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

Resistance exercise decreases heroin self-administration and alters gene expression in the nucleus accumbens of heroin-exposed rats.

PubMed

Smith, Mark A; Fronk, Gaylen E; Abel, Jean M; Lacy, Ryan T; Bills, Sarah E; Lynch, Wendy J

2018-04-01

Preclinical studies consistently report that aerobic exercise decreases drug self-administration and other forms of drug-seeking behavior; however, relatively few studies have examined other types of physical activity. The purpose of the present study was to examine the effects of resistance exercise (i.e., strength training) on heroin self-administration and mRNA expression of genes known to mediate opioid reinforcement and addictive behavior in the nucleus accumbens (NAc) of heroin-exposed rats. Female rats were obtained during late adolescence and divided into two groups. Resistance exercise rats were trained to climb a vertical ladder wearing a weighted vest; sedentary control rats were placed repeatedly on the ladder oriented horizontally on its side. All rats were implanted with intravenous catheters and trained to self-administer heroin on a fixed ratio (FR1) schedule of reinforcement. mRNA expression in the NAc core and shell was examined following behavioral testing. Resistance exercise significantly decreased heroin self-administration, resulting in a downward shift in the dose-effect curve. Resistance exercise also reduced mRNA expression for mu opioid receptors and dopamine D1, D2, and D3 receptors in the NAc core. Resistance exercise increased mRNA expression of dopamine D5 receptors in the NAc shell and increased mRNA expression of brain-derived neurotrophic factor (exons I, IIB, IIC, IV, VI, IX) in the NAc core. These data indicate that resistance exercise decreases the positive reinforcing effects of heroin and produces changes in opioid and dopamine systems in the NAc of heroin-exposed rats.

Intranasal naloxone administration by police first responders is associated with decreased opioid overdose deaths.

PubMed

Rando, Jessica; Broering, Derek; Olson, James E; Marco, Catherine; Evans, Stephen B

2015-09-01

This study sought to answer the question, "Can police officers administer intranasal naloxone to drug overdose victims to decrease the opioid overdose death rate?" This prospective interventional study was conducted in Lorain County, OH, from January 2011 to October 2014. Starting October 2013, trained police officers administered naloxone to suspected opioid overdose victims through a police officer naloxone prescription program (NPP). Those found by the county coroner to be positive for opioids at the time of death and those who received naloxone from police officers were included in this study. The rate of change in the total number of opioid-related deaths in Lorain County per quarter year, before and after initiation of the NPP, and the trend in the survival rate of overdose victims who were given naloxone were analyzed by linear regression. Significance was established a priori at P < .05. Data from 247 individuals were eligible for study inclusion. Opioid overdose deaths increased significantly before initiation of the police officer NPP with average deaths per quarter of 5.5 for 2011, 15.3 for 2012, and 16.3 for the first 9 months of 2013. After initiation of the police officer NPP, the number of opioid overdose deaths decreased each quarter with an overall average of 13.4. Of the 67 participants who received naloxone by police officers, 52 (77.6%) survived, and 8 (11.9%) were lost to follow-up. Intranasal naloxone administration by police first responders is associated with decreased deaths in opioid overdose victims. Copyright © 2015 Elsevier Inc. All rights reserved.

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.

Sibutramine administration decreases serum anti-Müllerian hormone (AMH) levels in women with polycystic ovary syndrome.

PubMed

Vosnakis, Christos; Georgopoulos, Neoklis A; Armeni, Anastasia K; Papadakis, Efstathios; Roupas, Nikolaos D; Katsikis, Ilias; Panidis, Dimitrios

2012-08-01

To investigate the effect of diet, physical exercise and sibutramine administration on serum anti-Müllerian hormone (AMH) levels, hormonal and metabolic parameters in overweight and obese patients with polycystic ovary syndrome (PCOS). Prospective clinical study, in an outpatient clinic setting, of 76 overweight and obese women with PCOS. All patients were placed on a hypocaloric diet, physical exercise plus sibutramine (10 mg per day) for the first month and then on either a hypocaloric diet, physical exercise plus sibutramine (10 mg per day) or a hypocaloric diet and physical exercise for the subsequent 6 months. Serum AMH levels, body composition, hormonal and metabolic features and insulin sensitivity indices were evaluated at baseline and at 4 and 7 months of treatment. Body weight reduction was greater in the sibutramine group. Moreover, serum FSH and testosterone levels decreased, and SHBG, free androgen index and all indices of insulin resistance significantly improved at 4 and 7 months. Serum AMH levels decreased only in PCOS women who received sibutramine, at both 4 and 7 months of treatment. A hypocaloric diet and a diet plus sibutramine both resulted in significant weight loss in overweight and obese women with PCOS. Patients who received sibutramine showed greater weight loss and improvement in hyperandrogenemia and insulin sensitivity after 7 months of treatment. Serum AMH levels significantly decreased at both 4 and 7 months of treatment only in PCOS women who received sibutramine, indicating a possible direct, gonadotropin independent effect of sibutramine on the ovarian production of AMH. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Decreases in cocaine self-administration with dual inhibition of the dopamine transporter and σ receptors.

PubMed

Hiranita, Takato; Soto, Paul L; Kohut, Stephen J; Kopajtic, Theresa; Cao, Jianjing; Newman, Amy H; Tanda, Gianluigi; Katz, Jonathan L

2011-11-01

Sigma receptor (σR) antagonists attenuate many behavioral effects of cocaine but typically not its reinforcing effects in self-administration procedures. However, the σR antagonist rimcazole and its N-propylphenyl analogs, [3-(cis-3,5-dimethyl-4-[3-phenylpropyl]-1-piperazinyl)-propyl]diphenylamine hydrochloride (SH 3-24) and 9-[3-(cis-3,5-dimethyl-4-[3-phenylpropyl]-1-piperazinyl)-propyl]carbazole hydrobromide (SH 3-28), dose-dependently decreased the maximal rates of cocaine self-administration without affecting comparable responding maintained by food reinforcement. In contrast, a variety of σR antagonists [N-phenethylpiperidine oxalate (AC927), N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(1-pyrrolidinyl)ethylamine dihydrobromide (BD 1008), N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(dimethylamino) ethylamine dihydrobromide (BD 1047), N-[2-(3,4-dichlorophenyl) ethyl]-4-methylpiperazine dihydrochloride (BD 1063), and N,N-dipropyl-2-[4-methoxy-3-(2-phenylethoxy)phenyl]-ethylamine monohydrochloride (NE-100)] had no effect on cocaine self-administration across the range of doses that decreased rates of food-maintained responding. Rimcazole analogs differed from selective σR antagonists in their dual affinities for σRs and the dopamine transporter (DAT) assessed with radioligand binding. Selective DAT inhibitors and σR antagonists were studied alone and in combination on cocaine self-administration to determine whether actions at both σRs and the DAT were sufficient to reproduce the effects of rimcazole analogs. Typical DAT inhibitors [2β-carbomethoxy-3β-(4-fluorophenyl)tropane (WIN 35,428), methylphenidate, and nomifensine] dose-dependently shifted the cocaine dose-effect curve leftward. Combinations of DAT inhibitor and σR antagonist doses that were behaviorally inactive alone decreased cocaine self-administration without effects on food-maintained responding. In addition, whereas the DAT inhibitors were self-administered at rates similar to those of

Decreases in Cocaine Self-Administration with Dual Inhibition of the Dopamine Transporter and σ Receptors

PubMed Central

Hiranita, Takato; Soto, Paul L.; Kohut, Stephen J.; Kopajtic, Theresa; Cao, Jianjing; Newman, Amy H.; Tanda, Gianluigi

2011-01-01

Sigma receptor (σR) antagonists attenuate many behavioral effects of cocaine but typically not its reinforcing effects in self-administration procedures. However, the σR antagonist rimcazole and its N-propylphenyl analogs, [3-(cis-3,5-dimethyl-4-[3-phenylpropyl]-1-piperazinyl)-propyl]diphenylamine hydrochloride (SH 3-24) and 9-[3-(cis-3,5-dimethyl-4-[3-phenylpropyl]-1-piperazinyl)-propyl]carbazole hydrobromide (SH 3-28), dose-dependently decreased the maximal rates of cocaine self-administration without affecting comparable responding maintained by food reinforcement. In contrast, a variety of σR antagonists [N-phenethylpiperidine oxalate (AC927), N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(1-pyrrolidinyl)ethylamine dihydrobromide (BD 1008), N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(dimethylamino) ethylamine dihydrobromide (BD 1047), N-[2-(3,4-dichlorophenyl) ethyl]-4-methylpiperazine dihydrochloride (BD 1063), and N,N-dipropyl-2-[4-methoxy-3-(2-phenylethoxy)phenyl]-ethylamine monohydrochloride (NE-100)] had no effect on cocaine self-administration across the range of doses that decreased rates of food-maintained responding. Rimcazole analogs differed from selective σR antagonists in their dual affinities for σRs and the dopamine transporter (DAT) assessed with radioligand binding. Selective DAT inhibitors and σR antagonists were studied alone and in combination on cocaine self-administration to determine whether actions at both σRs and the DAT were sufficient to reproduce the effects of rimcazole analogs. Typical DAT inhibitors [2β-carbomethoxy-3β-(4-fluorophenyl)tropane (WIN 35,428), methylphenidate, and nomifensine] dose-dependently shifted the cocaine dose-effect curve leftward. Combinations of DAT inhibitor and σR antagonist doses that were behaviorally inactive alone decreased cocaine self-administration without effects on food-maintained responding. In addition, whereas the DAT inhibitors were self-administered at rates similar to those of

Lorcaserin, a 5-HT2C Agonist, Decreases Nicotine Self-Administration in Female Rats

PubMed Central

Johnson, Joshua E.; Slade, Susan; Wells, Corinne; Cauley, Marty; Petro, Ann; Rose, Jed E.

2011-01-01

Lorcaserin, a selective 5-hydroxytryptamine2C (5-HT2C) agonist, has been shown to facilitate weight loss in obese populations. It was assessed for its efficacy in reducing nicotine self-administration in young adult female Sprague-Dawley rats. The effect of short-term doses (subcutaneous) on nicotine self-administration (0.03 mg/kg per infusion) with a fixed ratio 1 schedule was assessed in 3-h sessions. Short-term lorcaserin doses (0.3125–20 mg/kg) were administered in a counterbalanced order. Significant reduction of nicotine self-administration was achieved with all of the short-term doses in this range. Tests of lorcaserin on locomotor activity detected prominent sedative effects at doses greater than 1.25 mg/kg with more modest transient effects seen at 0.625 to 1.25 mg/kg. Long-term effects of lorcaserin on locomotor activity were tested with repeated injections with 0.625 mg/kg lorcaserin 10 times over 2 weeks. This low lorcaserin dose did not cause an overall change in locomotor activity relative to that of saline-injected controls. Long-term lorcaserin (0.625 mg/kg) significantly reduced nicotine self-administration over a 2-week period of repeated injections. Long-term lorcaserin at this same dose had no significant effects on food self-administration over the same 2-week period of repeated injections. These studies support development of the 5-HT2C agonist lorcaserin to aid tobacco smoking cessation. PMID:21636655

Lorcaserin, a 5-HT2C agonist, decreases nicotine self-administration in female rats.

PubMed

Levin, Edward D; Johnson, Joshua E; Slade, Susan; Wells, Corinne; Cauley, Marty; Petro, Ann; Rose, Jed E

2011-09-01

Lorcaserin, a selective 5-hydroxytryptamine(2C) (5-HT(2C)) agonist, has been shown to facilitate weight loss in obese populations. It was assessed for its efficacy in reducing nicotine self-administration in young adult female Sprague-Dawley rats. The effect of short-term doses (subcutaneous) on nicotine self-administration (0.03 mg/kg per infusion) with a fixed ratio 1 schedule was assessed in 3-h sessions. Short-term lorcaserin doses (0.3125-20 mg/kg) were administered in a counterbalanced order. Significant reduction of nicotine self-administration was achieved with all of the short-term doses in this range. Tests of lorcaserin on locomotor activity detected prominent sedative effects at doses greater than 1.25 mg/kg with more modest transient effects seen at 0.625 to 1.25 mg/kg. Long-term effects of lorcaserin on locomotor activity were tested with repeated injections with 0.625 mg/kg lorcaserin 10 times over 2 weeks. This low lorcaserin dose did not cause an overall change in locomotor activity relative to that of saline-injected controls. Long-term lorcaserin (0.625 mg/kg) significantly reduced nicotine self-administration over a 2-week period of repeated injections. Long-term lorcaserin at this same dose had no significant effects on food self-administration over the same 2-week period of repeated injections. These studies support development of the 5-HT(2C) agonist lorcaserin to aid tobacco smoking cessation.

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

Correlates of individual differences in compensatory nicotine self-administration in rats following a decrease in nicotine unit dose

PubMed Central

Harris, Andrew C.; Pentel, Paul R.; LeSage, Mark G.

2013-01-01

Rationale The ability of tobacco harm reduction strategies to produce significant reductions in toxin exposure is limited by compensatory increases in smoking behavior. Characterizing factors contributing to the marked individual variability in compensation may be useful for understanding this phenomenon and assessing the feasibility of harm reduction interventions. Objective To use an animal model of human compensatory smoking that involves a decrease in unit dose supporting nicotine self-administration (NSA) to examine potential contributors to individual differences in compensation. Methods Rats were trained for NSA during daily 23 hr sessions at a unit dose of 0.06 mg/kg/inf until responding was stable. The unit dose was then reduced to 0.03 mg/kg/inf for at least 10 sessions. Following reacquisition of NSA at the training dose and extinction, single-dose nicotine pharmacokinetic parameters were determined. Results Decreases in nicotine intake following dose reduction were proportionally less than the decrease in unit dose, indicating partial compensation. Compensatory increases in infusion rates were observed across the course of the 23 hr sessions. The magnitude of compensation differed considerably between rats. Rats exhibiting the highest baseline infusion rates exhibited the lowest levels of compensation. Nicotine pharmacokinetic parameters were not significantly correlated with compensation. Infusion rates immediately returned to pre-reduction levels when baseline conditions were restored. Conclusions These findings provide initial insights into correlates of individual differences in compensation following a reduction in nicotine unit dose. The present assay may be useful for characterizing mechanisms and potential consequences of the marked individual differences in compensatory smoking observed in humans. PMID:19475400

Long-term phenylbutyrate administration prevents memory deficits in Tg2576 mice by decreasing Abeta.

PubMed

Ricobaraza, Ana; Cuadrado-Tejedor, Mar; Garcia-Osta, Ana

2011-06-01

Aberrations in protein folding, processing, and/or degradation are common features of neurodegenerative diseases, such as Alzheimer's disease (AD). Sodium 4-phenylbutyrate (PBA) is a well-known histone deacetylase inhibitor, which increases gene transcription of a number of genes, and also exerts neuroprotective effects. PBA acts as a chemical chaperone reducing the load of mutant or unfolded proteins during cellular stress. Previously, we reported that 5-week administration of PBA reinstated memory loss and dendritic spine densities in the Tg2576 mouse model of AD. In this study we reported that chronic administration of PBA, starting before the onset of disease symptoms (6 month-old) prevents age-related memory deficits in Tg2576 mice. The amelioration of the memory impairment is associated to a decrease in amyloid beta pathology and the glial fibrillary acidic protein (GFAP), suggesting that inflammation was reduced in PBA-treated animals. Together, the beneficial effects of PBA make it a promising agent for the prevention of AD.

Acute intraperitoneal administration of taurine decreases the glycemia and reduces food intake in type 1 diabetic rats.

PubMed

Gomez, Rosane; Caletti, Greice; Arbo, Bruno Dutra; Hoefel, Ana Lúcia; Schneider, Ricardo; Hansen, Alana Witt; Pulcinelli, Rianne Remus; Freese, Luana; Bandiera, Solange; Kucharski, Luiz Carlos; Barros, Helena Maria Tanhauser

2018-07-01

Taurine, an amino acid with antioxidant and osmoregulatory properties, has been studied for its possible antidiabetic properties in type 1 and type 2 diabetic animals. In type 2 diabetic mice, taurine decreases blood glucose through increased insulin secretion and insulin receptor sensitization. However, insulin is absent in type 1 diabetic individuals. The aim of this study was to evaluate the effects of taurine on parameters related to the energy balance that could explain the metabolic action of this amino acid in type 1 diabetic rats. Control and streptozotocin-induced diabetic rats received saline or taurine (100 mg/kg/day), intraperitoneally, for 30 days. Parameters such as palatable food intake, gastrointestinal transit rate, serum glucose, insulin, leptin, and glucagon levels were measured 60 min after the last taurine administration. Liver, kidneys, heart, and retroperitoneal fat were dissected and weighted. Glycogen levels were measured in the liver and soleus muscle. Our results showed that acute taurine administration decreased glycemia. It also decreased food intake in diabetic rats, without affecting other metabolic parameters. Altogether, our results suggest that in type 1 diabetic rats, taurine decreases blood glucose by a non-insulin-dependent mechanism. Due to the safety profile of taurine, and its effect on glycemia, this amino acid may help to design new drugs to add benefit to insulin therapy in type 1 diabetic individuals. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

PYY[3-36] administration decreases the respiratory quotient and reduces adiposity in diet-induced obese mice.

PubMed

Adams, Sean H; Lei, Chunli; Jodka, Carolyn M; Nikoulina, Svetlana E; Hoyt, Julie A; Gedulin, Bronislava; Mack, Christine M; Kendall, Eric S

2006-01-01

In rodents, weight reduction after peptide YY[3-36] (PYY[3-36]) administration may be due largely to decreased food consumption. Effects on other processes affecting energy balance (energy expenditure, fuel partitioning, gut nutrient uptake) remain poorly understood. We examined whether s.c. infusion of 1 mg/(kg x d) PYY[3-36] (for up to 7 d) increased metabolic rate, fat combustion, and/or fecal energy loss in obese mice fed a high-fat diet. PYY[3-36] transiently reduced food intake (e.g., 25-43% lower at d 2 relative to pretreatment baseline) and decreased body weight (e.g., 9-10% reduction at d 2 vs. baseline) in 3 separate studies. Mass-specific metabolic rate in kJ/(kg x h) in PYY[3-36]-treated mice did not differ from controls. The dark cycle respiratory quotient (RQ) was transiently decreased. On d 2, it was 0.747 +/- 0.008 compared with 0.786 +/- 0.004 for controls (P < 0.001); light cycle RQ was reduced throughout the study in PYY[3-36]-treated mice (0.730 +/- 0.006) compared with controls (0.750 +/- 0.009; P < 0.001). Epididymal fat pad weight in PYY[3-36]-treated mice was approximately 50% lower than in controls (P < 0.01). Fat pad lipolysis ex vivo was not stimulated by PYY[3-36]. PYY[3-36] decreased basal gallbladder emptying in nonobese mice. Fecal energy loss was negligible ( approximately 2% of ingested energy) and did not differ between PYY[3-36]-treated mice and controls. Thus, negative energy balance after PYY[3-36] administration in diet-induced obese mice results from reduced food intake with a relative maintenance of mass-specific energy expenditure. Fat loss and reduced RQ highlight the potential for PYY[3-36] to drive increased mobilization of fat stores to help meet energy requirements in this model.

Significant decreases in blood propofol concentrations during adrenalectomy for phaeochromocytoma.

PubMed

Watanabe, Tatsunori; Hiraoka, Haruhiko; Araki, Takuya; Nagano, Daisuke; Aomori, Tohru; Nakamura, Tomonori; Yamamoto, Koujirou; Baba, Hiroshi

2017-10-01

The kinetics of propofol are influenced by cardiac output. The aim of this study was to examine changes in blood propofol concentrations during phaeochromocytoma surgery using target-controlled infusion (TCI) anaesthesia with propofol. This is a prospective observational study. Ten patients with phaeochromocytoma who underwent unilateral adrenalectomy were included. Cardiac output was measured using an arterial pressure-based cardiac output analysis method. The target blood propofol concentrations were adjusted to maintain an approximate bispectral index (BIS) value of 40 before initiating surgery. The settings remained constant during surgery. Blood samples for propofol concentrations were collected from the radial artery at seven time points: two before tumour manipulation (T1, 2), two during tumour manipulation (T3, 4), and three after tumour vein ligation (T4-7). BIS values, the arterial pressure cardiac index (APCI) and haemodynamic parameters were measured at the same time points as the blood samples. The prop-ratio was calculated by dividing blood propofol concentrations by target concentrations of TCI. APCI increased during tumour manipulation and after tumour vein ligation. The prop-ratio was reduced significantly by approximately 40% and showed a significant negative correlation with APCI. BIS values increased significantly and showed a significant negative correlation with the prop-ratio. The increased APCI during tumour manipulation and after tumour vein ligation was associated with markedly reduced blood propofol concentrations. These results reveal that significant decreases in the anaesthetic effect may be observed in patients undergoing phaeochromocytoma surgery even if TCI anaesthesia is used with propofol. © 2017 The British Pharmacological Society.

Oral administration of Aloe vera gel powder prevents UVB-induced decrease in skin elasticity via suppression of overexpression of MMPs in hairless mice.

PubMed

Saito, Marie; Tanaka, Miyuki; Misawa, Eriko; Yao, Ruiquing; Nabeshima, Kazumi; Yamauchi, Kouji; Abe, Fumiaki; Yamamoto, Yuki; Furukawa, Fukumi

2016-07-01

This study reports the effects of oral Aloe vera gel powder (AVGP) containing Aloe sterols on skin elasticity and the extracellular matrix in ultraviolet B (UVB)-irradiated hairless mice. Ten-week-old hairless mice were fed diets containing 0.3% AVGP for 8 weeks and irradiated UVB for 6 weeks. Mice treated with AVGP showed significant prevention of the UVB-induced decrease in skin elasticity. To investigate the mechanism underlying this suppression of skin elasticity loss, we measured the expression of matrix metalloproteinase (MMP)-2, -9, and -13. AVGP prevented both the UVB-induced increases in MMPs expressions. Moreover, we investigated hyaluronic acid (HA) content of mice dorsal skin and gene expression of HA synthase-2 (Has2). In the results, AVGP oral administration prevented UVB-induced decreasing in skin HA content and Has2 expression and attenuates the UVB-induced decrease in serum adiponectin, which promotes Has2 expression. These results suggested that AVGP has the ability to prevent the skin photoaging.

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

Concomitant administration of nitrous oxide and remifentanil reduces oral tissue blood flow without decreasing blood pressure during sevoflurane anesthesia in rabbits.

PubMed

Kasahara, Masataka; Ichinohe, Tatsuya; Okamoto, Sota; Okada, Reina; Kanbe, Hiroaki; Matsuura, Nobuyuki

2015-06-01

To determine whether continuous administration of nitrous oxide and remifentanil—either alone or together—alters blood flow in oral tissues during sevoflurane anesthesia. Eight male tracheotomized Japanese white rabbits were anesthetized with sevoflurane under mechanical ventilation. Heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), common carotid arterial blood flow (CCBF), tongue mucosal blood flow (TMBF), mandibular bone marrow blood flow (BBF), masseter muscle blood flow (MBF), upper alveolar tissue blood flow (UBF), and lower alveolar tissue blood flow (LBF) were recorded in the absence of all test agents and after administration of the test agents (50 % nitrous oxide, 0.4 μg/kg/min remifentanil, and their combination) for 20 min. Nitrous oxide increased SBP, DBP, MAP, CCBF, BBF, MBF, UBF, and LBF relative to baseline values but did not affect HR or TMBF. Remifentanil decreased all hemodynamic variables except DBP. Combined administration of nitrous oxide and remifentanil recovered SBP, DBP, MAP, and CCBF to baseline levels, but HR and oral tissue blood flow remained lower than control values. Our findings suggest that concomitant administration of nitrous oxide and remifentanil reduces blood flow in oral tissues without decreasing blood pressure during sevoflurane anesthesia in rabbits.

Central administration of insulin-like growth factor-I decreases depressive-like behavior and brain cytokine expression in mice

PubMed Central

2011-01-01

Exogenous administration of insulin-like growth factor (IGF)-I has anti-depressant properties in rodent models of depression. However, nothing is known about the anti-depressant properties of IGF-I during inflammation, nor have mechanisms by which IGF-I alters behavior following activation of the innate immune system been clarified. We hypothesized that central IGF-I would diminish depressive-like behavior on a background of an inflammatory response and that it would do so by inducing expression of the brain-derived neurotrophic factor (BDNF) while decreasing pro-inflammatory cytokine expression in the brain. IGF-I (1,000 ng) was administered intracerebroventricularly (i.c.v.) to CD-1 mice. Mice were subsequently given lipopolysaccharide i.c.v. (LPS, 10 ng). Sickness and depressive-like behaviors were assessed followed by analysis of brain steady state mRNA expression. Central LPS elicited typical transient signs of sickness of mice, including body weight loss, reduced feed intake and decreased social exploration toward a novel juvenile. Similarly, LPS increased time of immobility in the tail suspension test (TST). Pretreatment with IGF-I or antidepressants significantly decreased duration of immobility in the TST in both the absence and presence of LPS. To elucidate the mechanisms underlying the anti-depressant action of IGF-I, we quantified steady-state mRNA expression of inflammatory mediators in whole brain using real-time RT-PCR. LPS increased, whereas IGF-I decreased, expression of inflammatory markers interleukin-1ß (IL-1ß), tumor necrosis factor-(TNF)α, inducible nitric oxide synthase (iNOS) and glial fibrillary acidic protein (GFAP). Moreover, IGF-I increased expression of BDNF. These results indicate that IGF-I down regulates glial activation and induces expression of an endogenous growth factor that shares anti-depressant activity. These actions of IGF-I parallel its ability to diminish depressive-like behavior. PMID:21306618

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

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

PubMed

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

2014-10-20

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

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

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

PubMed Central

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

2012-01-01

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

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.

A single administration of methamphetamine to mice early in the light period decreases running wheel activity observed during the dark period

PubMed Central

Kitanaka, Nobue; Kitanaka, Junichi; Hall, F. Scott; Uhl, George R.; Watabe, Kaname; Kubo, Hitoshi; Takahashi, Hitoshi; Tatsuta, Tomohiro; Morita, Yoshio; Takemura, Motohiko

2014-01-01

Repeated intermittent administration of amphetamines acutely increases appetitive and consummatory aspects of motivated behaviors as well as general activity and exploratory behavior, including voluntary running wheel activity. Subsequently, if the drug is withdrawn, the frequency of these behaviors decrease, which is thought to be indicative of dysphoric symptoms associated with amphetamine withdrawal. Such decreases may be observed after chronic treatment or even after single drug administrations. In the present study, the effect of acute methamphetamine (METH) on running wheel activity, horizontal locomotion, appetitive behavior (food access), and consummatory behavior (food and water intake) was investigated in mice. A multi-configuration behavior apparatus designed to monitor the five behaviors was developed, where combined measures were recorded simultaneously. In the first experiment, naïve male ICR mice showed gradually increasing running wheel activity over three consecutive days after exposure to a running wheel, while mice without a running wheel showed gradually decreasing horizontal locomotion, consistent with running wheel activity being a positively motivated form of natural motor activity. In experiment 2, increased horizontal locomotion and food access, and decreased food intake, were observed for the initial 3 h after acute METH challenge. Subsequently, during the dark phase period decreased running wheel activity and horizontal locomotion were observed. The reductions in running wheel activity and horizontal locomotion may be indicative of reduced dopaminergic function, although it remains to be seen if these changes may be more pronounced after more prolonged METH treatments. PMID:22079320

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.

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

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

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.

Spleen stiffness is positively correlated with HVPG and decreases significantly after TIPS implantation.

PubMed

Buechter, Matthias; Manka, Paul; Theysohn, Jens M; Reinboldt, Marcus; Canbay, Ali; Kahraman, Alisan

2018-01-01

Transjugular intrahepatic portosystemic shunt (TIPS) is indicated in patients with decompensated portal hypertension (PH). Hepatic venous pressure gradient (HVPG) is considered gold standard for assessment of PH. Because HVPG measurement is invasive, non-invasive methods for evaluating severity of PH are warranted. We retrospectively correlated spleen stiffness as measured by FibroScan with HVPG in patients who underwent TIPS. Twenty-four patients with spleen stiffness measurement (SSM) one day before (D-1), one day after (D+1) and 28 days after TIPS (D+28) were included. SSM was positively correlated with pre-TIPS HVPG (HVPG <13mmHg, median SSM: 19.7±8.6kPa; HVPG 13-24mmHg, median SSM: 45.0±15.7kPa; HVPG >24mmHg, median SSM: 75.0±6.2kPa; p<0.05]; r 2 =0.72; p<0.001) and decreased significantly after TIPS implantation (D-1, median SSM: 67.1±17.3kPa; D+1, median SSM: 44.7±18.5kPa; D+28, median SSM: 35.6±17.0kPa; p<0.05), while liver stiffness measurement decrease was not statistically significant. Our study highlights the utility of SSM as non-invasive tool in patients with chronic liver disease in evaluating degree of PH potentially offering a confirmable additional parameter in surveillance of patients undergoing TIPS procedure. Copyright © 2017 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

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.

Regulation of glutamate transporter 1 (GLT-1) gene expression by cocaine self-administration and withdrawal.

PubMed

Kim, Ronald; Sepulveda-Orengo, Marian T; Healey, Kati L; Williams, Emily A; Reissner, Kathryn J

2018-01-01

Downregulation of the astroglial glutamate transporter GLT-1 is observed in the nucleus accumbens (NAc) following administration of multiple drugs of abuse. The decrease in GLT-1 protein expression following cocaine self-administration is dependent on both the amount of cocaine self-administered and the length of withdrawal, with longer access to cocaine and longer withdrawal periods leading to greater decreases in GLT-1 protein. However, the mechanism(s) by which cocaine downregulates GLT-1 protein remains unknown. We used qRT-PCR to examine gene expression of GLT-1 splice isoforms (GLT-1A, GLT-1B) in the NAc, prelimbic cortex (PL) and basolateral amygdala (BLA) of rats, following two widely used models of cocaine self-administration: short-access (ShA) self-administration, and the long-access (LgA) self-administration/incubation model. While downregulation of GLT-1 protein is observed following ShA cocaine self-administration and extinction, this model did not lead to a change in GLT-1A or GLT-1B gene expression in any brain region examined. Forced abstinence following ShA cocaine self-administration also was without effect. In contrast, LgA cocaine self-administration and prolonged abstinence significantly decreased GLT-1A gene expression in the NAc and BLA, and significantly decreased GLT-1B gene expression in the PL. No change was observed in NAc GLT-1A gene expression one day after LgA cocaine self-administration, indicating withdrawal-induced decreases in GLT-1A mRNA. In addition, LgA cocaine self-administration and withdrawal induced hypermethylation of the GLT-1 gene in the NAc. These results indicate that a decrease in NAc GLT-1 mRNA is only observed after extended access to cocaine combined with protracted abstinence, and that epigenetic mechanisms likely contribute to this effect. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

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

PubMed

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

2017-03-01

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

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

PubMed

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

2017-01-01

On January 1, 2012, reimbursement for inferior vena cava filters (IVCFs) became bundled by the Centers for Medicare and Medicaid Services. This resulted in ICVF placement (CPT code 37191) now yielding 4.71 relative value units (RVUs), a decrease from 15.6 RVUs for placement and associated procedures (CPT codes 37620, 36010, 75825-26, 75940-26). Our hypothesis was that IVCF utilization would decrease in response to this change as other procedures had done once they had become bundled. Including data from 2010 to 2011 (before bundling) and 2012 to 2014 (after bundling), we utilized 5% inpatient, outpatient, and carrier files of Medicare limited data sets and analyzed IVCF utilization before and after bundling across specialty types, controlling for total diagnosis of deep vein thrombosis (DVT) and pulmonary embolism (PE) (ICD-9 codes 453.xx and 415.xx, respectively) and placement location. In 2010 and 2011, the rates/10,000 DVT/PE diagnoses were 918 and 1,052, respectively (average 985). In 2012, 2013, and 2014, rates were 987, 877, and 605, respectively (average 823). Comparing each year individually, there is a significant difference (P < 0.0001) with 2012, 2013, and 2014 having lower rates of ICVF utilization. Comparing averages in the 2010-2011 and 2012-2014 groups, there is also a significant decrease in utilization after bundling (P < 0.0001). Following the bundling of reimbursement for IVCF placement, procedural utilization decreased significantly. More data from subsequent years will be needed to show if this decrease utilization continues to persist. Copyright © 2016 Elsevier Inc. All rights reserved.

Decreased rates of operant food self-administration are associated with reward deficits in high-fat feeding mice.

PubMed

Íbias, Javier; Miguéns, Miguel; Del Rio, Danila; Valladolid-Acebes, Ismael; Stucchi, Paula; Ambrosio, Emilio; Martín, Miriam; Morales, Lidia; Ruiz-Gayo, Mariano; Del Olmo, Nuria

2016-06-01

Highly palatable foods behave as appetitive reinforcers and tend to be consumed compulsively. Nevertheless, the motivation for this kind of diets in experimental diet-induced obesity models has not been well established. Our hypothesis is that obesity caused by a regular consumption of high-fat diet (HFD) occurs concomitantly with the inhibition of food reward. The ultimate goal of our study was to further analyze the extent to which the perception of food as an appetitive reinforcer is a necessary condition for obesity. We have evaluated the influence of HFD on operant food self-administration (FSA) during a whole light-dark (12-12-h) cycle in mice that consumed HFD either during 1, 4 or 8 weeks. The study has been complemented by a two-bottle free-choice assay between tap water and sweetened drinks. These data show that both 4- and 8-week HFD treatments induced a significant decrease in operant FSA rate. Moreover, HFD impaired the sweetened-conditioned flavor preference in the two-bottle choice assay. Our results, showing a reduction in how hard an animal is willing to work for food reinforcers, provide evidence that chronic consumption of HFD negatively contributes to the incentive motivation to acquire food/drink reinforcers. We demonstrate that energy homeostasis imbalance triggered by HFD is associated with the inhibition of hedonic feeding.

Gemfibrozil Concentrations are Significantly Decreased in the Presence of Lopinavir/ritonavir

PubMed Central

Busse, Kristin H.; Hadigan, Colleen; Chairez, Cheryl; Alfaro, Raul M.; Formentini, Elizabeth; Kovacs, Joseph A.; Penzak, Scott R.

2009-01-01

Objective: To determine the influence of a two-week course of lopinavir-ritonavir on the pharmacokinetics of the triglyceride-lowering agent, gemfibrozil. Methods: The study was conducted as an open label, single-sequence pharmacokinetic study in healthy human volunteers. Gemfibrozil pharmacokinetic parameter values were compared using a students t test after a single 600 mg dose was administered to healthy volunteers before, and after two weeks of lopinavir-ritonavir (400/100 mg) twice daily. Results: Fifteen healthy volunteers (8 males) completed the study. All study drugs were generally well-tolerated and no subjects withdrew participation. The geometric mean ratio (GMR, 90% CI) for gemfibrozil area under the plasma concentration-time curve (AUC0-∞) after 14 days of lopinavir-ritonavir compared to baseline was 0.59 (0.52, 0.67) (P < 0.001). All 15 study subjects experienced a reduction in gemfibrozil AUC0-∞ after lopinavir-ritonavir (range: −6% to −74%). The GMRs for gemfibrozil apparent oral clearance (Cl/F) and maximum concentration (Cmax) were 1.69 (1.41, 1.97) and 0.67 (0.49, 0.86) after 14 days of lopinavir-ritonavir versus baseline, respectively (P < 0.0001 and 0.01, respectively). Gemfibrozil elimination half-life did not change after lopinavir-ritonavir administration (P = 0.60). Conclusion: Lopinavir/ritonavir significantly reduced the systemic exposure of gemfibrozil by reducing gemfibrozil absorption. Clinicians treating HIV-infected patients with hypertriglyceridemia should be aware of this drug interaction. PMID:19648824

Gemfibrozil concentrations are significantly decreased in the presence of lopinavir-ritonavir.

PubMed

Busse, Kristin H; Hadigan, Colleen; Chairez, Cheryl; Alfaro, Raul M; Formentini, Elizabeth; Kovacs, Joseph A; Penzak, Scott R

2009-10-01

The objective of this study was to determine the influence of a 2-week course of lopinavir-ritonavir on the pharmacokinetics of the triglyceride-lowering agent, gemfibrozil. The study was conducted as an open label, single-sequence pharmacokinetic study in healthy human volunteers. Gemfibrozil pharmacokinetic parameter values were compared using a Student t test after a single 600-mg dose was administered to healthy volunteers before and after 2 weeks of lopinavir-ritonavir (400/100 mg) twice daily. Fifteen healthy volunteers (eight males) completed the study. All study drugs were generally well tolerated and no subjects withdrew participation. The geometric mean ratio (90% confidence interval) for gemfibrozil area under the plasma concentration-time curve after 14 days of lopinavir-ritonavir compared with baseline was 0.59 (0.52, 0.67) (P < 0.001). All 15 study subjects experienced a reduction in gemfibrozil area under the plasma concentration-time curve after lopinavir-ritonavir (range, -6% to -74%). The geometric mean ratios for gemfibrozil apparent oral clearance and maximum concentration were 1.69 (1.41, 1.97) and 0.67 (0.49, 0.86) after 14 days of lopinavir-ritonavir versus baseline, respectively (P < 0.0001 and 0.01, respectively). Gemfibrozil elimination half-life did not change after lopinavir-ritonavir administration (P = 0.60). Lopinavir-ritonavir significantly reduced the systemic exposure of gemfibrozil by reducing gemfibrozil absorption. Clinicians treating HIV-infected patients with hypertriglyceridemia should be aware of this drug interaction.

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

PubMed

Calderón-Garcidueñas, Lilian; Mora-Tiscareño, Antonieta; Franco-Lira, Maricela; Cross, Janet V; Engle, Randall; Aragón-Flores, Mariana; Gómez-Garza, Gilberto; Jewells, Valerie; Medina-Cortina, Humberto; Solorio, Edelmira; Chao, Chih-Kai; Zhu, Hongtu; Mukherjee, Partha S; Ferreira-Azevedo, Lara; Torres-Jardón, Ricardo; D'Angiulli, Amedeo

2013-01-01

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

Flavonol-rich dark cocoa significantly decreases plasma endothelin-1 and improves cognition in urban children

PubMed Central

Calderón-Garcidueñas, Lilian; Mora-Tiscareño, Antonieta; Franco-Lira, Maricela; Cross, Janet V.; Engle, Randall; Aragón-Flores, Mariana; Gómez-Garza, Gilberto; Jewells, Valerie; Weili, Lin; Medina-Cortina, Humberto; Solorio, Edelmira; Chao, Chih-kai; Zhu, Hongtu; Mukherjee, Partha S.; Ferreira-Azevedo, Lara; Torres-Jardón, Ricardo; D'Angiulli, Amedeo

2013-01-01

Air pollution exposures are linked to systemic inflammation, cardiovascular and respiratory morbidity and mortality, neuroinflammation and neuropathology in young urbanites. In particular, most Mexico City Metropolitan Area (MCMA) children exhibit subtle cognitive deficits, and neuropathology studies show 40% of them exhibiting frontal tau hyperphosphorylation and 51% amyloid-β diffuse plaques (compared to 0% in low pollution control children). We assessed whether a short cocoa intervention can be effective in decreasing plasma endothelin 1 (ET-1) and/or inflammatory mediators in MCMA children. Thirty gram of dark cocoa with 680 mg of total flavonols were given daily for 10.11 ± 3.4 days (range 9–24 days) to 18 children (10.55 years, SD = 1.45; 11F/7M). Key metabolite ratios in frontal white matter and in hippocampus pre and during cocoa intervention were quantified by magnetic resonance spectroscopy. ET-1 significantly decreased after cocoa treatment (p = 0.0002). Fifteen children (83%) showed a marginally significant individual improvement in one or both of the applied simple short memory tasks. Endothelial dysfunction is a key feature of exposure to particulate matter (PM) and decreased endothelin-1 bioavailability is likely useful for brain function in the context of air pollution. Our findings suggest that cocoa interventions may be critical for early implementation of neuroprotection of highly exposed urban children. Multi-domain nutraceutical interventions could limit the risk for endothelial dysfunction, cerebral hypoperfusion, neuroinflammation, cognitive deficits, structural volumetric detrimental brain effects, and the early development of the neuropathological hallmarks of Alzheimer's and Parkinson's diseases. PMID:23986703

Removal of the blue component of light significantly decreases retinal damage after high intensity exposure.

PubMed

Vicente-Tejedor, Javier; Marchena, Miguel; Ramírez, Laura; García-Ayuso, Diego; Gómez-Vicente, Violeta; Sánchez-Ramos, Celia; de la Villa, Pedro; Germain, Francisco

2018-01-01

Light causes damage to the retina (phototoxicity) and decreases photoreceptor responses to light. The most harmful component of visible light is the blue wavelength (400-500 nm). Different filters have been tested, but so far all of them allow passing a lot of this wavelength (70%). The aim of this work has been to prove that a filter that removes 94% of the blue component may protect the function and morphology of the retina significantly. Three experimental groups were designed. The first group was unexposed to light, the second one was exposed and the third one was exposed and protected by a blue-blocking filter. Light damage was induced in young albino mice (p30) by exposing them to white light of high intensity (5,000 lux) continuously for 7 days. Short wavelength light filters were used for light protection. The blue component was removed (94%) from the light source by our filter. Electroretinographical recordings were performed before and after light damage. Changes in retinal structure were studied using immunohistochemistry, and TUNEL labeling. Also, cells in the outer nuclear layer were counted and compared among the three different groups. Functional visual responses were significantly more conserved in protected animals (with the blue-blocking filter) than in unprotected animals. Also, retinal structure was better kept and photoreceptor survival was greater in protected animals, these differences were significant in central areas of the retina. Still, functional and morphological responses were significantly lower in protected than in unexposed groups. In conclusion, this blue-blocking filter decreases significantly photoreceptor damage after exposure to high intensity light. Actually, our eyes are exposed for a very long time to high levels of blue light (screens, artificial light LED, neons…). The potential damage caused by blue light can be palliated.

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.

Central administration of the anorexigenic peptide neuromedin U decreases alcohol intake and attenuates alcohol-induced reward in rodents.

PubMed

Vallöf, Daniel; Ulenius, Lisa; Egecioglu, Emil; Engel, Jörgen A; Jerlhag, Elisabet

2017-05-01

By investigating the neurochemical mechanisms through which alcohol activates the brain reward systems, novel treatment strategies for alcohol use disorder (AUD), a chronic relapsing disease, can be developed. In contrast to the common view of the function of gut-brain peptides, such as neuromedin U (NMU), to regulate food intake and appetite, a novel role in reinforcement mediation has been implied. The anorexigenic effects of NMU are mediated via NMU2 receptors, preferably in the arcuate nucleus and paraventricular nucleus. The expression of NMU2 receptors is also expressed in several reward-related areas in the brain, suggesting a role in reward regulation. The present experiments were therefore set up to investigate the effect of intracerebroventricular administration of NMU on alcohol-mediated behaviors in rodents. We found that central administration of NMU attenuated alcohol-induced locomotor stimulation, accumbal dopamine release and the expression of conditioned place preference in mice. In addition, NMU dose dependently decreased alcohol intake in high, but not in low, alcohol-consuming rats. Central NMU administration did not alter the blood alcohol concentrations nor change the corticosterone levels in rodents. Given that AUD is a major health-care challenge causing an enormous cost to society and novel treatment strategies are warranted, our data suggest that NMU analogues deserve to be evaluated as novel treatment of AUD in humans. © 2016 The Authors Addiction Biology published by John Wiley & Sons Ltd.

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

PubMed

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

2004-01-01

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

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

PubMed

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

2016-06-01

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

Chronic methamphetamine exposure significantly decreases microglia activation in the arcuate nucleus.

PubMed

Lloyd, Steven A; Corkill, Beau; Bruster, Matthew C; Roberts, Rick L; Shanks, Ryan A

2017-07-01

Methamphetamine is a powerful psychostimulant drug and its use and abuse necessitates a better understanding of its neurobiobehavioral effects. The acute effects of binge dosing of methamphetamine on the neurons in the CNS are well studied. However, the long-term effects of chronic, low-dose methamphetamine are less well characterized, especially in other cell types and areas outside of the major dopamine pathways. Mice were administered 5mg/kg/day methamphetamine for ten days and brain tissue was analyzed using histochemistry and image analysis. Increased microglia activity in the striatum confirmed toxic effects of methamphetamine in this brain region using this dosing paradigm. A significant decrease in microglia activity in the arcuate nucleus of the hypothalamus was observed with no effect noted on dopamine neurons in the arcuate nucleus. Given the importance of this area in homeostatic and neuroendocrine regulation, the current study highlights the need to more fully understand the systemic effects of chronic, low-dose methamphetamine use. The novel finding of microglia downregulation after chronic methamphetamine could lead to advances in understanding neuroinflammatory responses towards addiction treatment and protection from psychostimulant-induced neurotoxicity. Copyright © 2017 Elsevier B.V. All rights reserved.

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

Dextromethorphan Interactions with Histaminergic and Serotonergic Treatments to Reduce Nicotine Self-administration in Rats

PubMed Central

Briggs, Scott A.; Hall, Brandon J.; Wells, Corinne; Slade, Susan; Jaskowski, Paul; Morrison, Margaret; Rezvani, Amir H.; Rose, Jed E.; Levin, Edward D.

2015-01-01

Combining effective treatments with diverse mechanisms of action for smoking cessation may provide better therapy by targeting multiple points of control in the neural circuits underlying addiction. Previous research in a rat model has shown that dextromethorphan, which has α3β4 nicotinic and NMDA glutamatergic antagonist actions, significantly decreases nicotine self-administration. We have found in the rat model that the H1 histamine antagonist pyrilamine and the serotonin 5HT2c agonist lorcaserin also significantly reduce nicotine self-administration. The current studies were conducted to determine the interactive effects of dextromethorphan with pyrilamine and lorcaserin on nicotine self-administration in rats. Young adult female rats were fitted with jugular IV catheters and trained to self-administer a nicotine infusion dose of 0.03-mg/kg/infusion. In an initial dose-effect function study of dextromethorphan, we found a monotonic decrease in nicotine self-administration over a dose range of 1 to 30-mg/kg with a lowest effective dose of 3-mg/kg. Then, with two separate cohorts of rats, dextromethorphan (0, 3.3, and 10-mg/kg) interactions with pyrilamine (0, 4.43, and 13.3-mg/kg) were investigated as well as interactions with lorcaserin (0, 0.3125 and 0.625-mg/kg). In the pyrilamine-dextromethorphan interaction study, the acute dose of pyrilamine (13.3-mg/kg) as well as an acute dose of dextromethorphan caused a significant decrease in nicotine self-administration. There were mutually augmenting effects of these two drugs. The combination of dextromethorphan (10-mg/kg) and pyrilamine (13.3-mg/kg) significantly lowered nicotine self-administration relative to either 10-mg/kg of dextromethorphan alone (p<0.05) or 13.3-mg/kg of pyrilamine alone (p<0.0005). In the lorcaserin-dextromethorphan study, an acute dose of lorcaserin (0.312-mg/kg) as well as an acute dose of dextromethorphan (10-mg/kg) caused a significant decrease in nicotine self-administration

Dextromethorphan interactions with histaminergic and serotonergic treatments to reduce nicotine self-administration in rats.

PubMed

Briggs, Scott A; Hall, Brandon J; Wells, Corinne; Slade, Susan; Jaskowski, Paul; Morrison, Margaret; Rezvani, Amir H; Rose, Jed E; Levin, Edward D

2016-03-01

Combining effective treatments with diverse mechanisms of action for smoking cessation may provide better therapy by targeting multiple points of control in the neural circuits underlying addiction. Previous research in a rat model has shown that dextromethorphan, which has α3β4 nicotinic and NMDA glutamatergic antagonist actions, significantly decreases nicotine self-administration. We have found in the rat model that the H1 histamine antagonist pyrilamine and the serotonin 5HT2C agonist lorcaserin also significantly reduce nicotine self-administration. The current studies were conducted to determine the interactive effects of dextromethorphan with pyrilamine and lorcaserin on nicotine self-administration in rats. Young adult female rats were fitted with jugular IV catheters and trained to self-administer a nicotine infusion dose of 0.03-mg/kg/infusion. In an initial dose-effect function study of dextromethorphan, we found a monotonic decrease in nicotine self-administration over a dose range of 1 to 30-mg/kg with the lowest effective dose of 3-mg/kg. Then, with two separate cohorts of rats, dextromethorphan (0, 3.3, and 10-mg/kg) interactions with pyrilamine (0, 4.43, and 13.3-mg/kg) were investigated as well as interactions with lorcaserin (0, 0.3125 and 0.625-mg/kg). In the pyrilamine-dextromethorphan interaction study, an acute dose of pyrilamine (13.3-mg/kg) as well as an acute dose of dextromethorphan caused a significant decrease in nicotine self-administration. There were mutually augmenting effects of these two drugs. The combination of dextromethorphan (10-mg/kg) and pyrilamine (13.3-mg/kg) significantly lowered nicotine self-administration relative to either 10-mg/kg of dextromethorphan alone (p<0.05) or 13.3-mg/kg of pyrilamine alone (p<0.0005). In the lorcaserin-dextromethorphan study, an acute dose of lorcaserin (0.312-mg/kg) as well as an acute dose of dextromethorphan (10-mg/kg) caused a significant decrease in nicotine self-administration

Density increment and decreased survival of rat red blood cells induced by cadmium

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

Kunimoto, M.; Miura, T.

1986-01-01

Male Wistar rats were injected with CdCl/sub 2/ subcutaneously to examine in vivo effects of Cd on density and survival of red blood cells. During the 7 days after administration of 1.0 mg Cd/kg, the following sequence of events occurred: (1) a progressive increase in the amount of more dense red blood cells concomitant with a decrease in that of light red blood cells from the first to the third day; (2) an increase in the spleen weight at the third day; (3) a decrease in the hematocrit value and an increase in the amount of light red blood cellsmore » at the fifth day; and (4) a recovery of the hematocrit value at the seventh day. Five days after administration, the hematocrit value decreased in a dose-dependent mode and the decrease was significant at the 1% level at 1.0 and 1.5 mg Cd/kg. A highly significant splenomegaly was also observed at 0.5 to 1.5 mg Cd/kg. In order to label red blood cells in vivo, (/sup 3/H) diisopropylfluorophosphate ((/sup 3/H)DFP) was injected into rats. At Day 11, Cd at either 0.5 or 1.0 mg/kg was administered to (/sup 3/H)DFP-prelabeled animals. Cd administration accelerated /sup 3/H-labeled red cell clearance from the blood. Six days after Cd administration, the radioactivity of red blood cells was 76 and 68% of the control at 0.5 and 1.0 mg Cd/kg, respectively. In vitro treatment of rat red density and accelerated in vivo clearance of red blood cells from the recipient circulation. These results show that Cd at low dose can cause anemia by increasing red cell density and by accelerating red cell sequestration, presumably in the spleen.« less

The Impact of Bar Code Medication Administration Technology on Reported Medication Errors

ERIC Educational Resources Information Center

Holecek, Andrea

2011-01-01

The use of bar-code medication administration technology is on the rise in acute care facilities in the United States. The technology is purported to decrease medication errors that occur at the point of administration. How significantly this technology affects actual rate and severity of error is unknown. This descriptive, longitudinal research…

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

PubMed

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

2017-02-01

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

Epidural morphine and detomidine decreases postoperative hindlimb lameness in horses after bilateral stifle arthroscopy.

PubMed

Goodrich, Laurie R; Nixon, Alan J; Fubini, Susan L; Ducharme, Norm G; Fortier, Lisa A; Warnick, Lorin D; Ludders, John W

2002-01-01

To determine whether preoperative epidural administration of morphine and detomidine would decrease postoperative lameness after bilateral stifle arthroscopy in horses. Prospective clinical controlled study. Eight adult horses that had bilateral arthroscopic procedures, including drilling of cartilage and subchondral bone within the femoropatellar joints. Horses were randomly separated into 2 groups. Preoperatively, 4 horses were administered a combination of epidural morphine (0.2 mg/kg) and detomidine (30 microg/kg), and 4 horses were administered an equivalent volume of epidural saline (0.9% NaCl) solution. Postoperative pain was assessed using 6 video recordings made at hourly intervals of each horse at a walk. Assessments began 1 hour after recovery from anesthesia. The recordings were scrambled out of sequence and evaluated by 3 observers, unaware of treatment groups, who scored lameness from 0 to 4. Lameness scores of the 2 groups of horses were compared using a Wilcoxon's rank sum test. Heart and respiratory rates were also measured at each hourly interval and compared between groups using a repeated-measures ANOVA; statistical significance was set at P <.05. Preoperative administration of epidural morphine and detomidine significantly decreased lameness and heart rates after bilateral stifle arthroscopy. The greatest decrease was detected at hours 1 and 2 after recovery from anesthesia. We conclude that horses undergoing a painful arthroscopic procedure of the stifle joint benefit from the administration of preoperative epidural morphine and detomidine. Preoperative epidural administration of detomidine and morphine may be useful in decreasing postoperative pain after stifle arthroscopy as well as pain associated with other painful disorders involving the stifle joint, such as septic arthritis and trauma. Copyright 2002 by The American College of Veterinary Surgeons

Chronic administration of thiamine pyrophosphate decreases age-related histological atrophic testicular changes and improves sexual behavior in male Wistar rats.

PubMed

Hernández-Montiel, H L; Vásquez López, C M; González-Loyola, J G; Vega-Anaya, G C; Villagrán-Herrera, M E; Gallegos-Corona, M A; Saldaña, C; Ramos Gómez, M; García Horshman, P; García Solís, P; Solís-S, J C; Robles-Osorio, M L; Ávila Morales, J; Varela-Echavarría, A; Paredes Guerrero, R

2014-06-01

Aging is a multifactorial universal process and constitutes the most important risk factor for chronic-degenerative diseases. Although it is a natural process, pathological aging arises when these changes occur quickly and the body is not able to adapt. This is often associated with the generation of reactive oxygen species (ROS), inflammation, and a decrease in the endogenous antioxidant systems, constituting a physiopathological state commonly found in chronic-degenerative diseases. At the testicular level, aging is associated with tissue atrophy, decreased steroidogenesis and spermatogenesis, and sexual behavior disorders. This situation, in addition to the elevated generation of ROS in the testicular steroidogenesis, provides a critical cellular environment causing oxidative damage at diverse cellular levels. To assess the effects of a reduction in the levels of ROS, thiamine pyrophosphate (TPP) was chronically administered in senile Wistar rats. TPP causes an activation of intermediate metabolism routes, enhancing cellular respiration and decreasing the generation of ROS. Our results show an overall decrease of atrophic histological changes linked to aging, with higher levels of serum testosterone, sexual activity, and an increase in the levels of endogenous antioxidant enzymes in TPP-treated animals. These results suggest that TPP chronic administration decreases the progression of age-related atrophic changes by improving the intermediate metabolism, and by increasing the levels of antioxidant enzymes.

Long-Term Administration of Conjugated Estrogen and Bazedoxifene Decreased Murine Fecal β-Glucuronidase Activity Without Impacting Overall Microbiome Community.

PubMed

Chen, Karen Lee Ann; Liu, Xiaoji; Zhao, Yiru Chen; Hieronymi, Kadriye; Rossi, Gianluigi; Auvil, Loretta Sue; Welge, Michael; Bushell, Colleen; Smith, Rebecca Lee; Carlson, Kathryn E; Kim, Sung Hoon; Katzenellenbogen, John A; Miller, Michael Joseph; Madak-Erdogan, Zeynep

2018-05-25

Conjugated estrogens (CE) and Bazedoxifene (BZA) combination is used to alleviate menopause-associated symptoms in women. CE+BZA undergo first-pass-metabolism in the liver and deconjugation by gut microbiome via β-glucuronidase (GUS) enzyme inside the distal gut. To date, the impact of long-term exposure to CE+BZA on the gut microbiome or GUS activity has not been examined. Our study using an ovariectomized mouse model showed that CE+BZA administration did not affect the overall cecal or fecal microbiome community except that it decreased the abundance of Akkermansia, which was identified as a fecal biomarker correlated with weight gain. The fecal GUS activity was reduced significantly and was positively correlated with the abundance of Lactobacillaceae in the fecal microbiome. We further confirmed in Escherichia coli K12 and Lactobacillus gasseri ADH that Tamoxifen-, 4-hydroxy-Tamoxifen- and Estradiol-Glucuronides competed for GUS activity. Our study for the first time demonstrated that long-term estrogen supplementation directly modulated gut microbial GUS activity. Our findings implicate that long-term estrogen supplementation impacts composition of gut microbiota and microbial activity, which affects estrogen metabolism in the gut. Thus, it is possible to manipulate such activity to improve the efficacy and safety of long-term administered estrogens for postmenopausal women or breast cancer patients.

Decreasing the Time to Insulin Administration for Hospitalized Patients With Cystic Fibrosis-Related Diabetes.

PubMed

Smego, Allison; Lawson, Sarah; Courter, Joshua D; Warden, Deborah; Corathers, Sarah

2018-05-01

Children with cystic fibrosis-related diabetes (CFRD) represent a commonly hospitalized pediatric population whose members require insulin for blood glucose (BG) control. The aim of this quality improvement initiative was to increase the proportion of hospitalized patients with CFRD receiving insulin within 30 minutes of a BG check while decreasing severe hypo- and hyperglycemia episodes. Quality improvement methodology (gathering a team of stakeholders, identifying metrics, implementing iterative plan-do-study-act cycles and analysis of data over time) was applied in the setting of a cystic fibrosis unit in a tertiary care children's hospital. The percentage of patients with CFRD who received rapid-acting insulin within 30 minutes of a BG check and the rates of hypoglycemia (BG <70 mg/dL) and hyperglycemia (BG >200 mg/dL) were measured. Improvement interventions were focused on efficient communication among patients, nurses and providers; refining carbohydrate calculation; and sharing expectations with patients and caregivers. The proportion of rapid-acting insulin doses given within 30 minutes increased from a baseline mean 40% to a sustained mean of 78%. During active improvement interventions, success rates of 100% were achieved. Hyperglycemic events (BG >200 mg/dL) decreased from 125 events to 85 events per 100 rapid-acting insulin days. Hypoglycemic events (BG <70 mg/dL) remained low at <5 events per 100 rapid-acting insulin days. Systematic implementation of low-cost interventions successfully resulted in measurable improvement in timely rapid-acting insulin administration for hospitalized patients with CFRD and lower rates of severe hypo- and hyperglycemia on the unit. Future efforts will be directed to increase the reliability of interventions to maintain optimal performance and outcomes. Copyright © 2018 by the American Academy of Pediatrics.

Reversal of the toxic effects of cachectin by concurrent insulin administration.

PubMed

Fraker, D L; Merino, M J; Norton, J A

1989-06-01

Rats treated with recombinant human tumor necrosis factor-cachectin, 100 micrograms/kg ip twice daily for 5 consecutive days, had a 56% decrease in food intake, a 54% decrease in nitrogen balance, and a 23-g decrease in body weight gain vs. saline-treated controls. Concurrent neutral protamine hagedorn insulin administration of 2 U/100 g sc twice daily reversed all of these changes to control levels without causing any treatment deaths. The improvement seen with insulin was dose independent. Five days of cachectin treatment caused a severe interstitial pneumonitis, periportal inflammation in the liver, and an increase in wet organ weight in the heart, lungs, kidney, and spleen. Concurrent insulin treatment led to near total reversal of these histopathologic changes. Cachectin treatment did not significantly change blood glucose levels from control values of 130-140 mg/dl, but insulin plus cachectin caused a significant decrease in blood glucose from 1 through 12 h after injection. Administration of high-dose insulin can near totally reverse the nutritional and histopathologic toxicity of sublethal doses of cachectin in rats.

