magnetic measurement show that the amorphous flakes in membrane are in-plane arrangement. A model, which considers the effect of flake arrangement on demagnetizing factor Nd and permeability, is proposed. The effect of the arrangement of flakes is equivalent to an effective Nd, which is equal to 1/3 and zero for random and complete in-plane arrangements, respectively. Due to in-plane arrangement of amorphous flakes, the decreased Nd leads to significantly enhanced permeability for the amorphous-membrane-filler composites, based on the Maxwell-Garret mixing law.

Blended learning on medication administration for new nurses: integration of e-learning and face-to-face instruction in the classroom.

PubMed

Sung, Young Hee; Kwon, In Gak; Ryu, Eunjung

2008-11-01

This study analyzed the effects of a blended learning program on medication administration by new nurses using a non-equivalent groups design. A medication education program using blended learning (including e-learning) was administered to 26 new nurses, while face-to-face instruction in the classroom was given to 24 new nurses. The following dependent variables were compared: degree of knowledge of medication, self-efficacy of medication administration, medication-administration ability, and satisfaction with the learning program. The experimental, blended learning group showed a significantly higher level of knowledge of medication and satisfaction with the comprehensiveness of their medication learning, but the self-efficacy of medication administration, medication-administration ability, and other items related to their learning satisfaction did not differ significantly from that in the control group. These results suggest that blended learning integrating e-learning and face-to-face instruction in the classroom is useful for enhancing medication knowledge. An e-learning program can reduce the lecturing time and cost of repeated topics such as medication, suggesting that it can be an effective component in nurse education programs.

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.

Intratumoral immunocytokine treatment results in enhanced antitumor effects.

PubMed

Johnson, Erik E; Lum, Hillary D; Rakhmilevich, Alexander L; Schmidt, Brian E; Furlong, Meghan; Buhtoiarov, Ilia N; Hank, Jacquelyn A; Raubitschek, Andrew; Colcher, David; Reisfeld, Ralph A; Gillies, Stephen D; Sondel, Paul M

2008-12-01

Immunocytokines (IC), consisting of tumor-specific monoclonal antibodies fused to the immunostimulatory cytokine interleukin 2 (IL2), exert significant antitumor effects in several murine tumor models. We investigated whether intratumoral (IT) administration of IC provided enhanced antitumor effects against subcutaneous tumors. Three unique ICs (huKS-IL2, hu14.18-IL2, and GcT84.66-IL2) were administered systemically or IT to evaluate their antitumor effects against tumors expressing the appropriate IC-targeted tumor antigens. The effect of IT injection of the primary tumor on a distant tumor was also evaluated. Here, we show that IT injection of IC resulted in enhanced antitumor effects against B16-KSA melanoma, NXS2 neuroblastoma, and human M21 melanoma xenografts when compared to intravenous (IV) IC injection. Resolution of both primary and distant subcutaneous tumors and a tumor-specific memory response were demonstrated following IT treatment in immunocompetent mice bearing NXS2 tumors. The IT effect of huKS-IL2 IC was antigen-specific, enhanced compared to IL2 alone, and dose-dependent. Hu14.18-IL2 also showed greater IT effects than IL2 alone. The antitumor effect of IT IC did not always require T cells since IT IC induced antitumor effects against tumors in both SCID and nude mice. Localization studies using radiolabeled (111)In-GcT84.66-IL2 IC confirmed that IT injection resulted in a higher concentration of IC at the tumor site than IV administration. In conclusion, we suggest that IT IC is more effective than IV administration against palpable tumors. Further testing is required to determine how to potentially incorporate IT administration of IC into an antitumor regimen that optimizes local and systemic anticancer therapy.

Macroporous Inverse Opal-like MoxC with Incorporated Mo Vacancies for Significantly Enhanced Hydrogen Evolution.

PubMed

Li, Feng; Zhao, Xianglong; Mahmood, Javeed; Okyay, Mahmut Sait; Jung, Sun-Min; Ahmad, Ishfaq; Kim, Seok-Jin; Han, Gao-Feng; Park, Noejung; Baek, Jong-Beom

2017-07-25

The hydrogen evolution reaction (HER) is one of the most important pathways for producing pure and clean hydrogen. Although platinum (Pt) is the most efficient HER electrocatalyst, its practical application is significantly hindered by high-cost and scarcity. In this work, an Mo x C with incorporated Mo vacancies and macroporous inverse opal-like (IOL) structure (Mo x C-IOL) was synthesized and studied as a low-cost efficient HER electrocatalyst. The macroporous IOL structure was controllably fabricated using a facile-hard template strategy. As a result of the combined benefits of the Mo vacancies and structural advantages, including appropriate hydrogen binding energy, large exposed surface, robust IOL structure and fast mass/charge transport, the synthesized Mo x C-IOL exhibited significantly enhanced HER electrocatalytic performance with good stability, with performance comparable or superior to Pt wire in both acidic and alkaline solutions.

Nursing Home Administrator Quality Improvement Self-Efficacy Scale.

PubMed

Siegel, Elena O; Zisberg, Anna; Bakerjian, Debra; Zysberg, Leehu

Nursing home (NH) quality improvement (QI) is challenging. The critical role of NH leaders in successful QI is well established; however, current options for assessing the QI capabilities of leaders such as the licensed NH administrator are limited. This article presents the development and preliminary validation of an instrument to measure NH administrator self-efficacy in QI. We used a mixed-methods cross-sectional design to develop and test the measure. For item generation, 39 NH leaders participated in qualitative interviews. Item reduction and content validity were established with a sample of eight subject matter experts. A random sample of 211 administrators from NHs with the lowest and highest Centers for Medicare and Medicaid Services Five-Star Quality ratings completed the measure. We conducted exploratory and confirmatory factor analyses and tested the measure for internal reliability and convergent, discriminant, and known group validity. The final measure included five subscales and 32 items. Confirmatory factor analysis reaffirmed the factorial structure with good fit indices. The new measure's subscales correlated with valid measures of self-efficacy and locus of control, supporting the measure's convergent and discriminant validity. Significant differences in most of the subscales were found between the objective (Centers for Medicare and Medicaid Services Five-Star Quality rating) and subjective (Self-Rated Facility QI Index) quality outcomes, supporting the measure's known group validity. The instrument has usefulness to both NH organizations and individual NH administrators as a diagnostic tool to identify administrators with higher/lower chances of successfully implementing QI. Organizations and individuals can use this diagnostic to identify the administrator's professional development needs for QI, in general, and specific to the instrument's five subscales, informing directions for in-house training, mentoring, and outside professional

Butter feeding enhances TNF-alpha production from macrophages and lymphocyte adherence in murine small intestinal microvessels.

PubMed

Fujiyama, Yoichi; Hokari, Ryota; Miura, Soichiro; Watanabe, Chikako; Komoto, Shunsuke; Oyama, Tokushige; Kurihara, Chie; Nagata, Hiroshi; Hibi, Toshifumi

2007-11-01

Dietary fat is known to modulate immune functions. Intake of an animal fat-rich diet has been linked to increased risk of inflammation; however, little is known about how animal fat ingestion directly affects intestinal immune function. The objective of this study was to assess the effect of butter feeding on lymphocyte migration in intestinal mucosa and the changes in adhesion molecules and cytokines involved in this effect. T-lymphocytes isolated from the spleen were fluorescence-labeled and injected into recipient mice. Butter was administered into the duodenum, and villus microvessels of the small intestinal mucosa were observed under an intravital microscope. mRNA expression of adhesion molecules and cytokines in the intestinal mucosa were determined by quantitative PCR. The effect of butter feeding on tumor necrosis factor (TNF)-alpha mRNA expression of intestinal macrophages was also determined. Intraluminal butter administration significantly increased lymphocyte adherence to intestinal microvessels accompanied by increases in expression levels of adhesion molecules ICAM-1, MAdCAM-1 and VCAM-1. This accumulation was significantly attenuated by anti-MAdCAM-1 and anti-ICAM-1 antibodies. Butter administration significantly increased TNF-alpha in the lamina proprial macrophages but not interleukin-6. Anti-TNF-alpha treatment attenuated the enhanced expression of adhesion molecules induced by butter administration. T-lymphocyte adherence to microvessels of the small intestinal mucosa was significantly enhanced after butter ingestion. This enhancement is due to increase in expression levels of adhesion molecules of the intestinal mucosa, which is mediated by TNF-alpha from macrophages in the intestinal lamina propria.

Changes in cytokine and nitric oxide secretion by rat alveolar macrophages after oral administration of bacterial extracts.

PubMed Central

Broug-Holub, E; Persoons, J H; Schornagel, K; Kraal, G

1995-01-01

Oral administration of the bacterial immunomodulator Broncho-Vaxom (OM-85), a lysate of eight bacteria strains commonly causing respiratory disease, has been shown to enhance the host defence of the respiratory tract. In this study we examined the effect of orally administered (in vivo) OM-85 on stimulus-induced cytokine and nitric oxide secretion by rat alveolar macrophages in vitro. The results show that alveolar macrophages isolated from OM-85-treated rats secreted significantly more nitric oxide, tumour necrosis factor-alpha (TNF-alpha) and IL-1 beta upon in vitro stimulation with lipopolysaccharide (LPS), whereas, in contrast, LPS-induced IL-6 secretion was significantly lower. The observed effects of in vivo OM-85 treatment on stimulus-induced cytokine secretion in vitro are not due to a direct effect of OM-85 on the cells, because in vitro incubation of alveolar macrophages with OM-85 did not result in altered activity, nor did direct intratracheal instillation of OM-85 in the lungs of rats result in altered alveolar macrophage activity in vitro. It is hypothesized that oral administration of OM-85 leads to priming of alveolar macrophages in such a way that immune responses are non-specifically enhanced upon stimulation. The therapeutic action of OM-85 may therefore result from an enhanced clearance of infectious bacteria from the respiratory tract due to increased alveolar macrophage activity. PMID:7648713

Enhanced self-administration of the CB1 receptor agonist WIN55,212-2 in olfactory bulbectomized rats: evaluation of possible serotonergic and dopaminergic underlying mechanisms

PubMed Central

Amchova, Petra; Kucerova, Jana; Giugliano, Valentina; Babinska, Zuzana; Zanda, Mary T.; Scherma, Maria; Dusek, Ladislav; Fadda, Paola; Micale, Vincenzo; Sulcova, Alexandra; Fratta, Walter; Fattore, Liana

2013-01-01

Depression has been associated with drug consumption, including heavy or problematic cannabis use. According to an animal model of depression and substance use disorder comorbidity, we combined the olfactory bulbectomy (OBX) model of depression with intravenous drug self-administration procedure to verify whether depressive-like rats displayed altered voluntary intake of the CB1 receptor agonist WIN55,212-2 (WIN, 12.5 μg/kg/infusion). To this aim, olfactory-bulbectomized (OBX) and sham-operated (SHAM) Lister Hooded rats were allowed to self-administer WIN by lever-pressing under a continuous [fixed ratio 1 (FR-1)] schedule of reinforcement in 2 h daily sessions. Data showed that both OBX and SHAM rats developed stable WIN intake; yet, responses in OBX were constantly higher than in SHAM rats soon after the first week of training. In addition, OBX rats took significantly longer to extinguish the drug-seeking behavior after vehicle substitution. Acute pre-treatment with serotonin 5HT1B receptor agonist, CGS-12066B (2.5–10 mg/kg), did not significantly modify WIN intake in OBX and SHAM Lister Hooded rats. Furthermore, acute pre-treatment with CGS-12066B (10 and 15 mg/kg) did not alter responses in parallel groups of OBX and SHAM Sprague Dawley rats self-administering methamphetamine under higher (FR-2) reinforcement schedule with nose-poking as operandum. Finally, dopamine levels in the nucleus accumbens (NAc) of OBX rats did not increase in response to a WIN challenge, as in SHAM rats, indicating a dopaminergic dysfunction in bulbectomized rats. Altogether, our findings suggest that a depressive-like state may alter cannabinoid CB1 receptor agonist-induced brain reward function and that a dopaminergic rather than a 5-HT1B mechanism is likely to underlie enhanced WIN self-administration in OBX rats. PMID:24688470

Credit Enhancement Overview Guide

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

Financing Solutions Working Group

2014-01-01

Provides considerations for state and local policymakers and energy efficiency program administrators designing and implementing successful credit enhancement strategies for residential and commercial buildings.

Enamel matrix derivative enhances tissue formation around scaffolds used for tissue engineering of ligaments.

PubMed

Messenger, Michael P; Raïf, El M; Seedhom, Bahaa B; Brookes, Steven J

2010-02-01

The following in vitro translational study investigated whether enamel matrix derivative (EMD), an approved biomimetic treatment for periodontal disease (Emdogain) and hard-to-heal wounds (Xelma), enhanced synovial cell colonization and protein synthesis around a scaffold used clinically for in situ tissue engineering of the torn anterior cruciate ligament (ACL). Synovial cells were enzymatically extracted from bovine synovium and dynamically seeded onto polyethylene terephthalate (PET) scaffolds. The cells were cultured in low-serum medium (0.5% FBS) for 4 weeks with either a single administration of EMD at the start of the 4 week period or multiple administrations of EMD at regular intervals throughout the 4 weeks. Samples were harvested and evaluated using the Hoechst DNA assay, BCA protein assay, cresolphthalein complexone calcium assay, SDS-PAGE, ELISA and electron microscopy. A significant increase in cell number (DNA) (p < 0.01), protein content (p < 0.01) and TGFbeta1 synthesis (p < 0.01) was observed with multiple administrations of EMD. Additionally, SDS-PAGE showed an increase in high molecular weight proteins, characteristic of the fibril-forming collagens. Electron microscopy supported these findings, showing that scaffolds treated with multiple administrations of EMD were heavily coated with cells and extracellular matrix (ECM) that enveloped the fibres. Multiple administrations of EMD to synovial cell-seeded scaffolds enhanced the formation of tissue in vitro. Additionally, it was shown that EMD enhanced TGFbeta1 synthesis of synovial cells, suggesting a potential mode of action for EMD's capacity to stimulate tissue regeneration.

Bacterial-Mediated Knockdown of Tumor Resistance to an Oncolytic Virus Enhances Therapy

PubMed Central

Cronin, Michelle; Le Boeuf, Fabrice; Murphy, Carola; Roy, Dominic G; Falls, Theresa; Bell, John C; Tangney, Mark

2014-01-01

Oncolytic viruses (OVs) and bacteria share the property of tumor-selective replication following systemic administration. In the case of nonpathogenic bacteria, tumor selectivity relates to their ability to grow extracellularly within tumor stroma and is therefore ideally suited to restricting the production of bacterially produced therapeutic agents to tumors. We have previously shown the ability of the type 1 interferon antagonist B18R to enhance the replication and spread of vesicular stomatitis virus (VSV) by overcoming related cellular innate immunity. In this study, we utilized nonpathogenic bacteria (E. coli) expressing B18R to facilitate tumor-specific production of B18R, resulting in a microenvironment depleted of bioactive antiviral cytokine, thus “preconditioning” the tumor to enhance subsequent tumor destruction by the OV. Both in vitro and in vivo infection by VSVΔ51 was greatly enhanced by B18R produced from E. coli. Moreover, a significant increase in therapeutic efficacy resulted from intravenous (IV) injection of bacteria to tumor-bearing mice 5 days prior to IV VSVΔ51 administration, as evidenced by a significant reduction in tumor growth and increased survival in mice. Our strategy is the first example where two such diverse microorganisms are rationally combined and demonstrates the feasibility of combining complementary microorganisms to improve therapeutic outcome. PMID:24569832

Effect of an administrative intervention on rates of screening for domestic violence in an urban emergency department.

PubMed

Larkin, G L; Rolniak, S; Hyman, K B; MacLeod, B A; Savage, R

2000-09-01

This study measured the effects of an administrative intervention on health care provider compliance with universal domestic violence screening protocols. We used a simple, interrupted-time-series design in a stratified random sample of female emergency department patients 18 years or older (n = 1638 preintervention, n = 1617 postintervention). The intervention was a 4-tiered hospital-approved disciplinary action, and the primary outcome was screening compliance. Preintervention and postintervention screening rates were 29.5% and 72.8%, respectively. Before the intervention, screening was worse on the night shift (odds ratio [OR] = 0.46, 95% confidence interval [CI] = 0.31, 0.68) and with psychiatric patients (OR = 0.34, 95% CI = 0.14, 0.85); after the intervention, no previous screening barriers remained significant. An administrative intervention significantly enhanced compliance with universal domestic violence screening.

Administration of steroids after 34 weeks gestation enhances fetal lung maturity profiles

PubMed Central

Shanks, Anthony; Gross, Gilad; Shim, Tammy; Allsworth, Jenifer; Bildirici, Ibrahim; Sadovsky, Yoel

2013-01-01

Objective To estimate the effect of antenatal glucocorticoid administration on fetal lung maturity in pregnancies with known fetal lung immaturity between the 34th and 37th weeks of gestation. Study Design Pregnancies between 340/7-366/7 weeks undergoing amniocentesis to determine fetal lung maturity were targeted. Women with negative results (TDx-FLM-II < 45 mg/g) were randomized to intramuscular (IM) glucocorticoid injection or no treatment. A repeat TDx-FLM-II test was obtained one week after enrollment. Results 32 women who met inclusion criteria were randomized. Seven women delivered within a week of testing for fetal lung maturity, and were excluded from the analysis. Ten received glucocorticoid and 15 did not. Women assigned to glucocorticoids had a mean increase TDx-FLM-II in one week of 28.37 mg/g. Women assigned to no-treatment had an increase of 9.76 mg/g (p <0.002). Conclusion A single course of IM glucocorticoids after 34 weeks in pregnancies with documented fetal lung immaturity significantly increases TDx- FLM-II. PMID:20478551

Oral bioavailability enhancement and hepatoprotective effects of thymoquinone by self-nanoemulsifying drug delivery system.

PubMed

Kalam, Mohd Abul; Raish, Mohammad; Ahmed, Ajaz; Alkharfy, Khalid M; Mohsin, Kazi; Alshamsan, Aws; Al-Jenoobi, Fahad I; Al-Mohizea, Abdullah M; Shakeel, Faiyaz

2017-07-01

Thymoquinone (TQ) is a poorly water soluble bioactive compound which shows poor oral bioavailability upon oral administration. Due to poor aqueous solubility and bioavailability of TQ, various self-nanoemulsifying drug delivery systems (SNEDDS) of TQ were developed and evaluated for enhancement of its hepatoprotective effects and oral bioavailability. Hepatoprotective and pharmacokinetic studies of TQ suspension and TQ-SNEDDS were carried out in rat models. Different SNEDDS formulations of TQ were developed and thermodynamically stable TQ-SNEDDS were characterized for physicochemical parameters and evaluated for drug release studies via dialysis membrane. Optimized SNEDDS formulation of TQ was selected for further evaluation of in vivo evaluation. In vivo hepatoprotective investigations showed significant hepatoprotective effects for optimized TQ-SNEDDS in comparison with TQ suspension. The oral administration of optimized SNEDDS showed significant improvement in in vivo absorption of TQ in comparison with TQ suspension. The relatively bioavailability of TQ was enhanced 3.87-fold by optimized SNEDDS in comparison with TQ suspension. The results of this research work indicated the potential of SNEDDS in enhancing relative bioavailability and therapeutic effects of natural bioactive compounds such as TQ. Copyright © 2017 Elsevier B.V. All rights reserved.

Change and administrative barriers: nurse educators' perceptions concerning the use of simulators.

PubMed

Abell, Cathy H; Keaster, Ric

2012-01-01

The purpose of this descriptive correlational research study was twofold: to examine the adoption of simulators in the nursing classroom and the relationship between adoption and nurse educators' perceptions of established change strategies as followed by program administrators. The use of simulators in education is important and requires many nurse educators to change their current teaching strategies. Data were collected from a purposive population using a demographic questionnaire, the nursing practice questionnaire (NPQ), and the change process survey. The overall diffusion score, as measured by the NPQ, was 2.6. A statistically significant correlation was noted between level of use and the perception of established change strategies being followed (r = .340, p < .01). Findings indicate that nurse educators adopt simulators sometimes when appropriate. Administrators of nursing programs can enhance this change by using established change strategies.

Guaifenesin enhances the analgesic potency of ibuprofen, nimesulide and celecoxib in mice.

PubMed

Sliva, Jiri; Dolezal, Tomas; Sykora, David; Vosmanska, Magda; Krsiak, Miloslav

2009-01-01

Previously, we found that guaifenesin enhances analgesia induced by paracetamol. The aim of the present study was to determine whether guaifenesin is able to also increase analgesic activity in the non-steroid anti-inflammatory drugs ibuprofen, nimesulide and celecoxib. In addition we investigated the influence of guaifenesin on plasma levels of nimesulide. A model of visceral pain consisting of intraperitoneal injection of acetic acid (writhing test) was used. Levels of nimesulide in plasma were measured by HPLC. All drugs were given orally and tested in mice. Guaifenesin alone did not produce any antinociceptive effect. Simultaneous administration of guaifenesin (200 mg/kg) and subanalgesic doses of ibuprofen (10 and 30 mg/kg), nimesulide (10 and 20 mg/kg) or celecoxib (1 and 5 mg/kg) resulted in a significant antinociceptive effects. The plasma levels of nimesulide were significantly higher in combination with guaifenesin at 30, 60 and 90 min after oral administration in comparison to nimesulide monotherapy. The present results suggest that guaifenesin might enhance the analgesic activity of various non-steroidal anti-inflammatory drugs.

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.

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.

Isoflavones enhance pharmacokinetic exposure of active lovastatin acid via the upregulation of carboxylesterase in high-fat diet mice after oral administration of Xuezhikang capsules.

PubMed

Feng, Dong; Ge, Chun; Tan, Zhao-Yi; Sun, Jian-Guo; Xie, Yuan; Yao, Lan; Yan, Cai-Xia; Aa, Ji-Ye; Wang, Guang-Ji

2018-06-19

Xuezhikang capsule (XZK) is a traditional Chinese medicine that contains lovastatin (Lv) for hyperlipidemia treatment, although it has fewer side effects than Lv. However, the pharmacokinetic mechanisms contributing to its distinct efficacy and low side effects are unclear. Mice were fed a high-fat diet (HFD) for 6 weeks to induce hyperlipidemia. We first conducted the pharmacokinetic studies in HFD mice following oral administration of Lv (10 mg/kg, i.g.) and found that HFD remarkably decreased the active form of Lv (the lovastatin acid, LvA) exposure in the circulation system, especially in the targeting organ liver, with a declined conversion from Lv to LvA, whereas the Lv (responsible for myotoxicity) exposure in muscle markedly increased. Then we compared the pharmacokinetic profiles of Lv in HFD mice after the oral administration of XZK (1200 mg/kg, i.g.) or an equivalent dose of Lv (10 mg/kg, i.g.). A higher exposure of LvA and lower exposure of Lv were observed after XZK administration, suggesting a pharmacokinetic interaction of some ingredients in XZK. Further studies revealed that HFD promoted the inflammation and inhibited carboxylesterase (CES) activities in the intestine and the liver, thus contributing to the lower transformation of Lv into LvA. In contrast, XZK inhibited the inflammation and upregulated CES in the intestine and the liver. Finally, we evaluated the effects of monacolins and phytosterols, the fractional extracts of isoflavones, on inflammatory LS174T or HepG2 cells, which showed that isoflavones inhibited inflammation, upregulated CES, and markedly enhanced the conversion of Lv into LvA. For the first time, we provide evidence that isoflavones and Lv in XZK act in concert to enhance the efficacy and reduce the side effects of Lv.

Plasma GH responses to GHRH, arginine, L-dopa, pyridostigmine, sequential administrations of GHRH and combined administration of PD and GHRH in Turner's syndrome.

PubMed

Hanew, K; Tanaka, A; Utsumi, A

1998-02-01

To investigate GH secretory capacities in patients with Turner's syndrome, GHRH, arginine, L-dopa and pyridostigmine (PD) were administered singly and GHRH was administered sequentially for 3 days. In addition, plasma GH and TSH responses to GHRH and TRH after pretreatment with PD were analyzed to investigate whether the hypothalamic cholinergic somatostatinergic system functioned normally. The maximal GH responses to GHRH, L-dopa and PD were significantly smaller in Turner's syndrome (no.=14) than in normal short children (NSC, no.=14). However, there was no difference in plasma GH responses to arginine between the two groups. In ten patients with Turner's syndrome, the plasma GH response to GHRH did not improve even after the sequential 3-day administrations. Although plasma GH and TSH responses to GHRH and TRH were significantly enhanced by the pretreatment of PD in NSC (no.=12), these responses were not enhanced in Turner's syndrome. Plasma GH response to GHRH in Turner's syndrome with normal body fat was still significantly lower than in NSC. It is therefore concluded that somatotroph sensitivity to GHRH is decreased in Turner's syndrome and that this may be due to the primary defects of the somatotrophs rather than to the increased body fat. In addition, the network of cholinergic-somatostatinergic systems seemed to be impaired in these patients, while the activity of hypothalamic somatostatin neurons was thought to be maintained.

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.

Design and Efficacy of Nanogels Formulations for Intranasal Administration.

PubMed

Aderibigbe, Blessing A; Naki, Tobeka

2018-05-23

Nanogels are drug delivery systems that can bypass the blood-brain barrier and deliver drugs to the desired site when administered intranasally. They have been used as a drug delivery platform for the management of brain diseases such as Alzheimer disease, migraine, schizophrenia and depression. nanogels have also been developed as vaccine carriers for the protection of bacterial infections such as influenza, meningitis, pneumonia and as veterinary vaccine carriers for the protection of animals from encephalomyelitis and mouth to foot disease. It has been developed as vaccine carriers for the prevention of lifestyle disease such as obesity. Intranasal administration of therapeutics using nanogels for the management of brain diseases revealed that the drug transportation was via the olfactory nerve pathway resulting in rapid drug delivery to the brain with excellent neuroprotective effect. The application of nanogels as vaccine carriers also induced significant responses associated with protective immunity against selected bacterial and viral infections. This review provides a detailed information on the enhanced therapeutic effects, mechanisms and biological efficacy of nanogels for intranasal administration.

Image enhancement filters significantly improve reading performance for low vision observers

NASA Technical Reports Server (NTRS)

Lawton, T. B.

1992-01-01

As people age, so do their photoreceptors; many photoreceptors in central vision stop functioning when a person reaches their late sixties or early seventies. Low vision observers with losses in central vision, those with age-related maculopathies, were studied. Low vision observers no longer see high spatial frequencies, being unable to resolve fine edge detail. We developed image enhancement filters to compensate for the low vision observer's losses in contrast sensitivity to intermediate and high spatial frequencies. The filters work by boosting the amplitude of the less visible intermediate spatial frequencies. The lower spatial frequencies. These image enhancement filters not only reduce the magnification needed for reading by up to 70 percent, but they also increase the observer's reading speed by 2-4 times. A summary of this research is presented.

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

Effects of post-session administration of methylene blue on fear extinction and contextual memory in adults with claustrophobia.

PubMed

Telch, Michael J; Bruchey, Aleksandra K; Rosenfield, David; Cobb, Adam R; Smits, Jasper; Pahl, Sandra; Gonzalez-Lima, F

2014-10-01

Preclinical studies have shown that low-dose methylene blue increases mitochondrial cytochrome oxidase activity in the brain and improves memory retention after learning tasks, including fear extinction. The authors report on the first controlled experiment to examine the memory-enhancing effects of posttraining methylene blue administration on retention of fear extinction and contextual memory following fear extinction training. Adult participants displaying marked claustrophobic fear were randomly assigned to double-blind administration of 260 mg of methylene blue (N=23) or administration of placebo (N=19) immediately following six 5-minute extinction trials in an enclosed chamber. Retesting occurred 1 month later to assess fear renewal as indexed by peak fear during exposure to a nontraining chamber, with the prediction that the effects of methylene blue would vary as a function of fear reduction achieved during extinction training. Incidental contextual memory was assessed 1 and 30 days after training to assess the cognitive-enhancing effects of methylene blue independent of its effects on fear attenuation. Consistent with predictions, participants displaying low end fear posttraining showed significantly less fear at the 1-month follow-up if they received methylene blue posttraining compared with placebo. In contrast, participants displaying moderate to high levels of posttraining fear tended to fare worse at the follow-up if they received methylene blue posttraining. Methylene blue's enhancement of contextual memory was unrelated to initial or posttraining claustrophobic fear. Methylene blue enhances memory and the retention of fear extinction when administered after a successful exposure session but may have a deleterious effect on extinction when administered after an unsuccessful exposure session.

Evaluation of intraaxial enhancing brain tumors on magnetic resonance imaging: intraindividual crossover comparison of gadobenate dimeglumine and gadopentetate dimeglumine for visualization and assessment, and implications for surgical intervention.

PubMed

Kuhn, Matthew J; Picozzi, Piero; Maldjian, Joseph A; Schmalfuss, Ilona M; Maravilla, Kenneth R; Bowen, Brian C; Wippold, Franz J; Runge, Val M; Knopp, Michael V; Wolansky, Leo J; Gustafsson, Lars; Essig, Marco; Anzalone, Nicoletta

2007-04-01

The goal in this article was to compare 0.1 mmol/kg doses of gadobenate dimeglumine (Gd-BOPTA) and gadopentetate dimeglumine, also known as gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA), for enhanced magnetic resonance (MR) imaging of intraaxial brain tumors. Eighty-four patients with either intraaxial glioma (47 patients) or metastasis (37 patients) underwent two MR imaging examinations at 1.5 tesla, one with Gd-BOPTA as the contrast agent and the other with Gd-DTPA. The interval between fully randomized contrast medium administrations was 2 to 7 days. The T1-weighted spin echo and T2-weighted fast spin echo images were acquired before administration of contrast agents and T1-weighted spin echo images were obtained after the agents were administered. Acquisition parameters and postinjection acquisition times were identical for the two examinations in each patient. Three experienced readers working in a fully blinded fashion independently evaluated all images for degree and quality of available information (lesion contrast enhancement, lesion border delineation, definition of disease extent, visualization of the lesion's internal structures, global diagnostic preference) and quantitative enhancement (that is, the extent of lesion enhancement after contrast agent administration compared with that seen before its administration [hereafter referred to as percent enhancement], lesion/brain ratio, and contrast/noise ratio). Differences were tested with the Wilcoxon signed-rank test. Reader agreement was assessed using kappa statistics. Significantly better diagnostic information/imaging performance (p < 0.0001, all readers) was obtained with Gd-BOPTA for all visualization end points. Global preference for images obtained with Gd-BOPTA was expressed for 42 (50%), 52 (61.9%), and 56 (66.7%) of 84 patients (readers 1, 2, and 3, respectively) compared with images obtained with Gd-DTPA contrast in four (4.8%), six (7.1%), and three (3.6%) of 84 patients. Similar

Feeding enhances skeletal growth and energetic stores of an Atlantic coral under significantly elevated CO2

NASA Astrophysics Data System (ADS)

Drenkard, L.; Cohen, A. L.; McCorkle, D. C.; dePutron, S.; Zicht, A.

2011-12-01

Many corals living under the relatively acidic conditions of naturally high-CO2 reefs are calcifying as fast or faster than their conspecifics on naturally low CO2 reefs. These observations are inconsistent with most experimental work that shows a negative impact of ocean acidification on coral calcification. We investigated the link between coral nutritional (energetic) status and the calcification response to significantly elevated CO2. Juveniles of the Atlantic brooding coral, Favia fragum were reared for three weeks under fully crossed CO2 and feeding conditions: ambient (μar =1.6+-0.2) and high CO2 (μar =3.7+-0.3); fed and unfed. In most measured parameters, the effect of feeding is much stronger than the effect of CO2. Nutritionally enhanced (fed) corals, regardless of CO2 condition, have higher concentrations of total lipid and their skeletons are both significantly larger and more developmentally advanced than those of corals relying solely on autotrophy. In measurements of corallite weight, where the impact of CO2 is most apparent, no statistical difference is observed between unfed corals under ambient CO2 conditions and fed corals reared under 1600 ppm CO2. Our results suggest that coral energetic status, which can be enhanced by heterotrophic feeding but depleted by stressors such as bleaching, will play a key role in the coral response to ocean acidification and thus, in the resilience of reef ecosystems under climate change.

Glutathione-Enhancing Agents Protect against Steatohepatitis in a Dietary Model

PubMed Central

Im, Hee-Jeong; Chen, Theresa S.; de Villiers, Willem J. S.; McClain, Craig J.

2010-01-01

Nonalcoholic fatty liver (NAFL) and steatohepatitis (NASH) may accompany obesity, diabetes, parenteral nutrition, jejeuno-ileal bypass, and chronic inflammatory bowel disease. Currently there is no FDA approved and effective therapy available. We investigated the potential efficacy of those agents that stimulate glutathione (GSH) biosynthesis on the development of experimental steatohepatitis. Rats fed (ad libitum) amino acid based methionine-choline deficient (MCD) diet were further gavaged with (1) vehicle (MCD), (2) S-adenosylmethionine (SAMe), or (3) 2(RS)-n-propylthiazolidine-4(R)-carboxylic acid (PTCA). Results: MCD diet significantly reduced hematocrit, and this abnormality improved in the treated groups (p < 0.01). Serum transaminases were considerably elevated (AST: 5.8-fold; ALT: 3.22-fold) in MCD rats. However, administration of GSH-enhancing agents significantly suppressed these abnormal enzyme activities. MCD rats developed severe liver pathology manifested by fatty degeneration, inflammation, and necrosis, which significantly improved with therapy. Blood levels of GSH were significantly depleted in MCD rats but normalized in the treated groups. Finally, RT-PCR measurements showed a significant upregulation of genes involved in tissue remodeling and fibrosis (matrix metalloproteinases, collagen-α1), suppressor of cytokines signaling1, and the inflammatory cytokines (IL-1β, IL-6, TNF-α, and TGF-β) in the livers of rats fed MCD. GSH-enhancing therapies significantly attenuated the expression of deleterious proinflammatory and fibrogenic genes in this dietary model. This is the first report that oral administration of SAMe and PTCA provide protection against liver injury in this model and suggests therapeutic applications of these compounds in NASH patients. PMID:16498637

Electroactive biodegradable polyurethane significantly enhanced Schwann cells myelin gene expression and neurotrophin secretion for peripheral nerve tissue engineering.

PubMed

Wu, Yaobin; Wang, Ling; Guo, Baolin; Shao, Yongpin; Ma, Peter X

2016-05-01

Myelination of Schwann cells (SCs) is critical for the success of peripheral nerve regeneration, and biomaterials that can promote SCs' neurotrophin secretion as scaffolds are beneficial for nerve repair. Here we present a biomaterials-approach, specifically, a highly tunable conductive biodegradable flexible polyurethane by polycondensation of poly(glycerol sebacate) and aniline pentamer, to significantly enhance SCs' myelin gene expression and neurotrophin secretion for peripheral nerve tissue engineering. SCs are cultured on these conductive polymer films, and the biocompatibility of these films and their ability to enhance myelin gene expressions and sustained neurotrophin secretion are successfully demonstrated. The mechanism of SCs' neurotrophin secretion on conductive films is demonstrated by investigating the relationship between intracellular Ca(2+) level and SCs' myelination. Furthermore, the neurite growth and elongation of PC12 cells are induced by adding the neurotrophin medium suspension produced from SCs-laden conductive films. These data suggest that these conductive degradable polyurethanes that enhance SCs' myelin gene expressions and sustained neurotrophin secretion perform great potential for nerve regeneration applications. Copyright © 2016 Elsevier Ltd. All rights reserved.

Enhancing marketing recruitment strategies: administrator tenure and nursing expenditures.

PubMed

Gunby, Norris White

2005-01-01

When recruiting nurses, long-term care facilities require an ability to identify salient organizational characteristics that are attractive to potential nursing services candidates vis-à-vis their competitors. The findings of this study suggest that information on administrative tenure can be utilized to attract applicants by appealing to criteria within their high-involvement job search activities. High-involvement applicants proactively seek recruitment content that provides essential job attributes that match their needs and skills and are more apt to be a higher quality candidate. Based upon the study's findings, managers are offered marketing strategy recommendations for tailoring recruiting messages that appeal to high-involvement job seekers.

Significance of diffusion weighted imaging (DWI) as an improving factor in contrast enhanced magnetic resonance imaging (MRI) enterography in evaluation of patients with Crohn's disease.

PubMed

Imširović, Bilal; Zerem, Enver; Efendić, Alma; Mekić Abazović, Alma; Zerem, Omar; Djedović, Muhamed

2018-08-01

Aim To determine capabilities and potential of contrast enhanced magnetic resonance imaging (MRI) enterography in order to establish the diagnosis and to evaluate severity and activity of intestinal inflammation. Methods Fifty-five patients with suspicion for presence of Crohn's disease were evaluated. All patients underwent contrast enhanced MRI enterography and diffusion weighted imaging (DWI), and subsequently endoscopic examination or surgical treatment. Four parameters were analysed: thickening of the bowel wall, and presence of abscess, fistula and lymphadenopathy. Results Comparing results of DWI and contrast enhanced MRI enterography a significant difference between results given through diffusion and histopathological test was found, e.g. a significant difference between results obtained through diffusion and MRI enterography was found. MRI enterography sensitiveness for bowel wall thickening was 97.7% and specificity 70%, whilst DWI sensitivity for bowel wall thickening was 84% and specificity 100%. The diagnostics of abscess and fistula showed no significant difference between DWI and MRI, while in lymphadenopathy significant difference between contrast enhanced MRI enterography and DWI was found. Conclusion Contrast enhanced MRI enterography in combination with DWI allows for excellent evaluation of disease activity, but also problems or complications following it. The examination can be repeated, controlled, and it can contribute to monitoring of patients with this disease. Copyright© by the Medical Assotiation of Zenica-Doboj Canton.

