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Sample records for administered kava kava

  1. Toxicity of kava kava.

    PubMed

    Fu, Peter P; Xia, Qingsu; Guo, Lei; Yu, Hongtao; Chan, Po-Chuen

    2008-01-01

    Kava is a traditional beverage of various Pacific Basin countries. Kava has been introduced into the mainstream U.S. market principally as an anti-anxiety preparation. The effects of the long-term consumption of kava have not been documented adequately. Preliminary studies suggest possible serious organ system effects. The potential carcinogenicity of kava and its principal constituents are unknown. As such, kava extract was nominated for the chronic tumorigenicity bioassay conducted by the National Toxicology Program (NTP). At present toxicological evaluation of kava extract is being conducted by the NTP. The present review focuses on the recent findings on kava toxicity and the mechanisms by which kava induces hepatotoxicity.

  2. Kava lactones and the kava-kava controversy.

    PubMed

    Whitton, Peter A; Lau, Andrew; Salisbury, Alicia; Whitehouse, Julie; Evans, Christine S

    2003-10-01

    Kava-kava is a traditional beverage of the South Pacific islanders and has had centuries of use without major side effects. Standardised extracts of kava-kava produced in Europe have led to many serious health problems and even to death. The extraction process (aqueous vs. acetone in the two types of preparations) is responsible for the difference in toxicity as extraction of glutathione in addition to the kava lactones is important to provide protection against hepatotoxicity. The Michael reaction between glutathione and kava lactones, resulting in opening of the lactone ring, reduces the side effects of the kava kava extracts. This protective activity was demonstrated using Acanthamoebae castellanii in which 100% cell death occurred with 100 mg ml(-1) kava lactones alone, and 40% cell death with a mixture of 100 mg ml (-1)glutathione and 100 mg ml (-1) kava lactones. A comparison of kava lactone toxicity with other pharmaceutical products is discussed and recommendations made for safe usage of kava-kava products

  3. Role of ethanol in kava hepatotoxicity.

    PubMed

    Li, X Z; Ramzan, I

    2010-04-01

    Kava is known for its recreational, ceremonial and medicinal use in the Pacific. The aqueous non-alcoholic drink of kava rhizome produces intoxicating, relaxing and soothing effects. While kava's medicinal effects receive worldwide recognition, kava-containing products came under scrutiny after over 100 reports of spontaneous adverse hepatic effects. Many mechanisms have been postulated to explain the unexpected toxicity, one being pharmacokinetic interactions between kavalactones and co-administered drugs involving cytochrome P450 enzyme system. Alcohol is often co-injested in kava hepatotoxicity cases. This review evaluates the possible hepatotoxicity mechanisms involving alcohol and kava.

  4. The adverse effects of kava.

    PubMed

    Kava, R

    2001-03-01

    In Fiji, kava is also known as yaqona or grog. A convenient sample of 300 kava drinkers in Nadi, Lautoka, Ba and Sigatoka were studied to see whether local people in Fiji experienced side effects of kava use. Because males usually consume kava in Fiji, we approached specific groups of people and asked them to participate in the survey. To evaluate the side effects of kava consumption, we interviewed housewives of male kava drinkers regarding specific effects of kava. We interviewed these housewives during kava drinking sessions since they were usually not taking part in the kava drinking. We also interviewed employers of these kava drinkers and the market vendors in Nadi Town since they were closely involved with kava drinkers. Wives of kava users felt deprived of basic family needs due to the amount of money spent on kava. In Urban schools, 64% males and 46.2% had tried kava. The present study aims to assess the prevalence of side effects of kava usage among a community sample of kava drinkers in Fiji and to compare the result with some of the side effects provided by other studies. The questionnaire also asked how much kava was consumed and the reasons. Since kava use is very much part of our everyday culture and existence, convincing people to change their behavior and kava consumption is a major tasks. I hope that this study would emphasize the need at a national level to educate people on the harmful effects of kava and the need for the health ministry to view very heavy kava intake as contributing to morbidity in Fiji.

  5. Toxicokinetics of Kava

    PubMed Central

    Rowe, Anthony; Zhang, Lillian Yuan; Ramzan, Iqbal

    2011-01-01

    Kava is traditionally consumed by South Pacific islanders as a drink and became popular in Western society as a supplement for anxiety and insomnia. Kava extracts are generally well tolerated, but reports of hepatotoxicity necessitated an international reappraisal of its safety. Hepatotoxicity can occur as an acute, severe form or a chronic, mild form. Inflammation appears to be involved in both forms and may result from activation of liver macrophages (Kupffer cells), either directly or via kava metabolites. Pharmacogenomics may influence the severity of this inflammatory response. PMID:21541070

  6. Sebotropic eruption associated with use of oral kava kava supplement.

    PubMed

    Huynh, J C; Asgari, M M; Moore, M M

    2014-10-01

    Supplement use is prevalent, and its use is increasing among older adults. Dermatologists need to be aware of the adverse cutaneous effects that can result from herbal supplement use. A 55-year-old man presented with an eruption in a sebotropic distribution after consuming kava kava for 3 weeks, which resolved after discontinuation of the supplement. This case highlights the need for clinicians to consider kava kava in the differential of sebotropic eruptions. The biology, mechanism of action, and potential systemic and cutaneous effects of kava kava are reviewed.