Nucleus accumbens shell excitability is decreased by methamphetamine self-administration and increased by 5-HT2C receptor inverse agonism and agonism

PubMed Central

Graves, Steven M.; Clark, Mary J.; Traynor, John R.; Hu, Xiu-Ti; Napier, T. Celeste

2014-01-01

Methamphetamine profoundly increases brain monoamines and is a widely abused psychostimulant. The effects of methamphetamine self-administration on neuron function are not known for the nucleus accumbens, a brain region involved in addictive behaviors, including drug-seeking. One therapeutic target showing preclinical promise at attenuating psychostimulant-seeking is 5-HT2C receptors; however, the effects of 5-HT2C receptor ligands on neuronal physiology are unclear. 5-HT2C receptor agonism decreases psychostimulant-mediated behaviors, and the putative 5-HT2C receptor inverse agonist, SB 206553, attenuates methamphetamine-seeking in rats. To ascertain the effects of methamphetamine, and 5-HT2C receptor inverse agonism and agonism, on neuronal function in the nucleus accumbens, we evaluated methamphetamine, SB 206553, and the 5-HT2C receptor agonist and Ro 60-0175, on neuronal excitability within the accumbens shell subregion using whole-cell current-clamp recordings in forebrain slices ex vivo. We reveal that methamphetamine self-administration decreased generation of evoked action potentials. In contrast, SB 206553 and Ro 60-0175 increased evoked spiking, effects that were prevented by the 5-HT2C receptor antagonist, SB 242084. We also assessed signaling mechanisms engaged by 5-HT2C receptors, and determined that accumbal 5-HT2C receptors stimulated Gq, but not Gi/o. These findings demonstrate that methamphetamine-induced decreases in excitability of neurons within the nucleus accumbens shell were abrogated by both 5-HT2C inverse agonism and agonism, and this effect likely involved activation of Gq–mediated signaling pathways. PMID:25229719

GC protein-derived macrophage-activating factor decreases α-N-acetylgalactosaminidase levels in advanced cancer patients.

PubMed

Thyer, Lynda; Ward, Emma; Smith, Rodney; Branca, Jacopo Jv; Morucci, Gabriele; Gulisano, Massimo; Noakes, David; Eslinger, Robert; Pacini, Stefania

2013-08-01

α- N -acetylgalactosaminidase (nagalase) accumulates in the serum of cancer patients and its activity correlates with tumor burden, aggressiveness and clinical disease progression. The administration of GC protein-derived macrophage-activating factor (GcMAF) to cancer patients with elevated levels of nagalase has been associated with a decrease of serum nagalase activity and with significant clinical benefits. Here, we report the results of the administration of GcMAF to a heterogeneous cohort of patients with histologically diverse, advanced neoplasms, generally considered as "incurable" diseases. In most cases, GcMAF therapy was initiated at late stages of tumor progression. As this is an open-label, non-controlled, retrospective analysis, caution must be employed when establishing cause-effect relationships between the administration GcMAF and disease outcome. However, the response to GcMAF was generally robust and some trends emerged. All patients (n = 20) presented with elevated serum nagalase activity, well above normal values. All patients but one showed a significant decrease of serum nagalase activity upon weekly GcMAF injections. Decreased nagalase activity was associated with improved clinical conditions and no adverse side effects were reported. The observations reported here confirm and extend previous results and pave the way to further studies aimed at assessing the precise role and indications for GcMAF-based anticancer immunotherapy.

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.

Progressive Care Nurses Improving Patient Safety by Limiting Interruptions During Medication Administration.

PubMed

Flynn, Fran; Evanish, Julie Q; Fernald, Josephine M; Hutchinson, Dawn E; Lefaiver, Cheryl

2016-08-01

Because of the high frequency of interruptions during medication administration, the effectiveness of strategies to limit interruptions during medication administration has been evaluated in numerous quality improvement initiatives in an effort to reduce medication administration errors. To evaluate the effectiveness of evidence-based strategies to limit interruptions during scheduled, peak medication administration times in 3 progressive cardiac care units (PCCUs). A secondary aim of the project was to evaluate the impact of limiting interruptions on medication errors. The percentages of interruptions and medication errors before and after implementation of evidence-based strategies to limit interruptions were measured by using direct observations of nurses on 2 PCCUs. Nurses in a third PCCU served as a comparison group. Interruptions (P < .001) and medication errors (P = .02) decreased significantly in 1 PCCU after implementation of evidence-based strategies to limit interruptions. Avoidable interruptions decreased 83% in PCCU1 and 53% in PCCU2 after implementation of the evidence-based strategies. Implementation of evidence-based strategies to limit interruptions in PCCUs decreases avoidable interruptions and promotes patient safety. ©2016 American Association of Critical-Care Nurses.

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

PubMed

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

1996-01-01

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

Natrium dischargement from peripheral blood as a predominant factor influenced by the administration of banana (Musa paradisiaca) on elderly female hypertensive patient

NASA Astrophysics Data System (ADS)

Pramono, A.; Noriko, N.; Komara, S. B.

2017-04-01

Hypertension is more common in eldery female that triggered by diet and lifestyle changes. Bananas were not only useful for the food, but also for hypertension therapy and preserving life. Administration of bananas decreased blood pressure in hypertensive patients. This study aims to identify of factors that influenced by the administration of banana (Musa paradisiaca) on elderly female hypertensive patient. Twenty of eldery female patient were divided into 2 respondents group: control (11 patients) and treatment (9 patients). The treatment groups received banana twice a day during 2 weeks, but the control group didn’t. Here, we showed the administration of banana significantly decreased blood pressure on elderly female hypertensive patient (p = 0.00) in both systole and diastole. There was a significant decrease in sodium levels (p = 0.037) in the blood, but potassium levels remained the same. Erythrocyte sedimentation level (p = 0.136) and trombocyte count (p = 0.176) in treatment group, were not affected by banana administration. Taken together, banana administration on elderly female hypertensive patient decreased the blood pressure significantly, greatly affected by the natrium dischargement from the blood. Thus, our findings contribute to preliminary comprehension of banana effect on hypertension reduction.

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

PubMed

Maguire, David R; France, Charles P

2016-04-01

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

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

PubMed Central

Maguire, David R.; France, Charles P.

2015-01-01

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

High Fat Diet-Induced Skeletal Muscle Wasting Is Decreased by Mesenchymal Stem Cells Administration: Implications on Oxidative Stress, Ubiquitin Proteasome Pathway Activation, and Myonuclear Apoptosis

PubMed Central

Aravena, Javier; Cabrera, Daniel; Simon, Felipe; Ezquer, Fernando

2016-01-01

Obesity can lead to skeletal muscle atrophy, a pathological condition characterized by the loss of strength and muscle mass. A feature of muscle atrophy is a decrease of myofibrillar proteins as a result of ubiquitin proteasome pathway overactivation, as evidenced by increased expression of the muscle-specific ubiquitin ligases atrogin-1 and MuRF-1. Additionally, other mechanisms are related to muscle wasting, including oxidative stress, myonuclear apoptosis, and autophagy. Stem cells are an emerging therapy in the treatment of chronic diseases such as high fat diet-induced obesity. Mesenchymal stem cells (MSCs) are a population of self-renewable and undifferentiated cells present in the bone marrow and other mesenchymal tissues of adult individuals. The present study is the first to analyze the effects of systemic MSC administration on high fat diet-induced skeletal muscle atrophy in the tibialis anterior of mice. Treatment with MSCs reduced losses of muscle strength and mass, decreases of fiber diameter and myosin heavy chain protein levels, and fiber type transitions. Underlying these antiatrophic effects, MSC administration also decreased ubiquitin proteasome pathway activation, oxidative stress, and myonuclear apoptosis. These results are the first to indicate that systemically administered MSCs could prevent muscle wasting associated with high fat diet-induced obesity and diabetes. PMID:27579157

Lysergic acid diethylamide (LSD) administration selectively downregulates serotonin2 receptors in rat brain.

PubMed

Buckholtz, N S; Zhou, D F; Freedman, D X; Potter, W Z

1990-04-01

A dosage regimen of lysergic acid diethylamide (LSD) that reliably produces behavioral tolerance in rats was evaluated for effects on neurotransmitter receptor binding in rat brain using a variety of radioligands selective for amine receptor subtypes. Daily administration of LSD [130 micrograms/kg (0.27 mumol/kg) intraperitoneally (IP)] for 5 days produced a decrease in serotonin2 (5-hydroxytryptamine2, 5-HT2) binding in cortex (measured 24 hours after the last drug administration) but did not affect binding to other receptor systems (5-HT1A, 5-HT1B, beta-adrenergic, alpha 1- or alpha 2-adrenergic, D2-dopaminergic) or to a recognition site for 5-HT uptake. The decrease was evident within 3 days of LSD administration but was not demonstrable after the first LSD dose. Following 5 days of LSD administration the decrease was still present 48 hours, but not 96 hours, after the last administration. The indole hallucinogen psilocybin [1.0 mg/kg (3.5 mumol/kg) for 8 days] also produced a significant decrease in 5HT2 binding, but neither the nonhallucinogenic analog bromo-LSD [1.3 mg/kg (2.4 mumol/kg) for 5 days] nor mescaline [10 mg/kg (40.3 mumol/kg) for 5 or 10 days] affected 5-HT2 binding. These observations suggest that LSD and other indole hallucinogens may act as 5-HT2 agonists at postsynaptic 5-HT2 receptors. Decreased 5-HT2 binding strikingly parallels the development and loss of behavioral tolerance seen with repeated LSD administration, but the decreased binding per se cannot explain the gamut of behavioral tolerance and cross-tolerance phenomena among the indole and phenylethylamine hallucinogens.

Phenobarbital administration every eight hours: improvement of seizure management in idiopathic epileptic dogs with decreased phenobarbital elimination half-life.

PubMed

Stabile, F; Barnett, C R; De Risio, L

2017-02-18

Estimated prevalence of canine idiopathic epilepsy is 0.6 per cent in the first-opinion canine population in the UK. Phenobarbital monotherapy has been reported to reduce/eradicate seizure activity in 60-93 per cent of idiopathic epileptic dogs (IEDs). The objective of this study was to evaluate safety and efficacy of the administration of phenobarbital orally every eight hours in IEDs with phenobarbital elimination half-life less than 20 hours. Medical records of 10 IEDs in which steady state trough serum phenobarbital levels were within the reference range and phenobarbital elimination half-life had become less than 20 hours following prolonged administration every 12 hours were reviewed. Side effects and seizure frequency when phenobarbital was administered every 12 hours or 8 hours were compared. In all dogs the side effects of the antiepileptic medication treatment improved. When phenobarbital was administered every eight hours, 9/10 dogs experienced improvement in seizure frequency and 8/10 dogs maintained seizure freedom for a period three times longer than the longest interictal interval period previously recorded. Reduction in the severity and number of clusters of seizures was recorded in one of the remaining two dogs. The administration of phenobarbital orally every eight hours in IEDs with decreased phenobarbital elimination half-life appears safe and can improve seizure management. The results of this study were presented in abstract form (poster) for the 28th symposium of the European Society of Veterinary Neurology - European College of Veterinary Neurology (ESVN), September 18-19, 2015, Amsterdam, Netherlands. British Veterinary Association.

Prophylactic Oral Administration of Magnesium Ameliorates Dextran Sulfate Sodium-Induced Colitis in Mice through a Decrease of Colonic Accumulation of P2X7 Receptor-Expressing Mast Cells.

PubMed

Ohbori, Kenshi; Fujiwara, Makiko; Ohishi, Akihiro; Nishida, Kentaro; Uozumi, Yoshinobu; Nagasawa, Kazuki

2017-01-01

The number of patients with colitis has been increasing year by year. Recently, intestinal inflammation, as one of the factors for its onset, has been demonstrated to be induced by P2X7 receptor-mediated activation of colonic immune cells such as mast cells. Activation of P2X7 receptor (P2X7R) is known to be inhibited by divalent metal cations such as magnesium, but whether or not magnesium administration prevents/relieves colitis is unknown so far. Here, we report that oral (per os (p.o.)) administration of MgCl 2 and ingestion of commercially available magnesium-rich mineral hard water relieves dextran sulfate sodium (DSS)-induced colitis in mice. Colitis was induced through ingestion of a 3% (w/v) DSS solution ad libitum for 10 d. Brilliant blue G (BBG, a P2X7R antagonist), MgCl 2 or magnesium-rich mineral hard water was administered p.o. to mice via gastric intubation once a day or ad libitum from a day before DSS administration for 11 times or 11 d, respectively. DSS-treated mice exhibited a low disease activity index, a short colon and a high histological score compared to in control mice. As BBG (250 mg/kg, p.o.), administration of a MgCl 2 solution (100 or 500 mg/kg, p.o.) and ad libitum ingestion of the magnesium-rich mineral hard water (212 ppm as magnesium) partially, but significantly, attenuated the severity of colitis by decreasing the accumulation of P2X7R-immunopositive mast cells in the colon. Therefore, prophylactic p.o. administration/ingestion of magnesium is considered to be partially effective to protect mice against DSS-induced colitis by inhibiting P2X7R-mediated activation/accumulation of colonic mast cells.

Long-term administration with levonorgestrel decreases allopregnanolone levels and alters GABA(A) receptor subunit expression and anxiety-like behavior.

PubMed

Porcu, Patrizia; Mostallino, Maria Cristina; Sogliano, Cristiana; Santoru, Francesca; Berretti, Roberta; Concas, Alessandra

2012-08-01

Fluctuations in the concentrations of the neuroactive steroid allopregnanolone are thought to influence γ-amino-butyric acid type A (GABA(A)) receptor gene expression and function. Long-term treatment with ethinyl estradiol (EE) plus levonorgestrel (LNG), two of the most widely used steroids in the hormonal contraceptive pill, decreases allopregnanolone levels in rat cerebral cortex and plasma, alters GABA(A) receptor expression and induces anxiety-like behavior. We evaluated which component of the hormonal contraceptive pill is responsible for the aforementioned changes. Female rats were injected subcutaneously (s.c.) with EE (0.030 mg) or LNG (0.125 mg) once a day for 4 weeks. Compared to the respective vehicle-treated control groups, EE decreased cerebral cortical levels of allopregnanolone, progesterone and pregnenolone by 76, 72 and 33%, respectively and hippocampal levels by 52, 56 and 50%, respectively. Likewise, LNG decreased cerebral cortical levels of allopregnanolone, progesterone and pregnenolone by 75, 68 and 33%, respectively, and hippocampal levels by 55, 65 and 60%, respectively. Administration of LNG, but not EE, increased the abundance of the γ2 subunit peptide in cerebral cortex and hippocampus by 38 and 59%, respectively. Further, LNG, but not EE, decreased the time spent and the number of entries into the open arms of the elevated plus maze by 56 and 43%, respectively, an index of anxiety-like behavior. These results suggest that alterations in GABA(A) receptor subunit expression and anxiety-like behavior induced by long-term treatment with combined EE/LNG appear to be caused by LNG. Given that both EE and LNG decrease allopregnanolone levels in a similar manner, these results further suggest that changes in allopregnanolone levels are not associated with GABA(A) receptor expression. Copyright © 2012 Elsevier Inc. All rights reserved.

The Absence of Fever Is Associated With Higher Mortality and Decreased Antibiotic and IV Fluid Administration in Emergency Department Patients With Suspected Septic Shock.

PubMed

Henning, Daniel J; Carey, Jeremy R; Oedorf, Kimie; Day, Danielle E; Redfield, Colby S; Huguenel, Colin J; Roberts, Jonathan C; Sanchez, Leon D; Wolfe, Richard E; Shapiro, Nathan I

2017-06-01

This study evaluates whether emergency department septic shock patients without a fever (reported or measured) receive less IV fluids, have decreased antibiotic administration, and suffer increased in-hospital mortality. This was a secondary analysis of a prospective, observational study of patients with shock. The study was conducted in an urban, academic emergency department. The original study enrolled consecutive adult (aged 18 yr or older) emergency department patients from November 11, 2012, to September 23, 2013, who met one of the following shock criteria: 1) systolic blood pressure less than 90 mm Hg after at least 1L IV fluids, 2) new vasopressor requirement, or 3) systolic blood pressure less than 90 mm Hg and IV fluids held for concern of fluid overload. The current study is limited to patients with septic shock. Patients were grouped as febrile if they had a subjective fever or a measured temperature >100.4°F documented in the emergency department; afebrile patients lacked both. Among 378 patients with septic shock, 207 of 378 (55%; 50-60%) were febrile by history or measurement. Afebrile patients had lower rates of antibiotic administration in the emergency department (81% vs 94%; p < 0.01), lower mean volumes of IV fluids (2,607 vs 3,013 mL; p < 0.01), and higher in-hospital mortality rates (33% vs 11%; p < 0.01). After adjusting for bicarbonate less than 20 mEq/L, lactate concentration, respiratory rate greater than or equal to 24 breaths/min, emergency department antibiotics, and emergency department IV fluids volume, being afebrile remained a significant predictor of in-hospital mortality (odds ratio, 4.3; 95% CI, 2.2-8.2; area under the curve = 0.83). In emergency department patients with septic shock, afebrile patients received lower rates of emergency department antibiotic administration, lower mean IV fluids volume, and suffered higher in-hospital mortality.

The potency of fluvoxamine to reduce ethanol self-administration decreases with concurrent availability of food.

PubMed

Ginsburg, Brett C; Pinkston, Jonathan W; Lamb, Richard J

2012-04-01

The selective serotonin reuptake inhibitor fluvoxamine reduces responding for ethanol at lower doses than responding for food when each is available in separate components or separate groups of rats. However, when both are available concurrently and deliveries earned per session are equal, this apparent selectivity inverts and food-maintained behavior is more sensitive than ethanol-maintained behavior to rate-decreasing effects of fluvoxamine. Here, we investigated further the impact that concurrent access to both food and ethanol has on the potency of fluvoxamine. Fluvoxamine (5.6-17.8 mg/kg) potency was assessed under conditions in which food and ethanol were available concurrently and response rates were equal [average variable intervals (VIs) 405 and 14 s for food and ethanol, respectively], as well as when density of food delivery was increased (average VI 60 s for food and VI 14 s for ethanol). The potency of fluvoxamine was also determined when only ethanol was available (food extinction and average VI 14 s for ethanol) and under multiple VIs (VI 30 s for food and ethanol) wherein either food or ethanol was the only programmed reinforcement available during each component. Fluvoxamine was less potent at decreasing ethanol self-administration when food was available concurrently {ED50 [95% confidence limit (CL): 8.2 (6.5-10.3) and 10.7 (7.9-14.4)]} versus when ethanol was available in isolation [ED50: 4.0 (2.7-5.9) and 5.1 (4.3-6.0)]. Effects on food were similar under each condition in which food was available. The results demonstrate that the potency of fluvoxamine in reducing ethanol-maintained behavior depends on whether ethanol is available in isolation or in the context of concurrently scheduled food reinforcement.

GC protein-derived macrophage-activating factor decreases α-N-acetylgalactosaminidase levels in advanced cancer patients

PubMed Central

Thyer, Lynda; Ward, Emma; Smith, Rodney; Branca, Jacopo JV; Morucci, Gabriele; Gulisano, Massimo; Noakes, David; Eslinger, Robert; Pacini, Stefania

2013-01-01

α-N-acetylgalactosaminidase (nagalase) accumulates in the serum of cancer patients and its activity correlates with tumor burden, aggressiveness and clinical disease progression. The administration of GC protein-derived macrophage-activating factor (GcMAF) to cancer patients with elevated levels of nagalase has been associated with a decrease of serum nagalase activity and with significant clinical benefits. Here, we report the results of the administration of GcMAF to a heterogeneous cohort of patients with histologically diverse, advanced neoplasms, generally considered as “incurable” diseases. In most cases, GcMAF therapy was initiated at late stages of tumor progression. As this is an open-label, non-controlled, retrospective analysis, caution must be employed when establishing cause-effect relationships between the administration GcMAF and disease outcome. However, the response to GcMAF was generally robust and some trends emerged. All patients (n = 20) presented with elevated serum nagalase activity, well above normal values. All patients but one showed a significant decrease of serum nagalase activity upon weekly GcMAF injections. Decreased nagalase activity was associated with improved clinical conditions and no adverse side effects were reported. The observations reported here confirm and extend previous results and pave the way to further studies aimed at assessing the precise role and indications for GcMAF-based anticancer immunotherapy. PMID:24179708

Paroxetine decreased plasma exposure of glyburide partly via inhibiting intestinal absorption in rats.

PubMed

Jiang, Shuwen; Zhao, Weiman; Chen, Yang; Zhong, Zeyu; Zhang, Mian; Li, Feng; Xu, Ping; Zhao, Kaijing; Li, Ying; Liu, Li; Liu, Xiaodong

2015-06-01

Accumulating evidences have shown that diabetes is often accompanied with depression, thus it is possible that oral antidiabetic agent glyburide and antidepressive agent paroxetine are co-administered in diabetic patients. The aim of this study was to assess interactions between glyburide and paroxetine in rats. Effect of paroxetine on pharmacokinetics of orally administered glyburide was investigated. Effect of naringin (NAR), an inhibitor of rat intestinal organic anion transporting polypeptides 1a5 (Oatp1a5), on pharmacokinetics of glyburide was also studied. The results showed that co-administration of paroxetine markedly reduced plasma exposure and prolonged Tmax of glyburide, accompanied by significant increase in fecal excretion of glyburide. Co-administration of naringin also significantly decreased plasma exposure of glyburide. Data from intestinal perfusion experiments showed that both paroxetine and naringin significantly inhibited intestinal absorption of glyburide. Caco-2 cells were used to investigate whether paroxetine and naringin affected intestinal transport of glyburide and fexofenadine (a substrate of Oatp1a5). The results showed that both paroxetine and naringin greatly inhibited absorption of glyburide and fexofenadine. All results gave a conclusion that co-administration of paroxetine decreased plasma exposure of glyburide in rats via inhibiting intestinal absorption of glyburide, which may partly be attributed to the inhibition of intestinal Oatp1a5 activity. Copyright © 2015 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.

5 CFR 894.510 - When may I decrease my type of enrollment?

Code of Federal Regulations, 2013 CFR

2013-01-01

... 5 Administrative Personnel 2 2013-01-01 2013-01-01 false When may I decrease my type of enrollment? 894.510 Section 894.510 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL... Changing Enrollment § 894.510 When may I decrease my type of enrollment? (a) You may decrease your type of...

Multiple oral dosing of ketoconazole influences pharmacokinetics of quinidine after intravenous and oral administration in beagle dogs.

PubMed

Kuroha, M; Shirai, Y; Shimoda, M

2004-10-01

In this study, we investigated the effect of multiple oral dosing of ketoconazole (KTZ) on pharmacokinetics of quinidine (QN), a CYP3A substrate with low hepatic clearance, after i.v. and oral administration in beagle dogs. Four dogs were given p.o. KTZ for 20 days (200 mg, b.i.d.). QN was administered either i.v. (1 mg/kg) or p.o. (100 mg) 10 and 20 days before the KTZ treatment and 10 and 20 days after start of KTZ treatment. Multiple oral dosing of KTZ decreased significantly alpha and beta, whereas increased t(1/2beta), V(1), and k(a). The KTZ treatment also decreased significantly both total body clearance (Cl(tot)) and oral clearance (Cl(oral)). No significant change in bioavailability was observed in the presence of KTZ. Co-administration of KTZ increased C(max) of QN to about 1.5-fold. Mean resident time after i.v. administration (MRT(i.v.)), and after oral administration (MRT(p.o.)) of QN were prolonged to about twofold, whereas mean absorption time (MAT) was decreased to 50%. Volume of distribution at steady state (V(d(ss))) of QN was unchanged in the presence of KTZ. These alterations may be because of a decrease in metabolism of QN by inhibition of KTZ on hepatic CYP3A activity. In conclusion, multiple oral dosing of KTZ affected largely pharmacokinetics of QN after i.v. and oral administration in beagle dogs. Therefore, KTZ at a clinical dosing regimen may markedly change the pharmacokinetics of drugs primarily metabolized by CYP3A with low hepatic clearance in dogs. In clinical use, much attention should be paid to concomitant administration of KTZ with the drug when given either p.o. or i.v.

Bardoxolone Methyl Decreases Megalin and Activates Nrf2 in the Kidney

PubMed Central

Chertow, Glenn M.; Hebbar, Sudarshan; Vaziri, Nosratola D.; Ward, Keith W.; Meyer, Colin J.

2012-01-01

Inflammation and oxidative stress are hallmarks and mediators of the progression of CKD. Bardoxolone methyl, a potent activator of the nuclear factor erythroid 2–related factor 2 (Nrf2)–mediated antioxidant and anti-inflammatory response, increases estimated GFR and decreases BUN, serum phosphorus, and uric acid concentrations in patients with moderate to severe CKD. However, it also increases albuminuria, which is associated with inflammation and disease progression. Therefore, we investigated whether this bardoxolone methyl–induced albuminuria may result from the downregulation of megalin, a protein involved in the tubular reabsorption of albumin and lipid-bound proteins. Administration of bardoxolone methyl to cynomolgus monkeys significantly decreased the protein expression of renal tubular megalin, which inversely correlated with the urine albumin-to-creatinine ratio. Moreover, daily oral administration of bardoxolone methyl to monkeys for 1 year did not lead to any adverse effects on renal histopathologic findings but did reduce serum creatinine and BUN, as observed in patients with CKD. Finally, the bardoxolone methyl–induced decrease in megalin corresponded with pharmacologic induction of renal Nrf2 targets, including NAD(P)H:quinone oxidoreductase 1 enzyme activity and glutathione content. This result indicates that Nrf2 may have a role in megalin regulation. In conclusion, these data suggest that the increase in albuminuria that accompanies bardoxolone methyl administration may result, at least in part, from reduced expression of megalin, which seems to occur without adverse effects and with strong induction of Nrf2 targets. PMID:22859857

Bardoxolone methyl decreases megalin and activates nrf2 in the kidney.

PubMed

Reisman, Scott A; Chertow, Glenn M; Hebbar, Sudarshan; Vaziri, Nosratola D; Ward, Keith W; Meyer, Colin J

2012-10-01

Inflammation and oxidative stress are hallmarks and mediators of the progression of CKD. Bardoxolone methyl, a potent activator of the nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated antioxidant and anti-inflammatory response, increases estimated GFR and decreases BUN, serum phosphorus, and uric acid concentrations in patients with moderate to severe CKD. However, it also increases albuminuria, which is associated with inflammation and disease progression. Therefore, we investigated whether this bardoxolone methyl-induced albuminuria may result from the downregulation of megalin, a protein involved in the tubular reabsorption of albumin and lipid-bound proteins. Administration of bardoxolone methyl to cynomolgus monkeys significantly decreased the protein expression of renal tubular megalin, which inversely correlated with the urine albumin-to-creatinine ratio. Moreover, daily oral administration of bardoxolone methyl to monkeys for 1 year did not lead to any adverse effects on renal histopathologic findings but did reduce serum creatinine and BUN, as observed in patients with CKD. Finally, the bardoxolone methyl-induced decrease in megalin corresponded with pharmacologic induction of renal Nrf2 targets, including NAD(P)H:quinone oxidoreductase 1 enzyme activity and glutathione content. This result indicates that Nrf2 may have a role in megalin regulation. In conclusion, these data suggest that the increase in albuminuria that accompanies bardoxolone methyl administration may result, at least in part, from reduced expression of megalin, which seems to occur without adverse effects and with strong induction of Nrf2 targets.

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

PubMed

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

2005-01-01

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

A dose-up of ursodeoxycholic acid decreases transaminases in hepatitis C patients

PubMed Central

Sato, Shuichi; Miyake, Tatsuya; Tobita, Hiroshi; Oshima, Naoki; Ishine, Junichi; Hanaoka, Takuya; Amano, Yuji; Kinoshita, Yoshikazu

2009-01-01

AIM: To examine whether a dose-up to 900 mg of ursodeoxycholic acid (UDCA) decreases transaminases in hepatitis C patients. METHODS: From January to December 2007, patients with chronic hepatitis C or compensated liver cirrhosis with hepatitis C virus (HCV) (43-80 years old) showing positive serum HCV-RNA who had already taken 600 mg/d of UDCA were recruited into this study. Blood parameters were examined at 4, 8 and 24 wk after increasing the dose of oral UDCA from 600 to 900 mg/d. RESULTS: Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transpeptidase (GGT) levels were significantly decreased following the administration of 900 mg/d as compared to 600 mg/d. The decrease in ALT from immediately before the dose-up of UDCA to 8 wk after the dose-up was 14.3 IU/L, while that for AST was 10.5 IU/L and for GGT was 9.8 IU/L. Platelet count tended to increase after the dose-up of UDCA, although it did not show a statistically significant level (P = 0.05). Minor adverse events were observed in 3 cases, although no drop-outs from the study occurred. CONCLUSION: Oral administration of 900 mg/d of UDCA was more effective than 600 mg/d for reducing ALT, AST, and GGT levels in patients with HCV-related chronic liver disease. PMID:19522030

Metoprolol decreases the plasma exposure of metformin via the induction of liver, kidney and muscle uptake in rats.

PubMed

Ma, Yan-Rong; Shi, A-Xi; Qin, Hong-Yan; Zhang, Tiffany; Wu, Yan-Fang; Zhang, Guo-Qiang; Wu, Xin-An

2016-12-01

Drug interactions are one of the commonest causes of side effects, particularly in long-term therapy. The aim of the current study was to investigate the possible effects of metoprolol on the pharmacokinetics of metformin in rats and to clarify the mechanism of drug interaction. In this study, rats were treated with metformin alone or in combination with metoprolol. Plasma, urine and tissue concentrations of metformin were determined by HPLC. Western blotting and real-time qPCR were used to evaluate the expression of rOCTs and rMATE1. The results showed that, after single or 7-day repeated administration, the plasma concentrations of metformin in the co-administration group were significantly decreased compared with that in the metformin group. However, the parameter V/F of metformin in the co-administration group was markedly increased compared with that in the metformin group. The hepatic, renal and muscular K p of metformin were markedly elevated after co-administration with metoprolol. Consistently, metformin uptake in rat kidney slices was significantly induced by metoprolol. In addition, multiple administrations of metoprolol significantly reduced the expression of rMATE1 in rat kidney as well as the urinary excretion of metformin. Importantly, after long-term administration, lactic acid and uric acid levels in the co-administration group were increased by 25% and 26%, respectively, compared with that in the metformin group. These results indicate that metoprolol can decrease the plasma concentration of metformin via the induction of hepatic, renal and muscular uptake, and long-term co-administration of metformin and metoprolol can cause elevated lactic acid and uric acid levels. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

[Preliminary study of clinical significance of decreased D(L)CO in patients with left ventricular heart failure].

PubMed

Tan, Xiao-yue; Sun, Xing-guo; Hu, Sheng-shou; Zhang, Jian; Huang, Jie; Chen, Zhi-gao; Ma, Li

2015-07-01

This study aimed to investigate the feature of D(L)CO (Diffusion Lung Capacity for Carbon Monoxide) in CHF (left ventricular heart failure) patients, underlying pathophysiological mechanism and clinical significance. We retrospectively studied the D(L)CO, pulmonary ventilation function, cardiopulmonary exercise testing and related clinical information in severer HF patients. Peak VO2 severely decreased to 34 ± 7 percentage of predicted(%pred) and anaerobic threshold to 48 ± 11%pred in all patients. D(L)CO moderately decreased to 63 ± 12%pred and there were 25 patients lower than 80%pred. FVC, FEV1, FEV1/FVC and TLC were 75 ± 14%pred, 71 ± 17%pred, 97 ± 11%pred, and 79 ± 13%pred, which indicated borderline or mild restrictive ventilatory dysfunction. The decrease of D(L)CO was more severe than those of TLC, FEV1 and FVC. For patients with severe CHF, cardiopulmonary exercise function is extremely limited, D(L)CO generally moderately declines and ventilation function is merely mildly limited. D(L)CO is the parameter for cardiopulmonary coupling, reflecting limitation of the cardiovascular dysfunction while without ventilatory limit.

Impact of electronic order management on the timeliness of antibiotic administration in critical care patients.

PubMed

Cartmill, Randi S; Walker, James M; Blosky, Mary Ann; Brown, Roger L; Djurkovic, Svetolik; Dunham, Deborah B; Gardill, Debra; Haupt, Marilyn T; Parry, Dean; Wetterneck, Tosha B; Wood, Kenneth E; Carayon, Pascale

2012-11-01

To examine the effect of implementing electronic order management on the timely administration of antibiotics to critical-care patients. We used a prospective pre-post design, collecting data on first-dose IV antibiotic orders before and after the implementation of an integrated electronic medication-management system, which included computerized provider order entry (CPOE), pharmacy order processing and an electronic medication administration record (eMAR). The research was performed in a 24-bed adult medical/surgical ICU in a large, rural, tertiary medical center. Data on the time of ordering, pharmacy processing and administration were prospectively collected and time intervals for each stage and the overall process were calculated. The overall turnaround time from ordering to administration significantly decreased from a median of 100 min before order management implementation to a median of 64 min after implementation. The first part of the medication use process, i.e., from order entry to pharmacy processing, improved significantly whereas no change was observed in the phase from pharmacy processing to medication administration. The implementation of an electronic order-management system improved the timeliness of antibiotic administration to critical-care patients. Additional system changes are required to further decrease the turnaround time. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Sublingual administration of detomidine in horses: sedative effect, analgesia and detection time.

PubMed

L'Ami, Jiske J; Vermunt, Lian E; van Loon, Johannes P A M; Sloet van Oldruitenborgh-Oosterbaan, Marianne M

2013-05-01

A single dose of 40 μg/kg bodyweight (BW) of oromucosal detomidine gel was administered sublingually to 10 healthy Dutch Warmblood mares aged 7 ± 4 years (mean ± SD) and BW 580 ± 69 kg. Blood and urine samples were collected before and for 8 days following administration and evaluated qualitatively in an FEI Reference Laboratory and quantitatively in a research laboratory. Clinical effects were evaluated at baseline and for 24 h after administration. Sedation was determined using head height and scores of reaction to auditory and mixed auditory/sensory stimuli. Mechanical nociceptive thresholds (MNTs) were assessed using pressure algometry to evaluate analgesia. Heart rate (HR) was measured and ataxia scored. All horses were considered negative for detomidine in blood samples by 48 h post-administration and in urine by 60 h. These results indicated that a safe withdrawal time for detomidine oromucosal gel may be 72 h following a single sublingual administration of 40 μg/kgBW. Decreases in HR and head height were maximal at 40 and 60 min post-administration, respectively. The maximal decrease in response to stimuli was observed at 100 min. Ataxia was maximal at 60 min. At 40 and 80 min MNTs were significantly increased compared to baseline. All parameters, except the MNTs of two locations, which were decreased, returned to baseline values within 24 h post-administration. Copyright © 2012 Elsevier Ltd. All rights reserved.

A possible mechanism for the decrease in serum thyroxine level by phenobarbital in rodents

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

Kato, Yoshihisa, E-mail: kato@kph.bunri-u.ac.jp; Suzuki, Hiroshi; Haraguchi, Koichi

2010-12-15

Effects of phenobarbital (PB) on the levels of serum thyroid hormones such as total thyroxine (T{sub 4}) and triiodothyronine were examined in male mice, hamsters, rats, and guinea pigs. One day after the final administration of PB (80 mg/kg, intraperitoneal, once daily for 4 days), significant decreases in the levels of the serum total T{sub 4} and free T{sub 4} occurred in mice, hamsters, and rats, while a significant decrease in the level of serum triiodothyronine was observed in hamsters and rats among the animals examined. In addition, a significant decrease in the level of serum thyroid-stimulating hormone was observedmore » in only hamsters among the rodents examined. Significant increases in the level and activity of hepatic T{sub 4}-UDP-glucuronosyltransferase (UGT1A) after the PB administration occurred in mice, hamsters, and rats, while the increase in the amount of biliary [{sup 125}I]T{sub 4}-glucuronide after an intravenous injection of [{sup 125}I]T{sub 4} to the PB-pretreated animals occurred only in rats. In mice, rats, and hamsters, but not guinea pigs, PB pretreatment promoted the clearance of [{sup 125}I]T{sub 4} from the serum, led to a significant increase in the steady-state distribution volumes of [{sup 125}I]T{sub 4}, and raised the concentration ratio (Kp value) of the liver to serum and the liver distribution of [{sup 125}I]T{sub 4}. The present findings indicate that the PB-mediated decreases in the serum T{sub 4} level in mice, hamsters, and rats, but not guinea pigs, occur mainly through an increase in the accumulation level of T{sub 4} in the liver.« less

Optimal precurarizing dose of rocuronium to decrease fasciculation and myalgia following succinylcholine administration.

PubMed

Kim, Kyu Nam; Kim, Kyo Sang; Choi, Hoon Il; Jeong, Ji Seon; Lee, Hee-Jong

2014-06-01

Succinylcholine commonly produces frequent adverse effects, including muscle fasciculation and myalgia. The current study identified the optimal dose of rocuronium to prevent succinylcholine-induced fasciculation and myalgia and evaluated the influence of rocuronium on the speed of onset produced by succinylcholine. This randomized, double-blinded study was conducted in 100 patients randomly allocated into five groups of 20 patients each. Patients were randomized to receive 0.02, 0.03, 0.04, 0.05 and 0.06 mg/kg rocuronium as a precurarizing dose. Neuromuscular monitoring after each precurarizing dose was recorded from the adductor pollicis muscle using acceleromyography with train-of-four stimulation of the ulnar nerve. All patients received succinylcholine 1.5 mg/kg at 2 minutes after the precurarization, and were assessed the incidence and severity of fasciculations, while myalgia was assessed at 24 hours after surgery. The incidence and severity of visible muscle fasciculation was significantly less with increasing the amount of precurarizing dose of rocuronium (P < 0.001). Those of myalgia tend to decrease according to increasing the amount of precurarizing dose of rocuronium, but there was no significance (P = 0.072). The onset time of succinylcholine was significantly longer with increasing the amount of precurarizing dose of rocuronium (P < 0.001). Precurarization with 0.04 mg/kg rocuronium was the optimal dose considering the reduction in the incidence and severity of fasciculation and myalgia with acceptable onset time, and the safe and effective precurarization.

Oxidative metabolism of limbic structures after acute administration of diazepam, alprazolam and zolpidem.

PubMed

González-Pardo, Héctor; Conejo, Nélida M; Arias, Jorge L

2006-08-30

The effects of acute administration of two benzodiazepines and a non-benzodiazepine hypnotic on behavior and brain metabolism were evaluated in rats. After testing the behavioral action of the benzodiazepines on the open field and the elevated plus-maze, the effects of the three drugs on neuronal metabolism of particular limbic regions were measured using cytochrome c oxidase (CO) histochemistry. Diazepam (5 mg/kg i.p.) and alprazolam (0.5 mg/kg i.p.) induced clear anxiolytic effects and a decrease in locomotion, whereas zolpidem (2 mg/kg i.p.) caused an intense hypnotic effect. The anxiolytic effects of alprazolam were distinguishable from diazepam due to the pharmacological and clinical profile of this triazolobenzodiazepine. CO activity decreased significantly in almost all the limbic regions evaluated after zolpidem administration. However, significant prominent decreases in CO activity were found after diazepam treatment in the medial mammillary nucleus, anteroventral thalamus, cingulate cortex, dentate gyrus and basolateral amygdala. Alprazolam caused similar decreases in CO activity, with the exception of the prelimbic and cingulate cortices, where significant increases were detected. In agreement with previous studies using other functional mapping techniques, our results indicate that particular benzodiazepines and non-benzodiazepine hypnotics induce selective changes in brain oxidative metabolism.

Medication calculation and administration workshop and hurdle assessment increases student awareness towards the importance of safe practices to decrease medication errors in the future.

PubMed

Wallace, Darlene; Woolley, Torres; Martin, David; Rasalam, Roy; Bellei, Maria

2016-01-01

Medication errors are the second most frequently reported hospital incident in Australia and are a global concern. A "Medication Calculation and Administration" workshop followed by a "hurdle" assessment (compulsory task mandating a minimum level of performance as a condition of passing the course) was introduced into Year 2 of the James Cook University medical curriculum to decrease dosage calculation and administration errors among graduates. This study evaluates the effectiveness of this educational activity as a long-term strategy to teach medical students' essential skills in calculating and administering medications. This longitudinal study used a pre- and post-test design to determine whether medical students retained their calculation and administration skills over a period of 4 years. The ability to apply basic mathematical skills to medication dose calculation, principles of safe administration (Part 1), and ability to access reference materials to check indications, contraindications, and writing the medication order with correct abbreviations (Part 2) were compared between Year 2 and 6 assessments. Scores for Parts 1, 2 and total scores were nearly identical from Year 2 to Year 6 (P = 0.663, 0.408, and 0.472, respectively), indicating minimal loss of knowledge by students in this period. Most Year 6 students (86%) were able to recall at least 5 of the "6 Rights of Medication Administration" while 84% reported accessing reference material and 91% reported checking their medical calculations. The "Medication Calculation and Administration" workshop with a combined formative and summative assessment - a "hurdle" - promotes long-term retention of essential clinical skills for medical students. These skills and an awareness of the problem are strategies to assist medical graduates in preventing future medication-related adverse events.

Aspirin decreases platelet uptake on Dacron vascular grafts in baboons

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

Mackey, W.C.; Connolly, R.J.; Callow, A.D.

The influence of a single dose of aspirin (5.4-7.4 mg/kg) on platelet uptake on 4-mm Dacron interposition grafts was studied in a baboon model using gamma camera scanning for 111-Indium labeled platelets. In vitro assessment of platelet function after aspirin administration revealed that in the baboon, as in the human, aspirin abolished arachidonic acid-induced platelet aggregation, prolonged the lag time between exposure to collagen and aggregation, and decreased plasma thromboxane B2 levels. Aspirin also prolonged the template bleeding time. Scans for 111-Indium labeled platelets revealed that pretreatment with a single dose of aspirin decreased platelet uptake on 4-mm Dacron carotidmore » interposition grafts. This decrease in platelet uptake was associated with a significant improvement in 2-hour graft patency and with a trend toward improved 2-week patency.« less

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

Statewide ban on recreational fires resulted in a significant decrease in campfire-related summer burn center admissions.

PubMed

Hoang, David Manh; Reid, Dixie; Lentz, Christopher William

2013-01-01

Every summer, there is an increase in the number of burn injuries caused by accidents around campfires. Because of the prevalence of drought, high winds, and uncontrolled wild fires, a statewide ban on recreational fires was instituted in New Mexico from June to July 2011. We hypothesized that this legislation would have a significant impact on burn admissions caused by campfire-related injuries. A retrospective review of summer admissions to a state burn center was conducted to assess the effect of this ban on recreational fire injuries, and these data were compared with that of the previous summer when no ban was in effect. All burn admissions to a state burn center were reviewed from Memorial Day to Labor Day in 2010 and 2011. Data collected included cause, % TBSA, age, days of hospitalization, intensive care unit days, and total surface area grafted. Nonparametric statistical analysis was performed with Fisher exact test for dichotomous data and Mann-Whitney test for continuous data with significance at P < .05. There were 164 burn center admissions between Memorial Day and Labor Day in 2010 (n = 82) and 2011 (n = 82). Compared with all summer burn center admissions, patients injured by campfires were younger (18 vs 37 years; P = .002) with smaller total surface area burns (3.2 vs 6.2%; P = .41) and had shorter lengths of stay (10-11 vs 6-7 days; P = .62). There was more than a 3-fold decrease in burn admissions due to recreational fires during the study period (n = 14 [17%] in 2010 and 4 [5%] in 2011; P = .02). This resulted in a decrease in the number of patient-days from 91 in 2010 to 25 in 2011. Half of the camp fire admissions required skin grafts to definitively close the wounds (6/14 in 2010 and 2/4 in 2011). Recreational fire bans targeted at controlling wildfires during conditions favoring rapid spread were associated with a 3- to 4-fold decrease in campfire-related burn admissions. Compared with a summer when no fire ban was in effect, the number of

Long-term administration of Greek Royal Jelly decreases GABA concentration in the striatum and hypothalamus of naturally aged Wistar male rats.

PubMed

Pyrzanowska, Justyna; Wawer, Adriana; Joniec-Maciejak, Ilona; Piechal, Agnieszka; Blecharz-Klin, Kamilla; Graikou, Konstantia; Chinou, Ioanna; Widy-Tyszkiewicz, Ewa

2018-05-14

Royal Jelly (RJ) is a unique substance obtained from bees that has been used widely in European and Asian traditional medicine for its potential to prevent signs of aging through its antioxidative, anti-inflammatory, anti-hyperglycemic and anti-hypercholesterolemic properties. We recently reported an enhancement in spatial memory along with changes in monoaminergic transmission in aged rats after chronic RJ administration. Here, we aim to further explore the action of RJ on central nervous system activity by examining levels of amino acids in selected brain structures of aged male Wistar rats following 2-months of Greek RJ administration. RJ powder was previously chemically characterized and given orally (50 or 100 mg of powder/kg b.w./day) by gastric gavage. The concentrations of amino acids (alanine, aspartic acid, gamma-aminobutyric acid, glutamic acid, histidine and taurine) in the brain regions examined (prefrontal cortex, hippocampus, striatum and hypothalamus) were quantified using HPLC. We also examined basic biochemical parameters of renal and hepatic activity, as damage of these organs could potentially explain the changes in brain function and behavior. Upon biochemical examination, a decrease in the concentration of gamma-aminobutyric acid was observed in both the striatum and hypothalamus. Liver and kidney functions were not changed by chronic RJ-administration. Our results provide insight toward understanding the mechanism of action of RJ and its effects on neurotransmission in the central nervous system. Copyright © 2018 Elsevier B.V. All rights reserved.

Quality improvements in decreasing medication administration errors made by nursing staff in an academic medical center hospital: a trend analysis during the journey to Joint Commission International accreditation and in the post-accreditation era

PubMed Central

Wang, Hua-fen; Jin, Jing-fen; Feng, Xiu-qin; Huang, Xin; Zhu, Ling-ling; Zhao, Xiao-ying; Zhou, Quan

2015-01-01

Background Medication errors may occur during prescribing, transcribing, prescription auditing, preparing, dispensing, administration, and monitoring. Medication administration errors (MAEs) are those that actually reach patients and remain a threat to patient safety. The Joint Commission International (JCI) advocates medication error prevention, but experience in reducing MAEs during the period of before and after JCI accreditation has not been reported. Methods An intervention study, aimed at reducing MAEs in hospitalized patients, was performed in the Second Affiliated Hospital of Zhejiang University, Hangzhou, People’s Republic of China, during the journey to JCI accreditation and in the post-JCI accreditation era (first half-year of 2011 to first half-year of 2014). Comprehensive interventions included organizational, information technology, educational, and process optimization-based measures. Data mining was performed on MAEs derived from a compulsory electronic reporting system. Results The number of MAEs continuously decreased from 143 (first half-year of 2012) to 64 (first half-year of 2014), with a decrease in occurrence rate by 60.9% (0.338% versus 0.132%, P<0.05). The number of MAEs related to high-alert medications decreased from 32 (the second half-year of 2011) to 16 (the first half-year of 2014), with a decrease in occurrence rate by 57.9% (0.0787% versus 0.0331%, P<0.05). Omission was the top type of MAE during the first half-year of 2011 to the first half-year of 2014, with a decrease by 50% (40 cases versus 20 cases). Intravenous administration error was the top type of error regarding administration route, but it continuously decreased from 64 (first half-year of 2012) to 27 (first half-year of 2014). More experienced registered nurses made fewer medication errors. The number of MAEs in surgical wards was twice that in medicinal wards. Compared with non-intensive care units, the intensive care units exhibited higher occurrence rates of MAEs

Quality improvements in decreasing medication administration errors made by nursing staff in an academic medical center hospital: a trend analysis during the journey to Joint Commission International accreditation and in the post-accreditation era.

PubMed

Wang, Hua-Fen; Jin, Jing-Fen; Feng, Xiu-Qin; Huang, Xin; Zhu, Ling-Ling; Zhao, Xiao-Ying; Zhou, Quan

2015-01-01

Medication errors may occur during prescribing, transcribing, prescription auditing, preparing, dispensing, administration, and monitoring. Medication administration errors (MAEs) are those that actually reach patients and remain a threat to patient safety. The Joint Commission International (JCI) advocates medication error prevention, but experience in reducing MAEs during the period of before and after JCI accreditation has not been reported. An intervention study, aimed at reducing MAEs in hospitalized patients, was performed in the Second Affiliated Hospital of Zhejiang University, Hangzhou, People's Republic of China, during the journey to JCI accreditation and in the post-JCI accreditation era (first half-year of 2011 to first half-year of 2014). Comprehensive interventions included organizational, information technology, educational, and process optimization-based measures. Data mining was performed on MAEs derived from a compulsory electronic reporting system. The number of MAEs continuously decreased from 143 (first half-year of 2012) to 64 (first half-year of 2014), with a decrease in occurrence rate by 60.9% (0.338% versus 0.132%, P<0.05). The number of MAEs related to high-alert medications decreased from 32 (the second half-year of 2011) to 16 (the first half-year of 2014), with a decrease in occurrence rate by 57.9% (0.0787% versus 0.0331%, P<0.05). Omission was the top type of MAE during the first half-year of 2011 to the first half-year of 2014, with a decrease by 50% (40 cases versus 20 cases). Intravenous administration error was the top type of error regarding administration route, but it continuously decreased from 64 (first half-year of 2012) to 27 (first half-year of 2014). More experienced registered nurses made fewer medication errors. The number of MAEs in surgical wards was twice that in medicinal wards. Compared with non-intensive care units, the intensive care units exhibited higher occurrence rates of MAEs (1.81% versus 0.24%, P<0

Development of the National Transplant Program Has Significantly Decreased but Not Ended Transplant Tourism in Montenegro.

PubMed

Ratkovic, M; Basic Jukic, N; Kastelan, Z; Radunovic, D; Kavaric, P; Brezak, J; Topalovic Grkovic, M; Hudolin, T; Prelevic, V

2018-06-01

Organ transplantation has prolonged and improved the lives of many patients around the world. However, a widespread shortage of donors remains the main factor that has led to organ trafficking and transplant tourism. To stop transplant tourism and to provide optimal treatment for its citizens with end-stage renal disease, Montenegro started performing renal transplantations in September 2012. Thirty-five transplantations have been performed since that time, 34 from living donors and only 1 from a deceased donor. This practice has significantly decreased but not ended transplant tourism in Montenegro. Copyright © 2018 Elsevier Inc. All rights reserved.

Decreased Fibrogenesis After Treatment with Pirfenidone in a Newly Developed Mouse Model of Intestinal Fibrosis.

PubMed

Meier, Remo; Lutz, Christian; Cosín-Roger, Jesus; Fagagnini, Stefania; Bollmann, Gabi; Hünerwadel, Anouk; Mamie, Celine; Lang, Silvia; Tchouboukov, Alexander; Weber, Franz E; Weber, Achim; Rogler, Gerhard; Hausmann, Martin

2016-03-01

Fibrosis as a common problem in patients with Crohn's disease is a result of an imbalance toward excessive tissue repair. At present, there is no specific treatment option. Pirfenidone is approved for the treatment of idiopathic pulmonary fibrosis with both antifibrotic and anti-inflammatory effects. We subsequently investigated the impact of pirfenidone treatment on development of fibrosis in a new mouse model of intestinal fibrosis. Small bowel resections from donor mice were transplanted subcutaneously into the neck of recipients. Animals received either pirfenidone (100 mg/kg, three times daily, orally) or vehicle. After administration of pirfenidone, a significantly decreased collagen layer thickness was revealed as compared to vehicle (9.7 ± 1.0 versus 13.5 ± 1.5 µm, respectively, **P < 0.001). Transforming growth factor-β and matrix metalloproteinase-9 were significantly decreased after treatment with pirfenidone as confirmed by real-time PCR (0.42 ± 0.13 versus 1.00 ± 0.21 and 0.46 ± 0.24 versus 1.00 ± 0.62 mRNA expression level relative to GAPDH, respectively, *P < 0.05). Significantly decreased transforming growth factor-β after administration of pirfenidone was confirmed by Western blotting. In our mouse model, intestinal fibrosis can be reliably induced and is developed within 7 days. Pirfenidone partially prevented the development of fibrosis, making it a potential treatment option against Crohn's disease-associated fibrosis.

Modulatory effects of alpha-lipoic acid (ALA) administration on insulin sensitivity in obese PCOS patients.

PubMed

Genazzani, A D; Shefer, K; Della Casa, D; Prati, A; Napolitano, A; Manzo, A; Despini, G; Simoncini, T

2018-05-01

To evaluate the efficacy of alpha-lipoic acid (ALA) administration on hormonal and metabolic parameters of obese PCOS patients. A group of 32 obese PCOS patients were selected after informed consent. 20 patients referred to have first grade relatives with diabetes type I or II. Hormonal and metabolic parameters as well as OGTT were evaluated before and after 12 weeks of ALA integrative administration (400 mg per os every day). ALA administration significantly decreased insulin, glucose, BMI and HOMA index. Hyperinsulinemia and insulin response to OGTT decreased both as maximal response (Δmax) and as AUC. PCOS with diabetes relatives showed the decrease also of triglyceride and GOT. Interestingly in all PCOS no changes occurred on all hormonal parameters involved in reproduction such as LH, FSH, and androstenedione. ALA integrative administration at a low dosage as 400 mg daily improved the metabolic impairment of all PCOS patients especially in those PCOS with familiar diabetes who have a higher grade of risk of NAFLD and predisposition to diabetes.

Self-administration of cocaine, cannabis and heroin in the human laboratory: benefits and pitfalls.

PubMed

Haney, Margaret

2009-01-01

The objective of this review is to describe self-administration procedures for modeling addiction to cocaine, cannabis and heroin in the human laboratory, the benefits and pitfalls of the approach, and the methodological issues unique to each drug. In addition, the predictive validity of the model for testing treatment medications will be addressed. The results show that all three drugs of abuse are reliably and robustly self-administered by non-treatment-seeking research volunteers. In terms of pharmacotherapies, cocaine use is extraordinarily difficult to disrupt either in the laboratory or in the clinic. A range of medications has been shown to significantly decrease cocaine's subjective effects and craving without decreasing either cocaine self-administration or cocaine abuse by patients. These negative data combined with recent positive findings with modafinil suggest that self-administration procedures are an important intermediary step between pre-clinical and clinical studies. In terms of cannabis, a recent study suggests that medications that improve sleep and mood during cannabis withdrawal decrease the resumption of marijuana self-administration in abstinent volunteers. Clinical data on patients seeking treatment for their marijuana use are needed to validate these laboratory findings. Finally, in contrast to cannabis or cocaine dependence, there are three efficacious Food and Drug Administration-approved medications to treat opioid dependence, all of which decrease both heroin self-administration and subjective effects in the human laboratory. In summary, self-administration procedures provide meaningful behavioral data in a small number of individuals. These studies contribute to our understanding of the variables maintaining cocaine, marijuana and heroin intake, and are important in guiding the development of more effective drug treatment programs.

Aripiprazole maintenance increases smoked cocaine self-administration in humans

PubMed Central

Rubin, Eric; Foltin, Richard W.

2011-01-01

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

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

PubMed

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

2013-01-01

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

Pivagabine decreases stress-related hormone secretion in women with hypothalamic amenorrhea.

PubMed

Genazzani, A D; Stomati, M; Bersi, C; Luisi, S; Fedalti, M; Santuz, M; Esposito, G; Petraglia, F; Genazzani, A R

2000-09-01

Stress-induced neuroendocrine activities influence the regulation of endocrine glands and axes. Weight loss-related hypothalamic amenorrhea is a typical stress-induced physiopathological condition. It is characterized by increased adrenal cortex activation and by reduced GH, LH, FSH and gonadal steroid hormone levels. The aim of the present study was to investigate the effects of pivagabine, a neurotropic drug (1800 mg/day for 7 days) or placebo administration on ACTH, cortisol, GH, LH, FSH and PRL plasma levels in patients with hypothalamic amenorrhea related to weight loss. Hormonal parameters and the pulsatile release of cortisol (6-hour pulsatility, sampling every 10 minutes) were evaluated before and after 7 days of treatment. Pivagabine administration significantly reduced mean plasma ACTH (from 21.7+/-1.7 to 15.4+/-1.2 pg/ml, p<0.05) and cortisol levels (from 12.2+/-0.7 to 9.7+/-0.7 ng/ml, p<0.05) and increased GH levels (from 1.4+/-0.5 to 3.0+/-0.9 ng/ml, p<0.05). A significant reduction of cortisol pulse amplitude was observed (p<0.01) while no change in pulse frequency occurred. No changes were observed in placebo-treated subjects. LH, FSH and PRL levels were not modified by placebo or pivagabine administration. In conclusion, in patients with hypothalamic amenorrhea related to weight loss pivagabine induced a significant decrease of cortisol secretion and an increase of GH release by pivagabine administration, suggesting that this drug exerts a specific neuroendocrine modulatory role.

Disruption of frontal-parietal connectivity during conscious sedation by propofol administration.

PubMed

Kim, Pil-Jong; Kim, Hong-Gee; Noh, Gyu-Jeong; Koo, Yong-Seo; Shin, Teo Jeon

2017-09-27

The sedative state is a transitional state from wakefulness to general anesthesia. However, little is understood regarding the mechanism of conscious sedation, different from general anesthesia while maintaining wakefulness. In this study, we aimed to investigate changes in functional connectivity of the parietal-frontal network, implicated in wakefulness during conscious sedation induced by propofol infusion. The electroencephalography was obtained at the frontal and parietal areas of adult volunteers who maintain wakefulness during low-dose propofol infusion (1.5 mg/kg/h) over 1 h. Spectral Granger causality (GC) (δ, θ, α, β, and γ frequency bands) and time-domain GC were calculated during each stage of awake (before propofol administration), sedation, and recovery (after discontinuation of propofol). We also calculated the phase-locking index and compared it with GC during each stage. A decrease in GC from the frontal to parietal areas was observed particularly in the low-frequency bands during propofol administration. Contrary to the GC changes in the frontoparietal direction, GC from the parietal to frontal areas was increased in the high-frequency bands during propofol administration and significantly decreased after discontinuation of propofol. In summary, we showed that frontal-parietal neural networks were significantly changed differently by the frequency of the brain rhythm and the directions of connections during sedation by propofol administration. Our result suggests that the alteration of brain interaction may induce sedative state lying between awake and general anesthesia.

Does des-acyl ghrelin improve glycemic control in obese diabetic subjects by decreasing acylated ghrelin levels?

PubMed

Özcan, Behiye; Neggers, Sebastian J C M M; Miller, Anne Reifel; Yang, Hsiu-Chiung; Lucaites, Virginia; Abribat, Thierry; Allas, Soraya; Huisman, Martin; Visser, Jenny A; Themmen, Axel P N; Sijbrands, Eric J G; Delhanty, Patric J D; van der Lely, Aart Jan

2014-06-01

The objective of this study was to assess the effects of a continuous overnight infusion of des-acyl ghrelin (DAG) on acylated ghrelin (AG) levels and glucose and insulin responses to a standard breakfast meal (SBM) in eight overweight patients with type 2 diabetes. Furthermore, in the same patients and two additional subjects, the effects of DAG infusion on AG concentrations and insulin sensitivity during a hyperinsulinemic-euglycemic clamp (HEC) were assessed. A double-blind, placebo-controlled cross-over study design was implemented, using overnight continuous infusions of 3 and 10  μg DAG/kg per h and placebo to study the effects on a SBM. During a HEC, we studied the insulin sensitivity. We observed that, compared with placebo, overnight DAG administration significantly decreased postprandial glucose levels, both during continuous glucose monitoring and at peak serum glucose levels. The degree of improvement in glycemia was correlated with baseline plasma AG concentrations. Concurrently, DAG infusion significantly decreased fasting and postprandial AG levels. During the HEC, 2.5  h of DAG infusion markedly decreased AG levels, and the M-index, a measure of insulin sensitivity, was significantly improved in the six subjects in whom we were able to attain steady-state euglycemia. DAG administration was not accompanied by many side effects when compared with placebo. DAG administration improves glycemic control in obese subjects with type 2 diabetes through the suppression of AG levels. DAG is a good candidate for the development of compounds in the treatment of metabolic disorders or other conditions with a disturbed AG:DAG ratio, such as type 2 diabetes mellitus or Prader-Willi syndrome. © 2014 European Society of Endocrinology.