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...

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...

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

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.

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

Substrate co-doping modulates electronic metal–support interactions and significantly enhances single-atom catalysis

DOE PAGES

Shi, Jinlei; Wu, Jinghe; Zhao, Xingju; ...

2016-10-07

Transitional metal nanoparticles or atoms deposited on appropriate substrates can lead to highly economical, efficient, and selective catalysis. One of the greatest challenges is to control the electronic metal–support interactions (EMSI) between the supported metal atoms and the substrate so as to optimize their catalytic performance. Here, from first-principles calculations, we show that an otherwise inactive Pd single adatom on TiO 2(110) can be tuned into a highly effective catalyst, e.g. for O 2 adsorption and CO oxidation, by purposefully selected metal–nonmetal co-dopant pairs in the substrate. Such an effect is proved here to result unambiguously from a significantly enhancedmore » EMSI. A nearly linear correlation is noted between the strength of the EMSI and the activation of the adsorbed O 2 molecule, as well as the energy barrier for CO oxidation. Particularly, the enhanced EMSI shifts the frontier orbital of the deposited Pd atom upward and largely enhances the hybridization and charge transfer between the O 2 molecule and the Pd atom. Upon co-doping, the activation barrier for CO oxidation on the Pd monomer is also reduced to a level comparable to that on the Pd dimer which was experimentally reported to be highly efficient for CO oxidation. The present findings provide new insights into the understanding of the EMSI in heterogeneous catalysis and can open new avenues to design and fabricate cost-effective single-atom-sized and/or nanometer-sized catalysts.« less

PKCδ inhibition enhances tyrosine hydroxylase phosphorylation in mice after methamphetamine treatment

PubMed Central

Nguyen, Xuan-Khanh Thi; Bing, Guoying; Bach, Jae-Hyung; Park, Dae Hun; Nakayama, Keiichi; Ali, Syed F.; Kanthasamy, Anumantha G.; Cadet, Jean L.; Nabeshima, Toshitaka; Kim, Hyoung-Chun

2014-01-01

The present study was designed to evaluate the specific role of protein kinase C (PKC) δ in methamphetamine (MA)-induced dopaminergic toxicity. A multiple-dose administration regimen of MA significantly increases PKCδ expression, while rottlerin, a PKCδ inhibitor, significantly attenuates MA-induced hyperthermia and behavioural deficits. These behavioural effects were not significantly observed in PKCδ antisense oligonucleotide (ASO)-treated- or PKCδ knockout (−/−)-mice. There were no MA-induced significant decreases of dopamine (DA) content or tyrosine hydroxylase (TH) expression in the striatum in rottlerin-treated-, ASO-treated- or PKCδ (−/−)-mice. The administration of MA also results in a significant decrease of TH phosphorylation at ser 40, but not ser 31, while the inhibition of PKCδ consistently and significantly attenuates MA-induced reduction in the phosphorylation of TH at ser 40. Therefore, these results suggest that the MA-induced enhancement of PKCδ expression is a critical factor in the impairment of TH phosphorylation at ser 40 and that pharmacological or genetic inhibition of PKCδ may be protective against MA-induced dopaminergic neurotoxicity in vivo. PMID:21672585

Agonist anti-GITR antibody significantly enhances the therapeutic efficacy of Listeria monocytogenes-based immunotherapy.

PubMed

Shrimali, Rajeev; Ahmad, Shamim; Berrong, Zuzana; Okoev, Grigori; Matevosyan, Adelaida; Razavi, Ghazaleh Shoja E; Petit, Robert; Gupta, Seema; Mkrtichyan, Mikayel; Khleif, Samir N

2017-08-15

We previously demonstrated that in addition to generating an antigen-specific immune response, Listeria monocytogenes (Lm)-based immunotherapy significantly reduces the ratio of regulatory T cells (Tregs)/CD4 + and myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment. Since Lm-based immunotherapy is able to inhibit the immune suppressive environment, we hypothesized that combining this treatment with agonist antibody to a co-stimulatory receptor that would further boost the effector arm of immunity will result in significant improvement of anti-tumor efficacy of treatment. Here we tested the immune and therapeutic efficacy of Listeria-based immunotherapy combination with agonist antibody to glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR) in TC-1 mouse tumor model. We evaluated the potency of combination on tumor growth and survival of treated animals and profiled tumor microenvironment for effector and suppressor cell populations. We demonstrate that combination of Listeria-based immunotherapy with agonist antibody to GITR synergizes to improve immune and therapeutic efficacy of treatment in a mouse tumor model. We show that this combinational treatment leads to significant inhibition of tumor-growth, prolongs survival and leads to complete regression of established tumors in 60% of treated animals. We determined that this therapeutic benefit of combinational treatment is due to a significant increase in tumor infiltrating effector CD4 + and CD8 + T cells along with a decrease of inhibitory cells. To our knowledge, this is the first study that exploits Lm-based immunotherapy combined with agonist anti-GITR antibody as a potent treatment strategy that simultaneously targets both the effector and suppressor arms of the immune system, leading to significantly improved anti-tumor efficacy. We believe that our findings depicted in this manuscript provide a promising and translatable strategy that can enhance the overall

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.

Hyperintense Dentate Nuclei on T1-Weighted MRI: Relation to Repeat Gadolinium Administration

PubMed Central

Adin, M.E.; Kleinberg, L.; Vaidya, D.; Zan, E.; Mirbagheri, S.; Yousem, D.M.

2016-01-01

BACKGROUND AND PURPOSE A hyperintense appearance of the dentate nucleus on T1-weighted MR images has been related to various clinical conditions, but the etiology remains indeterminate. We aimed to investigate the possible associations between a hyperintense appearance of the dentate nucleus on T1-weighted MR images in patients exposed to radiation and factors including, but not limited to, the cumulative number of contrast-enhanced MR images, amount of gadolinium administration, dosage of ionizing radiation, and patient demographics. MATERIALS AND METHODS The medical records of 706 consecutive patients who were treated with brain irradiation at The Johns Hopkins Medical Institutions between 1995 and 2010 were blindly reviewed by 2 readers. RESULTS One hundred eighty-four subjects were included for dentate nuclei analysis. Among the 184 subjects who cumulatively underwent 2677 MR imaging studies following intravenous gadolinium administration, 103 patients had hyperintense dentate nuclei on precontrast T1-weighted MR images. The average number of gadolinium-enhanced MR imaging studies performed in the group with normal dentate nuclei was significantly lower than that of the group with hyperintense dentate nuclei. The average follow-up time was 62.5 months. No significant difference was observed between hyperintense and normal dentate nuclei groups in terms of exposed radiation dose, serum creatinine and calcium/phosphate levels, patient demographics, history of chemotherapy, and strength of the scanner. No dentate nuclei abnormalities were found on the corresponding CT scans of patients with hyperintense dentate nuclei (n = 44). No dentate nuclei abnormalities were found in 53 healthy volunteers. CONCLUSIONS Repeat performance of gadolinium-enhanced studies likely contributes to a long-standing hyperintense appearance of dentate nuclei on precontrast T1-weighted-MR images. PMID:26294649

Nano-Advantage in Enhanced Drug Delivery with Biodegradable Nanoparticles: Contribution of Reduced Clearance

PubMed Central

Kadam, Rajendra S.; Bourne, David W. A.

2012-01-01

The aim of this study was to investigate the contribution of reduced apparent clearance to the enhanced exposure reported for biodegradable nanoparticles after extravascular and intravascular routes of administration. Plasma concentration profiles for drug and nanoparticle formulations after administration by intravenous, intraduodenal, and oral routes were extracted from the literature. Data were fit to pharmacokinetic models using BOOMER. The compartmental pharmacokinetic analysis of literature data for six drugs (camptothecin, 9-nitrocamptothecin, epirubicin, vinpocetine, clozapine, and cyclosporine) showed that the encapsulation of drug molecules in nanoparticles significantly reduced the apparent clearance and prolonged the apparent circulation half-life compared with those for the plain drug. Positively charged nanoparticles assessed in this study had lower apparent clearance, lower elimination rate constant values, and longer apparent circulation half-life than neutral and negatively charged nanoparticles. After oral administration, a reduction in apparent clearance contributed substantially to elevations in plasma drug exposure with nanoparticles. For the drugs and delivery systems examined, the nano-advantage in drug delivery enhancement can be explained, in part, by reduced clearance. PMID:22498894

Investigation of effects of time of measurement and modes of administration on cadmium accumulation in rat liver under some medicinal plants food supplemented diet

PubMed Central

Nwokocha, Chukwuemeka R.; Younger-Coleman, Novie; Nwokocha, Magdalene; Owu, Daniel U.; Iwuala, Moses

2014-01-01

Context and Objectives: Cadmium (Cd) toxicity leads to cell and organ damage, we comparatively examined the protection ability of different medicinal plants on Cd liver accumulation following different treatment interventions and modes of administration. Materials and Methods: Rats were fed either 7% w/w Zingiber officinale, 7% w/w Allium Sativum, 10% w/w Lycopersicon esculentum, 5%, w/w Garcinia kola (all in rat chow), while Cd (200 ppm) was given in drinking water. Additives were administered together with (mode 1), a week after (mode 2) or a week before metal exposure (mode 3) for a period of six weeks. Cd liver was determined using AAS and compared using analysis of variance (ANOVA). Results: All additives significantly (P <0.5) reduced the accumulation of Cd in the liver. After adjusting for time and mode of administration, mean %protection for week 4 was significantly lower by 14.1% (P=0.02) from that for week 2 but the means did not differ with respect to additive used or mode of administration, no statistically significant interaction between modes of administration and either of additives used or time of administration in their respective relationships to percentage protection from Cd. Conclusion: Additives significantly reduced Cd accumulation through a reduction in absorption and enhancement of metal excretion. PMID:25002805

Investigation of effects of time of measurement and modes of administration on cadmium accumulation in rat liver under some medicinal plants food supplemented diet.

PubMed

Nwokocha, Chukwuemeka R; Younger-Coleman, Novie; Nwokocha, Magdalene; Owu, Daniel U; Iwuala, Moses

2014-07-01

Cadmium (Cd) toxicity leads to cell and organ damage, we comparatively examined the protection ability of different medicinal plants on Cd liver accumulation following different treatment interventions and modes of administration. Rats were fed either 7% w/w Zingiber officinale, 7% w/w Allium Sativum, 10% w/w Lycopersicon esculentum, 5%, w/w Garcinia kola (all in rat chow), while Cd (200 ppm) was given in drinking water. Additives were administered together with (mode 1), a week after (mode 2) or a week before metal exposure (mode 3) for a period of six weeks. Cd liver was determined using AAS and compared using analysis of variance (ANOVA). All additives significantly (P <0.5) reduced the accumulation of Cd in the liver. After adjusting for time and mode of administration, mean %protection for week 4 was significantly lower by 14.1% (P=0.02) from that for week 2 but the means did not differ with respect to additive used or mode of administration, no statistically significant interaction between modes of administration and either of additives used or time of administration in their respective relationships to percentage protection from Cd. Additives significantly reduced Cd accumulation through a reduction in absorption and enhancement of metal excretion.

23 CFR 710.511 - Transportation enhancements.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 23 Highways 1 2014-04-01 2014-04-01 false Transportation enhancements. 710.511 Section 710.511 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RIGHT-OF-WAY AND ENVIRONMENT RIGHT-OF-WAY AND REAL ESTATE Property Acquisition Alternatives § 710.511 Transportation enhancements. (a...

23 CFR 710.511 - Transportation enhancements.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 23 Highways 1 2013-04-01 2013-04-01 false Transportation enhancements. 710.511 Section 710.511 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RIGHT-OF-WAY AND ENVIRONMENT RIGHT-OF-WAY AND REAL ESTATE Property Acquisition Alternatives § 710.511 Transportation enhancements. (a...

23 CFR 710.511 - Transportation enhancements.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 23 Highways 1 2011-04-01 2011-04-01 false Transportation enhancements. 710.511 Section 710.511 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RIGHT-OF-WAY AND ENVIRONMENT RIGHT-OF-WAY AND REAL ESTATE Property Acquisition Alternatives § 710.511 Transportation enhancements. (a...

23 CFR 710.511 - Transportation enhancements.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 23 Highways 1 2012-04-01 2012-04-01 false Transportation enhancements. 710.511 Section 710.511 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RIGHT-OF-WAY AND ENVIRONMENT RIGHT-OF-WAY AND REAL ESTATE Property Acquisition Alternatives § 710.511 Transportation enhancements. (a...

NMDA receptors regulate nicotine-enhanced brain reward function and intravenous nicotine self-administration: role of the ventral tegmental area and central nucleus of the amygdala.

PubMed

Kenny, Paul J; Chartoff, Elena; Roberto, Marisa; Carlezon, William A; Markou, Athina

2009-01-01

Nicotine is considered an important component of tobacco responsible for the smoking habit in humans. Nicotine increases glutamate-mediated transmission throughout brain reward circuitries. This action of nicotine could potentially contribute to its intrinsic rewarding and reward-enhancing properties, which motivate consumption of the drug. Here we show that the competitive N-methyl-D-aspartate (NMDA) receptor antagonist LY235959 (0.5-2.5 mg per kg) abolished nicotine-enhanced brain reward function, reflected in blockade of the lowering of intracranial self-stimulation (ICSS) thresholds usually observed after experimenter-administered (0.25 mg per kg) or intravenously self-administered (0.03 mg per kg per infusion) nicotine injections. The highest LY235959 dose (5 mg per kg) tested reversed the hedonic valence of nicotine from positive to negative, reflected in nicotine-induced elevations of ICSS thresholds. LY235959 doses that reversed nicotine-induced lowering of ICSS thresholds also markedly decreased nicotine self-administration without altering responding for food reinforcement, whereas the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor antagonist NBQX had no effects on nicotine intake. In addition, nicotine self-administration upregulated NMDA receptor subunit expression in the central nucleus of the amygdala (CeA) and ventral tegmental area (VTA), suggesting important interactions between nicotine and the NMDA receptor. Furthermore, nicotine (1 microM) increased NMDA receptor-mediated excitatory postsynaptic currents in rat CeA slices, similar to its previously described effects in the VTA. Finally, infusion of LY235959 (0.1-10 ng per side) into the CeA or VTA decreased nicotine self-administration. Taken together, these data suggest that NMDA receptors, including those in the CeA and VTA, gate the magnitude and valence of the effects of nicotine on brain reward systems, thereby regulating motivation to consume the drug.

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

Low-protein diet promotes sodium chloride-enhanced gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats.

PubMed

Iishi, H; Tatsuta, M; Baba, M; Hirasawa, R; Sakai, N; Yano, H; Uehara, H; Nakaizumi, A

1999-07-01

Sodium chloride (NaCl) initiates and promotes experimental carcinogenesis in rats. We recently found that a high-protein diet attenuates NaCl-enhanced gastric carcinogenesis in Wistar rats. To investigate the effect of a purified low-protein diet on NaCl-enhanced gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in Wistar rats, rats were fed a purified diet with an equalized caloric content containing 1% or 2% NaCl and 25% casein (normal-protein diet) or 10% casein (low-protein diet) after oral treatment with MNNG for 25 weeks. In week 52, neither 1% nor 2% NaCl had a significant effect on gastric carcinogenesis in rats fed a normal-protein diet. However, oral administration of 2%, but not 1%, NaCl significantly increased the incidence of gastric cancers in rats fed a low-protein diet. Oral administration of 2% NaCl also significantly increased the bromodeoxyuridine (BrdU)-labeling index and the ornithine decarboxylase (ODC) activity and decreased apoptosis of gastric cancers in rats fed a low-protein diet. However, 2% NaCl had no significant effect on these three parameters in rats fed a normal-protein diet. These findings indicate that a low-protein diet enhances the effect of NaCl in gastric carcinogenesis and that this enhancement may be mediated by increased cell proliferation and reduced apoptosis of gastric cancers.

Experience-Dependent Effects of Cocaine Self-Administration/Conditioning on Prefrontal and Accumbens Dopamine Responses

PubMed Central

Ikegami, Aiko; Olsen, Christopher M.; D’Souza, Manoranjan S.; Duvauchelle, Christine L.

2008-01-01

Experiments were performed to examine the effects of cocaine self-administration and conditioning experience on operant behavior, locomotor activity, and nucleus accumbens (NAcc) and prefrontal cortex (PFC) dopamine (DA) responses. Sensory cues were paired with alternating cocaine and nonreinforcement during 12 (limited training) or 40 (long-term training) daily operant sessions. After limited training, NAcc DA responses to cocaine were significantly enhanced in the presence of cocaine-associated cues compared with nonreward cues and significantly depressed after cocaine-paired cues accompanied a nonreinforced lever response. PFC DA levels were generally nonresponsive to cues after the same training duration. However, after long-term training, cocaine-associated cues increased the magnitude of cocaine-stimulated PFC DA levels significantly over levels observed with nonreinforcement cues. Conversely, conditioned cues no longer influenced NAcc DA levels after long-term training. In addition, cocaine-stimulated locomotor activity was enhanced by cocaine-paired cues after long-term, but not after limited, training. Findings demonstrate that cue-induced cocaine expectation exerts a significant impact on dopaminergic and behavioral systems, progressing from mesolimbic to mesocortical regions and from latent to patent behaviors as cocaine and associative experiences escalate. PMID:17469929

Ability of Mn2+ to Permeate the Eye and Availability of Manganese-enhanced Magnetic Resonance Imaging for Visual Pathway Imaging via Topical Administration

PubMed Central

Chen, Yao; Shi, Chun-Yan; Li, Ying; Hu, Yun-Tao; Han, Hong-Bin; Sun, Xiao-Dong; Salvi, Satyajeet S; Ma, Zhi-Zhong

2016-01-01

Background: Manganese-enhanced magnetic resonance imaging (MEMRI) for visual pathway imaging via topical administration requires further research. This study investigated the permeability of the corneal epithelium and corneal toxicity after topical administration of Mn2+ to understand the applicability of MEMRI. Methods: Forty New Zealand rabbits were divided into 0.05 mol/L, 0.10 mol/L, and 0.20 mol/L groups as well as a control group (n = 10 in each group). Each group was further subdivided into epithelium-removed and epithelium-intact subgroups (n = 5 in each subgroup). Rabbits were given 8 drops of MnCl2 in 5 min intervals. The Mn2+ concentrations in the aqueous and vitreous humors were analyzed using inductively coupled plasma-mass spectrometry at different time points. MEMRI scanning was carried out to image the visual pathway after 24 h. The corneal toxicity of Mn2+ was evaluated with corneal imaging and pathology slices. Results: Between the aqueous and vitreous humors, there was a 10 h lag for the peak Mn2+ concentration times. The intraocular Mn2+ concentration increased with the concentration gradients of Mn2+ and was higher in the epithelium-removed subgroup than that in the epithelium-intact subgroup. The enhancement of the visual pathway was achieved in the 0.10 mol/L and 0.20 mol/L epithelium-removed subgroups. The corresponding peak concentrations of Mn2+ were 5087 ± 666 ng/ml, 22920 ± 1188 ng/ml in the aqueous humor and 884 ± 78 ng/ml, 2556 ± 492 ng/ml in the vitreous body, respectively. Corneal injury was evident in the epithelium-removed and 0.20 mol/L epithelium-intact subgroups. Conclusions: The corneal epithelium is a barrier to Mn2+, and the iris and lens septum might be another intraocular barrier to the permeation of Mn2+. An elevated Mn2+ concentration contributes to the increased permeation of Mn2+, higher MEMRI signal, and corneal toxicity. The enhancement of the visual pathway requires an effective Mn2+ concentration in the vitreous

The tendency to sign-track predicts cue-induced reinstatement during nicotine self-administration, and is enhanced by nicotine but not ethanol

PubMed Central

Versaggi, Cassandra L.; King, Christopher P.; Meyer, Paul J.

2016-01-01

Rationale Some individuals are particularly responsive to reward-associated stimuli (“cues”), including the effects of these cues on craving and relapse to drug-seeking behavior. In the cases of nicotine and alcohol, cues may acquire these abilities via the incentive-enhancing properties of the drug. Objectives To determine the interaction between cue-responsivity and nicotine reinforcement, we studied the patterns of nicotine self-administration in rats categorized based on their tendency to approach a food predictive cue (“sign-trackers”) or a reward-delivery location (“goal-trackers”). In a second experiment, we determined whether nicotine and ethanol altered the incentive value of a food cue. Methods Rats were classified as sign- or goal-trackers during a Pavlovian conditioned approach paradigm. Rats then self-administered intravenous nicotine (0.03 mg/kg infusions) followed by extinction and cue induced reinstatement tests. We also tested the effects of nicotine (0.4 mg/kg base s.c.) or ethanol (0.7 g/kg i.p.) on the approach to, and reinforcing efficacy of, a food cue. Results Sign-trackers showed greater reinstatement in response to a nicotine cue. Further, nicotine enhanced sign-tracking but not goal-tracking to a food cue, and also enhanced responding for the food cue during the conditioned reinforcement test. Conversely, ethanol reduced sign-tracking and increased goal-tracking, but had no effect on conditioned reinforcement. Conclusions Our studies demonstrate that the tendency to attribute incentive value to a food cue predicts enhanced cue-induced reinstatement. Additionally, the incentive value of food cues is differentially modulated by nicotine and ethanol, which may be related to the reinforcing effects of these drugs. PMID:27282365

The tendency to sign-track predicts cue-induced reinstatement during nicotine self-administration, and is enhanced by nicotine but not ethanol.

PubMed

Versaggi, Cassandra L; King, Christopher P; Meyer, Paul J

2016-08-01

Some individuals are particularly responsive to reward-associated stimuli ("cues"), including the effects of these cues on craving and relapse to drug-seeking behavior. In the cases of nicotine and alcohol, cues may acquire these abilities via the incentive-enhancing properties of the drug. To determine the interaction between cue-responsivity and nicotine reinforcement, we studied the patterns of nicotine self-administration in rats categorized based on their tendency to approach a food-predictive cue ("sign-trackers") or a reward-delivery location ("goal-trackers"). In a second experiment, we determined whether nicotine and ethanol altered the incentive value of a food cue. Rats were classified as sign- or goal-trackers during a Pavlovian conditioned approach paradigm. Rats then self-administered intravenous nicotine (0.03 mg/kg infusions) followed by extinction and cue-induced reinstatement tests. We also tested the effects of nicotine (0.4 mg/kg base s.c.) or ethanol (0.7 g/kg i.p.) on the approach to, and reinforcing efficacy of, a food cue. Sign-trackers showed greater reinstatement in response to a nicotine cue. Further, nicotine enhanced sign-tracking but not goal-tracking to a food cue and also enhanced responding for the food cue during the conditioned reinforcement test. Conversely, ethanol reduced sign-tracking and increased goal-tracking, but had no effect on conditioned reinforcement. Our studies demonstrate that the tendency to attribute incentive value to a food cue predicts enhanced cue-induced reinstatement. Additionally, the incentive value of food cues is differentially modulated by nicotine and ethanol, which may be related to the reinforcing effects of these drugs.

Significantly enhanced photocatalytic activity of visible light responsive AgBr/Bi2Sn2O7 heterostructured composites

NASA Astrophysics Data System (ADS)

Hu, Chaohao; Zhuang, Jing; Zhong, Liansheng; Zhong, Yan; Wang, Dianhui; Zhou, Huaiying

2017-12-01

Heterostructured AgBr/Bi2Sn2O7 photocatalysts were synthesized successfully via the ultrasonic-assisted chemical precipitation method. XRD, FT-IR, FE-SEM, TEM, XPS, UV-vis-DRS and PL spectroscopy were used to characterize the phase structure, morphology, chemical composition, oxidation state, and optical properties of AgBr/Bi2Sn2O7 heterojunction. The photocatalytic activity of as-prepared catalysts was evaluated by the degradation of RhB under visible light irradiation. The obtained AgBr/Bi2Sn2O7 composite with the 1:1 molar ratio exhibited significantly enhanced photocatalytic performance. Further first-principles calculations indicated that the hybridization interaction between Ag and O atoms at AgBr/Bi2Sn2O7 interface is expected to be beneficial for enhancing the charge transfer and improving the photocatalytic activity of heterostructured composites.

Thiolated polycarbophil/glutathione: defining its potential as a permeation enhancer for oral drug administration in comparison to sodium caprate.

PubMed

Perera, Glen; Barthelmes, Jan; Vetter, Anja; Krieg, Christof; Uhlschmied, Cindy; Bonn, Günther K; Bernkop-Schnürch, Andreas

2011-08-01

Thiolated polyacrylates were shown to be permeation enhancers with notable potential. The aim of this study was to evaluate the permeation enhancing properties of a thiolated polycarbophil/glutathione (PCP-Cys/GSH) system for oral drug application in comparison to a well-established permeation enhancer, namely sodium caprate. In vitro permeation studies were conducted in Ussing-type chambers with sodium fluoresceine (NaFlu) and fluoresceine isothiocyanate labeled dextran (molecular mass 4 kDa; FD4) as model compounds. Bioavailability studies were carried out in Sprague Dawley rats with various formulations. Moreover, cytotoxic effects of both permeation enhancers were compared. Permeation enhancement ratios of 1% sodium caprate were found to be 3.0 (FD4) and 2.3 (NaFlu), whereas 1% PCP-Cys/0.5% GSH displayed enhancement ratios of 2.4 and 2.2. Both excipients performed at a similar level in vivo. Sodium caprate solutions increased oral bioavailability 2.2-fold (FD4) and 2.3-fold (NaFlu), while PCP-Cys hydrogels led to a 3.2-fold and 2.2-fold enhancement. Cell viability experiments revealed a significantly higher tolerance of Caco-2 cells towards 0.5% PCP-Cys (81% survival) compared to 0.5% sodium caprate (5%). As PCP-Cys is not absorbed from mucosal membranes due to its comparatively high molecular mass, systemic side-effects can be excluded. In conclusion, both systems displayed a similar potency for permeation enhancement of hydrophilic compounds. However, PCP-Cys seems to be less harmful to cultured cells.

Co-administration with cell penetrating peptide enhances the oral bioavailability of docetaxel-loaded nanoparticles.

PubMed

Bu, Xiangyuan; Zhu, Tao; Ma, Yiran; Shen, Qi

2015-05-01

This study proposes a novel docetaxel (DTX) cyclodextrin inclusion-loaded poly (lactic-co-glycolic acid) (PLGA) nanoparticles (D-CNPs) system with cell penetrating peptide (CPP), and evaluates its potential for oral administration of DTX. Heptaarginine (R7) was used as the CPP. D-CNPs were prepared by the double-emulsification method. The mean particle size and zeta potential of the resulting D-CNPs were 198.7 ± 12.56 nm and -27.25 ± 4.62 mV, respectively, and their mean encapsulation efficiency and drug loading were 80.35 ± 6.37% and 1.02 ± 0.15%, respectively. The morphology of the D-CNPs was observed by scanning electron microscope (SEM) and transmission electron microscope (TEM). The release behavior of the D-CNPs was studied by using the dialysis method. The relative bioavailability of D-CNPs and D-CNPs co-administered with R7 was enhanced about 5.57- and 9.43-fold, respectively, compared with the free DTX suspension. Furthermore, D-CNPs with R7 displayed maximum cytotoxicity against MCF-7 cells in MTT assay. D-CNPs co-administered with R7 showed markedly higher fluorescence intensity than D-CNPs without CPP. The results suggest that the D-CNPs co-administered with R7 could be a potential delivery system with excellent therapeutic efficacy for targeting the drugs to cancer cells.

Carbon-tuned bonding method significantly enhanced the hydrogen storage of BN-Li complexes.

PubMed

Deng, Qing-ming; Zhao, Lina; Luo, You-hua; Zhang, Meng; Zhao, Li-xia; Zhao, Yuliang

2011-11-01

Through first-principles calculations, we found doping carbon atoms onto BN monolayers (BNC) could significantly strengthen the Li bond on this material. Unlike the weak bond strength between Li atoms and the pristine BN layer, it is observed that Li atoms are strongly hybridized and donate their electrons to the doped substrate, which is responsible for the enhanced binding energy. Li adsorbed on the BNC layer can serve as a high-capacity hydrogen storage medium, without forming clusters, which can be recycled at room temperature. Eight polarized H(2) molecules are attached to two Li atoms with an optimal binding energy of 0.16-0.28 eV/H(2), which results from the electrostatic interaction of the polarized charge of hydrogen molecules with the electric field induced by positive Li atoms. This practical carbon-tuned BN-Li complex can work as a very high-capacity hydrogen storage medium with a gravimetric density of hydrogen of 12.2 wt%, which is much higher than the gravimetric goal of 5.5 wt % hydrogen set by the U.S. Department of Energy for 2015.

Airport capacity enhancement plan

DOT National Transportation Integrated Search

1986-01-01

The first edition of the Airport Capacity Enhancement Plan has been developed : by the Federal Aviation Administration's newly established Airport Capacity Program : Office (ACPO). The plan is intended to increase the capacity and efficient utiliza :...

5-Aminolevulinic Acid Induced Fluorescence Is a Powerful Intraoperative Marker for Precise Histopathological Grading of Gliomas with Non-Significant Contrast-Enhancement

PubMed Central

Widhalm, Georg; Kiesel, Barbara; Woehrer, Adelheid; Traub-Weidinger, Tatjana; Preusser, Matthias; Marosi, Christine; Prayer, Daniela; Hainfellner, Johannes A.; Knosp, Engelbert; Wolfsberger, Stefan

2013-01-01

Background Intraoperative identification of anaplastic foci in diffusely infiltrating gliomas (DIG) with non-significant contrast-enhancement on MRI is indispensible to avoid histopathological undergrading and subsequent treatment failure. Recently, we found that 5-aminolevulinic acid (5-ALA) induced protoporphyrin IX (PpIX) fluorescence can visualize areas with increased proliferative and metabolic activity in such gliomas intraoperatively. As treatment of DIG is predominantely based on histopathological World Health Organisation (WHO) parameters, we analyzed whether PpIX fluorescence can detect anaplastic foci according to these criteria. Methods We prospectively included DIG patients with non-significant contrast-enhancement that received 5-ALA prior to resection. Intraoperatively, multiple samples from PpIX positive and negative intratumoral areas were collected using a modified neurosurgical microscope. In all samples, histopathological WHO criteria and proliferation rate were assessed and correlated to the PpIX fluorescence status. Results A total of 215 tumor specimens were collected in 59 patients. Of 26 WHO grade III gliomas, 23 cases (85%) showed focal PpIX fluorescence, whereas 29 (91%) of 33 WHO grade II gliomas were PpIX negative. In intratumoral areas with focal PpIX fluorescence, mitotic rate, cell density, nuclear pleomorphism, and proliferation rate were significantly higher than in non-fluorescing areas. The positive predictive value of focal PpIX fluorescence for WHO grade III histology was 85%. Conclusions Our study indicates that 5-ALA induced PpIX fluorescence is a powerful marker for intraoperative identification of anaplastic foci according to the histopathological WHO criteria in DIG with non-significant contrast-enhancement. Therefore, application of 5-ALA optimizes tissue sampling for precise histopathological diagnosis independent of brain-shift. PMID:24204718

5-Aminolevulinic acid induced fluorescence is a powerful intraoperative marker for precise histopathological grading of gliomas with non-significant contrast-enhancement.

PubMed

Widhalm, Georg; Kiesel, Barbara; Woehrer, Adelheid; Traub-Weidinger, Tatjana; Preusser, Matthias; Marosi, Christine; Prayer, Daniela; Hainfellner, Johannes A; Knosp, Engelbert; Wolfsberger, Stefan

2013-01-01

Intraoperative identification of anaplastic foci in diffusely infiltrating gliomas (DIG) with non-significant contrast-enhancement on MRI is indispensible to avoid histopathological undergrading and subsequent treatment failure. Recently, we found that 5-aminolevulinic acid (5-ALA) induced protoporphyrin IX (PpIX) fluorescence can visualize areas with increased proliferative and metabolic activity in such gliomas intraoperatively. As treatment of DIG is predominantely based on histopathological World Health Organisation (WHO) parameters, we analyzed whether PpIX fluorescence can detect anaplastic foci according to these criteria. We prospectively included DIG patients with non-significant contrast-enhancement that received 5-ALA prior to resection. Intraoperatively, multiple samples from PpIX positive and negative intratumoral areas were collected using a modified neurosurgical microscope. In all samples, histopathological WHO criteria and proliferation rate were assessed and correlated to the PpIX fluorescence status. A total of 215 tumor specimens were collected in 59 patients. Of 26 WHO grade III gliomas, 23 cases (85%) showed focal PpIX fluorescence, whereas 29 (91%) of 33 WHO grade II gliomas were PpIX negative. In intratumoral areas with focal PpIX fluorescence, mitotic rate, cell density, nuclear pleomorphism, and proliferation rate were significantly higher than in non-fluorescing areas. The positive predictive value of focal PpIX fluorescence for WHO grade III histology was 85%. Our study indicates that 5-ALA induced PpIX fluorescence is a powerful marker for intraoperative identification of anaplastic foci according to the histopathological WHO criteria in DIG with non-significant contrast-enhancement. Therefore, application of 5-ALA optimizes tissue sampling for precise histopathological diagnosis independent of brain-shift.

Modulation of systemic and mucosal immunity against an inactivated vaccine of Newcastle disease virus by oral co-administration of live attenuated Salmonella enterica serovar Typhimurium expressing chicken interleukin-18 and interferon-α

PubMed Central

RAHMAN, Md. Masudur; UYANGAA, Erdenebelig; HAN, Young Woo; HUR, Jin; PARK, Sang-Youel; LEE, John Hwa; KIM, Koanhoi; EO, Seong Kug

2014-01-01

Newcastle disease (ND) is a highly contagious disease of chickens causing significant economic losses worldwide. Due to limitations in the efficacy against currently circulating ND viruses, existing vaccination strategies require improvements, and incorporating immunomodulatory cytokines with existing vaccines might be a novel approach. Here, we investigated the systemic and mucosal immunomodulatory properties of oral co-administration of chicken interleukin-18 (chIL-18) and chicken interferon-α (chIFN-α) using attenuated Salmonella enterica serovar Typhimurium on an inactivated ND vaccine. Our results demonstrate that oral administration of S. enterica serovar Typhimurium expressing chIL-18 or chIFN-α provided enhanced systemic and mucosal immune responses, as determined by serum hemagglutination inhibition antibody and NDV Ag-specific IgG as well as NDV Ag-specific IgA in lung and duodenal lavages of chickens immunized with inactivated ND vaccine via the intramuscular or intranasal route. Notably, combined oral administration of S. enterica serovar Typhimurium expressing chIL-18 and chIFN-α significantly enhanced systemic and mucosal immunity in ND-vaccinated chickens, compared to single administration of S. enterica serovar Typhimurium expressing chIL-18 or chIFN-α. In addition, oral co-administration of S. enterica serovar Typhimurium expressing chIL-18 and chIFN-α provided enhanced NDV Ag-specific proliferation of peripheral blood mononuclear cells and Th1-biased cell-mediated immunity, compared to single administration of either construct. Therefore, our results provide valuable insight into the modulation of systemic and mucosal immunity by incorporation of immunomodulatory chIL-18 and chIFN-α using Salmonella vaccines into existing ND vaccines. PMID:25502364

Dissolution and bioavailability enhancement of alpha-asarone by solid dispersions via oral administration.

PubMed

Deng, Li; Wang, Yu; Gong, Tao; Sun, Xun; Zhang, Zhi-Rong

2017-11-01

Alpha (α)-asarone (1-propenyl-2,4,5-methoxybenzol) (ARE) has been extensively used to treat chronic obstructive pulmonary diseases (COPD), bronchial asthma, pneumonia, and epilepsy. Due to its poor solubility and bioavailability, ARE was clinically administered via intravenous injection. However, severe allergies were often reported due to the presence of solublizers in the injection formulation. In our study, we sought to explore the biopharmaceutical classification of ARE, elucidate the mechanisms behind ARE absorption, and to develop a viable formulation to improve the oral bioavailability of ARE. ARE was not a P-glycoprotein substrate, which was absorbed in the passive mode without site specificity in the gastrointestinal tract. Solid dispersions prepared using hydrophilic matrix materials such as Pluronic F68, and polyethylene glycol (PEG) of varying molecular weights (PEG4K, PEG10K, and PEG20K) were proven to significantly improve the dissolution of ARE in vitro and the oral bioavailability of ARE in rats, which represent a promising strategy for the oral administration of ARE and other BCS II compounds.

Effects of GHRP-2 and Cysteamine Administration on Growth Performance, Somatotropic Axis Hormone and Muscle Protein Deposition in Yaks (Bos grunniens) with Growth Retardation

PubMed Central

Hu, Rui; Wang, Zhisheng; Peng, Quanhui; Zou, Huawei; Wang, Hongze; Yu, Xiaoqiang; Jing, Xiaoping; Wang, Yixin; Cao, Binghai; Bao, Shanke; Zhang, Wenhua; Zhao, Suonan; Ji, Hanzhong; Kong, Xiangying; Niu, Quanxi

2016-01-01

The objective of this study was to investigate the effects of growth hormone-releasing peptide-2 (GHRP-2) and cysteamine (CS) administration on growth performance in yaks with growth retardation and try to elucidate its regulatory mechanisms. Trial 1, thirty-six 1-year-old Qinghai high plateau yaks (body weight 38–83.2 kg) were randomly chosen for body weight and jugular blood samples collection. The relationship between body weight and serum GHRH (P < 0.05, R = 0.45), GH (P < 0.05, R = 0.47), IGF-1 (P < 0.05, R = 0.62) was significantly correlated in yaks colonies with lighter body weights. Trial 2, fifteen 1-year-old Qinghai high plateau yaks with growth retardation (average body weight 54.8 ± 8.24 kg) were randomly selected and assigned to negative control group (NG), GHRP-2 injection group (GG) and cysteamine feeding group (CG), with 5 yaks per group. Another five 1-year-old Qinghai high plateau yaks with normal growth performance (average body weight 75.3 ± 2.43 kg) were selected as positive control group (PG). The average daily gain (ADG) of the GG and CG were significantly higher than those in the PG and NG (P < 0.05). Both GHRP-2 and CS administration significantly enhanced the myofiber diameter and area of skeletal muscle (P<0.05). GHRP-2 significantly enhanced the serum GH and IGF-1 levels (P < 0.05), and up-regulated GHR, IGF-1 and IGF-1R mRNA expression in the liver and skeletal muscle (P < 0.05), enhanced the mRNA expression of PI3K, AKt and mTOR in the skeletal muscle (P<0.05). CS significantly reduced the serum SS levels and the hypothalamus SS mRNA expression (P < 0.05), and enhanced GHR and IGF-1 mRNA expression in the liver (P < 0.05), decreased the mRNA expression of muscle atrophy F-box (Atrogin-1) and muscle ring finger 1 (MuRF1) mRNA (P < 0.05). Conclusions: Growth retardation in yaks was primarily due to somatotropic axis hormones secretion deficiency. Both GHRP-2 and CS administration can accelerate growth performance and GH, IGF-1

Effects of GHRP-2 and Cysteamine Administration on Growth Performance, Somatotropic Axis Hormone and Muscle Protein Deposition in Yaks (Bos grunniens) with Growth Retardation.

PubMed

Hu, Rui; Wang, Zhisheng; Peng, Quanhui; Zou, Huawei; Wang, Hongze; Yu, Xiaoqiang; Jing, Xiaoping; Wang, Yixin; Cao, Binghai; Bao, Shanke; Zhang, Wenhua; Zhao, Suonan; Ji, Hanzhong; Kong, Xiangying; Niu, Quanxi

2016-01-01

The objective of this study was to investigate the effects of growth hormone-releasing peptide-2 (GHRP-2) and cysteamine (CS) administration on growth performance in yaks with growth retardation and try to elucidate its regulatory mechanisms. Trial 1, thirty-six 1-year-old Qinghai high plateau yaks (body weight 38-83.2 kg) were randomly chosen for body weight and jugular blood samples collection. The relationship between body weight and serum GHRH (P < 0.05, R = 0.45), GH (P < 0.05, R = 0.47), IGF-1 (P < 0.05, R = 0.62) was significantly correlated in yaks colonies with lighter body weights. Trial 2, fifteen 1-year-old Qinghai high plateau yaks with growth retardation (average body weight 54.8 ± 8.24 kg) were randomly selected and assigned to negative control group (NG), GHRP-2 injection group (GG) and cysteamine feeding group (CG), with 5 yaks per group. Another five 1-year-old Qinghai high plateau yaks with normal growth performance (average body weight 75.3 ± 2.43 kg) were selected as positive control group (PG). The average daily gain (ADG) of the GG and CG were significantly higher than those in the PG and NG (P < 0.05). Both GHRP-2 and CS administration significantly enhanced the myofiber diameter and area of skeletal muscle (P<0.05). GHRP-2 significantly enhanced the serum GH and IGF-1 levels (P < 0.05), and up-regulated GHR, IGF-1 and IGF-1R mRNA expression in the liver and skeletal muscle (P < 0.05), enhanced the mRNA expression of PI3K, AKt and mTOR in the skeletal muscle (P<0.05). CS significantly reduced the serum SS levels and the hypothalamus SS mRNA expression (P < 0.05), and enhanced GHR and IGF-1 mRNA expression in the liver (P < 0.05), decreased the mRNA expression of muscle atrophy F-box (Atrogin-1) and muscle ring finger 1 (MuRF1) mRNA (P < 0.05). Growth retardation in yaks was primarily due to somatotropic axis hormones secretion deficiency. Both GHRP-2 and CS administration can accelerate growth performance and GH, IGF-1 secretion in yaks

Airport Capacity Enhancement Plan.

DOT National Transportation Integrated Search

1986-01-01

The first edition of the Airport Capacity Enhancement Plan has been developed by the Federal Aviation Administration's newly established Airport Capacity Program Office (ACPO). The plan is intended to increase the capacity and efficient utilization o...

Airport Capacity Enhancement Plan

DOT National Transportation Integrated Search

1987-01-01

The first edition of the Airport Capacity Enhancement Plan has been developed by the Federal Aviation Administration's newly established Airport Capacity Program Office (ACPO). The plan is intended to increase the capacity and efficient utilization o...

Subchronic Oral Bromocriptine Methanesulfonate Enhances Open Field Novelty-Induced Behavior and Spatial Memory in Male Swiss Albino Mice.

PubMed

Onaolapo, Olakunle James; Onaolapo, Adejoke Yetunde

2013-01-01

This study set out to assess the neurobehavioral effects of subchronic, oral bromocriptine methanesulfonate using the open field and the Y-maze in healthy male mice. Sixty adult Swiss albino mice were assigned into three groups. Controls received normal saline, while test groups received bromocriptine methanesulfonate at 2.5 and 5 mg/kg/day, respectively, for a period of 21 days. Neurobehavioral tests were carried out on days 1 and 21 after administration. Open field assessment on day 1 after administration revealed significant increase in grooming at 2.5 and 5 mg/kg, while horizontal and vertical locomotion showed no significant changes. Day 1 also showed no significant changes in Y-maze alternation. On day 21, horizontal locomotion, rearing, and grooming were increased significantly at 2.5 and 5 mg/kg doses after administration; also, spatial memory was significantly enhanced at 2.5 mg/kg. In conclusion, the study demonstrates the ability of oral bromocriptine to affect neurobehavior in normal mice. It also suggests that there is a cumulative effect of oral bromocriptine on the behaviors studied with more changes being seen after subchronic administration rather than after a single oral dose.

Minimizing human error in radiopharmaceutical preparation and administration via a bar code-enhanced nuclear pharmacy management system.

PubMed

Hakala, John L; Hung, Joseph C; Mosman, Elton A

2012-09-01

The objective of this project was to ensure correct radiopharmaceutical administration through the use of a bar code system that links patient and drug profiles with on-site information management systems. This new combined system would minimize the amount of manual human manipulation, which has proven to be a primary source of error. The most common reason for dosing errors is improper patient identification when a dose is obtained from the nuclear pharmacy or when a dose is administered. A standardized electronic transfer of information from radiopharmaceutical preparation to injection will further reduce the risk of misadministration. Value stream maps showing the flow of the patient dose information, as well as potential points of human error, were developed. Next, a future-state map was created that included proposed corrections for the most common critical sites of error. Transitioning the current process to the future state will require solutions that address these sites. To optimize the future-state process, a bar code system that links the on-site radiology management system with the nuclear pharmacy management system was proposed. A bar-coded wristband connects the patient directly to the electronic information systems. The bar code-enhanced process linking the patient dose with the electronic information reduces the number of crucial points for human error and provides a framework to ensure that the prepared dose reaches the correct patient. Although the proposed flowchart is designed for a site with an in-house central nuclear pharmacy, much of the framework could be applied by nuclear medicine facilities using unit doses. An electronic connection between information management systems to allow the tracking of a radiopharmaceutical from preparation to administration can be a useful tool in preventing the mistakes that are an unfortunate reality for any facility.

Significantly enhanced energy output from 3D ordered macroporous structured Fe2O3/Al nanothermite film.

PubMed

Zhang, Wenchao; Yin, Baoqing; Shen, Ruiqi; Ye, Jiahai; Thomas, Jason A; Chao, Yimin

2013-01-23

A three-dimensionally ordered macroporous Fe(2)O(3)/Al nanothermite membrane has been prepared with a polystyrene spheres template. The nanothermite, with an enhanced interfacial contact between fuel and oxidizer, outputs 2.83 kJ g(-1) of energy. This is significantly more than has been reported before. This approach, fully compatible with MEMS technology, provides an efficient way to produce micrometer thick three-dimensionally ordered nanostructured thermite films with overall spatial uniformity. These exciting achievements will greatly facilitate potential for the future development of applications of nanothermites.

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

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

49 CFR 1.81 - Delegations to all Administrators.

Code of Federal Regulations, 2013 CFR

2013-10-01

... sections in this part. (4) Carry out the functions of the Secretary concerning environmental enhancement by... refuges, and historic sites) and 23 U.S.C. 138 as they relate to matters within the primary responsibility of each Operating Administration. (5) Carry out the functions of the Secretary under the National...

49 CFR 1.81 - Delegations to all Administrators.

Code of Federal Regulations, 2014 CFR

2014-10-01

... sections in this part. (4) Carry out the functions of the Secretary concerning environmental enhancement by... refuges, and historic sites) and 23 U.S.C. 138 as they relate to matters within the primary responsibility of each Operating Administration. (5) Carry out the functions of the Secretary under the National...

49 CFR 1.81 - Delegations to all Administrators.

Code of Federal Regulations, 2012 CFR

2012-10-01

... sections in this part. (4) Carry out the functions of the Secretary concerning environmental enhancement by... refuges, and historic sites) and 23 U.S.C. 138 as they relate to matters within the primary responsibility of each Operating Administration. (5) Carry out the functions of the Secretary under the National...

Enhancement of Th1-biased protective immunity against avian influenza H9N2 virus via oral co-administration of attenuated Salmonella enterica serovar Typhimurium expressing chicken interferon-α and interleukin-18 along with an inactivated vaccine

PubMed Central

2012-01-01

Background Control of currently circulating re-assorted low-pathogenicity avian influenza (LPAI) H9N2 is a major concern for both animal and human health. Thus, an improved LPAI H9N2 vaccination strategy is needed to induce complete immunity in chickens against LPAI H9N2 virus strains. Cytokines play a crucial role in mounting both the type and extent of an immune response generated following infection with a pathogen or after vaccination. To improve the efficacy of inactivated LPAI H9N2 vaccine, attenuated Salmonella enterica serovar Typhimurium was used for oral co-administration of chicken interferon-α (chIFN-α) and chicken interleukin-18 (chIL-18) as natural immunomodulators. Results Oral co-administration of S. enterica serovar Typhimurium expressing chIFN-α and chIL-18, prior to vaccination with inactivated AI H9N2 vaccine, modulated the immune response of chickens against the vaccine antigen through enhanced humoral and Th1-biased cell-mediated immunity, compared to chickens that received single administration of S. enterica serovar Typhimurium expressing either chIFN-α or chIL-18. To further test the protective efficacy of this improved vaccination regimen, immunized chickens were intra-tracheally challenged with a high dose of LPAI H9N2 virus. Combined administration of S. enterica serovar Typhimurium expressing chIFN-α and chIL-18 showed markedly enhanced protection compared to single administration of the construct, as determined by mortality, clinical severity, and feed and water intake. This enhancement of protective immunity was further confirmed by reduced rectal shedding and replication of AIV H9N2 in different tissues of challenged chickens. Conclusions Our results indicate the value of combined administration of chIFN-α and chIL-18 using a Salmonella vaccine strain to generate an effective immunization strategy in chickens against LPAI H9N2. PMID:22776696

Potential for enhancing external beam radiotherapy for lung cancer using high-Z nanoparticles administered via inhalation

NASA Astrophysics Data System (ADS)

Hao, Yao; Altundal, Yucel; Moreau, Michele; Sajo, Erno; Kumar, Rajiv; Ngwa, Wilfred

2015-09-01

Nanoparticle-aided radiation therapy is emerging as a promising modality to enhance radiotherapy via the radiosensitizing action of high atomic number (Z) nanoparticles. However, the delivery of sufficiently potent concentrations of such nanoparticles to the tumor remain a challenge. This study investigates the dose enhancement to lung tumors due to high-Z nanoparticles (NPs) administered via inhalation during external beam radiotherapy. Here NPs investigated include: cisplatin nanoparticles (CNPs), carboplatin nanoparticles (CBNPs), and gold nanoparticles (GNPs). Using Monte Carlo-generated megavoltage energy spectra, a previously employed analytic method was used to estimate dose enhancement to lung tumors due to radiation-induced photoelectrons from the NPs administered via inhalation route (IR) in comparison to intravenous (IV) administration. Previous studies have indicated about 5% of FDA-approved cisplatin concentrations reach the lung via IV. Meanwhile recent experimental studies indicate that 3.5-14.6 times higher concentrations of NPs can reach the lung by IR compared to IV. Taking these into account, the dose enhancement factor (DEF) defined as the ratio of the radiotherapy dose with and without nanoparticles was calculated for a range of NPs concentrations and tumor sizes. The DEF for IR was then compared with that for IV. For IR with 3.5 times higher concentrations than IV, and 2 cm diameter tumor, clinically significant DEF values of up to 1.19, 1.26, and 1.51 were obtained for CNPs, CBNPs and GNPs. In comparison values of 1.06, 1.08, and 1.15 were obtained via IV administration. For IR with 14.6 times higher concentrations, even higher DEF values were obtained e.g. 1.81 for CNPs. Results also showed that the DEF increased with increasing field size or decreasing tumor volume, as expected. The results of this work indicate that IR administration of targeted high-Z CNPs/CBNPs/GNPs could enable clinically significant DEF to lung tumors compared to IV

E-Government Goes Semantic Web: How Administrations Can Transform Their Information Processes

NASA Astrophysics Data System (ADS)

Klischewski, Ralf; Ukena, Stefan

E-government applications and services are built mainly on access to, retrieval of, integration of, and delivery of relevant information to citizens, businesses, and administrative users. In order to perform such information processing automatically through the Semantic Web,1 machine-readable2 enhancements of web resources are needed, based on the understanding of the content and context of the information in focus. While these enhancements are far from trivial to produce, administrations in their role of information and service providers so far find little guidance on how to migrate their web resources and enable a new quality of information processing; even research is still seeking best practices. Therefore, the underlying research question of this chapter is: what are the appropriate approaches which guide administrations in transforming their information processes toward the Semantic Web? In search for answers, this chapter analyzes the challenges and possible solutions from the perspective of administrations: (a) the reconstruction of the information processing in the e-government in terms of how semantic technologies must be employed to support information provision and consumption through the Semantic Web; (b) the required contribution to the transformation is compared to the capabilities and expectations of administrations; and (c) available experience with the steps of transformation are reviewed and discussed as to what extent they can be expected to successfully drive the e-government to the Semantic Web. This research builds on studying the case of Schleswig-Holstein, Germany, where semantic technologies have been used within the frame of the Access-eGov3 project in order to semantically enhance electronic service interfaces with the aim of providing a new way of accessing and combining e-government services.

Post-training amphetamine administration enhances memory consolidation in appetitive Pavlovian conditioning: Implications for drug addiction.

PubMed

Simon, Nicholas W; Setlow, Barry

2006-11-01

It has been suggested that some of the addictive potential of psychostimulant drugs of abuse such as amphetamine may result from their ability to enhance memory for drug-related experiences through actions on memory consolidation. This experiment examined whether amphetamine can specifically enhance consolidation of memory for a Pavlovian association between a neutral conditioned stimulus (CS-a light) and a rewarding unconditioned stimulus (US-food), as Pavlovian conditioning of this sort plays a major role in drug addiction. Male Long-Evans rats were given six training sessions consisting of 8 CS presentations followed by delivery of the food into a recessed food cup. After the 1st, 3rd, and 5th session, rats received subcutaneous injections of amphetamine (1.0 or 2.0 mg/kg) or saline vehicle immediately following training. Conditioned responding was assessed using the percentage of time rats spent in the food cup during the CS relative to a pre-CS baseline period. Both amphetamine-treated groups showed significantly more selective conditioned responding than saline controls. In a control experiment, there were no differences among groups given saline, 1.0 or 2.0 mg/kg amphetamine 2 h post-training, suggesting that immediate post-training amphetamine enhanced performance specifically through actions on memory consolidation rather than through non-mnemonic processes. This procedure modeled Pavlovian learning involved in drug addiction, in which the emotional valence of a drug reward is transferred to neutral drug-predictive stimuli such as drug paraphernalia. These data suggest that amphetamine may contribute to its addictive potential through actions specifically on memory consolidation.

Intensity and Pattern of Enhancement on CESM: Prognostic Significance and its Relation to Expression of Podoplanin in Tumor Stroma - A Preliminary Report.

PubMed

Luczynska, Elzbieta; Niemiec, Joanna; Heinze, Sylwia; Adamczyk, Agnieszka; Ambicka, Aleksandra; Marcyniuk, Paulina; Rudnicki, Wojciech; Mitus, Jerzy W; Dyczek, Sonia; Rys, Janusz; Sas-Korczynska, Beata

2018-02-01

It is possible that the degree of enhancement on contrast-enhanced spectral mammography (CESM), a new diagnostic method, might provide prognostic information for breast cancer patients. Therefore, in a group of 82 breast cancer patients, we analyzed the prognostic significance of degree and pattern of enhancement on CESM as well as its relation to: (a) breast cancer immunophenotype (based on ER/PR/HER2 status) (b) podoplanin expression in cancer stroma (lymphatic vessel density plus podoplanin-positivity of cancer-associated fibroblasts), and (c) other histological parameters. For each tumor the intensity of enhancement on CESM was qualitatively assessed as strong or weak/medium, while the pattern - as homogenous and heterogenous. Herein we report, for the first time, that strong and heterogenous enhancement on CESM was related to unfavorable disease-free survival of breast cancer patients (p=0.005). Moreover, the strong enhancement was more frequent in large and node-positive tumors (pT>1, pN>0) (p=0.002), as well as in carcinomas with podoplanin-sparse stroma (p=0.008). Intensity and pattern of enhancement on CESM might provide (together with the results of other diagnostic imaging methods) not only the confirmation of presence or absence of tumor, but also prognostic information. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Optimizing administrative datasets to examine acute kidney injury in the era of big data: workgroup statement from the 15(th) ADQI Consensus Conference.

PubMed

Siew, Edward D; Basu, Rajit K; Wunsch, Hannah; Shaw, Andrew D; Goldstein, Stuart L; Ronco, Claudio; Kellum, John A; Bagshaw, Sean M

2016-01-01

providing complementary information on the context in which AKI occurs are possible. Administrative databases may also help enhance the conduct of and inform clinical or registry-based pragmatic studies. Data sources largely restricted to North American and Europe. Administrative data are rapidly growing and evolving, and represent an unprecedented opportunity to address knowledge gaps in AKI. Progress will require continued efforts to improve awareness of the impact of AKI on public health, engage key stakeholders, and develop tangible strategies to reconfigure infrastructure to improve the reporting and phenotyping of AKI. WHY IS THIS REVIEW IMPORTANT?: Rapid growth in the size and availability of administrative data has enhanced the clinical study of acute kidney injury (AKI). However, significant limitations exist in coding that hinder our ability to better understand its epidemiology and address knowledge gaps. The following consensus-based review discusses how administrative data have been used to study AKI, identify current limitations, and suggest how these data sources might be enhanced to improve the future study of this disease. WHAT ARE THE KEY MESSAGES?: The current coding structure of administrative data is hindered by a lack of sensitivity, standardization to properly classify severity, and limited clinical phenotyping. These limitations combined with reduced awareness of AKI and the subjective nature of reporting limit understanding of disease burden across settings and time periods. As administrative data become more sophisticated and complex, important opportunities to employ more objective criteria to diagnose and stage AKI as well as improve contextual phenotyping exist that can help address knowledge gaps and improve care.

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…

Prognostic value of contrast-enhanced MR mammography in patients with breast cancer.

PubMed

Fischer, U; Kopka, L; Brinck, U; Korabiowska, M; Schauer, A; Grabbe, E

1997-01-01

The objective of this study was to evaluate the prognostic value of contrast-enhanced MR mammography in patients with breast cancer. A total of 190 patients with breast cancer (37 noninvasive carcinomas, 153 invasive carcinomas) underwent dynamic contrast-enhanced MR mammography preoperatively. Using 1.5-T unit, T1-weighted sequences (2D FLASH) were obtained repeatedly one time before and five times after IV administration of 0.1 mmol gadopentetate-dimeglumine per kilogram body weight. The findings on MR imaging were correlated with histopathologically defined prognostic factors (histological type, tumor size, tumor grading, metastasis in lymph nodes). In addition, immunohistochemically defined prognostic factors (c-erbB-1, c-erbB-2, p53, Ki-67) were correlated with the signal increase on MR mammogram in 40 patients. There was no significant correlation between the findings on MR mammography and the histopathological type of carcinoma, the grading, and the lymphonodular status. Noninvasive carcinomas showed a higher rate of moderate (38 %) or low (27 %) enhancement on MR imaging than invasive carcinomas (6 and 3 %). The results on MR mammography and the results of immunohistochemical stainings did not correlate significantly. Noninvasive carcinomas showed significantly lower enhancement than invasive carcinomas. However, the signal behavior of contrast-enhanced MR mammography is not related to established histopathological prognostic parameters as subtyping, grading, nodal status, and the expression of certain oncogenes/tumor suppressor genes.

[The Influence of Preoperative Oral Carbohydrate Administration on Perioperative Blood Sugar Levels and Patients' Satisfaction].

PubMed

Morita, Tomotaka; Kita, Takashi; Masada, Kyoko; Nagata, Takako; Sasaki, Shigeta

2016-06-01

After introducing preoperative oral carbohydrate as a part of enhanced recovery after surgery (ERAS) protocols, we assessed the influence of carbohydrate administration on the perioperative blood sugar levels (BS), the variation of vital signs and patients' satisfaction. After IRB's approval and obtaining patients' consent, patients were divided into two groups; taking carbohydrate (Group AW) or not (Group NAW). Anesthesia was induced and maintained with total intravenous anesthesia using propofol, remifentanil and rocuronium. We measured BS six times during perioperative period. We also compared blood pressures and heart rates during induction of anesthesia. Moreover, we carried out questionnaire surveys about degree of satisfaction for ERAS among patients and nurses. Heart rates were significantly higher in Group AW (P < 0.05), but there were no significant difference in blood pressures or BS between the groups. Patients in Group AW had more anxiety for surgeries (P = 0.003), but more than 85% of patients and nurses were satisfied with carbohydrates. The carbohydrate administration had little influence on the perioperative vital signs. However, we gained high reputations from patients and paramedics.

Elementary Administrators' Perceptions of the Blended Coaching Model on Their Development as Transformational Leaders

ERIC Educational Resources Information Center

Noche, Alma

2016-01-01

Purpose: The purpose of this ethnographic research was to study the culture and experiences of elementary administrators who were coached in the blended coaching model. This study used a qualitative ethnographic design to explore the context and processes of the coaching experience of elementary administrators that enhanced transformational…

Comparison of Low-Dose Higher-Relaxivity and Standard-Dose Lower-Relaxivity Contrast Media for Delayed-Enhancement MRI: A Blinded Randomized Crossover Study.

PubMed

Cheong, Benjamin Y C; Duran, Cihan; Preventza, Ourania A; Muthupillai, Raja

2015-09-01

The gadolinium-based MRI contrast agent gadobenate dimeglumine has nearly twice the MR relaxivity of gadopentetate dimeglumine at 1.5 T. The purpose of this study was to determine whether a lower dose (0.1 mmol/kg) of gadobenate dimeglumine can be used to obtain delayed-enhancement MR images comparable to those obtained with a standard dose (0.2 mmol/kg) of gadopentetate dimeglumine. In this blinded randomized crossover study, 20 patients with known myocardial infarction underwent two separate delayed-enhancement MRI examinations after receiving 0.1 mmol/kg gadobenate dimeglumine and 0.2 mmol/kg gadopentetate dimeglumine (random administration). The conspicuity of lesion enhancement 5, 10, and 20 minutes after contrast administration was quantified as relative enhancement ratio (RER). With either gadolinium-based contrast agent, damaged myocardium had higher signal intensity than normal remote myocardium (RER > 4) on delayed-enhancement MR images, and the blood RER declined over time after contrast administration. The blood RER was not significantly higher for gadobenate dimeglumine than for gadopentetate dimeglumine at 5 and 10 minutes. Nevertheless, there was a larger reduction in blood RER for gadobenate dimeglumine than for gadopentetate dimeglumine between 5 and 10 minutes and between 10 and 20 minutes. The volumes of enhancement were similar for gadobenate dimeglumine (13.6 ± 8.8 cm(3)) and gadopentetate dimeglumine (13.5 ± 8.9 cm(3)) (p = 0.98). The mean difference in Bland-Altman analysis for delayed-enhancement volume between the agents was 0.1 cm(3). Qualitatively and quantitatively, delayed-enhancement MR images of ischemic myocardium obtained with 0.1 mmol/kg gadobenate dimeglumine are comparable to those obtained with 0.2 mmol/kg gadopentetate dimeglumine 5, 10, and 20 minutes after contrast administration.

Managing in a Culture of Debate: Enhancing Administrative Effectiveness through Procedural Fairness

ERIC Educational Resources Information Center

Moshavi, Dan; Standifird, Stephen

2017-01-01

The contestability of ideas is at the heart of a healthy academic institution. As a result, administrators face the challenge of making and implementing difficult decisions in an environment that is designed to explicitly create thoughtful discord. We argue that procedural fairness--explaining how and why important decisions are made--is an…

Significantly enhanced robustness and electrochemical performance of flexible carbon nanotube-based supercapacitors by electrodepositing polypyrrole

NASA Astrophysics Data System (ADS)

Chen, Yanli; Du, Lianhuan; Yang, Peihua; Sun, Peng; Yu, Xiang; Mai, Wenjie

2015-08-01

Here, we report robust, flexible CNT-based supercapacitor (SC) electrodes fabricated by electrodepositing polypyrrole (PPy) on freestanding vacuum-filtered CNT film. These electrodes demonstrate significantly improved mechanical properties (with the ultimate tensile strength of 16 MPa), and greatly enhanced electrochemical performance (5.6 times larger areal capacitance). The major drawback of conductive polymer electrodes is the fast capacitance decay caused by structural breakdown, which decreases cycling stability but this is not observed in our case. All-solid-state SCs assembled with the robust CNT/PPy electrodes exhibit excellent flexibility, long lifetime (95% capacitance retention after 10,000 cycles) and high electrochemical performance (a total device volumetric capacitance of 4.9 F/cm3). Moreover, a flexible SC pack is demonstrated to light up 53 LEDs or drive a digital watch, indicating the broad potential application of our SCs for portable/wearable electronics.

The Healthcare Administrator's Associate: an experiment in distributed healthcare information systems.

PubMed Central

Fowler, J.; Martin, G.

1997-01-01

The Healthcare Administrator's Associate is a collection of portable tools designed to support analysis of data retrieved via the Internet from diverse distributed healthcare information systems by means of the InfoSleuth system of distributed software agents. Development of these tools is part of an effort to enhance access to diverse and geographically distributed healthcare data in order to improve the basis upon which administrative and clinical decisions are made. PMID:9357686

Combined effects of interleukin-7 and stem cell factor administration on lymphopoiesis after murine bone marrow transplantation.

PubMed

Chung, Brile; Min, Dullei; Joo, Lukas W; Krampf, Mark R; Huang, Jing; Yang, Yujun; Shashidhar, Sumana; Brown, Janice; Dudl, Eric P; Weinberg, Kenneth I

2011-01-01

The decreased ability of the thymus to generate T cells after bone marrow transplantation (BMT) is a clinically significant problem. Interleukin (IL)-7 and stem cell factor (SCF) induce proliferation, differentiation, and survival of thymocytes. Although previous studies have shown that administration of recombinant human IL-7 (rhIL-7) after murine and human BMT improves thymopoiesis and immune function, whether administration of SCF exerts similar effects is unclear. To evaluate independent or combinatorial effects of IL-7 and SCF in post-BMT thymopoiesis, bone marrow (BM)-derived mesenchymal stem cells transduced ex vivo with the rhIL-7 or murine SCF (mSCF) genes were cotransplanted with T cell-depleted BM cells into lethally irradiated mice. Although rhIL-7 and mSCF each improved immune reconstitution, the combination treatment had a significantly greater effect than either cytokine alone. Moreover, the combination treatment significantly increased donor-derived common lymphoid progenitors (CLPs) in BM, suggesting that transplanted CLPs expand more rapidly in response to IL-7 and SCF and may promote immune reconstitution. Our findings demonstrate that IL-7 and SCF might be therapeutically useful for enhancing de novo T cell development. Furthermore, combination therapy may allow the administration of lower doses of IL-7, thereby decreasing the likelihood of IL-7-mediated expansion of mature T cells. 2011. Published by Elsevier Inc.

Mesenchymal stem cells enhance autophagy and increase β-amyloid clearance in Alzheimer disease models

PubMed Central

Shin, Jin Young; Park, Hyun Jung; Kim, Ha Na; Oh, Se Hee; Bae, Jae-Sung; Ha, Hee-Jin; Lee, Phil Hyu

2014-01-01

Current evidence suggests a central role for autophagy in Alzheimer disease (AD), and dysfunction in the autophagic system may lead to amyloid-β (Aβ) accumulation. Using in vitro and in vivo AD models, the present study investigated whether mesenchymal stem cells (MSCs) could enhance autophagy and thus exert a neuroprotective effect through modulation of Aβ clearance In Aβ-treated neuronal cells, MSCs increased cellular viability and enhanced LC3-II expression compared with cells treated with Aβ only. Immunofluorescence revealed that MSC coculture in Aβ-treated neuronal cells increased the number of LC3-II-positive autophagosomes that were colocalized with a lysosomal marker. Ultrastructural analysis revealed that most autophagic vacuoles (AVs) in Aβ-treated cells were not fused with lysosomes, whereas a large portion of autophagosomes were conjoined with lysosomes in MSCs cocultured with Aβ-treated neuronal cells. Furthermore, MSC coculture markedly increased Aβ immunoreactivity colocalized within lysosomes and decreased intracellular Aβ levels compared with Aβ-treated cells. In Aβ-treated animals, MSC administration significantly increased autophagosome induction, final maturation of late AVs, and fusion with lysosomes. Moreover, MSC administration significantly reduced the level of Aβ in the hippocampus, which was elevated in Aβ-treated mice, concomitant with increased survival of hippocampal neurons. Finally, MSC coculture upregulated BECN1/Beclin 1 expression in AD models. These results suggest that MSCs significantly enhance autolysosome formation and clearance of Aβ in AD models, which may lead to increased neuronal survival against Aβ toxicity. Modulation of the autophagy pathway to repair the damaged AD brain using MSCs would have a significant impact on future strategies for AD treatment. PMID:24149893

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.

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

Crosstalk between liver antioxidant and the endocannabinoid systems after chronic administration of the FAAH inhibitor, URB597, to hypertensive rats

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

Biernacki, Michał; Łuczaj, Wojciech; Gęgotek, Agni

Hypertension is accompanied by perturbations to the endocannabinoid and antioxidant systems. Thus, potential pharmacological treatments for hypertension should be examined as modulators of these two metabolic systems. The aim of this study was to evaluate the effects of chronic administration of the fatty acid amide hydrolase (FAAH) inhibitor [3-(3-carbamoylphenyl)phenyl]N-cyclohexylcarbamate (URB597) on the endocannabinoid system and on the redox balance in the livers of DOCA-salt hypertensive rats. Hypertension caused an increase in the levels of endocannabinoids [anandamide (AEA), 2-arachidonoyl-glycerol (2-AG) and N-arachidonoyl-dopamine (NADA)] and CB{sub 1} receptor and the activities of FAAH and monoacylglycerol lipase (MAGL). These effects were accompanied bymore » an increase in the level of reactive oxygen species (ROS), a decrease in antioxidant activity/level, enhanced expression of transcription factor Nrf2 and changes to Nrf2 activators and inhibitors. Moreover, significant increases in lipid, DNA and protein oxidative modifications, which led to enhanced levels of proapoptotic caspases, were also observed. URB597 administration to the hypertensive rats resulted in additional increases in the levels of AEA, NADA and the CB{sub 1} receptor, as well as decreases in vitamin E and C levels, glutathione peroxidase and glutathione reductase activities and Nrf2 expression. Thus, after URB597 administration, oxidative modifications of cellular components were increased, while the inflammatory response was reduced. This study revealed that chronic treatment of hypertensive rats with URB597 disrupts the endocannabinoid system, which causes an imbalance in redox status. This imbalance increases the levels of electrophilic lipid peroxidation products, which later participate in metabolic disturbances in liver homeostasis. - Highlights: • Chronic administration of URB597 to hypertensive rats reduces liver inflammation. • URB597 enhances the redox imbalance

SEQUOIA: significance enhanced network querying through context-sensitive random walk and minimization of network conductance.

PubMed

Jeong, Hyundoo; Yoon, Byung-Jun

2017-03-14

Network querying algorithms provide computational means to identify conserved network modules in large-scale biological networks that are similar to known functional modules, such as pathways or molecular complexes. Two main challenges for network querying algorithms are the high computational complexity of detecting potential isomorphism between the query and the target graphs and ensuring the biological significance of the query results. In this paper, we propose SEQUOIA, a novel network querying algorithm that effectively addresses these issues by utilizing a context-sensitive random walk (CSRW) model for network comparison and minimizing the network conductance of potential matches in the target network. The CSRW model, inspired by the pair hidden Markov model (pair-HMM) that has been widely used for sequence comparison and alignment, can accurately assess the node-to-node correspondence between different graphs by accounting for node insertions and deletions. The proposed algorithm identifies high-scoring network regions based on the CSRW scores, which are subsequently extended by maximally reducing the network conductance of the identified subnetworks. Performance assessment based on real PPI networks and known molecular complexes show that SEQUOIA outperforms existing methods and clearly enhances the biological significance of the query results. The source code and datasets can be downloaded from http://www.ece.tamu.edu/~bjyoon/SEQUOIA .

Airport Capacity Enhancement Plan 1988

DOT National Transportation Integrated Search

1988-01-01

The Airport Capacity Enhancement Plan plays a major role in the Federal Aviation Administration's (FAA) effort to increase airport capacity and efficiency without compromising the safety of passengers or the environment. The Plan identifies the cause...

Airport Capacity Enhancement Plan 1989

DOT National Transportation Integrated Search

1989-05-01

The Airport Capacity Enhancement Plan plays a major role in the Federal Aviation Administration's (FAA) effort to increase airport capacity and efficiency without compromising the safety of passengers or the environment. The Plan identifies the cause...

An ethical framework for nursing service administration.

PubMed

Christensen, P J

1988-04-01

Nurses as administrators are responsible for creating an ethical work environment in which nurses' human welfare is promoted. Bureaucratic organizations can dehumanize people, wherein human welfare suffers in the midst of institutional constraints. Amid these conditions nurses' ethical competence cannot develop nor can nurses maintain a sense of personal integrity. Applying concepts from nursing and general ethics to administrative practice provides a basis for developing an ethical framework for management. The proposed framework involves ethical awareness, principled reasoning, moral commitment to the profession and to one another, and primary consideration for human welfare with strategies to promote it. Use of these components when making decisions in daily practice and on a policy level enhances the well-being of nurses working in organizations.

Effects of intermittent versus continuous parathyroid hormone administration on condylar chondrocyte proliferation and differentiation

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

Liu, Qi; Wan, Qilong; Yang, Rongtao

Highlights: Black-Right-Pointing-Pointer Different PTH administration exerts different effects on condylar chondrocyte. Black-Right-Pointing-Pointer Intermittent PTH administration suppresses condylar chondrocyte proliferation. Black-Right-Pointing-Pointer Continuous PTH administration maintains condylar chondrocyte proliferating. Black-Right-Pointing-Pointer Intermittent PTH administration enhances condylar chondrocyte differentiation. -- Abstract: Endochondral ossification is a complex process involving chondrogenesis and osteogenesis regulated by many hormones and growth factors. Parathyroid hormone (PTH), one of the key hormones regulating bone metabolism, promotes osteoblast differentiation and osteogenesis by intermittent administration, whereas continuous PTH administration inhibits bone formation. However, the effects of PTH on chondrocyte proliferation and differentiation are still unclear. In this study, intermittent PTH administration presentedmore » enhanced effects on condylar chondrocyte differentiation and bone formation, as demonstrated by increased mineral nodule formation and alkaline phosphatase (ALP) activity, up-regulated runt-related transcription factor 2 (RUNX2), ALP, collagen type X (COL10a1), collagen type I (COL1a1), osteocalcin (OCN), bone sialoprotein (BSP), bone morphogenetic protein 2 (BMP2) and osterix (OSX) mRNA and/or protein expression. On the contrary, continuous PTH administration promoted condylar chondrocyte proliferation and suppressed its differentiation, as demonstrated by up-regulated collagen type II (COL2a1) mRNA expression, reduced mineral nodule formation and down-regulated expression of the mRNAs and/or proteins mentioned above. Our data suggest that PTH can regulate condylar chondrocyte proliferation and differentiation, depending on the type of PTH administration. These results provide new insight into the effects of PTH on condylar chondrocytes and new evidence for using local PTH administration to cure

Enhanced Antimalarial Activity by a Novel Artemether-Lumefantrine Lipid Emulsion for Parenteral Administration

PubMed Central

Ma, Yufan; Lu, Tingli; Zhao, Wen; Wang, Ying; Chen, Ting; Mei, Qibing

2014-01-01

Artemether and lumefantrine (also known as benflumetol) are difficult to formulate for parenteral administration because of their low aqueous solubility. Cremophor EL as an emulsion excipient has been shown to cause serious side effects. This study reports a method of preparation and the therapeutic efficacies of novel lipid emulsion (LE) delivery systems with artemether, lumefantrine, or artemether in combination with lumefantrine, for parenteral administration. Their physical and chemical stabilities were also evaluated. Furthermore, the in vivo antimalarial activities of the lipid emulsions developed were tested in Plasmodium berghei-infected mice. Artemether, lumefantrine, or artemether in combination with lumefantrine was encapsulated in an oil phase, and the in vivo performance was assessed by comparison with artesunate for injection. It was found that the lumefantrine lipid emulsion (LUM-LE) and artemether-lumefantrine lipid emulsion (ARM-LUM-LE-3) (1:6) began to decrease the parasitemia levels after only 3 days, and the parasitemia inhibition was 90% at doses of 0.32 and 0.27 mg/kg, respectively, with immediate antimalarial effects greater than those of the positive-control group and constant antimalarial effects over 30 days. LUM-LE and ARM-LUM-LE-3 demonstrated the best performance in terms of chemical and physical stabilities and antiplasmodial efficacy, with a mean particle size of 150 nm, and they have many favorable properties for parenteral administration, such as biocompatibility, physical stability, and ease of preparation. PMID:24982079

Combined administration of low molecular weight sodium alginate boosted immunomodulatory, disease resistance and growth enhancing effects of Lactobacillus plantarum in Nile tilapia (Oreochromis niloticus).