Protective effects of coenzyme q(10) on decreased oxidative stress resistance induced by simvastatin.

PubMed

Kettawan, Aikkarach; Takahashi, Takayuki; Kongkachuichai, Ratchanee; Charoenkiatkul, Somsri; Kishi, Takeo; Okamoto, Tadashi

2007-05-01

The effects of simvastatin, an inhibitor of 3-hydroxy-3-methylglutaryl CoA reductase (HMG-CoA reductase), on oxidative stress resistance and the protective effects of coenzyme Q (CoQ) were investigated. When simvastatin was administered orally to mice, the levels of oxidized and reduced CoQ(9) and CoQ(10) in serum, liver, and heart, decreased significantly when compared to those of control. The levels of thiobarbituric acid reactive substances induced by Fe(2+)-ascorbate in liver and heart mitochondria also increased significantly with simvastatin. Furthermore, cultured cardiac myocytes treated with simvastatin exhibited less resistance to oxidative stress, decreased time to the cessation of spontaneous beating in response to H(2)O(2) addition, and decreased responsiveness to electrical field stimulation. These results suggested that oral administration of simvastatin suppresses the biosynthesis of CoQ, which shares the same biosynthesis pathway as cholesterol up to farnesyl pyrophosphate, thus compromising the physiological function of reduced CoQ, which possesses antioxidant activity. However, these undesirable effects induced by simvastatin were alleviated by coadministering CoQ(10) with simvastatin to mice. Simvastatin also reduced the activity of NADPH-CoQ reductase, a biological enzyme that converts oxidized CoQ to the corresponding reduced CoQ, while CoQ(10) administration improved it. These findings may also support the efficacy of coadministering CoQ(10) with statins.

Protection from JP-8 jet fuel induced immunotoxicity by administration of aerosolized substance P.

PubMed

Harris, D T; Sakiestewa, D; Robledo, R F; Witten, M

1997-01-01

Chronic exposure to jet fuel has been shown to cause human liver dysfunction, emotional dysfunction, abnormal electroencephalograms, shortened attention spans, and decreased sensorimotor speed. The United States Air Force has decided to implement the widespread use of JP-8 jet fuel in its operations, although a thorough understanding of its potential effects upon exposed personnel is unclear. Exposure to potential environment toxicants such as JP-8 may have significant effects on host physiology. Previous studies in mice have shown that short-term, low concentration JP-8 exposure had significant effects on the immune system; e.g., decreased viable immune cell numbers, decreased immune organ weights, and loss on immune function that persisted for extended periods of time (i.e., up to 4 weeks post-exposure). Previous studies have shown that JP-8 induced pulmonary dysfunction was associated with a decrease in levels of the neuropeptide substance P (SP) in lung lavage fluids. It was found that administration of aerosolized SP was able to protect exposed animals from such JP-8 induced pulmonary changes. In the current study, aerosolized SP was analyzed for its effects on JP-i induced immunotoxicity in exposed mice. It was observed that SP administration could protect JP-8 exposed animals from losses of viable immune cell numbers, but not losses in immune organ weights. Further, exposure of animals to SP inhibitors generally increased the immunotoxicity of JP-8 exposure. SP appeared to act on all immune cell populations equally as analyzed by flow cytometry, as no one immune cell population appeared to be preferentially protected by SP. Also, SP administration was capable of protecting JP-8 exposed animals from loss of immune function at all concentrations of JP-8 utilized (250-2500 mg/m3). Significantly, SP only needed to be administered for 15 minutes after JP-8 exposure, and was active at both 1 microM and 1 nM concentrations. Thus, SP administration appears to be a

Administration order of midazolam/fentanyl for moderate dental sedation.

PubMed

Lobb, Douglas; Clarke, Alix; Lai, Hollis

2018-02-01

The purpose of this study is to investigate the effects of administration order when a sedative drug (midazolam) and an opioid analgesic drug (fentanyl) is applied for moderate intravenous (IV) sedation in dentistry. A retrospective chart review was conducted in one dental clinic during its transition from a midazolam-first to a fentanyl-first protocol for dental procedures requiring moderate IV sedation. Physiological parameters, drug administration times, patient recovery times, drug dosages, and patient recall and satisfaction were investigated for differences. A total of 76 charts (40 midazolam-first and 36 fentanyl-first administrations), were used in the analysis. Administering midazolam first resulted in an average 4.38 min (52%) decrease in administration times (P < 0.001), and a decrease in procedural recollection immediately following the procedure (P = 0.03), and 24 to 48 hours later (P = 0.009). Administering fentanyl first required an average of 2.43 mg (29%) less midazolam (P < 0.001). No significant differences were found for change in vital signs, minimum oxygen saturation levels, recovery times, and patient satisfaction (P > 0.05). Oxygen saturation levels did not drop below 90% for either group; however, 5 cases in the fentanyl-first group fell to between 90% and 92%, compared with 0 cases in the midazolam-first group. The administration order of fentanyl and midazolam may have different effects on patients and the sedation procedure. Findings from this study should be used to facilitate discussion among dental practitioners and to guide additional research investigating this topic.

Administration order of midazolam/fentanyl for moderate dental sedation

PubMed Central

2018-01-01

Background The purpose of this study is to investigate the effects of administration order when a sedative drug (midazolam) and an opioid analgesic drug (fentanyl) is applied for moderate intravenous (IV) sedation in dentistry. Methods A retrospective chart review was conducted in one dental clinic during its transition from a midazolam-first to a fentanyl-first protocol for dental procedures requiring moderate IV sedation. Physiological parameters, drug administration times, patient recovery times, drug dosages, and patient recall and satisfaction were investigated for differences. Results A total of 76 charts (40 midazolam-first and 36 fentanyl-first administrations), were used in the analysis. Administering midazolam first resulted in an average 4.38 min (52%) decrease in administration times (P < 0.001), and a decrease in procedural recollection immediately following the procedure (P = 0.03), and 24 to 48 hours later (P = 0.009). Administering fentanyl first required an average of 2.43 mg (29%) less midazolam (P < 0.001). No significant differences were found for change in vital signs, minimum oxygen saturation levels, recovery times, and patient satisfaction (P > 0.05). Oxygen saturation levels did not drop below 90% for either group; however, 5 cases in the fentanyl-first group fell to between 90% and 92%, compared with 0 cases in the midazolam-first group. Conclusions The administration order of fentanyl and midazolam may have different effects on patients and the sedation procedure. Findings from this study should be used to facilitate discussion among dental practitioners and to guide additional research investigating this topic. PMID:29556559

First record of Anopheles minimus C and significant decrease of An. minimus A in central Vietnam.

PubMed

Garros, Claire; Marchand, Ron P; Quang, Nguyen Tuyen; Hai, Nguyen Son; Manguin, Sylvie

2005-06-01

Before August 1998, in the Khanh Phu commune (central Vietnam), Anopheles minimus s.l. individuals were identified as species A and showed the typical species A wing form. After a significant decrease over the 3 years 1999-2001, an increase in 2002 of An. minimus s.l. possessing a different wing pattern was observed. To determine the specific status of the An. minimus species collected in 2002 and to follow changes in the species composition, an allele-specific polymerase chain reaction was applied to samples collected from 1993 to 2002. This study reports the first record of An. minimus C in central Vietnam and, since 1998, a significant reduction of An. minimus A that coincided with the wide use of permethrin-treated bednets. This change in anopheline composition may have important consequences on malaria transmission. This work shows that the geographic distribution of malaria vectors in southeast Asia is only partially known and highlights the importance of species identification for understanding changes in the vector composition as a result of selective vector control.

Essential oil of clove (Eugenia caryophyllata) augments the humoral immune response but decreases cell mediated immunity.

PubMed

Halder, Sumita; Mehta, Ashish K; Mediratta, Pramod K; Sharma, Krishna K

2011-08-01

The present study was undertaken to explore the effect of the essential oil isolated from the buds of Eugenia caryophyllata on some immunological parameters. Humoral immunity was assessed by measuring the hemagglutination titre to sheep red blood cells and delayed type hypersensitivity was assessed by measuring foot pad thickness. Clove oil administration produced a significant increase in the primary as well as secondary humoral immune response. In addition, it also produced a significant decrease in foot pad thickness compared with the control group. Thus, these results suggest that clove oil can modulate the immune response by augmenting humoral immunity and decreasing cell mediated immunity. Copyright © 2011 John Wiley & Sons, Ltd.

Comparison between topical and intravenous administration of tranexamic acid in primary total hip arthroplasty.

PubMed

Ueno, Masaya; Sonohata, Motoki; Fukumori, Norio; Kawano, Shunsuke; Kitajima, Masaru; Mawatari, Masaaki

2016-01-01

Tranexamic acid has been reported to be safer with topical administration than with intravenous administration in total knee arthroplasty. However, the most effective administration route of tranexamic acid in total hip arthroplasty remains controversial. This study compared the effectiveness of topical tranexamic acid administration with that of intravenous tranexamic acid administration in total hip arthroplasty. We retrospectively examined the medical records of 886 patients with osteoarthritis of the hip joint, who had undergone unilateral primary total hip arthroplasty. The patients were divided into a control group (n = 302; did not receive tranexamic acid), topical group (n = 265; topically administered 2 g tranexamic acid in 30 mL normal saline via drain tubes placed in the joint before wound closure along with posterior soft tissue repair), and intravenous group (n = 319; intravenously administered 1 g tranexamic acid before skin incision along with posterior soft tissue repair). Data on blood loss, hemoglobin levels, transfusion rates, and occurrence of deep vein thrombosis and pulmonary embolization were collected. The mean operation times were approximately 40 min in all of the groups. The operation time and intra-operative blood loss were significantly lower in the control group than in the topical and intravenous groups. However, the post-operative blood loss, total blood loss, and decrease in the hemoglobin level were significantly higher in the control group than in the topical and intravenous groups. There were no significant differences in terms of blood loss and systemic complications between the tranexamic acid administration methods. Tranexamic acid reduces both post-operative and total blood loss in total hip arthroplasty. Moreover, a lower amount of tranexamic acid can be used to reduce blood loss in total hip arthroplasty with intravenous tranexamic acid administration than with topical tranexamic acid administration. Therefore, we

Leukocyte and platelet changes following low-dose lipopolysaccharide administration in five dogs.

PubMed

Flatland, B; Fry, M M; LeBlanc, C J; Rohrbach, B W

2011-02-01

Effects of low-dose LPS (0.1 μg/kg i.v.) on leukocyte and platelet parameters measured using an Advia 120 hematology analyzer were investigated. Five dogs received a saline sham treatment prior to LPS, and blood was collected before and 3, 6, and 24 h post-treatment. LPS-treated dogs had mild neutrophil toxic change and increased neutrophil bands at 3 and 6 h. Compared to saline-treated controls, total leukocyte, neutrophil, and monocyte counts of LPS-treated dogs were significantly decreased at 3 h and increased at 24 h. Compared to baseline, total leukocyte counts of LPS-treated dogs were significantly decreased at 3 h and increased at 24 h. Mean platelet volume was significantly increased and mean platelet component concentration was decreased at 3 h compared to baseline. Platelet count was significantly decreased at 3 and 6 h; plateletcrit did not change significantly. High dosage is not required in order to detect LPS-mediated hematologic effects in dogs. Low-dose LPS administration causes significant changes in leukocyte and platelet indices in dogs without causing severe clinical signs or death. Copyright © 2010 Elsevier Ltd. All rights reserved.

Obesity Decreases Perioperative Tissue Oxygenation

PubMed Central

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

2005-01-01

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

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

PubMed Central

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

2011-01-01

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

Rhynchophylla total alkaloid rescues autophagy, decreases oxidative stress and improves endothelial vasodilation in spontaneous hypertensive rats.

PubMed

Li, Chao; Jiang, Feng; Li, Yun-Lun; Jiang, Yue-Hua; Yang, Wen-Qing; Sheng, Jie; Xu, Wen-Juan; Zhu, Qing-Jun

2018-03-01

Autophagy plays an important role in alleviating oxidative stress and stabilizing atherosclerotic plaques. However, the potential role of autophagy in endothelial vasodilation function has rarely been studied. This study aimed to investigate whether rhynchophylla total alkaloid (RTA) has a positive role in enhancing autophagy through decreasing oxidative stress, and improving endothelial vasodilation. In oxidized low-density lipoprotein (ox-LDL)-treated human umbilical vein endothelial cells (HUVECs), RTA (200 mg/L) significantly suppressed ox-LDL-induced oxidative stress through rescuing autophagy, and decreased cell apoptosis. In spontaneous hypertensive rats (SHR), administration of RTA (50 mg·kg -1 ·d -1 , ip, for 6 weeks) improved endothelin-dependent vasodilation of thoracic aorta rings. Furthermore, RTA administration significantly increased the antioxidant capacity and alleviated oxidative stress through enhancing autophagy in SHR. In ox-LDL-treated HUVECs, we found that the promotion of autophagy by RTA resulted in activation of the AMP-activated protein kinase (AMPK) signaling pathway. Our results show that RTA treatment rescues the ox-LDL-induced autophagy impairment in HUVECs and improves endothelium-dependent vasodilation function in SHR.

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

PubMed

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

2016-04-01

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

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

Severe hypophosphataemia after intravenous iron administration.

PubMed

Blazevic, A; Hunze, J; Boots, J M M

2014-01-01

Currently, in many centres, intravenous administration of iron is becoming increasingly popular because of higher efficacy and decreased side effects, mainly gastrointestinal, compared with oral iron therapy. Studies of intravenous ferric carboxymaltose administration in the postpartum setting and in patients with non-dialysis-dependent chronic kidney disease revealed a decrease in serum phosphate levels that was generally asymptomatic and transient. Here, we report four cases of severe and symptomatic hypophosphataemia after intravenous iron administration. All patients received this as therapy for iron deficiency anaemia due to heavy menstrual bleeding. In most cases, a pre-existent disorder in the phosphate homeostasis existed, such as a secondary (cases 3 and 4) or tertiary hyperparathyroidism (case 1). However, in the second case there were no risk factors for a dysregulation of the phosphate homeostasis. Based on these findings, we conclude that severe and symptomatic hypophosphatemia can occur as a side effect of intravenous iron administration and can persist for months after administration. Especially patients with low phosphate levels prior to therapy due to concomitant disorders in phosphate homeostasis (e.g. hyperparathyroidism, vitamin D deficiency) are at risk.

Parenteral diclofenac infusion significantly decreases brain-tissue oxygen tension in patients with poor-grade aneurysmal subarachnoid hemorrhage

PubMed Central

2013-01-01

Introduction Diclofenac, a nonsteroidal antiinflammatory drug, is commonly used as antipyretic therapy in intensive care. The purpose of this study was to investigate the effects of parenteral diclofenac infusion on brain homeostasis, including brain-tissue oxygen tension (PbtO2) and brain metabolism after aneurysmal subarachnoid hemorrhage (aSAH). Methods We conducted a prospective, observational study with retrospective analysis of 21 consecutive aSAH patients with multimodal neuromonitoring. Cerebral perfusion pressure (CPP), mean arterial pressure (MAP), intracranial pressure (ICP), body temperature, and PbtO2 were analyzed after parenteral diclofenac infusion administered over a 34-minute period (20 to 45 IQR). Data are given as mean ± standard error of mean and median with interquartile range (IQR), as appropriate. Time-series data were analyzed by using a general linear model extended by generalized estimation equations (GEEs). Results One-hundred twenty-three interventions were analyzed. Body temperature decreased from 38.3°C ± 0.05°C by 0.8°C ± 0.06°C (P < 0.001). A 10% decrease in MAP and CPP (P < 0.001) necessitated an increase of vasopressors in 26% (n = 32), colloids in 33% (n = 41), and crystalloids in 5% (n = 7) of interventions. PbtO2 decreased by 13% from a baseline value of 28.1 ± 2.2 mm Hg, resulting in brain-tissue hypoxia (PbtO2 <20 mm Hg) in 38% (n = 8) of patients and 35% (n = 43) of interventions. PbtO2 <30 mm Hg before intervention was associated with brain-tissue hypoxia after parenteral diclofenac infusion (likelihood ratio, 40; AUC, 93%; 95% confidence interval (CI), 87% to 99%; P < 0.001). Cerebral metabolism showed no significant changes after parenteral diclofenac infusion. Conclusions Parenteral diclofenac infusion after aSAH effectively reduces body temperature, but may lead to CPP decrease and brain-tissue hypoxia, which were both associated with poor outcome after aSAH. PMID:23663770

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.

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

PubMed

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

2016-05-01

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

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

PubMed

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

2002-03-01

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

Genetic sphingosine kinase 1 deficiency significantly decreases synovial inflammation and joint erosions in murine TNF-alpha-induced arthritis.

PubMed

Baker, DeAnna A; Barth, Jeremy; Chang, Raymond; Obeid, Lina M; Gilkeson, Gary S

2010-08-15

Sphingosine kinase 1 (SphK1) is an enzyme that converts sphingosine to bioactive sphingosine-1-phosphate. Recent in vitro data suggest a potential role of SphK1 in TNF-alpha-mediated inflammation. Our aims in this study were to determine the in vivo significance of SphK1 in TNF-alpha-mediated chronic inflammation and to define which pathogenic mechanisms induced by TNF-alpha are SphK1 dependent. To pursue these aims, we studied the effect of SphK1 deficiency in an in vivo model of TNF-alpha-induced chronic inflammatory arthritis. Transgenic hTNF-alpha mice, which develop spontaneous inflammatory erosive arthritis beginning at 14-16 wk, were crossed with SphK1 null mice (SphK1(-/-)), on the C57BL6 genetic background. Beginning at 4 mo of age, hTNF/SphK1(-/-) mice had significantly less severe clinically evident paw swelling and deformity, less synovial and periarticular inflammation, and markedly decreased bone erosions as measured quantitatively through micro-CT images. Mechanistically, the mice lacking SphK1 had less articular cyclooxygenase 2 protein and fewer synovial Th17 cells than did hTNF/SphK1(+/+) littermates. Microarray analysis and real-time RT-PCR of the ankle synovial tissue demonstrated that hTNF/SphK1(-/-) mice had increased transcript levels of suppressor of cytokine signaling 3 compared with hTNF/SphK1(+/+) mice, likely also contributing to the decreased inflammation in the SphK1-deficient mice. Finally, significantly fewer mature osteoclasts were detected in the ankle joints of hTNF/SphK1(-/-) mice compared with hTNF/SphK1(+/+) mice. These data indicate that SphK1 plays a key role in hTNF-alpha-induced inflammatory arthritis via impacting synovial inflammation and osteoclast number.

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.

Administration of different Lactobacillus strains in fermented oatmeal soup: in vivo colonization of human intestinal mucosa and effect on the indigenous flora.

PubMed Central

Johansson, M L; Molin, G; Jeppsson, B; Nobaek, S; Ahrné, S; Bengmark, S

1993-01-01

In vivo colonization by different Lactobacillus strains on human intestinal mucosa of healthy volunteers was studied together with the effect of Lactobacillus administration on different groups of indigenous bacteria. A total of 19 test strains were administered in fermented oatmeal soup containing 5 x 10(6) CFU of each strain per ml by using a dose of 100 ml of soup per day for 10 days. Biopsies were taken from both the upper jejunum and the rectum 1 day before administration was started and 1 and 11 days after administration was terminated. The administration significantly increased the Lactobacillus counts on the jejunum mucosa, and high levels remained 11 days after administration was terminated. The levels of streptococci increased by 10- to 100-fold in two persons, and the levels of sulfite-reducing clostridia in the jejunum decreased by 10- to 100-fold in three of the volunteers 1 day after administration was terminated. In recta, the anaerobic bacterium counts and the gram-negative anaerobic bacterium counts decreased significantly by the end of administration. Furthermore, a decrease in the number of members of the Enterobacteriaceae by 1,000-fold was observed on the rectal mucosa of two persons. Randomly picked Lactobacillus isolates were identified phenotypically by API 50CH tests and genotypically by the plasmid profiles of strains and by restriction endonuclease analysis of chromosomal DNAs.(ABSTRACT TRUNCATED AT 250 WORDS) Images PMID:8439146

Decrease of Plasma Glucose by Hibiscus taiwanensis in Type-1-Like Diabetic Rats

PubMed Central

Wang, Lin-Yu; Chung, Hsien-Hui

2013-01-01

Hibiscus taiwanensis (Malvaceae) is widely used as an alternative herb to treat disorders in Taiwan. In the present study, it is used to screen the effect on diabetic hyperglycemia in streptozotocin-induced diabetic rats (STZ-diabetic rats). The extract of Hibiscus taiwanensis showed a significant plasma glucose-lowering action in STZ-diabetic rats. Stems of Hibiscus taiwanensis are more effective than other parts to decrease the plasma glucose in a dose-dependent manner. Oral administration of Hibiscus taiwanensis three times daily for 3 days into STZ-diabetic rats increased the sensitivity to exogenous insulin showing an increase in insulin sensitivity. Moreover, similar repeated administration of Hibiscus taiwanensis for 3 days in STZ-diabetic rats produced a marked reduction of phosphoenolpyruvate carboxykinase (PEPCK) expression in liver and an increased expression of glucose transporter subtype 4 (GLUT 4) in skeletal muscle. Taken together, our results suggest that Hibiscus taiwanensis has the ability to lower plasma glucose through an increase in glucose utilization via elevation of skeletal GLUT 4 and decrease of hepatic PEPCK in STZ-diabetic rats. PMID:23690841

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

PubMed

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

2013-09-01

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

Antioxidant properties of MDL and MMDL, two nicergoline metabolites, during chronic administration of haloperidol.

PubMed

Vairetti, Mariapia; Battaglia, Angelo; Carfagna, Nicola; Luigi Canonico, Pier; Bertè, Francantonio; Richelmi, Plinio

2002-10-18

We evaluated the effects of 10-alpha-methoxy-9,10-dihydrolysergol (MDL) and 1-methyl-10-alpha-methoxy-9,10-dihydrolysergol (MMDL), two nicergoline metabolites, during chronic treatment with haloperidol in rats. Haloperidol induced a significant decrease in the glutathione (GSH) content in selected areas of the brain and in the liver. Prolonged administration of MDL, MMDL or nicergoline antagonized the haloperidol-induced GSH decrease. Lipid peroxidation in the cortex and striatum was suppressed by MDL, MMDL or nicergoline administration. Our results show that MDL, MMDL and nicergoline have antioxidant activity, preventing not only GSH depletion but also lipid peroxidation. These observations suggest beneficial properties of MDL and MMDL in the treatment of neuroleptic-induced side effects. Copyright 2002 Elsevier Science B.V.

13 CFR 107.585 - Voluntary decrease in Licensee's Regulatory Capital.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Voluntary decrease in Licensee's Regulatory Capital. 107.585 Section 107.585 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION SMALL BUSINESS INVESTMENT COMPANIES Managing the Operations of a Licensee Voluntary Decrease in Licensee...

Investigation into the mechanism(s) that leads to platelet decreases in cynomolgus monkeys during administration of ISIS-104838, a 2'-MOE-modified antisense oligonucleotide.

PubMed

Narayanan, P K; Shen, L; Curtis, B R; Bourdon, M; Nolan, J P; Zhou, F; Christian, B; Gupta, S; Schaubhut, J L; Greenlee, S; Hoffmaster, C; Burel, S; Witztum, J L; Engelhardt, J A; Henry, S P

2018-05-29

ISIS 104838, a 2'-O-methoxyethyl (2'-MOE)-modified antisense oligonucleotide (ASO), causes a moderate, reproducible, dose-dependent, but self-limiting decrease in platelet (PLT) counts in monkeys and humans. To determine the etiology of PLT decrease in cynomolgus monkeys, a 12-week repeat dose toxicology study in 5 cynomolgus monkeys given subcutaneous injections of ISIS 104838 (30 to 60 mg/kg/week). Monkeys were also injected intravenously with 111In-oxine-labeled PLTs to investigate PLT sequestration. In response to continued dosing, PLT counts were decreased by 50 to 90% by day 30 in all monkeys. PLT decreases were accompanied by 2- to 4.5-fold increases in immunoglobulin M(IgM), which were typified by a 2-to-5-fold increase in anti-platelet factor 4 (PF4) IgM and anti-PLT IgM, respectively. Monocyte chemotactic protein 1 (MCP-1) increased upon dosing of ISIS 104838, concomitant with a 2- to 6-fold increase in monocyte-derived extracellular vesicles (EVs), indicating monocyte activation but not PLT activation. Despite a 2- to- 3-fold increase in von Willebrand factor (VWF) antigen in all monkeys following ASO administration, only two monkeys showed a 2 to 4-fold increase in endothelial EVs. Additionally, a 25-45% increase in PLT sequestration in liver and spleen was also observed. Collectively, these results suggest the overall increase in total IgM, anti-PLT IgM and/or anti-PF4 IgM, in concert with monocyte activation contributed to increased PLT sequestration in spleen and liver, leading to decreased PLTs in peripheral blood.

[Clinical significance of gastrointestinal decontamination under protected environment].

PubMed

Nagao, T; Yonekura, S; Komatsuda, M; Nozaki, H; Arimori, S; Sawamura, S; Ozawa, A; Sasaki, S

1991-01-01

Many infections are caused by the patient's own oro-intestinal microbial flora under a protected environment. Thirty-eight patients with acute leukemia and two patients with blast crisis of chronic myelocytic leukemia were treated under a protected environment with or without prophylactic antibiotics. Antibiotics used for decontamination were vancomycin (V), polymyxin B (P) and nystatin (N). The number of patients in the VPN, PN and the no antibiotic group were 13, 13 and 14, respectively. While the intestinal microbial flora was almost completely eliminated in VPN group, the number of bacteria decreased slightly in PN group. The mean number of pharyngeal and anorectal bacterial species decreased most markedly in the VPN group, but there were no significant differences among the three groups. The number of febrile days was significantly lower in the VPN and PN group than the no antibiotics group with neutrophil counts of less than 100 microliters. The average number of episodes of infection per patient was lowest in VPN group and highest in the no antibiotic group. These data indicate that VPN administration is effective for eliminating intestinal bacterial flora and resultantly protecting endogenous infections.

Ipragliflozin Improves Glycemic Control and Decreases Body Fat in Patients With Type 2 Diabetes Mellitus.

PubMed

Kawata, Takehiro; Iizuka, Takashi; Iemitsu, Kotaro; Takihata, Masahiro; Takai, Masahiko; Nakajima, Shigeru; Minami, Nobuaki; Umezawa, Shinichi; Kanamori, Akira; Takeda, Hiroshi; Ito, Shogo; Kikuchi, Taisuke; Amemiya, Hikaru; Kaneshiro, Mizuki; Mokubo, Atsuko; Takuma, Tetsuo; Machimura, Hideo; Tanaka, Keiji; Asakura, Taro; Kubota, Akira; Aoyanagi, Sachio; Hoshino, Kazuhiko; Ishikawa, Masashi; Matsuzawa, Yoko; Obana, Mitsuo; Sasai, Nobuo; Kaneshige, Hideaki; Minagawa, Fuyuki; Saito, Tatsuya; Shinoda, Kazuaki; Miyakawa, Masaaki; Tanaka, Yasushi; Terauchi, Yasuo; Matsuba, Ikuro

2017-07-01

Ipragliflozin, a sodium-glucose transporter 2 inhibitor, was administered to patients with type 2 diabetes mellitus for 24 weeks to evaluate its effect on glycemic control and body composition. This was an investigator-initiated multicenter prospective intervention study in which ipragliflozin (50 mg) was administered once daily and glycemic control, blood pressure, body weight (BW), body composition (measured by a biological impedance method), the lipid profile, and adverse events were evaluated after 4, 12, and 24 weeks of treatment. Efficacy and safety up to 24 weeks of ipragliflozin therapy were analyzed in 367 patients and 451 patients, respectively. Hemoglobin A1c decreased significantly from 8.07% at the start of ipragliflozin therapy to 7.26% in week 24 (P < 0.001). Fasting and postprandial blood glucose levels were significantly reduced by ipragliflozin. In week 24, there were significant decreases from baseline in BW (-2.6 kg), waist circumference (-2.9 cm), and body fat mass (-1.9 kg) (P < 0.001). The body water mass and mineral mass were decreased significantly by 0.5 and by 0.1 kg, respectively (P < 0.001), whereas the protein mass did not change significantly. Intracellular water mass did not change significantly, whereas extracellular water mass showed a significant decrease of 0.5 kg (P < 0.001). Muscle mass did not change in the upper and lower limbs, but that of the trunk decreased significantly (P < 0.001). There was a significant decrease in the fasting triglyceride level and a significant increase in fasting high-density lipoprotein cholesterol level, while low-density lipoprotein cholesterol was unchanged. Adverse events occurred in 23.5% of the patients, with a high frequency of genital infections, such as vulvovaginal candidiasis (3.1%) and genital pruritus (1.8%). Adverse drug reactions were noted in 13.7% of the patients. Administration of ipragliflozin for 24 weeks improved glycemic control and decreased BW. Reduction of body fat

Ibuprofen therapy resulted in significantly decreased tissue bacillary loads and increased survival in a new murine experimental model of active tuberculosis.

PubMed

Vilaplana, Cristina; Marzo, Elena; Tapia, Gustavo; Diaz, Jorge; Garcia, Vanesa; Cardona, Pere-Joan

2013-07-15

C3HeB/FeJ mice infected with Mycobacterium tuberculosis were used in an experimental animal model mimicking active tuberculosis in humans to evaluate the effect of antiinflammatory agents. No other treatment but ibuprofen was given, and it was administered when the animals' health started to deteriorate. Animals treated with ibuprofen had statistically significant decreases in the size and number of lung lesions, decreases in the bacillary load, and improvements in survival, compared with findings for untreated animals. Because antiinflammatory agents are already on the market, further clinical trials should be done to evaluate this effect in humans as soon as possible, to determine their suitability as coadjuvant tuberculosis treatment.

Assessment of low-dose cisplatin as a model of nausea and emesis in beagle dogs, potential for repeated administration.

PubMed

Kenward, Hannah; Pelligand, Ludovic; Elliott, Jonathan

2014-08-01

Cisplatin is a highly emetogenic cancer chemotherapy agent, which is often used to induce nausea and emesis in animal models. The cytotoxic properties of cisplatin also cause adverse events that negatively impact on animal welfare preventing repeated administration of cisplatin. In this study, we assessed whether a low (subclinical) dose of cisplatin could be utilized as a model of nausea and emesis in the dog while decreasing the severity of adverse events to allow repeated administration. The emetic, nausea-like behavior and potential biomarker response to both the clinical dose (70 mg/m2) and low dose (15 mg/m2) of cisplatin was assessed. Plasma creatinine concentrations and granulocyte counts were used to assess adverse effects on the kidneys and bone marrow, respectively. Nausea-like behavior and emesis was induced by both doses of cisplatin, but the latency to onset was greater in the low-dose group. No significant change in plasma creatinine was detected for either dose groups. Granulocytes were significantly reduced compared with baseline (P = 0.000) following the clinical, but not the low-dose cisplatin group. Tolerability of repeated administration was assessed with 4 administrations of an 18 mg/m2 dose cisplatin. Plasma creatinine did not change significantly. Cumulative effects on the granulocytes occurred, they were significantly decreased (P = 0.03) from baseline at 3 weeks following cisplatin for the 4th administration only. Our results suggest that subclinical doses (15 and 18 mg/m2) of cisplatin induce nausea-like behavior and emesis but have reduced adverse effects compared with the clinical dose allowing for repeated administration in crossover studies.

Use of Electronic Medication Administration Records to Reduce Perceived Stress and Risk of Medication Errors in Nursing Homes.

PubMed

Alenius, Malin; Graf, Peter

2016-07-01

Concerns have been raised about the effects of current medication administration processes on the safety of many of the aspects of medication administration. Keeping electronic medication administration records could decrease many of these problems. Unfortunately, there has not been much research on this topic, especially in nursing homes. A prospective case-control survey was consequently performed at two nursing homes; the electronic record system was introduced in one, whereas the other continued to use paper records. The personnel were asked to fill in a questionnaire of their perceptions of stress and risk of medication errors at baseline (n = 66) and 20 weeks after the intervention group had started recording medication administration electronically (n = 59). There were statistically significant decreases in the perceived risk of omitting a medication, of medication errors occurring because of communication problems, and of medication errors occurring because of inaccurate medication administration records in the intervention group (all P < .01 vs the control group). The perceived overall daily stress levels were also reduced in the intervention group (P < .05). These results indicate that the utilization of electronic medication administration records will reduce many of the concerns regarding the medication administration process.

Assessment of human 4-hydroxynonenal, 8-isoprostane concentrations and glutathione reductase activity after synbiotics administration.

PubMed

Kleniewska, Paulina; Pawliczak, Rafał

2018-05-30

Probiotics and prebiotics have become an object of intense research, to identify methods of mitigating oxidative stress. Over the past few years, the number of in vitro and in vivo studies, related to antioxidant properties of probiotics/prebiotics has significantly increased. The aim of the present study was to assess whether probiotic in combination with prebiotic influences the level of human 4-hydroxynonenal, 8-isoprostane and glutathione reductase activity. Experiments were carried out on healthy volunteers (male and female). All oxidative stress markers were measured in blood plasma pre- and post-administration of synbiotic. The administration of synbiotic resulted in a significant decrease in 4-hydroxynonenal in the female-synbiotic group (p < 0.05), 8-isoprostanes in the female-synbiotic group and male-synbiotic group (p < 0.05) and non-significant increase in the activity of glutathione reductase (p > 0.05) vs. control. The present results show that supplementation of synbiotics contributed to the decrease in oxidative stress parameters in the female patients. Copyright © 2018 Medical University of Bialystok. Published by Elsevier B.V. All rights reserved.

Drug administration adjustments for elderly patients with dysphagia: A case report.

PubMed

Mastroianni, Patrícia de Carvalho; Forgerini, Marcela

2018-01-01

An elderly patient, aged 76 years, diagnosed with dysphagia, depression, hypothyroidism, Alzheimer's disease and mild cognitive deficit, was identified with sertraline and levothyroxine- drug-related problems. Medication Therapy Management (MTM) was used to adjust therapy to the patient's needs by macerating sertraline tablets and solubilizing them in 10-30 mL of orange juice. The patient was advised to take levothyroxine after fasting. Six months later, pharmaceutical follow-up identified an increase in the Mini-Mental State Exam score from 22 to 26 and a decrease in the Clinical Dementia Rating (CDR) scale score from 1.0 to 0.5 in conjunction with mood and physical improvements, as well as a significant decrease in aggressiveness and agitation. Cognitive deficit may be a result of poor drug administration procedures, leading to drug ineffectiveness. Optimizing levothyroxine and sertraline administration, based on knowledge of their physicochemical properties, improves their clinical effectiveness, including the cognition of patients with Alzheimer's disease and dysphagia.

Administration of Bifidobacterium breve Decreases the Production of TNF-α in Children with Celiac Disease.

PubMed

Klemenak, Martina; Dolinšek, Jernej; Langerholc, Tomaž; Di Gioia, Diana; Mičetić-Turk, Dušanka

2015-11-01

Increasing evidence suggests that not only genetics, but also environmental factors like gut microbiota dysbiosis play an important role in the pathogenesis of celiac disease (CD). The aim of our study was to investigate the effect of two probiotic strains Bifidobacterium breve BR03 and B. breve B632 on serum production of anti-inflammatory cytokine interleukin 10 (IL-10) and pro-inflammatory cytokine tumor necrosis factor alpha (TNF-α) in children with CD. The study was a double-blinded, placebo-controlled trial that included 49 children with CD on gluten-free diet (GFD) randomized into two groups and 18 healthy children in the control group. The first group (24 children with CD) daily received B. breve BR03 and B632 (2 × 10(9) colony-forming units) and the second group (25 children with CD) received placebo for 3 months. TNF-α levels were significantly decreased in the first group after receiving B. breve for 3 months. On follow-up, 3 months after receiving probiotics, TNF-α levels increased again. Children with CD who were on GFD for less than 1 year showed similar baseline TNF-α levels as children who were on GFD for more than 1 year. IL-10 levels were in all groups of patients below detection level. Probiotic intervention with B. breve strains has shown a positive effect on decreasing the production of pro-inflammatory cytokine TNF-α in children with CD on GFD.

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

PubMed

Petridis, Ioannis G; Fthenakis, George C

2014-02-01

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

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.

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

PubMed

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

2016-09-01

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

Exogenous NAD+ decreases oxidative stress and protects H2O2-treated RPE cells against necrotic death through the up-regulation of autophagy

PubMed Central

Zhu, Ying; Zhao, Ke-ke; Tong, Yao; Zhou, Ya-li; Wang, Yi-xiao; Zhao, Pei-quan; Wang, Zhao-yang

2016-01-01

Increased oxidative stress, which can lead to the retinal pigment epithelium (RPE) cell death by inducing ATP depletion and DNA repair, is believed to be a prominent pathology in age-related macular degeneration (AMD). In the present study, we showed that and 0.1 mM nicotinamide adenine dinucleotide (NAD+) administration significantly blocked RPE cell death induced by 300 μM H2O2. Further investigation showed that H2O2 resulted in increased intracellular ROS level, activation of PARP-1 and subsequently necrotic death of RPE cells. Exogenous NAD+ administration significantly decreased intracellular and intranuclear ROS levels in H2O2-treated RPE cells. In addition, NAD+ administration to H2O2-treated RPE cells inhibited the activation of PARP-1 and protected the RPE cells against necrotic death. Moreover, exogenous NAD+ administration up-regulated autophagy in the H2O2-treated RPE cells. Inhibition of autophagy by LY294002 blocked the decrease of intracellular and intranuclear ROS level. Besides, inhibition of autophagy by LY294002 abolished the protection of exogenous NAD+ against H2O2-induced cell necrotic death. Taken together, our findings indicate that that exogenous NAD+ administration suppresses H2O2-induced oxidative stress and protects RPE cells against PARP-1 mediated necrotic death through the up-regulation of autophagy. The results suggest that exogenous NAD+ administration might be potential value for the treatment of AMD. PMID:27240523

Exogenous NAD(+) decreases oxidative stress and protects H2O2-treated RPE cells against necrotic death through the up-regulation of autophagy.

PubMed

Zhu, Ying; Zhao, Ke-Ke; Tong, Yao; Zhou, Ya-Li; Wang, Yi-Xiao; Zhao, Pei-Quan; Wang, Zhao-Yang

2016-05-31

Increased oxidative stress, which can lead to the retinal pigment epithelium (RPE) cell death by inducing ATP depletion and DNA repair, is believed to be a prominent pathology in age-related macular degeneration (AMD). In the present study, we showed that and 0.1 mM nicotinamide adenine dinucleotide (NAD(+)) administration significantly blocked RPE cell death induced by 300 μM H2O2. Further investigation showed that H2O2 resulted in increased intracellular ROS level, activation of PARP-1 and subsequently necrotic death of RPE cells. Exogenous NAD(+) administration significantly decreased intracellular and intranuclear ROS levels in H2O2-treated RPE cells. In addition, NAD(+) administration to H2O2-treated RPE cells inhibited the activation of PARP-1 and protected the RPE cells against necrotic death. Moreover, exogenous NAD(+) administration up-regulated autophagy in the H2O2-treated RPE cells. Inhibition of autophagy by LY294002 blocked the decrease of intracellular and intranuclear ROS level. Besides, inhibition of autophagy by LY294002 abolished the protection of exogenous NAD(+) against H2O2-induced cell necrotic death. Taken together, our findings indicate that that exogenous NAD(+) administration suppresses H2O2-induced oxidative stress and protects RPE cells against PARP-1 mediated necrotic death through the up-regulation of autophagy. The results suggest that exogenous NAD(+) administration might be potential value for the treatment of AMD.

Fndc5 knockdown induced suppression of mitochondrial integrity and significantly decreased cardiac differentiation of mouse embryonic stem cells.

PubMed

Nazem, Shima; Rabiee, Farzaneh; Ghaedi, Kamran; Babashah, Sadegh; Sadeghizadeh, Majid; Nasr-Esfahani, Mohammad Hossein

2018-06-01

Fibronectin type III domain-containing 5 protein (Fndc5) is a glycosylated protein with elevated expression in high energy demanded tissues as heart, brain, and muscle. It has been shown that upregulation of Fndc5 is regulated by peroxisome proliferator-activated receptor-γ coactivator-1 alpha (PGC-1α), which is known as a master regulator of mitochondrial function and biogenesis. Also, our group indicated that Fndc5 expression increases gradually during cardiac differentiation of mouse embryonic stem cells (mESCs). In this paper, to clarify the importance of Fndc5 in cardiac differentiation, we south to knock down Fndc5 expression by generation a stably transduced mESC line that derives the expression of a short hairpin RNA (shRNA) against Fndc5 gene following doxycycline (Dox) induction. Knock-down of Fndc5 demonstrated a considerable decrease in expression of cardiac progenitor and cardiomyocyte markers. Considering the fact that mitochondria play a crucial role in cardiac differentiation of ESCs, we investigated the role of Fndc5, as a downstream target of PGC1-α, on mitochondrial indices. Results showed that expression of nuclear encoded mitochondrial genes including PGC1-α, Atp5b, Ndufb5, and SOD2 significantly decreased. Moreover, mitochondrial membrane potential (ΔΨm) and relative ATP content of cardiomyocytes decreased markedly with relative ROS level increase. Together, our results suggest that Fndc5 attenuates process of cardiac differentiation of mESCs which is associated with modulation of mitochondrial function and gene expression. © 2017 Wiley Periodicals, Inc.

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

PubMed

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

2013-06-01

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

Induction of testicular damage by daily methamphetamine administration in rats.

PubMed

Lin, Ji-Fan; Lin, Yi-Hsuan; Liao, Po-Cheng; Lin, Yi-Chia; Tsai, Te-Fu; Chou, Kuang-Yu; Chen, Hung-En; Tsai, Shiow-Chwen; Hwang, Thomas I-Sheng

2014-02-28

Methamphetamine (METH)-induced brain damage and apoptosis within the central nervous system are well documented. This study was conducted to investigate the toxic effects of daily METH administration on the testes in a rat model. Male Sprague-Dawley rats (5 weeks old, ~100 g, n = 64) were divided into two groups and treated with vehicle (saline, control) or METH (10 mg/kg) for 15, 30, 60 and 90 days. The results showed that daily administration of METH decreased the body, testicular and epididymis weights as well as the serum levels of total testosterone. The increased apoptotic index (Bad/Bcl2 expression ratio) and levels of cleaved caspase-3 indicated that apoptosis had occurred in the testes of the METH-treated rats. The oxidative stress levels increased as the reduced and oxidized glutathione (GSH/GSSG) ratio decreased. The overall sperm counts decreased at 15 and 90 days, where- as morphologically abnormal sperm counts increased at 30, 60 and 90 days in the METH-treated rats. This study demonstrates that daily exposure to METH significantly reduced the number and quality of sperm in rats. The underlying pathophysiological mechanisms likely include the reduction of serum testosterone levels and the increase of oxidative stress and apoptosis in the rat testes.

Decreased activity and expression of intestinal oligopeptide transporter PEPT1 in rats with hyperthyroidism in vivo.

PubMed

Ashida, Kayoko; Katsura, Toshiya; Saito, Hideyuki; Inui, Ken-ichi

2004-06-01

To examine the effect of thyroid hormone status on PEPT1 in vivo, the activity and expression of PEPT1 in the small intestine were examined in euthyroid and hyperthyroid rats. Hyperthyroidism was induced by treating rats with L-thyroxine (12 mg/L) in the drinking water for 21 days. Transport activity was measured by everted small intestinal preparations and in situ intestinal loop technique. Expressions of PEPT1 mRNA and protein were evaluated by competitive polymerase chain reaction and Western blotting, respectively. The uptake of [14C]glycylsarcosine by everted small intestinal preparations was significantly decreased in hyperthyroid rats, whereas that of methyl-alpha-D-[14C(U)]-glucopyranoside was not altered. Kinetic analysis showed that the Vmax value for [14C]glycylsarcosine uptake was significantly decreased in hyperthyroid rats, whereas the Km value was not affected. The mean portal vein concentrations after intrajejunal administration of [14C]glycylsarcosine were also decreased in hyperthyroid rats. Moreover, hyperthyroidism caused a significant decrease in the expression of PEPT1 mRNA in the small intestine, whereas the expression of Na+/glucose cotransporter (SGLT1) mRNA was not changed. The level of PEPT1 protein was also decreased in the small intestine of hyperthyroid rats. These results indicate that in hyperthyroid rats, the activity and expression of PEPT1 were decreased in the small intestine.

Improving patient safety using the sterile cockpit principle during medication administration: a collaborative, unit-based project.

PubMed

Fore, Amanda M; Sculli, Gary L; Albee, Doreen; Neily, Julia

2013-01-01

  To implement the sterile cockpit principle to decrease interruptions and distractions during high volume medication administration and reduce the number of medication errors.   While some studies have described the importance of reducing interruptions as a tactic to reduce medication errors, work is needed to assess the impact on patient outcomes.   Data regarding the type and frequency of distractions were collected during the first 11 weeks of implementation. Medication error rates were tracked 1 year before and after 1 year implementation.   Simple regression analysis showed a decrease in the mean number of distractions, (β = -0.193, P = 0.02) over time. The medication error rate decreased by 42.78% (P = 0.04) after implementation of the sterile cockpit principle.   The use of crew resource management techniques, including the sterile cockpit principle, applied to medication administration has a significant impact on patient safety.   Applying the sterile cockpit principle to inpatient medical units is a feasible approach to reduce the number of distractions during the administration of medication, thus, reducing the likelihood of medication error. 'Do Not Disturb' signs and vests are inexpensive, simple interventions that can be used as reminders to decrease distractions. © 2012 Blackwell Publishing Ltd.

The chronic oral administration of arginine aspartate decreases secretion of IGF-1 and IGFBP-3 in healthy volunteers.

PubMed

Blazejewski, Sylvie; Georges, Agnès; Forest, Karelle; Corcuff, Jean-Benoît; Abouelfath, Abdelilah; Girodet, Pierre-Olivier; Kamagate, Mamadou; Jacquet, Alain; Pillet, Odile; Bordenave, Laurence; Moore, Nicholas

2009-06-01

To investigate the effect of chronic oral arginine aspartate on the growth hormone (GH), GH-releasing hormone (GHRH), insulin-like growth factor-1 (IGF-1) and IGF-binding protein-3 (IGFBP-3) secretions in healthy volunteers. Twenty-three healthy non-athlete volunteer males were administered arginine aspartate (30 g) orally once daily at 21:00 h for 21 consecutive days. Subjects were hospitalized on days 0, 1, 3, 5, 7, 14 and 21 of treatment. At each hospitalization, concentrations of GHRH, GH, IGF-1 and IGFBP-3 were measured over 4 h after arginine aspartate intake. GH, IGF-1 and IGFBP-3 concentrations were also determined over 12 h at days 0, 1 and 21. Compared with day 1, 4 h GH levels dropped at day 5 and subsequently rose to levels not significantly different from initial ones. The latter was substantiated by 12 h GH levels that did not significantly change from days 1 to 21. GHRH levels were not statistically different, although there was a trend in median values that seemed to inversely mirror those of GH. This dynamic over the course of the study for GH and GHRH was accompanied by a general decrease in IGF-1 and IGFBP-3. In healthy volunteers, a chronic oral treatment with 30 g/day arginine aspartate is followed by a decrease in IGF-1 and IGFBP-3 secretions.

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…

Bedtime administration of cilnidipine controls morning hypertension.

PubMed

Ashizawa, Naoto; Seto, Shinji; Shibata, Yoshisada; Yano, Katsusuke

2007-09-01

Morning blood pressure (BP) level plays an important role in the incidence of cardiovascular disease. Recently, Kario, et al proposed the usefulness of ME difference (morning minus evening systolic BP) and ME average (average of morning and evening systolic BP) for the evaluation of antihypertensive treatment. Cilnidipine is a novel calcium channel blocker (CCB) that exerts inhibitory actions not only on L-type but also on N-type calcium channels. We investigated the effect of bedtime administration of cilnidipine (10 mg) in addition to the antihypertensive treatment for uncontrolled morning hypertension. Twenty-three hypertensive outpatients (13 males and 10 females; mean age, 66.9 years) with stable antihypertensive medication and uncontrolled morning BP were studied using self-measured BP monitoring in the morning and evening. Morning SBP (P < 0.001) and DBP (P < 0.001) decreased significantly from 150.2 +/- 8.7 and 87.8 +/- 9.3 to 132.7 +/- 7.4 and 77.5 +/- 8.5 mmHg, respectively, after the addition of cilnidipine. Morning heart rate did not change (63.3 +/- 7.0 to 64.1 +/- 9.4). The evening SBP, but not DBP, decreased significantly after treatment. Both the ME average (P < 0.001) and ME difference (P < 0.01) significantly decreased from 143.0 +/- 9.2 and 14.3 +/- 12.4 to 131.3 +/- 7.2 and 2.8 +/- 9.2 mmHg after treatment, respectively. The microalbuminuria decreased from 39.6 +/- 13.2 to 27.3 +/- 8.4 mg/g Cr. In conclusion, L-/N-type CCB cilnidipine may be useful for patients with uncontrollable morning hypertension by reducing both ME average and ME difference.

Chronic Administration of a Combination of Six Herbs Inhibits the Progression of Hyperglycemia and Decreases Serum Lipids and Aspartate Amino Transferase Activity in Diabetic Rats

PubMed Central

Shafiee-Nick, Reza; Vafaee Bagheri, Farzaneh; Rakhshandeh, Hassan

2012-01-01

The effects of a polyherbal compound, containing six plants (Allium sativum, Cinnamomum zeylanicum, Nigella sativa, Punica granatum, Salvia officinalis and Teucrium polium) were tested on biochemical parameters in streptozotocin-induced diabetic rats. Streptozotocin caused an approximately 3-fold increase in fasting blood sugar level after 2 days. The diabetic control rats showed further increase in blood glucose after 30 days (384 ± 25 mg/dl in day 30 versus 280 ± 12 mg/dl in day 2, P < 0.001). Administration of the compound blocked the increase of blood glucose (272 ± 7 and 269 ± 48 mg/dl at day 2 and day 30, respectively). Also, there was significant difference in the level of triglyceride (60 ± 9 versus 158 ± 37 mg/dl, P < 0.01), total cholesterol (55 ± 2 versus 97 ± 11 mg/dl, P < 0.01) and aspartate amino transferase activity (75 ± 12 versus 129 ± 18 U/L, P < 0.05) between treated rats and diabetic control group. In conclusion, the MSEC inhibited the progression of hyperglycemia and decreased serum lipids and hepatic enzyme activity in diabetic rats. Therefore, it has the potential to be used as a natural product for the management of diabetes. PMID:23304131

Testosterone Administration Reduces Lying in Men

PubMed Central

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

2012-01-01

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

Persimmon Tannin Decreased the Glycemic Response through Decreasing the Digestibility of Starch and Inhibiting α-Amylase, α-Glucosidase, and Intestinal Glucose Uptake.

PubMed

Li, Kaikai; Yao, Fen; Du, Jing; Deng, Xiangyi; Li, Chunmei

2018-02-21

Regulation of postprandial blood glucose levels is an effective therapeutic proposal for type 2 diabetes treatment. In this study, the effect of persimmon tannin on starch digestion with different amylose levels was investigated both in vitro and in vivo. Oral administration of persimmon tannin-starch complexes significantly suppressed the increase of blood glucose levels and the area under the curve (AUC) in a dose-dependent manner compared with starch treatment alone in an in vivo rat model. Further study proved that persimmon tannin could not only interact with starch directly but also inhibit α-amylase and α-glucosidase strongly, with IC 50 values of 0.35 and 0.24 mg/mL, separately. In addition, 20 μg/mL of persimmon tannin significantly decreased glucose uptake and transport in Caco-2 cells model. Overall, our data suggested that persimmon tannin may alleviate postprandial hyperglycemia through limiting the digestion of starch as well as inhibiting the uptake and transport of glucose.

The effects of a repeated dose of a recombinant humanized anti-cocaine monoclonal antibody on cocaine self-administration in rats.

PubMed

Wetzel, Hanna N; Tsibulsky, Vladimir L; Norman, Andrew B

2016-11-01

Immunotherapy has shown potential as a treatment for cocaine abuse. The humanized recombinant anti-cocaine monoclonal antibody (mAb) with the preclinical designation h2E2 has been shown to decrease cocaine concentrations in the brain in rats, but its effects on cocaine self-administration behavior have never been tested. The amount of cocaine needed to reinstate self-administration behavior (priming threshold) was calculated and the inter-injection intervals at unit doses of 0.3μmol/kg and 3μmol/kg during maintained self-administration were measured over a five-week baseline period. Rats trained to self-administer cocaine were infused with two doses of h2E2 (120mg/kg i.v.) 35days apart. Priming threshold and inter-injection intervals were measured for 35days after both injections. After both injections of h2E2, priming thresholds were significantly increased (3-fold) compared to expected baseline and then gradually declined over 35days. A significant decrease (15-33%) in inter-injection intervals during maintained self-administration was also observed following both h2E2 infusions at the lower dose, and after the first injection at the higher dose. No significant decreases in body weight were observed after either injection, indicating a lack of toxicity following a second injection. These data predict that the safety and effectiveness of h2E2 will be maintained after multiple treatments of this potential immunotherapy for cocaine abuse. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The effects of a repeated dose of a recombinant humanized anti-cocaine monoclonal antibody on cocaine self-administration in rats

PubMed Central

Wetzel, Hanna N.; Tsibulsky, Vladimir L.; Norman, Andrew B.

2016-01-01

Background Immunotherapy has shown potential as a treatment for cocaine abuse. The humanized recombinant anti-cocaine monoclonal antibody (mAb) with the preclinical designation h2E2 has been shown to decrease cocaine concentrations in the brain in rats, but its effects on cocaine self-administration behavior have never been tested. Methods The amount of cocaine needed to reinstate self-administration behavior (priming threshold) was calculated and the inter-injection intervals at unit doses of 0.3 μmol/kg and 3 μmol/kg during maintained self-administration were measured over a five-week baseline period. Rats trained to self-administer cocaine were infused with two doses of h2E2 (120 mg/kg i.v.) 35 days apart. Priming threshold and inter-injection intervals were measured for 35 days after both injections. Results After both injections of h2E2, priming thresholds were significantly increased (3-fold) compared to expected baseline and then gradually declined over 35 days. A significant decrease (15–33%) in inter-injection intervals during maintained self-administration was also observed following both h2E2 at the lower dose, and after the first injection at the higher dose. No significant decreases in body weight were observed after either injection, indicating a lack of toxicity following a second injection. Conclusions These data predict that the safety and efficacy of h2E2 will be maintained after multiple treatments of this potential immunotherapy for cocaine abuse. PMID:27736682

A conscious rat model involving bradycardia and hypotension after oral administration: a toxicokinetical study of aconitine.

PubMed

Zhang, Panpan; Kong, Dezhi; Du, Qian; Zhao, Jing; Li, Qing; Zhang, Jianghua; Li, Tonghui; Ren, Leiming

2017-06-01

1. A model of aconitine-induced bradycardia and hypotension, which is similar to aconitine poisoning in humans, was constructed in conscious rats by oral administration. 2. Blood pressure (BP) and heart rate (HR) of Sprague-Dawley rats were measured using a volume pressure recording (VPR) system. The pharmacokinetics of toxic doses of aconitine and its metabolites were analyzed using UPLC-MS/MS. 3. The HR was significantly decreased by 29% at 2 h after oral administration of 200 μg/kg aconitine. When the dose was increased to 400 μg/kg, systolic BP and diastolic BP were significantly decreased by 11% and 12% at 2 h after the administration, except when bradycardia occurred at 2 h and 4 h. The drug concentration-time curve showed a double-peak phenomenon in rats administered a 400 μg/kg dose. The AUC 0-12 h value in the 400 μg/kg group significantly increased 0.8-fold compared to the 200 μg/kg group. Moreover, a high plasma concentration of 16-O-demethyaconitine was found in the rats that received two toxic doses. 4. In conclusion, bradycardia and hypotension are induced in conscious rats by a toxic dose of aconitine (400 μg/kg), and there was no significant difference in dose-normalized AUC 0-12 h values between oral administrations of 200 μg/kg and that of 400 μg/kg. However, the dose-normalized C max and AUC 0-12 h values in 200 μg/kg and 400 μg/kg groups were significantly smaller than those in 100 μg/kg group. The metabolites of aconitine, 16-O-demethyaconitine, and benzoylaconitine may also contribute to the hypotensive response.

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.

13 CFR 108.585 - Voluntary decrease in NMVC Company's Regulatory Capital.

Code of Federal Regulations, 2010 CFR

2010-01-01

...'s Regulatory Capital. 108.585 Section 108.585 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION NEW MARKETS VENTURE CAPITAL (âNMVCâ) PROGRAM Managing the Operations of a NMVC Company Voluntary Decrease in Regulatory Capital § 108.585 Voluntary decrease in NMVC Company's Regulatory Capital. You must...

Determinants of cocaine self-administration by laboratory animals.

PubMed

Woolverton, W L

1992-01-01

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

Use of radiotelemetry to evaluate respiratory depression produced by chronic methadone administration.

PubMed

Lewanowitsch, Tanya; White, Jason M; Irvine, Rodney J

2004-01-26

Illicit and therapeutic opioid administration can result in overdose due to opioid-induced respiratory depression. Research investigating the respiratory depressant effects of opioids has been limited due to difficulties associated with acquiring long-term respiratory data. This study examined the novel use of radiotelemetry to measure respiratory rate, heart rate, locomotor activity and blood pressure in rats treated chronically with methadone. Over 4 days of treatment, respiratory rate decreased, but partial tolerance appeared to develop during active (night) periods. Decreased heart rate was observed during the night periods and tolerance appeared to develop to this effect. Activity and blood pressure did not change with treatment. The effects of naloxone hydrochloride and naloxone methiodide administration on the methadone-treated rats were also examined and both antagonists increased respiratory rate and heart rate, with only naloxone hydrochloride producing significant increases in activity. Radiotelemetry offers a means of evaluating drug effects on respiratory rate continually in ambulatory, unstressed animals.

Meal Effects Confound Attempts to Counteract Rabeprazole-Induced Hypochlorhydria Decreases in Atazanavir Absorption.