PubMed

Van Doan, Hien; Hoseinifar, Seyed Hossein; Tapingkae, Wanaporn; Tongsiri, Sudaporn; Khamtavee, Pimporn

2016-11-01

The present study investigates the effects of combined or singular administration of low molecular weight sodium alginate (LWMSA) and Lactobacillus plantarum on innate immune response, disease resistance and growth performance of Nile tilapia (Oreochromis niloticus). Three hundred and twenty fish were supplied and randomly stocked in sixteen glass tanks (150 L) assigned to four treatments as follows: 0 g kg -1 LMWSA (Control, Diet 1), 10 g kg -1 LMWSA (Diet 2), 10 8  CFU g -1 L. plantarum (Diet 3), and 10 g kg -1 LMWSA + 10 8  CFU g -1 L. plantarum (Diet 4). Following 30 and 60 days of the feeding trial, serum lysozyme, phagocytosis, respiratory burst and alternative complement activities as well as growth performance parameters (specific growth rate, feed conversion ratio) were measured. Serum lysozyme, phagocytosis, respiratory burst, and alternative complement activities of fish were significantly stimulated by both LMWSA and L. plantarum diets, however, the highest innate immune response were observed in fish fed synbiotic diet. At the end of the experiment, eight fish per replication were randomly selected for a challenge test against Streptococcus agalactiae. The survival rate of the fish fed supplemented diets was significantly greater than the control treatment and the highest post challenge survival rate was observed in synbiotic diet. Furthermore, SGR and FCR were significantly improved in fish fed supplemented diets after 60 days and the highest growth performance was observed in fish fed synbiotic diet. These results suggest combined LMWSA and L. plantarum can be considered as a promising immunostimulant and growth enhancer in Nile tilapia diet. Copyright © 2016 Elsevier Ltd. All rights reserved.

ARRA Investments in Technology, Innovation, and K-12 Reform: The Digital Education Funding Cliff. A Preliminary Report on State Administration of the American Recovery & Reinvestment Act of 2009: Enhancing Education Through Technology Program

ERIC Educational Resources Information Center

State Educational Technology Directors Association, 2010

2010-01-01

This is the first in a forthcoming series of reports documenting state administration of educational technology funding included in the "American Recovery and Reinvestment Act of 2009" (ARRA). The ARRA included a $650 million allocation in ESEA Title II, Part D, commonly referred to as the "Enhancing Education through Technology…

Troubleshooting Assessment and Enhancement (TAE) Program: Design, Development, and Administration. Volume 1

DTIC Science & Technology

1991-04-01

Navy Personnel Research and Development Center San Diego, California 92152-6800 TN-91-12 April 1991 AD-A236 411 Troubleshooting Assessment and...Program: Design, Development, and Administration Harry B. Conner Navy Personnel Research and Development Center Cathryn Poirier Randy Ulrich Thomas...Systems Department Approved for public release; distribution is unlimited. Navy Personnel Research and Development Center San Diego, California 92152-6800

[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.

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.

The level of use of PDAs by nurse practitioners and administrative barriers.

PubMed

Abell, Cathy Hoots; Jepson, Terry; Gabbard, Jay

2012-10-01

The purpose of this descriptive, correlational research study was to examine the relationship between the level of use of PDAs by nurse practitioners and their perception of managers following established change strategies. A convenience sample of 159 NPs was obtained for the study. Findings included a low, positive correlation between the level of PDA use and total Change Process Survey score (r = 0.23) that was significant (P = .006) at the .01 level. The use of PDAs by NPs is important to patient safety; therefore, administrators must be aware of change strategies that may enhance the use of PDAs. Recommendations for future research include replicating the study using a larger, randomized sample.

Selective inhibition of phosphodiesterase 5 enhances glutamatergic synaptic plasticity and memory in mice.

PubMed

Uthayathas, Subramaniam; Parameshwaran, Kodeeswaran; Karuppagounder, Senthilkumar S; Ahuja, Manuj; Dhanasekaran, Muralikrishnan; Suppiramaniam, Vishnu

2013-11-01

Phosphodiesterases (PDEs) belong to a family of proteins that control metabolism of cyclic nucleotides. Targeting PDE5, for enhancing cellular function, is one of the therapeutic strategies for male erectile dysfunction. We have investigated whether in vivo inhibition of PDE5, which is expressed in several brain regions, will enhance memory and synaptic transmission in the hippocampus of healthy mice. We have found that acute administration of sildenafil, a specific PDE5 inhibitor, enhanced hippocampus-dependent memory tasks. To elucidate the underlying mechanism in the memory enhancement, effects of sildenafil on long-term potentiation (LTP) were measured. The level of LTP was significantly elevated, with concomitant increases in basal synaptic transmission, in mice treated with sildenafil (1 mg/kg/day) for 15 days compared to control mice. These results suggest that moderate PDE5 inhibition enhances memory by increasing synaptic plasticity and transmission in the hippocampus. Copyright © 2013 Wiley Periodicals, Inc.

Intravenous maternal -arginine administration to twin-bearing ewes during late pregnancy enhances placental growth and development.

PubMed

van der Linden, D S; Sciascia, Q; Sales, F; Wards, N J; Oliver, M H; McCoard, S A

2015-10-01

This study aimed to investigate if intravenous maternal Arg administration to well-fed twin-bearing ewes, from 100 to 140 d of gestation or birth, could enhance placental development and placental nutrient transport. Ewes received intravenous infusions of saline (control) or 345 μmol Arg HCl/kg of BW 3 times daily from d 100 of pregnancy (P100) to d 140 of pregnancy (P140; cohort 1) or from P100 to birth (cohort 2). At P140, ewes in cohort 1 were euthanized and individual placentae per fetus were dissected and placentomes were classed per type (A to D) and size (light to heavy). Placentome number and individual weight were recorded. As an indicator of placental nutrient transport, blood plasma was collected from the uterine ovarian vein (UOV), uterine artery (UA), and umbilical vein and artery at the time of euthanasia and analyzed for metabolites and free AA concentrations. The ewes in cohort 2 were allowed to lamb and lambs were weighed at birth. The expelled placenta was dissected and number of cotyledons and weights of total cotyledons, remaining fetal membranes, and total placenta were recorded. At P140, Arg-infused ewes had a 63% ( = 0.03) greater number of unoccupied caruncles than control ewes. No differences were observed for placental weight at P140. At birth, lambs from Arg-infused ewes tended to have 11% ( = 0.09) greater placental weight and 34% ( = 0.03) greater total cotyledon weight compared with control lambs. Arginine-infused ewes (Arg-infused) had increased concentrations of Arg ( = 0.0001) and ornithine (Orn; = 0.004) but decreased concentrations of Met ( = 0.01) and His ( = 0.02 and = 0.09, respectively) compared with control ewes in plasma UOV and UA. Fetuses from Arg-infused ewes had increased concentrations of Orn ( = 0.005) and decreased concentrations of His ( = 0.006), Met ( = 0.003), and Lys ( = 0.01) but no differences in Arg ( > 0.10) concentrations were found compared with control fetuses in umbilical artery and vein plasma. This

Raising the Bar on External Research Funding: Infrastructure and Strategies for Enhancing Faculty Productivity

ERIC Educational Resources Information Center

Chval, Kathryn B.; Nossaman, Larry D.

2014-01-01

Administrators seek faculty who have the expertise to secure external funding to support their research agenda. Administrators also seek strategies to support and enhance faculty productivity across different ranks. In this manuscript, we describe the infrastructure we established and strategies we implemented to enhance the research enterprise at…

Contrast enhancement of central nervous system lesions: multicenter intraindividual crossover comparative study of two MR contrast agents.

PubMed

Maravilla, Kenneth R; Maldjian, Joseph A; Schmalfuss, Ilona M; Kuhn, Matthew J; Bowen, Brian C; Wippold, Franz J; Runge, Val M; Knopp, Michael V; Kremer, Stephane; Wolansky, Leo J; Anzalone, Nicoletta; Essig, Marco; Gustafsson, Lars

2006-08-01

To prospectively compare gadobenate dimeglumine with gadopentetate dimeglumine (0.1 mmol per kilogram body weight) for enhanced magnetic resonance (MR) imaging of central nervous system (CNS) lesions. This study was HIPAA-compliant at U.S. centers and was conducted at all centers according to the Good Clinical Practice standard. Institutional review board and regulatory approval were granted; written informed consent was obtained. Seventy-nine men and 78 women (mean age, 50.5 years +/- 14.4 [standard deviation]) were randomized to group A (n = 78) or B (n = 79). Patients underwent two temporally separated 1.5-T MR imaging examinations. In randomized order, gadobenate followed by gadopentetate was administered in group A; order of administration was reversed in group B. Contrast agent administration (volume, speed of injection), imaging parameters before and after injection, and time between injections and postinjection acquisitions were identical for both examinations. Three blinded neuroradiologists evaluated images by using objective image interpretation criteria for diagnostic information end points (lesion border delineation, definition of disease extent, visualization of internal morphologic features of the lesion, enhancement of the lesion) and quantitative parameters (percentage of lesion enhancement, contrast-to-noise ratio [CNR]). Overall diagnostic preference in terms of lesion conspicuity, detectability, and diagnostic confidence was assessed. Between-group comparisons were performed with Wilcoxon signed rank test. Readers 1, 2, and 3 demonstrated overall preference for gadobenate in 75, 89, and 103 patients, compared with that for gadopentetate in seven, 10, and six patients, respectively (P < .0001). Significant (P < .0001) preference for gadobenate was demonstrated for diagnostic information end points, percentage of lesion enhancement, and CNR. Superiority of gadobenate was significant (P < .001) in patients with intraaxial and extraaxial lesions

Lycopersicon esculentum Extract Enhances Cognitive Function and Hippocampal Neurogenesis in Aged Mice

PubMed Central

Bae, Jung-Soo; Han, Mira; Shin, Hee Soon; Shon, Dong-Hwa; Lee, Soon-Tae; Shin, Chang-Yup; Lee, Yuri; Lee, Dong Hun; Chung, Jin Ho

2016-01-01

A decrease in adult neurogenesis is associated with the aging process, and this decrease is closely related to memory impairment. Tomato (Lycopersicon esculentum) is a fruit with diverse bioactive nutrients that is consumed worldwide. In this study, we investigated the cognition-enhancing effect of tomato ethanolic extracts (TEE) in aged mice. Six weeks of oral TEE administration in 12-month-old aged mice significantly increased their exploration time of novel objects when compared to vehicle-treated mice. The TEE supplement increased doublecortin (DCX)-positive cells and postsynaptic density-95 (PSD95) expression in mice hippocampus. Moreover, we found an increased expression of brain-derived neurotrophic factor (BDNF) and subsequently-activated extracellular-signal-regulated kinase (ERK)/cAMP response element binding (CREB) signaling pathway in the TEE-supplemented mice hippocampus. In conclusion, the oral administration of TEE exhibits a cognition-enhancing effect, and the putative underlying mechanism is the induction of BDNF signaling-mediated proliferation and synapse formation in the hippocampus. These findings indicate that TEE could be a candidate for treatment of age-related memory impairment and neurodegenerative disorders. PMID:27792185

Lycopersicon esculentum Extract Enhances Cognitive Function and Hippocampal Neurogenesis in Aged Mice.

PubMed

Bae, Jung-Soo; Han, Mira; Shin, Hee Soon; Shon, Dong-Hwa; Lee, Soon-Tae; Shin, Chang-Yup; Lee, Yuri; Lee, Dong Hun; Chung, Jin Ho

2016-10-26

A decrease in adult neurogenesis is associated with the aging process, and this decrease is closely related to memory impairment. Tomato ( Lycopersicon esculentum ) is a fruit with diverse bioactive nutrients that is consumed worldwide. In this study, we investigated the cognition-enhancing effect of tomato ethanolic extracts (TEE) in aged mice. Six weeks of oral TEE administration in 12-month-old aged mice significantly increased their exploration time of novel objects when compared to vehicle-treated mice. The TEE supplement increased doublecortin (DCX)-positive cells and postsynaptic density-95 (PSD95) expression in mice hippocampus. Moreover, we found an increased expression of brain-derived neurotrophic factor (BDNF) and subsequently-activated extracellular-signal-regulated kinase (ERK)/cAMP response element binding (CREB) signaling pathway in the TEE-supplemented mice hippocampus. In conclusion, the oral administration of TEE exhibits a cognition-enhancing effect, and the putative underlying mechanism is the induction of BDNF signaling-mediated proliferation and synapse formation in the hippocampus. These findings indicate that TEE could be a candidate for treatment of age-related memory impairment and neurodegenerative disorders.

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

Enhancement of frequency domain indices of heart rate variability by cholinergic stimulation with pyridostigmine bromide.

PubMed

Zarei, Ali Asghar; Foroutan, Seyyed Abbas; Foroutan, Seyyed Mohsen; Erfanian Omidvar, Abbas

2011-01-01

Pyridostigmine bromide (PB) is a reversible cholinesterase inhibitor. The aim of this study was to determine the effect of orally administration of single dose sustained-released tablet of pyridostigmine bromide (PBSR) on the frequency domain indices of heart rate variability (HRV). Thirty-two healthy young men were participated in this study. They were divided into 2 groups; the pyridostigmine group (n = 22) and the placebo group (n = 10). Electrocardiogram (ECG) was recorded at 10, 30, 60, 90, 120, 150, 180, 210, 240, 300 and 420 min after PBSR administration. At each time, simultaneously, a blood sample was prepared and PB plasma concentration was measured by high-performance liquid chromatography (HPLC) method. Statistical analysis showed that in different indices of HRV, there is a significant increase in low frequency (LF) band at 300 min, but no difference in high frequency band (HF). It also showed significant decreases in normalized high frequency band (Hfnu), normalized low frequency band (Lfnu) and LF/HF ratio at 120, 240 and 300 min after PBSR administration. Maximum plasma concentration of PB was 150 min after the administration. In conclusion, administration of a single dose PBSR can enhance the frequency domains indices of HRV and improvesympathovagal balance.

Enhancement of Frequency Domain Indices of Heart Rate Variability by Cholinergic Stimulation with Pyridostigmine Bromide

PubMed Central

Zarei, Ali Asghar; Foroutan, Seyyed Abbas; Foroutan, Seyyed Mohsen; Erfanian Omidvar, Abbas

2011-01-01

Pyridostigmine bromide (PB) is a reversible cholinesterase inhibitor. The aim of this study was to determine the effect of orally administration of single dose sustained-released tablet of pyridostigmine bromide (PBSR) on the frequency domain indices of heart rate variability (HRV). Thirty-two healthy young men were participated in this study. They were divided into 2 groups; the pyridostigmine group (n = 22) and the placebo group (n = 10). Electrocardiogram (ECG) was recorded at 10, 30, 60, 90, 120, 150, 180, 210, 240, 300 and 420 min after PBSR administration. At each time, simultaneously, a blood sample was prepared and PB plasma concentration was measured by high-performance liquid chromatography (HPLC) method. Statistical analysis showed that in different indices of HRV, there is a significant increase in low frequency (LF) band at 300 min, but no difference in high frequency band (HF). It also showed significant decreases in normalized high frequency band (Hfnu), normalized low frequency band (Lfnu) and LF/HF ratio at 120, 240 and 300 min after PBSR administration. Maximum plasma concentration of PB was 150 min after the administration. In conclusion, administration of a single dose PBSR can enhance the frequency domains indices of HRV and improvesympathovagal balance. PMID:24250427

School Psychologists' Management of Administrative Pressure to Practice Unethically

ERIC Educational Resources Information Center

Boccio, Dana E.; Weisz, Gaston; Lefkowitz, Rebecca

2016-01-01

In their role as child advocates, school psychologists strive to promote policies and practices that increase the availability of necessary academic and mental health services and enhance the well-being of children. However, administrative pressure to disregard ethical and legal mandates in favor of decisions that would prioritize the needs of the…

Significant Enhancement in the Thermoelectric Properties of PEDOT:PSS Films through a Treatment with Organic Solutions of Inorganic Salts.

PubMed

Fan, Zeng; Du, Donghe; Yu, Zhimeng; Li, Pengcheng; Xia, Yijie; Ouyang, Jianyong

2016-09-07

Conducting polymers have promising thermoelectric application because they have many advantages including abundant elements, mechanical flexibility, and nontoxicity. The thermoelectric properties of conducting polymers strongly depend on their chemical structure and microstructure. Here, we report a novel and facile method to significantly enhance the thermoelectric properties of poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) ( PSS) films through a treatment with organic solutions of inorganic salts. N,N-Dimethylformamide (DMF) and a common inorganic salt like zinc chloride (ZnCl2) are used as the solvent and solute of the solutions, respectively. The treatments can significantly increase both the Seebeck coefficient and electrical conductivity of the PSS films. The thermoelectric properties of the PSS films are sensitive to the experimental conditions, such as the salt concentration, treatment temperature, and the cation of the salts. After treatment at the optimal experimental conditions, the PSS films can exhibit a Seebeck coefficient of 26.1 μV/K and an electrical conductivity of over 1400 S/cm at room temperature. The corresponding power factor is 98.2 μW/(m·K(2)). The mechanism for the enhancement in the thermoelectric properties is attributed to the segregation of some PSSH chains from PSS and the conformation change of PEDOT chains as a result of the synergetic effects of inorganic salts and DMF.

An Archaeosome-Adjuvanted Vaccine and Checkpoint Inhibitor Therapy Combination Significantly Enhances Protection from Murine Melanoma

PubMed Central

Stark, Felicity C.; Weeratna, Risini D.; Deschatelets, Lise; Gurnani, Komal; Dudani, Renu; Krishnan, Lakshmi

2017-01-01

Archaeosomes constitute archaeal lipid vesicle vaccine adjuvants that evoke a strong CD8+ T cell response to antigenic cargo. Therapeutic treatment of murine B16-ovalbumin (B16-OVA) melanoma with archaeosome-OVA eliminates small subcutaneous solid tumors; however, they eventually resurge despite an increased frequency of circulating and tumor infiltrating OVA-CD8+ T cells. Herein, a number of different approaches were evaluated to improve responses, including dose number, interval, and the combination of vaccine with checkpoint inhibitors. Firstly, we found that tumor protection could not be enhanced by repetitive and/or delayed boosting to maximize the CD8+ T cell number and/or phenotype. The in vivo cytotoxicity of vaccine-induced OVA-CD8+ T cells was impaired in tumor-bearing mice. Additionally, tumor-infiltrating OVA-CD8+ T cells had an increased expression of programmed cell death protein-1 (PD-1) compared to other organ compartments, suggesting impaired function. Combination therapy of tumor-bearing mice with the vaccine archaeosome-OVA, and α-CTLA-4 administered concurrently as well as α-PD-1 and an α-PD-L1 antibody administered starting 9 days after tumor challenge given on a Q3Dx4 schedule (days 9, 12, 15 and 18), significantly enhanced survival. Following multi-combination therapy ~70% of mice had rapid tumor recession, with no detectable tumor mass after >80 days in comparison to a median survival of 17–22 days for untreated or experimental groups receiving single therapies. Overall, archaeosomes offer a powerful platform for delivering cancer antigens when used in combination with checkpoint inhibitor immunotherapies. PMID:29072624

Significant Enhancement of H2 Formation in Disk Galaxies under Strong Ram Pressure

NASA Astrophysics Data System (ADS)

Henderson, Benjamin; Bekki, Kenji

2016-05-01

We show for the first time that H2 formation on dust grains can be enhanced in disk galaxies under strong ram pressure (RP). We numerically investigate how the time evolution of H I and H2 components in disk galaxies orbiting a group/cluster of galaxies can be influenced by the hydrodynamical interaction between the gaseous components of the galaxies and the hot intracluster medium. We find that compression of H I caused by RP increases H2 formation in disk galaxies before RP rapidly strips H I, cutting off the fuel supply and causing a drop in H2 density. We also find that the level of this H2 formation enhancement in a disk galaxy under RP depends on the mass of its host cluster dark matter halo, the initial positions and velocities of the disk galaxy, and the disk inclination angle with respect to the orbital plane. We demonstrate that dust growth is a key factor in the evolution of the H I and H2 mass in disk galaxies under strong RP. We discuss how the correlation between H2 fractions and surface gas densities of disk galaxies evolves with time in the galaxies under RP. We also discuss whether galaxy-wide star formation rates (SFRs) in cluster disk galaxies can be enhanced by RP if the SFRs depend on H2 densities.

Significance of perianular enhancement associated with anular tears on magnetic resonance imagings in diagnosis of radiculopathy.

PubMed

Byun, Woo Mok; Ahn, Sang Ho; Ahn, Myun-Whan

2008-10-15

Retrospective analysis of magnetic resonance imaging (MRI) and clinical findings about chemical radiculitis-associated anular tear in patients with radiculopathy. To investigate MRI findings of the chemical radiculitis caused by anular tears and to determine whether chemical radiculitis detected by MRI is the cause of radiculopathy. Many studies document that irritation of adjacent nerve roots by a chemical mediator of inflammation from the nucleus pulposus may result in radiculopathy. Computed tomography (CT) discography may be the best examination for diagnosing discogenic chemical radiculitis but is too invasive. A reliable imaging method for replacing invasive provocative CT discography and diagnosing chemical radiculitis is required. The study population consisted of 12 patients with pain referred to leg(s) with or without low back pain who underwent lumbar spine MRI. All cases of our study demonstrated perianular enhancement caused by chemical radiculitis associated with anular tears. Patterns and locations of perianular enhancement adjacent to anular tears on MRI were assessed. MRI findings were compared with clinical symptoms and/or provocative transforaminal epidural injection (n = 6). For documentation of the relationship between perianular enhancement and radiculopathy, provocative CT discography was performed in 2 cases. Perianular enhancement associated with anular tears revealed thick linear patterns (2.5-7 mm thickness) along margins of anular tears on contrast enhanced axial T1-weighted images with fat suppression. Locations of perianular enhancement adjacent to anular tears were at foraminal (n = 6) and extraforaminal portions (n = 6). CT discography showed a leak of contrast from anular tear to the perianular regions. Pain reproduction at contrast leak level during discography showed concordant pain. There was an apparent correlation between perianular enhancement on MRI and clinical symptoms or provocative epidural nerve root injection in all

A Leptin-Mediated Central Mechanism in Analgesia-Enhanced Opioid Reward in Rats

PubMed Central

Lim, Grewo; Kim, Hyangin; McCabe, Michael F.; Chou, Chiu-Wen; Wang, Shuxing; Chen, Lucy L.; Marota, John J.A.; Blood, Anne; Breiter, Hans C.

2014-01-01

Opioid analgesics are commonly used in chronic pain management despite a potential risk of rewarding. However, it remains unclear whether opioid analgesia would enhance the opioid rewarding effect thereby contributing to opioid rewarding. Utilizing a rat paradigm of conditioned place preference (CPP) combined with ankle monoarthritis as a condition of persistent nociception, we showed that analgesia induced by either morphine or the nonsteroid anti-inflammatory drug ibuprofen increased CPP scores in arthritic rats, suggesting that analgesia itself had a rewarding effect. However, arthritic rats exhibited a significantly higher CPP score in response to morphine than ibuprofen. Thus, the rewarding effect of morphine was enhanced in the presence of persistent nociception, producing a phenomenon of analgesia-enhanced opioid reward. At the cellular level, administration of morphine activated a cascade of leptin expression, glial activation, and dopamine receptor upregulation in the nucleus accumbens (NAc), while administration of ibuprofen decreased glial activation with no effect on leptin expression in the NAc. Furthermore, the morphine rewarding effect was blocked in leptin deficient ob/ob mice or by neutralizing leptin or interleukin-1β in the NAc without diminishing morphine analgesia. The data indicate that systemic opioid can activate a leptin-mediated central mechanism in the NAc that led to the enhanced opioid rewarding effect. These findings provide evidence for an interaction between opioid analgesia and opioid rewarding, which may have implications in clinical opioid dose escalation in chronic pain management. PMID:25031415

Significantly enhancing enzymatic hydrolysis of rice straw after pretreatment using renewable ionic liquid-water mixtures.

PubMed

Hou, Xue-Dan; Li, Ning; Zong, Min-Hua

2013-05-01

Pretreatment of rice straw by using renewable cholinium lysine ionic liquid ([Ch][Lys] IL)-water mixtures and subsequent enzymatic hydrolysis of the residues were conducted in this work. There is a clear correlation between the delignification capacity of the pretreatment solvent and its basicity. After pretreatment, surface area and pore volume of rice straw increased significantly, which substantially improved polysaccharides accessibility to enzymes and thus enhanced polysaccharides digestion. By carefully controlling the pretreatment severity (IL content, temperature and duration), loss of readily extractable xylan could be minimized. The sugar yields of 81% for glucose and 48% for xylose were achieved in the enzymatic hydrolysis of rice straw after pretreatment with 20% [Ch][Lys]-water mixture at 90 °C for 1 h. This pretreatment process is highly promising for industrial application because of high sugar yields, low energy input, short pretreatment time, and being environmentally benign and highly tolerant to moisture. Copyright © 2013 Elsevier Ltd. All rights reserved.

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.

Administration of SIN-1 induces guinea pig airway hyperresponsiveness through inactivation of airway neutral endopeptidase.

PubMed

Kanazawa, H; Hirata, K; Yoshikawa, J

1999-12-01

Peroxynitrite plays an important role in the pathogenesis of airway inflammation. We have already found that peroxynitrite may contribute to decreased beta(2)-adrenoceptor responses in airway smooth muscle. However, it is not known whether peroxynitrite can alter neutral endopeptidase (EC 3.4.24.11; NEP) activity in the airways. This study was designed to determine whether peroxynitrite induces airway hyperresponsiveness to substance P (SP) and endothelin-1 (ET-1) through the inactivation of airway NEP. We examined whether the administration of S-morpholinosydnonimine (SIN-1), a compound that releases peroxynitrite, increased bronchoconstrictor responses to SP and ET-1 in anesthetized guinea pigs. In addition, we assayed NEP activity in the airways of SIN-1-exposed guinea pigs. Though SIN-1 (10(-7) M) alone had no effect on pulmonary resistance, pretreatment with SIN-1 significantly enhanced SP- and ET-1-induced bronchoconstriction. Pretreatment with phosphoramidon, an NEP inhibitor, also enhanced SP- and ET-1-induced bronchoconstriction. However, simultaneous administration of phosphoramidon and SIN-1 had no additive effect on SP- and ET-1-induced bronchoconstriction. Peroxynitrite formation by SIN-1 was completely inhibited by N-acetylcysteine (NAC) and glutathione (GSH) in vitro, and pretreatment with NAC and GSH significantly reversed the potentiation by SIN-1 of SP-induced bronchoconstriction. In addition, the NEP activity of the trachea after SIN-1 exposure was significantly reduced compared to the level in control guinea pigs (solvent for SIN-1: 30.0+/-4.2 fmol.min(-1).mg tissue(-1); 10(-7) M SIN-1; 15.5+/-4.5 fmol.min(-1).mg tissue(-1), p<0.05). These findings suggest that peroxynitrite induces airway hyperresponsiveness to SP and ET-1 through the inactivation of airway NEP, and that peroxynitrite is an important mediator of the alterations in airway functions.

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.

Dietary fructose enhances the incidence of precancerous hepatocytes induced by administration of diethylnitrosamine in rat

PubMed Central

2013-01-01

Background Nonalcoholic fatty liver disease (NAFLD) is a risk for hepatocellular carcinoma (HCC), but the association between a high-fructose diet and HCC is not fully understood. In this study, we investigated whether a high-fructose diet affects hepatocarcinogenesis induced by administration of diethylnitrosamine (DEN). Methods Seven-week-old male Sprague–Dawley rats were fed standard chow (controls), a high-fat diet (54% fat), or a high-fructose diet (66% fructose) for 8 weeks. All rats were given DEN at 50 μg/L in drinking water during the same period. Precancerous hepatocytes were detected by immunostaining of the placental form of glutathione-S-transferase (GST-P). The number of GST-P-positive hepatocytes was assessed in liver specimens. Results Serum levels of total cholesterol were similar among the three groups, but serum triglyceride, fasting blood glucose, and insulin levels were higher in the high-fructose group compared to the high-fat group. In contrast, hepatic steatosis was more severe in the high-fat group compared with the high-fructose and control groups, but the incidence of GST-P-positive specimens was significantly higher in the high-fructose group compared to the other two groups. The average number of GST-P-positive hepatocytes in GST-P positive specimens in the high-fructose group was also higher than those in the other two groups. This high prevalence of GST-P-positive hepatocytes was accompanied by higher levels of 8-hydroxydeoxyguanosine in serum and liver tissue. Conclusions These results indicate that dietary fructose, rather than dietary fat, increases the incidence of precancerous hepatocytes induced by administration of DEN via insulin resistance and oxidative stress in rat. Thus, excessive fructose intake may be a potential risk factor for hepatocarcinogenesis. PMID:24321741

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.

Nucleus accumbens feedforward inhibition circuit promotes cocaine self-administration

PubMed Central

Yu, Jun; Yan, Yijin; Li, King-Lun; Wang, Yao; Huang, Yanhua H.; Urban, Nathaniel N.; Nestler, Eric J.; Schlüter, Oliver M.; Dong, Yan

2017-01-01

The basolateral amygdala (BLA) sends excitatory projections to the nucleus accumbens (NAc) and regulates motivated behaviors partially by activating NAc medium spiny neurons (MSNs). Here, we characterized a feedforward inhibition circuit, through which BLA-evoked activation of NAc shell (NAcSh) MSNs was fine-tuned by GABAergic monosynaptic innervation from adjacent fast-spiking interneurons (FSIs). Specifically, BLA-to-NAcSh projections predominantly innervated NAcSh FSIs compared with MSNs and triggered action potentials in FSIs preceding BLA-mediated activation of MSNs. Due to these anatomical and temporal properties, activation of the BLA-to-NAcSh projection resulted in a rapid FSI-mediated inhibition of MSNs, timing-contingently dictating BLA-evoked activation of MSNs. Cocaine self-administration selectively and persistently up-regulated the presynaptic release probability of BLA-to-FSI synapses, entailing enhanced FSI-mediated feedforward inhibition of MSNs upon BLA activation. Experimentally enhancing the BLA-to-FSI transmission in vivo expedited the acquisition of cocaine self-administration. These results reveal a previously unidentified role of an FSI-embedded circuit in regulating NAc-based drug seeking and taking. PMID:28973852

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.

Medication administration error reporting and associated factors among nurses working at the University of Gondar referral hospital, Northwest Ethiopia, 2015.

PubMed

Bifftu, Berhanu Boru; Dachew, Berihun Assefa; Tiruneh, Bewket Tadesse; Beshah, Debrework Tesgera

2016-01-01

Medication administration is the final step/phase of medication process in which its error directly affects the patient health. Due to the central role of nurses in medication administration, whether they are the source of an error, a contributor, or an observer they have the professional, legal and ethical responsibility to recognize and report. The aim of this study was to assess the prevalence of medication administration error reporting and associated factors among nurses working at The University of Gondar Referral Hospital, Northwest Ethiopia. Institution based quantitative cross - sectional study was conducted among 282 Nurses. Data were collected using semi-structured, self-administered questionnaire of the Medication Administration Errors Reporting (MAERs). Binary logistic regression with 95 % confidence interval was used to identify factors associated with medication administration errors reporting. The estimated medication administration error reporting was found to be 29.1 %. The perceived rates of medication administration errors reporting for non-intravenous related medications were ranged from 16.8 to 28.6 % and for intravenous-related from 20.6 to 33.4 %. Education status (AOR =1.38, 95 % CI: 4.009, 11.128), disagreement over time - error definition (AOR = 0.44, 95 % CI: 0.468, 0.990), administrative reason (AOR = 0.35, 95 % CI: 0.168, 0.710) and fear (AOR = 0.39, 95 % CI: 0.257, 0.838) were factors statistically significant for the refusal of reporting medication administration errors at p-value <0.05. In this study, less than one third of the study participants reported medication administration errors. Educational status, disagreement over time - error definition, administrative reason and fear were factors statistically significant for the refusal of errors reporting at p-value <0.05. Therefore, the results of this study suggest strategies that enhance the cultures of error reporting such as providing a clear definition of

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.

The peripheral administration of a nitric oxide donor potentiates the local antinociceptive effects of a DOR agonist during chronic inflammatory pain in mice.

PubMed

Hervera, Arnau; Leánez, Sergi; Negrete, Roger; Pol, Olga

2009-10-01

Several works reveal that nitric oxide could enhance the peripheral antinociception induced by opioids during acute inflammation. Nonetheless, the role of nitric oxide in the local antinociceptive effects of delta-opioid receptor (DOR) agonists during chronic peripheral inflammation is not known. The aim of this study is to evaluate whether nitric oxide would enhance the local antinociceptive effects of a DOR agonist during chronic inflammatory pain in mice. Chronic inflammatory pain was induced by the subplantar administration of complete Freund's adjuvant (CFA; 30 microl) and thermal hyperalgesia assessed by plantar test. In C57BL/6J mice, we evaluated the local antinociceptive effects of a DOR agonist, [D-Pen2,5]-enkephalin (DPDPE) and a nitric oxide donor, DETA NONOate DETA/NO 2,2'-(hydroxynitrosohydrazino) Bis-Ethanamine (NOC-18) alone or combined (DPDPE plus NOC-18) at 1, 4, 7, and 10 days after CFA injection. The reversibility of the peripheral antinociceptive effects of DPDPE, alone or combined with NOC-18, was assessed with the local administration of selective (naltrindole) and non-selective (naloxone methiodide) DOR antagonists. The local administration of DPDPE or NOC-18 alone dose-dependently inhibited the thermal hyperalgesia induced by peripheral inflammation. Moreover, the co-administration of NOC-18 with DPDPE significantly increased the antinociceptive effects produced by DPDPE from 1 to 10 days of CFA-induced inflammatory pain (P < 0.05). These effects were completely blocked by naltrindole and naloxone methiodide. Our results demonstrate that nitric oxide might enhance the local antinociceptive effects of a DOR agonist during chronic inflammatory pain by interaction with peripheral DOR, representing a useful strategy for an efficient antinociceptive treatment of peripheral inflammatory pain.

Tissue disposition of the insect repellent DEET and the sunscreen oxybenzone following intravenous and topical administration in rats.

PubMed

Fediuk, Daryl J; Wang, Tao; Chen, Yufei; Parkinson, Fiona E; Namaka, Michael P; Simons, Keith J; Burczynski, Frank J; Gu, Xiaochen

2011-10-01

The insect repellent N,N-diethyl-m-toluamide (DEET) and sunscreen oxybenzone (OBZ) have been shown to produce synergistic permeation enhancement when applied concurrently in vitro and in vivo. The disposition of both compounds following intravenous administration (2 mg/kg of DEET or OBZ) and topical skin application (100 mg/kg of DEET and 40 mg/kg of OBZ) was determined in male Sprague-Dawley rats. Pharmacokinetic analysis was also conducted using compartmental and non-compartmental methods. A two-compartment model was deemed the best fit for intravenous administration. The DEET and oxybenzone permeated across the skin to accumulate in blood, liver and kidney following topical skin application. Combined use of DEET and oxybenzone accelerated the disappearance of both compounds from the application site, increased their distribution in the liver and significantly decreased the apparent elimination half-lives of both compounds (p < 0.05). Hepatoma cell studies revealed toxicity from exposure to all treatment concentrations, most notably at 72 h. Although DEET and oxybenzone were capable of mutually enhancing their percutaneous permeation and systemic distribution from topical skin application, there was no evidence of increased hepatotoxic deficits from concurrent application. Copyright © 2011 John Wiley & Sons, Ltd.

Ex vivo and in vivo diffusion of ropivacaine through spinal meninges: influence of absorption enhancers.

PubMed

Brandhonneur, Nolwenn; Dollo, Gilles; Ratajczak-Enselme, Maja; Deniau, Anne Laure; Chevanne, François; Estèbe, Jean Pierre; Legrand, Alain; Le Corre, Pascal

2011-02-14

Following epidural administration, cerebrospinal fluid bioavailability of local anesthetics is low, one major limiting factor being diffusion across the arachnoid mater barrier. The aim of this study was to evaluate the influence of absorption enhancers on the meningeal permeability of epidurally administered ropivacaine. Five enhancers known for their ability to increase drug permeability via transcellular and/or paracellular pathways, i.e. palmitoyl carnitine, ethylenediaminetetraacetic acid, sodium caprate, dodecylphosphocholine and pentylglycerol, were tested ex vivo on fresh specimen of meninges removed from cervical to lumbar level of rabbit spine following laminectomy and placed in diffusion chambers. Among them, sodium caprate lead to the best permeability improvement for both marker and drug (440% and 112% for mannitol and ropivacaine, respectively) and was therefore selected for in vivo study in a sheep model using microdialysis technique to evaluate epidural and intrathecal ropivacaine concentrations following epidural administration. Resulting dialysate and plasma concentrations were used to calculate pharmacokinetic parameters. Following sodium caprate pre-treatment, ropivacaine intrathecal maximal concentration (Cmax) was 1.6 times higher (78 ± 16 μg ml(-1) vs 129 ± 26 μg ml(-1), p<0.05) but the influence of the absorption enhancer was only effective the first 30 min following ropivacaine injection, as seen with the significantly increase of intrathecal AUC(0-30 min) (1629 ± 437 μg min ml(-1) vs 2477 ± 559 μg min ml(-1), p<0.05) resulting in a bioavailable fraction 130% higher 30 min after ropivavaine administration. Co-administration of local anesthetics with sodium caprate seems to allow a transient and reversible improvement of transmeningeal passage into intrathecal space. Copyright © 2010 Elsevier B.V. All rights reserved.

Food significantly reduces plasma concentrations of first-line anti-tuberculosis drugs.

PubMed

Kumar, Agibothu Kupparam Hemanth; Chandrasekaran, Vedachalam; Kumar, Angadi Kiran; Kawaskar, M; Lavanya, J; Swaminathan, Soumya; Ramachandran, Geetha

2017-04-01

Concomitant feeding and anti-tuberculosis (TB) drug administration are likely to reduce nausea and enhance compliance to treatment. However, food could lower plasma drug concentrations. This study was undertaken to examine the effect of food on two-hour plasma concentrations of rifampicin (RMP), isoniazid (INH) and pyrazinamide (PZA), and pharmacokinetics of these drugs in adult TB patients. Newly diagnosed adult TB patients were recruited from the Revised National Tuberculosis Control Programme (RNTCP) treatment centres in Chennai Corporation, Chennai, India. Two-hour post-dosing plasma concentrations were determined in 25 patients, and a semi-intensive pharmacokinetic study was undertaken in six patients. RMP, INH and PZA concentrations were determined by high-performance liquid chromatography. The geometric mean two-hour concentrations with food and under fasting conditions were 2.2 and 5.5 μg/ml for RMP (P<0.001), 3.9 and 11.3 μg/ml for INH (P<0.001), and 18.0 and 28.2 μg/ml for PZA (P<0.001), respectively. Drug administration with food caused the plasma concentration to decrease by 50, 45 and 34 per cent for RMP, INH and PZA, respectively. Significant decreases in peak concentrations and exposures of drugs and delay in time to attain peak concentrations of drugs when taken with food were also observed. Our findings showed that food lowered anti-TB drug concentrations significantly and delayed absorption. Patients may be explained the beneficial effects of taking anti-TB drugs in a fasting state and advised to do so. There is a need for more research on optimization of dosing to maximize efficacy and safety of currently used drugs.

Vgi for Land Administration - a Quality Perspective

NASA Astrophysics Data System (ADS)

Navratil, G.; Frank, A. U.

2013-05-01

Since the use of volunteered geographic information (VGI) or crowd sourced data (Goodchild, 2007) became more common, several people proposed the use of such methods of data collection for various fields. Success stories were Wikipedia encyclopaedia and OpenStreetMap (OSM), but also using VGI in land administration has been proposed. Robin McLaren proposed crowd sourcing as a way to get a new citizen collaboration model in land administration to enhance transparency and decrease costs (McLaren, 2011). Keenja et al. discussed the perception of VGI within the Dutch cadastre (Keenja, De Vries, Bennet, & Laarakker, 2012). Basiouka and Potsiou even discuss how crowd sourcing can be used to identify errors in the Hellenic cadastre (Basiouka & Potsiou, 2012). One problem of VGI is the quality control (compare Goodchild & Li, 2012). The problem with most data in a land administration system is that there is only a small group of people that can verify the correctness of information. The correct location of a boundary, for example, can only be assessed by the owners of the pieces of land touching at the boundary (and surveyors after investigation and measurement). How shall VGI then provide reliable data? Boundaries between areas of different use may be visible but land administration is often interested in ownership boundaries. In the paper we discuss the types of data used in land administration as discussed by Dale and McLaughlin (1999). These categories are then analyzed to identify the areas where VGI can actually provide reliable input. What we hope to learn from such an analysis is how to use the methodology of crowd sourcing for land administration, even if the data collection authoritatively.

The n-butanolic extract of Opuntia ficus-indica var. saboten enhances long-term memory in the passive avoidance task in mice.

PubMed

Kim, Jong Min; Kim, Dong Hyun; Park, Se Jin; Park, Dong Hyun; Jung, Seo Yun; Kim, Hyoung Ja; Lee, Yong Sup; Jin, Changbae; Ryu, Jong Hoon

2010-08-16

Opuntia ficus-indica var. saboten Makino (Cactaceae) is used to treat burns, edema, dyspepsia, and asthma in traditional medicine. The present study investigated the beneficial effects of the n-butanolic extract of O. ficus-indica var. saboten (BOF) on memory performance in mice and attempts to uncover the mechanisms underlying its action. Memory performance was assessed with the passive avoidance task, and western blotting and immunohistochemistry were used to measure changes in protein expression and cell survival. After the oral administration of BOF for 7 days, the latency time in the passive avoidance task was significantly increased relative to vehicle-treated controls (P<0.05). Western blotting revealed that the expression levels of brain-derived neurotrophic factor (BDNF), phosphorylated cAMP response element binding-protein (pCREB), and phosphorylated extracellular signal-regulated kinase (pERK) 1/2 were significantly increased in hippocampal tissue after 7 days of BOF administration (P<0.05). Doublecortin and 5-bromo-2-deoxyuridine immunostaining also revealed that BOF significantly enhanced the survival of immature neurons, but did not affect neuronal cell proliferation in the subgranular zone of the hippocampal dentate gyrus. These results suggest that the subchronic administration of BOF enhances long-term memory, and that this effect is partially mediated by ERK-CREB-BDNF signaling and the survival of immature neurons. Copyright (c) 2010 Elsevier Inc. All rights reserved.

Significant enhancement in thermoelectric properties of polycrystalline Pr-doped SrTiO3-δ ceramics originating from nonuniform distribution of Pr dopants

NASA Astrophysics Data System (ADS)

Dehkordi, Arash Mehdizadeh; Bhattacharya, Sriparna; He, Jian; Alshareef, Husam N.; Tritt, Terry M.

2014-05-01

Recently, we have reported a significant enhancement (>70% at 500 °C) in the thermoelectric power factor (PF) of bulk polycrystalline Pr-doped SrTiO3 ceramics employing a novel synthesis strategy which led to the highest ever reported values of PF among doped polycrystalline SrTiO3. It was found that the formation of Pr-rich grain boundary regions gives rise to an enhancement in carrier mobility. In this Letter, we investigate the electronic and thermal transport in Sr1-xPrxTiO3 ceramics in order to determine the optimum doping concentration and to evaluate the overall thermoelectric performance. Simultaneous enhancement in the thermoelectric power factor and reduction in thermal conductivity in these samples resulted in more than 30% improvement in the dimensionless thermoelectric figure of merit (ZT) for the whole temperature range over all previously reported maximum values. Maximum ZT value of 0.35 was obtained at 500 °C.

Comparative pharmacokinetic study of mangiferin after oral administration of pure mangiferin and US patented polyherbal formulation to rats.

PubMed

Kammalla, Ananth Kumar; Ramasamy, Mohan Kumar; Inampudi, Jyothi; Dubey, Govind Prasad; Agrawal, Aruna; Kaliappan, Ilango

2015-04-01

The US patented polyherbal formulation for the prevention and management of type II diabetes and its vascular complications was used for the present study. The xanthone glycoside mangiferin is one of the major effector constituents in the Salacia species with potential anti-diabetic activity. The pharmacokinetic differences of mangiferin following oral administration of pure mangiferin and polyherbal formulation containing Salacia species were studied with approximately the same dose 30 mg/kg mangiferin and its distribution among the major tissue in Wistar rats. Plasma samples were collected at different time points (15, 30, 60, 120, 180, 240, 360, 480, 600, 1,440, 2,160, and 2880 min) and subsequently analyzed using a validated simple and rapid LC-MS method. Plasma concentration versus time profiles were explored by non-compartmental analysis. Mangiferin plasma exposure was significantly increased when administered from formulation compared to the standard mangiferin. Mangiferin resided significantly longer in the body (last mean residence time (MRTlast)) when given in the form of the formulation (3.65 h). Cmax values of formulation (44.16 μg/mL) administration were elevated when compared to equivalent dose of the pure mangiferin (15.23 μg/mL). Tissue distribution study of mangiferin from polyherbal formulation was also studied. In conclusion, the exposure of mangiferin is enhanced after formulation and administration and could result in superior efficacy of polyherbal formulation when compared to an equivalent dose of mangiferin. The results indicate that the reason which delays the elimination of mangiferin and enhances its bioavailability might the interactions of the some other constituents present in the polyherbal formulation. Distribution study results indicate that mangiferin was extensively bound to the various tissues like the small intestine, heart, kidney, spleen, and liver except brain tissue.

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.

Enhancing Leadership in Colleges and Universities: A Case Approach

ERIC Educational Resources Information Center

Sandeen, Arthur

2011-01-01

In view of the serious challenges facing college and university administrators, it is encouraging to note the increased interest in improving leadership knowledge and skills. This book presents an additional option to college and university administrators in their efforts to enhance their leadership skills. The case study approach to improving…

Paracellular permeation-enhancing effect of AT1002 C-terminal amidation in nasal delivery

PubMed Central

Song, Keon-Hyoung; Kim, Sang-Bum; Shim, Chang-Koo; Chung, Suk-Jae; Kim, Dae-Duk; Rhee, Sang-Ki; Choi, Guang J; Kim, Chul-Hyun; Kim, Kiyoung

2015-01-01

Background The identification of permeation enhancers has gained interest in the development of drug delivery systems. A six-mer peptide, H-FCIGRL-OH (AT1002), is a tight junction modulator with promising permeation-enhancing activity. AT1002 enhances the transport of molecular weight markers or agents with low bioavailability with no cytotoxicity. However, AT1002 is not stable in neutral pH or after incubation under physiological conditions, which is necessary to fully uncover its permeation-enhancing effect. Thus, we increased the stability or mitigated the instability of AT1002 by modifying its terminal amino acids and evaluated its subsequent biological activity. Methods C-terminal-amidated (FCIGRL-NH2, Pep1) and N-terminal-acetylated (Ac-FCIGRL, Pep2) peptides were analyzed by liquid chromatography–mass spectrometry. We further assessed cytotoxicity on cell monolayers, as well as the permeation-enhancing activity following nasal administration of the paracellular marker mannitol. Results Pep1 was nontoxic to cell monolayers and showed a relatively low decrease in peak area compared to AT1002. In addition, administration of mannitol with Pep1 resulted in significant increases in the area under the plasma concentration–time curve and peak plasma concentration at 3.63-fold and 2.68-fold, respectively, compared to mannitol alone. In contrast, no increase in mannitol concentration was shown with mannitol/AT1002 or mannitol/Pep2 compared to the control. Thus, Pep1 increased the stability or possibly reduced the instability of AT1002, which resulted in an increased permeation-enhancing effect of AT1002. Conclusion These results suggest the potential usefulness of C-terminal-amidated AT1002 in enhancing nasal drug delivery, which may lead to the development of a practical drug delivery technology for drugs with low bioavailability. PMID:25848218

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…

Epidermal growth factor selectively enhances functional enterocyte adaptation after massive small bowel resection.

PubMed

Dunn, J C; Parungo, C P; Fonkalsrud, E W; McFadden, D W; Ashley, S W

1997-01-01

After massive small bowel resection, the intestine adapts to compensate. In addition to proliferation, enterocytes also undergo selective functional adaptation. In this study we examined the effect of intraperitoneal administration of epidermal growth factor (EGF) on the expression of the brush border dissacharidase sucrase, the sodium glucose cotransporter (SGLT1), and the sodium-potassium ATPase pump (NaK ATPase) by enterocytes in the remnant intestine after massive small bowel resection. Adult Lewis rats underwent either ileal transection or 70% proximal intestinal resection. These animals were subdivided into groups that received either saline or EGF intraperitoneally for 1 week. Ilea from each group were harvested 4 weeks postoperatively. Enterocytes were separated from these segments by calcium chelation. The total protein from the isolated cells was subjected to Western blot analysis. Administration of EGF to animals that underwent transection did not significantly alter the expression of sucrase, SGLT1, or NaK ATPase. After intestinal resection, the expressions of sucrase and SGLT1 were significantly increased. The combination of EGF administration and intestinal resection resulted in a further increase in SGLT1 expression. The intraperitoneal administration of EGF selectively enhanced the expression of SGLT1 by enterocytes after massive small bowel resection. Administration of EGF to sham-operated animals did not have similar effects. These results suggest that EGF augments the adaptive response and may therefore have a therapeutic role in the management of patients with short bowel syndrome.

Zero valent iron significantly enhances methane production from waste activated sludge by improving biochemical methane potential rather than hydrolysis rate.

PubMed

Liu, Yiwen; Wang, Qilin; Zhang, Yaobin; Ni, Bing-Jie

2015-02-05

Anaerobic digestion has been widely applied for waste activated sludge (WAS) treatment. However, methane production from anaerobic digestion of WAS is usually limited by the slow hydrolysis rate and/or poor biochemical methane potential of WAS. This work systematically studied the effects of three different types of zero valent iron (i.e., iron powder, clean scrap and rusty scrap) on methane production from WAS in anaerobic digestion, by using both experimental and mathematical approaches. The results demonstrated that both the clean and the rusty iron scrap were more effective than the iron powder for improving methane production from WAS. Model-based analysis showed that ZVI addition significantly enhanced methane production from WAS through improving the biochemical methane potential of WAS rather than its hydrolysis rate. Economic analysis indicated that the ZVI-based technology for enhancing methane production from WAS is economically attractive, particularly considering that iron scrap can be freely acquired from industrial waste. Based on these results, the ZVI-based anaerobic digestion process of this work could be easily integrated with the conventional chemical phosphorus removal process in wastewater treatment plant to form a cost-effective and environment-friendly approach, enabling maximum resource recovery/reuse while achieving enhanced methane production in wastewater treatment system.

Zero Valent Iron Significantly Enhances Methane Production from Waste Activated Sludge by Improving Biochemical Methane Potential Rather Than Hydrolysis Rate

PubMed Central

Liu, Yiwen; Wang, Qilin; Zhang, Yaobin; Ni, Bing-Jie

2015-01-01

Anaerobic digestion has been widely applied for waste activated sludge (WAS) treatment. However, methane production from anaerobic digestion of WAS is usually limited by the slow hydrolysis rate and/or poor biochemical methane potential of WAS. This work systematically studied the effects of three different types of zero valent iron (i.e., iron powder, clean scrap and rusty scrap) on methane production from WAS in anaerobic digestion, by using both experimental and mathematical approaches. The results demonstrated that both the clean and the rusty iron scrap were more effective than the iron powder for improving methane production from WAS. Model-based analysis showed that ZVI addition significantly enhanced methane production from WAS through improving the biochemical methane potential of WAS rather than its hydrolysis rate. Economic analysis indicated that the ZVI-based technology for enhancing methane production from WAS is economically attractive, particularly considering that iron scrap can be freely acquired from industrial waste. Based on these results, the ZVI-based anaerobic digestion process of this work could be easily integrated with the conventional chemical phosphorus removal process in wastewater treatment plant to form a cost-effective and environment-friendly approach, enabling maximum resource recovery/reuse while achieving enhanced methane production in wastewater treatment system. PMID:25652244

Zero Valent Iron Significantly Enhances Methane Production from Waste Activated Sludge by Improving Biochemical Methane Potential Rather Than Hydrolysis Rate

NASA Astrophysics Data System (ADS)

Liu, Yiwen; Wang, Qilin; Zhang, Yaobin; Ni, Bing-Jie

2015-02-01

Anaerobic digestion has been widely applied for waste activated sludge (WAS) treatment. However, methane production from anaerobic digestion of WAS is usually limited by the slow hydrolysis rate and/or poor biochemical methane potential of WAS. This work systematically studied the effects of three different types of zero valent iron (i.e., iron powder, clean scrap and rusty scrap) on methane production from WAS in anaerobic digestion, by using both experimental and mathematical approaches. The results demonstrated that both the clean and the rusty iron scrap were more effective than the iron powder for improving methane production from WAS. Model-based analysis showed that ZVI addition significantly enhanced methane production from WAS through improving the biochemical methane potential of WAS rather than its hydrolysis rate. Economic analysis indicated that the ZVI-based technology for enhancing methane production from WAS is economically attractive, particularly considering that iron scrap can be freely acquired from industrial waste. Based on these results, the ZVI-based anaerobic digestion process of this work could be easily integrated with the conventional chemical phosphorus removal process in wastewater treatment plant to form a cost-effective and environment-friendly approach, enabling maximum resource recovery/reuse while achieving enhanced methane production in wastewater treatment system.

Liposomal temozolomide drug delivery using convection enhanced delivery.

PubMed

Nordling-David, Mirjam M; Yaffe, Roni; Guez, David; Meirow, Hadar; Last, David; Grad, Etty; Salomon, Sharona; Sharabi, Shirley; Levi-Kalisman, Yael; Golomb, Gershon; Mardor, Yael

2017-09-10

Even though some progress in diagnosis and treatment has been made over the years, there is still no definitive treatment available for Glioblastoma multiforme (GBM). Convection-enhanced delivery (CED), a continuous infusion-mediated pressure gradient via intracranial catheters, studied in clinical trials, enables in situ drug concentrations several orders of magnitude greater than those achieved by systemic administration. We hypothesized that the currently limited efficacy of CED could be enhanced by a liposomal formulation, thus achieving enhanced drug localization to the tumor site with minimal toxicity. We hereby describe a novel approach for treating GBM by CED of liposomes containing the known chemotherapeutic agent, temozolomide (TMZ). A new technique for encapsulating TMZ in hydrophilic (PEGylated) liposomes, characterized by nano-size (121nm), low polydispersity index (<0.13) and with near-neutral charge (-ʒ,0.2mV), has been developed. Co-infusion of PEGylated Gd-DTPA liposomes and TMZ-liposomes by CED in GBM bearing rats, resulted in enhanced tumor detection with longer residence time than free Gd-DTPA. Treatment of GBM-bearing rats with either TMZ solution or TMZ-liposomes resulted in greater tumor inhibition and significantly higher survival. However, the longer survival and smaller tumor volumes exhibited by TMZ liposomal treatment in comparison to TMZ in solution were insignificant (p<0.053); and only significantly lower edema volumes were observed. Thus, there are no clear-cut advantages to use a liposomal delivery system of TMZ via CED over a drug solution. Copyright © 2017 Elsevier B.V. All rights reserved.

Observation of Significant Quantum Efficiency Enhancement from a Polarized Photocathode with Distributed Bragg Reflector

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

Zhang, Shukui; Poelker, Matthew; Stutzman, Marcy L.

2015-09-01

Polarized photocathodes with higher Quantum efficiency (QE) would help to reduce the technological challenge associated with producing polarized beams at milliampere levels, because less laser light would be required, which simplifies photocathode cooling requirements. And for a given amount of available laser power, higher QE would extend the photogun operating lifetime. The distributed Bragg reflector (DBR) concept was proposed to enhance the QE of strained-superlattice photocathodes by increasing the absorption of the incident photons using a Fabry-Perot cavity formed between the front surface of the photocathode and the substrate that includes a DBR, without compromising electron polarization. Here we presentmore » recent results showing QE enhancement of a GaAs/GaAsP strained-superlattice photocathode made with a DBR structure. Typically, a GaAs/GaAsP strained-superlattice photocathode without DBR provides a QE of 1%, at a laser wavelength corresponding to peak polarization. In comparison, the GaAs/GaAsP strained-superlattice photocathodes with DBR exhibited an enhancement of over 2 when the incident laser wavelength was tuned to meet the resonant condition for the Fabry-Perot resonator.« less

Dietary administration of a Gracilaria tenuistipitata extract enhances the immune response and resistance against Vibrio alginolyticus and white spot syndrome virus in the white shrimp Litopenaeus vannamei.

PubMed

Sirirustananun, Nuttarin; Chen, Jiann-Chu; Lin, Yong-Chin; Yeh, Su-Tuen; Liou, Chyng-Hwa; Chen, Li-Li; Sim, Su Sing; Chiew, Siau Li

2011-12-01

The haemogram, phenoloxidase (PO) activity, respiratory bursts (RBs), superoxide dismutase (SOD) activity, glutathione peroxidase (GPx) activity, lysozyme activity, and the mitotic index of haematopoietic tissue (HPT) were examined after the white shrimp Litopenaeus vannamei had been fed diets containing the hot-water extract of Gracilaria tenuistipitata at 0 (control), 0.5, 1.0, and 2.0 g kg(-1) for 7-35 days. Results indicated that these parameters directly increased with the amount of extract and time, but slightly decreased after 35 days. RBs, SOD activity, and GPx activity reached the highest levels after 14 days, whereas PO and lysozyme activities reached the highest levels after 28 days. In a separate experiment, white shrimp L. vannamei, which had been fed diets containing the extract for 14 days, were challenged with Vibrio alginolyticus at 2 × 10(6) cfu shrimp(-1) and white spot syndrome virus (WSSV) at 1 × 10(3) copies shrimp(-1), and then placed in seawater. The survival rate of shrimp fed the extract-containing diets was significantly higher than that of shrimp fed the control diet at 72-144 h post-challenge. We concluded that dietary administration of the G. tenuistipitata extract at ≤1.0 g kg(-1) could enhance the innate immunity within 14 days as evidenced by the increases in immune parameters and mitotic index of HPT in shrimp and their enhanced resistance against V. alginolyticus and WSSV infections. Shrimp fed the extract-containing diets showed a higher and continuous increase in the humoral response indicating its persistent role in innate immunity. Copyright © 2011 Elsevier Ltd. All rights reserved.

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.

Mechanical and Electrical Properties of a Polyimide Film Significantly Enhanced by the Addition of Single-Wall Carbon Nanotubes

NASA Technical Reports Server (NTRS)

Meador, Michael A.

2005-01-01

Single-wall carbon nanotubes have been shown to possess a combination of outstanding mechanical, electrical, and thermal properties. The use of carbon nanotubes as an additive to improve the mechanical properties of polymers and/or enhance their thermal and electrical conductivity has been a topic of intense interest. Nanotube-modified polymeric materials could find a variety of applications in NASA missions including large-area antennas, solar arrays, and solar sails; radiation shielding materials for vehicles, habitats, and extravehicular activity suits; and multifunctional materials for vehicle structures and habitats. Use of these revolutionary materials could reduce vehicle weight significantly and improve vehicle performance and capabilities.

A Summary of the FHWA Contract Administration Techniques for Quality Enhancement Study Tour (CATQEST)

DOT National Transportation Integrated Search

1994-06-01

There is a widespread impression in the United States that roads and highway structures in Europe are generally superior to comparable facilities in the United States. The joint industry and government project, the Contract Administration Techniques ...

Social defeat alters the acquisition of cocaine self-administration in rats: role of individual differences in cocaine-taking behavior.

PubMed

Kabbaj, M; Norton, C S; Kollack-Walker, S; Watson, S J; Robinson, T E; Akil, H

2001-12-01

It is known that social defeat can modulate cocaine self-administration. However, it is unclear whether this psychosocial stressor affects drug-taking behavior to the same extent across all individual animals, particularly those with differing propensities to self-administer psychostimulants. This study examined the effect of social defeat on cocaine self-administration in animals that differ in novelty-seeking behavior that predicts differences in drug self-administration. Male Sprague-Dawley rats were first classified into high-responder (HR) and low-responder (LR) groups. HR and LR rats were categorized based on their locomotor activity in a novel environment, with HR rats exhibiting higher locomotor activity than LR rats. Then, male rats were exposed on four occasions to an aggressive Long Evans male rat over the course of 4 days. Control rats were not exposed to the social defeat. All rats were subsequently implanted with jugular catheters and 3 days later placed into the self-administration box to study the acquisition of cocaine self-administration (0.25 mg per infusion). HR non-defeated animals self-administered more cocaine than the LR non-defeated animals. Following social defeat, the acquisition of cocaine self-administration is significantly delayed in HR rats and enhanced in LR rats. CONCLUSION The unique patterns of responsiveness in the HR and LR animals suggest that social defeat plays a role of equalizer of individual differences in drug-taking behavior.

Varenicline impairs extinction and enhances reinstatement across repeated cycles of nicotine self-administration in rats.

PubMed

Macnamara, Claire L; Holmes, Nathan M; Westbrook, R Fred; Clemens, Kelly J

2016-06-01

Varenicline is a partial nicotine receptor agonist widely prescribed as a smoking cessation medication. Repeated (or long-term) use of varenicline has been proposed as a treatment option for tobacco addiction. However the effect of repeated varenicline use on motivation for nicotine is unknown. Here the intravenous nicotine self-administration paradigm in rats was used to model the consequences of varenicline treatment across repeated cycles of administration, extinction and reinstatement. Rats acquired nicotine self-administration across 20 days before undergoing 6 days of extinction, where each extinction session was preceded by a single injection of varenicline or saline. This was followed by a single varenicline-free nicotine-primed reinstatement test. All rats then reacquired nicotine self-administration for 10 days followed by a second cycle of extinction. Across this period, rats either received a second cycle of varenicline (VAR-VAR) or saline (SAL-SAL), or the alternative treatment (SAL-VAR, VAR-SAL), followed by a final reinstatement test. Treatment with varenicline increased responding across the first cycle of extinction, but did not affect responding in the reinstatement test. Across the second cycle, varenicline again increased responding across extinction, and critically, rats treated with varenicline across cycle 1 and saline across cycle 2 (Group VAR-SAL) exhibited more reinstatement than rats in any other group. The effect of VAR on nicotine seeking was not due to its effects on locomotor activity. Instead, the results suggest that a history of VAR can increase vulnerability to reinstatement/relapse when its treatment is discontinued. The possible mechanisms of this increased vulnerability are discussed. Copyright © 2016 Elsevier Ltd. All rights reserved.

Multiple autophosphorylations significantly enhance the endoribonuclease activity of human inositol requiring enzyme 1α

PubMed Central

2014-01-01

Background Endoplasmic reticulum stress, caused by the presence of misfolded proteins, activates the stress sensor inositol-requiring enzyme 1α (IRE1α). The resulting increase in IRE1α RNase activity causes sequence-specific cleavage of X-box binding protein 1 (XBP1) mRNA, resulting in upregulation of the unfolded protein response and cellular adaptation to stress. The precise mechanism of human IRE1α activation is currently unclear. The role of IRE1α kinase activity is disputed, as results from the generation of various kinase-inactivating mutations in either yeast or human cells are discordant. Kinase activity can also be made redundant by small molecules which bind the ATP binding site. We set out to uncover a role for IRE1α kinase activity using wild-type cytosolic protein constructs. Results We show that concentration-dependent oligomerisation is sufficient to cause IRE1α cytosolic domain RNase activity in vitro. We demonstrate a role for the kinase activity by showing that autophosphorylation enhances RNase activity. Inclusion of the IRE1α linker domain in protein constructs allows hyperphosphorylation and further enhancement of RNase activity, highlighting the importance of kinase activity. We show that IRE1α phosphorylation status correlates with an increased propensity to form oligomeric complexes and that forced dimerisation causes great enhancement in RNase activity. In addition we demonstrate that even when IRE1α is forced to dimerise, by a GST-tag, phospho-enhancement of activity is still observed. Conclusions Taken together these experiments support the hypothesis that phosphorylation is important in modulating IRE1α RNase activity which is achieved by increasing the propensity of IRE1α to dimerise. This work supports the development of IRE1α kinase inhibitors for use in the treatment of secretory cancers. PMID:24524643

[Effects of preoperative oral carbohydrate administration on gastric contents].

PubMed

Sato, Chiaki; Shibuya, Hiromi; Nishino, Miho; Maeda, Akihiko; Shimakawa, Noriko; Okada, Toshiki

2012-08-01

Preoperative oral carbohydrate administration for adult patients has been recommended by European Society for Parenteral and Enteral Nutrition and Enhanced Recovery After Surgery. Although preoperative oral carbohydrate may improve patient satisfaction and perioperative glucose metabolism, its effects on the gastric contents remain controversial. We included 232 adult patients without gastrointestinal stenosis or occlusion. Seventy-four patients (group A) were not permitted to eat or drink before operation for eight hours, while 158 patients (group B) took oral carbohydrate (225 ml, 22.3% glucose) two hours before anesthesia induction. After induction, gastric contents were aspirated to examine its volume and pH. Although the mean volume of gastric contents of the patients in group B was significantly lower than that in group A, and gastric pH was also significantly smaller in group B, no patients suffered from aspiration during rapid induction. Fasting interval and gastric volume were inversely related, and almost all the patients with fasting interval above 150 minutes showed gastric contents volume smaller than 25 ml and gastric pH more than 2.5. We conclude that preoperative oral carbohydrate can be given safely, although the fasting interval should be 150 minutes in our diet regimen.

Security of Data, Stored in Information Systems of Bulgarian Municipal Administrations

NASA Astrophysics Data System (ADS)

Kapralyakov, Petko

2011-12-01

Massive influx of information technology in municipal administrations increases their efficiency in delivering public services but increased the risk of theft of confidential information electronically. The report proposed an approach for improving information security for small municipal governments in Bulgaria through enhanced intrusion detection and prevention system.

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.

75 FR 23781 - Agency Information Collection Activities; Proposed Collection; Comment Request; Administrative...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-04

... for the Clinical Laboratory Improvement Amendments of 1988 Categorization AGENCY: Food and Drug... notice solicits comments on administrative procedures for the Clinical Laboratory Improvement Amendments..., including the validity of the methodology and assumptions used; (3) ways to enhance the quality, utility...

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…

Stimulated hemopoiesis and enhanced survival following glucan treatment in sublethally and lethally irradiated mice

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

Patchen, M.L.; MacVittie, T.J.

1985-01-01

Hemopoietic effects of the reticuloendothelial agent glucan were assayed in normal mice and in mice hemopoietically depleted by exposure to /sup 60/Co radiation. In normal mice, glucan administration increased the content of bone marrow and splenic transplantable pluripotent hemopoietic stem cells (CFU-2), committed granulocyte-macrophage progenitor cells (GM-CFC), and pure macrophage progenitor cells (M-CFC). Erythroid progenitor cells (CFU-e) were increased only in the spleen. In sublethally irradiated mice (650 rads), glucan increased the number of endogeneous pluripotent hemopoietic stem cells (E-CFU) when administered either before or after irradiation. The most pronounced effects were observed when glucan was administered 1 day before,more » 1 h before, or 1 h after irradiation. In addition, the administration of glucan before lethal irradiation (900 rads) enhanced survival. The most significant results were seen when glucan was administered 1 day prior to irradiation. The possibility of using agents such as glucan to enhance hemopoietic reconstitution and prevent septicemia following chemotherapy and/or radiotherapy is discussed.« less

Gold nanoparticles: enhanced optical trapping and sensitivity coupled with significant heating.

PubMed

Seol, Yeonee; Carpenter, Amanda E; Perkins, Thomas T

2006-08-15

Gold nanoparticles appear to be superior handles in optical trapping assays. We demonstrate that relatively large gold particles (R(b)=50 nm) indeed yield a sixfold enhancement in trapping efficiency and detection sensitivity as compared to similar-sized polystyrene particles. However, optical absorption by gold at the most common trapping wavelength (1064 nm) induces dramatic heating (266 degrees C/W). We determined this heating by comparing trap stiffness from three different methods in conjunction with detailed modeling. Due to this heating, gold nanoparticles are not useful for temperature-sensitive optical-trapping experiments, but may serve as local molecular heaters. Also, such particles, with their increased detection sensitivity, make excellent probes for certain zero-force biophysical assays.

Allyl isothiocyanate increases carbohydrate oxidation through enhancing insulin secretion by TRPV1.

PubMed

Mori, Noriyuki; Kurata, Manami; Yamazaki, Hanae; Matsumura, Shigenobu; Hashimoto, Takashi; Kanazawa, Kazuki; Nadamoto, Tomonori; Inoue, Kazuo; Fushiki, Tohru

2018-04-01

The transient receptor potential (TRP) V1 is a cation channel belonging to the TRP channel family and it has been reported to be involved in energy metabolism, especially glucose metabolism. While, we have previously shown that intragastric administration of allyl isothiocyanate (AITC) enhanced glucose metabolism via TRPV1, the underlying mechanism has not been elucidated. In this study, we examined the relationship between insulin secretion and the increase in carbohydrate oxidation due to AITC. Intragastric administration of AITC elevated blood insulin levels in mice and AITC directly enhanced insulin secretion from isolated islets. These observations were not reproduced in TRPV1 knockout mice. Furthermore, AITC did not increase carbohydrate oxidation in streptozotocin-treated mice. These results suggest that intragastric administration of AITC could induce insulin secretion from islets via TRPV1 and that enhancement of insulin secretion was related to the increased carbohydrate oxidation due to AITC.

Withdrawal of repeated morphine enhances histamine-induced scratching responses in mice.

PubMed

Abe, Kenji; Kobayashi, Kanayo; Yoshino, Saori; Taguchi, Kyoji; Nojima, Hiroshi

2015-04-01

An itch is experientially well known that the scratching response of conditions such as atopic dermatitis is enhanced under psychological stress. Morphine is typical narcotic drug that induces a scratching response upon local application as an adverse drug reaction. Although long-term treatment with morphine will cause tolerance and dependence, morphine withdrawal can cause psychologically and physiologically stressful changes in humans. In this study, we evaluated the effects of morphine withdrawal on histamine-induced scratching behavior in mice. Administration of morphine with progressively increasing doses (10-50 mg/kg, i.p.) was performed for 5 consecutive days. At 3, 24, 48, and 72 hr after spontaneous withdrawal from the final morphine dose, histamine was intradermally injected into the rostral part of the back and then the number of bouts of scratching in 60 min was recorded and summed. We found that at 24 hr after morphine withdrawal there was a significant increase in histamine-induced scratching behavior. The spinal c-Fos positive cells were also significantly increased. The relative adrenal weight increased and the relative thymus weight decreased, both significantly. Moreover, the plasma corticosterone levels changed in parallel with the number of scratching bouts. These results suggest that morphine withdrawal induces a stressed state and enhances in histamine-induced scratching behavior. Increased reaction against histamine in the cervical vertebrae will participate in this stress-induced itch enhancement.

Significantly enhanced piezoelectricity in low-temperature sintered Aurivillius-type ceramics with ultrahigh Curie temperature of 800 °C

NASA Astrophysics Data System (ADS)

Cai, Kai; Huang, Chengcheng; Guo, Dong

2017-04-01

We report an Aurivillius-type piezoelectric ceramic (Ca1-2x (LiCe) x Bi4Ti3.99Zn0.01O15) that has an ultrahigh Curie temperature (T c) around 800 °C and a significantly enhanced piezoelectric coefficient (d 33), comparable to that of textured ceramics fabricated using the complicated templating method. Surprisingly, the highest d 33 of 26 pC/N was achieved at an unexpectedly low sintering temperature (T s) of only 920 °C (~200 °C lower than usual) despite the non-ideal density. Study of different synthesized samples indicates that a relatively low T s is crucial for suppressing Bi evaporation and abnormal grain growth, which are indispensable for high resistivity and effective poling due to decreased carrier density and restricted anisotropic conduction. Because the layered structure is sensitive to lattice defects, controlled Bi loss is considered to be crucial for maintaining structural order and spontaneous polarization. This low-T s system is very promising for practical applications due to its high piezoelectricity, low cost and high reproducibility. Contrary to our usual understanding, the results reveal that a delicate balance of density, Bi loss and grain morphology achieved by adjusting the sintering temperature is crucial for the enhancing performance in Aurivillius-type high-T c ceramics.

Optimized nano-transfersomal films for enhanced sildenafil citrate transdermal delivery: ex vivo and in vivo evaluation

PubMed Central

Badr-Eldin, Shaimaa M; Ahmed, Osamaa AA

2016-01-01

Sildenafil citrate (SLD) is a selective cyclic guanosine monophosphate-specific phosphodiesterase type 5 inhibitor used for the oral treatment of erectile dysfunction and, more recently, for other indications, including pulmonary hypertension. The challenges facing the oral administration of the drug include poor bioavailability and short duration of action that requires frequent administration. Thus, the objective of this work is to formulate optimized SLD nano-transfersomal transdermal films with enhanced and controlled permeation aiming at surmounting the previously mentioned challenges and hence improving the drug bioavailability. SLD nano-transfersomes were prepared using modified lipid hydration technique. Central composite design was applied for the optimization of SLD nano-transfersomes with minimized vesicular size. The independent variables studied were drug-to-phospholipid molar ratio, surfactant hydrophilic lipophilic balance, and hydration medium pH. The optimized SLD nano-transfersomes were developed and evaluated for vesicular size and morphology and then incorporated into hydroxypropyl methyl cellulose transdermal films. The optimized transfersomes were unilamellar and spherical in shape with vesicular size of 130 nm. The optimized SLD nano-transfersomal films exhibited enhanced ex vivo permeation parameters with controlled profile compared to SLD control films. Furthermore, enhanced bioavailability and extended absorption were demonstrated by SLD nano-transfersomal films as reflected by their significantly higher maximum plasma concentration (Cmax) and area under the curve and longer time to maxi mum plasma concentration (Tmax) compared to control films. These results highlighted the potentiality of optimized SLD nano-transfersomal films to enhance the transdermal permeation and the bioavailability of the drug with the possible consequence of reducing the dose and administration frequency. PMID:27103786

Optimized nano-transfersomal films for enhanced sildenafil citrate transdermal delivery: ex vivo and in vivo evaluation.