PubMed

Faber, Kathleen Panter; Wu, Hsin-Fang; Yago, Marc R; Xu, Xiaohui; Kadiyala, Pathanjali; Frassetto, Lynda A; Benet, Leslie Z

2017-03-01

Clinically relevant pharmacokinetic interactions exist between gastric acid-reducing agents and certain weakly basic drugs that rely on acidic environments for optimal oral absorption. In this study, we examine whether the administration of betaine hydrochloride under fed conditions can enhance the absorption of atazanavir, an HIV-1 protease inhibitor, during pharmacologically-induced hypochlorhydria. In this randomized, single-dose, 3 period, crossover study healthy volunteers received ritonavir-boosted atazanavir (atazanavir/ritonavir 300/100 mg) alone, following pretreatment with the proton pump inhibitor rabeprazole (20 mg twice daily), and with 1500 mg of betaine HCl after rabeprazole pretreatment. Atazanavir was administered with a light meal and gastric pH was monitored using the Heidelberg Capsule. Pretreatment with rabeprazole resulted in significant reductions in atazanavir C max (p < 0.01) and AUC 0-last (p < 0.001) (71 and 70%, respectively), and modest decreases in ritonavir C max and AUC last (p < 0.01) (40% and 41%, respectively). The addition of betaine HCl restored 13% of ATV C max and 12% of AUC last lost due to rabeprazole. The co-administration of rabeprazole with atazanavir resulted in significant decreases in atazanavir exposure. The addition of betaine HCl did not sufficiently mitigate the loss of ATV exposure observed during RAB-induced hypochlorhydria. Meal effects lead to a marked difference in the outcome of betaine HCl on atazanavir exposure than we previously reported for dasatanib under fasting conditions.

Neuroprotection and mechanisms of atractylenolide III in preventing learning and memory impairment induced by chronic high-dose homocysteine administration in rats.

PubMed

Zhao, H; Ji, Z-H; Liu, C; Yu, X-Y

2015-04-02

Studies demonstrated that chronic high-dose homocysteine administration induced learning and memory impairment in animals. Atractylenolide III (Aen-III), a neuroprotective constituent of Atractylodis macrocephalae Koidz, was isolated in our previous study. In this study, we investigated potential benefits of Aen-III in preventing learning and memory impairment following chronic high-dose homocysteine administration in rats. Results showed that administration of Aen-III significantly ameliorated learning and memory impairment induced by chronic high-dose homocysteine administration in rats, decreased homocysteine-induced reactive oxygen species (ROS) formation and restored homocysteine-induced decrease of phosphorylated protein kinase C expression level. Moreover, Aen-III protected primary cultured neurons from apoptotic death induced by homocysteine treatment. This study provides the first evidence for the neuroprotective effect of Aen-III in preventing learning and impairment induced by chronic administration of homocysteine. Aen-III may have therapeutic potential in treating homocysteine-mediated cognitive impairment and neuronal injury. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

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

PubMed

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

2002-10-01

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

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

PubMed

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

2015-01-01

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

Use of a subcutaneous glucose sensor to detect decreases in glucose concentration prior to observation in blood.

PubMed

Thomé-Duret, V; Reach, G; Gangnerau, M N; Lemonnier, F; Klein, J C; Zhang, Y; Hu, Y; Wilson, G S

1996-11-01

The development of a hypoglycemic alarm system using a subcutaneous glucose sensor implies that a decrease in blood glucose is rapidly followed by a decrease in the signal generated by the sensor. In a first set of experiments the linearity and the kinetics of the response of sensors implanted in the subcutaneous tissue of normal rats were investigated during a progressive increase in plasma glucose concentration: the sensitivities determined between 5 and 10 mM and between 10 and 15 mM were not significantly different, and a 5-10 min delay in the sensor's response was observed. In a second set of experiments, performed in diabetic rats, the kinetics of the decrease in subcutaneous glucose concentration following insulin administration was monitored during a decrease in plasma glucose level, from 15 to 3 mmol/L. During the 20 first min following insulin administration, the sensor monitored glucose concentration in subcutaneous tissue with no lag time. Subsequently, the decrease in the estimation of subcutaneous glucose concentration preceded that of plasma glucose. This phenomenon was not observed when the same sensors were investigated in vitro during a similar decrease in glucose concentration and may be due to a mechanism occurring in vivo, such as the effect of insulin on glucose transfer from the interstitial space to the cells surrounding the sensor. It reinforces the interest of the use of implantable glucose sensors as a part of a hypoglycemic alarm.

Anti-obesity effect of intranasal administration of galanin-like peptide (GALP) in obese mice

PubMed Central

Kageyama, Haruaki; Shiba, Kanako; Hirako, Satoshi; Wada, Nobuhiro; Yamanaka, Satoru; Nogi, Yukinori; Takenoya, Fumiko; Nonaka, Naoko; Hirano, Tsutomu; Inoue, Shuji; Shioda, Seiji

2016-01-01

Galanin-like peptide (GALP) has an anti-obesity effect in rats and mice. It has been reported that the uptake of GALP by the brain is higher after intranasal administration than with intravenous injection. This study therefore aimed to clarify the effect of intranasal administration of GALP on the feeding behavior of lean and obese mice. Autoradiography revealed the presence of 125I-GALP in the olfactory bulb and the brain microcirculation. The body weights of ob/ob mice gradually increased during vehicle treatment, but remained unchanged in response to repeated intranasal administration of GALP, with both ob/ob and diet-induced obese mice displaying significantly decreased food intake, water intake and locomotor activity when treated with GALP. These results suggest that intranasal administration is an effective route whereby GALP can exert its effect as an anti-obesity drug. PMID:27323911

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

PubMed

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

2017-02-01

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

Diazepam administration prevents testosterone decrease and lipofuscin accumulation in testis of mouse exposed to chronic noise stress.

PubMed

Ruffoli, R; Carpi, A; Giambelluca, M A; Grasso, L; Scavuzzo, M C; Giannessi F, F

2006-10-01

Lipofuscin is an autofluorescent and undegradable material, which accumulates in tissues during ageing and under different types of stress. Among these, oxidative stress represents a major trigger for lipofuscin formation. However, prolonged noise exposure is also an effective stressful stimuli. Diazepam may inhibit lipofuscinogenesis in liver and prevent the noise-induced reduction of the steroidogenesis in the adrenal gland. The aim of the study was to ascertain whether chronic noise exposure causes lipofuscin accumulation in mouse testis, and to evaluate the effects of diazepam administration. Eight-week old mice were either exposed for 6 weeks (6 h day(-1)) to white-noise (group A), or received diazepam (3 mg kg(-1), i.p.) before noise exposures (group B), while a further group was used as control (group C). Light fluorescence and transmission electron microscopy revealed lipofuscin in large amounts in the Leydig cells in mice of group A, which concomitantly had low serum testosterone levels; pre-treatment with diazepam occluded both effects. The present study indicates that: (i) chronic noise exposure causes lipofuscin accumulation at the level of the Leydig cells and a decrease in testosterone; (ii) all these effects are suppressed by pre-treatment with diazepam. As the Leydig cells represent the only cellular type of the interstitial testicular tissue having peripheral benzodiazepine receptors, these results could be explained by the capacity of the peripheral benzodiazepine receptors to prevent reactive oxygen species damage and to increase the resistance of these cells to oxidative stress.

Dapagliflozin significantly reduced liver fat accumulation associated with a decrease in abdominal subcutaneous fat in patients with inadequately controlled type 2 diabetes mellitus.

PubMed

Kurinami, Noboru; Sugiyama, Seigo; Yoshida, Akira; Hieshima, Kunio; Miyamoto, Fumio; Kajiwara, Keizo; Jinnouch, Katsunori; Jinnouchi, Tomio; Jinnouchi, Hideaki

2018-05-31

We examined dapagliflozin-induced changes in liver fat accumulation. We prospectively recruited Japanese patients with inadequately controlled type 2 diabetes mellitus (T2DM) [hemoglobin A1c (HbA1c) >7.0%]. Dapagliflozin (5 mg/day) or non-sodium glucose cotransporter 2 inhibitors (SGLT2i) was added to the patients' treatment regimen for 6 months. Changes in liver fat accumulation were assessed by the liver-to-spleen (L/S) attenuation ratio using abdominal computed tomography (CT). This study enrolled 55 Japanese T2DM patients. The L/S ratio significantly increased in the dapagliflozin group compared with the non-SGLT2i group. Abdominal subcutaneous fat area (SFA), visceral fat area, total fat area assessed by abdominal CT, aspartate aminotransferase, alanine aminotransferase (ALT), and γ-glutamyl transpeptidase decreased significantly only in the dapagliflozin group. Changes in the L/S ratio showed a significant negative relationship with changes in abdominal SFA, ALT, and non-esterified fatty acid. In sub-group analyses of non-insulin users, hepatic insulin extraction was assessed by the plasma C-peptide-to-insulin ratio, which was significantly increased in the dapagliflozin group but not in the non-SGLT2i group. In patients with inadequately controlled T2DM, additional dapagliflozin-treatment significantly reduced the liver fat accumulation associated with a decrease in abdominal SFA. Copyright © 2018 Elsevier B.V. All rights reserved.

Attenuation of cocaine self-administration by chronic oral phendimetrazine in rhesus monkeys.

PubMed

Czoty, P W; Blough, B E; Fennell, T R; Snyder, R W; Nader, M A

2016-06-02

Chronic treatment with the monoamine releaser d-amphetamine has been consistently shown to decrease cocaine self-administration in laboratory studies and clinical trials. However, the abuse potential of d-amphetamine is an obstacle to widespread clinical use. Approaches are needed that exploit the efficacy of the agonist approach but avoid the abuse potential associated with dopamine releasers. The present study assessed the effectiveness of chronic oral administration of phendimetrazine (PDM), a pro-drug for the monoamine releaser phenmetrazine (PM), to decrease cocaine self-administration in four rhesus monkeys. Each day, monkeys pressed a lever to receive food pellets under a 50-response fixed-ratio (FR) schedule of reinforcement and self-administered cocaine (0.003-0.56 mg/kg per injection, i.v.) under a progressive-ratio (PR) schedule in the evening. After completing a cocaine self-administration dose-response curve, sessions were suspended and PDM was administered (1.0-9.0 mg/kg, p.o., b.i.d.). Cocaine self-administration was assessed using the PR schedule once every 7 days while food-maintained responding was studied daily. When a persistent decrease in self-administration was observed, the cocaine dose-effect curve was re-determined. Daily PDM treatment decreased cocaine self-administration by 30-90% across monkeys for at least 4 weeks. In two monkeys, effects were completely selective for cocaine. Tolerance developed to initial decreases in food-maintained responding in the third monkey and in the fourth subject, fluctuations were observed that were lower in magnitude than effects on cocaine self-administration. Cocaine dose-effect curves were shifted down and/or rightward in three monkeys. These data provide further support for the use of agonist medications for cocaine abuse, and indicate that the promising effects of d-amphetamine extend to a more clinically viable pharmacotherapy. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Effects of Lorcaserin on Cocaine and Methamphetamine Self-Administration and Reinstatement of Responding Previously Maintained by Cocaine in Rhesus Monkeys.

PubMed

Gerak, Lisa R; Collins, Gregory T; France, Charles P

2016-12-01

Stimulant abuse is a serious public health issue for which there is no effective pharmacotherapy. The serotonin 2C [5-hydroxytryptamine 2C (5-HT 2C )] receptor agonist lorcaserin decreases some abuse-related effects of cocaine in monkeys and might be useful for treating stimulant abuse. The current study investigated the effectiveness of lorcaserin to reduce self-administration of either cocaine or methamphetamine and cocaine-induced reinstatement of extinguished responding. Four rhesus monkeys responded under a progressive-ratio (PR) schedule in which the response requirement increased after each cocaine infusion (32-320 μg/kg/infusion). A separate group of four monkeys responded under a fixed-ratio (FR) schedule for cocaine (32 μg/kg/infusion) and reinstatement of extinguished responding was examined following administration of noncontingent infusions of cocaine (0.1-1 mg/kg) that were combined with response-contingent presentations of the drug-associated stimuli. Finally, three monkeys responded under a FR schedule for methamphetamine (0.32-100 μg/kg/infusion). Lorcaserin (3.2 mg/kg) significantly decreased the final ratio completed (i.e., decreased break point) in monkeys responding under the PR schedule and reduced the reinstatement of responding for drug-associated stimuli following a noncontingent infusion of cocaine; these effects did not appear to change when lorcaserin was administered daily. The same dose of lorcaserin decreased responding for methamphetamine in two of the three monkeys, and the effect was maintained during daily lorcaserin administration; larger doses given acutely (10-17.8 mg/kg) significantly decreased responding for methamphetamine, although that effect was not sustained during daily lorcaserin administration. Together, these results indicate that lorcaserin might be effective in reducing cocaine and methamphetamine abuse and cocaine relapse at least in some individuals. Copyright © 2016 by The American Society for Pharmacology

Effects of Lorcaserin on Cocaine and Methamphetamine Self-Administration and Reinstatement of Responding Previously Maintained by Cocaine in Rhesus Monkeys

PubMed Central

Gerak, Lisa R.; Collins, Gregory T.

2016-01-01

Stimulant abuse is a serious public health issue for which there is no effective pharmacotherapy. The serotonin2C [5-hydroxytryptamine2C (5-HT2C)] receptor agonist lorcaserin decreases some abuse-related effects of cocaine in monkeys and might be useful for treating stimulant abuse. The current study investigated the effectiveness of lorcaserin to reduce self-administration of either cocaine or methamphetamine and cocaine-induced reinstatement of extinguished responding. Four rhesus monkeys responded under a progressive-ratio (PR) schedule in which the response requirement increased after each cocaine infusion (32–320 μg/kg/infusion). A separate group of four monkeys responded under a fixed-ratio (FR) schedule for cocaine (32 μg/kg/infusion) and reinstatement of extinguished responding was examined following administration of noncontingent infusions of cocaine (0.1–1 mg/kg) that were combined with response-contingent presentations of the drug-associated stimuli. Finally, three monkeys responded under a FR schedule for methamphetamine (0.32–100 μg/kg/infusion). Lorcaserin (3.2 mg/kg) significantly decreased the final ratio completed (i.e., decreased break point) in monkeys responding under the PR schedule and reduced the reinstatement of responding for drug-associated stimuli following a noncontingent infusion of cocaine; these effects did not appear to change when lorcaserin was administered daily. The same dose of lorcaserin decreased responding for methamphetamine in two of the three monkeys, and the effect was maintained during daily lorcaserin administration; larger doses given acutely (10–17.8 mg/kg) significantly decreased responding for methamphetamine, although that effect was not sustained during daily lorcaserin administration. Together, these results indicate that lorcaserin might be effective in reducing cocaine and methamphetamine abuse and cocaine relapse at least in some individuals. PMID:27650954

Nattokinase decreases plasma levels of fibrinogen, factor VII, and factor VIII in human subjects.

PubMed

Hsia, Chien-Hsun; Shen, Ming-Ching; Lin, Jen-Shiou; Wen, Yao-Ke; Hwang, Kai-Lin; Cham, Thau-Ming; Yang, Nae-Cherng

2009-03-01

Nattokinase, a serine proteinase from Bacillus subtilis, is considered to be one of the most active functional ingredients found in natto. In this study, we hypothesized that nattokinase could reduce certain factors of blood clotting and lipids that are associated with an increase risk for cardiovascular disease (CVD). Thus, an open-label, self-controlled clinical trial was conducted on subjects of the following groups: healthy volunteers (Healthy Group), patients with cardiovascular risk factors (Cardiovascular Group), and patients undergoing dialysis (Dialysis Group). All subjects ingested 2 capsules of nattokinase (2000 fibrinolysis units per capsule) daily orally for 2 months. The laboratory measurements were performed on the screening visit and, subsequently, regularly after the initiation of the study. The intent-to-treat analysis was performed on all 45 enrolled subjects. By use of mixed model analysis, a significant time effect, but not group effect, was observed in the change from baseline of fibrinogen (P = .003), factor VII (P < .001), and factor VIII (P < .001), suggesting that the plasma levels of the 3 coagulation factors continuously declined during intake; also, the extents of decrease were similar between groups. After 2 months of administration, fibrinogen, factor VII, and factor VIII decreased 9%, 14%, and 17%, respectively, for the Healthy Group; 7%, 13%, and 19%, respectively, for the Cardiovascular Group; and 10%, 7%, and 19%, respectively, for the Dialysis Group, whereas blood lipids were unaffected by nattokinase. No significant changes of uric acid or notable adverse events were observed in any of the subjects. In summary, this study showed that oral administration of nattokinase could be considered as a CVD nutraceutical by decreasing plasma levels of fibrinogen, factor VII, and factor VIII.

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.

Age and body composition influence TSH concentrations after administration of rhTSH.

PubMed

Holthausen, F F; von Müller, F; Happel, C; Kranert, W T; Grünwald, F

2015-01-01

Previous studies listed body surface area (BSA), lean body mass (LBM), and age as modifying factors on the TSH concentrations after administration of recombinant human thyrotropin (rhTSH). The purpose of this study was to identify the main modifying factors on serum TSH levels and to compare the stimulation via single rhTSH injection after a short thyroid hormone withdrawal (THW) with that of the standard stimulating protocol. 106 patients with differentiated thyroid cancer (DTC) undergoing radioiodine therapy (RIT) after rhTSH administration were obtained through chart review. Two groups were evaluated: Group I was treated with a single rhTSH administration after two weeks of T3 therapy followed by one week of THW. Group II was stimulated according to the international standard protocol via rhTSH injections for two consecutive days. Serum TSH concentrations were documented prior to rhTSH administration (day 1 TSH), one day after (day 3 TSH) and 3-6 days after (mean 4.2 days, day 6 TSH) the last rhTSH injection. The following data was collected: age, gender, weight, height, BMI, LBM, BSA, residual thyroid tissue, CRP, creatinine, GFR, liver enzymes, alkaline phosphatase, cholesterol, and triglycerides. Group I: Age combined with anthropometric factors like BMI (TSH increase and day 6 TSH), BSA (TSH decrease), and gender (day 6 TSH) are the main modifying factors on serum TSH concentrations after rhTSH administration. Group II: Age and lean body mass (LBM) showed a significant impact on day 3 TSH, TSH increase (day 3-day 1), and TSH decrease (day 6-day 3). Day 6 TSH was found to be influenced by GFR (group II). Age and anthropometric parameters have significant independent influence on TSH concentrations after rhTSH injection in both groups. Anthropometric parameters (BSA, LBM) and demographic parameters (female gender) show strong influence on TSH concentrations. Further research should be conducted to examine the influence of body compartments on TSH levels

The effect of peripheral chronic salsolinol administration on fat pad adipocytes morphological parameters.

PubMed

Aleksandrovych, Veronika; Kurnik, Magdalena; Białas, Magdalena; Bugajski, Andrzej; Thor, Piotr; Gil, Krzysztof

Salsolinol (1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline) is thought to regulate dopaminergic neurons and to act as a mediator in the neuroendocrine system. We have previously reported that exogenous salsolinol evokes enteric neuronal cell death, leading to the impairment of myenteric neurons density and abnormal intestinal transit in rats. We also observed significant reduction of body weight, related to the disrupted gastrointestinal homeostasis. e aim of current study was to evaluate the influence of prolonged salsolinol administration body weight, food intake, adipose tissue accumulation and fad pad adipocyte morphological parameters assessed by image analysis. Male Wistar rats were subjected to continuous intraperitoneal low dosing of salsolinol - 200 mg/kg in total with ALZET osmotic mini-pumps (Durtec, USA) for 2 or 4 weeks with either normal or high-fat diet. Appropriate groups served as the controls. Food intake, body weight were measured each morning. Both epididymal fat pads were dissected, weighted and processed for routine hematoxylin and eosin staining. e following parameters: cell area, perimeter, long and short axis, aspect ratio and circularity factor were assessed in stained specimens with the image analysis system (Multiscan, Poland). Salsolinol administration significantly reduced total body mass with no differences in total food intake between the groups. The epididymal fat pad weight over final body mass ratio was lower in salsolinol treated rats on high fat diet in comparison with the control groups. e area, perimeter, short and long axis of the fad pad adipocytes were significantly decreased in salsolinol treated animals in comparison with relevant controls. Salsolinol targets some regulatory mechanisms concerned with the basic rat metabolism. Prolonged peripheral salsolinol administration in rats significantly decreases the adipocyte size, and such effect is related to the weight loss and reduced adipose tissue accumulation.

Nitric oxide decreases coagulation protein function in rabbits as assessed by thromboelastography.

PubMed

Nielsen, V G

2001-02-01

Nitric oxide (NO) is administered via infusion of donors such as nitroglycerin or in inhaled form for treatment of ischemia and pulmonary hypertension, respectively. In rabbits, the NO donor, DETANONOate, decreases whole blood clotting function as assessed by thromboelastographic variables (R, reaction time; alpha, angle; and G, a measure of clot strength). I hypothesized that DETANONOate-derived NO would adversely affect coagulation protein and platelet function. Blood obtained from ear arteries of conscious rabbits (n = 8) anticoagulated with sodium citrate. The blood was then incubated with 0 or 10mM DETANONOate for 30 min. After incubation and recalcification, thromboelastography was performed for 60 min under four conditions: 1) 0mM DETANONOate, 2) 0mM DETANONOate with platelet inhibition with cytochalasin D, 3) 10mM DETANONOate, and 4) 10mM DETANONOate with platelet inhibition. DETANONOate significantly (P < 0.05) increased R and decreased alpha and G in samples with or without platelet inhibition, compared with samples not exposed to DETANONOate. Lastly, the percentage of total G (G(T)) attributable to platelet function (G(P)) was significantly more in the absence of DETANONOate (G(P) = 92.3% +/- 1.6%; mean +/- SD) than after exposure to DETANONOate (G(P) = 90.2% +/- 2.3%). DETANONOate-derived NO significantly decreased coagulation protein function and platelet function. Coagulation protein function may be similarly affected in clinical situations involving the administration of NO or NO donors.

In vivo measurements of T1 relaxation times in mouse brain associated with different modes of systemic administration of manganese chloride.

PubMed

Kuo, Yu-Ting; Herlihy, Amy H; So, Po-Wah; Bhakoo, Kishore K; Bell, Jimmy D

2005-04-01

To measure regional T1 and T2 values for normal C57Bl/6 mouse brain and changes in T1 after systemic administration of manganese chloride (MnCl2) at 9.4 T. C57Bl/6 mice were anesthetized and baseline T1 and T2 measurements obtained prior to measurement of T1 after administration of MnCl2 at 9.4 T. MnCl2 was administered systemically either by the intravenous (IV), intraperitoneal (IP), or subcutaneous (SC) routes. T1 and T2 maps for each MRI transverse slice were generated using commercial software, and T1 and T2 values of white matter (WM), gray matter (GM), pituitary gland, and lateral ventricle were obtained. When compared with baseline values at low-field, significant lengthening of the T1 values was shown at 9.4 T, while no significant change was seen for T2 values. Significant T1 shortening of the normal mouse brain was observed following IV, IP, and SC administration of MnCl2, with IV and IP showing similar acute effects. Significant decreases in T1 values were seen for the pituitary gland and the ventricles 15 minutes after either IV or IP injection. GM showed greater uptake of the contrast agent than WM at 15 and 45 minutes after either IV or IP injections. Although both structures are within the blood-brain barrier (BBB), GM and WM revealed a steady decrease in T1 values at 24 and 72 hours after MnCl2 injection regardless of the route of administration. Systemic administration of MnCl2 by IV and IP routes induced similar time-course of T1 changes in different regions of the mouse brain. Acute effects of MnCl2 administration were mainly influenced by either the presence or absence of BBB. SC injection also provided significant T1 change at subacute stage after MnCl2 administration. Copyright 2005 Wiley-Liss, Inc.

Repeated Famotidine Administration Results in a Diminished Effect on Intragastric pH in Dogs.

PubMed

Tolbert, M K; Graham, A; Odunayo, A; Price, J; Steiner, J M; Newkirk, K; Hecht, S

2017-01-01

Famotidine is an acid suppressant commonly administered to dogs. Prolonged famotidine use in people results in decreased efficacy, but the effect in dogs is unknown. To compare the effect of repeated oral administration of famotidine or placebo on intragastric pH and serum gastrin in dogs. We hypothesized that famotidine would have a diminished effect on intragastric pH on day 13 compared to day 1. Six healthy adult colony Beagles. Randomized, 2-factor repeated-measures crossover design. All dogs received oral placebo or 1.0 mg/kg famotidine q12h for 14 consecutive days. Intragastric pH monitoring was used to continuously record intragastric pH on treatment days 1-2 and 12-13. Mean pH as well as mean percentage time (MPT) that intragastric pH was ≥3 or ≥4 were compared between and within groups by analysis of variance. Serum gastrin was measured on days 0, 3, and 12 for each treatment. Continued administration of famotidine resulted in a significant decrease in mean pH, MPT ≥3, and MPT ≥4 (P < .0001) on day 12 and 13. This resulted in a mean decrease in pH by 1.63 on days 12 and 13 compared to days 1 and 2. Furthermore, a mean decrease of MPT ≥3 and MPT ≥4 by 33 and 45% was observed for the same time period, respectively. Continued administration of famotidine results in a diminished effect on intragastric pH in dogs. Caution is advised when recommending long-term, daily oral administration of famotidine to dogs. Copyright © 2016 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Sedative effects of midazolam and xylazine with or without ketamine and detomidine alone following intranasal administration in Ring-necked Parakeets.

PubMed

Vesal, Nasser; Eskandari, Mohammad H

2006-02-01

To evaluate the effects of intranasal administration of midazolam and xylazine (with or without ketamine) and detomidine and their specific antagonists in parakeets. Prospective study. 17 healthy adult Ring-necked Parakeets (Psittacula krameri) of both sexes (mean weight, 128.83+/-10.46 g [0.28+/-0.02 lb]). The dose of each drug or ketamine-drug combination administered intranasally that resulted in adequate sedation (ie, unrestrained dorsal recumbency maintained for >or=5 minutes) was determined; the onset of action, duration of dorsal recumbency, and duration of sedation associated with these treatments were evaluated. The efficacy of the reversal agents flumazenil, yohimbine, and atipamezole was also evaluated. In parakeets, intranasal administration of midazolam (7.3 mg/kg [3.32 mg/lb]) or detomidine (12 mg/kg [5.45 mg/lb]) caused adequate sedation within 2.7 and 3.5 minutes, respectively. Combinations of midazolam (3.65 mg/kg [1.66 mg/lb]) and xylazine (10 mg/kg [4.55 mg/lb]) with ketamine (40 to 50 mg/kg [18.2 to 22.7 mg/lb]) also achieved adequate sedation. Compared with detomidine, duration of dorsal recumbency was significantly longer with midazolam. Intranasal administration of flumazenil (0.13 mg/kg [0.06 mg/lb]) significantly decreased midazolam-associated recumbency time. Compared with the xylazineketamine combination, duration of dorsal recumbency was longer after midazolam-ketamine administration. Intranasal administration of flumazenil, yohimbine, or atipamezole significantly decreased the duration of sedation induced by midazolam, xylazine, or detomidine, respectively. Intranasal administration of sedative drugs appears to be an acceptable method of drug delivery in Ring-necked Parakeets. Reversal agents are also effective when administered via this route.

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.

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…

Improved accuracy of co-morbidity coding over time after the introduction of ICD-10 administrative data

PubMed Central

2011-01-01

Background Co-morbidity information derived from administrative data needs to be validated to allow its regular use. We assessed evolution in the accuracy of coding for Charlson and Elixhauser co-morbidities at three time points over a 5-year period, following the introduction of the International Classification of Diseases, 10th Revision (ICD-10), coding of hospital discharges. Methods Cross-sectional time trend evaluation study of coding accuracy using hospital chart data of 3'499 randomly selected patients who were discharged in 1999, 2001 and 2003, from two teaching and one non-teaching hospital in Switzerland. We measured sensitivity, positive predictive and Kappa values for agreement between administrative data coded with ICD-10 and chart data as the 'reference standard' for recording 36 co-morbidities. Results For the 17 the Charlson co-morbidities, the sensitivity - median (min-max) - was 36.5% (17.4-64.1) in 1999, 42.5% (22.2-64.6) in 2001 and 42.8% (8.4-75.6) in 2003. For the 29 Elixhauser co-morbidities, the sensitivity was 34.2% (1.9-64.1) in 1999, 38.6% (10.5-66.5) in 2001 and 41.6% (5.1-76.5) in 2003. Between 1999 and 2003, sensitivity estimates increased for 30 co-morbidities and decreased for 6 co-morbidities. The increase in sensitivities was statistically significant for six conditions and the decrease significant for one. Kappa values were increased for 29 co-morbidities and decreased for seven. Conclusions Accuracy of administrative data in recording clinical conditions improved slightly between 1999 and 2003. These findings are of relevance to all jurisdictions introducing new coding systems, because they demonstrate a phenomenon of improved administrative data accuracy that may relate to a coding 'learning curve' with the new coding system. PMID:21849089

Improved accuracy of co-morbidity coding over time after the introduction of ICD-10 administrative data.

PubMed

Januel, Jean-Marie; Luthi, Jean-Christophe; Quan, Hude; Borst, François; Taffé, Patrick; Ghali, William A; Burnand, Bernard

2011-08-18

Co-morbidity information derived from administrative data needs to be validated to allow its regular use. We assessed evolution in the accuracy of coding for Charlson and Elixhauser co-morbidities at three time points over a 5-year period, following the introduction of the International Classification of Diseases, 10th Revision (ICD-10), coding of hospital discharges. Cross-sectional time trend evaluation study of coding accuracy using hospital chart data of 3'499 randomly selected patients who were discharged in 1999, 2001 and 2003, from two teaching and one non-teaching hospital in Switzerland. We measured sensitivity, positive predictive and Kappa values for agreement between administrative data coded with ICD-10 and chart data as the 'reference standard' for recording 36 co-morbidities. For the 17 the Charlson co-morbidities, the sensitivity - median (min-max) - was 36.5% (17.4-64.1) in 1999, 42.5% (22.2-64.6) in 2001 and 42.8% (8.4-75.6) in 2003. For the 29 Elixhauser co-morbidities, the sensitivity was 34.2% (1.9-64.1) in 1999, 38.6% (10.5-66.5) in 2001 and 41.6% (5.1-76.5) in 2003. Between 1999 and 2003, sensitivity estimates increased for 30 co-morbidities and decreased for 6 co-morbidities. The increase in sensitivities was statistically significant for six conditions and the decrease significant for one. Kappa values were increased for 29 co-morbidities and decreased for seven. Accuracy of administrative data in recording clinical conditions improved slightly between 1999 and 2003. These findings are of relevance to all jurisdictions introducing new coding systems, because they demonstrate a phenomenon of improved administrative data accuracy that may relate to a coding 'learning curve' with the new coding system.

Multipotent mesenchymal stromal cells decrease transforming growth factor β1 expression in microglia/macrophages and down-regulate plasminogen activator inhibitor 1 expression in astrocytes after stroke.

PubMed

Xin, Hongqi; Chopp, Michael; Shen, Li Hong; Zhang, Rui Lan; Zhang, Li; Zhang, Zheng Gang; Li, Yi

2013-05-10

Multipotent mesenchymal stromal cells (MSCs) decrease the expression of transforming growth factor β1 (TGFβ1) in astrocytes and subsequently decrease astrocytic plasminogen activator inhibitor 1 (PAI-1) level in an autocrine manner. Since activated microglia/macrophages are also a source of TGFβ1 after stroke, we therefore tested whether MSCs regulate TGFβ1 expression in microglia/macrophages and subsequently alters PAI-1 expression after ischemia. TGFβ1 and its downstream effector phosphorylated SMAD 2/3 (p-SMAD 2/3) were measured in mice subjected to middle cerebral artery occlusion (MCAo). MSC treatment significantly decreased TGFβ1 protein expression in both astrocytes and microglia/macrophages in the ischemic boundary zone (IBZ) at day 14 after stroke. However, the p-SMAD 2/3 was only detected in astrocytes and decreased after MSC treatment. In vitro, RT-PCR results showed that the TGFβ1 mRNA level was increased in both astrocytes and microglia/macrophages in an astrocyte-microglia/macrophage co-culture system after oxygen-glucose deprived (OGD) treatment. MSCs treatment significantly decreased the above TGFβ1 mRNA level under OGD conditions, respectively. OGD increased the PAI-1 mRNA in astrocytes in the astrocyte-microglia/macrophage co-culture system, and MSC administration significantly decreased this level. PAI-1 mRNA was very low in microglia/macrophages compared with that in astrocytes under different conditions. Western blot results also verified that MSC administration significantly decreased p-SMAD 2/3 and PAI-1 level in astrocytes in astrocyte-microglia/macrophage co-culture system under OGD conditions. Our in vivo and in vitro data, in concert, suggest that MSCs decrease TGFβ1 expression in microglia/macrophages in the IBZ which contribute to the down-regulation of PAI-1 level in astrocytes. Published by Elsevier Ireland Ltd.

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

PubMed

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

2012-01-01

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

Co-treatment with grapefruit juice inhibits while chronic administration activates intestinal P-glycoprotein-mediated drug efflux.

PubMed

Panchagnula, R; Bansal, T; Varma, M V S; Kaul, C L

2005-12-01

P-Glycoprotein (P-gp) mediated efflux is recognized as a significant biochemical barrier affecting oral absorption for a number of drugs. Various conflicting reports have been published regarding the effects of grapefruit juice (GFJ) on P-gp-mediated drug efflux, in which GFJ has been shown both to inhibit and activate it. Hence, the present study adopted a two-way approach, involving both co-treatment and chronic administration. Bi-directional transport of paclitaxel (PCL) was carried out in the absence and presence of GFJ extract, in rat everted ileum sac. Further, the effect of chronic administration of GFJ to rats was characterized by permeability studies with indinavir (INDI). Co-treatment of GFJ extract at 100% concentration reduced the asymmetric transport of PCL (efflux ratio = 20.8) by increasing absorptive (A --> B) transport by 921% and reducing secretory (B --> A) transport by 41%. Further, GFJ showed a concentration dependent effect on PCL permeability. Imipramine, a passive permeability marker with absorptive permeability of 15.33 +/- 4.26 x 10(-6) cm/s showed no asymmetric transport and also no significant (P < 0.05) change in permeability in the presence of GFJ. Chronic administration of GFJ resulted in a significant decrease in absorptive transport of indinavir, which was even greater than that produced by rifampicin pretreatment. No change in permeability of propranolol, a passive permeability marker, was observed. Further, the decrease in absorptive transport of INDI was reversed by the P-gp inhibitor verapamil. In conclusion, GFJ extract inhibited P-gp-mediated efflux in co-treatment, whereas chronic administration led to increased levels of P-gp expression, thus having a profound effect on intestinal absorption and GFJ-drug interactions in vivo.

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

PubMed

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

1995-09-01

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

The effects of perphenazine on self-administration behavior.

PubMed

Johanson, C E; Kandel, D A; Bonese, K

1976-04-01

In Experiment 1.6 rhesus monkeys prepared with intravenous catheters responded on a fixed-ratio 10 schedule for either an injection of 0.2 mg/kg of cocaine or 0.5 mg/kg of pentobarbital during a daily 3 hr session. The substitution of saline or various doses of perphenazine resulted in very low rates of responding. These results indicate that perphenazine is not a positive reinforcer. Pretreating animals maintained on 0.1 mg/kg or 0.2 mg/kg of cocaine with perphenazine resulted in increases in rate of self-administration at some doses and a decrease in rate at higher doses. The dose of perphenazine which resulted in the maximal increase in cocaine self-administration was directly related to the dose of cocaine maintaining responding. Pretreating animals maintained on 0.5 mg/kg of pentobarbital with perphenazine had no effect at doses which increased cocaine self-administration but decreased rate of pentobarbital self-administration at higher doses. These results indicate that perphenazine is capable of antagonizing some of the effects of cocaine.

Oral administration of red ginseng powder fermented with probiotic alleviates the severity of dextran-sulfate sodium-induced colitis in a mouse model.

PubMed

Jang, Sun-Hee; Park, Jisang; Kim, Sae-Hae; Choi, Kyung-Min; Ko, Eun-Sil; Cha, Jeong-Dan; Lee, Young-Ran; Jang, Hyonseok; Jang, Yong-Suk

2017-03-01

Red ginseng is a well-known alternative medicine with anti-inflammatory activity. It exerts pharmacological effects through the transformation of saponin into metabolites by intestinal microbiota. Given that intestinal microflora vary among individuals, the pharmacological effects of red ginseng likely vary among individuals. In order to produce homogeneously effective red ginseng, we prepared probiotic-fermented red ginseng and evaluated its activity using a dextran sulfate sodium (DSS)-induced colitis model in mice. Initial analysis of intestinal damage indicated that the administration of probiotic-fermented red ginseng significantly decreased the severity of colitis, compared with the control and the activity was higher than that induced by oral administration of ginseng powder or probiotics only. Subsequent analysis of the levels of serum IL-6 and TNF-α, inflammatory biomarkers that are increased at the initiation stage of colitis, were significantly decreased in probiotic-fermented red ginseng-treated groups in comparison to the control group. The levels of inflammatory cytokines and mRNAs for inflammatory factors in colorectal tissues were also significantly decreased in probiotic-fermented red ginseng-treated groups. Collectively, oral administration of probiotic-fermented red ginseng reduced the severity of colitis in a mouse model, suggesting that it can be used as a uniformly effective red ginseng product. Copyright © 2017 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

Effect of acute and chronic MK-801 administration on extracellular glutamate and ascorbic acid release in the prefrontal cortex of freely moving mice on line with open-field behavior.

PubMed

Zuo, Dai-Ying; Zhang, Ya-Hong; Cao, Yue; Wu, Chun-Fu; Tanaka, Masatoshi; Wu, Ying-Liang

2006-04-04

The present study was designed to investigate the effects of acute and chronic administration of MK-801 (0.6 mg/kg), a noncompetitive NMDA-receptor antagonist on extracellular glutamate (Glu) and ascorbic acid (AA) release in the prefrontal cortex (PFC) of freely moving mice using in vivo microdialysis with open-field behavior. In line with earlier studies, acute administration of MK-801 induced an increase of Glu in the PFC. We also observed single MK-801 treatment increased AA release in the PFC. In addition, our results indicated that the basal AA levels in the PFC after MK-801 administration for 7 consecutive days were significantly decreased, and basal Glu levels also had a decreased tendency. After chronic administration (0.6 mg/kg, 7 days), MK-801 (0.6 mg/kg) challenge significantly decreased dialysate levels of AA and Glu. Our study also found that both acute and chronic administration of MK-801 induced hyperactivity in mice, but the intensity of acute administration was more than that of chronic administration. Furthermore, in all acute treatment mice, individual changes in Glu dialysate concentrations and the numbers of locomotion were positively correlated. In conclusion, this study may provide new evidence that a single MK-801 administration induces increases of dialysate AA and Glu concentrations in the PFC of freely moving mice, which are opposite to those induced by repeated MK-801 administration, with an unknown mechanism. Our results suggested that redox-response might play an important role in the model of schizophrenic symptoms induced by MK-801.

Serotonin antagonists fail to alter MDMA self-administration in rats.

PubMed

Schenk, Susan; Foote, Jason; Aronsen, Dane; Bukholt, Natasha; Highgate, Quenten; Van de Wetering, Ross; Webster, Jeremy

2016-09-01

Acute exposure to ±3,4-methylenedioxymethamphetamine (MDMA) preferentially increases release of serotonin (5-HT), and a role of 5-HT in many of the behavioral effects of acute exposure to MDMA has been demonstrated. A role of 5-HT in MDMA self-administration in rats has not, however, been adequately determined. Therefore, the present study measured the effect of pharmacological manipulation of some 5-HT receptor subtypes on self-administration of MDMA. Rats received extensive experience with self-administered MDMA prior to tests with 5-HT ligands. Doses of the 5-HT1A antagonist, WAY 100635 (0.1-1.0mg/kg), 5-HT1B antagonist, GR 127935 (1.0-3.0mg/kg), and the 5-HT2A antagonist, ketanserin (1.0-3.0mg/kg) that have previously been shown to decrease self-administration of other psychostimulants and that decreased MDMA-produced hyperactivity in the present study did not alter MDMA self-administration. Experimenter-administered injections of MDMA (10.0mg/kg, ip) reinstated extinguished drug-taking behavior, but this also was not decreased by any of the antagonists. In contrast, both WAY 100635 and ketanserin, but not GR 127935, decreased cocaine-produced drug seeking in rats that had been trained to self-administered cocaine. The 5-HT1A agonist, 8-OH-DPAT (0.1-1.0mg/kg), but not the 5-HT1B/1A agonist, RU 24969 (0.3-3.0mg/kg), decreased drug-seeking produced by the reintroduction of a light stimulus that had been paired with self-administered MDMA infusions. These findings suggest a limited role of activation of 5-HT1A, 5-HT1B or 5-HT2 receptor mechanisms in MDMA self-administration or in MDMA-produced drug-seeking following extinction. The data suggest, however, that 5-HT1A agonists inhibit cue-induced drug-seeking following extinction of MDMA self-administration and might, therefore, be useful adjuncts to therapies to limit relapse to MDMA use. Copyright © 2016 Elsevier Inc. All rights reserved.

Oral and intraperitoneal administration of quercetin decreased lymphocyte DNA damage and plasma lipid peroxidation induced by TSA in vivo.

PubMed

Chan, Shu-Ting; Lin, Yi-Chin; Chuang, Cheng-Hung; Shiau, Rong-Jen; Liao, Jiunn-Wang; Yeh, Shu-Lan

2014-01-01

Our previous study showed that quercetin enhances the anticancer effect of trichostatin A (TSA) in xenograft mice given quercetin intraperitoneally (10 mg/kg, 3 times/week). Herein, we investigate whether quercetin administered orally exerts such an effect and prevents the cytotoxic side effects of TSA. We found that quercetin given orally (20 and 100 mg/kg, 3 times/week) failed to enhance the antitumor effect of TSA although it increased the total quercetin concentration more than quercetin administered intraperitoneally in the plasma. The compound quercetin-3-glucuronide (Q3G) increased the most. However, quercetin administered intraperitoneally increased the total quercetin level in tumor tissues more than oral quercetin. Oral and intraperitoneal administration of quercetin similarly decreased lymphocyte DNA damage and plasma lipid peroxidation level induced by TSA. Furthermore, we found that the enhancing effect of Q3G on the antitumor effect of TSA and the incorporation of Q3G was less than that of quercetin in A549 cells. However, we found that A549 cells possessed the ability to convert Q3G to quercetin. In conclusion, different from quercetin administered intraperitoneally, quercetin administered orally failed to enhance the antitumor effect of TSA because of its metabolic conversion. However, it prevented TSA-induced DNA damage and lipid peroxidation.

Bifidobacterium animalis subsp. lactis decreases urinary oxalate excretion in a mouse model of primary hyperoxaluria

PubMed Central

Whittamore, Jonathan M.; Hatch, Marguerite

2015-01-01

Hyperoxaluria significantly increases the risk of calcium oxalate kidney stone formation. Since several bacteria have been shown to metabolize oxalate in vitro, including probiotic bifidobacteria, we focused on the efficiency and possible mechanisms by which bifidobacteria can infuence oxalate handling in vivo, especially in the intestines, and compared these results with the reported effects of Oxalobacter formigenes. Bifidobacterium animalis subsp. lactis DSM 10140 and B. adolescentis ATCC 15703 were administered to wild-type (WT) mice and to mice defcient in the hepatic enzyme alanine-glyoxylate aminotransferase (Agxt−/−, a mouse model of Primary Hyperoxaluria) that were fed an oxalate-supplemented diet. The administration of B. animalis subsp. lactis led to a significant decrease in urinary oxalate excretion in WT and Agxt−/− mice when compared to treatment with B. adolescent-is. Detection of B. animalis subsp. lactis in feces revealed that 3 weeks after oral gavage with the bacteria 64 % of WT mice, but only 37 % of Agxt−/− mice were colonized. Examining intestinal oxalate fuxes showed there were no significant changes to net oxalate secretion in colonized animals and were therefore not associated with the changes in urinary oxalate excretion. These results indicate that colonization with B. animalis subsp. lactis decreased urinary oxalate excretion by degrading dietary oxalate thus limiting its absorption across the intestine but it did not promote enteric oxalate excretion as reported for O. formigenes. Preventive or therapeutic administration of B. animalis subsp. lactis appears to have some potential to beneficially infuence dietary hyperoxaluria in mice. PMID:25269440

Aerobic exercise decreases the positive-reinforcing effects of cocaine.

PubMed

Smith, Mark A; Schmidt, Karl T; Iordanou, Jordan C; Mustroph, Martina L

2008-11-01

Aerobic exercise can serve as an alternative, non-drug reinforcer in laboratory animals and has been recommended as a potential intervention for substance abusing populations. Unfortunately, relatively little empirical data have been collected that specifically address the possible protective effects of voluntary, long-term exercise on measures of drug self-administration. The purpose of the present study was to examine the effects of chronic exercise on sensitivity to the positive-reinforcing effects of cocaine in the drug self-administration procedure. Female rats were obtained at weaning and immediately divided into two groups. Sedentary rats were housed individually in standard laboratory cages that permitted no exercise beyond normal cage ambulation; exercising rats were housed individually in modified cages equipped with a running wheel. After 6 weeks under these conditions, rats were surgically implanted with venous catheters and trained to self-administer cocaine on a fixed-ratio schedule of reinforcement. Once self-administration was acquired, cocaine was made available on a progressive ratio schedule and breakpoints were obtained for various doses of cocaine. Sedentary and exercising rats did not differ in the time to acquire cocaine self-administration or responding on the fixed-ratio schedule of reinforcement. However, on the progressive ratio schedule, breakpoints were significantly lower in exercising rats than sedentary rats when responding was maintained by both low (0.3mg/kg/infusion) and high (1.0mg/kg/infusion) doses of cocaine. In exercising rats, greater exercise output prior to catheter implantation was associated with lower breakpoints at the high dose of cocaine. These data indicate that chronic exercise decreases the positive-reinforcing effects of cocaine and support the possibility that exercise may be an effective intervention in drug abuse prevention and treatment programs.

Is catalase involved in the effects of systemic and pVTA administration of 4-methylpyrazole on ethanol self-administration?

PubMed

Peana, Alessandra T; Pintus, Francesca A; Bennardini, Federico; Rocchitta, Gaia; Bazzu, Gianfranco; Serra, Pier Andrea; Porru, Simona; Rosas, Michela; Acquas, Elio

2017-09-01

The oxidative metabolism of ethanol into acetaldehyde involves several enzymes, including alcohol dehydrogenase (ADH) and catalase-hydrogen peroxide (H 2 O 2 ). In this regard, while it is well known that 4-methylpyrazole (4-MP) acts by inhibiting ADH in the liver, little attention has been placed on its ability to interfere with fatty acid oxidation-mediated generation of H 2 O 2 , a mechanism that may indirectly affect catalase whose enzymatic activity requires H 2 O 2 . The aim of our investigation was twofold: 1) to evaluate the effect of systemic (i.p. [intraperitoneal]) and local (into the posterior ventral tegmental area, pVTA) administration of 4-MP on oral ethanol self-administration, and 2) to assess ex vivo whether or not systemic 4-MP affects liver and brain H 2 O 2 availability. The results show that systemic 4-MP reduced ethanol but not acetaldehyde or saccharin self-administration, and decreased the ethanol deprivation effect. Moreover, local intra-pVTA administration of 4-MP reduced ethanol but not saccharin self-administration. In addition, although unable to affect basal catalase activity, systemic administration of 4-MP decreased H 2 O 2 availability both in liver and in brain. Overall, these results indicate that 4-MP interferes with ethanol self-administration and suggest that its behavioral effects could be due to a decline in catalase-H 2 O 2 system activity as a result of a reduction of H 2 O 2 availability, thus highlighting the role of central catalase-mediated metabolism of ethanol and further supporting the key role of acetaldehyde in the reinforcing properties of ethanol. Copyright © 2017 Elsevier Inc. All rights reserved.

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...

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

PubMed Central

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

2015-01-01

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

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

Supraspinally-administered agmatine attenuates the development of oral fentanyl self-administration

PubMed Central

Wade, Carrie L.; Schuster, Daniel J.; Domingo, Kristine M.; Kitto, Kelley F.; Fairbanks, Carolyn A.

2009-01-01

The decarboxylation product of arginine, agmatine, has effectively reduced or prevented opioid-induced tolerance and dependence when given either systemically (intraperitoneally or subcutaneously) or centrally (intrathecally or intracerebroventricularly). Systemically administered agmatine also reduces the escalation phase of intravenous fentanyl self-administration in rats. The present study assessed whether centrally (intracerebroventricular, i.c.v.) delivered agmatine could prevent the development of fentanyl self-administration in mice. Mice were trained to respond under a fixed-ratio 1 (FR1) schedule for either fentanyl (0.7 μg/70 μl, p.o.) or food reinforcement. Agmatine (10 nmol/5 μl), injected i.c.v. 12-14h before the first session and every other evening (12-14h before session) for 2 weeks, completely attenuated oral fentanyl self-administration (but not food-maintained responding) compared to saline-injected controls. When agmatine was administered after fentanyl self-administration had been established (day 8) it had no attenuating effects on bar pressing. This dose of agmatine does not decrease locomotor activity as assessed by rotarod. The present findings significantly extend the previous observation that agmatine prevents opioid-maintained behavior to a chronic model of oral fentanyl self-administration as well as identifying a supraspinal site of action for agmatine inhibition of drug addiction. PMID:18495108

Interventions Delivered in Clinical Settings are Effective in Reducing Risk of HIV Transmission Among People Living with HIV: Results from the Health Resources and Services Administration (HRSA)’s Special Projects of National Significance Initiative

PubMed Central

Shade, Starley B.; Rose, Carol Dawson; Koester, Kimberly; Maiorana, Andre; Malitz, Faye E.; Bie, Jennifer; Kang-Dufour, Mi-Suk; Morin, Stephen F.

2010-01-01

To support expanded prevention services for people living with HIV, the US Health Resources and Services Administration (HRSA) sponsored a 5-year initiative to test whether interventions delivered in clinical settings were effective in reducing HIV transmission risk among HIV-infected patients. Across 13 demonstration sites, patients were randomized to one of four conditions. All interventions were associated with reduced unprotected vaginal and/or anal intercourse with persons of HIV-uninfected or unknown status among the 3,556 participating patients. Compared to the standard of care, patients assigned to receive interventions from medical care providers reported a significant decrease in risk after 12 months of participation. Patients receiving prevention services from health educators, social workers or paraprofessional HIV-infected peers reported significant reduction in risk at 6 months, but not at 12 months. While clinics have a choice of effective models for implementing prevention programs for their HIV-infected patients, medical provider-delivered methods are comparatively robust. PMID:20229132

Effect of ganaxolone and THIP on operant and limited-access ethanol self-administration

PubMed Central

Ramaker, Marcia J.; Strong, Moriah N.; Ford, Matthew M.; Finn, Deborah A.

2013-01-01

Recent evidence suggests that GABAA receptor ligands may regulate ethanol intake via effects at both synaptic and extrasynaptic receptors. For example, the endogenous neurosteroid, allopregnanolone (ALLO) has a similar pharmacological profile as ethanol, and it alters ethanol intake in rodent models. Additionally, recent evidence suggests that δ-subunit containing extrasynaptic GABAA receptors may confer high sensitivity to both ethanol and neurosteroids. The purpose of the present study was to determine the effects of ganaxolone (GAN; an ALLO analogue) and gaboxadol (THIP; a GABAA receptor agonist with selectivity for the extrasynaptic δ-subunit) on ethanol intake, drinking patterns, and bout characteristics in operant and limited access self-administration procedures. In separate studies, the effects of GAN (0 – 10 mg/kg) and THIP (2 – 16 mg/kg) were tested in C57BL/6J male mice provided with two-hour access to a two-bottle choice of water or 10% ethanol or trained to respond for 30 minutes of access to 10% ethanol. GAN had no overall significant effect on operant ethanol self-administration, but tended to decrease the latency to consume the first bout. In the limited-access procedure, GAN dose-dependently decreased ethanol intake. THIP dose-dependently decreased ethanol intake in both paradigms, altering both the consummatory and appetitive processes of operant self-administration as well as shifting the drinking patterns in both procedures. These results add to literature suggesting time-dependent effects of neurosteroids to promote the onset, and to subsequently decrease, ethanol drinking behavior, and they support a role for extrasynaptic GABAA receptor activation in ethanol reinforcement. PMID:22613838

Acute effects of oral melatonin administration on arterial distensibility, as determined by carotid-femoral pulse wave velocity, in healthy young men

PubMed Central

Yildiz, Mustafa; Sahin, Banu; Sahin, Alparslan

2006-01-01

The aim of the present study was to investigate the effects of melatonin administration on arterial distensibility by using carotid-femoral (aortic) pulse wave velocity (PWV) measurements in healthy young men. Ten men were studied (five men in the melatonin group and five men in the placebo group) by physicians. Carotid-femoral (aortic) PWV, blood pressure and plasma melatonin were measured in the supine position before and 60 min after oral administration of melatonin or placebo. Although carotid-femoral (aortic) PWV, systolic blood pressure and mean blood pressure were decreased, pulse wave propagation time and plasma melatonin levels were increased at 60 min after oral melatonin (1 mg) administration (P=0.04, P=0.04, P=0.04, P=0.04 and P=0.04, respectively). No significant differences were found between all parameters in the placebo group (P>0.05). In conclusion, these findings indicate that melatonin administration, compared with placebo, decreased carotid-femoral PWV and systolic blood pressure in the supine position in healthy young men. Administration of melatonin may have an inhibitory effect on sympathetic tone. PMID:18651024

Comparison of pediatric cardiac surgical mortality rates from national administrative data to contemporary clinical standards.

PubMed

Welke, Karl F; Diggs, Brian S; Karamlou, Tara; Ungerleider, Ross M

2009-01-01

Despite the superior coding and risk adjustment of clinical data, the ready availability, national scope, and perceived unbiased nature of administrative data make it the choice of governmental agencies and insurance companies for evaluating quality and outcomes. We calculated pediatric cardiac surgery mortality rates from administrative data and compared them with widely quoted standards from clinical databases. Pediatric cardiac surgical operations were retrospectively identified by ICD-9-CM diagnosis and procedure codes from the Nationwide Inpatient Sample (NIS) 1988-2005 and the Kids' Inpatient Database (KID) 2003. Cases were grouped into Risk Adjustment for Congenital Heart Surgery, version 1 (RACHS-1) categories. In-hospital mortality rates and 95% confidence intervals were calculated. A total of 55,164 operations from the NIS and 10,945 operations from the KID were placed into RACHS-1 categories. During the 18-year period, the overall NIS mortality rate for pediatric cardiac surgery decreased from 8.7% (95% confidence interval, 8.0% to 9.3%) to 4.6% (95% confidence interval, 4.3% to 5.0%). Mortality rates by RACHS-1 category decreased significantly as well. The KID and NIS mortality rates from comparable years were similar. Overall mortality rates derived from administrative data were higher than those from contemporary national clinical data, The Society of Thoracic Surgeons Congenital Heart Surgery Database, or published data from pediatric cardiac specialty centers. Although category-specific mortality rates were higher in administrative data than in clinical data, a minority of the relationships reached statistical significance. Despite substantial improvement, mortality rates from administrative data remain higher than those from clinical data. The discrepancy may be attributable to several factors: differences in database design and composition, differences in data collection and reporting structures, and variation in data quality.

Systemic L-Kynurenine sulfate administration disrupts object recognition memory, alters open field behavior and decreases c-Fos immunopositivity in C57Bl/6 mice.

PubMed

Varga, Dániel; Herédi, Judit; Kánvási, Zita; Ruszka, Marian; Kis, Zsolt; Ono, Etsuro; Iwamori, Naoki; Iwamori, Tokuko; Takakuwa, Hiroki; Vécsei, László; Toldi, József; Gellért, Levente

2015-01-01

L-Kynurenine (L-KYN) is a central metabolite of tryptophan degradation through the kynurenine pathway (KP). The systemic administration of L-KYN sulfate (L-KYNs) leads to a rapid elevation of the neuroactive KP metabolite kynurenic acid (KYNA). An elevated level of KYNA may have multiple effects on the synaptic transmission, resulting in complex behavioral changes, such as hypoactivity or spatial working memory deficits. These results emerged from studies that focused on rats, after low-dose L-KYNs treatment. However, in several studies neuroprotection was achieved through the administration of high-dose L-KYNs. In the present study, our aim was to investigate whether the systemic administration of a high dose of L-KYNs (300 mg/bwkg; i.p.) would produce alterations in behavioral tasks (open field or object recognition) in C57Bl/6j mice. To evaluate the changes in neuronal activity after L-KYNs treatment, in a separate group of animals we estimated c-Fos expression levels in the corresponding subcortical brain areas. The L-KYNs treatment did not affect the general ambulatory activity of C57Bl/6j mice, whereas it altered their moving patterns, elevating the movement velocity and resting time. Additionally, it seemed to increase anxiety-like behavior, as peripheral zone preference of the open field arena emerged and the rearing activity was attenuated. The treatment also completely abolished the formation of object recognition memory and resulted in decreases in the number of c-Fos-immunopositive-cells in the dorsal part of the striatum and in the CA1 pyramidal cell layer of the hippocampus. We conclude that a single exposure to L-KYNs leads to behavioral disturbances, which might be related to the altered basal c-Fos protein expression in C57Bl/6j mice.

Medicaid Coverage for Tobacco Dependence Treatments in Massachusetts and Associated Decreases in Smoking Prevalence

PubMed Central

Land, Thomas; Warner, Donna; Paskowsky, Mark; Cammaerts, Ayesha; Wetherell, LeAnn; Kaufmann, Rachel; Zhang, Lei; Malarcher, Ann; Pechacek, Terry; Keithly, Lois

2010-01-01

Background Approximately 50% of smokers die prematurely from tobacco-related diseases. In July 2006, the Massachusetts health care reform law mandated tobacco cessation coverage for the Massachusetts Medicaid population. The new benefit included behavioral counseling and all medications approved for tobacco cessation treatment by the U.S. Food and Drug Administration (FDA). Between July 1, 2006 and December 31, 2008, a total of 70,140 unique Massachusetts Medicaid subscribers used the newly available benefit, which is approximately 37% of all Massachusetts Medicaid smokers. Given the high utilization rate, the objective of this study is to determine if smoking prevalence decreased significantly after the initiation of tobacco cessation coverage. Methods and Findings Smoking prevalence was evaluated pre- to post-benefit using 1999 through 2008 data from the Massachusetts Behavioral Risk Factor Survey (BRFSS). The crude smoking rate decreased from 38.3% (95% C.I. 33.6%–42.9%) in the pre-benefit period compared to 28.3% (95% C.I.: 24.0%–32.7%) in the post-benefit period, representing a decline of 26 percent. A demographically adjusted smoking rate showed a similar decrease in the post-benefit period. Trend analyses reflected prevalence decreases that accrued over time. Specifically, a joinpoint analysis of smoking prevalence among Massachusetts Medicaid benefit-eligible members (age 18–64) from 1999 through 2008 found a decreasing trend that was coincident with the implementation of the benefit. Finally, a logistic regression that controlled for demographic factors also showed that the trend in smoking decreased significantly from July 1, 2006 to December 31, 2008. Conclusion These findings suggest that a tobacco cessation benefit that includes coverage for medications and behavioral treatments, has few barriers to access, and involves broad promotion can significantly reduce smoking prevalence. PMID:20305787

Dexmedetomidine reduces pain associated with rocuronium injection without causing a decrease in BIS values: a dose-response study.