PubMed

Badr-Eldin, Shaimaa M; Ahmed, Osamaa Aa

2016-01-01

Sildenafil citrate (SLD) is a selective cyclic guanosine monophosphate-specific phosphodiesterase type 5 inhibitor used for the oral treatment of erectile dysfunction and, more recently, for other indications, including pulmonary hypertension. The challenges facing the oral administration of the drug include poor bioavailability and short duration of action that requires frequent administration. Thus, the objective of this work is to formulate optimized SLD nano-transfersomal transdermal films with enhanced and controlled permeation aiming at surmounting the previously mentioned challenges and hence improving the drug bioavailability. SLD nano-transfersomes were prepared using modified lipid hydration technique. Central composite design was applied for the optimization of SLD nano-transfersomes with minimized vesicular size. The independent variables studied were drug-to-phospholipid molar ratio, surfactant hydrophilic lipophilic balance, and hydration medium pH. The optimized SLD nano-transfersomes were developed and evaluated for vesicular size and morphology and then incorporated into hydroxypropyl methyl cellulose transdermal films. The optimized transfersomes were unilamellar and spherical in shape with vesicular size of 130 nm. The optimized SLD nano-transfersomal films exhibited enhanced ex vivo permeation parameters with controlled profile compared to SLD control films. Furthermore, enhanced bioavailability and extended absorption were demonstrated by SLD nano-transfersomal films as reflected by their significantly higher maximum plasma concentration (C max) and area under the curve and longer time to maxi mum plasma concentration (T max) compared to control films. These results highlighted the potentiality of optimized SLD nano-transfersomal films to enhance the transdermal permeation and the bioavailability of the drug with the possible consequence of reducing the dose and administration frequency.

Local vs. systemic administration of bisphosphonates in rat cleft bone graft: A comparative study

PubMed Central

Lin, Lawrence; Olson, Jeffrey; Kwon, Taewoo; Bezouglaia, Olga; Tran, Jaime; Hoang, Michael; Bui, Kimberly; Kim, Reuben H.; Tetradis, Sotirios

2018-01-01

A majority of patients with orofacial cleft deformity requires cleft repair through a bone graft. However, elevated amount of bone resorption and subsequent bone graft failure remains a significant clinical challenge. Bisphosphonates (BPs), a class of anti-resorptive drugs, may offer great promise in enhancing the clinical success of bone grafting. In this study, we compared the effects of systemic and local delivery of BPs in an intraoral bone graft model in rats. We randomly divided 34 female 20-week-old Fischer F344 Inbred rats into four groups to repair an intraoral critical-sized defect (CSD): (1) Control: CSD without graft (n = 4); (2) Graft/Saline: bone graft with systemic administration of saline 1 week post-operatively (n = 10); (3) Graft/Systemic: bone graft with systemic administration of zoledronic acid 1 week post-operatively (n = 10); and (4) Graft/Local: bone graft pre-treated with zoledronic acid (n = 10). At 6-weeks post-operatively, microCT volumetric analysis showed a significant increase in bone fraction volume (BV/TV) in the Graft/Systemic (62.99 ±14.31%) and Graft/Local (69.35 ±13.18%) groups compared to the Graft/Saline (39.18±10.18%). Similarly, histological analysis demonstrated a significant increase in bone volume in the Graft/Systemic (78.76 ±18.00%) and Graft/Local (89.95 ±4.93%) groups compared to the Graft/Saline (19.74±18.89%). The local delivery approach resulted in the clinical success of bone grafts, with reduced graft resorption and enhanced osteogenesis and bony integration with defect margins while avoiding the effects of BPs on peripheral osteoclastic function. In addition, local delivery of BPs may be superior to systemic delivery with its ease of procedure as it involves simple soaking of bone graft materials in BP solution prior to graft placement into the defect. This new approach may provide convenient and promising clinical applications towards effectively managing cleft patients. PMID:29304080

Enhancement of antigen-specific CD4 + and CD8 + T cell responses using a self-assembled biologic nanolipoprotein particle vaccine

DOE PAGES

Weilhammer, Dina; Dunkle, Alexis D.; Blanchette, Craig D.; ...

2017-02-14

To address the need for vaccine platforms that induce robust cell-mediated immunity, we investigated the potential of utilizing self-assembling biologic nanolipoprotein particles (NLPs) as an antigen and adjuvant delivery system to induce antigen-specific murine T cell responses. Here, we utilized OT-I and OT-II TCR-transgenic mice to investigate the effects of NLP-mediated delivery of the model antigen ovalbumin (OVA) on T cell activation. Delivery of OVA with the TLR4 agonist monophosphoryl lipid A (MPLA) in the context of NLPs significantly enhanced the activation of both CD4 + and CD8 + T cells in vitro compared to co-administration of free OVA andmore » MPLA. Upon intranasal immunization of mice harboring TCR-transgenic cells, NLPs enhanced the adjuvant effects of MPLA and the in vivo delivery of OVA, leading to significantly increased expansion of CD4 + and CD8 + T cells in lung-draining lymph nodes. Therefore, NLPs are a promising vaccine platform for inducing T cell responses following intranasal administration.« less

Enhancement of antigen-specific CD4 + and CD8 + T cell responses using a self-assembled biologic nanolipoprotein particle vaccine

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

Weilhammer, Dina; Dunkle, Alexis D.; Blanchette, Craig D.

To address the need for vaccine platforms that induce robust cell-mediated immunity, we investigated the potential of utilizing self-assembling biologic nanolipoprotein particles (NLPs) as an antigen and adjuvant delivery system to induce antigen-specific murine T cell responses. Here, we utilized OT-I and OT-II TCR-transgenic mice to investigate the effects of NLP-mediated delivery of the model antigen ovalbumin (OVA) on T cell activation. Delivery of OVA with the TLR4 agonist monophosphoryl lipid A (MPLA) in the context of NLPs significantly enhanced the activation of both CD4 + and CD8 + T cells in vitro compared to co-administration of free OVA andmore » MPLA. Upon intranasal immunization of mice harboring TCR-transgenic cells, NLPs enhanced the adjuvant effects of MPLA and the in vivo delivery of OVA, leading to significantly increased expansion of CD4 + and CD8 + T cells in lung-draining lymph nodes. Therefore, NLPs are a promising vaccine platform for inducing T cell responses following intranasal administration.« less

D-cycloserine Deters Reacquisition of Cocaine Self-Administration by Augmenting Extinction Learning

PubMed Central

Nic Dhonnchadha, Bríd Á; Szalay, Jonathan J; Achat-Mendes, Cindy; Platt, Donna M; Otto, Michael W; Spealman, Roger D; Kantak, Kathleen M

2010-01-01

Augmentation of cue exposure (extinction) therapy with cognitive-enhancing pharmacotherapy may offer an effective strategy to combat cocaine relapse. To investigate this possibility at the preclinical level, rats and squirrel monkeys were trained to self-administer cocaine paired with a brief visual cue. Lever pressing was subsequently extinguished by withholding cocaine injections while maintaining response-contingent presentations of the cue. The glycine partial agonist D-cycloserine (DCS; 15 and 30 mg/kg in rats, 3 and 10 mg/kg in monkeys) was evaluated for its effects on the rate of extinction and subsequent reacquisition of cocaine self-administration. Compared with vehicle, pretreatment with 30 mg/kg DCS 0.5 h before extinction training reduced the number of responses and latency to reach the extinction criterion in rats, but neither dose of DCS altered these measures in monkeys. In both species, pretreatment with the higher dose of DCS before extinction training significantly attenuated reacquisition of cocaine self-administration compared with either extinction training in the absence of DCS or DCS in the absence of explicit extinction. Furthermore, treatment with 30 mg/kg DCS accompanied by brief handling (a stress induction) immediately after but not 6 h after extinction training attenuated reacquisition of cocaine self-administration in rats. No adverse effects of 10 mg/kg DCS were evident in quantitative observational studies in monkeys. The results suggest that DCS augmented consolidation of extinction learning to deter reacquisition of cocaine self-administration in rats and monkeys. The results suggest that DCS combined with exposure therapy may constitute a rational strategy for the clinical management of cocaine relapse. PMID:19741593

A comparison of the pharmacokinetics of three different preparations of total flavones of Hippophae rhamnoides in beagle dogs after oral administration.

PubMed

Duan, Jingze; Dang, Yang; Meng, Houjun; Wang, Huizhen; Ma, Ping; Li, Guowen; Wu, Tao; Xie, Yan

2016-06-01

Pharmacokinetic properties of isorhamnetin, quercetin, and kaempferol in three different total flavones of Hippophae rhamnoides (TFH) preparations were compared after oral administration to beagle dogs by a UPLC-MS method. The pharmacokinetic results showed that C max of isorhamnetin and quercetin in TFH solid dispersion (TFH-SD) and TFH self-emulsifying (TFH-SE) preparations was significantly enhanced than that in TFH preparations (p < 0.05). The AUCs of isorhamnetin and quercetin in TFH-SD were 5.9- and 3.1-fold higher than that of TFH, while the AUCs of isorhamnetin and quercetin in TFH-SE were 3.4- and 2.4-fold higher than that of TFH. These findings suggested that the oral bioavailability of isorhamnetin and quercetin in beagle dogs can be significantly increased in TFH-SD and TFH-SE preparations compared to TFH preparations, which was helpful to explore the new forms for oral administration TFH and explain their in vivo processes.

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.

L-Cysteine enhances nutrient absorption via a cystathionine-β-synthase-derived H2 S pathway in rodent jejunum.

PubMed

Xiao, Ailin; Li, Jing; Liu, Tianjian; Liu, Zhuxi; Wei, Chuanfei; Xu, Xiaomeng; Li, Qin; Li, Jingxin

2016-05-01

Hydrogen sulphide (H2 S) is generated endogenously from L-cysteine (L-Cys) by the enzymes cystathionine-β-synthase (CBS) and cystathionine-γ-lyase (CSE). In addition, L-Cys is commonly used as a precursor in the food and pharmaceutical industries. The aim of the present study is to determine whether L-Cys regulates intestinal nutrient transport. To that end, the presence of CBS and CSE in the jejunum epithelium was assessed by immunohistochemistry, Western blotting and the methylene blue assay. In addition, in vivo L-Cys (100 mg/kg, administered immediately after the glucose load) significantly increased blood glucose levels 30 min after the oral administration of glucose to mice. This effect of L-Cys was completely blocked by amino-oxyacetic acid (AOA; 50 mg/kg; administered at the same time as L-Cys) an inhibitor of CBS. Measurements of the short-circuit current (Isc) in the rat jejunum epithelium revealed that L-Cys (1 mmol/L; 6 min before the administration of L-alanine) enhances Na(+)-coupled L-alanine or glucose transport, and that this effect is inhibited by AOA (1 mmol/L;10 min before the administration of L-Cys), but not D,L-propargylglycine (PAG;1 mmol/L; 10 min before the administration of L-Cys), a CSE inhibitor. Notably, L-Cys-evoked enhancement of nutrient transport was alleviated by glibenclamide (Gli;0.1 mmol/L; 10 min before the administration of L-Cys), a K(+) channel blocker. Together, the data indicate that L-Cys enhances jejunal nutrient transport, suggesting a new approach to future treatment of nutrition-related maladies, including a range of serious health consequences linked to undernutrition. © 2016 John Wiley & Sons Australia, Ltd.

Tumor regression after intravenous administration of targeted vesicles entrapping the vitamin E α-tocotrienol.

PubMed

Karim, Reatul; Somani, Sukrut; Al Robaian, Majed; Mullin, Margaret; Amor, Rumelo; McConnell, Gail; Dufès, Christine

2017-01-28

The therapeutic potential of tocotrienol, a member of the vitamin E family of compounds with potent in vitro anti-cancer properties, is limited by its inability to specifically reach tumors following intravenous administration. The purpose of this study is to determine whether a novel tumor-targeted vesicular formulation of tocotrienol would suppress the growth of A431 epidermoid carcinoma and B16-F10 melanoma in vitro and in vivo. In this work, we demonstrated that novel transferrin-bearing multilamellar vesicles entrapping α-T3 resulted in a dramatically improved (by at least 52-fold) therapeutic efficacy in vitro on A431 cell line, compared to the free drug. In addition, the intravenous administration of tocotrienol entrapped in transferrin-bearing vesicles resulted in tumor suppression for 30% of A431 and 60% of B16-F10 tumors, without visible toxicity. Mouse survival was enhanced by >13days compared to controls administered with the drug solution only. This tumor-targeted, tocotrienol-based nanomedicine therefore significantly improved the therapeutic response in cancer treatment. Copyright © 2016 Elsevier B.V. All rights reserved.

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

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.

The effects of crew resource management on teamwork and safety climate at Veterans Health Administration facilities.

PubMed

Schwartz, Miriam E; Welsh, Deborah E; Paull, Douglas E; Knowles, Regina S; DeLeeuw, Lori D; Hemphill, Robin R; Essen, Keith E; Sculli, Gary L

2017-11-09

Communication failure is a significant source of adverse events in health care and a leading root cause of sentinel events reported to the Joint Commission. The Veterans Health Administration National Center for Patient Safety established Clinical Team Training (CTT) as a comprehensive program to enhance patient safety and to improve communication and teamwork among health care professionals. CTT is based on techniques used in aviation's Crew Resource Management (CRM) training. The aviation industry has reached a significant safety record in large part related to the culture change generated by CRM and sustained by its recurrent implementation. This article focuses on the improvement of communication, teamwork, and patient safety by utilizing a standardized, CRM-based, interprofessional, immersive training in diverse clinical areas. The Teamwork and Safety Climate Questionnaire was used to evaluate safety climate before and after CTT. The scores for all of the 27 questions on the questionnaire showed an increase from baseline to 12 months, and 11 of those increases were statistically significant. A recurrent training is recommended to maintain the positive outcomes. CTT enhances patient safety and reduces risk of patient harm by improving teamwork and facilitating clear, concise, specific and timely communication among health care professionals. © 2017 American Society for Healthcare Risk Management of the American Hospital Association.

[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.

76 FR 65107 - Recovery of Delinquent Debts-Treasury Offset Program Enhancements

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-20

... SOCIAL SECURITY ADMINISTRATION 20 CFR Parts 404, 408, 416, and 422 [Docket No. SSA-2010-0010] RIN 0960-AH19 Recovery of Delinquent Debts--Treasury Offset Program Enhancements AGENCY: Social Security... Recovery Policy, Social Security Administration, 6401 Security Boulevard, Baltimore, MD 21235-6401, (410...

Post-Session Administration of USP Methylene Blue Facilitates the Retention of Pathological Fear Extinction and Contextual Memory in Phobic Adults

PubMed Central

Telch, Michael J.; Bruchey, Aleksandra K.; Rosenfield, David; Cobb, Adam R.; Smits, Jasper; Pahl, Sandra; Gonzalez-Lima, F.

2015-01-01

Objective Preclinical studies have shown that low-dose USP methylene blue increases mitochondrial cytochrome oxidase activity in the brain and improves memory retention after learning tasks, including fear extinction. We report on the first controlled experiment to examine the memory-enhancing effects of post-training methylene blue administration on retention of fear extinction and contextual memory following fear extinction training. Method Adults (N = 42) displaying marked claustrophobic fear were randomized to double-blind administration of 260 mg of methylene blue versus placebo immediately following six five-minute extinction trials to an enclosed chamber. Retesting occurred one month later to assess fear renewal as indexed by peak fear during exposure to a non-trained enclosed chamber with the prediction that methylene blue's effects would vary as a function of fear reduction achieved during extinction training. Incidental contextual memory was assessed 1 and 30 days after training to assess the cognitive enhancing effects of methylene blue independent of its effects on fear attenuation. Results Consistent with predictions, participants displaying low end fear at post-training showed significantly less fear at follow-up if they received methylene blue post-training relative to placebo. In contrast, participants displaying moderate to high levels of post-training fear tended to fare worse at follow-up relative to placebo. Methylene blue's enhancement of contextual memory was unrelated to initial or post-training claustrophobic fear. Conclusions Methylene blue enhances memory and the retention of fear extinction when administered after a successful exposure session, but may have a deleterious effect on extinction when administered after an unsuccessful exposure session. PMID:25018057

Enhanced stereotyped response to amphetamine after pretreatment with small doses of molindone.

PubMed

Conway, P; Uretsky, N J

1983-05-01

Pretreatment of rats with small doses of the antipsychotic drug, molindone, enhanced the stereotyped behavioral response to amphetamine. In order to determine whether molindone enhanced amphetamine-induced stereotypy by the same mechanism as chronic administration of amphetamine or drugs that inhibit central noradrenergic transmission, the effect of these drugs on the stereotyped behavior produced by beta-phenethylamine (PEA) was compared. Following the administration of phenoxybenzamine, reserpine and diethyldithiocarbamate, the stereotyped response produced by beta-phenethylamine was intensified. In contrast, neither molindone nor chronic pretreatment with amphetamine altered beta-phenethylamine-induced stereotypy. As shown previously with chronic amphetamine pretreatment, molindone also failed to enhance the stereotyped response produced by apomorphine. However, in contrast to the effects of chronic administration of amphetamine, molindone both increased the striatal concentration of dihydroxyphenylacetic acid (DOPAC) and blocked the ability of small doses of apomorphine to decrease this dopamine (DA) metabolite. The doses of molindone that blocked the apomorphine-induced reduction in the concentration of DOPAC in the striatum correlated with the doses that enhanced amphetamine-induced stereotypy. Since the decrease in DOPAC in the striatum produced by apomorphine is thought to be mediated through the stimulation of striatal DA autoreceptors, these results suggest that molindone enhances amphetamine-induced stereotypy by selectively inhibiting DA autoreceptors.

A comparative study of the effect of some nutritional medicinal plants effect on lead accumulation in the liver following different modes of administration

PubMed Central

Nwokocha, Chukwuemeka; Younger-Coleman, Novie; Nwokocha, Magdalene; Owu, Daniel; Iwuala, Moses

2014-01-01

Context and Objectives: Lead (Pb) toxicity leads to cell damage in many organs of the body. Using different treatment interventions and modes of administration we comparatively examined the protective ability of some medicinal plants on liver Pb accumulation. Materials and Methods: Rats were fed on either 7% w/w Zingiber officinale, 7% w/w Allium sativum, 10% w/w Lycopersicon esculentum, 5%, w/w Garcinia kola (all in rat chow), while Pb (100 ppm) was given in drinking water. The additives were administered together with (mode 1), a week after exposure to (mode 2) or a week before metal exposure to (mode 3) the metal for a period of 6 weeks. The metal accumulations in the liver were determined using atomic absorption spectrometry and compared using analysis of variance. Results: Some additives significantly (P < 0.05) reduced, while others enhanced Pb accumulation. Mode 2 yielded the highest mean % protection and mode 3 the lowest, no significant interaction between modes of administration and time of measurement in their relationships to percentage protection, but there was statistically significant (P < 0.05) interaction between modes of administration and additive used in their relationships to percentage protection. Conclusion: Protective effects of medicinal plants are varied and depend on the nature of lead exposure. PMID:25276068

Bioavailability of metronidazole in rabbits after administration of a rectal suppository.

PubMed

Ofoefule, Sabinus I; Ibezim, Emmanuel C; Esimone, Okechukwu C; Pepple, Miriam N; Njoku, Chinedu N; Orisakwe, Ebere O

2004-01-01

The bioavailability of metronidazole in rabbits was studied using plasma concentration measurements after the administration of the drug in a hydrophilic (glycerogelatin) suppository form. The peak in the plasma concentration time curve occurred about 1 hour after administration, indicating that the rate of absorption is fast and equivalent to that observed in humans after oral administration. There was rapid elimination of the drug, as indicated by a relatively high elimination rate constant and low plasma half-life. The in vitro dissolution profile of the suppositories further confirms rapid absorption of the drug from the suppositories in the rectum. The presence of Tween 80 enhanced the in vitro release of metronidazole, but the presence of a hydrogenated vegetable oil lubricant (Lubritab) caused retardation in the drug release from the suppositories.

Screening and identification of proteins mediating senna induced gastrointestinal motility enhancement in mouse colon

PubMed Central

Wang, Xin; Zhong, Yue-Xia; Lan, Mei; Zhang, Zong-You; Shi, Yong-Quan; Lu, Ju; Ding, Jie; Wu, Kai-Cun; Jin, Jian-Ping; Pan, Bo-Rong; Fan, Dai Min

2002-01-01

AIM: To isolate the proteins involved in pharmacologic action of senna extract (SE) from mouse gastrointestinal tract and to explore the molecular mechanism of gastrointestinal motility change induced by SE. METHODS: SE was administrated to mice by different routes. Gastrointestinal motility of mice was observed using cathartic, gastrointestinal propellant movement experiments and X-ray analysis. Mouse model for gastrointestinal motility enhancement was established through continuous gastric administration of SE at progressively increased dose. At 3 h and week 3, 4, 6 and 10, morphological changes of gastrointestinal tissues were found under light microscope. Ultrastructural changes of intestinal and colonic tissues at week 6 were observed under transmission electron microscope. The colonic proteomic changes in model mice were examined by two-dimension polyacrylamide gel electrophoresis with immobilized pH gradient isoelectric focusing to screen the differentially expressed proteins, and their molecular masses and isoelectric points were determined. Two N-terminal sequences of the samples were also determined by mass spectrometry. RESULTS: SE (0.3 g) caused diarrhea after gastric administration in 1-6 h and enhanced gastrointestinal propellant (65.1% ± 7.5%; 45.8% ± 14.6%,P < 0.01) in mice, but intramuscular and hypodermic injection had no cathartic effect. X-ray analysis of gastrointestinal motility demonstrated that gastric administration of SE enhanced gastric evacuation and gastrointestinal transferring function. At 3 h and week 3 and 4 after gastric administration of SE, light microscopic examination revealed no apparent change in gastrointestinal mucosal tissues, but transmission electron microscopic examination revealed inflammatory changes in whole layer of intestinal and colonic wall. Twenty differential proteins were detected in the colonic tissues of the model mice by two-dimensional electrophoresis, and the N-terminal amino acid sequences of two

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.

Telehealth Applications to Enhance CKD Knowledge and Awareness Among Patients and Providers.

PubMed

Tuot, Delphine S; Boulware, L Ebony

2017-01-01

CKD affects 13% of the US adult population, causes excess mortality, and is associated with significant sociodemographic disparities. Optimal CKD management slows progression of disease and reduces cardiovascular-related outcomes. Resources for patients and primary care providers, major stakeholders in preventive CKD care, are critically needed to enhance understanding of the disease and to optimize CKD health, particularly because of the asymptomatic nature of kidney disease. Telehealth is defined as the use of electronic communication and telecommunications technology to support long-distance clinical health care, patient and professional health-related education, and public health and health administration. It provides new opportunities to enhance awareness and understanding among these important stakeholders. This review will examine the role of telehealth within existing educational theories, identify telehealth applications that can enhance CKD knowledge and behavior change among patients and primary care providers, and examine the advantages and disadvantages of telehealth vs usual modalities for education. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Pleiotrophin enhances PDGFB-induced gliomagenesis through increased proliferation of neural progenitor cells

PubMed Central

Zhang, Lei; Laaniste, Liisi; Jiang, Yiwen; Alafuzoff, Irina; Uhrbom, Lene; Dimberg, Anna

2016-01-01

Pleiotrophin (PTN) augments tumor growth by increasing proliferation of tumor cells and promoting vascular abnormalization, but its role in early gliomagenesis has not been evaluated. Through analysis of publically available datasets, we demonstrate that increased PTN mRNA expression is associated with amplification of chromosome 7, identified as one of the earliest steps in glioblastoma development. To elucidate the role of PTN in tumor initiation we employed the RCAS/tv-a model that allows glioma induction by RCAS-virus mediated expression of oncogenes in neural progenitor cells. Intracranial injection of RCAS-PTN did not induce glioma formation when administrated alone, but significantly enhanced RCAS-platelet derived growth factor (PDGF)B-induced gliomagenesis. PTN co-treatment augmented PDGFB-induced Akt activation in neural progenitor cells in vitro, and enhanced neural sphere size associated with increased proliferation. Our data indicates that PTN expression is associated with chromosome 7 gain, and that PTN enhances PDGFB-induced gliomagenesis by stimulating proliferation of neural progenitor cells. PMID:27806344

Pleiotrophin enhances PDGFB-induced gliomagenesis through increased proliferation of neural progenitor cells.

PubMed

Zhang, Lei; Laaniste, Liisi; Jiang, Yiwen; Alafuzoff, Irina; Uhrbom, Lene; Dimberg, Anna

2016-12-06

Pleiotrophin (PTN) augments tumor growth by increasing proliferation of tumor cells and promoting vascular abnormalization, but its role in early gliomagenesis has not been evaluated. Through analysis of publically available datasets, we demonstrate that increased PTN mRNA expression is associated with amplification of chromosome 7, identified as one of the earliest steps in glioblastoma development. To elucidate the role of PTN in tumor initiation we employed the RCAS/tv-a model that allows glioma induction by RCAS-virus mediated expression of oncogenes in neural progenitor cells. Intracranial injection of RCAS-PTN did not induce glioma formation when administrated alone, but significantly enhanced RCAS-platelet derived growth factor (PDGF)B-induced gliomagenesis. PTN co-treatment augmented PDGFB-induced Akt activation in neural progenitor cells in vitro, and enhanced neural sphere size associated with increased proliferation. Our data indicates that PTN expression is associated with chromosome 7 gain, and that PTN enhances PDGFB-induced gliomagenesis by stimulating proliferation of neural progenitor cells.

Induction of Fos expression in the rat forebrain after intragastric administration of monosodium L-glutamate, glucose and NaCl.

PubMed

Otsubo, H; Kondoh, T; Shibata, M; Torii, K; Ueta, Y

2011-11-24

l-glutamate, an umami taste substance, is a key molecule coupled to a food intake signaling pathway. Furthermore, recent studies have unveiled new roles for dietary glutamate on gut-brain axis communication via activation of gut glutamate receptors and subsequent vagus nerve. In the present study, we mapped activation sites of the rat forebrain after intragastric load of 60 mM monosodium l-glutamate (MSG) by measurement of Fos protein, a functional marker of neuronal activation. The same concentration of d-glucose (sweet) and NaCl (salty) was used as controls. MSG administration exclusively produced enhanced Fos expression in four hypothalamic regions (the medial preoptic area, lateral hypothalamic area, dorsomedial nucleus, and arcuate nucleus). On the other hand, glucose administration exclusively enhanced Fos induction in the nucleus accumbens. Both MSG and glucose enhanced Fos induction in three brain regions (the habenular nucleus, paraventricular nucleus, and central nucleus of the amygdala). However, MSG induced Fos inductions were more potent than those of glucose in the habenular nucleus and paraventricular nucleus. Importantly, the present study identified for the first time two brain areas (the paraventricular and arcuate hypothalamic nuclei) that are more potently activated by intragastric MSG loads compared with glucose and NaCl. Overall, our results suggest significant activation of a neural network comprising the habenular nucleus, amygdala, and the hypothalamic subnuclei following intragastric load with glutamate. Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

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.

Potentiation of amygdala AMPA receptor activity selectively promotes escalated alcohol self-administration in a CaMKII-dependent manner.

PubMed

Cannady, Reginald; Fisher, Kristen R; Graham, Caitlin; Crayle, Jesse; Besheer, Joyce; Hodge, Clyde W

2017-05-01

Growing evidence indicates that drugs of abuse gain control over the individual by usurping glutamate-linked mechanisms of neuroplasticity in reward-related brain regions. Accordingly, we have shown that glutamate α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) activity in the amygdala is required for the positive reinforcing effects of alcohol, which underlie the initial stages of addiction. It is unknown, however, if enhanced AMPAR activity in the amygdala facilitates alcohol self-administration, which is a kernel premise of glutamate hypotheses of addiction. Here, we show that low-dose alcohol (0.6 g/kg/30 minutes) self-administration increases phosphorylation (activation) of AMPAR subtype GluA1 S831 (pGluA1 S831) in the central amygdala (CeA), basolateral amygdala and nucleus accumbens core (AcbC) of selectively bred alcohol-preferring P-rats as compared with behavior-matched (non-drug) sucrose controls. The functional role of enhanced AMPAR activity was assessed via site-specific infusion of the AMPAR positive modulator, aniracetam, in the CeA and AcbC prior to alcohol self-administration. Intra-CeA aniracetam increased alcohol-reinforced but not sucrose-reinforced responding and was ineffective following intra-AcbC infusion. Because GluA1 S831 is a Ca2+/calmodulin-dependent protein kinase II (CaMKII) substrate, we sought to determine if AMPAR regulation of enhanced alcohol self-administration is dependent on CaMKII activity. Intra-CeA infusion of the cell-permeable CaMKII peptide inhibitor myristolated autocamtide-2-related inhibitory peptide (m-AIP) dose-dependently reduced alcohol self-administration. A subthreshold dose of m-AIP also blocked the aniracetam-induced escalation of alcohol self-administration, demonstrating that AMPAR-mediated potentiation of alcohol reinforcement requires CaMKII activity in the amygdala. Enhanced activity of plasticity-linked AMPAR-CaMKII signaling in the amygdala may promote escalated alcohol use

Potentiation of amygdala AMPA receptor activity selectively promotes escalated alcohol self-administration in a CaMKII-dependent manner

PubMed Central

Cannady, Reginald; Fisher, Kristen R.; Graham, Caitlin; Crayle, Jesse; Besheer, Joyce; Hodge, Clyde W.

2015-01-01

Growing evidence indicates that drugs of abuse gain control over the individual by usurping glutamate-linked mechanisms of neuroplasticity in reward-related brain regions. Accordingly, we have shown that glutamate α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) activity in the amygdala is required for the positive reinforcing effects of alcohol, which underlie the initial stages of addiction. It is unknown, however, if enhanced AMPAR activity in the amygdala facilitates alcohol self-administration, which is a kernel premise of glutamate hypotheses of addiction. Here we show that low-dose alcohol (0.6 g/kg/30-min) self-administration increases phosphorylation (activation) of AMPAR subtype GluA1 S831 (pGluA1 S831) in the central amygdala (CeA), basolateral amygdala, and nucleus accumbens core (AcbC) of selectively bred alcohol-preferring P-rats as compared to behavior-matched (non-drug) sucrose controls. The functional role of enhanced AMPAR activity was assessed via site-specific infusion of the AMPAR positive modulator, aniracetam, in the CeA and AcbC prior to alcohol self-administration. Intra-CeA aniracetam increased alcohol- but not sucrose-reinforced responding, and was ineffective following intra-AcbC infusion. Since GluA1 S831 is a Ca2+/calmodulin-dependent protein kinase II (CaMKII) substrate, we sought to determine if AMPAR regulation of enhanced alcohol self-administration is dependent on CaMKII activity. Intra-CeA infusion of the cell-permeable CaMKII peptide inhibitor m-AIP dose-dependently reduced alcohol self-administration. A sub-threshold dose of m-AIP also blocked the aniracetam-induced escalation of alcohol self-administration, demonstrating that AMPAR-mediated potentiation of alcohol reinforcement requires CaMKII activity in the amygdala. Enhanced activity of plasticity-linked AMPAR-CaMKII signaling in the amygdala may promote escalated alcohol use via increased positive reinforcement during the initial stages of addiction

Significantly enhanced UV luminescence by plasmonic metal on ZnO nanorods patterned by screen-printing.

PubMed

Zhao, Jun; Cui, Shuyuan; Zhang, Xingang; Li, Wenqing

2018-08-31

A smart synthetic method is conceived to construct large batches of ZnO nanostructures to meet market demand for light-emitting diodes. Utilizing the localized surface plasmon resonance of metal nanoparticles (NPs) facilitates the recombination of electron-hole pairs and the release of photons. Compared to raw ZnO nanorods (NRs), ZnO NRs@HfO 2 @Al NPs show a ∼120× enhancement in ultraviolet (UV) photoluminescence (PL), while ZnO NRs@HfO 2 @Ag NPs show a six-fold enhancement. Because the surface plasmon energy of Al is nearer the ZnO band gap, the PL enhancement of ZnO NRs covered with Al is stronger than that of those covered with Ag. Based on this analysis, three-dimensional graphical ZnO NR arrays were manufactured by screen-printing, a mass production technique. After covering the arrays with layers of HfO 2 and Al NPs, the UV PL intensities of the corresponding substrates were increased by approximately 16×. This indicates the potential to mass-produce highly efficient optoelectronic devices.

Exploring the Perceived Effectiveness of the School Administration: Studying the Enhancement of Organizational Practices

ERIC Educational Resources Information Center

Urrutia-Campos, Carlos Lenin

2016-01-01

Principals are facing complex educational scenarios such as an increasing diversity of minority groups in schools, adjustments in regulations, and higher academic standards that press school leaders to update or obtain professional skills. Administrators should be aware that current professional skills may not be sufficient to comply with new…

Clinical and neural effects of six-week administration of oxytocin on core symptoms of autism.

PubMed

Watanabe, Takamitsu; Kuroda, Miho; Kuwabara, Hitoshi; Aoki, Yuta; Iwashiro, Norichika; Tatsunobu, Natsubori; Takao, Hidemasa; Nippashi, Yasumasa; Kawakubo, Yuki; Kunimatsu, Akira; Kasai, Kiyoto; Yamasue, Hidenori

2015-11-01

Autism spectrum disorder is a prevalent neurodevelopmental disorder with no established pharmacological treatment for its core symptoms. Although previous literature has shown that single-dose administration of oxytocin temporally mitigates autistic social behaviours in experimental settings, it remains in dispute whether such potentially beneficial responses in laboratories can result in clinically positive effects in daily life situations, which are measurable only in long-term observations of individuals with the developmental disorder undergoing continual oxytocin administration. Here, to address this issue, we performed an exploratory, randomized, double-blind, placebo-controlled, crossover trial including 20 high-functional adult males with autism spectrum disorder. Data obtained from 18 participants who completed the trial showed that 6-week intranasal administration of oxytocin significantly reduced autism core symptoms specific to social reciprocity, which was clinically evaluated by Autism Diagnostic Observation Scale (P = 0.034, PFDR < 0.05, Cohen's d = 0.78). Critically, the improvement of this clinical score was accompanied by oxytocin-induced enhancement of task-independent resting-state functional connectivity between anterior cingulate cortex and dorso-medial prefrontal cortex (rho = -0.60, P = 0.011), which was measured by functional magnetic resonance imaging. Moreover, using the same social-judgement task as used in our previous single-dose oxytocin trial, we confirmed that the current continual administration also significantly mitigated behavioural and neural responses during the task, both of which were originally impaired in autistic individuals (judgement tendency: P = 0.019, d = 0.62; eye-gaze effect: P = 0.03, d = 0.56; anterior cingulate activity: P = 0.00069, d = 0.97; dorso-medial prefrontal activity: P = 0.0014, d = 0.92; all, PFDR < 0.05). Furthermore, despite its longer administration, these effect sizes of the 6-week intervention

Combined administration of mesenchymal stem cells overexpressing IGF-1 and HGF enhances neovascularization but moderately improves cardiac regeneration in a porcine model.

PubMed

Gómez-Mauricio, Guadalupe; Moscoso, Isabel; Martín-Cancho, María-Fernanda; Crisóstomo, Verónica; Prat-Vidal, Cristina; Báez-Díaz, Claudia; Sánchez-Margallo, Francisco M; Bernad, Antonio

2016-07-16

Insulin-like growth factor 1 (IGF-1) and hepatocyte growth factor (HGF) are among the most promising growth factors for promoting cardiorepair. Here, we evaluated the combination of cell- and gene-based therapy using mesenchymal stem cells (MSC) genetically modified to overexpress IGF-1 or HGF to treat acute myocardial infarction (AMI) in a porcine model. Pig MSC from adipose tissue (paMSC) were genetically modified for evaluation of different therapeutic strategies to improve AMI treatment. Three groups of infarcted Large White pigs were compared (I, control, non-transplanted; II, transplanted with paMSC-GFP (green fluorescent protein); III, transplanted with paMSC-IGF-1/HGF). Cardiac function was evaluated non-invasively using magnetic resonance imaging (MRI) for 1 month. After euthanasia and sampling of the animal, infarcted areas were studied by histology and immunohistochemistry. Intramyocardial transplant in a porcine infarct model demonstrated the safety of paMSC in short-term treatments. Treatment with paMSC-IGF-1/HGF (1:1) compared with the other groups showed a clear reduction in inflammation in some sections analyzed and promoted angiogenic processes in ischemic tissue. Although cardiac function parameters were not significantly improved, cell retention and IGF-1 overexpression was confirmed within the myocardium. The simultaneous administration of IGF-1- and HGF-overexpressing paMSC appears not to promote a synergistic effect or effective repair. The combined enhancement of neovascularization and fibrosis in paMSC-IGF-1/HGF-treated animals nonetheless suggests that sustained exposure to high IGF-1 + HGF levels promotes beneficial as well as deleterious effects that do not improve overall cardiac regeneration.

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…

eLearning or technology enhanced learning in medical education-Hope, not hype.

PubMed

Goh, Poh Sun

2016-09-01

This Personal View elaborates on my strong conviction that the excitement and positive feelings that many of us have for eLearning or Technology enhanced learning (TeL) is well founded, and will argue why our hopes are justified, and not misplaced. In a nutshell, I believe that eLearning or TeL is a significant advance from previous generations of educational innovation, and offers benefits for students, educators and administrators; by synergistically combining the capabilities of digital content, the Internet, and mobile technology, supported by software and applications or "Apps".

Hospice nurses' views on single nurse administration of controlled drugs.