PubMed

Joo, Jin; Baek, Jungwon; Lee, Jaemin

2014-09-01

To examine whether dexmedetomidine reduces the injection pain of propofol and rocuronium and to investigate whether the decrease in injection pain is associated with the known sedative action of dexmedetomidine. Randomized, double-blind, placebo-controlled clinical comparison study. Patients undergoing general anesthesia with intubation received 40 mg of 1% lidocaine (lidocaine group; n = 28), 0.25 μg/kg of dexmedetomidine (low-dose group; n = 27), 0.5 μg/kg of dexmedetomidine (subclinical dose group; n = 28), 1.0 μg/kg of dexmedetomidine (clinical dose group, n = 27), or normal saline (saline group; n = 28) before anesthetic induction. Pain associated with propofol and rocuronium injection was assessed using a 10-point verbal analog scale (VAS) and a 4-point withdrawal movement scale, respectively. The BIS value was measured 60 seconds after administration of the study drug, and at the time of rocuronium injection and intubation. The overall incidence of withdrawal movements due to rocuronium decreased significantly as the dose of dexmedetomidine increased (92.8%, 85.2%, 78.6%, and 51.9% in the saline, low-dose, subclinical dose, and clinical dose groups, respectively; P = 0.001). There was no significant difference in BIS values among the groups 60 seconds after study drug administration or at the time of rocuronium injection. Dexmedetomidine reduced pain associated with rocuronium injection in a dose-dependent manner. This effect was not associated with the decrease in BIS value. Copyright © 2014 Elsevier Inc. All rights reserved.

Oral Zinc Supplementation Decreases the Serum Iron Concentration in Healthy Schoolchildren: A Pilot Study

PubMed Central

de Brito, Naira Josele Neves; de Medeiros Rocha, Érika Dantas; de Araújo Silva, Alfredo; Costa, João Batista Sousa; França, Mardone Cavalcante; das Graças Almeida, Maria; Brandão-Neto, José

2014-01-01

The recognized antagonistic actions between zinc and iron prompted us to study this subject in children. A convenience sample was used. Thirty healthy children between 8 and 9 years of age were studied with the aim of establishing the effect of a 3-mo oral zinc supplementation on iron status. Fifteen individuals were given a placebo (control group), and 15 were given 10 mg Zn/day (experimental group). Blood samples were collected at 0, 60, 120, 180 and 210 min after a 12-h overnight fast, before and after placebo or zinc supplementation. This supplementation was associated with significant improvements in energy, protein, fat, carbohydrate, fiber, calcium, iron, and zinc intake in accordance with the recommendations for age and sex. The basal serum zinc concentration significantly increased after oral zinc supplementation (p < 0.001). However, basal serum iron concentrations and area under the iron curves significantly decreased in the experimental group (p < 0.0001) and remained at the same level throughout the 210-min study. The values obtained for hemoglobin, mean corpuscular volume, ferritin, transferrin, transferrin saturation, ceruloplasmin and total protein were within normal reference ranges. In conclusion, the decrease in serum iron was likely due to the effects of chronic zinc administration, and the decrease in serum iron was not sufficient to cause anemia. PMID:25192026

Accelerated skeletal muscle recovery after in vivo polyphenol administration.

PubMed

Myburgh, Kathryn H; Kruger, Maria J; Smith, Carine

2012-09-01

Acute skeletal muscle damage results in fiber disruption, oxidative stress and inflammation. We investigated cell-specific contributions to the regeneration process after contusion-induced damage (rat gastrocnemius muscle) with or without chronic grape seed-derived proanthocyanidolic oligomer (PCO) administration. In this placebo-controlled study, male Wistar rats were subjected to PCO administration for 2 weeks, after which they were subjected to a standardised contusion injury. Supplementation was continued after injury. Immune and satellite cell responses were assessed, as well as oxygen radical absorption capacity and muscle regeneration. PCO administration resulted in a rapid satellite cell response with an earlier peak in activation (Pax7⁺, CD56⁺, at 4 h post-contusion) vs. placebo groups (PLA) (P<.001: CD56⁺ on Day 5 and Pax7⁺ on Day 7). Specific immune-cell responses in PLA followed expected time courses (neutrophil elevation on Day 1; sustained macrophage elevation from Days 3 to 5). PCO dramatically decreased neutrophil elevation to nonsignificant, while macrophage responses were normal in extent, but significantly earlier (peak between Days 1 and 3) and completely resolved by Day 5. Anti-inflammatory cytokine, IL-10, increased significantly only in PCO (Day 3). Muscle fiber regeneration (MHC(f) content and central nuclei) started earlier and was complete by Day 14 in PCO, but not in PLA. Thus, responses by three crucial cell types involved in muscle recovery were affected by in vivo administration of a specific purified polyphenol in magnitude (neutrophil), time course (macrophages), or time course and activation state (satellite cell), explaining faster effective regeneration in the presence of proanthocyanidolic oligomers. Copyright © 2012 Elsevier Inc. All rights reserved.

Low doses of alcohol substantially decrease glucose metabolism in the human brain.

PubMed

Volkow, Nora D; Wang, Gene-Jack; Franceschi, Dinko; Fowler, Joanna S; Thanos, Panayotis Peter K; Maynard, Laurence; Gatley, S John; Wong, Christopher; Veech, Richard L; Kunos, George; Kai Li, Ting

2006-01-01

Moderate doses of alcohol decrease glucose metabolism in the human brain, which has been interpreted to reflect alcohol-induced decreases in brain activity. Here, we measure the effects of two relatively low doses of alcohol (0.25 g/kg and 0.5 g/kg, or 5 to 10 mM in total body H2O) on glucose metabolism in the human brain. Twenty healthy control subjects were tested using positron emission tomography (PET) and FDG after placebo and after acute oral administration of either 0.25 g/kg, or 0.5 g/kg of alcohol, administered over 40 min. Both doses of alcohol significantly decreased whole-brain glucose metabolism (10% and 23% respectively). The responses differed between doses; whereas the 0.25 g/kg dose predominantly reduced metabolism in cortical regions, the 0.5 g/kg dose reduced metabolism in cortical as well as subcortical regions (i.e. cerebellum, mesencephalon, basal ganglia and thalamus). These doses of alcohol did not significantly change the scores in cognitive performance, which contrasts with our previous results showing that a 13% reduction in brain metabolism by lorazepam was associated with significant impairment in performance on the same battery of cognitive tests. This seemingly paradoxical finding raises the possibility that the large brain metabolic decrements during alcohol intoxication could reflect a shift in the substrate for energy utilization, particularly in light of new evidence that blood-borne acetate, which is markedly increased during intoxication, is a substrate for energy production by the brain.

Comparison of drug administration logistics between prothrombin complex concentrates and plasma in the emergency department.

PubMed

Alarfaj, Sumaiah J; Jarrell, Daniel H; Patanwala, Asad E

2018-03-24

Prothrombin complex concentrate (PCC) is used as an alternative to fresh frozen plasma (FFP) for emergency bleeding. The primary objective of this study was to compare the time from order to start of administration between 3-factor PCC (PCC3), 4-factor (PCC4), and FFP in the emergency department (ED). The secondary objective was to evaluate the effect of an ED pharmacist on time to administration of PCCs. This was a single center three-arm retrospective cohort study. Adult patients in the ED with bleeding were included. The primary outcome measure was the time from order to administration, which was compared between PCC3, PCC4, and FFP. The time from order to administration was also compared when the ED pharmacist was involved versus not involved in the care of patients receiving PCC. There were 90 patients included in the study cohort (30 in each group). The median age was 69years (IQR 57-82years), and 57% (n=52) were male. The median time from order to administration was 36min (IQR 20-58min) for PCC3, 34min (IQR 18-48min) for PCC4, and 92min (IQR 63-133) for FFP (PCC3 versus PCC4, p=0.429; PCC3 versus FFP, p<0.001; PCC4 versus FFP, p<0.001). The median time from order to administration was significantly decreased when the ED pharmacist was involved (24min [IQR 15-35min] versus 42min [IQR 32-59min], p<0.001). Time from order to administration is faster with PCC than FFP. ED pharmacist involvement decreases the time from order to administration of PCC. Copyright © 2018. Published by Elsevier Inc.

Mice heterozygous for the Mdr2 gene demonstrate decreased PEMT activity and diminished steatohepatitis on the MCD diet.

PubMed

Igolnikov, Alexander C; Green, Richard M

2006-03-01

The administration of a methionine and choline deficient (MCD) diet to mice serves as an animal model of NASH. The multidrug resistant 2 (Mdr2) P-glycoprotein encodes for the canalicular phospholipid transporter, and Mdr2 (+/-) mice secrete 40% less phosphatidylcholine than wild-type mice. We have hypothesized that phosphatidylethanolamine-N-methyl transferase (PEMT) up-regulation is a consequence of MCD diet administration, and is important for the pathogenesis of steatohepatitis in this model. However, the effect of decreased phosphatidylcholine secretion and modulation of PEMT on the development of diet-induced steatohepatitis in Mdr2 (+/-) mice has not been explored. Thus, the purpose of the study is to examine the effects of the MCD diet on Mdr2 (+/-) mice. Mdr2 (+/-) and Mdr2 (+/+) mice were treated with an MCD or control diet for up to 30 days, and the severity of steatohepatitis, PEMT activity and hepatic S-adenosylmethionine (SAM), and S-adenosylhomocysteine (SAH) levels were measured. Serum ALT levels, hepatic inflammation, and PEMT activity were significantly lower, and hepatic SAM:SAH ratios were significantly higher in Mdr2 (+/-) mice at 7 and 30 days on the MCD diet. Mdr2 (+/-) mice have diminished susceptibility to MCD diet-induced NASH, which is associated with a relative decrease in PEMT activity and increased SAM:SAH ratios.

Effects of Oral Prednisone Administration on Serum Cystatin C in Dogs.

PubMed

Muñoz, J; Soblechero, P; Duque, F J; Macías-García, B; Ruiz, P; Zaragoza, C; Barrera, R

2017-11-01

Oral administration of glucocorticoid alters serum cystatin C (sCysC) concentration in humans. To determine if oral administration of prednisone alters sCysC in dogs without pre-existing renal disease. Forty six dogs were included: 10 dogs diagnosed with steroid responsive meningitis arteritis (SRMA; group A), 20 dogs diagnosed of pituitary-dependent hyperadrenocorticism (PDH; group B), and 16 healthy control dogs (group C). Retrospective observational study. SRMA diagnosed dogs were administered prednisone 4 mg/kg/24 h PO 7 days, reducing the dose to 2 mg/kg/24 h 7 days before medication withdrawal. In group A, sampling was performed at days 0, 7, 14 and a final control at day 21. Blood and urine samples were collected in the 3 groups, and in group A, sampling was performed at all time points (days 1, 7, 14, and 21). In group A, sCysC was significantly higher at day 7 compared to the control group (0.4 ± 0.04 mg/L vs. 0.18 ± 0.03 mg/L mean ± SEM respectively P < 0.01); sCysC values decreased to basal at day 14 when the dose was decreased and after 1 week of withdrawal of prednisone (0.27 ± 0.03 mg/L for group A at day 14 and 0.15 ± 0.02 mg/L at day 21; P > 0.05). Dogs with PDH included in group B did not have significant differences in sCysC (0.22 ± 0.03 mg/L) compared to control (P > 0.05). Oral administration of prednisone unlike altered endogenous glucocorticoid production, increases sCysC in dogs in a dose-dependent fashion. Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Iopanoic acid-induced decrease of circulating T3 causes a significant increase in GH responsiveness to GH releasing hormone in thyrotoxic patients.

PubMed

Ramos-Dias, J C; Lengyel, A M

1999-10-01

Thyroid hormones participate in GH synthesis and secretion, and an impaired GH response to many pharmacological stimuli, including GH releasing hormone (GHRH), has been found in thyrotoxicosis. Although the mechanisms involved in this process have not been fully elucidated, there is evidence that thyroid hormones could act at both hypothalamic and pituitary levels. There are no data in the literature about the effect of an acute reduction of circulating T3 levels on GH secretion in hyperthyroidism. The GH responsiveness to GHRH was therefore evaluated in a group of hyperthyroid patients during short-term treatment with iopanoic acid. Iopanoic acid is a compound that induces a rapid decrease in serum T3 levels, mainly by inhibition of peripheral conversion of T4 to T3. To the authors' knowledge, there is no evidence of a direct effect of iopanoic acid on GH secretion. Hyperthyroid patients were submitted to a GHRH test (100 microg, i.v.) before (day 0), and on days 4, 7 and 15 after oral treatment with iopanoic acid (3 g every 3 days) and propylthiouracil (200 mg every 8 h). A group of normal control subjects was also submitted to a single GHRH test (100 microg, i.v.). Nine patients with thyrotoxicosis (eight women, one man), with a mean age of 34 years, were studied. All patients had high serum levels of total T3 and total T4, and suppressed TSH levels. None of them had taken any medication for at least 3 months before the study. The patients were compared with a group of nine control subjects (five women, four men) with a mean age of 31 years. GH and TSH were measured by immunofluorometric assays. Total T3, total T4 and IGF-I were determined by radioimmunoassay. Albumin levels were measured by a colorimetric method. Iopanoic acid induced a rapid and maintained decrease in serum T3 concentrations, with a significant reduction on days 4, 7 and 15 compared with pre-treatment values. In hyperthyroidism, peak GH levels (mean +/- SE mU/l) after GHRH were significantly

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.

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

PubMed

Oberoi, Jyoti; Panda, Anup; Garg, Iti

2016-01-01

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

Effect of nitroglycerin administration on cardio-ankle vascular index.

PubMed

Shimizu, Kazuhiro; Yamamoto, Tomoyuki; Takahashi, Mao; Sato, Shuji; Noike, Hirofumi; Shirai, Kohji

2016-01-01

The purpose of this study was to clarify the difference between effects of nitroglycerin (NTG) on the functional stiffness in patients with and without coronary artery disease (CAD) using a newly developed stiffness index, cardio-ankle vascular index (CAVI). The two subject groups in this study were normal controls (n=31) and CAD patients (n=25). The normal controls had no medical history and were not on regular medications. On the other hand, the CAD patients had received various treatments like antihypertensive drugs, hypoglycemic agents, and statins. This study was conducted in CAD patients under medications. After a single sublingual administration of NTG 0.3 mg, CAVI, blood pressure (BP), and heart rate (HR) were measured every 5 minutes for 20 minutes. Comparisons of each parameter before and after taking NTG were evaluated for statistical significance using analysis of variance and post hoc tests. Tukey-Kramer test was used for post hoc comparisons. In the normal controls, CAVI significantly decreased from baseline after 5, 10, and 15 minutes (from 6.5±0.9 to 5.2±0.9, 5.5±0.9, and 5.7±0.9, respectively). Systolic BP and HR were not significantly changed. Diastolic BP significantly decreased from baseline after 5 and 10 minutes (from 72±8 to 64±9 and 63±9 mmHg, respectively). On the other hand, CAVI, HR, and diastolic BP were not changed significantly in CAD patients. Systolic BP was significantly decreased from baseline after 5, 10, and 15 minutes (from 147±16 to 131±14, 129±12, and 129±13 mmHg, respectively). In the comparison of the two groups, ΔCAVI was not significantly different between the normal controls and CAD patients (-1.4±0.7 vs -1.4±0.9, -1.1±0.7 vs -1.4±1.0, -0.8±0.7 vs -1.2±1.0, and -0.5±0.7 vs -1.1±1.0 at 5, 10, 15, and 20 minutes, respectively). ΔHR was not significantly different between the two groups. ΔSystolic BP in the CAD patients was significantly higher than in the normal controls at 5, 10, 15, and 20 minutes

Effect of nitroglycerin administration on cardio-ankle vascular index

PubMed Central

Shimizu, Kazuhiro; Yamamoto, Tomoyuki; Takahashi, Mao; Sato, Shuji; Noike, Hirofumi; Shirai, Kohji

2016-01-01

Purpose The purpose of this study was to clarify the difference between effects of nitroglycerin (NTG) on the functional stiffness in patients with and without coronary artery disease (CAD) using a newly developed stiffness index, cardio-ankle vascular index (CAVI). Subjects and methods The two subject groups in this study were normal controls (n=31) and CAD patients (n=25). The normal controls had no medical history and were not on regular medications. On the other hand, the CAD patients had received various treatments like antihypertensive drugs, hypoglycemic agents, and statins. This study was conducted in CAD patients under medications. After a single sublingual administration of NTG 0.3 mg, CAVI, blood pressure (BP), and heart rate (HR) were measured every 5 minutes for 20 minutes. Comparisons of each parameter before and after taking NTG were evaluated for statistical significance using analysis of variance and post hoc tests. Tukey–Kramer test was used for post hoc comparisons. Results In the normal controls, CAVI significantly decreased from baseline after 5, 10, and 15 minutes (from 6.5±0.9 to 5.2±0.9, 5.5±0.9, and 5.7±0.9, respectively). Systolic BP and HR were not significantly changed. Diastolic BP significantly decreased from baseline after 5 and 10 minutes (from 72±8 to 64±9 and 63±9 mmHg, respectively). On the other hand, CAVI, HR, and diastolic BP were not changed significantly in CAD patients. Systolic BP was significantly decreased from baseline after 5, 10, and 15 minutes (from 147±16 to 131±14, 129±12, and 129±13 mmHg, respectively). In the comparison of the two groups, ΔCAVI was not significantly different between the normal controls and CAD patients (−1.4±0.7 vs −1.4±0.9, −1.1±0.7 vs −1.4±1.0, −0.8±0.7 vs −1.2±1.0, and −0.5±0.7 vs −1.1±1.0 at 5, 10, 15, and 20 minutes, respectively). ΔHR was not significantly different between the two groups. ΔSystolic BP in the CAD patients was significantly higher than

Oral and Intraperitoneal Administration of Quercetin Decreased Lymphocyte DNA Damage and Plasma Lipid Peroxidation Induced by TSA In Vivo

PubMed Central

Chan, Shu-Ting; Shiau, Rong-Jen; Liao, Jiunn-Wang; Yeh, Shu-Lan

2014-01-01

Our previous study showed that quercetin enhances the anticancer effect of trichostatin A (TSA) in xenograft mice given quercetin intraperitoneally (10 mg/kg, 3 times/week). Herein, we investigate whether quercetin administered orally exerts such an effect and prevents the cytotoxic side effects of TSA. We found that quercetin given orally (20 and 100 mg/kg, 3 times/week) failed to enhance the antitumor effect of TSA although it increased the total quercetin concentration more than quercetin administered intraperitoneally in the plasma. The compound quercetin-3-glucuronide (Q3G) increased the most. However, quercetin administered intraperitoneally increased the total quercetin level in tumor tissues more than oral quercetin. Oral and intraperitoneal administration of quercetin similarly decreased lymphocyte DNA damage and plasma lipid peroxidation level induced by TSA. Furthermore, we found that the enhancing effect of Q3G on the antitumor effect of TSA and the incorporation of Q3G was less than that of quercetin in A549 cells. However, we found that A549 cells possessed the ability to convert Q3G to quercetin. In conclusion, different from quercetin administered intraperitoneally, quercetin administered orally failed to enhance the antitumor effect of TSA because of its metabolic conversion. However, it prevented TSA-induced DNA damage and lipid peroxidation. PMID:24868531

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

NFKB activity decreased in BALB/c mice with high fat diet and fructose

NASA Astrophysics Data System (ADS)

Nur'aini, Farida Dewi; Rahayu, Sri; Rifa'i, Muhaimin

2017-05-01

Excessive consumption of fat and fructose leads to obesity due to lipid accumulation. The excessive lipid causes hypertrophy in the adipocytes which lead to cell death. Consequently, dead adipocytes will produce adipokines, which cause macrophages and lymphocytes to infiltrate into the adipose tissue, elevating pro-inflammatory cytokines, thus triggering the production of pro-inflammatory cytokines through NFκB activity. Elicited soybeans extract (ESE) with bacteria and light contain Glyceollin and Isoflavones, which inhibit the activation of NFKB and reduce plasma cholesterol levels by upregulating cholesterol metabolism. This study aimed to analyze the effect of ESE against the relative number of CD4+ NFκB+ cells in BALB/c mice spleen after administrated by high-fat diet food and fructose (HFD) for 20 weeks. Mice were given orally with ESE after administrated by HFD at dose 78 mg/kgBW (D1), 104 mg/kgBW (D2), and 130 mg/kgBW (D3) for 4 weeks. This study also used positive control (HFD mice model without ESE treatment) and normal mice. Identification of NFKB activation was conducted using Flowcytometry analytical methods. Our result indicated that ESE could decrease significantly activation of NFκB in CD4 cell compare than positive control. The optimum dose that can decrease the relative number of CD4+ NFκB+ cells is dose 3.

Effects of caffeine on alcohol reinforcement: beverage choice, self-administration, and subjective ratings.

PubMed

Sweeney, Mary M; Meredith, Steven E; Evatt, Daniel P; Griffiths, Roland R

2017-03-01

Combining alcohol and caffeine is associated with increased alcohol consumption, but no prospective experimental studies have examined whether added caffeine increases alcohol consumption. This study examined how caffeine alters alcohol self-administration and subjective reinforcing effects in healthy adults. Thirty-one participants completed six double-blind alcohol self-administration sessions: three sessions with alcohol only (e.g., beverage A) and three sessions with alcohol and caffeine (e.g., beverage B). Participants chose which beverage to consume on a subsequent session (e.g., beverage A or B). The effects of caffeine on overall beverage choice, number of self-administered drinks, subjective ratings (e.g., Biphasic Alcohol Effects Scale), and psychomotor performance were examined. A majority of participants (65%) chose to drink the alcohol beverage containing caffeine on their final self-administration session. Caffeine did not increase the number of self-administered drinks. Caffeine significantly increased stimulant effects, decreased sedative effects, and attenuated decreases in psychomotor performance attributable to alcohol. Relative to nonchoosers, caffeine choosers reported overall lower stimulant ratings and reported greater drinking behavior prior to the study. Although caffeine did not increase the number of self-administered drinks, most participants chose the alcohol beverage containing caffeine. Given the differences in subjective ratings and pre-existing differences in self-reported alcohol consumption for caffeine choosers and nonchoosers, these data suggest that decreased stimulant effects of alcohol and heavier self-reported drinking may predict subsequent choice of combined caffeine and alcohol beverages. These predictors may identify individuals who would benefit from efforts to reduce risk behaviors associated with combining alcohol and caffeine.

Beta blocker infusion decreases the magnitude of core hypothermia after anesthesia induction.

PubMed

Inoue, S; Abe, R; Kawaguchi, M; Kobayashi, H; Furuya, H

2010-12-01

Beta-1-receptor blockade reduces heart rate, cardiac output, and arterial pressure while increasing peripheral vascular resistance. It is possible that beta blockers not only inhibit the core-to-peripheral re-distribution of body heat and cutaneous heat loss due to vasodilation after anesthesia induction but also reduce the convective transfer of heat from the core to peripheral tissues by decreasing cardiac output. The authors investigated whether the co-administration of esmolol or landiolol, ultra-short-acting beta blockers, attenuates the magnitude of initial re-distribution hypothermia after anesthesia induction and tracheal intubation. Immediately prior to the induction of anesthesia, patients were randomly assigned to receive 0.2 mg kg-1 of landiolol (landiolol group; N=30), 1 mg kg-1 of esmolol (esmolol group; N=30), or 0.1 mL kg-1 of saline (control group; N=30). Heart rate, blood pressure, cardiac output, and tympanic, forearm, and digit temperatures were recorded. Forearm minus fingertip skin-surface temperature gradients (temperature gradient) were calculated. Tympanic membrane temperatures 15 to 60 min after the induction of anesthesia were significantly higher in the esmolol group than in the control group although the temperature gradient was similar among the three groups. Both esmolol and landiolol inhibited the increase in HR and MAP after the induction of anesthesia and tracheal intubation. The cardiac index in the esmolol group was significantly lower than in the control group. The degree of hemodynamic attenuation after induction by esmolol was larger than that of landiolol. The co-administration of esmolol, but not landiolol, attenuated the magnitude of initial re-distribution hypothermia after anesthesia induction and tracheal intubation. Esmolol likely prevented initial hypothermia because it attenuated the convective transfer of heat from the core to peripheral tissues by decreasing cardiac output.

Pharmacokinetics and pharmacodynamics of detomidine following sublingual administration to horses.

PubMed

Dimaio Knych, Heather K; Stanley, Scott D

2011-10-01

To characterize pharmacokinetics and pharmacodynamics of detomidine gel administered sublingually in accordance with label instructions to establish appropriate withdrawal guidelines for horses before competition. 12 adult racehorses. Horses received a single sublingual administration of 0.04 mg of detomidine/kg. Blood samples were collected before and up to 72 hours after drug administration. Urine samples were collected for 5 days after detomidine administration. Plasma and urine samples were analyzed via liquid chromatography-mass spectrometry, and resulting data were analyzed by use of noncompartmental analysis. Chin-to-ground distance, heart rate and rhythm, glucose concentration, PCV, and plasma protein concentration were also assessed following detomidine administration. Mean ± SD terminal elimination half-life of detomidine was 1.5 ± 1 hours. Metabolite concentrations were below the limit of detection (0.02, 0.1, and 0.5 ng/mL for detomidine, carboxydetomidine, and hydroxydetomidine, respectively) in plasma by 24 hours. Concentrations of detomidine and its metabolites were below the limit of detection (0.05 ng/mL for detomidine and 0.10 ng/mL for carboxydetomidine and hydroxydetomidine) in urine by 3 days. All horses had various degrees of sedation after detomidine administration. Time of onset was ≤ 40 minutes, and duration of sedation was approximately 2 hours. Significant decreases, relative to values at time 0, were detected for chin-to-ground distance and heart rate. There was an increased incidence and exacerbation of preexisting atrioventricular blocks after detomidine administration. A 48-hour and 3-day withdrawal period for detection in plasma and urine samples, respectively, should be adopted for sublingual administration of detomidine gel.

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.

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

PubMed

Lukasiewicz, A; Lebkowska, U; Galar, M

2012-01-01

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

Correlation of ABO and Rh blood groups with transfusion administration and fever onset after hip surgery in children.

PubMed

Brdar, Radivoj; Petronic, Ivana; Nikolic, Dejan; Golubovic, Zoran; Bukva, Bojan; Radlovic, Vladimir; Abramovic, Dusan; Ducic, Sinisa; Colovic, Hristina

2012-01-01

Aim of our study was to evaluate distribution of ABO and Rh blood type groups in children after hip surgery regarding transfusion administration and fever presence. Four types of ABO blood groups (A; B; AB; O) and 2 types of Rh blood groups (Rh+; Rh-) were evaluated in group with administered transfusion (tr+) and without given transfusion (tr-); and in group with fever (fev+) and without fever (fev-), in 146 children after hip surgery. Tr+ and fev+ groups were divided into 3 groups (0-24h; 25-48h; 49-72h): for tr+ group (Group 1, Group 2, Group 3), and for fev+ group (Group A, Group B, Group C). AB blood group significantly decreased in Group 1 (χ2= 6.44; p<0.05) and A blood group in Group 3 in tr+ group (χ2= 7.68; p<0.01). O blood group significantly increased in Group 3 in tr+ group (χ2= 9.96; p<0.01). AB blood group significantly decreased in Groups B (χ2= 12.2; p<0.01) and C (χ2= 4.2; p<0.05) in fev+ versus fevgroup. B blood group significantly increased in Group C (χ2= 34.4; p<0.01) in fev+group. Administration of transfusion and fever onset in pediatric patients undergoing surgical correction of the hip is not influenced by the ABO and Rh blood groups system in humans. There is correlation between distribution of ABO blood groups with the time of transfusion administration and fever onset in children after hip surgery.

The sap of Acer okamotoanum decreases serum alcohol levels after acute ethanol ingestion in rats.

PubMed

Yoo, Yeong-Min; Jung, Eui-Man; Kang, Ha-Young; Choi, In-Gyu; Choi, Kyung-Chul; Jeung, Eui-Bae

2011-10-01

In the present study, we examined whether Acer okamotoanum (A. okamotoanum) sap decreased the serum alcohol and acetaldehyde levels after acute ethanol treatment in a rat model. Male rats were orally administered 25, 50 or 100% A. okamotoanum sap 30 min prior to oral challenge with 3 ml of ethanol (15 ml/kg of a 20% ethanol solution in water), and the blood concentrations of alcohol and acetaldehyde were analyzed up to 7 h after the treatment. Pre-treatment with the sap significantly decreased the blood ethanol and acetaldehyde concentrations after 5 h when compared with ethanol treatment alone (a negative control). The expression levels of liver alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) mRNA were increased significantly in animals pre-treated with A. okamotoanum sap when compared with negative and positive controls. The data suggest that sap pre-treatment enhanced the alcohol metabolism rate in the rat liver. To investigate the involvement of mitochondrial regulation in the ethanol-induced hepatocyte apoptosis, we carried out an immunohistochemical analysis of Bax and Bcl-2. Pre-treatment with sap significantly decreased Bax expression and increased Bcl-2 expression 7 h after ethanol administration when compared with the negative control. The data suggest that A. okamotoanum sap pre-treatment may reduce the alcohol-induced oxidative stress in the rat liver.

76 FR 60361 - Pistachios Grown in California, Arizona, and New Mexico; Decreased Assessment Rate

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-29

...; FV-983-2 IR] Pistachios Grown in California, Arizona, and New Mexico; Decreased Assessment Rate...: This rule decreases the assessment rate established for the Administrative Committee for Pistachios... weight pistachios. The Committee locally administers the marketing order which regulates the handling of...

Mitigating errors caused by interruptions during medication verification and administration: interventions in a simulated ambulatory chemotherapy setting

PubMed Central

Prakash, Varuna; Koczmara, Christine; Savage, Pamela; Trip, Katherine; Stewart, Janice; McCurdie, Tara; Cafazzo, Joseph A; Trbovich, Patricia

2014-01-01

Background Nurses are frequently interrupted during medication verification and administration; however, few interventions exist to mitigate resulting errors, and the impact of these interventions on medication safety is poorly understood. Objective The study objectives were to (A) assess the effects of interruptions on medication verification and administration errors, and (B) design and test the effectiveness of targeted interventions at reducing these errors. Methods The study focused on medication verification and administration in an ambulatory chemotherapy setting. A simulation laboratory experiment was conducted to determine interruption-related error rates during specific medication verification and administration tasks. Interventions to reduce these errors were developed through a participatory design process, and their error reduction effectiveness was assessed through a postintervention experiment. Results Significantly more nurses committed medication errors when interrupted than when uninterrupted. With use of interventions when interrupted, significantly fewer nurses made errors in verifying medication volumes contained in syringes (16/18; 89% preintervention error rate vs 11/19; 58% postintervention error rate; p=0.038; Fisher's exact test) and programmed in ambulatory pumps (17/18; 94% preintervention vs 11/19; 58% postintervention; p=0.012). The rate of error commission significantly decreased with use of interventions when interrupted during intravenous push (16/18; 89% preintervention vs 6/19; 32% postintervention; p=0.017) and pump programming (7/18; 39% preintervention vs 1/19; 5% postintervention; p=0.017). No statistically significant differences were observed for other medication verification tasks. Conclusions Interruptions can lead to medication verification and administration errors. Interventions were highly effective at reducing unanticipated errors of commission in medication administration tasks, but showed mixed effectiveness at

CDP-choline liposomes provide significant reduction in infarction over free CDP-choline in stroke

PubMed Central

Adibhatla, Rao Muralikrishna; Hatcher, J.F.; Tureyen, K.

2007-01-01

Cytidine-5′-diphosphocholine (CDP-choline, Citicoline, Somazina) is in clinical use (intravenous administration) for stroke treatment in Europe and Japan, while USA phase III stroke clinical trials (oral administration) were disappointing. Others showed that CDP-choline liposomes significantly increased brain uptake over the free drug in cerebral ischemia models. Liposomes were formulated as DPPC, DPPS, cholesterol, GM1 ganglioside; 7/4/7/1.57 molar ratio or 35.8/20.4/35.8/8.0 mol%. GM1 ganglioside confers long-circulating properties to the liposomes by suppressing phagocytosis. CDP-choline liposomes deliver the agent intact to the brain, circumventing the rate-limiting, cytidine triphosphate:phosphocholine cytidylyltransferase in phosphatidylcholine synthesis. Our data show that CDP-choline liposomes significantly ( P < 0.01) decreased cerebral infarction (by 62%) compared to the equivalent dose of free CDP-choline (by 26%) after 1 h focal cerebral ischemia and 24 h reperfusion in spontaneously hypertensive rats. Beneficial effects of CDP-choline liposomes in stroke may derive from a synergistic effect between the phospholipid components of the liposomes and the encapsulated CDP-choline. PMID:16153613

Wheel running decreases the positive reinforcing effects of heroin.

PubMed

Smith, Mark A; Pitts, Elizabeth G

2012-01-01

The purpose of this study was to examine the effects of voluntary wheel running on the positive reinforcing effects of heroin in rats with an established history of drug self-administration. Rats were assigned to sedentary (no wheel) and exercise (wheel) conditions and trained to self-administer cocaine under positive reinforcement contingencies. Rats acquiring cocaine self-administration were then tested with various doses of heroin during daily test sessions. Sedentary rats self-administered more heroin than exercising rats, and this effect was greatest at low and moderate doses of heroin. These data suggest that voluntary wheel running decreases the positive reinforcing effects of heroin.

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...

Improving efficiency and reducing administrative burden through electronic communication.

PubMed

Cook, Katlyn E; Ludens, Gail M; Ghosh, Amit K; Mundell, William C; Fleming, Kevin C; Majka, Andrew J

2013-01-01

The InBox messaging system is an internal, electronic program used at Mayo Clinic, Rochester, MN, to facilitate the sending, receiving, and answering of patient-specific messages and alerts. A standardized InBox was implemented in the Division of General Internal Medicine to decrease the time physicians, physician assistants, and nurse practitioners (clinicians) spend on administrative tasks and to increase efficiency. Clinicians completed surveys and a preintervention InBox pilot test to determine inefficiencies related to administrative burdens and defects (message entry errors). Results were analyzed using Pareto diagrams, value stream mapping, and root cause analysis to prioritize administrative-burden inefficiencies to develop a new, standardized InBox. Clinicians and allied health staff were the target of this intervention and received standardized InBox training followed by a postintervention pilot test for clinicians. Sixteen of 28 individuals (57%) completed the preintervention survey. Twenty-eight clinicians participated in 2 separate 8-day pilot tests (before and after intervention) for the standardized InBox. The number of InBox defects was substantially reduced from 37 (Pilot 1) to 7 (Pilot 2). Frequent InBox defects decreased from 25% to 10%. More than half of clinicians believed the standardized InBox positively affected their work, and 100% of clinicians reported no negative affect on their work. This project demonstrated the successful implementation of the standardized InBox messaging system. Initial assessments show substantial reduction of InBox entry defects and administrative tasks completed by clinicians. The findings of this project suggest increased clinician and allied health staff efficiency, satisfaction, improved clinician work-life balance, and decreased clinician burden caused by administrative tasks.

Prevention of Intraabdominal Adhesions by Local and Systemic Administration of Immunosuppressive Drugs

PubMed Central

Peker, Kemal; Inal, Abdullah; Sayar, Ilyas; Sahin, Murat; Gullu, Huriye; Inal, Duriye Gul; Isik, Arda

2013-01-01

Background: Intraperitoneal adhesion formation is a serious postsurgical issue. Adhesions develop after damage to the peritoneum by surgery, irradiation, infection or trauma. Objectives: Using a rat model, we compared the effectiveness of systemic and intraperitoneally administered common immunosuppressive drugs for prevention of postoperative intraperitoneal adhesions. Materials and Methods: Peritoneal adhesions were induced in 98 female Wistar-Albino rats by cecal abrasion and peritoneal excision. Rats were randomly separated into seven groups, each containing fourteen rats, and the standard experimental model was applied to all of rats. 14 days later, rats were euthanized, intraperitoneal adhesions were scored and tissues were examined histologically using hematoxylin/eosin and Masson’s trichrome staining. Results: Throughout the investigation, no animal died during or after surgery. In all of experimental groups, decrease in fibrosis was statistically significant. Decrease in fibrosis was most prominently in intraperitoneal tacrolimus group (P = 0.000), and decrease was least in intraperitoneal cyclosporine group (P = 0.022). Vascular proliferation was significantly decreased in all experimental groups (P < 0.05) except for systemic tacrolimus group (P = 0.139). Most prominent reduction in vascular proliferation was in intraperitoneal tacrolimus group (P = 0.000). Conclusions: Administration of immunosuppressive drugs is effective for prevention of intraperitoneal adhesions. PMID:24693396

Hypotensive effect of alpha-lipoic acid after a single administration in rats.

PubMed

Dudek, Magdalena; Razny, Katarzyna; Bilska-Wilkosz, Anna; Iciek, Malgorzata; Sapa, Jacek; Wlodek, Lidia; Filipek, Barbara

2016-05-01

The effect of alpha-lipoic acid on blood pressure was investigated many times in chronic studies, but there are no studies on the effect of this compound after a single administration. Alpha-lipoic acid is a drug used in diabetic neuropathy, often in obese patients, to treat hypertension. Therefore, knowledge of the potential antihypertensive effect of alpha-lipoic acid even after a single dose and possibly too much pressure reduction is interesting and useful. The mechanism of the hypotensive effect of alpha-lipoic acid was examined in normotensive rats in vivo after a single intraperitoneal administration, blood pressure in the left carotid artery of the rats was measured prior to the administration of the compounds (alpha- lipoic acid and/or glibenclamide) and 80 min thereafter. Alpha-lipoic acid at a dosage of 50 mg/kg b.w. i.p. significantly decreased the blood pressure from the 50th min after drug administration. This cardiovascular effect of this compound was reversed by glibenclamide, a selective KATP blocker. Glibenclamide alone at this dose did not significantly affect the blood pressure. Statistical significance was evaluated using two-way ANOVA. This suggests that alpha-lipoic acid affects ATP-dependent potassium channels. It is possible that this is an indirect effect of hydrogen sulfide because alpha-lipoic acid can increase its concentration. The results obtained in this study are very important because the patients taking alpha-lipoic acid may be treated for co-existing hypertension. Therefore, the possibility of blood pressure lowering by alpha-lipoic acid should be taken into account, although it does not lead to excessive orthostatic hypotension.

Apixaban decreases brain thrombin activity in a male mouse model of acute ischemic stroke.

PubMed

Bushi, Doron; Chapman, Joab; Wohl, Anton; Stein, Efrat Shavit; Feingold, Ekaterina; Tanne, David

2018-05-14

Factor Xa (FXa) plays a critical role in the coagulation cascade by generation of thrombin. During focal ischemia thrombin levels increase in the brain tissue and cause neural damage. This study examined the hypothesis that administration of the FXa inhibitor, apixaban, following focal ischemic stroke may have therapeutic potential by decreasing brain thrombin activity and infarct volume. Male mice were divided into a treated groups that received different doses of apixaban (2, 20, 100 mg/kg administered I.P.) or saline (controls) immediately after blocking the middle cerebral artery (MCA). Thrombin activity was measured by a fluorescence assay on fresh coronal slices taken from the mice brains 24 hr following the MCA occlusion. Infarct volume was assessed using triphenyltetrazolium chloride staining. A high dose of apixaban (100 mg/kg) significantly decreased thrombin activity levels in the ipsilateral hemisphere compared to the control group (Slice#5, p = .016; Slice#6, p = .016; Slice#7, p = .016; Slice#8, p = .036; by the nonparametric Mann-Whitney test). In addition, treatment with apixaban doses of both 100 mg/kg (32 ± 8% vs. 76 ± 7% in the treatment vs. control groups respectively; p = .005 by the nonparametric Mann-Whitney test) and 20 mg/kg (43 ± 7% vs. 76 ± 7% in the treatment vs. control groups respectively; p = .019 by the nonparametric Mann-Whitney test) decreased infarct volumes in areas surrounding the ischemic core (Slices #3 and #8). No brain hemorrhages were observed either in the treated or control groups. In summary, I.P. administration of high dose of apixaban immediately after MCA occlusion decreases brain thrombin activity and reduces infarct size. © 2018 Wiley Periodicals, Inc.

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

PubMed

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

2004-05-01

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

DETANONOate, a nitric oxide donor, decreases amiloride-sensitive alveolar fluid clearance in rabbits.

PubMed

Nielsen, V G; Baird, M S; Chen, L; Matalon, S

2000-04-01

Inhaled nitric oxide (NO) has been administered to animals to selectively reduce pulmonary hypertension via NO donors such as the NONOates. However, vectorial Na(+) transport across confluent monolayers of alveolar type II (ATII) pneumocytes has been decreased by NO. We tested the hypothesis that administration of the NO donor, DETANONOate, would decrease alveolar fluid clearance (AFC) in the rabbit in vivo. We instilled a solution of 5% albumin in 0.9% NaCl with 3 mM DETANONOate into anesthetized rabbits. Two hours later, similar AFC values were measured in the presence and absence of 3 mM DETANONOate (38 +/- 12% versus 43 +/- 13%; mean +/- SD). However, animals coadministered 1 mM amiloride with one of three doses of DETANONOate (100 microM, 300 microM, or 3 mM) had significantly (p < 0.05) greater AFC values (23 +/- 8, 20 +/- 14, 28 +/- 12%, respectively) than those administered amiloride alone (10 +/- 7%). When 5% albumin in a Cl(-)-free solution was administered in the presence or absence of 100 microM DETANONOate, neither AFC values nor alveolar Cl(-) concentrations were different. DETANONOate decreases the amiloride-sensitive fraction of AFC but does not decrease total AFC. DETANONOate does not influence total AFC secondary to an increase in the amiloride-insensitive fraction of AFC that is not associated with a decrease in alveolar Cl(-) secretion.

Cardiotoxicity in rabbits after long-term nandrolone decanoate administration.

PubMed

Vasilaki, Fotini; Tsitsimpikou, Christina; Tsarouhas, Konstantinos; Germanakis, Ioannis; Tzardi, Marias; Kavvalakis, Matthaios; Ozcagli, Eren; Kouretas, Dimitrios; Tsatsakis, Aristidis M

2016-01-22

Abuse of anabolic androgenic steroids is linked to a variety of cardiovascular complications. The aim of our study was to investigate the possible cardiovascular effects of nandrolone decanoate on young rabbits using echocardiography, histology and monitoring of telomerase activity, oxidative stress and biochemical markers. Fourteen rabbits were divided into three administration groups and the control group. Doses of 4mg/kg and 10mg/kg of nandrolone decanoate, given intramuscularly and subcutaneously, two days per week for six months were applied. A 4-months wash-out period followed. Focal fibrosis and inflammatory infiltrations of cardiac tissue were observed in the high dose groups. Thiobarbituric acid-reactive species (TBARS) levels were significantly increased in the high dose groups, while catalase activity decreased. Myocardial Performance Index (MPI) is the main echocardiographic index primarily affected by nandrolone administration in rabbits. Despite the preserved systolic performance, histological lesions observed associated with distorted MPI values, point to diastolic impairment of the thickened myocardium due to nandrolone treatment. Oxidative stress accumulates and telomerase activity in cardiac tissue rises. Subcutaneous administration seems to be more deleterious to the cardiovascular system, as oxidative stress, telomerase activity and biochemical markers do not appear to return into normal values in the wash-out period. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Effects of chronic systemic administration of the GABA(B) receptor agonist baclofen on food intake and body weight in rats.

PubMed

Patel, Sunit M; Ebenezer, Ivor S

2010-06-10

The effects of daily administration of physiological saline of baclofen (1 and 4mg/kg, i.p.) for 27 days were investigated on food intake and body weight in non-deprived rats in Experiment 1. Baclofen (1 and 4mg/kg) significantly increased daily short-term food intake when measured at 30min (F((2,15))=11.011, P<0.01) and 90min (F((2,15))=7.3801, P<0.01) over the 27 day experimental period.. Tolerance did not develop to the short-term hyperphagic effects of baclofen. Baclofen (1mg/kg) had no significant effects on body weight gain of the rats compared with controls. By contrast, baclofen (4mg/kg) significantly (P<0.05) decreased the body weight gain of the animals. In Experiment 2, the effect of daily administration of baclofen (4mg/kg, i.p.) for 24 days was investigated on 24h food intake in rats measured after the first, eight, fifteenth and twenty second injections. The 24h food intake of the animals was not significantly different from those of control rats on any of the measurement days (F((1,14))=1.602, ns). However, the body weight gain of the rats chronically treated with baclofen (4mg/kg) was significantly reduced. (F((1,14))=14.011, P<0.01). The observations that chronic administration of baclofen (4mg/kg) stimulates short-term food intake without affecting long term (24h) feeding, but decreases body weight gain, suggest that baclofen may act through different mechanisms to influence food intake and body weight.

Incidence and trends of central line associated pneumothorax using radiograph report text search versus administrative database codes.

PubMed

Reeson, Marc; Forster, Alan; van Walraven, Carl

2018-05-25

Central line associated pneumothorax (CLAP) could be a good quality of care indicator because they are objectively measured, clearly undesirable and possibly avoidable. We measured the incidence and trends of CLAP using radiograph report text search with manual review and compared them with measures using routinely collected health administrative data. For each hospitalisation to a tertiary care teaching hospital between 2002 and 2015, we searched all chest radiography reports for a central line with a sensitive computer algorithm. Screen positive reports were manually reviewed to confirm central lines. The index and subsequent chest radiography reports were screened for pneumothorax followed by manual confirmation. Diagnostic and procedural codes were used to identify CLAP in administrative data. In 685 044 hospitalisations, 10 819 underwent central line insertion (1.6%) with CLAP occurring 181 times (1.7%). CLAP risk did not change over time. Codes for CLAP were inaccurate (sensitivity 13.8%, positive predictive value 6.6%). However, overall code-based CLAP risk (1.8%) was almost identical to actual values possibly because patient strata with inflated CLAP risk were balanced by more common strata having underestimated CLAP risk. Code-based methods inflated central line incidence 2.2 times and erroneously concluded that CLAP risk decreased significantly over time. Using valid methods, CLAP incidence was similar to those in the literature but has not changed over time. Although administrative database codes for CLAP were very inaccurate, they generated CLAP risks very similar to actual values because of offsetting errors. In contrast to those from radiograph report text search with manual review, CLAP trends decreased significantly using administrative data. Hospital CLAP risk should not be measured using administrative data. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial

Comparison of time to loss of consciousness and maintenance of anesthesia following intraosseous and intravenous administration of propofol in rabbits.

PubMed

Mazaheri-Khameneh, Ramin; Sarrafzadeh-Rezaei, Farshid; Asri-Rezaei, Siamak; Dalir-Naghadeh, Bahram

2012-07-01

To compare time to loss of consciousness (LOC) and effective maintenance of anesthesia following intraosseous (IO) and IV administration of propofol in rabbits. Evaluation study. 24 New Zealand White rabbits. Rabbits were selected to receive IO (n = 6) or IV (6) bolus administration of 1% propofol (12.5 mg/kg [5.67 mg/lb]) only or an identical bolus of propofol IO (6) or IV (6) followed by a constant rate infusion (CRI; 1 mg/kg/min [0.45 mg/lb/min]) by the same route for 30 minutes. Physiologic variables were monitored at predetermined time points; time to LOC and durations of anesthesia and recovery were recorded. Following IO and IV bolus administration, mean time to LOC was 11.50 and 7.83 seconds, respectively; changes in heart rate, respiratory rate, oxygen saturation (as measured by pulse oximetry), and mean arterial blood pressure values were evident, but findings did not differ between groups. For the IO- and IV-CRI groups, propofol-associated changes in heart rate, oxygen saturation, and mean arterial blood pressure values were similar, and although mean arterial blood pressure decreased significantly from baseline, values remained > 60 mm Hg; respiratory rate decreased significantly during CRI in both groups, but remained higher in the IO-CRI group. Anesthesia and recovery time did not differ between the IO- and IV-CRI groups. In all evaluated aspects of anesthesia, IO administration of propofol was as effective as IV administration in rabbits. Results suggested that total IO anesthesia can be performed in rabbits with limited vascular access.

Subcutaneous Fentanyl Administration: A Novel Approach for Pain Management in a Rural and Suburban Prehospital Setting.

PubMed

Lebon, Johann; Fournier, Francis; Bégin, François; Hebert, Denise; Fleet, Richard; Foldes-Busque, Guilaume; Tanguay, Alain

2016-01-01

To determine the feasibility, safety, and effectiveness of the subcutaneous route of fentanyl administration by Basic Life Support-Emergency Medical Technicians (BLS-EMT) in a rural and suburban region, with the support of an online pain management medical control center. Retrospective study of patients who received subcutaneous fentanyl and were transported by BLS-EMT to the emergency department (ED) of an academic hospital between July 1, 2013 and January 1, 2014, inclusively. Fentanyl orders were obtained from emergency physicians via an online medical control (OLMC) center. Effectiveness was defined by changes in pain scores 15 minutes, 30 minutes, and 45+ minutes after initial fentanyl administration. Safety was evaluated by measuring vital signs, Ramsay sedation scores, and adverse events subsequent to fentanyl administration. Feasibility was defined as successful fentanyl administration by BLS-EMT. SPSS-20 was used for descriptive statistics, and independent t-tests and Mann-Whitney U tests were used to determine inter- and intra-group differences based on transport time. Two hundred and eighty-eight patients (288; 14 to 93 years old) with pain scores ≥7 were eligible for the study. Of the 284 (98.6%) who successfully received subcutaneous fentanyl, 35 had missing records or data, and 249 (86.5%) were included in analyses. Average pain score pre-fentanyl was 8.9 ± 1.1. Patients <70 years old received a higher dose of fentanyl than those ≥70 years old (1.4 ± 0.3 vs, 0.8 ± 0.2 mcg/kg, p < 0.05). Pain scores decreased significantly post-fentanyl administration and the proportion of patients achieving pain relief increased significantly (p < 0.05) over the course of transport to ED (15 minutes, 30 minutes, 45+ minutes). Only 1.6% of patients experienced adverse events, including hypotension (n = 2; 0.8%), nausea (n = 1; 0.4%), and Ramsay level >3 (n = 1; 0.4%). Prehospital subcutaneous fentanyl administration by BLS-EMT with the support of an OLMC

Reduction of nicotine self-administration by chronic nicotine infusion with H1 histamine blockade in female rats.

PubMed

Levin, Edward D; Hall, Brandon J; Chattopadhyay, Autri; Slade, Susan; Wells, Corinne; Rezvani, Amir H; Rose, Jed E

2016-08-01

Chronic nicotine infusion via transdermal patches has been widely shown to assist with smoking cessation. In particular, transdermal nicotine treatment prior to quitting smoking helps reduce ad libitum smoking and aids cessation Rose et al. (Nicotine Tob Res 11:1067-75, 2009). However, despite this success, the majority of smokers who use transdermal nicotine fail to permanently quit smoking. Additional treatments are needed. Tobacco addiction does not just depend on nicotinic receptor systems; a variety of neural systems are involved, including dopamine, norepinepherine, serotonin, and histamine. Given the involvement of a variety of neural systems in the circuits of addiction, combination therapy may offer improved efficacy for successful smoking cessation beyond single treatments alone. We have found that pyrilamine, an H1 histamine antagonist, significantly decreases nicotine self-administration in rats. The current study was conducted to confirm the effect of chronic nicotine infusion on ongoing nicotine self-administration and resumed access after enforced abstinence and to determine the interaction of chronic nicotine with an H1 antagonist treatment. Chronic nicotine infusion via osmotic minipump (2.5 and 5 mg/kg/day for 28 days) significantly reduced nicotine self-administration in a dose-dependent manner. Chronic nicotine infusion also reduced the resumption of nicotine self-administration after enforced abstinence. Chronic pyrilamine infusion (25 mg/kg/day for 14 days) also significantly reduced nicotine self-administration. The combination of chronic nicotine and pyrilamine reduced nicotine self-administration to a greater extent than treatment with either drug alone.

Using mobile devices to improve the safety of medication administration processes.

PubMed

Navas, H; Graffi Moltrasio, L; Ares, F; Strumia, G; Dourado, E; Alvarez, M

2015-01-01

Within preventable medical errors, those related to medications are frequent in every stage of the prescribing cycle. Nursing is responsible for maintaining each patients safety and care quality. Moreover, nurses are the last people who can detect an error in medication before its administration. Medication administration is one of the riskiest tasks in nursing. The use of information and communication technologies is related to a decrease in these errors. Including mobile devices related to 2D code reading of patients and medication will decrease the possibility of error when preparing and administering medication by nurses. A cross-platform software (iOS and Android) was developed to ensure the five Rights of the medication administration process (patient, medication, dose, route and schedule). Deployment in November showed 39% use.

Losartan Decreases Cardiac Muscle Fibrosis and Improves Cardiac Function in Dystrophin-Deficient Mdx Mice

PubMed Central

Spurney, Christopher F.; Sali, Arpana; Guerron, Alfredo D.; Iantorno, Micaela; Yu, Qing; Gordish-Dressman, Heather; Rayavarapu, Sree; van der Meulen, Jack; Hoffman, Eric P.; Nagaraju, Kanneboyina

2014-01-01

Recent studies showed that chronic administration of losartan, an angiotensin II type I receptor antagonist, improved skeletal muscle function in dystrophin-deficient mdx mice. In this study, C57BL/10ScSn-Dmdmdx/J female mice were either untreated or treated with losartan (n = 15) in the drinking water at a dose of 600 mg/L over a 6-month period. Cardiac function was assessed via in vivo high frequency echocardiography and skeletal muscle function was assessed using grip strength testing, Digiscan monitoring, Rotarod timing, and in vitro force testing. Fibrosis was assessed using picrosirius red staining and Image J analysis. Gene expression was evaluated using real-time polymerized chain reaction (RT-PCR). Percentage shortening fraction was significantly decreased in untreated (26.9% ± 3.5%) mice compared to losartan-treated (32.2% ± 4.2%; P < .01) mice. Systolic blood pressure was significantly reduced in losartan-treated mice (56 ± 6 vs 69 ± 7 mm Hg; P < .0005). Percentage cardiac fibrosis was significantly reduced in losartan-treated hearts (P < .05) along with diaphragm (P < .01), extensor digitorum longus (P < .05), and gastrocnemius (P < .05) muscles compared to untreated mdx mice. There were no significant differences in skeletal muscle function between treated and untreated groups. Chronic treatment with losartan decreases cardiac and skeletal muscle fibrosis and improves cardiac systolic function in dystrophin-deficient mdx mice. PMID:21304057

Effects of caffeine on alcohol reinforcement: Beverage choice, self-administration, and subjective ratings

PubMed Central

Sweeney, Mary M.; Meredith, Steven E.; Evatt, Daniel P.; Griffiths, Roland R.

2017-01-01

Rationale Combining alcohol and caffeine is associated with increased alcohol consumption, but no prospective experimental studies have examined whether added caffeine increases alcohol consumption. Objectives This study examined how caffeine alters alcohol self-administration and subjective reinforcing effects in healthy adults. Methods Thirty-one participants completed six double-blind alcohol self-administration sessions: three sessions with alcohol only (e.g., Beverage A) and three sessions with alcohol and caffeine (e.g., Beverage B). Participants chose which beverage to consume on a subsequent session (e.g., Beverage A or B). Effects of caffeine on overall beverage choice, number of self-administered drinks, subjective ratings (e.g., Biphasic Alcohol Effects Scale), and psychomotor performance were examined. Results A majority of participants (65%) chose to drink the alcohol beverage containing caffeine on their final self-administration session. Caffeine did not increase the number of self-administered drinks. Caffeine significantly increased stimulant effects, decreased sedative effects, and attenuated decreases in psychomotor performance attributable to alcohol. Relative to nonchoosers, caffeine choosers reported overall lower stimulant ratings, and reported greater drinking behavior prior to the study. Conclusions Although caffeine did not increase the number of self-administered drinks, most participants chose the alcohol beverage containing caffeine. Given the differences in subjective ratings and pre-existing differences in self-reported alcohol consumption for caffeine choosers and nonchoosers, these data suggest decreased stimulant effects of alcohol and heavier self-reported drinking may predict subsequent choice of combined caffeine and alcohol beverages. These predictors may identify individuals who would benefit from efforts to reduce risk behaviors associated with combining alcohol and caffeine. PMID:28108773

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.

Effects of chronic scopolamine administration on spatial working memory and hippocampal receptors related to learning.

PubMed

Doguc, Duygu K; Delibas, Namik; Vural, Huseyin; Altuntas, Irfan; Sutcu, Recep; Sonmez, Yonca

2012-12-01

Scopolamine has been used in neuropsychopharmacology as a standard drug that leads to symptoms mimicking cognitive deficits seen during the aging process in healthy humans and animals. Scopolamine is known to be a nonselective muscarinic receptor blocker, but its chronic effect on the expression of certain hippocampal receptors is not clear. The aim of the present study was to determine the effect of chronic scopolamine administration on hippocampal receptor expression and spatial working memory in two different learning tasks, the water maze and the eight-arm radial maze. Male rats (8-12 months) were trained in both tasks. Subsequently, different groups received physiological saline or 0.1, 0.8, or 2 mg/kg scopolamine hydrobromide, respectively, for 15 days. After drug administration, the rats were retested for both tasks, and hippocampal expressions of NR2A, NR2B, nAChRα7, and mAChRM1 receptors were assessed by western blotting analysis. In both tasks, the spatial working memory was decreased dose dependently in all groups compared with the control group. In terms of receptor expressions, 0.8 and 2 mg/kg scopolamine administration significantly decreased NR2A protein expression, which corroborates suggestions of an interaction between cholinergic and glutamatergic receptors in the hippocampus.

Neonatal finasteride administration decreases dopamine release in nucleus accumbens after alcohol and food presentation in adult male rats.

PubMed

Llidó, Anna; Bartolomé, Iris; Darbra, Sònia; Pallarès, Marc

2016-08-01

Endogenous levels of the neurosteroid (NS) allopregnanolone (AlloP) during neonatal stages are crucial for the correct development of the central nervous system (CNS). In a recent work we reported that the neonatal administration of AlloP or finasteride (Finas), an inhibitor of the enzyme 5α-reductase needed for AlloP synthesis, altered the voluntary consumption of ethanol and the ventrostriatal dopamine (DA) levels in adulthood, suggesting that neonatal NS manipulations can increase alcohol abuse vulnerability in adulthood. Moreover, other authors have associated neonatal NS alterations with diverse dopaminergic (DAergic) alterations. Thus, the aim of the present work is to analyse if manipulations of neonatal AlloP alter the DAergic response in the nucleus accumbens (NAcc) during alcohol intake in rats. We administered AlloP or Finas from postnatal day (PND) 5 to PND9. At PND98, we measured alcohol consumption using a two-bottle free-choice model (ethanol 10% (v/v)+glucose 3% (w/v), and glucose 3% (w/v)) for 12 days. On the last day of consumption, we measured the DA and 3,4-dihydroxyphenylacetic acid (DOPAC) release in NAcc in response to ethanol intake. The samples were obtained by means of in vivo microdialysis in freely moving rats, and DA and DOPAC levels were determined by means of high-performance liquid chromatography analysis (HPLC). The results revealed that neonatal Finas increased ethanol consumption in some days of the consumption phase, and decreased the DA release in the NAcc in response to solutions (ethanol+glucose) and food presentation. Taken together, these results suggest that neonatal NS alterations can affect alcohol rewarding properties. Copyright © 2016 Elsevier B.V. All rights reserved.

Decreased Fibronectin Production Significantly Contributes to Dysregulated Repair of Asthmatic Epithelium

PubMed Central

Kicic, Anthony; Hallstrand, Teal S.; Sutanto, Erika N.; Stevens, Paul T.; Kobor, Michael S.; Taplin, Christopher; Paré, Peter D.; Beyer, Richard P.; Stick, Stephen M.; Knight, Darryl A.

2010-01-01

Rationale: Damage to airway epithelium is followed by deposition of extracellular matrix (ECM) and migration of adjacent epithelial cells. We have shown that epithelial cells from children with asthma fail to heal a wound in vitro. Objectives: To determine whether dysregulated ECM production by the epithelium plays a role in aberrant repair in asthma. Methods: Airway epithelial cells (AEC) from children with asthma (n = 36), healthy atopic control subjects (n = 23), and healthy nonatopic control subjects (n = 53) were investigated by microarray, gene expression and silencing, transcript regulation analysis, and ability to close mechanical wounds. Measurements and Main Results: Time to repair a mechanical wound in vitro by AEC from healthy and atopic children was not significantly different and both were faster than AEC from children with asthma. Microarray analysis revealed differential expression of multiple gene sets associated with repair and remodeling in asthmatic AEC. Fibronectin (FN) was the only ECM component whose expression was significantly lower in asthmatic AEC. Expression differences were verified by quantitative polymerase chain reaction and ELISA, and reduced FN expression persisted in asthmatic cells over passage. Silencing of FN expression in nonasthmatic AEC inhibited wound repair, whereas addition of FN to asthmatic AEC restored reparative capacity. Asthmatic AEC failed to synthesize FN in response to wounding or cytokine/growth factor stimulation. Exposure to 5′, 2′deoxyazacytidine had no effect on FN expression and subsequent analysis of the FN promoter did not show evidence of DNA methylation. Conclusions: These data show that the reduced capacity of asthmatic epithelial cells to secrete FN is an important contributor to the dysregulated AEC repair observed in these cells. PMID:20110557

FDG-PET for Evaluating the Antitumor Effect of Intraarterial 3-Bromopyruvate Administration in a Rabbit VX2 Liver Tumor Model

PubMed Central

Park, Hee Sun; Jae, Hwan Jun; Kim, Young Il; Son, Kyu Ri; Lee, Min Jong; Park, Jae Hyung; Kang, Won Jun; Yoon, Jung Hwan; Chung, Hesson; Lee, Kichang

2007-01-01

Objective We wanted to investigate the feasibility of using FDG-PET for evaluating the antitumor effect of intraarterial administration of a hexokinase II inhibitor, 3-bromopyruvate (3-BrPA), in a rabbit VX2 liver tumor model. Materials and Methods VX2 carcinoma was grown in the livers of ten rabbits. Two weeks later, liver CT was performed to confirm appropriate tumor growth for the experiment. After tumor volume-matched grouping of the rabbits, transcatheter intraarterial administration of 3-BrPA was performed (1 mM and 5 mM in five animals each, respectively). FDG-PET scan was performed the day before, immediately after and a week after 3-BrPA administration. FDG uptake was semiquantified by measuring the standardized uptake value (SUV). A week after treatment, the experimental animals were sacrificed and the necrosis rates of the tumors were calculated based on the histopathology. Results The SUV of the VX2 tumors before treatment (3.87 ±1.51 [mean ±SD]) was significantly higher than that of nontumorous liver parenchyma (1.72 ±0.34) (p < 0.0001, Mann-Whitney U test). The SUV was significantly decreased immediately after 3-BrPA administration (2.05 ±1.21) (p = 0.002, Wilcoxon signed rank test). On the one-week follow up PET scan, the FDG uptake remained significantly lower (SUV 1.41 ±0.73) than that before treatment (p = 0.002), although three out of ten animals showed a slightly increasing tendency for the FDG uptake. The tumor necrosis rate ranged from 50.00% to 99.90% (85.48% ±15.87). There was no significant correlation between the SUV or the SUV decrease rate and the tumor necrosis rate in that range. Conclusion Even though FDG-PET cannot exactly reflect the tumor necrosis rate, FDG-PET is a useful modality for the early assessment of the antitumor effect of intraarterial administration of 3-BrPA in VX2 liver tumor. PMID:17554189

Concurrent administration effect of antibiotic and anti-inflammatory drugs on the immunotoxicity of bacterial endotoxins.

PubMed

El Amir, Azza M; Tanious, Dalia G; Mansour, Hanaa A

2017-11-01

Pseudomonas aeruginosa (P. aeruginosa) is a gram-negative bacterium that causes a variety of diseases in compromised hosts. Bacterial endotoxins such as lipopolysaccharide (LPS) are the major outer surface membrane components that are present in almost all gram-negative bacteria and act as extremely strong stimulators of innate immunity and inflammation of the airway. This study was undertaken to determine the effect of combined administration of Gentamicin (GENT) as an antibiotic and Dexamethasone (DEXA) as an anti-inflammatory drug on some immunological and histological parameters. After determination of LD 50 of P. aeruginosa, mice groups were injected with DEXA, GENT and lipopolysaccharide alone or in combination. Lipopolysaccharide single injection caused a significant increase of total leukocyte count, lymphocytes, neutrophils and levels of IgM and IgG. DEXA induced an increase of neutrophilia and lymphopenia. Immunological examination demonstrated that combined treatment has a significant effect of decreasing lymphocytes and IgG levels than single treatment does. Histological examination demonstrated that the inflammation of thymus, spleen, lymph node and liver decreases in mice that received combined treatment than those that received individual treatment. Concurrent administration of DEXA and GENT has a great effect on protecting organs against damage in case of endotoxemia. Copyright © 2017 Elsevier B.V. All rights reserved.

Alosetron use in clinical practice: significant improvement in irritable bowel syndrome symptoms evaluated using the US Food and Drug Administration composite endpoint.

PubMed

Lacy, Brian E; Nicandro, Jean Paul; Chuang, Emil; Earnest, David L

2018-01-01

Alosetron is approved to treat women with severe IBS and diarrhea (IBS-D) who have failed standard therapy. In our study, we aimed to evaluate alosetron efficacy using new US Food and Drug Administration (FDA) endpoints and utilization in clinical practice. This prospective, open-label, multicenter, observational 12-week study evaluated women with severe IBS-D enrolled in the alosetron prescribing program. The coprimary FDA endpoints were changes from baseline in stool consistency and abdominal pain severity. Responders achieved a 30% decrease compared with baseline in weekly average of the worst abdominal pain in the past 24 h, and a 50% or greater reduction from baseline in the number of days/week with at least one stool of type 6 (mushy) or type 7 (watery) consistency. Secondary endpoints included changes from baseline in stool frequency, fecal urgency and fecal incontinence. Enrolled patients ( n = 192) were primarily White (90.6%), with a mean age of 44.5 years. Patient and physician rating of IBS severity was between moderate and severe (85.9% concordance, Spearman coefficient 0.429, p < 0.0001). Alosetron 0.5 mg twice daily (82.8%) was the most common dosing regimen. A total of 152 alosetron-treated patients completed the study. Of 105 fully evaluable patients, 45% met the FDA composite endpoint responder criteria for ⩾50% of the study period. Improvements in all individual symptoms were statistically significant compared with baseline. There were no serious adverse events, cases of colonic ischemia, or complications of constipation. In a clinical practice setting study, alosetron demonstrated treatment success using a rigorous FDA composite endpoint and also improved multiple other IBS symptoms, including fecal urgency and incontinence in women with severe IBS-D [ClinicalTrials.gov identifier: NCT01257477].

The evaluation of long-term effects of cinnamon bark and olive leaf on toxicity induced by streptozotocin administration to rats.

PubMed

Onderoglu, S; Sozer, S; Erbil, K M; Ortac, R; Lermioglu, F

1999-11-01

The effects of cinnamon bark and olive leaf have been investigated on streptozotocin-induced tissue injury, and some biochemical and haematological changes in rats. The effects on glycaemia were also evaluated. Long-term administration of olive leaf caused significant improvement in tissue injury induced by streptozotocin treatment; the effect of cinnamon bark was less extent. No effects on blood glucose levels were detected. However, significant decreases in some increased biochemical and haematological parameters of streptozotocin-treated rats were observed. Aspartate aminotransferase, urea and cholesterol levels were significantly decreased by treatment with both plant materials, and alanine aminotransferase by treatment with olive leaf. Cinnamon bark also caused a significant decrease in platelet counts. In addition, any visible toxicity, except decrease in body weight gain, attributable to the long-term use of plant materials was not established in normal rats. The data indicate that long-term use of olive leaf and cinnamon bark may provide benefit against diabetic conditions. Determination of underlying mechanism(s) of beneficial effects, toxicity to other systems and clinical assessments of related plant materials are major topics requiring further studies.

Effects of chronic fentanyl administration on physical performance of aged rats

PubMed Central

Mitzelfelt, Jeremiah D.; DuPree, Jameson P.; Seo, Dong-oh; Carter, Christy S.; Morgan, Drake

2010-01-01

There is growing concern over the increasing use of opioids to treat chronic pain in the elderly primarily because of the potential increased sensitivity to the adverse side effects. Here, we use a preclinical model (male Brown Norway X F344 rats aged 12, 18, 24, and 30 months) to describe the outcome of chronic fentanyl administration (1.0 mg/kg/day) on various physiological and behavioral measures. Continuous fentanyl administration resulted in an initial decrease in food consumption, followed by the development of tolerance to this effect over a 4-week period and a subsequent increase in food consumption during withdrawal. This change in food consumption was associated with decreases in body weight (predominantly due to a loss of fat mass) that was maintained through early withdrawal. After one month of withdrawal, only the 12-month old animals had fully regained body weight. Fentanyl administration resulted in a decrease in grip strength and an increase in locomotor activity that did not differ across age groups. There was no effect of fentanyl administration on rotarod performance. These results demonstrate that while there is a delayed recovery of body mass with age, the observed changes in behavioral responses are uniform across ages. PMID:20951790

Administration of recombinant interleukin-11 improves the hemodynamic functions and decreases third space fluid loss in a porcine model of hemorrhagic shock and resuscitation.

PubMed

Honma, Kaneatsu; Koles, Nancy L; Alam, Hasan B; Rhee, Peter; Rollwagen, Florence M; Olsen, Cara; Keith, James C; Pollack, Matthew

2005-06-01

We have previously demonstrated that the administration of recombinant human interleukin-11 (rhIL-11) during resuscitation improves the blood pressure in a rodent model of hemorrhagic shock. The purpose of this study was to determine whether the effects of rhIL-11 could be reproduced in a large animal model and to elucidate the impact of rhIL-11 administration on the intravascular volume status and the degree of third space fluid loss after resuscitation. A 40% blood volume hemorrhage was induced in swine (n = 45, weight of 25-35 kg) followed by a 1-h shock period and resuscitation with 0.9% sodium chloride (three times the shed blood volume). The animals were randomized to receive sham hemorrhage (group I, sham); sham hemorrhage and 50 microg/kg rhIL-11 (group II, sham + IL-11); no drug (group III, saline); or 50 microg/kg rhIL-11 (group IV, IL-11). Blood and urine samples were obtained and analyzed at baseline, at the end of hemorrhaging, and thereafter once every hour. The pleural and peritoneal effusions were precisely quantified by using clinically accepted criteria. The mean arterial pressure (MAP) was higher postresuscitation (PR) in groups I, II, and IV (71.4 +/- 7.5 mmHg, 71.0 +/- 8.9 mmHg, and 72.9 +/- 12.3 mmHg, respectively) than in group III (59.9 +/- 10.9 mmHg), and the cardiac output of PR was higher in group IV (3.46 +/- 0.56 L/min) than in group III (2.99 +/- 0.62 L/min; P < 0.01). The difference in MAP between groups I and II became statistically significant at 40 min after rhIL-11 injection and such a difference persisted for 90 min. After resuscitation, the urine output was higher, and the urine specific gravity and third space fluid loss were lower in group IV (1434 +/- 325 mL and 1.0035, 82 +/- 21 mL) than in group III (958 +/- 390 mL and 1.0053, 125 +/- 32 mL; P < 0.05). In a porcine model of hemorrhagic shock, the administration of rhIL-11 at the start of resuscitation significantly improved the cardiac output and blood pressure. This

Administration of Rhodiola kirilowii Extracts during Mouse Pregnancy and Lactation Stimulates Innate but Not Adaptive Immunity of the Offspring

PubMed Central

Skopińska-Różewska, Ewa; Brewczyńska, Aleksandra

2017-01-01

The use of antibiotics during pregnancy and lactation is associated with an increased risk of developmental disorders. One of the natural medicinal plants—Rhodiola kirilowii, widely used as an immunostimulant in adults—might be a good alternative to antibiotic treatment. The aim of present study was to assess whether daily oral administration of 20 mg/kg of Rhodiola kirilowii aqueous (RKW) or 50% hydroalcoholic (RKW-A) extracts affected hematological and immunological parameters of 6-week-old mouse progeny. There was no significant change in hematological parameters of blood with the exception of hemoglobin, which was significantly higher (about 4%) in RKW group. Offspring of mothers fed Rhodiola kirilowii extracts had increased percentage of granulocytes and decreased percentage of lymphocytes. These changes correlated with decreased percentage of CD3+/CD4+ T-cells (RKW and RKW-A), decrease of CD8+ cells, and increase percentage of NK cells in RKW group. In addition, both types of Rhodiola kirilowii extracts stimulated granulocyte phagocytosis and increased level of respiratory burst. In conclusion, the long-term supplementation of mouse mothers during pregnancy and lactation with RKW or RKW-A extracts affects the immune system of their progeny. These results should be taken into consideration before administration of Rhodiola kirilowii to pregnant and lactating women. PMID:29214185

Brain regions mediating α3β4 nicotinic antagonist effects of 18-MC on nicotine self-administration

PubMed Central

Glick, Stanley D.; Sell, Elizabeth M.; McCallum, Sarah E; Maisonneuve, Isabelle M.

2011-01-01

18-methoxycoronaridine (18-MC), a putative anti-addictive agent, has been shown to decrease the self-administration of several drugs of abuse in rats. 18-MC is a potent antagonist at α3β4 nicotinic receptors. Consistent with high densities of α3β4 nicotinic receptors being located in the medial habenula and the interpeduncular nucleus, 18-MC has been shown to act in these regions to decrease both morphine and methamphetamine self-administration. The present study was conducted to determine if 18-MC’s effect on nicotine self-administration is mediated by acting in these same brain regions. Because moderate densities of α3β4 receptors occur in the dorsolateral tegmentum, ventral tegmental area, and basolateral amygdala, these brain areas were also examined as potential sites of action of 18-MC. Local administration of 18-MC into either the medial habenula, the basolateral amygdala or the dorsolateral tegmentum decreased nicotine self-administration. Surprisingly, local administration of 18-MC into the interpeduncular nucleus increased nicotine self-administration while local administration of 18-MC into the ventral tegmental area had no effect on nicotine self-administration. Similar effects were produced by local administration of either mecamylamine or conotoxin AuIB. These data are consistent with the hypothesis that 18-MC decreases nicotine self-administration by indirectly modulating the dopaminergic mesolimbic pathway via blockade of α3β4 nicotinic receptors in the medial habenula, basolateral amygdala, and dorsolateral tegmentum. The data also suggest that an action of 18-MC in the interpeduncular nucleus may attenuate aversive and/or depressive effects of nicotine. PMID:21871879

Decrease in oral bioavailability of ciclosporin by intravenous pulse of methylprednisolone succinate in rats.

PubMed

Konishi, Hiroki; Sumi, Masaki; Shibata, Nobuhito; Takada, Kanji; Minouchi, Tokuzo; Yamaji, Akira

2004-10-01

We examined the effects of high-dose methylprednisolone on the bioavailability of orally administered ciclosporin in rats. To emulate the clinical protocol of methylprednisolone pulse therapy, methylprednisolone sodium succinate (MPS), a prodrug of methylprednisolone, was intravenously administered as repeated doses (66.3 mg kg(-1)) for 3 days. The area under the blood ciclosporin concentration versus time curve after oral administration was significantly reduced by 60% by pulse treatment with MPS. Based on our previous finding that the total body clearance of ciclosporin was reduced by about 20% by the same methylprednisolone pulse protocol, the extent of reduction in the oral bioavailability of ciclosporin was estimated to be approximately 50%, indicating a drug interaction between high-dose methylprednisolone and orally administered ciclosporin, which affected the absorption process. In rats treated with MPS, an in-situ efflux experiment using rhodamine-123 demonstrated that the reverse transport function of P-glycoprotein (P-gp) in the small intestine was significantly enhanced, although there was no significant increase in the intestinal microsomal activity of triazolam alpha- and 4-hydroxylation, metabolic probes for CYP3A. In addition, a significant decrease was observed in the amount of secreted bile acids serving as an enhancer of gastrointestinal absorption of ciclosporin in MPS treatment. To directly estimate the absorptive capacity, an in-situ absorption test was conducted using a closed-loop of small intestine in control and MPS-treated rats. Intestinal absorption of ciclosporin was significantly decreased, not only in the absence of bile flow but also by treatment with MPS, which well reflected the change in the in-vivo pharmacokinetic behaviour of ciclosporin after methylprednisolone pulsing. These results demonstrate that bioavailability of ciclosporin is markedly reduced by MPS pulse treatment, and the mechanism of this interaction was confirmed to

Lauroyl-L-aspartate decreased food intake and body temperature in neonatal chicks.

PubMed

Erwan, E; Chowdhury, V S; Ito, K; Furuse, M

2013-11-15

We hypothesized that the effects of L- and D-amino acids might be influenced when conjugated with fatty acid. Thus, the effects of oral administration of lauroyl-L-aspartate (Lau-L-Asp) as well as lauroyl-D-aspartate (Lau-D-Asp) were examined. In Experiment 1, oral administration of both Lau-L-Asp and Lau-D-Asp decreased food intake while L- or D-Asp did not influence food intake. Interestingly, only Lau-L-Asp decreased body temperature. Experiment 2 was conducted to determine whether non-conjugated mixture of L-Asp plus lauric acid has same effects under ad libitum feeding conditions. Lau-L-Asp decreased food intake and body temperature, but L-Asp plus lauric acid did not show any effect studied. In Experiment 3, we found that Lau-L-Asp declined food intake as well as time-dependently suppressed the body temperature in fasted chicks. However, L-Asp plus lauric acid did not show any effect. These results suggest that Lau-L-Asp may exert anorexigenic and hypothermic actions in chicks. © 2013.

Safety of perioperative ketorolac administration in pediatric appendectomy.

PubMed

Naseem, Hibbut-Ur-Rauf; Dorman, Robert Michael; Ventro, George; Rothstein, David H; Vali, Kaveh

2017-10-01

postoperative infection or transabdominal drainage (1% in the uncomplicated group and 5% in the complicated group). Median postoperative LOS was 1 d and mean cost was $9811 ± $9509. On bivariate analysis, ketorolac administration was associated with a decrease in same-visit surgical complications (P = 0.004) and cost ($459 decrease, P < 0.001) but was not associated with readmission, postoperative LOS, or postoperative infection. On multivariate analysis, ketorolac administration was associated with a significant decrease in any complication (adjusted odds ratio 0.89, 95% confidence interval 0.80-0.99) and cost (analysis of variance P < 0.001) but was not associated with readmission, postoperative LOS, or postoperative infection. Based on a large, contemporary data set from children's hospitals, ketorolac administration in the immediate postoperative period after appendectomy for appendicitis is common and was not associated with an increase in postoperative LOS, postoperative infection, or any-cause 30-d readmission. Ketorolac was, however, independently associated with a lower overall rate of postoperative complications and cost in this population. Copyright © 2017 Elsevier Inc. All rights reserved.

Administration of dried Aloe vera gel powder reduced body fat mass in diet-induced obesity (DIO) rats.

PubMed

Misawa, Eriko; Tanaka, Miyuki; Nabeshima, Kazumi; Nomaguchi, Kouji; Yamada, Muneo; Toida, Tomohiro; Iwatsuki, Keiji

2012-01-01

The aim of the present study was to investigate the anti-obesity effects of Aloe vera gel administration in male Sprague-Dawley (SD) rats with diet-induced obesity (DIO). SD rats at 7 wk of age were fed either a standard diet (10 kcal% fat) (StdD) or high-fat (60 kcal% fat) diet (HFD) during the experimental period. Four weeks after of HFD-feeding, DIO rats (11 wk of age) were orally administered with two doses of Aloe vera gel powder (20 and 200 mg/kg/d) for 90 d. Body weights (g) and body fat (%) of HFD fed rats were significantly higher than those of StdD-fed rats. Although a modest decrease of body weight (g) was observed with the administration of dried Aloe vera gel powder, both subcutaneous and visceral fat weight (g) and body fat (%) were reduced significantly in Aloe vera gel-treated rats. Serum lipid parameters elevated by HFD were also improved by the Aloe vera gel treatment. The oxygen consumption (VO(2)), an index of energy expenditure, was decreased in HFD-fed rats compared with that in StdD-fed rats. Administration of Aloe vera gel reversed the change in VO(2) in the HFD-fed rats. These results suggest that intake of Aloe vera gel reduced body fat accumulation, in part, by stimulation of energy expenditure. Aloe vera gel might be beneficial for the prevention and improvement of diet-induced obesity.

Protective effect of alpha-lipoic acid in methotrexate-induced ovarian oxidative injury and decreased ovarian reserve in rats.

PubMed

Soylu Karapinar, Oya; Pinar, Neslihan; Özcan, Oğuzhan; Özgür, Tümay; Dolapçıoğlu, Kenan

2017-08-01

To determine whether the possible oxidative effect of methotrexate (Mtx) on ovary and to evaluate the effectiveness of alpha lipoic acid (ALA), which may be useful in many oxidative stress models. Thirty-two female Wistar-albino rats were randomly divided into four groups; control group, alpha lipoic acid group (ALA 100 mg/kg, 10 days), multiple dose Mtx group (Mtx 1 mg/kg 1, 3, 5, 7 days) and Mtx and ALA group (Mtx 1 mg/kg 1, 3, 5, 7 days and ALA 100 mg/kg, 10 days). Serum total antioxidant status (TAS), total oxidant status (TOS) and oxidative stress index (OSI), tumor necrosis factor-alpha (TNF-α), tissue malondialdehyde (MDA) and activities of glutathione peroxidase (GSH-Px) and catalase (CAT) and anti-Mullerian hormone (AMH) and total ovarian follicle count were evaluated. Mtx administration caused a significant decrease in TAS, a significant increase in TOS and OSI, a significant increase in MDA levels and a decrease in GSH-Px and CAT activity. Moreover the proinflammatory cytokine (TNF-α) was increased in the Mtx group. And AMH values and total follicle count were significantly decreased in Mtx group. However, ALA treatment reversed biochemical results and AMH levels and total follicle count. Alpha lipoic acid ameliorates methotrexate induced oxidative damage of ovarian in rats.

Effect of Gymnema sylvestre Administration on Metabolic Syndrome, Insulin Sensitivity, and Insulin Secretion.

PubMed

Zuñiga, Laura Y; González-Ortiz, Manuel; Martínez-Abundis, Esperanza

2017-08-01

Gymnema sylvestre is a medicinal plant whose consumption has demonstrated benefits on lipid and glucose levels, blood pressure, and body weight (BWt). The aim of this study was to evaluate the effect of G. sylvestre administration on metabolic syndrome (MetS), insulin secretion, and insulin sensitivity. A randomized, double-blind, placebo-controlled clinical trial was carried out in 24 patients (without pharmacological treatment), 30-60 years old, with diagnosis of MetS in accordance with the modified International Diabetes Federation criteria. Patients were randomly assigned to receive G. sylvestre or placebo twice daily before breakfast and dinner in 300 mg capsules for a total of 600 mg per day for 12 weeks. Before and after the intervention, the components of MetS were evaluated as well as BWt, body mass index (BMI), total cholesterol, low-density lipoprotein cholesterol, and very low-density lipoprotein (VLDL). Area under the curve of glucose and insulin, phases of insulin secretion, and insulin sensitivity were calculated. Statistical analysis was performed using Wilcoxon signed-rank, Mann-Whitney U, and chi-square tests; P ≤ .05 was considered statistically significant. After G. sylvestre administration, significant decreases in BWt (81.3 ± 10.6 kg vs. 77.9 ± 8.4 kg, P = .02), BMI (31.2 ± 2.5 kg/m 2 vs. 30.4 ± 2.2 kg/m 2 , P = .02), and VLDL levels (0.45 ± 0.15 mmol/dL vs. 0.35 ± 0.15 mmol/dL, P = .05) were observed, without modifying the components of MetS, insulin secretion, and insulin sensitivity. In conclusion, G. sylvestre administration decreased BWt, BMI, and VLDL levels in subjects with MetS, without changes in insulin secretion and insulin sensitivity.

Integrating technology to improve medication administration.

PubMed

Prusch, Amanda E; Suess, Tina M; Paoletti, Richard D; Olin, Stephen T; Watts, Starann D

2011-05-01

The development, implementation, and evaluation of an i.v. interoperability program to advance medication safety at the bedside are described. I.V. interoperability integrates intelligent infusion devices (IIDs), the bar-code-assisted medication administration system, and the electronic medication administration record system into a bar-code-driven workflow that populates provider-ordered, pharmacist-validated infusion parameters on IIDs. The purpose of this project was to improve medication safety through the integration of these technologies and decrease the potential for error during i.v. medication administration. Four key phases were essential to developing and implementing i.v. interoperability: (a) preparation, (b) i.v. interoperability pilot, (c) preliminary validation, and (d) expansion. The establishment of pharmacy involvement in i.v. interoperability resulted in two additional safety checks: pharmacist infusion rate oversight and nurse independent validation of the autoprogrammed rate. After instituting i.v. interoperability, monthly compliance to the telemetry drug library increased to a mean ± S.D. of 72.1% ± 2.1% from 56.5% ± 1.5%, and the medical-surgical nursing unit's drug library monthly compliance rate increased to 58.6% ± 2.9% from 34.1% ± 2.6% (p < 0.001 for both comparisons). The number of manual pump edits decreased with both telemetry and medical-surgical drug libraries, demonstrating a reduction from 56.9 ± 12.8 to 14.2 ± 3.9 and from 61.2 ± 15.4 to 14.7 ± 3.8, respectively (p < 0.001 for both comparisons). Through the integration and incorporation of pharmacist oversight for rate changes, the telemetry and medical-surgical patient care areas demonstrated a 32% reduction in reported monthly errors involving i.v. administration of heparin. By integrating two stand-alone technologies, i.v. interoperability was implemented to improve medication administration. Medication errors were reduced, nursing workflow was simplified, and

78 FR 69985 - Irish Potatoes Grown in Colorado; Decreased Assessment Rate for Area No. 2

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-22

...; FV13-948-2 IR] Irish Potatoes Grown in Colorado; Decreased Assessment Rate for Area No. 2 AGENCY... decreases the assessment rate established for the Colorado Potato Administrative Committee, Area No. 2... potatoes handled. The Committee locally administers the marketing order, which regulates the handling of...

Newborn Hypoxia/Anoxia Inhibits Cardiomyocyte Proliferation and Decreases Cardiomyocyte Endowment in the Developing Heart: Role of Endothelin-1

PubMed Central

Paradis, Alexandra N.; Gay, Maresha S.; Wilson, Christopher G.; Zhang, Lubo

2015-01-01

In the developing heart, cardiomyocytes undergo terminal differentiation during a critical window around birth. Hypoxia is a major stress to preterm infants, yet its effect on the development and maturation of the heart remains unknown. We tested the hypothesis in a rat model that newborn anoxia accelerates cardiomyocyte terminal differentiation and results in reduced cardiomyocyte endowment in the developing heart via an endothelin-1-dependent mechanism. Newborn rats were exposed to anoxia twice daily from postnatal day 1 to 3, and hearts were isolated and studied at postnatal day 4 (P4), 7 (P7), and 14 (P14). Anoxia significantly increased HIF-1α protein expression and pre-proET-1 mRNA abundance in P4 neonatal hearts. Cardiomyocyte proliferation was significantly decreased by anoxia in P4 and P7, resulting in a significant reduction of cardiomyocyte number per heart weight in the P14 neonates. Furthermore, the expression of cyclin D2 was significantly decreased due to anoxia, while p27 expression was increased. Anoxia has no significant effect on cardiomyocyte binucleation or myocyte size. Consistently, prenatal hypoxia significantly decreased cardiomyocyte proliferation but had no effect on binucleation in the fetal heart. Newborn administration of PD156707, an ETA-receptor antagonist, significantly increased cardiomyocyte proliferation at P4 and cell size at P7, resulting in an increase in the heart to body weight ratio in P7 neonates. In addition, PD156707 abrogated the anoxia-mediated effects. The results suggest that hypoxia and anoxia via activation of endothelin-1 at the critical window of heart development inhibits cardiomyocyte proliferation and decreases myocyte endowment in the developing heart, which may negatively impact cardiac function later in life. PMID:25692855

Using lean to improve medication administration safety: in search of the "perfect dose".

PubMed

Ching, Joan M; Long, Christina; Williams, Barbara L; Blackmore, C Craig

2013-05-01

At Virginia Mason Medical Center (Seattle), the Collaborative Alliance for Nursing Outcomes (CALNOC) Medication Administration Accuracy Quality Study was used in combination with Lean quality improvement efforts to address medication administration safety. Lean interventions were targeted at improving the medication room layout, applying visual controls, and implementing nursing standard work. The interventions were designed to prevent medication administration errors through improving six safe practices: (1) comparing medication with medication administration record, (2) labeling medication, (3) checking two forms of patient identification, (4) explaining medication to patient, (5) charting medication immediately, and (6) protecting the process from distractions/interruptions. Trained nurse auditors observed 9,244 doses for 2,139 patients. Following the intervention, the number of safe-practice violations decreased from 83 violations/100 doses at baseline (January 2010-March 2010) to 42 violations/100 doses at final follow-up (July 2011-September 2011), resulting in an absolute risk reduction of 42 violations/100 doses (95% confidence interval [CI]: 35-48), p < .001). The number of medication administration errors decreased from 10.3 errors/100 doses at baseline to 2.8 errors/100 doses at final follow-up (absolute risk reduction: 7 violations/100 doses [95% CI: 5-10, p < .001]). The "perfect dose" score, reflecting compliance with all six safe practices and absence of any of the eight medication administration errors, improved from 37 in compliance/100 doses at baseline to 68 in compliance/100 doses at the final follow-up. Lean process improvements coupled with direct observation can contribute to substantial decreases in errors in nursing medication administration.

Selective Perioperative Administration of Pasireotide is More Cost-Effective Than Routine Administration for Pancreatic Fistula Prophylaxis.

PubMed

Denbo, Jason W; Slack, Rebecca S; Bruno, Morgan; Cloyd, Jordan M; Prakash, Laura; Fleming, Jason B; Kim, Michael P; Aloia, Thomas A; Vauthey, Jean-Nicolas; Lee, Jeffrey E; Katz, Matthew H G

2017-04-01

In a randomized trial, pasireotide significantly decreased the incidence and severity of postoperative pancreatic fistula (POPF). Subsequent analyses concluded that its routine use is cost-effective. We hypothesized that selective administration of the drug to patients at high risk for POPF would be more cost-effective. Consecutive patients who did not receive pasireotide and underwent pancreatoduodenectomy (PD) or distal pancreatectomy (DP) between July 2011 and January 2014 were distributed into groups based on their risk of POPF using a multivariate recursive partitioning regression tree analysis (RPA) of preoperative clinical factors. The costs of treating hypothetical patients in each risk group were then computed based upon actual institutional hospital costs and previously published relative risk values associated with pasireotide. Among 315 patients who underwent pancreatectomy, grade B/C POPF occurred in 64 (20%). RPA allocated patients who underwent PD into four groups with a risk for grade B/C POPF of 0, 10, 29, or 60% (P < 0.001) on the basis of diagnosis, pancreatic duct diameter, and body mass index. Patients who underwent DP were allocated to three groups with a grade B/C POPF risk of 14, 26, or 44% (P = 0.05) on the basis of pancreatic duct diameter alone. Although the routine administration of pasireotide to all 315 patients would have theoretically saved $30,892 over standard care, restriction of pasireotide to only patients at high risk for POPF would have led to a cost savings of $831,916. Preoperative clinical characteristics can be used to characterize patients' risk for POPF following pancreatectomy. Selective administration of pasireotide only to patients at high risk for grade B/C POPF may maximize the cost-efficacy of prophylactic pasireotide.

MitoQ modulates oxidative stress and decreases inflammation following hemorrhage.

PubMed

Powell, Rebecca D; Swet, Jacob H; Kennedy, Kenneth L; Huynh, Toan T; Murphy, Michael P; Mckillop, Iain H; Evans, Susan L

2015-03-01

Oxidative stress associated with hemorrhagic shock and reperfusion (HSR) results in the production of superoxide radicals and other reactive oxygen species, leading to cell damage and multiple-organ dysfunction. We sought to determine if MitoQ, a mitochondria-targeted antioxidant, reduces morbidity in a rat model of HSR by limiting oxidative stress. HSR was achieved in male rats by arterial blood withdrawal to a mean arterial pressure of 25 ± 2 mm Hg for 1 hour before resuscitation. MitoQ (5 mg/kg), TPP (triphenylphosphonium, 5 mg/kg) or saline (0.9% vol./vol.) was administered intravenously 30 minutes before resuscitation, followed by an intraperitoneal administration (MitoQ, 20 mg/kg) immediately after resuscitation (n = 5 per group). Morbidity was assessed based on cumulative markers of animal distress (0-10 scale). Rats were sacrificed 2 hours after procedure completion, and liver tissue was collected and processed for histology or assayed for lipid peroxidation (thiobarbituric acid reactive substance [TBARS]) or endogenous antioxidant (catalase, glutathione peroxidase [GPx], and superoxide dismutase) activity. HSR significantly increased morbidity as well as TBARS and catalase activities versus sham. Conversely, no difference in GPx or superoxide dismutase activity was measured between sham, HSR, and TPP, MitoQ administration reduced morbidity versus HSR (5.8 ± 0.3 vs. 7.6 ± 0.3; p < 0.05), while TPP administration significantly reduced hepatic necrosis versus both HSR and HSR-MitoQ (1.2 ± 0.1 vs. 2.0 ± 0.2 vs. 1.9 ± 0.2; p < 0.05, n = 5). Analysis of oxidative stress demonstrated increased TBARS and GPx in HSR-MitoQ versus sham (12.0 ± 1.1 μM vs. 6.2 ± 0.5 μM and 37.9 ± 3.0 μmol/min/mL vs. 22.9 ± 2.7 μmol/min/mL, TBARS and GPx, respectively, n = 5; p < 0.05). Conversely, catalase activity in HSR-MitoQ was reduced versus HSR (1.96 ± 1.17 mol/min/mL vs. 2.58 ± 1.81 mol/min/mL; n = 5; p < 0.05). Finally, MitoQ treatment decreased tumor necrosis

Effect of oral ketoconazole on first-pass effect of nifedipine after oral administration in dogs.

PubMed

Kuroha, Masanori; Kayaba, Hideki; Kishimoto, Shizuka; Khalil, Waleed F; Shimoda, Minoru; Kokue, Eiichi

2002-03-01

The long-term oral ketoconazole (KTZ) treatment extensively inhibits hepatic CYP3A activity. We investigated the effect of the KTZ treatment on hepatic and intestinal extraction of nifedipine (NIF) using beagle dogs. Four dogs were given orally KTZ for 20 days (200 mg, bid). NIF was administered either intravenously (0.5 mg/kg) or orally (20 mg) 10 and 20 days before the KTZ treatment and 10 and 20 days after start of KTZ treatment. CLtot of NIF after intravenous administration decreased to about 50% during the KTZ treatment. C(max) and AUC after oral administration increased to 2.5-fold and fourfold, respectively, by the KTZ treatment. The hepatic extraction ratio of NIF decreased to about a half by KTZ. A significant decrease in intestinal extraction ratio was not observed. In conclusion, the KTZ treatment inhibits hepatic extraction more profoundly than intestinal extraction of NIF. Therefore, inhibition of hepatic extraction of NIF by the KTZ treatment mainly results in substantial increase in systemic bioavailability in dogs. Because KTZ inhibits human CYP3A activities similar to canine CYP3A activities, the long-term oral KTZ treatment may dramatically increase bioavailability of NIF or other CYP3A substrates in humans. Copyright 2002 Wiley-Liss, Inc. and the American Pharmaceutical Association.

Effects of oral administration of tilmicosin on pulmonary inflammation in piglets experimentally infected with Actinobacillus pleuropneumoniae.

PubMed

Nerland, Erin M; LeBlanc, Justin M; Fedwick, Jason P; Morck, Douglas W; Merrill, John K; Dick, Paul; Paradis, Marie-Anne; Buret, Andre G

2005-01-01

To determine the effects of oral administration of tilmicosin in piglets experimentally infected with Actinobacillus pleuropneumoniae. Forty 3-week-old specific-pathogen free piglets. Piglets were assigned to 1 of 4 groups as follows: 1) uninfected sham-treated control piglets; 2) infected untreated piglets that were intratracheally inoculated with 10(7) CFUs of A pleuropneumoniae; 3) infected treated piglets that were intratracheally inoculated with A pleuropneumoniae and received tilmicosin in feed (400 ppm [microg/g]) for 7 days prior to inoculation; or 4) infected treated piglets that were intratracheally inoculated with A pleuropneumoniae and received chlortetracycline (CTC) in feed (1100 ppm [microg/gl) for 7 days prior to inoculation. Bronchoalveolar lavage (BAL) fluid and lung tissue specimens of piglets for each group were evaluated at 3 or 24 hours after inoculation. For each time point, 4 to 6 piglets/group were studied. Feeding of CTC and tilmicosin decreased bacterial load in lungs of infected piglets. Tilmicosin delivered in feed, but not CTC, enhanced apoptosis in porcine BAL fluid leukocytes. This was associated with a decrease in LTB4 concentrations in BAL fluid of tilmicosin-treated piglets, compared with untreated and CTC-treated piglets, and also with a significant decrease in the number of pulmonary lesions. Tilmicosin inhibited infection-induced increases in rectal temperatures, as measured in untreated and CTC-treated piglets. Pulmonary neutrophil infiltration and prostaglandin E2 concentrations in the BAL fluid were not significantly different among groups at any time. Oral administration of tilmicosin to infected piglets induces apoptosis in BAL fluid leukocytes and decreases BAL fluid LTB4 concentrations and inflammatory lung lesions.

Reinforcing effectiveness of nicotine in nonhuman primates: effects of nicotine dose and history of nicotine self-administration.

PubMed

Kohut, Stephen J; Bergman, Jack

2016-07-01

Despite the high prevalence of nicotine use in humans, robust nicotine self-administration has been difficult to demonstrate in laboratory animals. A parametric analysis of nicotine self-administration was conducted to study its reinforcing effects in nonhuman primates. Adult rhesus macaques (N = 6) self-administered intravenous (IV) nicotine (0.001-0.1 mg/kg) under a fixed-ratio (FR)1 schedule of reinforcement during daily 90-min sessions. Next, the demand function relating drug intake and response cost was determined by increasing the FR across sessions during the availability of each of several unit doses of nicotine (0.0032-0.032 mg/kg/inj). The reinforcing effects of 0.01 mg/kg/inj cocaine and 1 g banana-flavored food pellets were also determined under similar testing conditions. Finally, the nicotine demand function was re-determined after approximately 8 months of daily IV nicotine self-administration. IV nicotine self-administration followed an inverted U-shaped pattern, with the peak number of injections maintained by 0.0032 mg/kg/inj. Self-administration of each reinforcer (food pellets, IV cocaine, and IV nicotine) decreased as FR size increased. Application of the exponential model of demand showed that demand elasticity for nicotine was (1) dose-dependent and lowest for 0.0032 mg/kg/inj; (2) for 0.0032 mg/kg/inj, similar to that of food pellets and significantly higher than cocaine; and (3) decreased after 8 months of daily nicotine self-administration. These data show that, though high levels of nicotine self-administration can be achieved under simple FR schedules in nonhuman primates, its reinforcing effectiveness is dose-related but limited and may increase over time.

Neuromuscular blocking agent administration for emergent tracheal intubation is associated with decreased prevalence of procedure-related complications.

PubMed

Wilcox, Susan R; Bittner, Edward A; Elmer, Jonathan; Seigel, Todd A; Nguyen, Nicole Thuy P; Dhillon, Anahat; Eikermann, Matthias; Schmidt, Ulrich

2012-06-01

Emergent intubation is associated with a high rate of complications. Neuromuscular blocking agents are routinely used in the operating room and emergency department to facilitate intubation. However, use of neuromuscular blocking agents during emergent airway management outside of the operating room and emergency department is controversial. We hypothesized that the use of neuromuscular blocking agents is associated with a decreased prevalence of hypoxemia and reduced rate of procedure-related complications. Five hundred sixty-six patients undergoing emergent intubations in two tertiary care centers, Massachusetts General Hospital, Boston, MA, and the University of California Los Angeles, Ronald Reagan Medical Center, Los Angeles, CA, were enrolled in a prospective, observational study. The 112 patients intubated during cardiopulmonary resuscitation were excluded, leaving 454 patients for analysis. All intubations were supervised by attendings trained in Critical Care Medicine. We measured intubating conditions, oxygen saturation during and 5 mins following intubation. We assessed the prevalence of procedure-related complications defined as esophageal intubation, traumatic intubation, aspiration, dental injury, and endobronchial intubation. The use of neuromuscular blocking agents was associated with a lower prevalence of hypoxemia (10.1% vs. 17.4%, p = .022) and a lower prevalence of procedure-related complications (3.1% vs. 8.3%, p = .012). This association persisted in a multivariate analysis, which controlled for airway grade, sedation, and institution. Use of neuromuscular blocking agents was associated with significantly improved intubating conditions (laryngeal view, p = .014; number of intubation attempts, p = .049). After controlling for the number of intubation attempts and laryngoscopic view, muscle relaxant use is an independent predictor of complications associated with emergency intubation (p = .037), and there is a trend towards improvement of

Intravenous administration of oxytocin in rats acutely decreases deprivation-induced chow intake, but it fails to affect consumption of palatable solutions.

PubMed

Klockars, Anica; Brunton, Chloe; Li, Lu; Levine, Allen S; Olszewski, Pawel K

2017-07-01

Despite its limited ability to cross the blood-brain barrier, peripherally administered oxytocin (OT) acutely decreases food intake, most likely via the brainstem and hypothalamic mechanisms. Studies performed to date have focused mainly on the effects of subcutaneous or intraperitoneal OT on the consumption of only solid calorie-dense diets (either standard or high-fat), whereas it is unknown whether, similarly to central OT, peripherally administered peptide reduces intake of calorie-dilute and non-caloric palatable solutions. In this project, we established that 0.1μg/kg intravenous (IV) OT is the lowest anorexigenic dose, decreasing deprivation-induced standard chow intake by ca. 40% in rats and its effect does not stem from aversion. We then used this dose in paradigms in which effects of centrally acting OT ligands on consumption of palatable solutions had been previously reported. We found that IV OT did not change episodic intake of individually presented palatable solutions containing 10% sucrose, 0.1% saccharin, combined 10% sucrose-0.1% saccharin or 4.1%. Intralipid and it failed to affect daily scheduled consumption of a sucrose solution in non-deprived rats. In a two-bottle choice test, IV OT did not shift animals' preference from sucrose to Intralipid. Finally, OT injected IV prior to the simultaneous presentation chow and a sucrose solution in food-deprived rats significantly decreased chow intake, whereas sugar water consumption remained unchanged. We conclude that IV OT reduces deprivation-induced chow intake without causing aversion, but the dose effective in decreasing energy-driven consumption of high-calorie food fails to affect consumption of palatable calorie-dilute solutions. Copyright © 2017 Elsevier Inc. All rights reserved.

Dandelion (Taraxacum officinale) decreases male rat fertility in vivo.

PubMed

Tahtamouni, Lubna H; Alqurna, Noor M; Al-Hudhud, Mariam Y; Al-Hajj, Hameed A

2011-04-26

Taraxacum officinale (L.) Weber ex F.H. Wigg. is commonly used in Jordan folk medicine for the treatment of panophthalmitis, chronic constipation, and diabetes. In addition, herbalists prescribe the aqueous extract of Taraxacum officinale to enhance male's fertility. The current work was undertaken to investigate the validity and/or invalidity of the aqueous extract of Taraxacum officinale on enhancing the reproductive activity in male rat. Thirty three adult male rats were divided into three groups. Experimental groups received the aqueous extract of Taraxacum officinale orally for 60 days in two different sublethal doses; 1/10 LD(50) as high dose and 1/20 LD(50) as low dose, whereas the control group received distilled water. The administration of the aqueous extract of Taraxacum officinale resulted in a significant decrease in testis weight in the two experimental groups in comparison to the control group but had no effect on body or organ weight. The extract of this plant caused a decrease of the following in the two experimental groups, compared to the control group: sperm count, motility and normal morphology, pregnancy rate and diameter and wall thickness of seminiferous tubules. Also, distortion of morphology of the seminiferous tubules and arrest in spermatogenesis was observed in the experimental groups. In addition, the percentage of sperm with damaged chromatin integrity was significantly higher in the two experimental groups. From the present study, we can conclude that the aqueous extract of Taraxacum officinale acts as an anti-fertility agent rather than a fertility booster as prescribed by Jordanian herbalists. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Mitigating errors caused by interruptions during medication verification and administration: interventions in a simulated ambulatory chemotherapy setting.

PubMed

Prakash, Varuna; Koczmara, Christine; Savage, Pamela; Trip, Katherine; Stewart, Janice; McCurdie, Tara; Cafazzo, Joseph A; Trbovich, Patricia

2014-11-01

Nurses are frequently interrupted during medication verification and administration; however, few interventions exist to mitigate resulting errors, and the impact of these interventions on medication safety is poorly understood. The study objectives were to (A) assess the effects of interruptions on medication verification and administration errors, and (B) design and test the effectiveness of targeted interventions at reducing these errors. The study focused on medication verification and administration in an ambulatory chemotherapy setting. A simulation laboratory experiment was conducted to determine interruption-related error rates during specific medication verification and administration tasks. Interventions to reduce these errors were developed through a participatory design process, and their error reduction effectiveness was assessed through a postintervention experiment. Significantly more nurses committed medication errors when interrupted than when uninterrupted. With use of interventions when interrupted, significantly fewer nurses made errors in verifying medication volumes contained in syringes (16/18; 89% preintervention error rate vs 11/19; 58% postintervention error rate; p=0.038; Fisher's exact test) and programmed in ambulatory pumps (17/18; 94% preintervention vs 11/19; 58% postintervention; p=0.012). The rate of error commission significantly decreased with use of interventions when interrupted during intravenous push (16/18; 89% preintervention vs 6/19; 32% postintervention; p=0.017) and pump programming (7/18; 39% preintervention vs 1/19; 5% postintervention; p=0.017). No statistically significant differences were observed for other medication verification tasks. Interruptions can lead to medication verification and administration errors. Interventions were highly effective at reducing unanticipated errors of commission in medication administration tasks, but showed mixed effectiveness at reducing predictable errors of detection in

Oral administration of probiotic bacteria (E. coli Nissle, E. coli O83, Lactobacillus casei) influences the severity of dextran sodium sulfate-induced colitis in BALB/c mice.

PubMed

Kokesová, A; Frolová, L; Kverka, M; Sokol, D; Rossmann, P; Bártová, J; Tlaskalová-Hogenová, H

2006-01-01

Our study examined whether repeated preventive oral administration of live probiotic bacterial strains Escherichia coli O83:K24:H31 (Ec O83), Escherichia coli Nissle 1917 O6:K5:H1 (Ec Nis) and Lactobacillus casei DN 114001 (Lc) can protect mice against dextran sodium sulfate (DSS)-induced colitis. A significant decrease in average symptom score was observed in Ec O83-, Ec Nis- and Lc-pretreated group (p < 0.05). Significant differences in body mass loss between Lc pretreated mice with DSS-induced colitis were found when compared with nontreated mice (p < 0.05). PBS pretreated mice had a significantly shorter colon than Ec O83-, Ec Nis- and Lc-pretreated mice (p < 0.05). Administration of Lc significantly decreased the severity of DSS induced histological marks of inflammation (p < 0.05). A significant difference (p < 0.05) was also found in specific IgA level against given probiotic in enteral fluid between colitic mice and healthy mice pretreated with Ec 083 and Ec Nis.

Learning mechanisms to limit medication administration errors.

PubMed

Drach-Zahavy, Anat; Pud, Dorit

2010-04-01

This paper is a report of a study conducted to identify and test the effectiveness of learning mechanisms applied by the nursing staff of hospital wards as a means of limiting medication administration errors. Since the influential report ;To Err Is Human', research has emphasized the role of team learning in reducing medication administration errors. Nevertheless, little is known about the mechanisms underlying team learning. Thirty-two hospital wards were randomly recruited. Data were collected during 2006 in Israel by a multi-method (observations, interviews and administrative data), multi-source (head nurses, bedside nurses) approach. Medication administration error was defined as any deviation from procedures, policies and/or best practices for medication administration, and was identified using semi-structured observations of nurses administering medication. Organizational learning was measured using semi-structured interviews with head nurses, and the previous year's reported medication administration errors were assessed using administrative data. The interview data revealed four learning mechanism patterns employed in an attempt to learn from medication administration errors: integrated, non-integrated, supervisory and patchy learning. Regression analysis results demonstrated that whereas the integrated pattern of learning mechanisms was associated with decreased errors, the non-integrated pattern was associated with increased errors. Supervisory and patchy learning mechanisms were not associated with errors. Superior learning mechanisms are those that represent the whole cycle of team learning, are enacted by nurses who administer medications to patients, and emphasize a system approach to data analysis instead of analysis of individual cases.

Treated domestic sewage irrigation significantly decreased the CH4, N2O and NH3 emissions from paddy fields with straw incorporation

NASA Astrophysics Data System (ADS)

Xu, Shanshan; Hou, Pengfu; Xue, Lihong; Wang, Shaohua; Yang, Linzhang

2017-11-01

Straw incorporation and domestic sewage irrigation have been recommended as an environmentally friendly agricultural practice and are widely used not only in China but also in other countries. The individual effects on yield and environmental impacts have been studied extensively, but the comprehensive effect when straw returning and domestic sewage irrigation are combined together has seldom been reported. This study was conducted to examine the effects of straw returning and domestic sewage irrigation on rice yields, greenhouse gas emissions (GHGs) and ammonia (NH3) volatilization from paddy fields from 2015 to 2016. The results showed that the rice yield was not affected by the irrigation water sources and straw returning under the same total N input, which was similar in both years. Due to the rich N in the domestic sewage, domestic sewage irrigation could reduce approximately 45.2% of chemical nitrogen fertilizer input without yield loss. Compared to straw removal treatments, straw returning significantly increased the CH4 emissions by approximately 7-9-fold under domestic sewage irrigation and 13-14-fold under tap water irrigation. Straw returning also increased the N2O emissions under the two irrigation water types. In addition, the seasonal NH3 volatilization loss was significantly increased by 88.8% and 61.2% under straw returning compared to straw removal in 2015 and 2016, respectively. However, domestic sewage irrigation could decrease CH4 emissions by 24.5-26.6%, N2O emissions by 37.0-39.0% and seasonal NH3 volatilization loss by 27.2-28.3% under straw returning compared to tap water irrigation treatments. Global warming potentials (GWP) and greenhouse gas intensities (GHGI) were significantly increased with straw returning compared with those of straw removal, while they were decreased by domestic sewage irrigation under straw returning compared to tap water irrigation. Significant interactions between straw returning and domestic sewage irrigation on

Intravenous Tranexamic Acid Decreases Allogeneic Transfusion Requirements in Periacetabular Osteotomy.

PubMed

Bryan, Andrew J; Sanders, Thomas L; Trousdale, Robert T; Sierra, Rafael J

2016-01-01

Bernese (Ganz) periacetabular osteotomy is associated with significant blood loss and the need for perioperative transfusion. Tranexamic acid decreases blood loss and minimizes transfusion rates in total joint arthroplasty. However, no reports have described its use in patients undergoing Bernese periacetabular osteotomy. This study reports the use of intravenous tranexamic acid in these patients. The study included 137 patients (150 hips) who underwent isolated periacetabular osteotomy at a single institution between 2003 and 2014. Of these, 68 patients (75 hips) received intravenous tranexamic acid 1 g at the time of incision and 1 g at the time of closure. A group of 69 patients (75 hips) served as control subjects who underwent periacetabular osteotomy without administration of intravenous tranexamic acid. Thromboembolic disease was defined as deep venous thrombosis or pulmonary embolism occurring within 6 weeks of surgery. Outcomes measured included transfusion requirements, pre- and postoperative hemoglobin values, operative times, and thromboembolic disease rates. Aspirin was used as the thromboembolic prophylactic regimen in 95% of patients. The rate of allogeneic transfusion was 0 in the tranexamic acid group compared with 21% in the control group (P=.0001). No significant difference was found in the autologous cell salvage requirement (.96 vs 1.01; P=.43) or the thromboembolic disease rate between the tranexamic acid group and the control group (2.67% vs 1.33%; P=.31). The use of intravenous tranexamic acid led to a decreased transfusion requirement with no increased risk of thromboembolic disease in this contemporary cohort of patients undergoing periacetabular osteotomy. Copyright 2016, SLACK Incorporated.

Effect of formulation- and administration-related variables on deposition pattern of nasal spray pumps evaluated using a nasal cast.

PubMed

Kundoor, Vipra; Dalby, Richard N

2011-08-01

To systematically evaluate the effect of formulation- and administration-related variables on nasal spray deposition using a nasal cast. Deposition pattern was assessed by uniformly coating a transparent nose model with Sar-Gel®, which changes from white to purple on contact with water. Sprays were subsequently discharged into the cast, which was then digitally photographed. Images were quantified using Adobe® Photoshop. The effects of formulation viscosity (which influences droplet size), simulated administration techniques (head orientation, spray administration angle, spray nozzle insertion depth), spray pump design and metering volume on nasal deposition pattern were investigated. There was a significant decrease in the deposition area associated with sprays of increasing viscosity. This appeared to be mediated by an increase in droplet size and a narrowing of the spray plume. Administration techniques and nasal spray pump design also had a significant effect on the deposition pattern. This simple color-based method provides quantitative estimates of the effects that different formulation and administration variables may have on the nasal deposition area, and provides a rational basis on which manufacturers of nasal sprays can base their patient instructions or post approval changes when it is impractical to optimize these using a clinical study.

A forskolin derivative, colforsin daropate hydrochloride, inhibits the decrease in cortical renal blood flow induced by noradrenaline or angiotensin II in anesthetized rats.

PubMed

Ogata, Junichi; Minami, Kouichiro; Segawa, Kayoko; Uezono, Yasuhito; Shiraishi, Munehiro; Yamamoto, Chikako; Sata, Takeyoshi; Sung-Teh, Kim; Shigematsu, Akio

2004-01-01

A forskolin derivative, colforsin daropate hydrochloride (CDH), acts directly on adenylate cyclase to increase the intracellular cyclic adenosine monophosphate levels which produce a positive inotropic effect and a lower blood pressure. However, little is known about the effects of CDH on the renal function. We used laser Doppler flowmetry to measure the cortical renal blood flow (RBF) in male Wistar rats given a continuous intravenous infusion of CDH and evaluated the effects of CDH on the noradrenaline (NA) and angiotensin II (AngII) induced increases in blood pressure and reductions in RBF. Continuous intravenous administration of CDH at 0.25 microg/kg/min did not affect the mean arterial pressure (MAP), but increased heart rate and RBF. Continuous intravenous administration of CDH at high doses (0.5-0.75 microg/kg/min) decreased the MAP, with little effect on the RBF. The administration of exogenous NA (1.7 microg/kg) increased the MAP and decreased the RBF. However, a bolus injection of NA did not decrease the RBF during continuous intravenous administration of CDH, and CDH did not affect the NA-induced increase in MAP. The administration of exogenous AngII (100 ng/kg) increased MAP and decreased RBF and heart rate, but a bolus injection of AngII did not decrease RBF during continuous intravenous administration of CDH. These results suggest that CDH plays a protective role against the pressor effects and the decrease in RBF induced by NA or AngII. Copyright 2004 S. Karger AG, Basel

5 CFR 894.511 - What are the QLEs that are consistent with decreasing my type of enrollment?

Code of Federal Regulations, 2010 CFR

2010-01-01

... 5 Administrative Personnel 2 2010-01-01 2010-01-01 false What are the QLEs that are consistent with decreasing my type of enrollment? 894.511 Section 894.511 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) FEDERAL EMPLOYEES DENTAL AND VISION...

5 CFR 894.511 - What are the QLEs that are consistent with decreasing my type of enrollment?

Code of Federal Regulations, 2011 CFR

2011-01-01

... 5 Administrative Personnel 2 2011-01-01 2011-01-01 false What are the QLEs that are consistent with decreasing my type of enrollment? 894.511 Section 894.511 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) FEDERAL EMPLOYEES DENTAL AND VISION...

Chronic administration during early adulthood does not alter the hormonally-dependent disruptive effects of delta-9-tetrahydrocannabinol (Δ9-THC) on complex behavior in female rats.

PubMed

Winsauer, Peter J; Sutton, Jessie L

2014-02-01

This study examined whether chronic Δ(9)-THC during early adulthood would produce the same hormonally-dependent deficits in learning that are produced by chronic Δ(9)-THC during adolescence. To do this, either sham-operated (intact) or ovariectomized (OVX) female rats received daily saline or 5.6 mg/kg of Δ(9)-THC i.p. for 40 days during early adulthood. Following chronic administration, and a drug-free period to train both a learning and performance task, acute dose-effect curves for Δ(9)-THC (0.56-10 mg/kg) were established in each of the four groups (intact/saline, intact/THC, OVX/saline and OVX/THC). The dependent measures of responding under the learning and performance tasks were the overall response rate and the percentage of errors. Although the history of OVX and chronic Δ(9)-THC in early adulthood did not significantly affect non-drug or baseline behavior under the tasks, acute administration of Δ(9)-THC produced both rate-decreasing and error-increasing effects on learning and performance behavior, and these effects were dependent on their hormone condition. More specifically, both intact groups were more sensitive to the rate-decreasing and error-increasing effects of Δ(9)-THC than the OVX groups irrespective of chronic Δ(9)-THC administration, as there was no significant main effect of chronic treatment and no significant interaction between chronic treatment (saline or Δ(9)-THC) and the dose of Δ(9)-THC administered as an adult. Post mortem examination of 10 brain regions also indicated there were significant differences in agonist-stimulated GTPγS binding across brain regions, but no significant effects of chronic treatment and no significant interaction between the chronic treatment and cannabinoid signaling. Thus, acute Δ(9)-THC produced hormonally-dependent effects on learning and performance behavior, but a period of chronic administration during early adulthood did not alter these effects significantly, which is contrary to what we

Evidence of thyroxine formation following iodine administration in Sprague-Dawley rats

NASA Technical Reports Server (NTRS)

Thrall, K. D.; Sauer, R. L.; Bull, R. J.

1992-01-01

Iodine (I2) has been proposed to be used as a water disinfectant on the manned space station. Previous work has shown that subchronic administration of I2 to Sprague-Dawley rats in drinking water significantly increases plasma thyroxine/triiodothyronine (T4/T3) levels. This is not observed with iodide (I-) treatment. The present study addresses the possibility that I2 reacts with deiodinated T4 metabolites in the gastrointestinal tract to resynthesize T4. Incubation of diiodothyronine (T2), T3, or reverse T3 with I2 in phosphate-buffered saline resulted in the formation of T4 as measured by radioimmunoassay. Washes from the initial segments of the small intestine of the rat show that substrates are present that react with I2 to produce T4. Single oral doses of I2 to rats produced significant dose-related increases in serum T4 and decreases in T3 concentrations after 2 h. Administration of an equivalent dose of I- did not alter significantly plasma T4 concentrations. Higher concentrations of a radioactive substance that bound a T4-specific antibody are present in plasma of animals treated with 125I2 compared to 125I-. These data support the hypothesis that I2 reacts with metabolites of thyroid hormone in the gastrointestinal tract to resynthesize T4 and elevate its levels in blood.