PubMed

Taylor, Vanessa; Middleton-Green, Laura; Carding, Sally; Perkins, Paul

2015-07-01

The involvement of two nurses to dispense and administer controlled drugs is routine practice in most clinical areas despite there being no legal or evidence-based rationale. Indeed, evidence suggests this practice enhances neither safety nor care. Registered nurses at two hospices agreed to change practice to single nurse dispensing and administration of controlled drugs (SNAD). Participants' views on SNAD were evaluated before and after implementation. The aim of this study was to explore the views and experiences of nurses who had implemented SNAD and to identify the views and concerns of those who had not yet experienced SNAD. Data was obtained through semi-structured interviews. Qualitative thematic analysis of interview transcripts identified three key themes: practice to enhance patient benefit and care; practice to enhance nursing care and satisfaction; and practice to enhance organisational safety. The findings have implications for the understanding of influences on medicines safety in clinical practice and for hospice policy makers.

SIGNIFICANT ENHANCEMENT OF H{sub 2} FORMATION IN DISK GALAXIES UNDER STRONG RAM PRESSURE

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

Henderson, Benjamin; Bekki, Kenji

We show for the first time that H{sub 2} formation on dust grains can be enhanced in disk galaxies under strong ram pressure (RP). We numerically investigate how the time evolution of H i and H{sub 2} components in disk galaxies orbiting a group/cluster of galaxies can be influenced by the hydrodynamical interaction between the gaseous components of the galaxies and the hot intracluster medium. We find that compression of H i caused by RP increases H{sub 2} formation in disk galaxies before RP rapidly strips H i, cutting off the fuel supply and causing a drop in H{sub 2}more » density. We also find that the level of this H{sub 2} formation enhancement in a disk galaxy under RP depends on the mass of its host cluster dark matter halo, the initial positions and velocities of the disk galaxy, and the disk inclination angle with respect to the orbital plane. We demonstrate that dust growth is a key factor in the evolution of the H i and H{sub 2} mass in disk galaxies under strong RP. We discuss how the correlation between H{sub 2} fractions and surface gas densities of disk galaxies evolves with time in the galaxies under RP. We also discuss whether galaxy-wide star formation rates (SFRs) in cluster disk galaxies can be enhanced by RP if the SFRs depend on H{sub 2} densities.« less

42 CFR 433.11 - Enhanced FMAP rate for children.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 4 2011-10-01 2011-10-01 false Enhanced FMAP rate for children. 433.11 Section 433... Administration Provisions § 433.11 Enhanced FMAP rate for children. (a) Subject to the conditions in paragraph (b... targeted low-income children described in § 435.4 or § 436.3 of this chapter; and (2) Services provided to...

42 CFR 433.11 - Enhanced FMAP rate for children.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 4 2010-10-01 2010-10-01 false Enhanced FMAP rate for children. 433.11 Section 433... Administration Provisions § 433.11 Enhanced FMAP rate for children. (a) Subject to the conditions in paragraph (b... targeted low-income children described in § 435.4 or § 436.3 of this chapter; and (2) Services provided to...

42 CFR 433.11 - Enhanced FMAP rate for children.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 4 2012-10-01 2012-10-01 false Enhanced FMAP rate for children. 433.11 Section 433... Administration Provisions § 433.11 Enhanced FMAP rate for children. (a) Subject to the conditions in paragraph (b... targeted low-income children described in § 435.4 or § 436.3 of this chapter; and (2) Services provided to...

42 CFR 433.11 - Enhanced FMAP rate for children.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 4 2014-10-01 2014-10-01 false Enhanced FMAP rate for children. 433.11 Section 433... Administration Provisions § 433.11 Enhanced FMAP rate for children. (a) Subject to the conditions in paragraph (b... targeted low-income children described in § 435.4 or § 436.3 of this chapter; and (2) Services provided to...

42 CFR 433.11 - Enhanced FMAP rate for children.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 4 2013-10-01 2013-10-01 false Enhanced FMAP rate for children. 433.11 Section 433... Administration Provisions § 433.11 Enhanced FMAP rate for children. (a) Subject to the conditions in paragraph (b... targeted low-income children described in § 435.4 or § 436.3 of this chapter; and (2) Services provided to...

Phencyclidine administration during neurodevelopment alters network activity in prefrontal cortex and hippocampus in adult rats.

PubMed

Kjaerby, Celia; Hovelsø, Nanna; Dalby, Nils Ole; Sotty, Florence

2017-08-01

Symptoms of schizophrenia have been linked to insults during neurodevelopment such as NMDA receptor (NMDAR) antagonist exposure. In animal models, this leads to schizophrenia-like behavioral symptoms as well as molecular and functional changes within hippocampal and prefrontal regions. The aim of this study was to determine how administration of the NMDAR antagonist phencyclidine (PCP) during neurodevelopment affects functional network activity within the hippocampus and medial prefrontal cortex (mPFC). We recorded field potentials in vivo after electrical brain stem stimulation and observed a suppression of evoked theta power in ventral hippocampus, while evoked gamma power in mPFC was enhanced in rats administered with PCP neonatally. In addition, increased gamma synchrony elicited by acute administration of the NMDAR antagonist MK-801 was exaggerated in neonatal PCP animals. These data suggest that NMDAR antagonist exposure during brain development alters functional networks within hippocampus and mPFC possibly contributing to the reported behavioral symptoms of this animal model of schizophrenia. NEW & NOTEWORTHY We show that insults with a NMDA receptor antagonist during neurodevelopment lead to suppressed evoked theta oscillations in ventral hippocampus in adult rats, while evoked gamma oscillations are enhanced and hypersensitive to an acute challenge with a NMDA receptor antagonist in prefrontal cortex. These observations reveal the significance of neurodevelopmental disturbances in the evolvement of schizophrenia-like symptoms and contribute to the understanding of the functional deficits underlying aberrant behavior in this disease. Copyright © 2017 the American Physiological Society.

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...

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...

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...

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...

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...

Nerve growth factor enhances cough via a central mechanism of action.

PubMed

El-Hashim, Ahmed Z; Jaffal, Sahar M; Al-Rashidi, Fatma T; Luqmani, Yunus A; Akhtar, Saghir

2013-08-01

The mechanisms involved in enhanced cough induced by central and inhaled NGF in guinea pigs were investigated. Cough and airway function were assessed by plethysmography following inhaled or intracerebroventricular (i.c.v.) NGF treatment. Expression of TrkA and/or TRPV1 was determined in bronchi and/or brainstem by real-time PCR and immunoblotting. I.c.v. and inhaled NGF enhanced citric acid induced-cough and airway obstruction. Pretreatment (i.c.v.) with antagonists of TrkA (K252a) or TRPV1 (IRTX) significantly reduced both the NGF (i.c.v.) enhanced cough and airway obstruction whereas the NK1 antagonist (FK888) inhibited only cough. The H1 antagonist (cetirizine) did not affect either. Inhaled NGF increased phosphorylation of TrkA receptors in the bronchi but not the brainstem at 0.5h post-treatment. TrkA mRNA was elevated at 0.5h in the bronchi and at 24h in the brainstem while TRPV1 mRNA was elevated from 0.5h to 24h in brainstem and at 24h in the bronchi. Pretreatment (i.c.v.) with IRTX, but not K252a, significantly inhibited the inhaled NGF-enhanced cough. Central NGF administration enhances cough and airway obstruction by mechanisms dependent on central activation of TrkA, TRPV1 and NK1 receptors while inhaled NGF enhances cough via a mechanism dependent on central TRPV1 and not TrkA receptors. These data show that NGF, in addition to its effects on the airways, has an important central mechanism of action in the enhancement of cough. Therefore, therapeutic strategies targeting NGF signaling in both the airways and CNS may be more effective in the management of cough. Copyright © 2013 Elsevier Ltd. All rights reserved.

Development of NASA Technical Standards Program Relative to Enhancing Engineering Capabilities

NASA Technical Reports Server (NTRS)

Gill, Paul S.; Vaughan, William W.

2003-01-01

The enhancement of engineering capabilities is an important aspect of any organization; especially those engaged in aerospace development activities. Technical Standards are one of the key elements of this endeavor. The NASA Technical Standards Program was formed in 1997 in response to the NASA Administrator s directive to develop an Agencywide Technical Standards Program. The Program s principal objective involved the converting Center-unique technical standards into Agency wide standards and the adoption/endorsement of non-Government technical standards in lieu of government standards. In the process of these actions, the potential for further enhancement of the Agency s engineering capabilities was noted relative to value of being able to access Agencywide the necessary full-text technical standards, standards update notifications, and integration of lessons learned with technical standards, all available to the user from one Website. This was accomplished and is now being enhanced based on feedbacks from the Agency's engineering staff and supporting contractors. This paper addresses the development experiences with the NASA Technical Standards Program and the enhancement of the Agency's engineering capabilities provided by the Program s products. Metrics are provided on significant aspects of the Program.

Protection against bovine tuberculosis induced by oral vaccination of cattle with Mycobacterium bovis BCG is not enhanced by co-administration of mycobacterial protein vaccines.

PubMed

Wedlock, D Neil; Aldwell, Frank E; Vordermeier, H Martin; Hewinson, R Glyn; Buddle, Bryce M

2011-12-15

Mycobacterium bovis bacille Calmette-Guérin (BCG) delivered to calves by the oral route in a formulated lipid matrix has been previously shown to induce protection against bovine tuberculosis. A study was conducted in cattle to determine if a combination of a low dose of oral BCG and a protein vaccine could induce protective immunity to tuberculosis while not sensitising animals to tuberculin. Groups of calves (10 per group) were vaccinated by administering 2 × 10(7)colony forming units (CFU) of BCG orally or a combination of 2 × 10(7)CFU oral BCG and a protein vaccine comprised of M. bovis culture filtrate proteins (CFP) formulated with the adjuvants Chitin and Gel 01 and delivered by the intranasal route, or CFP formulated with Emulsigen and the TLR2 agonist Pam(3)CSK(4) and administered by the subcutaneous (s.c.) route. Two further groups were vaccinated with the CFP/Chitin/Gel 01 or CFP/Emulsigen/Pam(3)CSK(4) vaccines alone. Positive control groups were given 10(8)CFU oral BCG or 10(6)CFU s.c. BCG while a negative control group was non-vaccinated. All animals were challenged with M. bovis 15 weeks after vaccination and euthanized and necropsied at 16 weeks following challenge. Groups of cattle vaccinated with s.c. BCG, 10(8)CFU or 2 × 10(7)CFU oral BCG showed significant reductions in seven, three and four pathological or microbiological disease parameters, respectively, compared to the results for the non-vaccinated group. There was no evidence of protection in calves vaccinated with the combination of oral BCG and CFP/Emulsigen/Pam(3)CSK(4) or oral BCG and CFP/Chitin/Gel 01 or vaccinated with the protein vaccines alone. Positive responses in the comparative cervical skin test at 12 weeks after vaccination were only observed in animals vaccinated with s.c. BCG, 10(8)CFU oral BCG or a combination of 2 × 10(7)CFU oral BCG and CFP/Chitin/Gel 01. In conclusion, co-administration of a protein vaccine, administered by either systemic or mucosal routes with oral

Vitamin C metabolites, independent of smoking status, significantly enhance leukocyte, but not plasma ascorbate concentrations.

PubMed

Moyad, Mark A; Combs, Maile A; Vrablic, Angelica S; Velasquez, Janet; Turner, Benilda; Bernal, Samuel

2008-10-01

The objective of this study was to test the effects of acute doses of vitamin C alone, calcium ascorbate with vitamin C metabolites, and placebo, on total plasma and leukocyte vitamin C concentrations over 24 hours. A double-blind, placebo-controlled, four-way crossover study was performed consisting of four separate phases lasting 24 hours each and utilizing one of four oral 1000-mg preparations within each phase (one of vitamin C alone, two separate vitamin C formulations of calcium ascorbate with vitamin C metabolites, and placebo). There was a 7-day washout between phases, and blood draws at seven time points within each phase of the study for a total of 28 serologic measurements per subject and 420 total measurements for the entire clinical trial. Vitamin C concentration in plasma and leukocytes were measured by high-performance liquid chromatography at baseline and at six sequential time periods over 24 hours. Fifteen healthy males were enrolled, aged 18-39 years; nine were had never smoked and six were chronic smokers. No significant difference in plasma vitamin C levels was observed when comparing the different preparations. However, at 24 hours, calcium ascorbate with metabolites resulted in significantly higher concentrations of vitamin C in leukocytes (P<0.0001) compared with vitamin C alone. These results were similar for both metabolite formulations, and independent of smoking status. Regardless of smoking status, vitamin C metabolites may enhance leukocyte utilization of vitamin C itself, despite no consistent difference in plasma levels among the different preparations. A larger clinical investigation is warranted to confirm these preliminary findings, and to determine the clinical relevance of this impact on overall immune function.

Co-administration of delta- and mu-opioid receptor agonists promotes peripheral opioid receptor function

PubMed Central

Schramm, Cicely L.; Honda, Christopher N.

2010-01-01

Enhancement of peripheral opioid analgesia following tissue injury or inflammation in animal models is well-documented, but clinical results of peripheral opioid therapy remain inconsistent. Previous studies in the central nervous system have shown that co-administration of μ- and δ-opioid receptor agonists can enhance analgesic outcomes; however, less is known about the functional consequences of opioid receptor interactions in the periphery. The present study examines the effects of intraplantar injection of the μ- and δ-opioid receptor agonists, morphine and deltorphin, alone and in combination on behavioral tests of nociception in naïve rats and on potassium-evoked release of CGRP from sciatic nerves of naïve rats. Neither drug alone affected nociceptive behaviors or CGRP release. Two separate measures of mechanical nociceptive sensitivity remained unchanged after co-administration of the two drugs. In contrast, when deltorphin was co-injected with morphine, dose-dependent and peripherally-restricted increases in paw withdrawal latencies to radiant heat were observed. Similarly, concentration-dependent inhibition of CGRP release was observed when deltorphin and morphine were administered in sequence prior to potassium stimulation. However, no inhibition was observed when morphine was administered prior to deltorphin. All combined opioid effects were blocked by co-application of antagonists. Deltorphin exposure also enhanced the in vivo and in vitro effects of another μ-opioid receptor agonist, DAMGO. Together, these results suggest that under normal conditions, δ-opioid receptor agonists enhance the effect of μ-opioid receptor agonists in the periphery, and local co-administration of δ- and μ-opioid receptor agonists may improve results of peripheral opioid therapy for the treatment of pain. PMID:20970925

Protect and enhance: Lowi's juridical democracy and the prevention of significant deterioration of air quality

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

Meiburg, A.S.

1986-01-01

The capture of Federal regulatory agencies by the groups they were supposed to be regulating has been a topic of concern in the traditional literature of public administration. In his influential book The End of Liberalism, Professor Theordore Lowi suggested that capture resulted in part from vauge delegations of authority of Congress to regulatory agencies. Lowi argued that democracy would be better served if Congress were more specific in drafting laws, if agencies made greater use of formal rulemaking in implementing them, and if the courts rejected statutes which contained excessively vague delegations of authority - a remedy which hemore » labeled juridicial democracy. This dissertation examines Lowi's theory in light of the experience of Congress and the Environmental Protection Agency (EPA) with the requirements of the Clean Air Act to prevent the significant deterioration of air quality in areas where air was already relatively clean. The history of the program to develop and carry out these requirements, known as PSD, is described in detail from its inception in the late 1960's through EPA's final regulations in 1980. Special attention is given to the actions taken by EPA after environmental groups successfully used the courts to force EPA to develop a PSD program in 1974, how Congress responded by amending the Clean Air Act in 1977, and the difficulties these amendments and subsequent additional court reviews caused for EPA.« less

Oral administration of fisetin promotes the induction of hippocampal long-term potentiation in vivo.

PubMed

He, Wen-Bin; Abe, Kazuho; Akaishi, Tatsuhiro

2018-01-01

To explore memory enhancing effect of the flavonoid fisetin, we investigated the effect of oral administration of flavonoids on the induction of long-term potentiation (LTP) at hippocampal CA1 synapses of anesthetized rats. Among four flavonoids (fisetin, quercetin, luteolin and myricetin) tested, only fisetin significantly facilitated the induction of hippocampal LTP. The effect of oral fisetin was abolished by intracerebroventricular injection of U0126, an agent that was previously found to inhibit its effect in hippocampal slices in vitro. These results suggest that orally administered fisetin crosses the blood-brain barrier and promotes synaptic functions in the hippocampus. Copyright © 2018 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

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

Role of tangeretin as a potential bioavailability enhancer for silybin: Pharmacokinetic and pharmacological studies.

PubMed

Yuan, Zhong-Wen; Li, Ya-Zhuo; Liu, Zhong-Qiu; Feng, Sen-Ling; Zhou, Hua; Liu, Chang-Xiao; Liu, Liang; Xie, Ying

2018-02-01

Biological responses of a variety of naturally occurring compounds in vivo were restrained by their poor oral bioavailability. Silybin, as one of the active ingredients of silymarin, has presented promising bioactivity for the treatment of chronic liver diseases and cancer. However, its exposure in body was limited. In this study, silybin was demonstrated to be substrates of both BCRP and MRP2 by utilizing monolayer Caco-2 cell model and confirmed in MDCK cells overexpressing specific efflux transporter. Of all compounds screened, tangeretin, a potent inhibitor of efflux transporters of BCRP, MRP2 and P-gp, was able to enhance exposure of silybin by inhibiting functions of the barriers mediating transcellular transport. Moreover, study carried out in sandwich-cultured rat hepatocyte (SCH) model showed that the biliary excretion index (BEI) and in vitro biliary clearance of silybin decreased as levels of tangeretin increased, indicating efflux transporters mediating biliary excretion of silybin might be involved. Pharmacokinetic behaviors of silybin in rats were altered by co-administration of tangeretin, in terms of increased AUC and Cmax of silybin by comparing with that of silybin given alone. In addition, results coming from CCl 4 -induced acute liver injury rat model revealed that protection effect of silybin against liver damage in the presence of tangeretin was significantly enhanced. All these data were evident that efflux transporters play a critical role in transcellular transport of silybin and account for its low bioavailability. Enhanced bioavailability of silybin with co-administration of tangeretin by significantly inhibiting the efflux transporters further boost its bioactivity which is of particular importance in clinical use. Copyright © 2017. Published by Elsevier Ltd.

Fresh onion juice enhanced copulatory behavior in male rats with and without paroxetine-induced sexual dysfunction.

PubMed

Allouh, Mohammed Z; Daradka, Haytham M; Al Barbarawi, Mohammed M; Mustafa, Ayman G

2014-02-01

Onion (Allium cepa) is one of the most commonly cultivated species of the family Liliaceae, and has long been used in dietary and therapeutic applications. Treatment with fresh onion juice has been reported to promote testosterone production in male rats. Testosterone is the male sex hormone responsible for enhancing sexual libido and potency. This study aimed to investigate the effects of onion juice on copulatory behavior of sexually potent male rats and in male rats with paroxetine-induced sexual dysfunction. Sexually experienced male rats were divided into seven groups: a control group, three onion juice-treated groups, a paroxetine-treated group, and two groups treated with paroxetine plus different doses of onion juice. At the end of the treatments, sexual behavior parameters and testosterone levels were measured and compared among the groups. Administration of onion juice significantly reduced mount frequency and latency and increased the copulatory efficacy of potent male rats. In addition, administration of onion juice attenuated the prolonged ejaculatory latency period induced by paroxetine and increased the percentage of ejaculating rats. Serum testosterone levels increased significantly by onion juice administration. However, a significant reduction in testosterone because of paroxetine therapy was observed. This reduction was restored to normal levels by administration of onion juice. This study conclusively demonstrates that fresh onion juice improves copulatory behavior in sexually potent male rats and in those with paroxetine-induced sexual dysfunction by increasing serum testosterone levels.

Does administrative support negate the consequences of nurse abuse?

PubMed

Azar, Mathilde; Badr, Lina Kurdahi; Samaha, Helen; Dee, Vivien

2016-01-01

To assess the relationship between disruptive/abusive situations and the 'intention to leave' nursing. While every nurse deserves to feel safe in his or her working environment, nurse abuse remains a common occurrence worldwide. Only when hospitals are safe, is retention enhanced and patient care improved. A cross-sectional survey was conducted with 1053 nurses. Almost 70% of nurses experienced stressful disruptive/abusive situations that were mainly caused by patients/families. The majority felt skilled in dealing with these situations, yet around 40% considered leaving nursing because of disruption/abuse. Stress from disruption/abuse, the skill in dealing with abuse and the administrations' support were the best predictors for the 'intention to leave'. It may not be the amount of abuse per se that affects the nurses' intention to leave, but rather how the abuse is perceived, the skill in dealing with it and the support received from administration. The support received from nursing administration may negate the effect of stress and the 'intention to leave' because of disruptive/abusive situations. This should behove nurse managers and administrators to have a system in place to provide support for nurses, which in turn could improve job satisfaction and retention. © 2015 John Wiley & Sons Ltd.

Enhancing the Predictive Potential of Personality: Isolating Multiple Components of Trait Expression via a Single Administration Design

DTIC Science & Technology

2015-03-01

109 8.0 Arts, Design, Entertainment, Media, Sports , and Recreation 100 7.4 Information Technology 86 6.3 Office and Administrative Support 74 5.5...55 4.1 Government and Public Administration 35 2.6 Community and Social Service 29 2.1 Manufacturing 29 2.1 Hospitality and Tourism 25 1.8...playing a sport ; exercising; or doing yard work or housework. % Not descriptive of me % Somewhat descriptive of me % Very descriptive of me N/A

Oral Administration of Lactobacillus plantarum Strain AYA Enhances IgA Secretion and Provides Survival Protection against Influenza Virus Infection in Mice

PubMed Central

Kikuchi, Yosuke; Kunitoh-Asari, Ayami; Hayakawa, Katsuyuki; Imai, Shinjiro; Kasuya, Kenji; Abe, Kimio; Adachi, Yu; Fukudome, Shin-ichi; Takahashi, Yoshimasa; Hachimura, Satoshi

2014-01-01

The mucosal immune system provides the first line of defense against inhaled and ingested pathogenic microbacteria and viruses. This defense system, to a large extent, is mediated by the actions of secretory IgA. In this study, we screened 140 strains of lactic acid bacteria for induction of IgA production by murine Peyer’s patch cells. We selected one strain and named it Lactobacillus plantarum AYA. We found that L. plantarum AYA-induced production of IL-6 in Peyer’s patch dendritic cells, with this production promoting IgA+ B cells to differentiate into IgA-secreting plasma cells. We also observed that oral administration of L. plantarum AYA in mice caused an increase in IgA production in the small intestine and lung. This production of IgA correlated strongly with protective ability, with the treated mice surviving longer than the control mice after lethal influenza virus infection. Our data therefore reveals a novel immunoregulatory role of the L. plantarum AYA strain which enhances mucosal IgA production and provides protection against respiratory influenza virus infection. PMID:24466081

Oral administration of Lactobacillus plantarum strain AYA enhances IgA secretion and provides survival protection against influenza virus infection in mice.

PubMed

Kikuchi, Yosuke; Kunitoh-Asari, Ayami; Hayakawa, Katsuyuki; Imai, Shinjiro; Kasuya, Kenji; Abe, Kimio; Adachi, Yu; Fukudome, Shin-Ichi; Takahashi, Yoshimasa; Hachimura, Satoshi

2014-01-01

The mucosal immune system provides the first line of defense against inhaled and ingested pathogenic microbacteria and viruses. This defense system, to a large extent, is mediated by the actions of secretory IgA. In this study, we screened 140 strains of lactic acid bacteria for induction of IgA production by murine Peyer's patch cells. We selected one strain and named it Lactobacillus plantarum AYA. We found that L. plantarum AYA-induced production of IL-6 in Peyer's patch dendritic cells, with this production promoting IgA(+) B cells to differentiate into IgA-secreting plasma cells. We also observed that oral administration of L. plantarum AYA in mice caused an increase in IgA production in the small intestine and lung. This production of IgA correlated strongly with protective ability, with the treated mice surviving longer than the control mice after lethal influenza virus infection. Our data therefore reveals a novel immunoregulatory role of the L. plantarum AYA strain which enhances mucosal IgA production and provides protection against respiratory influenza virus infection.

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.

Lack of dopamine supersensitivity in rats after chronic administration of blonanserin: Comparison with haloperidol.

PubMed

Hashimoto, Takashi; Baba, Satoko; Ikeda, Hiroko; Oda, Yasunori; Hashimoto, Kenji; Shimizu, Isao

2018-07-05

Long-term treatment with antipsychotic drugs in patients with schizophrenia can lead to dopamine supersensitivity psychosis. It is reported that repeated administration of haloperidol caused dopamine supersensitivity in rats. Blonanserin is an atypical antipsychotic drug with high affinity for dopamine D 2 , D 3 and serotonin 2A receptors. In this study, we investigated whether chronic administration of blonanserin leads to dopamine supersensitivity. Following oral treatment with blonanserin (0.78 mg/kg) or haloperidol (1.1 mg/kg) twice daily for 28 days, the dopamine D 2 agonist quinpirole-induced hyperlocomotion test and a dopamine D 2 receptor binding assay were conducted. We found that haloperidol significantly enhanced both quinpirole-induced hyperlocomotion and striatal dopamine D 2 receptor density in rats. On the other hand, repeated administration of blonanserin had no effect on either locomotor activity or striatal dopamine D 2 receptor density. Further, our results show that mRNA levels of dopamine D 2 and D 3 receptors in several brain regions were unaffected by repeated administration of both agents. In addition, we examined the effect of the dopamine D 3 receptor antagonist PG-01037 on development of dopamine supersensitivity induced by chronic haloperidol treatment and showed that PG-01037 prevents the development of supersensitivity to quinpirole in chronic haloperidol-treated rats. Given the higher affinity of blonanserin at dopamine D 3 receptors than haloperidol, antagonism of blonanserin at dopamine D 3 receptors may play a role in lack of dopamine supersensitivity after chronic administration. The present findings suggest long-term treatment with antipsychotic dose of blonanserin may be unlikely to lead to dopamine supersensitivity. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

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.

Peripheral Administration of a Long-Acting Peptide Oxytocin Receptor Agonist Inhibits Fear-Induced Freezing.

PubMed

Modi, Meera E; Majchrzak, Mark J; Fonseca, Kari R; Doran, Angela; Osgood, Sarah; Vanase-Frawley, Michelle; Feyfant, Eric; McInnes, Heather; Darvari, Ramin; Buhl, Derek L; Kablaoui, Natasha M

2016-08-01

Oxytocin (OT) modulates the expression of social and emotional behaviors and consequently has been proposed as a pharmacologic treatment of psychiatric diseases, including autism spectrum disorders and schizophrenia; however, endogenous OT has a short half-life in plasma and poor permeability across the blood-brain barrier. Recent efforts have focused on the development of novel drug delivery methods to enhance brain penetration, but few efforts have aimed at improving its half-life. To explore the behavioral efficacy of an OT analog with enhanced plasma stability, we developed PF-06655075 (PF1), a novel non-brain-penetrant OT receptor agonist with increased selectivity for the OT receptor and significantly increased pharmacokinetic stability. PF-06478939 was generated with only increased stability to disambiguate changes to selectivity versus stability. The efficacy of these compounds in evoking behavioral effects was tested in a conditioned fear paradigm. Both central and peripheral administration of PF1 inhibited freezing in response to a conditioned fear stimulus. Peripheral administration of PF1 resulted in a sustained level of plasma concentrations for greater than 20 hours but no detectable accumulation in brain tissue, suggesting that plasma or cerebrospinal fluid exposure was sufficient to evoke behavioral effects. Behavioral efficacy of peripherally administered OT receptor agonists on conditioned fear response opens the door to potential peripheral mechanisms in other behavioral paradigms, whether they are mediated by direct peripheral activation or feed-forward responses. Compound PF1 is freely available as a tool compound to further explore the role of peripheral OT in behavioral response. Copyright © 2016 The Author(s).

Oral administration with diosgenin enhances the induction of intestinal T helper 1-like regulatory T cells in a murine model of food allergy.

PubMed

Huang, Chung-Hsiung; Wang, Chia-Chi; Lin, Yu-Chin; Hori, Masatoshi; Jan, Tong-Rong

2017-01-01

Although the development of T helper (Th)1-like regulatory T (Treg) cells under Th1 inflammatory conditions has been reported, the role of Th1-like Treg cells in Th2 allergic responses remains mostly unclear. We previously demonstrated that diosgenin, the major sapogenin contained in the Chinese yam, attenuated food allergy and augmented Th1 and Treg immune responses. In this study, we hypothesized that diosgenin may enhance the induction of Th1-like Treg cells in the gut of mice with food allergy. Ovalbumin (OVA)-sensitized BALB/c mice were gavaged daily with diosgenin and received repeatedly intragastric ovalbumin challenges to induce intestinal allergic responses. The induction of Foxp3 + Treg cells co-expressing Th1-type transcription factors, cytokines and chemokines in the intestine was examined, and the mRNA expression of the chemokines corresponding to Th1-like Treg cells was measured. Diosgenin administration increased the number of Foxp3 + Treg cells co-expressing Th1 markers, including CCR5, CXCR3, IFN-γ and T-bet in the intestine, and enhanced populations of Foxp3 + IFN-γ + and Foxp3 + T-bet + cells that expressed the regulatory cytokine IL-10 in the Peyer's patches. Diosgenin also augmented the intestinal expression of CXCR3, CCL3, and CXCL10. Concordantly, diosgenin increased the number of CXCR3 + Foxp3 + IL-10 cells in the Peyer's patches. Our data demonstrated the enhanced induction of Th1-like Treg cells in allergic mice treated with diosgenin, providing evidence to suggest a role for Th1-like Treg cells in diosgenin-mediated anti-allergic effects against Th2-type allergy. Copyright © 2016 Elsevier B.V. All rights reserved.

Regional Intraosseous Administration of Prophylactic Antibiotics is More Effective Than Systemic Administration in a Mouse Model of TKA.

PubMed

Young, Simon W; Roberts, Tim; Johnson, Sarah; Dalton, James P; Coleman, Brendan; Wiles, Siouxsie

2015-11-01

antibiotics was more effective than same-dose IV administration in reducing bacterial load on recovered implants (median CFUs < 7.0 × 10(0) vs 2.83 × 10(2), p = 0.0183). IORA of prophylactic cefazolin and vancomycin was more effective than the same dose of antibiotic given systemically. The effectiveness of vancomycin in particular was enhanced by IORA of prophylactic antibiotics despite using a lower dose. Our study supports previous studies of IORA of prophylactic antibiotics in humans and suggests this novel form of administration has the potential to enhance the effectiveness of prophylaxis in TKA. Because of concerns regarding antibiotic stewardship, IORA of prophylactic vancomycin may be more appropriately restricted to patients having TKA who are at greater risk of infection, and clinical trials are in progress.

Changes in sleep electroencephalogram and nocturnal hormone secretion after administration of the antidyskinetic agent sarizotan in healthy young male volunteers.

PubMed

Kuenzel, Heike E; Steiger, Axel; Held, Katja; Antonijevic, Irina A; Frieboes, Ralf-Michael; Murck, Harald

2005-07-01

Sarizotan is a 5-HT(1A) agonist with high affinity to D(3) and D(4) receptors. In animal experiments, the drug shows a strong anti-cataleptic effect and suppresses effectively dyskinesias in animal models of L: -dopa-induced dyskinesia and of tardive dyskinesia. Data from an open pilot study in patients with Parkinson's disease show clear indication of a treatment effect against L: -dopa-induced dyskinesia. CNS-active drugs are known to modulate sleep electroencephalogram (EEG) and sleep-related hormone secretion. 5-HT(1A) agonists suppress rapid-eye movement (REM) sleep and enhance the secretion of ACTH, cortisol, prolactin and growth hormone (GH) at daytime. We hypothesised that sarizotan shares these effects. Furthermore, we were interested in the influence of sarizotan on leptin, which participates in the regulation of the energy balance and is enhanced after various psychoactive drugs. Ten healthy male subjects were investigated twice in a double-blind, placebo-controlled crossover design. Sleep EEG and nocturnal hormone secretion of ACTH, cortisol, prolactin, GH and leptin were examined after oral administration of either placebo or 20 mg of sarizotan at night. After administration of sarizotan, a significant reduction of REM sleep and total sleep time in conventional sleep EEG and a significant reduction of sigma- and theta-power in spectral analysis were observed. The main effect on nocturnal hormone secretion was a significant elevation of prolactin and of ACTH in the first half of the night. While REM sleep was suppressed, the endocrine effects of 20 mg sarizotan at night were weak. Its sleep-endocrine profile is comparable to the effects provoked by selective 5-HT reuptake inhibitors.

Probiotic helminth administration in relapsing-remitting multiple sclerosis: a phase 1 study.

PubMed

Fleming, J O; Isaak, A; Lee, J E; Luzzio, C C; Carrithers, M D; Cook, T D; Field, A S; Boland, J; Fabry, Z

2011-06-01

Probiotic treatment strategy based on the hygiene hypothesis, such as administration of ova from the non-pathogenic helminth, Trichuris suis, (TSO) has proven safe and effective in autoimmune inflammatory bowel disease. To study the safety and effects of TSO in a second autoimmune disease, multiple sclerosis (MS), we conducted the phase 1 Helminth-induced Immunomodulatory Therapy (HINT 1) study. Five subjects with newly diagnosed, treatment-naive relapsing-remitting multiple sclerosis (RRMS) were given 2500 TSO orally every 2 weeks for 3 months in a baseline versus treatment control exploratory trial. The mean number of new gadolinium-enhancing magnetic resonance imaging (MRI) lesions (n-Gd+) fell from 6.6 at baseline to 2.0 at the end of TSO administration, and 2 months after TSO was discontinued, the mean number of n-Gd+ rose to 5.8. No significant adverse effects were observed. In preliminary immunological investigations, increases in the serum level of the cytokines IL-4 and IL-10 were noted in four of the five subjects. TSO was well tolerated in the first human study of this novel probiotic in RRMS, and favorable trends were observed in exploratory MRI and immunological assessments. Further investigations will be required to fully explore the safety, effects, and mechanism of action of this immunomodulatory treatment.

l-Serine Enhances Light-Induced Circadian Phase Resetting in Mice and Humans.

PubMed

Yasuo, Shinobu; Iwamoto, Ayaka; Lee, Sang-Il; Ochiai, Shotaro; Hitachi, Rina; Shibata, Satomi; Uotsu, Nobuo; Tarumizu, Chie; Matsuoka, Sayuri; Furuse, Mitsuhiro; Higuchi, Shigekazu

2017-12-01

Background: The circadian clock is modulated by the timing of ingestion or food composition, but the effects of specific nutrients are poorly understood. Objective: We aimed to identify the amino acids that modulate the circadian clock and reset the light-induced circadian phase in mice and humans. Methods: Male CBA/N mice were orally administered 1 of 20 l-amino acids, and the circadian and light-induced phase shifts of wheel-running activity were analyzed. Antagonists of several neurotransmitter pathways were injected before l-serine administration, and light-induced phase shifts were analyzed. In addition, the effect of l-serine on the light-induced phase advance was investigated in healthy male students (mean ± SD age 22.2 ± 1.8 y) by using dim-light melatonin onset (DLMO) determined by saliva samples as an index of the circadian phase. Results: l-Serine administration enhanced light-induced phase shifts in mice (1.86-fold; P < 0.05). Both l-serine and its metabolite d-serine, a coagonist of N -methyl-d-aspartic acid (NMDA) receptors, exerted this effect, but d-serine concentrations in the hypothalamus did not increase after l-serine administration. The effect of l-serine was blocked by picrotoxin, an antagonist of γ-aminobutyric acid A receptors, but not by MK801, an antagonist of NMDA receptors. l-Serine administration altered the long-term expression patterns of clock genes in the suprachiasmatic nuclei. After advancing the light-dark cycle by 6 h, l-serine administration slightly accelerated re-entrainment to the shifted cycle. In humans, l-serine ingestion before bedtime induced significantly larger phase advances of DLMO after bright-light exposure during the morning (means ± SEMs-l-serine: 25.9 ± 6.6 min; placebo: 12.1 ± 7.0 min; P < 0.05). Conclusion: These results suggest that l-serine enhances light-induced phase resetting in mice and humans, and it may be useful for treating circadian disturbances. © 2017 American Society for Nutrition.

Rapid and reversible enhancement of blood–brain barrier permeability using lysophosphatidic acid

PubMed Central

On, Ngoc H; Savant, Sanjot; Toews, Myron; Miller, Donald W

2013-01-01

The present study characterizes the effects of lysophosphatidic acid (LPA) on blood–brain barrier (BBB) permeability focusing specifically on the time of onset, duration, and magnitude of LPA-induced changes in cerebrovascular permeability in the mouse using both magnetic resonance imaging (MRI) and near infrared fluorescence imaging (NIFR). Furthermore, potential application of LPA for enhanced drug delivery to the brain was also examined by measuring the brain accumulation of radiolabeled methotrexate. Exposure of primary cultured brain microvessel endothelial cells (BMECs) to LPA produced concentration-dependent increases in permeability that were completely abolished by clostridium toxin B. Administration of LPA disrupted BBB integrity and enhanced the permeability of small molecular weight marker gadolinium diethylenetriaminepentaacetate (Gd-DTPA) contrast agent, the large molecular weight permeability marker, IRdye800cwPEG, and the P-glycoprotein efflux transporter probe, Rhodamine 800 (R800). The increase in BBB permeability occurred within 3 minutes after LPA injection and barrier integrity was restored within 20 minutes. A decreased response to LPA on large macromolecule BBB permeability was observed after repeated administration. The administration of LPA also resulted in 20-fold enhancement of radiolabeled methotrexate in the brain. These studies indicate that administration of LPA in combination with therapeutic agents may increase drug delivery to the brain. PMID:24045401

One day access to a running wheel reduces self-administration of d-methamphetamine, MDMA and Methylone

PubMed Central

Aarde, Shawn M.; Miller, Michelle L.; Creehan, Kevin M.; Vandewater, Sophia A.; Taffe, Michael A.