Administration of melatonin protects against acetylsalicylic acid-induced impairment of male reproductive function in mice

PubMed Central

Emami, Niloufar Hedayati; Lafout, Farzaneh Mahmoudi; Mohammadghasemi, Fahimeh

2018-01-01

Objective(s): Melatonin, an important hormone secreted by the epiphysis, is a powerful anti-oxidant with a high potential to neutralize medical toxins. The goal of this study was to demonstrate the beneficial effect of melatonin on epididymal sperm and reproductive parameters in mice treated with acetylsalicylic acid (ASA). Materials and Methods: Male adult mice were divided into four treatment groups: control, ASA, melatonin, and ASA+melatonin. Mice were administered ASA (50 mg/kg, orally) and/or melatonin (10 mg/kg, intraperitoneally), or vehicle control, for 14 days. Sperm count, sperm motility, and sperm morphology were evaluated to assess fertility. A colorimetric assay was used to measure serum total antioxidant capacity (TAC). A sperm chromatin dispersion (SCD) test was used to assess sperm chromatin integrity. Sex hormone levels were measured by ELISA. Results: Compared to the control group, ASA treatment resulted in a significant decrease in sperm parameters (P<0.05), as well as a decrease in the integrity of sperm chromatin (P<0.01). ASA treatment also reduced serum testosterone and TAC levels (P<0.05). Co-administration of melatonin with ASA significantly improved epididymal sperm parameters and increased serum testosterone and TAC levels compared to the ASA-treated group. LH level was not different in the combined treatment group compared to control or ASA treatment. Conclusion: Short-term administration of ASA (50 mg/kg) has adverse effects on male reproductive function in mice. Co-administration of melatonin protects against ASA-induced impairment of male reproductive function by preventing the reduction in serum TAC and testosterone levels seen with ASA treatment alone. PMID:29456808

Stereotactic Administration of Edaravone Ameliorates Collagenase-Induced Intracerebral Hemorrhage in Rat.

PubMed

Zhang, Yan; Yang, Yang; Zhang, Guang-Zhu; Gao, Mou; Ge, Guang-Zhi; Wang, Qin-Qin; Ji, Xin-Chao; Sun, Yi-Lin; Zhang, Hong-Tian; Xu, Ru-Xiang

2016-10-01

Edaravone is widely used for treating ischemic stroke, but it is not still confirmed in intracerebral hemorrhage (ICH) as an ideal medication targeting the brain parenchyma. We aimed to investigate the neuroprotective effects of stereotactic administration of edaravone (SI) into the brain parenchyma. Intracerebral hemorrhage rat models were established by infusion of collagenase into the caudate nucleus. Neural functional recovery was assessed using modified neurological severity scores (mNSS). A comparative study of therapeutic effects between SI and intraperitoneal injection of edaravone (IP) involved in cerebral edema, blood-brain barrier (BBB) permeability, hematoma absorption, inflammatory response and neuronal apoptosis. Compared with IP, the mNSS was significantly (P < 0.05) improved by SI; cerebral edema and BBB permeability were dramatically ameliorated (P < 0.05); IL-4 and IL-10 levels increased, but IL-1β and TNF-α levels significantly decreased; neuron apoptosis decreased markedly (P < 0.05); and caspase-3 and Bax expression significantly dropped, but Bcl-2 increased in SI group (P < 0.05). SI markedly improved neurological deficits in ICH rat models via antiinflammatory and antiapoptosis mechanisms and promoted M2-type microglia differentiation. SI was effective in rats with collagenase-induced ICH. © 2016 The Authors. CNS Neuroscience & Therapeutics Published by John Wiley & Sons Ltd.

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

PubMed

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

2001-02-01

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

Effects of introducing an administrative .05% blood alcohol concentration limit on law enforcement patterns and alcohol-related collisions in Canada.

PubMed

Blais, Étienne; Bellavance, François; Marcil, Alexandra; Carnis, Laurent

2015-09-01

Except for Quebec, all Canadian provinces have introduced administrative laws to lower the permitted blood alcohol concentration (BAC) to .05% or .04% for driving-or having the care of-a motor vehicle. Using linear mixed effects models for longitudinal data, this study evaluates the effect of administrative BAC laws on fatal alcohol related crashes and law enforcement patterns in Canada from 1987 to 2010. Results reveal a significant decrease of 3.7% (95% C.I.: 0.9-6.5%) in fatally injured drivers with a BAC level equal or greater than .05% following the introduction of these laws. Reductions were also observed for fatally injured drivers with BAC levels greater that .08% and .15%. The introduction of administrative BAC laws led neither to significant changes in the rate of driving while impaired (DWI) incidents reported by police officers nor in the probability of being charged for DWI under the Criminal Code. Copyright © 2015 Elsevier Ltd. All rights reserved.

The effects of co-administration of benzhexol on the peripheral pharmacokinetics of oral levodopa in young volunteers.

PubMed

Roberts, J; Waller, D G; von Renwick, A G; O'Shea, N; Macklin, B S; Bulling, M

1996-04-01

1. The effects of benzhexol on the absorption and pharmacokinetics of an oral dose of levodopa have been studied in 10 young healthy volunteers. Subjects were given a suspension of levodopa (250 mg) 90 min after either benzhexol (5 mg) or placebo in a randomized cross over design with doses separated by at least 1 week; on each occasion carbidopa was given 1 h before and 5 h after the dose of levodopa. Soluble paracetamol and radiolabelled DTPA were given with the levodopa as markers of gastric emptying. 2. Most subjects showed two peaks in the levodopa plasma concentration-time curve on the placebo day, with the second minor peak occurring 1-2 h after the dose. After benzhexol administration all subjects showed two or more peak levodopa concentrations in plasma. Benzhexol administration caused a significant decrease in the maximum concentration (43%; P < 0.05) of the initial peak and an increase (22%; P < 0.1) in the maximum concentration of the second peak. This change in absorption profile caused by benzhexol significantly altered the ratios of the second peak compared with the initial peak for both the maximum concentrations (P < 0.02) and for the AUC values (P < 0.05). Benzhexol administration did not affect the total AUC of levodopa (7.30 +/- 1.09 vs 7.19 +/- 1.26 micrograms ml-1 h; means +/- s.d.). 3. The plasma concentration-time curves for paracetamol showed similar profiles to those for levodopa and the ratios of the peak concentrations and AUC values for the second peak compared with the initial peak were increased significantly by benzhexol administration (P < 0.05). The total AUC of paracetamol was not affected by benzhexol administration (39.4 +/- 8.2 vs 40.0 +/- 8.9 micrograms ml-1 h; mean +/- s.d.) 4. Benzhexol altered the gastric emptying profile, shown by gamma-scintigraphy, with a reduced extent of initial emptying prior to the establishment of the plateau which is characteristic of levodopa administration in the fasting state. In consequence the

Decreased mental time travel to the past correlates with default-mode network disintegration under lysergic acid diethylamide.

PubMed

Speth, Jana; Speth, Clemens; Kaelen, Mendel; Schloerscheidt, Astrid M; Feilding, Amanda; Nutt, David J; Carhart-Harris, Robin L

2016-04-01

This paper reports on the effects of LSD on mental time travel during spontaneous mentation. Twenty healthy volunteers participated in a placebo-controlled crossover study, incorporating intravenous administration of LSD (75 μg) and placebo (saline) prior to functional magnetic resonance imaging (fMRI). Six independent, blind judges analysed mentation reports acquired during structured interviews performed shortly after the functional magnetic resonance imaging (fMRI) scans (approximately 2.5 h post-administration). Within each report, specific linguistic references to mental spaces for the past, present and future were identified. Results revealed significantly fewer mental spaces for the past under LSD and this effect correlated with the general intensity of the drug's subjective effects. No differences in the number of mental spaces for the present or future were observed. Consistent with the previously proposed role of the default-mode network (DMN) in autobiographical memory recollection and ruminative thought, decreased resting-state functional connectivity (RSFC) within the DMN correlated with decreased mental time travel to the past. These results are discussed in relation to potential therapeutic applications of LSD and related psychedelics, e.g. in the treatment of depression, for which excessive reflection on one's past, likely mediated by DMN functioning, is symptomatic. © The Author(s) 2016.

Relationship between frequency of pilocarpine administration and salivary IgA level.

PubMed

Smith, D J; Taubman, M A; Ebersole, J L; King, W

1982-12-01

The effect of repetitive administration of pilocarpine nitrate on the salivary volume and salivary IgA concentration was studied in the NIH white hamster. One and one-half to three-fold increases in salivary volume, coupled with decreases of 1/3 to 2/3 in IgA concentration, occurred as the frequency of administration of pilocarpine increased.

Intestinal microbiota and oral administration of Enterococcus faecium associated with the growth performance of new-born piglets.

PubMed

Wang, Y B; Du, W; Fu, A K; Zhang, X P; Huang, Y; Lee, K H; Yu, K; Li, W F; Li, Y L

2016-09-01

The oral administration of Enterococcus faecium EF1 to new-born suckling and weaning piglets along with their growth performances and intestinal microbiota was investigated in this study. Twenty-four new-born piglets were initially divided into 2 groups. The probiotics group received 2 ml of 10% sterilised skimmed milk by oral gavage supplemented with 6×10(8) cfu/ml viable E. faecium EF1 at the first, the third and the fifth day after birth, while the control group received 2 ml of 10% sterilised skimmed milk without probiotics at the same time. Results showed that oral administration of E. faecium EF1 was associated with a remarkable increase on the body weight of piglets for both suckling and weaning periods, by 30.73% (P<0.01) and 320.84% (P<0.01), and also decreased the diarrhoea rate, by 43.21% (P<0.05) and 71.42% (P<0.05), respectively. In addition, 454-pyrosequencing analysis revealed that there was no significant difference in the intestinal microbial diversity of the suckling piglets between the two groups; nevertheless, when compared to the control group, the relative abundance of Firmicutes in the probiotics group was substantially augmented, while the relative abundance of Proteobacteria, Bacteroidetes and Fusobacteria diminished. However, results indicated that oral administration of E. faecium EF1 did not have any influence on the relative abundance of Firmicutes in weaning piglets rather than increasing the relative abundance of Bacteroidetes and decreasing the relative abundance of Proteobacteria. Furthermore, at the level of the Firmicutes phylum, the relative abundance of Lactobacillales in the probiotic group increased significantly. These findings suggest that oral administration of E. faecium EF1 to new-born piglets could improve the growth performance and intestinal microbiota of piglets for both suckling and weaning periods.

Mast cell stabilization decreases cardiomyocyte and LV function in dogs with isolated mitral regurgitation.

PubMed

Pat, Betty; Killingsworth, Cheryl; Chen, Yuanwen; Gladden, James D; Walcott, Greg; Powell, Pamela C; Denney, Thomas; Gupta, Himanshu; Desai, Ravi; Tillson, Michael; Dillon, A Ray; Dell'italia, Louis J

2010-09-01

Mast cells are increased in isolated mitral regurgitation (MR) in the dog and may mediate extracellular matrix loss and left ventricular (LV) dilatation. We tested the hypothesis that mast cell stabilization would attenuate LV remodeling and improve function in the MR dog. MR was induced in adult dogs randomized to no treatment (MR, n = 5) or to the mast cell stabilizer, ketotifen (MR + MCS, n = 4) for 4 months. LV hemodynamics were obtained at baseline and after 4 months of MR and magnetic resonance imaging (MRI) was performed at sacrifice. MRI-derived, serial, short-axis LV end-diastolic (ED) and end-systolic (ES) volumes, LVED volume/mass ratio, and LV 3-dimensional radius/wall thickness were increased in MR and MR + MCS dogs compared with normal dogs (n = 6) (P < .05). Interstitial collagen was decreased by 30% in both MR and MR + MCS versus normal dogs (P < .05). LV contractility by LV maximum time-varying elastance was significantly depressed in MR and MR + MCS dogs. Furthermore, cardiomyocyte fractional shortening was decreased in MR versus normal dogs and further depressed in MR + MCS dogs (P < .05). In vitro administration of ketotifen to normal cardiomyocytes also significantly decreased fractional shortening and calcium transients. Chronic mast cell stabilization did not attenuate eccentric LV remodeling or collagen loss in MR. However, MCS therapy had a detrimental effect on LV function because of a direct negative inotropic effect on cardiomyocyte function. Published by Elsevier Inc.

Effects of environmental enrichment on self-administration of the short-acting opioid remifentanil in male rats.

PubMed

Hofford, Rebecca S; Chow, Jonathan J; Beckmann, Joshua S; Bardo, Michael T

2017-12-01

Opioid abuse is a major problem around the world. Identifying environmental factors that contribute to opioid abuse and addiction is necessary for decreasing this epidemic. In rodents, environmental enrichment protects against the development of low dose stimulant self-administration, but studies examining the effect of enrichment and isolation (compared to standard housing) on the development of intravenous opioid self-administration have not been conducted. The present study investigated the role of environmental enrichment on self-administration of the short-acting μ-opioid remifentanil. Rats were raised in an enriched condition (Enr), standard condition (Std), or isolated condition (Iso) beginning at 21 days of age and were trained to lever press for 1 or 3 μg/kg/infusion remifentanil in young adulthood. Acquisition of self-administration and responding during increasing fixed ratio requirements were assessed, and a dose-response curve was generated. In all phases, Enr rats lever pressed significantly less than Std and Iso rats, with Enr rats pressing between 9 and 40% the amount of Iso rats. Enr rats did not acquire remifentanil self-administration when trained with 1 μg/kg/infusion, did not increase responding over increasing FR when trained at either dose, and their dose-response curves were flattened compared to Std and Iso rats. When expressed as economic demand curves, Enr rats displayed a decrease in both essential value (higher α) and reinforcer intensity (Q 0 ) compared to Std and Iso rats at the 1 μg/kg/infusion training dose. Environmental enrichment reduced remifentanil intake, suggesting that social and environmental novelty may protect against opioid abuse.

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…

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

PubMed

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

2010-11-01

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

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.

Momordica charantia Administration Improves Insulin Secretion in Type 2 Diabetes Mellitus.

PubMed

Cortez-Navarrete, Marisol; Martínez-Abundis, Esperanza; Pérez-Rubio, Karina G; González-Ortiz, Manuel; Villar, Miriam Méndez-Del

2018-02-12

An improvement in parameters of glycemic control has been observed with Momordica charantia in patients with type 2 diabetes mellitus (T2DM). It is unknown whether this improvement is through a modification of insulin secretion, insulin sensitivity, or both. We hypothesized that M. charantia administration can improve insulin secretion and/or insulin sensitivity in patients with T2DM, without pharmacological treatment. The objective of the study was to evaluate the effect of M. charantia administration on insulin secretion and sensitivity. A randomized, double-blinded, placebo-controlled, clinical trial was carried out in 24 patients who received M. charantia (2000 mg/day) or placebo for 3 months. A 2-h oral glucose tolerance test (OGTT) was done before and after the intervention to calculate areas under the curve (AUC) of glucose and insulin, total insulin secretion (insulinogenic index), first phase of insulin secretion (Stumvoll index), and insulin sensitivity (Matsuda index). In the M. charantia group, there were significant decreases in weight, body mass index (BMI), fat percentage, waist circumference (WC), glycated hemoglobin A1c (A1C), 2-h glucose in OGTT, and AUC of glucose. A significant increase in insulin AUC (56,562 ± 36,078 vs. 65,256 ± 42,720 pmol/L/min, P = .043), in total insulin secretion (0.29 ± 0.18 vs. 0.41 ± 0.29, P = .028), and during the first phase of insulin secretion (557.8 ± 645.6 vs. 1135.7 ± 725.0, P = .043) was observed after M. charantia administration. Insulin sensitivity was not modified with any intervention. In conclusion, M. charantia administration reduced A1C, 2-h glucose, glucose AUC, weight, BMI, fat percentage, and WC, with an increment of insulin AUC, first phase and total insulin secretion.

Access to a running wheel inhibits the acquisition of cocaine self-administration.

PubMed

Smith, Mark A; Pitts, Elizabeth G

2011-12-01

Physical activity decreases cocaine self-administration in laboratory animals and is associated with positive outcomes in substance abuse treatment programs; however, less is known about its efficacy in preventing the establishment of regular patterns of substance use in drug-naive individuals. The purpose of the present study was to examine the effects of access to a running wheel on the acquisition of cocaine self-administration in experimentally naive rats. Male, Long-Evans rats were obtained at weaning and assigned to sedentary (no wheel) or exercising (access to wheel) conditions immediately upon arrival. After six weeks, rats were surgically implanted with intravenous catheters and placed in operant conditioning chambers for 2 h/day for 15 consecutive days. Each session began with a noncontingent priming infusion of cocaine, followed by a free-operant period in which each response on the active lever produced an infusion of cocaine on a fixed ratio (FR1) schedule of reinforcement. For days 1-5, responding was reinforced with 0.25 mg/kg/infusion cocaine; for days 6-15, responding was reinforced with 0.75 mg/kg/infusion cocaine. In addition, all rats were calorically restricted during days 11-15 to 85% to 95% of their free-feeding body weight. Compared to sedentary rats, exercising rats acquired cocaine self-administration at a significantly slower rate and emitted significantly fewer active lever presses during the 15 days of behavioral testing. These data indicate that access to a running wheel inhibits the acquisition of cocaine self-administration, and that physical activity may be an effective intervention in substance abuse prevention programs. Copyright © 2011 Elsevier Inc. All rights reserved.

Acetazolamide-mediated decrease in strong ion difference accounts for the correction of metabolic alkalosis in critically ill patients

PubMed Central

Moviat, Miriam; Pickkers, Peter; van der Voort, Peter HJ; van der Hoeven, Johannes G

2006-01-01

Introduction Metabolic alkalosis is a commonly encountered acid–base derangement in the intensive care unit. Treatment with the carbonic anhydrase inhibitor acetazolamide is indicated in selected cases. According to the quantitative approach described by Stewart, correction of serum pH due to carbonic anhydrase inhibition in the proximal tubule cannot be explained by excretion of bicarbonate. Using the Stewart approach, we studied the mechanism of action of acetazolamide in critically ill patients with a metabolic alkalosis. Methods Fifteen consecutive intensive care unit patients with metabolic alkalosis (pH ≥ 7.48 and HCO3- ≥ 28 mmol/l) were treated with a single administration of 500 mg acetazolamide intravenously. Serum levels of strong ions, creatinine, lactate, weak acids, pH and partial carbon dioxide tension were measured at 0, 12, 24, 48 and 72 hours. The main strong ions in urine and pH were measured at 0, 3, 6, 12, 24, 48 and 72 hours. Strong ion difference (SID), strong ion gap, sodium–chloride effect, and the urinary SID were calculated. Data (mean ± standard error were analyzed by comparing baseline variables and time dependent changes by one way analysis of variance for repeated measures. Results After a single administration of acetazolamide, correction of serum pH (from 7.49 ± 0.01 to 7.46 ± 0.01; P = 0.001) was maximal at 24 hours and sustained during the period of observation. The parallel decrease in partial carbon dioxide tension was not significant (from 5.7 ± 0.2 to 5.3 ± 0.2 kPa; P = 0.08) and there was no significant change in total concentration of weak acids. Serum SID decreased significantly (from 41.5 ± 1.3 to 38.0 ± 1.0 mEq/l; P = 0.03) due to an increase in serum chloride (from 105 ± 1.2 to 110 ± 1.2 mmol/l; P < 0.0001). The decrease in serum SID was explained by a significant increase in the urinary excretion of sodium without chloride during the first 24 hours (increase in urinary SID: from 48.4 ± 15.1 to 85.3 ± 7

Neonatal manipulation of oxytocin prevents lipopolysaccharide-induced decrease in gene expression of growth factors in two developmental stages of the female rat.

PubMed

Bakos, Jan; Lestanova, Zuzana; Strbak, Vladimir; Havranek, Tomas; Bacova, Zuzana

2014-10-01

Oxytocin production and secretion is important for early development of the brain. Long-term consequences of manipulation of oxytocin system might include changes in markers of brain plasticity - cytoskeletal proteins and neurotrophins. The aim of the present study was (1) to determine whether neonatal oxytocin administration affects gene expression of nestin, microtubule-associated protein-2 (MAP-2), brain derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in the brain of two developmental stages of rat and (2) to evaluate whether neonatal oxytocin administration protects against lipopolysaccharide (LPS) induced inflammation. Neonatal oxytocin did not prevent a decrease of body weight in the LPS treated animals. Oxytocin significantly increased gene expression of BDNF in the right hippocampus in 21-day and 2-month old rats of both sexes. Gene expression of NGF and MAP-2 significantly increased in males treated with oxytocin. Both, growth factors and intermediate filament-nestin mRNA levels, were reduced in females exposed to LPS. Oxytocin treatment prevented a decrease in the gene expression of only growth factors. In conclusion, neonatal manipulation of oxytocin has developmental and sex-dependent effect on markers of brain plasticity. These results also indicate, that oxytocin may be protective against inflammation particularly in females. Copyright © 2014 Elsevier Ltd. All rights reserved.

Systemic administration of low dosage of tetanus toxin decreases cell proliferation and neuroblast differentiation in the mouse hippocampal dentate gyrus

PubMed Central

Yan, Bing Chun; Kim, In Hye; Park, Joon Ha; Ahn, Ji Hyeon; Cho, Jeong-Hwi; Chen, Bai Hui; Lee, Jae-Chul; Choi, Jung Hoon; Yoo, Ki-Yeon; Lee, Choong Hyun; Cho, Jun Hwi

2013-01-01

In the present study, we investigated the effect of Tetaus toxin (TeT) on cell proliferation and neuroblast differentiation using specific markers: 5-bromo-2-deoxyuridine (BrdU) as an exogenous marker for cell proliferation, Ki-67 as an endogenous marker for cell proliferation and doublecortin (DCX) as a marker for neuroblasts in the mouse hippocampal dentate gyrus (DG) after TeT treatment. Mice were intraperitoneally administered 2.5 and 10 ng/kg TeT and sacrificed 15 days after the treatment. In both the TeT-treated groups, no neuronal death occurred in any layers of the DG using neuronal nuclei (NeuN, a neuron nuclei maker) and Fluoro-Jade B (F-J B, a high-affinity fluorescent marker for the localization of neuronal degeneration). In addition, no significant change in glial activation in both the 2.5 and 10 ng/kg TeT-treated-groups was found by GFAP (a marker for astrocytes) and Iba-1 (a marker for microglia) immunohistochemistry. However, in the 2.5 ng/kg TeT-treated-group, the mean number of BrdU, Ki-67 and DCX immunoreactive cells, respectively, were apparently decreased compared to the control group, and the mean number of each in the 10 ng/kg TeT-treated-group was much more decreased. In addition, processes of DCX-immunoreactive cells, which projected into the molecular layer, were short compared to those in the control group. In brief, our present results show that low dosage (10 ng/kg) TeT treatment apparently decreased cell proliferation and neuroblast differentiation in the mouse hippocampal DG without distinct gliosis as well as any loss of adult neurons. PMID:24106509

[Morphometric anatomic study and clinical significance of lunate fossa].

PubMed

Aldemir, Cengiz; Önder, Merve; Doğan, Ali; Duygun, Fatih; Oğuz, Nurettin

2015-01-01

This study aims to investigate the depth, transverse and sagittal diameters of lunate fossa which is a significant structure of the wrist in terms of reducing the risk for volar plate screws, which are administered in distal radius fractures, from penetrating into the joint. Depth, transverse and sagittal diameters of lunate fossa in 50 right and 50 left adult dried radius bones without distal tip damage were measured by using MicroscribeG2X from the MicroScribe G series. Mean lunate fossa depth: left 2.419886±0.51 mm/right 2.543052±0.78 mm, mean lunate fossa sagittal diameter: left 19.656±1.57 mm/right 18.796±1.53 mm, mean lunate fossa transverse diameter: left 11.382±0.65 mm/right 11.106±0.91 mm. There was no statistically significant difference between right and left depth values of lunate fossa (p=0.320), whereas there was statistically significant difference between right and left transverse and sagittal diameters (p=0.006, p=0.048). Measurements involving depth of lunate fossa may guide the development of new anatomic plates and decrease complications like the penetration of screw into joint whilst volar plate administrations.

49 CFR 219.602 - FRA Administrator's determination of random drug testing rate.

Code of Federal Regulations, 2012 CFR

2012-10-01

... Random Alcohol and Drug Testing Programs § 219.602 FRA Administrator's determination of random drug... percentage rate for random drug testing must be 50 percent of covered employees. (b) The FRA Administrator's decision to increase or decrease the minimum annual percentage rate for random drug testing is based on the...

49 CFR 219.602 - FRA Administrator's determination of random drug testing rate.

Code of Federal Regulations, 2014 CFR

2014-10-01

... Random Alcohol and Drug Testing Programs § 219.602 FRA Administrator's determination of random drug... percentage rate for random drug testing must be 50 percent of covered employees. (b) The FRA Administrator's decision to increase or decrease the minimum annual percentage rate for random drug testing is based on the...

49 CFR 219.602 - FRA Administrator's determination of random drug testing rate.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Random Alcohol and Drug Testing Programs § 219.602 FRA Administrator's determination of random drug... percentage rate for random drug testing must be 50 percent of covered employees. (b) The FRA Administrator's decision to increase or decrease the minimum annual percentage rate for random drug testing is based on the...

49 CFR 219.602 - FRA Administrator's determination of random drug testing rate.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Random Alcohol and Drug Testing Programs § 219.602 FRA Administrator's determination of random drug... percentage rate for random drug testing must be 50 percent of covered employees. (b) The FRA Administrator's decision to increase or decrease the minimum annual percentage rate for random drug testing is based on the...

49 CFR 219.602 - FRA Administrator's determination of random drug testing rate.

Code of Federal Regulations, 2013 CFR

2013-10-01

... Random Alcohol and Drug Testing Programs § 219.602 FRA Administrator's determination of random drug... percentage rate for random drug testing must be 50 percent of covered employees. (b) The FRA Administrator's decision to increase or decrease the minimum annual percentage rate for random drug testing is based on the...

The timing of administration of a clinically relevant dose of losartan influences the healing process after contusion induced muscle injury.

PubMed

Kobayashi, Tetsuo; Uehara, Kenji; Ota, Shusuke; Tobita, Kimimasa; Ambrosio, Fabrisia; Cummins, James H; Terada, Satoshi; Fu, Freddie H; Huard, Johnny

2013-01-15

Losartan (Los) is a Food and Drug Administration-approved antihypertensive medication that has a well-tolerated side effect profile. We have demonstrated that treatment with Los immediately after injury was effective at promoting muscle healing and inducing an antifibrotic effect in a murine model of skeletal muscle injury. We initially investigated the minimum effective dose of Los administration immediately after injury and subsequently determined whether the timing of administering a clinically relevant dose of Los would influence its effectiveness at improving muscle healing after muscle injury. In the first part of this study, mice were administered 3, 10, 30, or 300 mg·kg(-1)·day(-1) of Los immediately after injury, and the healing process was evaluated histologically and physiologically 4 wk after injury. In the second study, the clinically relevant dose of 10 mg·kg(-1)·day(-1) was administered immediately or started at 3 or 7 days postinjury. The administration of 300 mg·kg(-1)·day(-1) immediately following injury led to a significant increase in muscle regeneration, a significant decrease in fibrosis, and an improvement in muscle function. Moreover, we observed a significant decrease in fibrosis and a significant increase in muscle regeneration at 4 wk postinjury, when the clinically relevant dose of 10 mg·kg(-1)·day(-1) was administered at 3 or 7 days postinjury. Functional evaluation also demonstrated a significant improvement compared with the injured untreated control when Los treatment was initiated 3 days after injury. Our study revealed accelerated muscle healing when the 300 mg·kg(-1)·day(-1) of Los was administered immediately after injury and a clinically relevant dose of 10 mg·kg(-1)·day(-1) of Los was administered at 3 or 7 days postinjury.

N-acetylaspartylglutamate Inhibits Heroin Self-Administration and Heroin-Seeking Behaviors Induced by Cue or Priming in Rats.

PubMed

Zhu, Huaqiang; Lai, Miaojun; Chen, Weisheng; Mei, Disen; Zhang, Fuqiang; Liu, Huifeng; Zhou, Wenhua

2017-08-01

Activation of presynaptic group II metabotropic glutamate receptors (mGluR2/3) inhibits drug reward and drug-seeking behavior, but the role of N-acetylaspartylglutamate (NAAG), an agonist of endogenous mGluR2/3, in heroin reward and heroin-seeking behavior remained unclear. Here, we aimed to explore the effects of exogenous NAAG on heroin self-administration and heroin-seeking behavior. First, rats were trained to self-administer heroin under a fixed ratio 1 (FR1) schedule for 10 days, then received NAAG (50 or 100 μg/10 μL in each nostril) in the absence or presence of LY341495 (1 mg/kg, i.p.), an antagonist of mGluR2/3, on day 11 and the effects of NAAG on heroin self-administration under FR1 were recorded for 3 consecutive days. Motivation was assessed in heroin self-administration under a progressive ratio schedule on day 11 in another 5 groups with the same doses of NAAG. Additional rats were withdrawn for 14 days after 14 days of heroin self-administration, then received the same pharmacological pretreatment and were tested for heroin-seeking behaviors induced by heroin priming or cues. The results showed that intranasal administration of NAAG significantly decreased intravenous heroin self-administration on day 12, but not on day 11. Pretreatment with LY341495 prior to testing on day 12 prevented the inhibitory effect of NAAG on heroin reinforcement. The break-point for reward motivation was significantly reduced by NAAG. Moreover, NAAG also significantly inhibited the heroin-seeking behaviors induced by heroin priming or cues and these were restored by pretreatment with LY341495. These results demonstrated that NAAG, via activation of presynaptic mGluR2/3, attenuated the heroin reinforcement, heroin motivational value, and heroin-seeking behavior, suggesting that it may be used as an adjunct treatment for heroin addiction.

Does the use of a brief cryotherapy intervention with analgesic administration improve pain management after total knee arthroplasty?

PubMed

Wittig-Wells, Deborah; Johnson, Ifeya; Samms-McPherson, Jacqueline; Thankachan, Soosan; Titus, Bobina; Jacob, Ani; Higgins, Melinda

2015-01-01

Prior studies have evaluated only the prolonged use of cryotherapy as a nonpharmacologic pain intervention. The purpose of this study was to determine whether a 30-minute application of cryotherapy at the time pain medication was given after a total knee arthroplasty (TKA) provided better pain relief than analgesic drugs alone. A pretest, posttest, randomized controlled trial study design with crossover was used to evaluate the effects of cryotherapy on postoperative pain and satisfaction with pain management. A convenience sample of postoperative knee replacement patients constituted participants in the study. Two sequential episodes of pain requiring analgesic administration were studied in each patient, one with a 30-minute cryotherapy application and the other without cryotherapy. Dependent variables were changes in pain (posttest minus pretest) and level of satisfaction with pain management. Data were analyzed with repeated-measures analysis of variance, with p < .05 considered significant. During two sequential treatments for postoperative pain, a total of 29 TKA patients received analgesic medication administration alone for one pain episode and analgesic medication administration with a brief cryotherapy administration for the other pain episode. No significant difference between the two treatments was found for changes in pain scores after the treatments or patient satisfaction with pain management (p > .05). The order in which the treatments were provided was found to be significant (p = .02) for scores on patient satisfaction with pain management, with cryotherapy as the treatment for the second pain episode having higher scores than when delivered for the first pain episode. Sixty minutes after analgesic administration with or without cryotherapy, average pain scores remained greater than 7. In TKA patients, the short-term application of cryotherapy with analgesic medication administration did not significantly decrease pain or improve patient

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

PubMed

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

2011-04-01

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

Plasma disposition and faecal excretion of oxfendazole, fenbendazole and albendazole following oral administration to donkeys.

PubMed

Gokbulut, Cengiz; Akar, Ferda; McKellar, Quintin A

2006-07-01

Fenbendazole (FBZ), oxfendazole (fenbendazole sulphoxide, FBZSO), and albendazole (ABZ) were administered orally to donkeys at 10mg/kg bodyweight. Blood and faecal samples were collected from 1 to 120 h post-treatment. The plasma and faecal samples were analysed by high performance liquid chromatography (HPLC). The parent molecule and its sulphoxide and sulphone (FBZSO(2)) metabolites did not reach detectable concentrations in any plasma samples following FBZ administration. ABZ was also not detected in any plasma samples, but its sulphoxide and sulphone metabolites were detected, demonstrating that ABZ was completely metabolised by first-pass mechanisms in donkeys. Maximum plasma concentrations (C(max)) of FBZSO (0.49microg/mL) and FBZSO(2) (0.60microg/mL) were detected at (t(max)) 5.67 and 8.00h, respectively, following administration of FBZSO. The area under the curve (AUC) of the sulphone metabolite (10.33microg h/mL) was significantly higher than that of the parent drug FBZSO (5.17microg h/mL). C(max) of albendazole sulphoxide (ABZSO) (0.08g/mL) and albendazole sulphone (ABZSO(2)) (0.04microg/mL) were obtained at 5.71 and 8.00h, respectively, following ABZ administration. The AUC of the sulphoxide metabolite (0.84microg h/mL) of ABZ was significantly higher than that of the sulphone metabolite (0.50microg h/mL). The highest dry-faecal concentrations of parent molecules were detected at 32, 34 and 30h for FBZSO, FBZ and ABZ, respectively. The sulphide metabolite was significantly higher than the parent molecule after FBZSO administration. The parent molecule was predominant in the faecal samples following FBZ administration. After ABZ administration, the parent molecule was significantly metabolised, probably by gastrointestinal microflora, to its sulphoxide metabolite (ABZSO) that showed a similar excretion profile to the parent molecule in the faecal samples. The AUC of the parent FBZ was significantly higher than that of FBZSO and ABZ in faeces. It is

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

PubMed

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

1991-04-01

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

Jejunal administration of glucose enhances acyl ghrelin suppression in obese humans

PubMed Central

Sidani, Reem M.; Garcia, Anna E.; Antoun, Joseph; Isbell, James M.; Abumrad, Naji N.

2016-01-01

Ghrelin is a gastric hormone that stimulates hunger and worsens glucose metabolism. Circulating ghrelin is decreased after Roux-en-Y gastric bypass (RYGB) surgery; however, the mechanism(s) underlying this change is unknown. We tested the hypothesis that jejunal nutrient exposure plays a significant role in ghrelin suppression after RYGB. Feeding tubes were placed in the stomach or jejunum in 13 obese subjects to simulate pre-RYGB or post-RYGB glucose exposure to the gastrointestinal (GI) tract, respectively, without the confounding effects of caloric restriction, weight loss, and surgical stress. On separate study days, the plasma glucose curves obtained with either gastric or jejunal administration of glucose were replicated with intravenous (iv) infusions of glucose. These “isoglycemic clamps” enabled us to determine the contribution of the GI tract and postabsorptive plasma glucose to acyl ghrelin suppression. Plasma acyl ghrelin levels were suppressed to a greater degree with jejunal glucose administration compared with gastric glucose administration (P < 0.05). Jejunal administration of glucose also resulted in a greater suppression of acyl ghrelin than the corresponding isoglycemic glucose infusion (P ≤ 0.01). However, gastric and isoglycemic iv glucose infusions resulted in similar degrees of acyl ghrelin suppression (P > 0.05). Direct exposure of the proximal jejunum to glucose increases acyl ghrelin suppression independent of circulating glucose levels. The enhanced suppression of acyl ghrelin after RYGB may be due to a nutrient-initiated signal in the jejunum that regulates ghrelin secretion. PMID:27279247

Evaluation of the pharmacodynamics and pharmacokinetics of brucine following transdermal administration.

PubMed

Chen, Jun; Hu, Wei; Qu, Ye-Qing; Dong, Jie; Gu, Wei; Gao, Ying; Fang, Yun; Fang, Fang; Chen, Zhi-Peng; Cai, Bao-Chang

2013-04-01

Before the design of brucine-containing transdermal formulations, the pharmacodynamics and pharmacokinetics of brucine following transdermal administration should be evaluated. In this study, the effect of addition of ethanol on solubility of bruicne was investigated and 20% ethanol was added into PBS to obtain 10mg/mL brucine solution. Then three transdermal doses (10, 20 and 40 mg/kg) were administered to mice to evaluate pharmacological activity. It had been demonstrated that brucine possessed analgesic and anti-inflammatory activity in a dose-dependent manner. Cytotoxicities of brucine against various tumor cells including skin tumor cell were also compared in vitro. Brucine was found to possess antitumor activity in a concentration and time-dependent manner and gastrointestinal tumor cells seemed to be more sensitive to brucine. Then in vitro skin permeation behavior and in vivo pharmacokinetics following transdermal administration were further investigated. The cumulative amounts of brucine across mouse skin in vitro were found to be higher than 90%. The absolute bioavailability of brucine was determined to be 40.83%. And compared with intravenous administration, MRT and T1/2 values were increased about 8~12-fold by transdermal route. Moreover, fluctuations of drug levels were found to be significantly decreased in tissues, especially in brain. Finally, no dermal toxicity of brucine was observed. The results of this study indicated that transdermal administration might be beneficial for the sustained efficacy and reduced toxicity of brucine. Copyright © 2013 Elsevier B.V. All rights reserved.

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

PubMed

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

2014-02-01

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

Intraductal administration of a polymeric nanoparticle formulation of curcumin (NanoCurc) significantly attenuates incidence of mammary tumors in a rodent chemical carcinogenesis model: Implications for breast cancer chemoprevention in at-risk populations

PubMed Central

Chun, Yong Soon; Maitra, Anirban; Sukumar, Saraswati

2012-01-01

Multiple lines of evidence support a role for curcumin in cancer chemoprevention. Nonetheless, despite its reported efficacy and safety profile, clinical translation of curcumin has been hampered by low oral bioavailability, requiring infeasible ‘mega’ doses for achieving detectable tissue levels. We have engineered a polymeric nanoparticle encapsulated formulation of curcumin (NanoCurc) to harness its full therapeutic potential. In the current study, we assessed the chemoprevention efficacy of NanoCurc administered via direct intraductal (i.duc) injection in a chemical carcinogen-induced rodent mammary cancer model. Specifically, Sprague–Dawley rats exposed to systemic N-methyl-N-nitrosourea were randomized to receive either oral free curcumin at a previously reported ‘mega’ dose (200mg/kg) or by direct i.duc injection of free curcumin or NanoCurc, respectively, each delivering 168 µg equivalent of curcumin per rodent teat (a ~20-fold lower dose per animal compared to oral administration). All three chemoprevention modalities resulted in significantly lower mammary tumor incidence compared with control rats; however, there was no significant difference in cancer incidence between the oral dosing and either i.duc arms. On the other hand, mean tumor size, was significantly smaller in the i.duc NanoCurc cohort compared with i.duc free curcumin (P < 0.0001), suggesting the possibility of better resectability for ‘breakthrough’ cancers. Reduction in cancer incidence was associated with significant decrease in nuclear factor -κB activation in the NanoCurc treated mammary epithelium explants, compared to either control or oral curcumin-administered rats. Our studies confirm the potential for i.duc NanoCurc as an alternative to the oral route for breast cancer chemoprevention in high-risk cohorts. PMID:22831956

Metabolism of halofantrine to its equipotent metabolite, desbutylhalofantrine, is decreased when orally administered with ketoconazole.

PubMed

Khoo, S M; Porter, J H; Edwards, G A; Charman, W N

1998-12-01

Halofantrine (Hf) is a highly lipophilic antimalarial with poor and erratic absorption. Published data indicates that the oral bioavailability of Hf was increased 3-fold in humans and 12-fold in dogs when administered postprandially; however, the proportional formation of the active desbutyl metabolite (desbutylhalofantrine, Hfm) decreased 2.4-fold in humans and 6.8-fold in dogs (Milton et al., Br. J. Clin. Pharmacol. 1989, 28, 71-77; Humberstone et al., J. Pharm. Sci. 1996, 85, 525-529). The current study was undertaken to confirm the putative involvement of CYP3A4 in the N-dealkylation of Hf to Hfm by administering Hf with and without ketoconazole (KC), a specific CYP3A4 inhibitor, and measuring the resulting plasma concentration profiles of Hf and Hfm. The plasma Hfm/Hf AUC(0-72 h) ratio after fasted oral administration of Hf without KC was 0.56, whereas the ratio after fasted oral administration with KC was less than 0.05. It is likely that both hepatic and prehepatic (enterocyte-based) CYP3A4 contributed to metabolism of Hf to Hfm after oral administration. Interestingly, the low plasma Hfm/Hf AUC ratios observed after fasted administration of Hf with KC were similar to the low values previously observed when Hf was administered postprandially (despite increased Hf absorption). The mechanism(s) by which postprandial administration of Hf led to a decrease in its metabolism are unknown, but based on the current data, could include inhibition of CYP3A4-mediated metabolism by components of the ingested meal. Other possibilities include a lipid-induced postprandial recruitment of intestinal lymphatic transport or avoidance of metabolism during transport through the enterocyte into the portal blood. Further studies are required to determine the relative contributions by which these different processes may decrease the presystemic metabolism of Hf.

Accelerated blood clearance phenomenon upon cross-administration of PEGylated nanocarriers in beagle dogs

PubMed Central

Wang, Chunling; Cheng, Xiaobo; Su, Yuqing; Pei, Ying; Song, Yanzhi; Jiao, Jiao; Huang, Zhenjun; Ma, Yanfei; Dong, Yinming; Yao, Ying; Fan, Jingjing; Ta, Han; Liu, Xinrong; Xu, Hui; Deng, Yihui

2015-01-01

The cross-administration of nanocarriers modified by poly(ethylene glycol) (PEG), named PEGylated nanocarriers, a type of combination therapy, is becoming an increasingly important method of long-term drug delivery, to decrease side effects, avoid multidrug resistance, and increase therapeutic efficacy. However, repeated injections of PEGylated nanocarriers induces the accelerated blood clearance (ABC) phenomenon, prevents long circulation, and can cause adverse effects owing to alterations in the biodistribution of the drug. Although the nature of the ABC phenomenon that is induced by repeated injections of PEGylated nanocarriers has already been studied in detail, there are few reports on the immune response elicited by the cross-administration of PEGylated nanocarriers. In this study, we investigated the ABC phenomenon induced by the intravenous cross-administration of various PEGylated nanocarriers, including PEGylated liposomes (PL), PEG micelles (PM), PEGylated solid lipid nanoparticles (PSLN), and PEGylated emulsions (PE), in beagle dogs. The results indicated that the magnitude of the immune response elicited by the cross-administration was in the following order (from the strongest to the weakest): PL, PE, PSLN, PM. It is specifically PEG in the brush structure that elicits a significant immune response, in both the induction phase and the effectuation phase. Furthermore, the present study suggests that there is a considerable difference between the effect of repeated injections and cross-administration, depending on the colloidal structure. This work is a preliminary investigation into the cross-administration of PEGylated nanocarriers, and our observations can have serious implications for the design of combination therapies that use PEGylated vectors. PMID:25999716

[Job satisfaction in an Italian university: difference between academic and technical-administrative staff].

PubMed

Ghislieri, Chiara; Colombo, Lara; Molino, Monica; Zito, Margherita; Curzi, Ylenia; Fabbri, Tommaso

2014-01-01

The changes in the academic world led to an increase in job demands and a decrease in the available job resources. In recent years, the positive image of work in academia has gradually blurred. The present study, within the theoretical framework of the job demands-resources model, aimed to analyse the relationship between some job demands (workload, work-family conflict and emotional dissonance) and some job resources (autonomy, supervisors' support and co-workers' support) and job satisfaction in a medium-sized Italian University, by observing the differences between the academic staff (professors and researchers) and the technical-administrative staff The research was conducted by administering a self-report questionnaire which allowed to detect job satisfaction and the mentioned variables. Respondents were 477 (177 from academic staff and 300 from technical-administrative staff). The analysis of variance (independent samples t-test) showed significant differences in variables of interest between academic staff and technical-administrative staff. Multiple regression pointed out that job autonomy is the main determinant of job satisfaction in the academic staff sample, whereas supervisor support is the main determinant of job satisfaction in the technical-administrative staff sample. This research represents one of the first Italian studies on these topics in the academic context and highlights the importance of further in-depth examinations of specific job dynamics for both teaching and technical-administrative staff. Among practical implications, the importance of keeping high levels of job autonomy for academic staff and of fostering an effective leadership development for technical-administrative staff emerged.

Characteristics of Interruptions During Medication Administration:An Integrative Review of Direct Observational Studies.

PubMed

Schroers, Ginger

2018-06-26

The purpose of this review was to synthesize and summarize data gathered by direct observation of the characteristics of interruptions in the context of nursing medication administration in hospital settings. Interruptions are prevalent during the medication administration process performed by nurses in hospital settings and have been found to be associated with an increase in frequency and severity of nursing medication administration errors. In addition, interruptions decrease task efficiency, leading to longer medication administration completion times. Integrative review. The electronic databases Cumulative Index of Nursing and Allied Health Literature (CINAHL), PubMED, PsyARTICLES, and Google Scholar were searched using the terms "interruptions" AND "medication administration" AND "direct observation". Nine articles met the inclusion criteria. Interruptions are likely to occur at least once during nursing medication administration processes in hospital settings. This finding applies to medication administered to one patient, termed a medication pass, and medication administered to multiple patients, termed a mediation round. Interruptions are most commonly caused by another nurse, staff member, or are self-initiated, and last approximately one minute in length. A raised awareness among staff of the most common sources of interruptions may encourage changes that lead to a decrease in the occurrence of interruptions. In addition, nurse leaders can apply an understanding of the common characteristics of interruptions to guide research, policies, and educational methods aimed at interruption management strategies. The findings from this review can be used to guide the identification and development of targeted interventions and strategies that would have the most substantial impact to reduce and manage interruptions during medication administration. Interruption management strategies have the potential to lead to a decrease in medication errors and an increase in

Antagonistic targeting of the histamine H3 receptor decreases caloric intake in higher mammalian species.

PubMed

Malmlöf, Kjell; Hastrup, Sven; Wulff, Birgitte Schellerup; Hansen, Barbara C; Peschke, Bernd; Jeppesen, Claus Bekker; Hohlweg, Rolf; Rimvall, Karin

2007-04-15

The main purpose of this study was to examine the effects of a selective histamine H(3) receptor antagonist, NNC 38-1202, on caloric intake in pigs and in rhesus monkeys. The compound was given intragastrically (5 or 15 mg/kg), to normal pigs (n=7) and subcutaneously (1 or 0.1mg/kg) to obese rhesus monkeys (n=9). The energy intake recorded following administration of vehicle to the same animals served as control for the effect of the compound. In addition, rhesus monkey and pig histamine H(3) receptors were cloned from hypothalamic tissues and expressed in mammalian cell lines. The in vitro antagonist potencies of NNC 38-1202 at the H(3) receptors were determined using a functional GTPgammaS binding assay. Porcine and human H(3) receptors were found to have 93.3% identity at the amino acid level and the close homology between the monkey and human H(3) receptors (98.4% identity) was confirmed. The antagonist potencies of NNC 38-1202 at the porcine, monkey and human histamine H(3) receptors were high as evidenced by K(i)-values being clearly below 20 nM, whereas the K(i)-value on the rat H(3) receptor was significantly higher (56+/-6.0 nM). NNC 38-1202, given to pigs in a dose of 15 mg/kg, produced a significant (p<0.05) reduction (55%) of calorie intake compared with vehicle alone, (132.6+/-10.0 kcal/kgday versus 59.7+/-10.2 kcal/kgday). In rhesus monkeys administration of 0.1 and 1mg/kg decreased (p<0.05) average calorie intakes by 40 and 75%, respectively. In conclusion, the present study demonstrates that antagonistic targeting of the histamine H(3) receptor decreases caloric intake in higher mammalian species.

The effect of repeated diazepam administration on myocardial function in the ischemia-reperfused isolated rat heart.

PubMed

Shackebaei, Dareuosh; Kayhani, Bijan; Godini, Aliashraf; Pourshanazari, Aliasghar; Reshadat, Sohyla

2009-06-01

To evaluate whether repeated diazepam administration affects the heart in ischemia-reperfusion. This study was performed at the Medical Biology Research Center, Kermanshah, Iran, from March to September 2008. Four groups of rats were subjected to a daily injection of diazepam (group 1 [0.5 mg/kg for 21 days], group II [2.5 mg/kg for 5 days], and group III [5 mg/kg for 5 days] intraperitoneally), and saline solution (21 days) in the control groups. Isolated, perfused hearts were subjected to 40 minutes global ischemia, and 45 minutes reperfusion. The left ventricular developed pressure (LVDP), heart rate, and coronary flow were measured. Rate pressure product (RPP) was calculated. In reperfusion, released lactate dehydrogenase (LDH) enzyme in effluent was measured. It was observed that the recovery of the RPP and LVDP in reperfusion significantly decreased in the test group III (n=9) in comparison to the control (n=8). During the reperfusion period, the released LDH significantly increased in test group II (n=8) and group III in comparison with the control. The results show that repeated administration of diazepam (5 mg/kg for 5 days) reduced the cardiac performance in reperfusion, and significantly exacerbated the ischemia-reperfusion injury. It is probably mediated by the changing of cardiac susceptibility in ischemia due to repeated administration of diazepam.

Maternal intrapartum antibiotics and decreased vertical transmission of Lactobacillus to neonates during birth.

PubMed

Keski-Nisula, Leea; Kyynäräinen, Hanna-Reetta; Kärkkäinen, Ulla; Karhukorpi, Jari; Heinonen, Seppo; Pekkanen, Juha

2013-05-01

To estimate the transmission of maternal vaginal microbiota to neonates during term delivery, focusing on Lactobacillus flora in relation to various obstetric clinical factors. Fifty consecutive pregnant healthy women with singleton term pregnancies and their newborn infants. Vertical transmission of Lactobacillus flora to the newborn during delivery was evaluated in 45 mother-newborn pairs. Lactobacillus-dominant mixed flora was detected in 90% (N = 45) of vaginal samples, but only in 28% (N = 14) of neonatal cultures (transmission rate 31%). All neonates with Lactobacillus-dominant mixed flora had findings similar to those in maternal cultures. Cocci-dominant flora was the most common finding in neonates. Administration of antibiotics to the mother during the intrapartum period before birth and duration of rupture of membranes (ROM), regardless of maternal antibiotic treatment, were associated significantly with a decreased transmission rate of Lactobacillus-dominant mixed flora to neonates. Maternal intrapartum antibiotics and prolonged expectant management after ROM were associated with decreased transmission rate of vaginal Lactobacillus flora to the neonate during birth. As early colonization of Lactobacillus flora may have a preventive role in the development of allergic diseases later, the significance of intrapartum prophylactic antibiotics needs to be highlighted in forthcoming studies, especially as regards immunological development of the offspring. ©2013 The Author(s)/Acta Paediatrica ©2013 Foundation Acta Paediatrica.

Respiratory reflexes in spontaneously breathing anesthetized dogs in response to nasal administration of sevoflurane, isoflurane, or halothane.

PubMed

Mutoh, T; Kanamaru, A; Suzuki, H; Tsubone, H; Nishimura, R; Sasaki, N

2001-03-01

To characterize respiratory reflexes elicited by nasal administration of sevoflurane (Sevo), isoflurane (Iso), or halothane (Hal) in anesthetized dogs. 8 healthy Beagles. A permanent tracheostomy was created in each dog. Two to 3 weeks later, dogs were anesthetized by IV administration of thiopental and alpha-chloralose. Nasal passages were isolated such that inhalant anesthetics could be administered to the nasal passages while the dogs were breathing 100% O2 via the tracheostomy. Respiratory reflexes in response to administration of each anesthetic at 1.2 and 2.4 times the minimum alveolar concentration (MAC) and the full vaporizer setting (5%) were recorded. Reflexes in response to administration of 5% of each anesthetic also were recorded following administration of lidocaine to the nasal passages. Nasal administration of Sevo, Iso, and Hal induced an immediate ventilatory response characterized by a dose-dependent increase in expiratory time and a resulting decrease in expired volume per unit of time. All anesthetics had a significant effect, but for Sevo, the changes were smaller in magnitude. Responses to administration of each anesthetic were attenuated by administration of lidocaine to the nasal passages. Nasal administration of Sevo at concentrations generally used for mask induction of anesthesia induced milder reflex inhibition of breathing, presumably via afferent neurons in the nasal passages, than that of Iso or Hal. Respiratory reflexes attributable to stimulation of the nasal passages may contribute to speed of onset and could promote a smoother induction with Sevo, compared with Iso or Hal.

One Month of Oral Morphine Decreases Gray Matter Volume in the Right Amygdala of Individuals with Low Back Pain: Confirmation of Previously Reported Magnetic Resonance Imaging Results.

PubMed

Lin, Joanne C; Chu, Larry F; Stringer, Elizabeth Ann; Baker, Katharine S; Sayyid, Zahra N; Sun, John; Campbell, Kelsey A; Younger, Jarred W

2016-08-01

Prolonged exposure to opioids is known to produce neuroplastic changes in animals; however, few studies have investigated the effects of short-term prescription opioid use in humans. A previous study from our laboratory demonstrated a dosage-correlated volumetric decrease in the right amygdala of participants administered oral morphine daily for 1 month. The purpose of this current study was to replicate and extend the initial findings. Twenty-one participants with chronic low back pain were enrolled in this double-blind, placebo-controlled study. Participants were randomized to receive daily morphine (n = 11) or a matched placebo (n = 10) for 1 month. High-resolution anatomical images were acquired immediately before and after the treatment administration period. Morphological gray matter changes were investigated using tensor-based morphometry, and significant regions were subsequently tested for correlation with morphine dosage. Decreased gray matter volume was observed in several reward- and pain-related regions in the morphine group, including the bilateral amygdala, left inferior orbitofrontal cortex, and bilateral pre-supplementary motor areas. Morphine administration was also associated with significant gray matter increases in cingulate regions, including the mid cingulate, dorsal anterior cingulate, and ventral posterior cingulate. Many of the volumetric increases and decreases overlapped spatially with the previously reported changes. Individuals taking placebo for 1 month showed neither gray matter increases nor decreases. The results corroborate previous reports that rapid alterations occur in reward-related networks following short-term prescription opioid use. © 2015 American Academy of Pain Medicine.

Changes in plasma volume during bed rest - Effects of menstrual cycle and estrogen administration

NASA Technical Reports Server (NTRS)

Fortney, S. M.; Beckett, W. S.; Carpenter, A. J.; Davis, J.; Drew, H.

1988-01-01

The effect of increased blood estrogen concentration, caused either during normal menstrual cycles or by exogenous administration of premarin, on the bed-rest (BR) induced decrease in plasma volume (PV) was investigated. In women who underwent duplicate 11-day BR without estrogen supplementation, the PV was found to decrease significantly, during the first 5 days of BR, to a lower level at which it remained for the rest of the BR period. In women who began BR in the periovulatory stage of the menstrual cycle, the loss of PV was delayed, while women who began BR during other stages of the cycle exhibited the usual trend of the PV decrease during the BR. In women who underwent a single 12-day BR period while taking premarin (1.25 mg/day), PV was found to decrease during the first 4-5 days of BR, but then returned toward the pre-BR level during the remainder of the BR, indicating that estrogens have a role in stabilizing body fluid volume.

Drug-administration sequence of target-controlled propofol and remifentanil influences the onset of rocuronium. A double-blind, randomized trial.

PubMed

Na, H S; Hwang, J W; Park, S H; Oh, A Y; Park, H P; Jeon, Y T; Do, S H

2012-05-01

Remifentanil is known to cause bradycardia and hypotension, as well as the decreases of cardiac output (CO). We hypothesized that hemodynamic suppression by remifentanil would affect the onset time of rocuronium. This study investigated whether the onset of rocuronium was influenced by the drug-administration sequence during induction of anesthesia with target-controlled infusion of propofol and remifentanil. Healthy adult patients (n = 126) undergoing elective surgery under general anesthesia were randomized into two groups according to drug-administration sequence. In Remi-Pro-Rocu group (n = 62), remifentanil was infused first, followed by propofol. Then, rocuronium was administered lastly. In Pro-Rocu-Remi group (n = 64), propofol, rocuronium, and remifentanil were given in that order. As a primary outcome, the onset time of rocuronium was measured. Mean arterial pressure (MAP), heart rate (HR), CO, and stroke volume were recorded before anesthesia (T1), at injection of rocuronium (T2), immediately before and after intubation (T3 and T4). In Remi-Pro-Roc group, the onset of rocuronium was delayed significantly compared with Pro-Rocu-Remi group [median (interquartile range); 130 (105-150) vs. 90 (71-100) s, P < 0.001]. At the time of rocuronium injection (T2), MAP, HR, and CO were significantly lower in Remi-Pro-Rocu group than Pro-Rocu-Remi group (P < 0.001). The onset time of rocuronium is prolonged significantly by early administration of remifentanil during target-controlled infusion of propofol and remifentanil, and it may be due to the decreased CO caused by remifentanil. © 2012 The Authors. Acta Anaesthesiologica Scandinavica © 2012 The Acta Anaesthesiologica Scandinavica Foundation.

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.

The Effects of Stereotactic Cerebroventricular Administration of Albumin, Mannitol, Hypertonic Sodium Chloride, Glycerin and Dextran in Rats with Experimental Brain Edema.

PubMed

Ates, Tuncay; Gezercan, Yurdal; Menekse, Guner; Turkoz, Yusuf; Parlakpinar, Hakan; Okten, Ali Ihsan; Akyuva, Yener; Onal, Selami Cagatay

2017-01-01

To evaluate the effects of cerebroventricular administration of hyperoncotic/hyperosmotic agents on edematous brain tissue in rats with experimental head trauma. The study included 54 female Sprague-Dawley rats with weights ranging between 200 and 250 g. Six experimental groups were examined with each group containing 9 rats. All rats were exposed to head trauma, and treatment groups were administered 2 µl of one of the drugs (albumin, mannitol, hypertonic sodium chloride (NaCl), glycerin and dextran) 6, 12 and 24 hours after the trauma via the cerebroventricular route and using a stereotactic device. Rats were sacrificed 48 hours after the trauma, and brain tissues were extracted without damage. Biochemical analyses including reduced glutathione (GSH), nitric oxide (NO), malondialdehyde (MDA), tumor necrosis factor alpha (TNF-α), and interleukin 1 beta (IL-1β) were performed on the injured left hemisphere. Compared with the control group, the albumin, mannitol, 3% NaCl and glycerin treatment groups revealed dramatic increases in GSH levels (p < 0.001). Levels of MDA, which is the end-product of brain edema and lipid peroxidation, failed to show a statistically significant decrease, but there was a decreasing trend observed in the inter-group comparisons. NO levels were also decreased in the 3% NaCl treatment group. An analysis of TNF-α and IL-1β, two proinflammatory cytokines associated with the trauma, revealed that IL-1β decreased significantly in all treatment groups (p=0.001), whereas no significant difference was detected in TNF-α levels. Cerebroventricular administration of hyperoncotic/hyperosmotic agents provides substantial effects on the treatment of brain edema.

Plasma concentrations of midazolam during continuous subcutaneous administration in palliative care.

PubMed

Bleasel, M D; Peterson, G M; Dunne, P F

1994-01-01

We have investigated the steady-state plasma concentrations of midazolam during continuous subcutaneous administration in palliative care. Using a sensitive gas chromatography with electron capture detector assay, plasma concentrations of midazolam were measured in 11 patients (median age 68 years; range 47-82 years; six females) receiving the drug by continuous subcutaneous infusion (median rate 20 mg/day; range 10-60 mg/day). While not significant, the infusion rate tended to decrease with increasing age of the patient (Spearman's p = -0.51; p = 0.11). The steady-state plasma concentration range was 10-147 ng/ml, with a median of 30 ng/ml. Infusion rates and plasma concentrations of midazolam were correlated (Spearman's p = 0.71; p < 0.05). No other significant relationships were found between plasma concentrations and the variables of age, sex and liver function.

Hypophosphatemia is Associated with the Serial Administration of Triple-Dose Gadolinium to Patients for Brain MRI.