2015-01-01

Background Exercise influences drug craving and consumption in humans and drug self-administration in laboratory animals, but the effects can be variable. Improved understanding of how exercise affects drug intake or craving would enhance applications of exercise programs to human drug users attempting cessation. Methods Rats were trained in the intravenous self-administration (IVSA) of d-methamphetamine (METH; 0.05 mg/kg/inf), 3,4-methylenedioxymethamphetamine (MDMA; 0.5 mg/kg/inf) or methylone (0.5 mg/kg/inf). Once IVSA was established, the effect of ~22 hrs of wheel access in the home cage on subsequent drug taking was assessed in a two cohort crossover design. Results Provision of home cage wheel access during the day prior to IVSA sessions significantly decreased the self-administration of METH, MDMA and methylone. At the individual level, there was no correlation between the amount a rat used the wheel and the size of the individual’s decrease in drug intake. Conclusions Wheel access can reduce self-administration of a variety of psychomotor stimulants. It does so immediately, i.e., without a need for weeks of exercise prior to drug access. This study therefore indicates that future mechanistic investigations should focus on acute effects of exercise. In sum, the results predict that exercise programs can be used to decrease stimulant drug use in individuals even with no exercise history and an established drug taking pattern. PMID:25863714

Modulation of cytotoxic T lymphocyte, natural killer cell, antibody-dependent cellular cytotoxicity, and antibody-dependent complement-mediated cytotoxicity by Vernonia cinerea L. and vernolide-A in BALB/c mice via enhanced production of cytokines IL-2 and IFN-γ.

PubMed

Pratheeshkumar, Poyil; Kuttan, Girija

2012-02-01

Effect of Vernonia cinerea L. and vernolide-A on cell-mediated immune (CMI) response was studied in normal as well as tumor-bearing BALB/c mice. Administration of V. cinerea and vernolide-A significantly enhanced natural killer (NK) cell activity in both normal as well as tumor-bearing animals, and the activity was observed earlier than in tumor-bearing control animals. Antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent complement-mediated cytotoxicity (ACC) were also enhanced significantly in both normal as well as tumor-bearing animals after V. cinerea and vernolide-A administration compared with untreated control tumor-bearing animals. Extract and vernolide-A showed a significant increase in cytotoxic T lymphocyte (CTL) production in both the in vivo and in vitro models. The level of cytokines such as interleukin (IL)-2 and interferon (IFN)-γ were also enhanced by the treatment of V. cinerea and vernolide-A in both normal as well as tumor-bearing animals. This study demonstrated that V. cinerea extract and vernolide-A stimulate the CTL, NK cell, ADCC, and ADCC through enhanced secretion of IL-2 and IFN-γ.

Cognition Enhancing and Neuromodulatory Propensity of Bacopa monniera Extract Against Scopolamine Induced Cognitive Impairments in Rat Hippocampus.

PubMed

Pandareesh, M D; Anand, T; Khanum, Farhath

2016-05-01

Cognition-enhancing activity of Bacopa monniera extract (BME) was evaluated against scopolamine-induced amnesic rats by novel object recognition test (NOR), elevated plus maze (EPM) and Morris water maze (MWM) tests. Scopolamine (2 mg/kg body wt, i.p.) was used to induce amnesia in rats. Piracetam (200 mg/kg body wt, i.p.) was used as positive control. BME at three different dosages (i.e., 10, 20 and 40 mg/kg body wt.) improved the impairment induced by scopolamine by increasing the discrimination index of NOR and by decreasing the transfer latency of EPM and escape latency of MWM tests. Our results further elucidate that BME administration has normalized the neurotransmitters (acetylcholine, glutamate, 5-hydroxytryptamine, dopamine, 3,4 dihydroxyphenylacetic acid, norepinephrine) levels that were altered by scopolamine administration in hippocampus of rat brain. BME administration also ameliorated scopolamine effect by down-regulating AChE and up-regulating BDNF, muscarinic M1 receptor and CREB expression in brain hippocampus confirms the potent neuroprotective role and these results are in corroboration with the earlier in vitro studies. BME administration showed significant protection against scopolamine-induced toxicity by restoring the levels of antioxidant and lipid peroxidation. These results indicate that, cognition-enhancing and neuromodulatory propensity of BME is through modulating the expression of AChE, BDNF, MUS-1, CREB and also by altering the levels of neurotransmitters in hippocampus of rat brain.

Enhancement of myofibrillar proteolysis following infusion of amino acid mixture correlates positively with elevation of core body temperature in rats.

PubMed

Yamaoka, Ippei; Mikura, Mayumi; Nishimura, Masuhiro; Doi, Masako; Kawano, Yuichi; Nakayama, Mitsuo

2008-12-01

Administration of an amino acid (AA) mixture stimulates muscle protein synthesis and elevates core body temperature (T(b)), as characteristically found under anesthetic conditions. We tested the hypothesis that not only AA given, but also AA produced by degradation of endogenous muscular protein are provided for muscle protein synthesis, which is further reflected in T(b) modifications. Rats were intravenously administered an AA mixture or saline in combination with the anesthetic propofol or lipid emulsion. We measured plasma 3-methylhistidine (MeHis) concentrations as an index of myofibrillar protein degradation, rectal temperature and mRNA expression of atrogin-1, MuRF-1 and ubiquitin in gastrocnemius and soleus muscles of rats following 3 h infusion of test solutions. T(b) did not differ significantly between conscious groups, but was higher in the AA group than in the saline group among anesthetized rats. Plasma MeHis concentrations were higher in the AA group than in the saline group under both conditions. Plasma MeHis levels correlated positively with T(b) of rats under both conditions. AA administration decreased mRNA levels of atrogin-1 and ubiquitin in gastrocnemius muscle and all mRNA levels in soleus muscle. These results suggest that AA administration enhances myofibrillar protein degradation and that the change is a determinant of T(b) modification by AA administration. However, the mechanisms underlying AA administration-associated enhancement of myofibrillar proteolysis remains yet to be determined.

Complex imaging features of accidental cerebral intraventricular gadolinium administration.

PubMed

Nayak, Nita B; Huang, Jimmy C; Hathout, Gasser M; Shaba, Wisam; El-Saden, Suzie M

2013-05-01

Gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA) is a contrast agent commonly used for enhancing MRI. In this paper, the authors report on 2 cases of postoperative inadvertent administration of Gd-DTPA directly into a ventriculostomy tubing side port that was mistaken for intravenous tubing. Both cases demonstrated a low signal on MRI throughout the ventricular system and dependent portions of the subarachnoid spaces, which was originally believed to be CSF with areas of T1 shortening in the nondependent portions of the subarachnoid spaces, and misinterpreted as basal leptomeningeal enhancement and meningitis. The authors propose that the appearance of profound T1 hypointensity within the ventricles and diffuse susceptibility artifact along the ependyma is pathognomonic of intraventricular Gd-DTPA and should be recognized.

Coordinating Technological Resources in a Non-Technical Profession: The Administrative Computer User Group.

ERIC Educational Resources Information Center

Rollo, J. Michael; Marmarchev, Helen L.

1999-01-01

The explosion of computer applications in the modern workplace has required student affairs professionals to keep pace with technological advances for office productivity. This article recommends establishing an administrative computer user groups, utilizing coordinated web site development, and enhancing working relationships as ways of dealing…

Enhancement of Intermittent Androgen Ablation Therapy by Finasteride Administration in Animal Models

DTIC Science & Technology

2003-02-01

that intermittent androgen ablation therapy can be enhanced by finasteride , an inhibitor of T to DHT conversion, To test our hypothesis in animal...models, it is necessary to deliver exogenous T at physiologic levels and finasteride over a long period of time, We have worked out conditions to deliver T and finasteride in nude mice, which will allow us to test our hypothesis.

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,…

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

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 :...

Enhancing the Effectiveness of Significant Event Analysis: Exploring Personal Impact and Applying Systems Thinking in Primary Care

PubMed Central

McNaughton, Elaine; Bruce, David; Holly, Deirdre; Forrest, Eleanor; Macleod, Marion; Kennedy, Susan; Power, Ailsa; Toppin, Denis; Black, Irene; Pooley, Janet; Taylor, Audrey; Swanson, Vivien; Kelly, Moya; Ferguson, Julie; Stirling, Suzanne; Wakeling, Judy; Inglis, Angela; McKay, John; Sargeant, Joan

2016-01-01

Introduction: Significant event analysis (SEA) is well established in many primary care settings but can be poorly implemented. Reasons include the emotional impact on clinicians and limited knowledge of systems thinking in establishing why events happen and formulating improvements. To enhance SEA effectiveness, we developed and tested “guiding tools” based on human factors principles. Methods: Mixed-methods development of guiding tools (Personal Booklet—to help with emotional demands and apply a human factors analysis at the individual level; Desk Pad—to guide a team-based systems analysis; and a written Report Format) by a multiprofessional “expert” group and testing with Scottish primary care practitioners who submitted completed enhanced SEA reports. Evaluation data were collected through questionnaire, telephone interviews, and thematic analysis of SEA reports. Results: Overall, 149/240 care practitioners tested the guiding tools and submitted completed SEA reports (62.1%). Reported understanding of how to undertake SEA improved postintervention (P < .001), while most agreed that the Personal Booklet was practical (88/123, 71.5%) and relevant to dealing with related emotions (93/123, 75.6%). The Desk Pad tool helped focus the SEA on systems issues (85/123, 69.1%), while most found the Report Format clear (94/123, 76.4%) and would recommend it (88/123, 71.5%). Most SEA reports adopted a systems approach to analyses (125/149, 83.9%), care improvement (74/149, 49.7), or planned actions (42/149, 28.2%). Discussion: Applying human factors principles to SEA potentially enables care teams to gain a systems-based understanding of why things go wrong, which may help with related emotional demands and with more effective learning and improvement. PMID:27583996

Enhancing the Effectiveness of Significant Event Analysis: Exploring Personal Impact and Applying Systems Thinking in Primary Care.

PubMed

Bowie, Paul; McNaughton, Elaine; Bruce, David; Holly, Deirdre; Forrest, Eleanor; Macleod, Marion; Kennedy, Susan; Power, Ailsa; Toppin, Denis; Black, Irene; Pooley, Janet; Taylor, Audrey; Swanson, Vivien; Kelly, Moya; Ferguson, Julie; Stirling, Suzanne; Wakeling, Judy; Inglis, Angela; McKay, John; Sargeant, Joan

2016-01-01

Significant event analysis (SEA) is well established in many primary care settings but can be poorly implemented. Reasons include the emotional impact on clinicians and limited knowledge of systems thinking in establishing why events happen and formulating improvements. To enhance SEA effectiveness, we developed and tested "guiding tools" based on human factors principles. Mixed-methods development of guiding tools (Personal Booklet-to help with emotional demands and apply a human factors analysis at the individual level; Desk Pad-to guide a team-based systems analysis; and a written Report Format) by a multiprofessional "expert" group and testing with Scottish primary care practitioners who submitted completed enhanced SEA reports. Evaluation data were collected through questionnaire, telephone interviews, and thematic analysis of SEA reports. Overall, 149/240 care practitioners tested the guiding tools and submitted completed SEA reports (62.1%). Reported understanding of how to undertake SEA improved postintervention (P < .001), while most agreed that the Personal Booklet was practical (88/123, 71.5%) and relevant to dealing with related emotions (93/123, 75.6%). The Desk Pad tool helped focus the SEA on systems issues (85/123, 69.1%), while most found the Report Format clear (94/123, 76.4%) and would recommend it (88/123, 71.5%). Most SEA reports adopted a systems approach to analyses (125/149, 83.9%), care improvement (74/149, 49.7), or planned actions (42/149, 28.2%). Applying human factors principles to SEA potentially enables care teams to gain a systems-based understanding of why things go wrong, which may help with related emotional demands and with more effective learning and improvement.

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.

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)

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…

Gaining hospital administrators' attention: ways to improve physician-hospital management dialogue.

PubMed

Cohn, Kenneth H; Gill, Sandra L; Schwartz, Richard W

2005-02-01

Despite marked differences in training and professional interests, physicians and hospital managers face similar problems stemming from the unprecedented rate of change in the health care delivery system: failure of reimbursement to keep pace with rising costs, new therapeutic modalities, increasing government and managed care regulations, heightened consumerism, and an aging patient population. In the face of these mounting challenges, both physicians and hospital managers could benefit significantly from a climate of collaboration and interdependence. This article presents a "case report" of a community teaching hospital in which practicing physicians and hospital administrators collaborated to develop an operating plan for the next 3 years to improve the practice environment. The physicians recommended new clinical priorities to enhance service to patients and families, to improve physician-physician communication, to develop clinical protocols, and to build coordinated diagnostic treatment centers, which the administration has implemented. Physicians and hospital managers can no longer pass on cost increases at will to patients and third-party payers. Nor can physicians and managers ignore the heightened power of patients and third-party payers. Effective dialogue and collaboration are in all parties' interests to optimize patient care and to develop innovative services. Despite the tensions created by competition and rapid change, transformation from a blaming to a learning environment may be a key strategic advantage in today's health care marketplace.

Studies of drug delivery systems for a therapeutic agent used in osteoporosis. I. Pharmacodynamics (hypocalcemic effect) of elcatonin in rabbits following rectal administration of hollow-type suppositories containing elcatonin.

PubMed

Watanabe, Y; Mizufune, Y; Kubomura, A; Kiriyama, M; Utoguchi, N; Matsumoto, M

1998-11-01

In this study, we developed a new hollow-type suppository containing elcatonin ((Asu1,7)-eel calcitonin, ECT), a synthetic derivative of eel calcitonin, which produces hypocalcemia, as a pharmaceutical preparation for self administration, to be used instead of parenteral injections for patients with osteoporosis. The absorption of ECT from the rectal mucous membrane was evaluated by observation of the decrease in serum calcium (Ca) concentrations following rectal administration in rabbits. ECT was efficiently absorbed from the rectum and effectively decreased serum Ca concentrations. The data of the area under the percent decrease in serum Ca concentration (deltaCa%)-time curve (deltaCa%-AUC), assumed to be an index of the pharmacodynamics (pharmacological effect) of ECT, indicated that similar hypocalcemic effects were obtained following rectal and intravenous administrations of ECT. In regard to the effect of coadministration of other compounds on rectal absorption of ECT, no significant difference in the deltaCa%-AUC between rectal ECT administration with or without nafamostat mesilate (a protease inhibitor) was observed. However, the coadministration of ECT with cytochalasin B or monensin (endocytosis inhibitors) significantly decreased the deltaCa%-AUC, indicating that rectal ECT absorption is probably inhibited by endocytosis inhibitors. On the other hand, it was found that sodium decanoate, a medium-chain fatty acid (sodium salt), significantly enhanced the rectal absorption of ECT. We conclude that this ECT hollow-type suppository offers promise as a new method for the administration of ECT.

Did the corporatization of Portuguese hospitals significantly change their productivity?

PubMed

Ferreira, Diogo; Marques, Rui Cunha

2015-04-01

This paper aims to investigate if the market structure reforms in the Portuguese health system have improved hospital performance and productivity. A robust non-parametric Malmquist index is applied to measure group performance. The significance of the results achieved is examined using a conditional and non-conditional subsampling bootstrapped-based methodology, enhanced by the likelihood cross validation criterion based on the k-nearest neighbors method. The sample contains information about 216 non-corporatized and 176 corporatized Portuguese hospitals for the period 2002–2009. Five models were applied, based on three study dimensions (internment, emergencies and doctor visits). The results show that although corporatized hospitals presented the highest efficiency consistency, they had also the lowest levels of productivity, while the hospitals under the traditional administrative public management system were the ones with the best average performance. However, several best practices were also found in all groups, being the limited companies were often dominated by both noncorporatized and public enterprise entities. Consistent output ranges where all groups present dominance over the others were also identified. It was possible to conclude that the more autonomy the hospital had from the Ministry of Health, the lower was its productivity.

Cannabidiol (CBD) Enhances Lipopolysaccharide (LPS)-Induced Pulmonary Inflammation in C57BL/6 Mice

PubMed Central

Karmaus, Peer W. F.; Wagner, James G.; Harkema, Jack R.; Kaminski, Norbert E.; Kaplan, Barbara L.F.

2012-01-01

Cannabidiol (CBD) is a plant-derived cannabinoid that has been predominantly characterized as anti-inflammatory. However, it is clear that immune effects of cannabinoids can vary with cannabinoid concentration, or type or magnitude of immune stimulus. The present studies demonstrate that oral administration of CBD enhanced lipopolysaccharide (LPS)-induced pulmonary inflammation in C57BL/6 mice. The enhanced inflammatory cell infiltrate as observed in bronchoalveolar lavage fluid (BALF) was comprised mainly of neutrophils, with some monocytes. Concomitantly, CBD enhanced pro-inflammatory cytokine mRNA production, including tumor necrosis factor-α (Tnfa), interleukins (IL) 6 and 23 (Il6, Il23), and granulocyte colony stimulating factor (Gcsf). These results demonstrate that the CBD-mediated enhancement of LPS-induced pulmonary inflammation is mediated at the level of transcription of a variety of pro-inflammatory genes. The significance of these studies is that CBD is part of a therapeutic currently in use for spasticity and pain in multiple sclerosis patients, and therefore it is important to further understand mechanisms by which CBD alters immune function. PMID:23173851

Cannabidiol (CBD) enhances lipopolysaccharide (LPS)-induced pulmonary inflammation in C57BL/6 mice.

PubMed

Karmaus, Peer W F; Wagner, James G; Harkema, Jack R; Kaminski, Norbert E; Kaplan, Barbara L F

2013-01-01

Cannabidiol (CBD) is a plant-derived cannabinoid that has been predominantly characterized as anti-inflammatory. However, it is clear that immune effects of cannabinoids can vary with cannabinoid concentration, or type or magnitude of immune stimulus. The present studies demonstrate that oral administration of CBD enhanced lipopolysaccharide (LPS)-induced pulmonary inflammation in C57BL/6 mice. The enhanced inflammatory cell infiltrate as observed in bronchoalveolar lavage fluid (BALF) was comprised mainly of neutrophils, with some monocytes. Concomitantly, CBD enhanced pro-inflammatory cytokine mRNA production, including tumor necrosis factor-α (Tnfa), interleukins (IL)-5 and -23 (Il6, Il23), and granulocyte colony stimulating factor (Gcsf). These results demonstrate that the CBD-mediated enhancement of LPS-induced pulmonary inflammation is mediated at the level of transcription of a variety of pro-inflammatory genes. The significance of these studies is that CBD is part of a therapeutic currently in use for spasticity and pain in multiple sclerosis patients, and therefore it is important to further understand mechanisms by which CBD alters immune function.

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.

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…

Pharmacological kynurenine 3-monooxygenase enzyme inhibition significantly reduces neuropathic pain in a rat model.

PubMed

Rojewska, Ewelina; Piotrowska, Anna; Makuch, Wioletta; Przewlocka, Barbara; Mika, Joanna

2016-03-01

Recent studies have highlighted the involvement of the kynurenine pathway in the pathology of neurodegenerative diseases, but the role of this system in neuropathic pain requires further extensive research. Therefore, the aim of our study was to examine the role of kynurenine 3-monooxygenase (Kmo), an enzyme that is important in this pathway, in a rat model of neuropathy after chronic constriction injury (CCI) to the sciatic nerve. For the first time, we demonstrated that the injury-induced increase in the Kmo mRNA levels in the spinal cord and the dorsal root ganglia (DRG) was reduced by chronic administration of the microglial inhibitor minocycline and that this effect paralleled a decrease in the intensity of neuropathy. Further, minocycline administration alleviated the lipopolysaccharide (LPS)-induced upregulation of Kmo mRNA expression in microglial cell cultures. Moreover, we demonstrated that not only indirect inhibition of Kmo using minocycline but also direct inhibition using Kmo inhibitors (Ro61-6048 and JM6) decreased neuropathic pain intensity on the third and the seventh days after CCI. Chronic Ro61-6048 administration diminished the protein levels of IBA-1, IL-6, IL-1beta and NOS2 in the spinal cord and/or the DRG. Both Kmo inhibitors potentiated the analgesic properties of morphine. In summary, our data suggest that in neuropathic pain model, inhibiting Kmo function significantly reduces pain symptoms and enhances the effectiveness of morphine. The results of our studies show that the kynurenine pathway is an important mediator of neuropathic pain pathology and indicate that Kmo represents a novel pharmacological target for the treatment of neuropathy. Copyright © 2015 Elsevier Ltd. All rights reserved.

The cardioprotection granted by metoprolol is restricted to its administration prior to coronary reperfusion

PubMed Central

Ibanez, Borja; Cimmino, Giovanni; Prat-González, Susanna; Vilahur, Gemma; Hutter, Randolph; García, Mario J.; Fuster, Valentin; Sanz, Javier; Badimon, Lina; Badimon, Juan J.

2013-01-01

Background Myocardial infarct size is a strong predictor of cardiovascular events. Intravenous metoprolol before coronary reperfusion has been shown to reduce infarct size; however, it is unknown whether oral metoprolol initiated early after reperfusion, as clinical guidelines recommend, is similarly cardioprotective. We compared the extent of myocardial salvage associated with intravenous pre-reperfusion-metoprolol administration in comparison with oral post-reperfusion-metoprolol or placebo. We also studied the effect on suspected markers of reperfusion injury. Methods Thirty Yorkshire-pigs underwent a reperfused myocardial infarction, being randomized to pre-reperfusion-metoprolol, post-reperfusion-metoprolol or placebo. Cardiac magnetic resonance imaging was performed in eighteen pigs at day 3 for the quantification of salvaged myocardium. The amounts of at-risk and infarcted myocardium were quantified using T2-weighted and post-contrast delayed enhancement imaging, respectively. Twelve animals were sacrificed after 24 h for reperfusion injury analysis. Results The pre-reperfusion-metoprolol group had significantly larger salvaged myocardium than the post-reperfusion-metoprolol or the placebo groups (31±4%, 13±6%, and 7±3% of myocardium at-risk respectively). Post-mortem analyses suggest lesser myocardial reperfusion injury in the pre-reperfusion-metoprolol in comparison with the other 2 groups (lower neutrophil infiltration, decreased myocardial apoptosis, and higher activation of the salvage-kinase phospho-Akt). Salvaged myocardium and reperfusion injury pair wise comparisons proved there were significant differences between the pre-reperfusion-metoprolol and the other 2 groups, but not among the latter two. Conclusions The intravenous administration of metoprolol before coronary reperfusion results in larger myocardial salvage than its oral administration initiated early after reperfusion. If confirmed in the clinical setting, the timing and route of �

Synergistic interaction between baclofen administration into the median raphe nucleus and inconsequential visual stimuli on investigatory behavior of rats

PubMed Central

Vollrath-Smith, Fiori R.; Shin, Rick

2011-01-01

Rationale Noncontingent administration of amphetamine into the ventral striatum or systemic nicotine increases responses rewarded by inconsequential visual stimuli. When these drugs are contingently administered, rats learn to self-administer them. We recently found that rats self-administer the GABAB receptor agonist baclofen into the median (MR) or dorsal (DR) raphe nuclei. Objectives We examined whether noncontingent administration of baclofen into the MR or DR increases rats’ investigatory behavior rewarded by a flash of light. Results Contingent presentations of a flash of light slightly increased lever presses. Whereas noncontingent administration of baclofen into the MR or DR did not reliably increase lever presses in the absence of visual stimulus reward, the same manipulation markedly increased lever presses rewarded by the visual stimulus. Heightened locomotor activity induced by intraperitoneal injections of amphetamine (3 mg/kg) failed to concur with increased lever pressing for the visual stimulus. These results indicate that the observed enhancement of visual stimulus seeking is distinct from an enhancement of general locomotor activity. Visual stimulus seeking decreased when baclofen was co-administered with the GABAB receptor antagonist, SCH 50911, confirming the involvement of local GABAB receptors. Seeking for visual stimulus also abated when baclofen administration was preceded by intraperitoneal injections of the dopamine antagonist, SCH 23390 (0.025 mg/kg), suggesting enhanced visual stimulus seeking depends on intact dopamine signals. Conclusions Baclofen administration into the MR or DR increased investigatory behavior induced by visual stimuli. Stimulation of GABAB receptors in the MR and DR appears to disinhibit the motivational process involving stimulus–approach responses. PMID:21904820

Gadolinium-enhanced cardiovascular magnetic resonance: administered dose in relationship to United States Food and Drug Administration (FDA) guidelines.

PubMed

Nacif, Marcelo S; Arai, Andrew E; Lima, Joao A C; Bluemke, David A

2012-02-29

Myocardial late gadolinium enhancement was originally validated using higher than label-recommended doses of gadolinium chelate. The objective of this study was to evaluate available evidence for various gadolinium dosing regimens used for CMR. The relationship of gadolinium dose warnings (due to nephrogenic systemic fibrosis) announced in 2008 to gadolinium dosing regimens was also examined. We conducted a meta-analysis of peer reviewed publications from January, 2004 to December, 2010. Major subject search headings (MeSh) terms from the National Library of Medicine's PubMed were: contrast media, gadolinium, heart, magnetic resonance imaging; searches were limited to human studies with abstracts published in English. Case reports, review articles, editorials, MRA related papers and all reports that did not indicate gadolinium type or weight-based dose were excluded. For all included references, full text was available to determine the total administered gadolinium dose on a per kg basis. Average and median dose values were weighted by the number of subjects in each study. 399 publications were identified in PubMed; 233 studies matched the inclusion criteria, encompassing 19,934 patients with mean age 54.2 ± 11.4 (range 9.3 to 76 years). 34 trials were related to perfusion testing and 199 to myocardial late gadolinium enhancement. In 2004, the weighted-median and weighted-mean contrast dose were 0.15 and 0.16 ± 0.06 mmol/kg, respectively. Median contrast doses for 2005-2010 were: 0.2 mmol/kg for all years, respectively. Mean contrast doses for the years 2005-2010 were: 0.19 ± 0.03, 0.18 ± 0.04, 0.18 ± 0.10, 0.18 ± 0.03, 0.18 ± 0.04 and 0.18 ± 0.04 mmol/kg, respectively (p for trend, NS). Gadopentetate dimeglumine was the most frequent gadolinium type [114 (48.9%) studies]. No change in mean gadolinium dose was present before, versus after the Food and Drug Administration (FDA) black box warning (p > 0.05). Three multi-center dose ranging trials have been

Lifting of Administrative Stay for Hydrogen Sulfide

EPA Pesticide Factsheets

EPA lifted the Administrative Stay of the TRI reporting requirements for hydrogen sulfide. Hydrogen sulfide can reasonably be anticipated to cause chronic health effects in humans and significant adverse effects in aquatic organisms.

75 FR 20717 - Federal Housing Administration: Continuation of FHA Reform; Strengthening Risk Management Through...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-20

... Administration: Continuation of FHA Reform; Strengthening Risk Management Through Responsible FHA-Approved...) that are designed to strengthen FHA by improving its management of risk. This final rule increases the... designed to enhance FHA's risk management functions. The announcement preceded completion of an independent...

Suppression by nimesulide of bombesin-enhanced peritoneal metastasis of intestinal adenocarcinomas induced by azoxymethane in Wistar rats.

PubMed

Iishi, Hiroyasu; Tatsuta, Masaharu; Baba, Miyako; Yano, Hiroyuki; Higashino, Koji; Mukai, Mutsuko; Akedo, Hitoshi

2003-01-01

The effects of the cyclooxygenase (COX)-2 inhibitor nimesulide on bombesin-enhanced peritoneal metastasis of azoxymethane (AOM)-induced intestinal adenocarcinomas were investigated in male Wistar rats. From the beginning of the study, the rats were given 10 weekly s.c. injections of AOM (7.4 mg/kg body weight) and s.c. injections of bombesin (40 microg/kg body weight) every other day. From week 16, the rats were given chow pellets containing 200 ppm or 400 ppm nimesulide ad libitum until termination of the study at week 45. Nimesulide at the higher dose significantly decreased the incidence of bombesin-enhanced metastasis to the peritoneum at week 45, although its administration had little or no effect on the location, histologic type, depth of involvement or infiltrating growth patterns of the tumors. Nimesulide also significantly decreased the incidence of bombesin-enhanced lymphatic vessel invasion by adenocarcinomas. Finally, it also inhibited bombesin-induced matrix metalloproteinase (MMP)-9 and pro-MMP-9 inductions. Our findings indicate that nimesulide may inhibit cancer metastasis through inhibition of pro-MMP-9 and MMP-9 inductions.

Race and Gender Bias in the Administration of Corporal Punishment.

ERIC Educational Resources Information Center

Shaw, Steven R.; Braden, Jeffery B.

1990-01-01

Examined disciplinary actions taken by school building administrators after receiving discipline referral to identify evidence of race and gender bias in administration of corporal punishment (CP). Analysis of discipline files (n=6,244) demonstrated statistically significant relationships between race and CP and between gender and CP. Results…

Implementing the Team Approach in Higher Education: Important Questions and Advice for Administrators

ERIC Educational Resources Information Center

Lara, Tracy M.; Hughey, Aaron W.

2008-01-01

Many companies have implemented the team approach as a way to empower their employees in an effort to enhance productivity, quality and overall profitability. While application of the concept to higher education administration has been limited, colleges and universities could benefit from the team approach if implemented appropriately and…

A Logic for Inclusion of Administrative Domains and Administrators in Multi-domain Authorization

NASA Astrophysics Data System (ADS)

Iranmanesh, Zeinab; Amini, Morteza; Jalili, Rasool

Authorization policies for an administrative domain or a composition of multiple domains in multi-domain environments are determined by either one administrator or multiple administrators' cooperation. Several logic-based models for multi-domain environments' authorization have been proposed; however, they have not considered administrators and administrative domains in policies' representation. In this paper, we propose the syntax, proof theory, and semantics of a logic for multi-domain authorization policies including administrators and administrative domains. Considering administrators in policies provides the possibility of presenting composite administration having applicability in many collaborative applications. Indeed, administrators and administrative domains stated in policies can be used in authorization. The presented logic is based on modal logic and utilizes two calculi named the calculus of administrative domains and the calculus of administrators. It is also proved that the logic is sound. A case study is presented signifying the logic application in practical projects.

Mutual enhancement of IL-2 and IL-7 on DNA vaccine immunogenicity mainly involves regulations on their receptor expression and receptor-expressing lymphocyte generation.

PubMed

Zhang, Yonghong; Liang, Shuang; Li, Xiujin; Wang, Liyue; Zhang, Jianlou; Xu, Jian; Huo, Shanshan; Cao, Xuebin; Zhong, Zhenyu; Zhong, Fei

2015-07-09

Our previous study showed that IL-2 and IL-7 could mutually enhance the immunogenicity of canine parvovirus VP2 DNA vaccine, although the underlying mechanism remained unknown. Here, we used the OVA gene as a DNA vaccine in a mouse model to test their enhancement on DNA vaccine immunogenicity and to explore the molecular mechanism. Results showed that both IL-2 and IL-7 genes significantly increased the immunogenicity of OVA DNA vaccine in mice. Co-administration of IL-2 and IL-7 genes with OVA DNA significantly increased OVA-specific antibody titers, T cell proliferation and IFN-γ production compared with IL-2 or IL-7 alone, confirming that IL-2 and IL-7 mutually enhanced DNA vaccine immunogenicity. Mechanistically, we have shown that IL-2 significantly stimulated generation of IL-7 receptor-expressing lymphocytes, and that IL-7 significantly induced IL-2 receptor expression. These results contribute to an explanation of the mechanism of the mutual effects of IL-2 and IL-7 on enhancing DNA vaccine immunogenicity and provided a basis for further investigation on their mutual effects on adjuvant activity and immune regulation. Copyright © 2015 Elsevier Ltd. All rights reserved.

The Effect of the Oral Administration of Leucine on Endothelial Function, Glucose and Insulin Concentrations in Healthy Subjects.

PubMed

Argyrakopoulou, Georgia; Kontrafouri, Paraskevi; Eleftheriadou, Ioanna; Kokkinos, Alexander; Arapostathi, Christina; Kyriaki, Despoina; Perrea, Despoina; Revenas, Constantinos; Katsilambros, Nicholas; Tentolouris, Nicholas

2018-06-11

The aim of our study was to investigate the potential differential effect of hyperglycaemia and hyperinsulinaemia induced by glucose infusion alone and in combination with leucine consumption on endothelial function in healthy individuals. Ten male volunteers were examined in random order twice. In one visit, they consumed 250 ml water (baseline) and 30 min later glucose was infused iv. In the other visit, they consumed 250 ml water with 25 g of leucine and 30 min later the same amount of glucose was infused. Serum glucose and insulin were measured at baseline and every 10 min after glucose infusion for 1 h. Endothelial function was evaluated by measurement of flow mediated vasodilatation (FMD) at baseline, 10 and 60 min after glucose infusion. In both visits, glucose levels increased to the same degree, whereas insulin response was significantly higher after leucine administration. FMD values declined significantly compared to baseline 10 min after glucose infusion in the control visit (6.9±2.7 vs. 3.2±3.5%, respectively, p=0.006), while no significant change was observed when glucose infusion was followed by leucine consumption. Acute hyperglycaemia impairs endothelial function in healthy male individuals. Leucine administration prevents hyperglycaemia-mediated endothelial dysfunction probably due to enhanced insulin secretion. © Georg Thieme Verlag KG Stuttgart · New York.

Medication administration and interruptions in nursing homes: A qualitative observational study.

PubMed

Odberg, Kristian Ringsby; Hansen, Britt Saetre; Aase, Karina; Wangensteen, Sigrid

2018-03-01

To contribute in-depth knowledge of the characteristics of medication administration and interruptions in nursing homes. The following research questions guided the study: How can the medication administration process in nursing homes be described? How can interruptions during the medication administration process in nursing homes be characterized? Medication administration is a vital process across healthcare settings, and earlier research in nursing homes is sparse. The medication administration process is prone to interruptions that may lead to adverse drug events. On the other hand, interruptions may also have positive effects on patient safety. A qualitative observational study design was applied. Data were collected using partial participant observations. An inductive content analysis was performed. Factors that contributed to the observed complexity of medication administration in nursing homes were the high number of single tasks, varying degree of linearity, the variability of technological solutions, demands regarding documentation and staff's apparent freedom as to how and where to perform medication-related activities. Interruptions during medication administration are prevalent and can be characterised as passive (e.g., alarm and background noises), active (e.g., discussions) or technological interruptions (e.g., use of mobile applications). Most interruptions have negative outcomes, while some have positive outcomes. A process of normalisation has taken place whereby staff put up with second-rate technological solutions, noise and interruptions when they are performing medication-related tasks. Before seeking to minimise interruptions during the medication administration process, it is important to understand the interconnectivity of the elements using a systems approach. Staff and management need to be aware of the normalisation of interruptions. Knowledge of the complexity of medication administration may raise awareness and highlight the importance

Significant enhancement in thermoelectric properties of polycrystalline Pr-doped SrTiO{sub 3−δ} ceramics originating from nonuniform distribution of Pr dopants

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

Dehkordi, Arash Mehdizadeh, E-mail: amehdiz@g.clemson.edu; Bhattacharya, Sriparna; He, Jian

2014-05-12

Recently, we have reported a significant enhancement (>70% at 500 °C) in the thermoelectric power factor (PF) of bulk polycrystalline Pr-doped SrTiO{sub 3} ceramics employing a novel synthesis strategy which led to the highest ever reported values of PF among doped polycrystalline SrTiO{sub 3}. It was found that the formation of Pr-rich grain boundary regions gives rise to an enhancement in carrier mobility. In this Letter, we investigate the electronic and thermal transport in Sr{sub 1−x}Pr{sub x}TiO{sub 3} ceramics in order to determine the optimum doping concentration and to evaluate the overall thermoelectric performance. Simultaneous enhancement in the thermoelectric power factormore » and reduction in thermal conductivity in these samples resulted in more than 30% improvement in the dimensionless thermoelectric figure of merit (ZT) for the whole temperature range over all previously reported maximum values. Maximum ZT value of 0.35 was obtained at 500 °C.« less

Intermittent parathyroid hormone administration improves periodontal healing in rats.

PubMed

Vasconcelos, Daniel Fernando Pereira; Marques, Marcelo Rocha; Benatti, Bruno Braga; Barros, Silvana Pereira; Nociti, Francisco Humberto; Novaes, Pedro Duarte

2014-05-01

Intermittent administration of parathyroid hormone (PTH) promotes new bone formation in patients with osteoporosis and bone fractures. It was shown previously that PTH also reduces periodontitis-related bone loss. The aim of this study is to evaluate the effect of treatment with PTH on periodontal healing in rats. Fenestration defects were created at the buccal surface of the distal root of the mandibular first molars, and both periodontal ligament (PDL) and cementum were removed. Animals were then assigned to two groups (eight animals per group): group 1: control, placebo administration; and group 2: test, human PTH (hPTH) 1-34 administration at a concentration of 40 μg/kg. For both groups, the animals were injected every 2 days, and the animals were sacrificed at 14 and 21 days after surgery. Specimens were harvested and processed for routine decalcified histologic sections. The following parameters were assessed: 1) remaining bone defect extension (RBDE); 2) newly formed bone density (NFBD); 3) total callus area (TCA); 4) osteoclast number (ON) in the callus region; and 5) newly formed dental cementum-like tissue (NFC). Birefringence of root PDL reattachment was also evaluated. Birefringence analysis showed root PDL reattachment for both groups 21 days after treatment. Intermittent hPTH 1-34 administration decreased RBDE (P <0.01) and increased NFBD (P <0.01), TCA (P <0.01), area of NFC (P <0.01), and ON in the callus region (P <0.01). Within the limits of the present study, intermittent administration of hPTH 1-34 led to an enhanced periodontal healing process compared with non-treated animals.

Asenapine Effects on Cognitive and Monoamine Dysfunction Elicited by Subchronic Phencyclidine Administration

PubMed Central