PubMed

Wolansky, Leo J; Cadavid, Diego; Punia, Vineet; Kim, Soyeon; Cheriyan, Jojy; Haghighi, Mershad; Cook, Stuart D

2015-01-01

The purpose of this study is to report a metabolic abnormality associated with frequent, triple-dose Gadolinium (TdGd) use in MS patients during BECOME trial. Potential clinical adverse events and lab abnormalities were monitored at each monthly MRI visit. Hypophosphatemia was defined as phosphate <2.5 mg/dL. Statistical analysis included McNemar's test for pairwise comparisons across visits and generalized estimating equations (GEE) to fit models over time. Eight hundred seventy seven phosphate values were analyzed from the first 12 months. Compared with 4% of subjects at screening, an average of 15.1% (95% confidence interval (CI): 11.4%-19.7%) of patients had hypophosphatemia at visits from months 1 to 12, during which subjects received serial TdGd. Forty four of seventy five (59%) patients developed hypophosphatemia at least once. We also found a significant increasing trend in hypophosphatemia by visit when treatment groups were evaluated together or separately (p < .001). There was a statistically significant decrease in frequency to 9.8% (95% CI: 4.6-19.8%) by month 24 (p = .005) coinciding with a period of less frequent gadolinium administration. Serial TdGd in MS patients, unrelated to immunomodulatory treatment, was associated with increased frequency of hypophosphatemia that progressed with cumulative triple-dose and markedly decreased in second year, with less frequent triple-dose administration. Copyright © 2015 by the American Society of Neuroimaging.

Intratracheal Administration of Budesonide/Surfactant to Prevent Bronchopulmonary Dysplasia.

PubMed

Yeh, Tsu F; Chen, Chung M; Wu, Shou Y; Husan, Zahid; Li, Tsai C; Hsieh, Wu S; Tsai, Chang H; Lin, Hung C

2016-01-01

Bronchopulmonary dysplasia (BPD) is an important complication of mechanical ventilation in preterm infants, and no definite therapy can eliminate this complication. Pulmonary inflammation plays a crucial role in its pathogenesis, and glucocorticoid is one potential therapy to prevent BPD. To compare the effect of intratracheal administration of surfactant/budesonide with that of surfactant alone on the incidence of death or BPD. A clinical trial was conducted in three tertiary neonatal centers in the United States and Taiwan, in which 265 very-low-birth-weight infants with severe respiratory distress syndrome who required mechanical ventilation and inspired oxygen (fraction of inspired oxygen, ≥50%) within 4 hours of birth were randomly assigned to one of two groups (131 intervention and 134 control). The intervention infants received surfactant (100 mg/kg) and budesonide (0.25 mg/kg), and the control infants received surfactant only (100 mg/kg), until each infant required inspired O2 at less than 30% or was extubated. The intervention group had a significantly lower incidence of BPD or death (55 of 131 [42.0%] vs. 89 of 134 [66%]; risk ratio, 0.58; 95% confidence interval, 0.44-0.77; P < 0.001; number needed to treat, 4.1; 95% confidence interval, 2.8-7.8). The intervention group required significantly fewer doses of surfactant than did the control group. The intervention group had significantly lower interleukin levels (IL-1, IL-6, IL-8) in tracheal aspirates at 12 hours and lower IL-8 at 3-5 and 7-8 days. In very-low-birth-weight infants with severe respiratory distress syndrome, intratracheal administration of surfactant/budesonide compared with surfactant alone significantly decreased the incidence of BPD or death without immediate adverse effect. Clinical trial registered with www.clinicaltrials.gov (NCT-00883532).

Brain regions mediating α3β4 nicotinic antagonist effects of 18-MC on methamphetamine and sucrose self-administration

PubMed Central

Glick, Stanley D.; Sell, Elizabeth M.; Maisonneuve, Isabelle M.

2008-01-01

The novel iboga alkaloid congener 18-methoxycoronaridine (18-MC) is a putative anti-addictive agent that has been shown, in rats, to decrease the self-administration of several drugs of abuse. Previous work has established that 18-MC is a potent antagonist at α3β4 nicotinic receptors. Because high densities of α3β4 nicotinic receptors occur in the medial habenula and the interpeduncular nucleus and moderate densities occur in the dorsolateral tegmentum, ventral tegmental area, and basolateral amygdala, the present study was conducted to determine if 18-MC could act in these brain areas to modulate methamphetamine self-administration in rats. Local administration of 18-MC into either the medial habenula, the interpeduncular area or the basolateral amygdala decreased methamphetamine self-administration. Similar results were produced by local administration into the same brain areas of two other α3β4 nicotinic antagonists, mecamylamine and α-conotoxin AuIB. Local administration of 18-MC, or the other antagonists, into the dorsolateral tegmentum or the ventral tegmental area had no effect on methamphetamine self-administration. In contrast, local administration of 18-MC and the other antagonists decreased sucrose self-administration when administered into the dorsolateral tegmentum or basolateral amygdala but had no effect when infused into the medial habenula, interpeduncular nucleus, or ventral tegmental area. These data are consistent with the hypothesis that 18-MC decreases methamphetamine self-administration by indirectly modulating the dopaminergic mesolimbic pathway via blockade of α3β4 nicotinic receptors in the habenulo-interpeduncular pathway and the basolateral amygdala. The data also suggest that the basolateral amygdala along with a different pathway involving α3β4 receptors in the dorsolateral tegmentum mediate the effect of 18-MC on sucrose self-administration. PMID:18930043

Effect of intermittent oral administration of ponazuril on experimental Sarcocystis neurona infection of horses.

PubMed

Mackay, Robert J; Tanhauser, Susan T; Gillis, Karen D; Mayhew, Ian G; Kennedy, Tom J

2008-03-01

To evaluate the effect of intermittent oral administration of ponazuril on immunoconversion against Sarcocystis neurona in horses inoculated intragastrically with S neurona sporocysts. 20 healthy horses that were seronegative for S neurona-specific IgG. 5 control horses were neither inoculated with sporocysts nor treated. Other horses (5 horses/group) each received 612,500 S neurona sporocysts via nasogastric tube (day 0) and were not treated or were administered ponazuril (20 mg/kg, PO) every 7 days (beginning on day 5) or every 14 days (beginning on day 12) for 12 weeks. Blood and CSF samples were collected on day - 1 and then every 14 days after challenge for western blot assessment of immunoconversion. Clinical signs of equine protozoal myeloencephalitis (EPM) were monitored, and tissues were examined histologically after euthanasia. Sera from all challenged horses yielded positive western blot results within 56 days. Immunoconversion in CSF was detected in only 2 of 5 horses that were treated weekly; all other challenged horses immunoconverted within 84 days. Weekly administration of ponazuril significantly reduced the antibody response against the S neurona 17-kd antigen in CSF. Neurologic signs consistent with EPM did not develop in any group; likewise, histologic examination of CNS tissue did not reveal protozoa or consistent degenerative or inflammatory changes. Administration of ponazuril every 7 days, but not every 14 days, significantly decreased intrathecal anti-S neurona antibody responses in horses inoculated with S neurona sporocysts. Protocols involving intermittent administration of ponazuril may have application in prevention of EPM.

Effects of chronic varenicline treatment on nicotine, cocaine, and concurrent nicotine+cocaine self-administration.

PubMed

Mello, Nancy K; Fivel, Peter A; Kohut, Stephen J; Carroll, F Ivy

2014-04-01

Nicotine dependence and cocaine abuse are major public health problems, and most cocaine abusers also smoke cigarettes. An ideal treatment medication would reduce both cigarette smoking and cocaine abuse. Varenicline is a clinically available, partial agonist at α4β2* and α6β2* nicotinic acetylcholine receptors (nAChRs) and a full agonist at α7 nAChRs. Varenicline facilitates smoking cessation in clinical studies and reduced nicotine self-administration, and substituted for the nicotine-discriminative stimulus in preclinical studies. The present study examined the effects of chronic varenicline treatment on self-administration of IV nicotine, IV cocaine, IV nicotine+cocaine combinations, and concurrent food-maintained responding by five cocaine- and nicotine-experienced adult rhesus monkeys (Macaca mulatta). Varenicline (0.004-0.04 mg/kg/h) was administered intravenously every 20 min for 23 h each day for 7-10 consecutive days. Each varenicline treatment was followed by saline-control treatment until food- and drug-maintained responding returned to baseline. During control treatment, nicotine+cocaine combinations maintained significantly higher levels of drug self-administration than nicotine or cocaine alone (P<0.05-0.001). Varenicline dose-dependently reduced responding maintained by nicotine alone (0.0032 mg/kg/inj) (P<0.05), and in combination with cocaine (0.0032 mg/kg/inj) (P<0.05) with no significant effects on food-maintained responding. However, varenicline did not significantly decrease self-administration of a low dose of nicotine (0.001 mg/kg), cocaine alone (0.0032 and 0.01 mg/kg/inj), or 0.01 mg/kg cocaine combined with the same doses of nicotine. We conclude that varenicline selectively attenuates the reinforcing effects of nicotine alone but not cocaine alone, and its effects on nicotine+cocaine combinations are dependent on the dose of cocaine.

Effects of Chronic Varenicline Treatment on Nicotine, Cocaine, and Concurrent Nicotine+Cocaine Self-Administration

PubMed Central

Mello, Nancy K; Fivel, Peter A; Kohut, Stephen J; Carroll, F Ivy

2014-01-01

Nicotine dependence and cocaine abuse are major public health problems, and most cocaine abusers also smoke cigarettes. An ideal treatment medication would reduce both cigarette smoking and cocaine abuse. Varenicline is a clinically available, partial agonist at α4β2* and α6β2* nicotinic acetylcholine receptors (nAChRs) and a full agonist at α7 nAChRs. Varenicline facilitates smoking cessation in clinical studies and reduced nicotine self-administration, and substituted for the nicotine-discriminative stimulus in preclinical studies. The present study examined the effects of chronic varenicline treatment on self-administration of IV nicotine, IV cocaine, IV nicotine+cocaine combinations, and concurrent food-maintained responding by five cocaine- and nicotine-experienced adult rhesus monkeys (Macaca mulatta). Varenicline (0.004–0.04 mg/kg/h) was administered intravenously every 20 min for 23 h each day for 7–10 consecutive days. Each varenicline treatment was followed by saline-control treatment until food- and drug-maintained responding returned to baseline. During control treatment, nicotine+cocaine combinations maintained significantly higher levels of drug self-administration than nicotine or cocaine alone (P<0.05–0.001). Varenicline dose-dependently reduced responding maintained by nicotine alone (0.0032 mg/kg/inj) (P<0.05), and in combination with cocaine (0.0032 mg/kg/inj) (P<0.05) with no significant effects on food-maintained responding. However, varenicline did not significantly decrease self-administration of a low dose of nicotine (0.001 mg/kg), cocaine alone (0.0032 and 0.01 mg/kg/inj), or 0.01 mg/kg cocaine combined with the same doses of nicotine. We conclude that varenicline selectively attenuates the reinforcing effects of nicotine alone but not cocaine alone, and its effects on nicotine+cocaine combinations are dependent on the dose of cocaine. PMID:24304823

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

PubMed

Slawecki, C J; Samson, H H

1997-09-01

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

Effects of oral administration of caffeine and D-ribose on mental fatigue.

PubMed

Ataka, Suzuka; Tanaka, Masaaki; Nozaki, Satoshi; Mizuma, Hiroshi; Mizuno, Kei; Tahara, Tsuyoshi; Sugino, Tomohiro; Shirai, Tomoko; Kajimoto, Yoshitaka; Kuratsune, Hirohiko; Kajimoto, Osami; Watanabe, Yasuyoshi

2008-03-01

We examined the effects of administering two different candidate antifatigue substances, caffeine and D-ribose, on mental fatigue. In a double-blinded, placebo-controlled, three-way crossover design, 17 healthy volunteers were randomized to oral caffeine (200 mg/d), D-ribose (2000 mg/d), or placebo for 8 d. As fatigue-inducing mental tasks, subjects performed a 30-min Uchida-Kraepelin psychodiagnostic test and a 30-min advanced trail-making test on four occasions. During the tasks, the task performance of the caffeine group was better than that of the placebo group. However, after the fatigue-inducing tasks, although subjective perception of fatigue, motivation, or sleepiness was not significantly different, plasma branched-chain amino acid levels in the caffeine group were lower than those of the placebo group. Administration of D-ribose had no effect. Because plasma branched-chain amino acid levels are decreased by mental fatigue, these results suggest that administration of caffeine improved task performance through the enhancement of central nervous system activity without increasing the sensation of fatigue. However, further decreases in branched-chain amino acid levels indicate that caffeine might promote deeper fatigue than placebo. Unfortunately, research subsequent to our study design has shown that D-ribose dosing higher than we used is needed to see a clinical effect and therefore no conclusions can be made from this study as to the efficacy of D-ribose.

[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.

Neurotoxicity of misonidazole in rats following intravenous administration.

PubMed

Graziano, M J; Henck, J W; Meierhenry, E F; Gough, A W

1996-06-01

Misonidazole is a hypoxic cell radiosensitizer that induces a peripheral neuropathy in humans after exceeding a schedule-dependent cumulative threshold dose. Clinical studies of misonidazole have been conducted using oral administration, whereas most other radiosensitizers have been administered intravenously. Since route of exposure can potentially influence the toxicity of xenobiotics, the objective of this study was to assess the neurotoxicity of misonidazole in rats following intravenous dosing using a battery of routine clinical, neurofunctional, biochemical, and histopathologic screening methods. Male Sprague-Dawley rats were administered intravenous doses of misonidazole at 0 (vehicle control), 100, 200, 300, or 400 mg kg-1 once per day, 5 days per week, for 2 weeks. Animals were evaluated for neurofunctional and pathological changes following termination of treatment (Days 15-17) and at the end of a 4 week observation period (Days 43-45). During the dosing phase, hypoactivity, salivation, rhinorrhea, chromodacryorrhea, rough pelage and ataxia were observed at 400 mg kg-1, and body weight gain of the 300 and 400 mg kg-1 groups was significantly decreased relative to the vehicle controls by 24% and 49%, respectively. Corresponding reductions in food consumption were 8% and 23%, respectively. Although most 400 mg kg-1 animals appeared normal on Day 15 prior to the neurofunctional evaluations, rotorod testing precipitated a number of clinical signs including: ataxia, impaired righting reflex, excessive rearing, tremors, vocalization, circling, head jerking, excessive sniffing and hyperactivity. All of these animals recovered and appeared normal from Day 17 through study termination. There were no treatment-related effects on motor activity, acoustic startle response, rotorod performance, forelimb group strength, toe and tail pinch reflexes, tibial nerve beta-glucuronidase activity or tail nerve conduction velocity. Although hindlimb grip strength of the 400 mg

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.

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

PubMed

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

2016-02-01

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

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

PubMed

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

2012-01-01

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

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.

A somatostatin analog improves tilt table tolerance by decreasing splanchnic vascular conductance

PubMed Central

Florian, J. P.; Curren, M. J.; Pawelczyk, J. A.

2012-01-01

Splanchnic hemodynamics and tilt table tolerance were assessed after an infusion of placebo or octreotide acetate, a somatostatin analog whose vascular effects are largely confined to the splanchnic circulation. We hypothesized that reductions in splanchnic blood flow (SpBF) and splanchnic vascular conductance (SpVC) would be related to improvements in tilt table tolerance. In randomized, double-blind, crossover trials, hemodynamic variables were collected in 14 women and 16 men during baseline, 70° head-up tilt (HUT), and recovery. A repeated-measures analysis of variance was used to compare changes from baseline with respect to sex and condition. HUT elicited an increase in heart rate and decreases in mean arterial pressure, cardiac index, stroke index, and systemic vascular conductance. Additionally, SpVC and non-SpVC were lower during HUT. Octreotide reduced SpBF and SpVC and increased systemic vascular conductance and non-SpVC. Changes in SpBF and SpVC between supine and HUT were smaller in women (P < 0.05). Tilt table tolerance was increased after administration of octreotide [median tilt time: 15.7 vs. 37.0 min (P < 0.05) and 21.8 vs. 45.0 min (P < 0.05) for women and men, respectively]. A significant relationship existed between change (Δ) in SpBF (placebo-octreotide) and Δtilt time in women (Δtilt time = 2.5–0.0083 ΔSpBF, P < 0.01), but not men (Δtilt time = 3.41–0.0008 ΔSpBF, P = 0.59). In conclusion, administration of octreotide acetate improved tilt table tolerance, which was associated with a decrease in SpVC. In women, but not men, the magnitude of reduction in SpBF was positively associated with improvements in tilt tolerance. PMID:22345429

Effect of N-acetylcysteine administration on homocysteine level, oxidative damage to proteins, and levels of iron (Fe) and Fe-related proteins in lead-exposed workers.

PubMed

Kasperczyk, Sławomir; Dobrakowski, Michał; Kasperczyk, Aleksandra; Romuk, Ewa; Rykaczewska-Czerwińska, Monika; Pawlas, Natalia; Birkner, Ewa

2016-09-01

N-Acetylcysteine (NAC) could be included in protocols designed for the treatment of lead toxicity. Therefore, in this study, we decided to investigate the influence of NAC administration on homocysteine (Hcy) levels, oxidative damage to proteins, and the levels of iron (Fe), transferrin (TRF), and haptoglobin (HPG) in lead (Pb)-exposed workers. The examined population (n = 171) was composed of male employees who worked with Pb. They were randomized into four groups. Workers who were not administered any antioxidants, drugs, vitamins, or dietary supplements were classified as the reference group (n = 49). The remaining three groups consisted of workers who were treated orally with NAC at three different doses (1 × 200, 2 × 200, or 2 × 400 mg) for 12 weeks. After the treatment, blood Pb levels significantly decreased in the groups receiving NAC compared with the reference group. The protein concentration was not affected by NAC administration. In contrast, Hcy levels significantly decreased or showed a strong tendency toward lower values depending on the NAC dose. Levels of the protein carbonyl groups were significantly decreased in all of the groups receiving NAC. Conversely, glutamate dehydrogenase activity was significantly elevated in all of the groups receiving NAC, while the level of protein thiol groups was significantly elevated only in the group receiving 200 mg of NAC. Treatment with NAC did not significantly affect Fe and TRF levels, whereas HPG levels showed a tendency toward lower values. Treatment with NAC normalized the level of Hcy and decreased oxidative stress as measured by the protein carbonyl content; this effect occurred in a dose-dependent manner. Moreover, small doses of NAC elevated the levels of protein thiol groups. Therefore, NAC could be introduced as an alternative therapy for chronic Pb toxicity in humans. © The Author(s) 2015.

The time dependent association of adrenaline administration and survival from out-of-hospital cardiac arrest.

PubMed

Ewy, Gordon A; Bobrow, Bentley J; Chikani, Vatsal; Sanders, Arthur B; Otto, Charles W; Spaite, Daniel W; Kern, Karl B

2015-11-01

Recommended for decades, the therapeutic value of adrenaline (epinephrine) in the resuscitation of patients with out-of-hospital cardiac arrest (OHCA) is controversial. To investigate the possible time-dependent outcomes associated with adrenaline administration by Emergency Medical Services personnel (EMS). A retrospective analysis of prospectively collected data from a near statewide cardiac resuscitation database between 1 January 2005 and 30 November 2013. Multivariable logistic regression was used to analyze the effect of the time interval between EMS dispatch and the initial dose of adrenaline on survival. The primary endpoints were survival to hospital discharge and favourable neurologic outcome. Data from 3469 patients with witnessed OHCA were analyzed. Their mean age was 66.3 years and 69% were male. An initially shockable rhythm was present in 41.8% of patients. Based on a multivariable logistic regression model with initial adrenaline administration time interval (AATI) from EMS dispatch as the covariate, survival was greatest when adrenaline was administered very early but decreased rapidly with increasing (AATI); odds ratio 0.94 (95% Confidence Interval (CI) 0.92-0.97). The AATI had no significant effect on good neurological outcome (OR=0.96, 95% CI=0.90-1.02). In patients with OHCA, survival to hospital discharge was greater in those treated early with adrenaline by EMS especially in the subset of patients with a shockable rhythm. However survival rapidly decreased with increasing adrenaline administration time intervals (AATI). Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Decreasing radiation exposure on pediatric portable chest radiographs.

PubMed

Hawking, Nancy G; Sharp, Ted D

2013-01-01

To determine whether additional shielding designed for pediatric patients during portable chest exams that ascertain endotracheal tube placement would significantly decrease the amount of scatter radiation. Children aged 24 months or younger were intubated and received daily morning chest radiographs to determine endotracheal tube placement. For each measurement, the amount of scatter radiation decreased by more than 20% from a nonshielded exposure to a shielded exposure. There was a significant decrease in scatter radiation when using the lead shielding device along with appropriate collimation vs appropriate collimation alone. These results suggest that applying additional shielding to appropriately collimated chest radiographs could significantly reduce scatter radiation and therefore the overall dose to young children.

The effect of cisplatin administration on certain trace elements homeostasis in rats and the protective effect of silver birch (Betula pendula) sap.

PubMed

Muselin, Florin; Dumitrescu, Eugenia; Berbecea, Adina; Doma, Alexandru Octavian; Brezovan, Diana; Savici, Jelena; Trif, Alexandra; Cristina, Romeo Teodor

2018-02-07

A clinically active structure with known antitumor activities is cisplatin (CDDP), but this it comes with toxicity characteristics which can be faded by the beneficial effects of Silver birch (Betula pendula) sap. We aimed to assess the cisplatin activity on: Mn, Mg, Cu, Fe and Zn homeostasis in rats and to observe the effect of birch sap. Healthy Wistar rats (n = 10/group) were divided in four groups: Control: receiving 1 mL saline I.P. way + water; E1: cisplatin 20 mg kgbw -1 , I.P.; E2: cisplatin 20 mg kgbw -1 , I.P. + birch sap and Control sap group: 1 mL saline I.P. + birch sap. Blood was collected: at the trial's start and after 48 h, and blood and organs (liver, kidney and spleen) for the cytoarchitecture investigation and readings were sampled after seven days. Samples were processed in nitric acid by microwave digestion and readings were completed by flame atomic absorption spectroscopy, the outcomes being statistically analyzed by ANOVA. Cisplatin produced a significant imbalance in the trace elements homeostasis, the birch sap administration recovering them usual homeostasis status. Comparatively with the Control, rats exposed to cisplatin presented a not significant (p > 0.05) decrease of Zn (-26.74%) and Mg (-10.25%), a significant (p < 0.05) decrease of Cu (-27.73%) at 48 h, a highly significant (p < 0.01) decrease of Cu (-56.08%) and Fe (-85.35%) at seven days after administration and a not significant (p > 0.05) increase of Mn (+28.16%). Birch sap administration after Cisplatin was followed by restoration or nevertheless significant increase (p < 0.05) of the investigated trace elements Zn (+56.88% to 48 h/+89.94% after seven days), Mg (+26.86%/+95.74%), Cu (+23.13%/+74.56%), Fe (+39.64%/+440.11%) and Mn (+4.30%/+15.87%), suggesting them defence against cisplatin. Histology revealed the order of main altered organs after the CDDP exposure: kidney, spleen and liver. The study recommended the

A Retrospective Chart Review of Two Different Insulin Administration Systems on Glycemic Control in Older Adults in Long-Term Care.

PubMed

Boonin, Alan; Balinski, Brenda; Sauter, Jerry; Martinez, Joe; Abbott, Scott

2017-01-01

The current retrospective chart review compared glycemic control and cost impact of two insulin administration systems, V-Go ® versus usual care with standard of care (SOC) insulin injections, in eight patients residing in a nursing home (NH). A total of 1,937 blood glucose (BG) values were collected over 61 days. Significant improvements were observed for the V-Go versus SOC group in time in range 100 mg/dL to 200 mg/dL (V-Go 59.09% vs. SOC 34.02%; p < 0.001), reduced BG fluctuations as measured by standard deviation (V-Go 61.2 vs. SOC 92.1; p < 0.001), and improved mean daily BG (V-Go 159.38 mg/dL vs. SOC 223.86 mg/dL; p < 0.001). The estimated A1c change, calculated from BG values, decreased from 8.9% to 7.2% in the V-Go group and increased from 9.0% to 9.4% in the SOC group. Compared to SOC, use of V-Go decreased the mean time for insulin administration by nursing staff by 26.3 minutes per patient per day and associated labor costs by $328.75 per patient per month. Insulin administration with V-Go may improve glycemic control and reduce administration costs compared to existing care in the NH setting. [Journal of Gerontological Nursing, 43(1), 10-16.]. Copyright 2017, SLACK Incorporated.

Exogenous galanin attenuates spatial memory impairment and decreases hippocampal β-amyloid levels in rat model of Alzheimer's disease.

PubMed

Li, Lei; Yu, Liling; Kong, Qingxia

2013-11-01

One of the major pathological characteristics of Alzheimer's disease (AD) is the presence of enhanced deposits of beta-amyloid peptide (Aβ). The neuropeptide galanin (GAL) and its receptors are overexpressed in degenerating brain regions in AD. The functional consequences of galaninergic systems plasticity in AD are unclear. The objective of the present study was to investigate whether exogenous galanin could attenuate spatial memory impairment and hippocampal Aβ aggregation in rat model of AD. The effects of Aβ, galanin, galanin receptor 1 agonist M617 and galanin receptor 2 agonist AR-M1896 on spatial memory were tested by Morris water maze. The effects of Aβ, galanin, M617 and AR-M1896 on hippocampal Aβ protein expression were evaluated by western blot assay. The expression of galanin, galanin receptors 1 and 2 in rats' hippocampus were detected by real time PCR and western blot assay. The results showed that (1) Galanin administration was effective in improving the spatial memory and decreasing hippocampal Aβ levels after intracerebroventricular injection of Aβ; (2) AR-M1896 rather than M617 could imitate these effects of galanin; (3) GAL and GALR2 mRNA and protein levels increased significantly in hippocampus after Aβ administration, while GALR1 mRNA and protein levels did not change; (4) GAL, AR-M1896 and M617 administration did not show significant effect on GAL, GalR1 and GalR2 mRNA and protein levels in hippocampus after Aβ administration. These results implied that galanin receptor 2, but not receptor 1 was involved in the protective effects against spatial memory impairment and hippocampal Aβ aggregation.

Symptomatology of recurrent low back pain in nursing and administrative professions

PubMed Central

Läubli, Thomas; Hodler, Juerg; Klipstein, Andreas

2007-01-01

The aim of the present study was to explore if (a) recurrent low back pain (LBP) has different symptomatologies in cases from occupations with predominantly sitting postures compared to cases from occupations involving dynamic postures and frequent lifting and (b) if in the two occupational groups, different factors were associated with the presence of recurrent LBP. Hundred and eleven female subjects aged between 45 and 62 years with a long-standing occupation either in administrative or nursing professions, with and without recurrent LBP were examined. An extensive evaluation of six areas of interest (pain and disability, clinical examination, functional tests, MR examination, physical and psychosocial workplace factors) was performed. The variables from the six areas of interest were analyzed for their potential to discriminate between the four groups of subjects (administrative worker and nurses with and without recurrent LBP) by canonical discriminant analysis. As expected, the self-evaluation of physical and psychosocial workplace factors showed significant differences between the two occupational groups, which holds true for cases as well as for controls (P < 0.01). The functional tests revealed a tendency for rather good capacity in nurses with LBP and a decreased capacity in administrative personnel with LBP (P = 0.049). Neither self completed pain and disability questionnaires nor clinical examination or MR imaging revealed any significant difference between LBP cases from sedentary and non-sedentary occupations. When comparing LBP cases and controls within the two occupational groups, the functional tests revealed significant differences (P = 0.0001) yet only in administrative personnel. The clinical examination on the other hand only discriminated between LBP cases and controls in the nurses group (P < 0.0001). Neither MRI imaging nor self reported physical and psychosocial workplace factors discriminated between LBP cases and controls from

Decreased allopregnanolone induced by hormonal contraceptives is associated with a reduction in social behavior and sexual motivation in female rats.

PubMed

Santoru, Francesca; Berretti, Roberta; Locci, Andrea; Porcu, Patrizia; Concas, Alessandra

2014-09-01

Allopregnanolone is a neurosteroid involved in depression, memory, social, and sexual behavior. We have previously demonstrated that treatment with a combination of ethinylestradiol (EE) and levonorgestrel (LNG), two compounds frequently used in hormonal contraception, decreased brain allopregnanolone concentrations. These changes may contribute to some of the emotional and sexual disorders observed in hormonal contraceptive users. We thus examined whether the reduction in allopregnanolone concentrations induced by long-term EE/LNG administration was associated with altered emotional, learning, social, and sexual behaviors. Rats were orally treated with a combination of EE (0.030 mg) and LNG (0.125 mg) once a day for 4 weeks and were subjected to behavioral tests 24 h after the last administration. EE/LNG treatment reduced immobility behavior in the forced swim test, without affecting sucrose preference and spatial learning and memory. In the resident-intruder test, EE/LNG-treated rats displayed a decrease in dominant behaviors associated with a reduction in social investigation. In the paced mating test, EE/LNG treated rats showed a reduction in proceptive behaviors, while the lordosis quotient was not affected. Progesterone, but not estradiol, administration to EE/LNG-treated rats increased sexual activity and cerebrocortical allopregnanolone concentrations. Prior administration of finasteride decreased allopregnanolone concentrations and abolished the increase in proceptivity induced by progesterone administration. The decrease in brain allopregnanolone concentrations induced by EE/LNG treatment is associated with a reduction in social behavior and sexual motivation in female rats. These results might be relevant to the side effects sometimes exhibited by women taking hormonal contraceptives.

The effects of co-administration of benzhexol on the peripheral pharmacokinetics of oral levodopa in young volunteers

PubMed Central

ROBERTS, J.; WALLER, D. G.; RENWICK, A. G.; O'SHEA, N.; MACKLIN, B. S.; BULLING, M.

1996-01-01

1 The effects of benzhexol on the absorption and pharmacokinetics of an oral dose of levodopa have been studied in 10 young healthy volunteers. Subjects were given a suspension of levodopa (250 mg) 90 min after either benzhexol (5 mg) or placebo in a randomized cross over design with doses separated by at least 1 week; on each occasion carbidopa was given 1 h before and 5 h after the dose of levodopa. Soluble paracetamol and radiolabelled DTPA were given with the levodopa as markers of gastric emptying. 2 Most subjects showed two peaks in the levodopa plasma concentration–time curve on the placebo day, with the second minor peak occurring 1–2 h after the dose. After benzhexol administration all subjects showed two or more peak levodopa concentrations in plasma. Benzhexol administration caused a significant decrease in the maximum concentration (43%; P<0.05) of the initial peak and an increase (22%; P<0.1) in the maximum concentration of the second peak. This change in absorption profile caused by benzhexol significantly altered the ratios of the second peak compared with the initial peak for both the maximum concentrations (P<0.02) and for the AUC values (P<0.05). Benzhexol administration did not affect the total AUC of levodopa (7.30±1.09 vs 7.19±1.26 μg ml−1 h; means±s.d.). 3 The plasma concentration–time curves for paracetamol showed similar profiles to those for levodopa and the ratios of the peak concentrations and AUC values for the second peak compared with the initial peak were increased significantly by benzhexol administration (P<0.05). The total AUC of paracetamol was not affected by benzhexol administration (39.4±8.2 vs 40.0±8.9 μg ml−1 h; mean±s.d.) 4 Benzhexol altered the gastric emptying profile, shown by γ-scintigraphy, with a reduced extent of initial emptying prior to the establishment of the plateau which is characteristic of levodopa administration in the fasting state. In consequence the ratio of

Significant decrease of saturation index in erythrocytes membrane from subjects with non-alcoholic fatty liver disease (NAFLD).

PubMed

Notarnicola, Maria; Caruso, Maria Gabriella; Tutino, Valeria; Bonfiglio, Caterina; Cozzolongo, Raffaele; Giannuzzi, Vito; De Nunzio, Valentina; De Leonardis, Giampiero; Abbrescia, Daniela I; Franco, Isabella; Intini, Vincenza; Mirizzi, Antonella; Osella, Alberto R

2017-08-23

The lipidomic profiling of erythrocyte membranes is expected to provide a peculiar scenario at molecular level of metabolic and nutritional pathways which may influence the lipid balance and the adaptation and homeostasis of the organism. Considering that lipid accumulation in the cell is important in promoting tissue inflammation, the purpose of this study is to analyze the fatty acid profile in red blood cell membranes of patients with Non-Alcoholic Fatty Liver Disease (NAFLD), in order to identify and validate membrane profiles possibly associated with the degree of hepatic damage. This work presents data obtained at baseline from 101 subjects that participated to a nutritional trial (registration number: NCT02347696) enrolling consecutive subjects with NAFLD. Diagnosis of liver steatosis was performed by using vibration-controlled elastography implemented on FibroScan. Fatty acids, extracted from phospholipids of erythrocyte membranes, were quantified by gas chromatography method. The subjects with severe NAFLD showed a significant decrease of the ratio of stearic acid to oleic acid (saturation index, SI) compared to controls, 1.281 ± 0.31 vs 1.5 ± 0.29, respectively. Low levels of SI in red blood cell membranes, inversely associated with degree of liver damage, suggest that an impairment of circulating cell membrane structure can reflect modifications that take place in the liver. Subjects with severe NAFLDalso showed higher levels of elongase 5 enzymatic activity, evaluated as vaccenic acid to palmitoleic acid ratio. Starting from these evidences, our findings show the importance of lipidomic approach in the diagnosis and the staging of NAFLD.

Low dose naltrexone administration in morphine dependent rats attenuates withdrawal-induced norepinephrine efflux in forebrain.

PubMed

Van Bockstaele, Elisabeth J; Qian, Yaping; Sterling, Robert C; Page, Michelle E

2008-05-15

The administration of low dose opioid antagonists has been explored as a potential means of detoxification in opiate dependence. Previous results from our laboratory have shown that concurrent administration of low dose naltrexone in the drinking water of rats implanted with subcutaneous morphine pellets attenuates behavioral and biochemical signs of withdrawal in brainstem noradrenergic nuclei. Noradrenergic projections originating from the nucleus tractus solitarius (NTS) and the locus coeruleus (LC) have previously been shown to be important neural substrates involved in the somatic expression of opiate withdrawal. The hypothesis that low dose naltrexone treatment attenuates noradrenergic hyperactivity typically associated with opiate withdrawal was examined in the present study by assessing norepinephrine tissue content and norepinephrine efflux using in vivo microdialysis coupled to high performance liquid chromatography (HPLC) with electrochemical detection (ED). The frontal cortex (FC), amygdala, bed nucleus of the stria terminalis (BNST) and cerebellum were analyzed for tissue content of norepinephrine following withdrawal in morphine dependent rats. Naltrexone-precipitated withdrawal elicited a significant decrease in tissue content of norepinephrine in the BNST and amygdala. This decrease was significantly attenuated in the BNST of rats that received low dose naltrexone pre-treatment compared to controls. No significant difference was observed in the other brain regions examined. In a separate group of rats, norepinephrine efflux was assessed with in vivo microdialysis in the BNST or the FC of morphine dependent rats or placebo treated rats subjected to naltrexone-precipitated withdrawal that received either naltrexone in their drinking water (5 mg/L) or unadulterated water. Following baseline dialysate collection, withdrawal was precipitated by injection of naltrexone and sample collection continued for an additional 4 h. At the end of the experiment

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.

Enterobacter cloacae administration induces hepatic damage and subcutaneous fat accumulation in high-fat diet fed mice.

PubMed

Keskitalo, Anniina; Munukka, Eveliina; Toivonen, Raine; Hollmén, Maija; Kainulainen, Heikki; Huovinen, Pentti; Jalkanen, Sirpa; Pekkala, Satu

2018-01-01

Accumulating evidence indicates that gut microbiota plays a significant role in obesity, insulin resistance and associated liver disorders. Family Enterobacteriaceae and especially Enterobacter cloacae strain B29 have been previously linked to obesity and hepatic damage. The underlying mechanisms, however, remain unclear. Therefore, we comprehensively examined the effects of E. cloacae subsp. cloacae (ATCC® 13047™) administration on host metabolism of mice fed with high-fat diet (HFD). C57BL/6N mice were randomly divided into HFD control, chow control, and E. cloacae treatment groups. The E. cloacae treatment group received live bacterial cells in PBS intragastrically twice a week, every other week for 13 weeks. Both control groups received PBS intragastrically. After the 13-week treatment period, the mice were sacrificed for gene and protein expression and functional analyses. Our results show that E. cloacae administration increased subcutaneous fat mass and the relative proportion of hypertrophic adipocytes. Both subcutaneous and visceral fat had signs of decreased insulin signaling and elevated lipolysis that was reflected in higher serum glycerol levels. In addition, E. cloacae -treated mice had significantly higher hepatic AST and AST/ALT ratio, and their liver histology indicated fibrosis, demonstrating that E. cloacae subsp. cloacae administration promotes hepatic damage in HFD fed mice.

The Early Impact of an Administrative Processing Fee on Manuscript Submissions at The Journal of Bone & Joint Surgery.

PubMed

Nwachukwu, Benedict U; Schairer, William W; So, Conan; Bernstein, Jaime L; Herndon, James; Dodwell, Emily R

2016-10-05

There was a dramatic increase in the volume of manuscripts submitted to The Journal of Bone & Joint Surgery (JBJS) between 2009 and 2012. This resulted in increased journal administrative costs. To offset this financial burden, in May 2013, JBJS started charging authors an administrative processing fee at the time of submission. The purpose of this study was to assess the impact of the administrative fee on the volume and characteristics of manuscripts submitted to JBJS. Our analysis included 866 manuscripts submitted to JBJS between November 2012 and November 2013. We compared manuscripts submitted 6 months prior to fee implementation and prior to the announcement (denoted as the baseline group), in the several months prior to fee implementation but after the fee implementation announcement (denoted as the fee announcement group), and in the 6 months after fee implementation (denoted as the fee implementation group). Manuscripts were reviewed for institutional and author demographic characteristics, as well as for general study characteristics. In the first full calendar year (2014) after the implementation of the fee, the annual volume of submissions to JBJS declined by 33.5% compared with the annual submission volume in 2010 to 2012. In a comparative analysis, the geographical region of origin (p = 0.003), level of evidence (p < 0.0001), funding, and specialty differed between the 3 submission periods. However, subgroup analyses demonstrated that differences were attributable to the fee announcement group and that there were few important differences between the baseline and fee implementation groups. Reporting of funding information improved significantly between the baseline and fee implementation groups; in the post-fee implementation period, studies were more likely to have declared no external funding source (p = 0.001). The administrative processing fee at JBJS has been associated with a decrease in submission volume, but, overall, there has not been a

Decreasing unnecessary utilization in acute bronchiolitis care: results from the value in inpatient pediatrics network.

PubMed

Ralston, Shawn; Garber, Matthew; Narang, Steve; Shen, Mark; Pate, Brian; Pope, John; Lossius, Michele; Croland, Trina; Bennett, Jeff; Jewell, Jennifer; Krugman, Scott; Robbins, Elizabeth; Nazif, Joanne; Liewehr, Sheila; Miller, Ansley; Marks, Michelle; Pappas, Rita; Pardue, Jeanann; Quinonez, Ricardo; Fine, Bryan R; Ryan, Michael

2013-01-01

Acute viral bronchiolitis is the most common diagnosis resulting in hospital admission in pediatrics. Utilization of non-evidence-based therapies and testing remains common despite a large volume of evidence to guide quality improvement efforts. Our objective was to reduce utilization of unnecessary therapies in the inpatient care of bronchiolitis across a diverse network of clinical sites. We formed a voluntary quality improvement collaborative of pediatric hospitalists for the purpose of benchmarking the use of bronchodilators, steroids, chest radiography, chest physiotherapy, and viral testing in bronchiolitis using hospital administrative data. We shared resources within the network, including protocols, scores, order sets, and key bibliographies, and established group norms for decreasing utilization. Aggregate data on 11,568 hospitalizations for bronchiolitis from 17 centers was analyzed for this report. The network was organized in 2008. By 2010, we saw a 46% reduction in overall volume of bronchodilators used, a 3.4 dose per patient absolute decrease in utilization (95% confidence interval [CI] 1.4-5.8). Overall exposure to any dose of bronchodilator decreased by 12 percentage points as well (95% CI 5%-25%). There was also a statistically significant decline in chest physiotherapy usage, but not for steroids, chest radiography, or viral testing. Benchmarking within a voluntary pediatric hospitalist collaborative facilitated decreased utilization of bronchodilators and chest physiotherapy in bronchiolitis. Copyright © 2012 Society of Hospital Medicine.

Saccharomyces boulardii Administration Changes Gut Microbiota and Attenuates D-Galactosamine-Induced Liver Injury.

PubMed

Yu, Lei; Zhao, Xue-Ke; Cheng, Ming-Liang; Yang, Guo-Zhen; Wang, Bi; Liu, Hua-Juan; Hu, Ya-Xin; Zhu, Li-Li; Zhang, Shuai; Xiao, Zi-Wen; Liu, Yong-Mei; Zhang, Bao-Fang; Mu, Mao

2017-05-02

Growing evidence has shown that gut microbiome is a key factor involved in liver health. Therefore, gut microbiota modulation with probiotic bacteria, such as Saccharomyces boulardii, constitutes a promising therapy for hepatosis. In this study, we aimed to investigate the protective effects of S. boulardii on D-Galactosamine-induced liver injury in mice. Liver function test and histopathological analysis both suggested that the liver injury can be effectively attenuated by S. boulardii administration. In the meantime, S. boulardii induced dramatic changes in the gut microbial composition. At the phylum level, we found that S. boulardii significantly increased in the relative abundance of Bacteroidetes, and decreased the relative abundance of Firmicutes and Proteobacteria, which may explain the hepatic protective effects of S. boulardii. Taken together, our results demonstrated that S. boulardii administration could change the gut microbiota in mice and alleviate acute liver failure, indicating a potential protective and therapeutic role of S. boulardii.

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.

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.

Optimizing the electronic health record to standardize administration and documentation of nutritional supplements.

PubMed

Citty, Sandra W; Kamel, Amir; Garvan, Cynthia; Marlowe, Lee; Westhoff, Lynn

2017-01-01

Malnutrition in hospitalized patients is a major cause for hospital re-admission, pressure ulcers and increased hospital costs. Methods to improve the administration and documentation of nutritional supplements for hospitalized patients are needed to improve patient care, outcomes and resource utilization. Staff at a medium-sized academic health science center hospital in the southeastern United States noted that nutritional supplements ordered for patients at high risk for malnutrition were not offered or administered to patients in a standardized manner and/or not documented clearly in the electronic health record as per prescription. This paper reports on a process improvement project that redesigned the ordering, administration and documentation process of oral nutritional supplements in the electronic health record. By adding nutritional products to the medication order sets and adding an electronic nutrition administration record (ENAR) tab, the multidisciplinary team sought to standardize nutritional supplement ordering, documentation and administration at prescribed intervals. This process improvement project used a triangulated approach to evaluating pre- and post-process change including: medical record reviews, patient interviews, and nutrition formula room log reports. Staff education and training was carried out prior to initiation of the system changes. This process change resulted in an average decrease in the return of unused nutritional formula from 76% returned at baseline to 54% post-process change. The process change resulted in 100% of nutritional supplement orders having documentation about nutritional medication administration and/or reason for non-administration. Documentation in the ENAR showed that 41% of ONS orders were given and 59% were not given. Significantly more patients reported being offered the ONS product (p=0.0001) after process redesign and more patients (5% before ENAR and 86% after ENAR reported being offered the correct

Effect of Artemisia dracunculus Administration on Glycemic Control, Insulin Sensitivity, and Insulin Secretion in Patients with Impaired Glucose Tolerance.

PubMed

Méndez-Del Villar, Miriam; Puebla-Pérez, Ana M; Sánchez-Peña, María J; González-Ortiz, Luis J; Martínez-Abundis, Esperanza; González-Ortiz, Manuel

2016-05-01

To evaluate the effect of Artemisia dracunculus on glycemic control, insulin sensitivity, and insulin secretion in patients with impaired glucose tolerance (IGT). A randomized, double blind, placebo-controlled clinical trial was performed in 24 patients with diagnosis of IGT. Before and after the intervention, glucose and insulin levels were measured every 30 min for 2 h after a 75-g dextrose load, along with glycated hemoglobin A1c (A1C) and lipid profile. Twelve patients received A. dracunculus (1000 mg) before breakfast and dinner for 90 days; the remaining 12 patients received placebo. Area under the curve (AUC) of glucose and insulin, total insulin secretion, first phase of insulin secretion, and insulin sensitivity were calculated. Wilcoxon signed-rank, Mann-Whitney U, and chi-square tests were used for statistical analyses. The institutional ethics committee approved the protocol. After A. dracunculus administration, there were significant decreases in systolic blood pressure (SBP; 120.0 ± 11.3 vs. 113.0 ± 11.2 mmHg, P < .05), A1C (5.8 ± 0.3 vs. 5.6% ± 0.4%, P < .05), AUC of insulin (56,136.0 ± 27,426.0 vs. 44,472.0 ± 23,370.0 pmol/L, P < .05), and total insulin secretion (0.45 ± 0.23 vs. 0.35 ± 0.18, P < .05), with a significant increase in high-density lipoprotein cholesterol (HDL-C) (1.3 ± 0.3 vs. 1.4 ± 0.3 mmol/L, P < .05). There were no significant differences after placebo administration. A. dracunculus administration for 90 days in patients with IGT significantly decreased SBP, A1C, AUC of insulin, and total insulin secretion with a significant increase in HDL-C levels.

Long-term administration of pDC-Stimulative Lactococcus lactis strain decelerates senescence and prolongs the lifespan of mice.

PubMed

Sugimura, Tetsu; Jounai, Kenta; Ohshio, Konomi; Suzuki, Hiroaki; Kirisako, Takayoshi; Sugihara, Yoshihiko; Fujiwara, Daisuke

2018-05-01

The decline in immune function caused by aging increases the risk of infectious diseases, tumorigeneses and chronic inflammation, resulting in accelerating senescence. We previously reported a lactic acid bacteria, Lactococcus lactis strain Plasma (synonym of Lactococcus lactis subsp. lactis JCM 5805, Lc-Plasma), that stimulates plasmacytoid dendritic cells (pDCs), which play a crucial role in phylaxis from viral infection. In this study, we investigated the anti-aging effects of long-term oral administration of Lc-Plasma in a senescence-accelerated mouse strain, SAMP6. Mice given Lc-Plasma showed a significant improvement in survival rate at 82 weeks and a decreased senescence score as compared with control mice throughout this study. Anatomic analysis at 82 weeks revealed that the frequency of altered hepatocellular foci was significantly lower, and the incidence of other pathological findings in the liver and lungs tended to be lower in Lc-Plasma mice than in control mice. Transcription level of the IL-1β gene in lungs also tended to be lower in Lc-Plasma mice. Furthermore, the thinning of skin and age-related decrease in muscle mass were also significantly suppressed in the Lc-Plasma group as compared with the control group. Consistent with these phenotypic features, pDCs activity was significantly higher in Lc-Plasma mice than in control mice. In conclusion, long-term administration of Lc-Plasma can decelerate senescence and prolong lifespan via maintenance of the immune system due to activation of pDCs. Copyright © 2018 Elsevier B.V. All rights reserved.

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

PubMed

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

2013-03-01

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

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.

Calbindins decreased after space flight

NASA Technical Reports Server (NTRS)

Sergeev, I. N.; Rhoten, W. B.; Carney, M. D.

1996-01-01

Exposure of the body to microgravity during space flight causes a series of well-documented changes in Ca2+ metabolism, yet the cellular and molecular mechanisms leading to these changes are poorly understood. Calbindins, vitamin D-dependent Ca2+ binding proteins, are believed to have a significant role in maintaining cellular Ca2+ homeostasis. In this study, we used biochemical and immunocytochemical approaches to analyze the expression of calbindin-D28k and calbindin-D9k in kidneys, small intestine, and pancreas of rats flown for 9 d aboard the space shuttle. The effects of microgravity on calbindins in rats from space were compared with synchronous Animal Enclosure Module controls, modeled weightlessness animals (tail suspension), and their controls. Exposure to microgravity resulted in a significant and sustained decrease in calbindin-D28k content in the kidney and calbindin-D9k in the small intestine of flight animals, as measured by enzyme-linked immunosorbent assay (ELISA). Modeled weightlessness animals exhibited a similar decrease in calbindins by ELISA. Immunocytochemistry (ICC) in combination with quantitative computer image analysis was used to measure in situ the expression of calbindins in the kidney and the small intestine, and the expression of insulin in pancreas. There was a large decrease of immunoreactivity in renal distal tubular cell-associated calbindin-D28k and in intestinal absorptive cell-associated calbindin-D9k of space flight and modeled weightlessness animals compared with matched controls. No consistent difference in pancreatic insulin immunoreactivity between space flight, modeled weightlessness, and controls was observed. Regression analysis of results obtained by quantitative ICC and ELISA for space flight, modeled weightlessness animals, and their controls demonstrated a significant correlation. These findings after a short-term exposure to microgravity or modeled weightlessness suggest that a decreased expression of calbindins

The relation between cerebral serotonin levels and conditioned behaviour in the rat following the administration of LSD-25 and UML.

PubMed

Torre, M; Torre, E; Bogetto, F

1975-01-01

Successive daily injections of LSD-25 and UML (1-methyl-d-lysergic acid butanolamide) caused progressive depression of brain 5-HT levels in the rat. On the fourth day, the decrease was significant with respect to the highly significant fall observed after a single administration, whereas it had been shown earlier that conditioned behaviour is no longer affected by LSD-25 after 3 days and that simultaneous administration of a single dose of LSD-25 and UML is equally ineffective in this respect. Its depression of 5-HT levels, however, has now been shown to be equal to that of LSD-25 alone at doses that influence conditioned behaviour. The findings indicate that changes in such behaviour are not dependent on brain 5-HT levels and that no link exists between such levels and the psychotomimetic effect of LSD-25 in man.

Histologic characteristics and local cellular immunity of the gland of the third eyelid after topical ophthalmic administration of 2% cyclosporine for treatment of dogs with keratoconjunctivitis sicca.

PubMed

Izci, Celal; Celik, Ilhami; Alkan, Fahrettin; Ogurtan, Zeki; Ceylan, Cengiz; Sur, Emrah; Ozkan, Yasemin

2002-05-01

To evaluate the efficacy of topical administration of a 2% solution of cyclosporine (CsA) for treatment of dogs with keratoconjunctivitis sicca (KCS) and to correlate results with histopathologic characteristics and local cellular immunity of the gland of the third eyelid. 24 dogs with bilateral KCS. Lacrimal secretion was measured, using Schirmer tear test (STT) strips. Leukocyte and T-lymphocyte subsets were determined in blood samples. Histopathologic changes as well as CD4+, CD8+, and alpha-naphthyl-acetate esterase-positive (ANAE+) lymphocytes were evaluated. Clinical signs resolved at the end of 1 month in conjunction with significantly increased STT values, compared with baseline values. Fifteen and 30 days after discontinuation of CsA treatment, a decrease was observed in STT values in both eyes; however, only values for the right eye were significantly different. There was a significant decrease in the number of lymphocytes and ANAE+ lymphocytes 15 and 30 days after discontinuation of CsA treatment, compared with baseline values. Differences were not observed in number of CD4+ lymphocytes among treatment groups. However, there was a significant decrease in number of CD8+ lymphocytes with reversal of the CD4+:CD8+ in both eyes after CsA treatment for 30 days, compared with the control group. Increased secretory activity and decreased lymphocyte infiltration were characteristic histopathologic findings. Topical administration of a 2% solution of CsA was effective for the treatment of dogs with KCS. Strict follow-up monitoring is required after the cessation of treatment because of the possibility of recurrence of KCS.

Effects of 2-deoxy-D-glucose administration on cytokine production in BDF1 mice

NASA Technical Reports Server (NTRS)

Dreau, D.; Morton, D. S.; Foster, M.; Fowler, N.; Sonnenfeld, G.

2000-01-01

Physical exercise and diet changes have been shown to affect immune parameters, and similar effects are also induced by the administration of a nonmetabolizable glucose analog, 2-deoxy-D-glucose (2-DG). The present study was designed to characterize the effects of glucoprivation induced by 2-DG administration on concentrations of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and IL-6 in the blood and interferon-gamma (IFN-gamma), IL-2, and IL-4 in vitro production by partially purified T splenocytes in BDF1 mice. Mice (n = 8 per group) were injected intraperitoneally one or three times with 0, 500, 750, or 1000 mg/kg of 2-DG, and blood and spleens were collected 2 h after the last injection. Partially purified T splenocytes were cultured 24 h in the presence of concanavalin A (ConA). A significant increase in the corticosterone levels with the amount of 2-DG injected was observed after one or three injections (p<0.05). The amount of 2-DG injected was associated with an increase in TNF-alpha, IL-1beta, and IL-6 concentrations in the blood of mice after one or three injections of 2-DG (p<0.05). A significant decrease in in vitro proliferation of partially purified splenocytes in the presence of ConA was associated with a decrease in IFN-gamma production in the culture supernatants and an increase in IL-1 receptor expression on the cell surface (p<0.05).

Suppression of cocaine self-administration in monkeys: effects of delayed punishment.

PubMed

Woolverton, William L; Freeman, Kevin B; Myerson, Joel; Green, Leonard

2012-04-01

Delaying presentation of a drug can decrease its effectiveness as a reinforcer, but the effect of delaying punishment of drug self-administration is unknown. This study examined whether a histamine injection could punish cocaine self-administration in a drug-drug choice, whether delaying histamine would decrease its effectiveness, and whether the effects of delay could be described within a delay discounting framework. Monkeys were implanted with double-lumen catheters to allow separate injection of cocaine and histamine. In discrete trials, subjects first chose between cocaine (50 or 100 μg/kg/inj) alone and an injection of the same dose of cocaine followed immediately by an injection of histamine (0.37-50 μg/kg). Next, they chose between cocaine followed immediately by histamine and cocaine followed by an equal but delayed dose of histamine. When choosing between cocaine alone and cocaine followed immediately by histamine, preference increased with histamine dose from indifference to >80% choice of cocaine alone. When choosing between cocaine followed by immediate histamine and cocaine followed by delayed histamine, monkeys showed strong position preferences. When delayed histamine was associated with the nonpreferred position, preference for that option increased with delay from ≤30% to >85%. The corresponding decrease in choice of the preferred position was well described by a hyperboloid discounting function. Histamine can function as a punisher in the choice between injections of cocaine and delay can decrease its effectiveness as a punisher. The effects of delaying punishment of drug self-administration can be conceptualized within the delay discounting framework.

Thyrotrophin-releasing hormone decreases feeding and increases body temperature, activity and oxygen consumption in Siberian hamsters.

PubMed

Schuhler, S; Warner, A; Finney, N; Bennett, G W; Ebling, F J P; Brameld, J M

2007-04-01

Thyrotrophin-releasing hormone (TRH) is known to play an important role in the control of food intake and energy metabolism in addition to its actions on the pituitary-thyroid axis. We have previously shown that central administration of TRH decreases food intake in Siberian hamsters. This species is being increasingly used as a physiological rodent model in which to understand hypothalamic control of long-term changes in energy balance because it accumulates fat reserves in long summer photoperiods, and decreases food intake and body weight when exposed to short winter photoperiods. The objectives of our study in Siberian hamsters were: (i) to investigate whether peripheral administration of TRH would mimic the effects of central administration of TRH on food intake and whether these effects would differ dependent upon the ambient photoperiod; (ii) to determine whether TRH would have an effect on energy expenditure; and (iii) to investigate the potential sites of action of TRH. Both peripheral (5-50 mg/kg body weight; i.p.) and central (0.5 microg/ml; i.c.v.) administration of TRH decreased food intake, and increased locomotor activity, body temperature and oxygen consumption in the Siberian hamster, with a rapid onset and short duration of action. Systemic treatment with TRH was equally effective in suppressing feeding regardless of ambient photoperiod. The acute effects of TRH are likely to be centrally mediated and independent of its role in the control of the production of thyroid hormones. We conclude that TRH functions to promote a catabolic energetic state by co-ordinating acute central and chronic peripheral (thyroid-mediated) function.

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

PubMed Central

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

2005-01-01

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

Decreased sodium:potassium ratios in cats: 49 cases.

PubMed

Bell, Rory; Mellor, Dominic J; Ramsey, Ian; Knottenbelt, Clare

2005-06-01

Sodium:potassium (Na:K) ratios are often reported in feline biochemical panels, although the importance of this measurement has not been investigated. The aims of this study were to document the range of feline disease states associated with a decreased Na:K ratio, to determine the prevalence of this biochemical abnormality in a referral hospital population, and to identify any particular disease that was more likely to have a decreased Na:K ratio. A group of 49 cats with decreased Na:K ratios was compared with a group of 50 cats with normal Na:K ratios that were randomly selected from the same hospital population. Twelve of the 49 cats (24.5%) had gastrointestinal disease, 10 (20.4%) had urinary disease, 8 (16.3%) had endocrine disease, 8 (16.3%) had cardiorespiratory disease, and 5 (10.0%) had diseases affecting other body systems. Six (12.2%) had artifactually decreased Na:K ratios. No cat was identified with hypoadrenocorticism. Statistical analysis revealed that, although none of these disease states was significantly over- or under-represented in the affected group, a significantly higher proportion of cats with decreased Na:K ratio had body cavity effusions (P = .025). Serum potassium concentrations were significantly higher in the affected group (P < .0001), but there was no significant difference in mean sodium concentration between the 2 groups. Decreased Na:K ratios frequently occur in cats with diseases other than hypoadrenocorticism, including cats with effusions. These findings should be considered when evaluating cats with this biochemical abnormality.

Impact of the Di(2-Ethylhexyl) Phthalate Administration on Trace Element and Mineral Levels in Relation of Kidney and Liver Damage in Rats.

PubMed

Aydemir, Duygu; Karabulut, Gözde; Şimşek, Gülsu; Gok, Muslum; Barlas, Nurhayat; Ulusu, Nuriye Nuray

2018-04-13

Di(2-ethylhexyl) phthalate (DEHP) is a widely used synthetic polymer in the industry. DEHP may induce reproductive and developmental toxicity, obesity, carcinogenesis and cause abnormal endocrine function in both human and wildlife. The aim of this study was to investigate trace element and mineral levels in relation of kidney and liver damage in DEHP-administered rats. Therefore, prepubertal male rats were dosed with 0, 100, 200, and 400 mg/kg/day of DEHP. At the end of the experiment, trace element and mineral levels, glucose-6-phosphate dehydrogenase (G6PD), 6-phosphogluconate dehydrogenase (6-PGD), glutathione reductase (GR) and glutathione S-transferase (GST) enzyme activities were evaluated in the serum, liver, and kidney samples of rats. Furthermore, serum clinical biochemistry parameters, organ/body weight ratios and histological changes were investigated to evaluate impact of DEHP more detailed. Our data indicated that sodium (Na), calcium (Ca), potassium (K), lithium (Li), rubidium (Rb) and cesium (Cs) levels significantly decreased, however iron (Fe) and selenium (Se) concentrations significantly increased in DEHP-administered groups compared to the control in the serum samples. On the other hand, upon DEHP administration, selenium concentration, G6PD and GR activities were significantly elevated, however 6-PGD activity significantly decreased compared to the control group in the kidney samples. Decreased G6PD activity was the only significant change between anti-oxidant enzyme activities in the liver samples. Upon DEHP administration, aberrant serum biochemical parameters have arisen and abnormal histological changes were observed in the kidney and liver tissue. In conclusion, DEHP may induce liver and kidney damage, also result abnormalities in the trace element and mineral levels.

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