  7. Kava Linked to Liver Damage

    MedlinePlus

    ... of these countries to remove kava from the market. Although liver damage appears to be rare, the FDA believes consumers should be informed of this potential risk. Kava, a member of the pepper family, ...

  8. Kava hepatotoxicity: a European view.

    PubMed

    Teschke, Rolf; Schwarzenboeck, Alexander; Akinci, Ahmet

    2008-10-03

    Kava was well tolerated and considered as devoid of major side effects only until 1998 when the first report of assumed kava hepatotoxicity appeared. Causality of hepatotoxicity for kava +/- comedicated drugs was evident after the use of predominantly ethanolic and acetonic kava extracts in Germany (n=7), Switzerland (n=2), United States (n=1), and Australia (n=1) as well as after aqueous extracts in New Caledonia (n=2). Compliance regarding the recommendation for daily kava dose and duration was ascertained in only a few patients, including 2 from Germany and Switzerland. Since 450 millions of daily doses of kava extracts equating to 15 millions of monthly doses were sold in Germany and Switzerland, hepatotoxicity by kava appeared to be rare--similar to other herbal remedies, dietary supplements, and synthetic drugs. Risk factors were found in most patients and include daily kava overdose, prolonged therapy, and comedication with up to 5 other herbal remedies, dietary supplements, and synthetic drugs. Kava hepatotoxicity was not reported until 1998, thus raising the question of inferior quality of the kava raw material at times of the kava boom later on. Insufficiently defined regulatory guidelines to produce kava extracts are of some concern. Open questions refer not only to kava cultivars, but also to analytical methods and definitions of extract media and contents. Future strategies should therefore focus on the solution of a standard methodology of ascertaining quality that can assure a high degree of reliability in conjunction with actions by regulators, physicians, manufacturers, and producers. A medical advisory is also recommended as part of the labelling.

  9. Rhabdomyolysis associated with kava ingestion.

    PubMed

    Bodkin, Ryan; Schneider, Sandra; Rekkerth, Donna; Spillane, Linda; Kamali, Michael

    2012-05-01

    We report a case of rhabdomyolysis temporally related to the ingestion of a large amount of kava. Kava is a naturally occurring plant used in the United States and elsewhere in the world for its sedative properties. A previous case report also related rhabdomyolysis to the ingestion of kava. It is not clear whether this is an action of the kava itself, perhaps, due to its action on voltage ion channels or, perhaps, due to an adulterant in the product. Our patient developed peak creatine phosphokinase levels in excess of 30 000 U/L but had no significant renal damage.

  10. Kava hepatotoxicity: pathogenetic aspects and prospective considerations.

    PubMed

    Teschke, Rolf

    2010-10-01

    Kava hepatotoxicity is a well-defined herb-induced liver injury, caused by the use of commercial anxyolytic ethanolic and acetonic kava extracts, and of traditional recreational aqueous kava extracts. The aim of this review is to elucidate possible pathogenetic factors for the development of kava-induced liver injury, considering also confounding variables. In patients with liver disease in a causal relation to kava ± comedication, confounding factors include non-adherence to therapy recommendations and comedication consisting of synthetic and herbal drugs and dietary supplements including herbal ones and herbs-kava mixtures. Various possible pathogenetic factors have to be discussed and comprise metabolic interactions with exogenous compounds at the hepatic microsomal cytochrome P450 level; genetic enzyme deficiencies; toxic constituents and metabolites derived from the kava extract including impurities and adulterations; cyclooxygenase inhibition; P-glycoprotein alterations; hepatic glutathione depletion; solvents and solubilizers of the extracts; and kava raw material of poor quality. In particular, inappropriate kava plant parts and unsuitable kava cultivars may have been used sometimes for manufacturing the kava extracts instead of the rhizome of a noble cultivar of the kava plant (Piper methysticum G. Forster). In conclusion, kava hepatotoxicity occurred independently of the extraction medium used for the kava extracts and may primarily be attributed to daily overdose, prolonged treatment and to a few kava extract batches of poor quality; by improving kava quality and adherence to therapy recommendation under avoidance of comedication, liver injury by kava should be a preventable disease, at least to a major extent.

  11. Effect of goldenseal (Hydrastis canadensis) and kava kava (Piper methysticum) supplementation on digoxin pharmacokinetics in humans.

    PubMed

    Gurley, Bill J; Swain, Ashley; Barone, Gary W; Williams, D Keith; Breen, Philip; Yates, C Ryan; Stuart, Leslie B; Hubbard, Martha A; Tong, Yudong; Cheboyina, Sreekhar

    2007-02-01

    Phytochemical-mediated modulation of P-glycoprotein (P-gp) and other drug transporters may give rise to many herb-drug interactions. Serial plasma concentration-time profiles of the P-gp substrate, digoxin, were used to determine whether supplementation with goldenseal or kava kava modified P-gp activity in vivo. Twenty healthy volunteers were randomly assigned to receive a standardized goldenseal (3210 mg daily) or kava kava (1227 mg daily) supplement for 14 days, followed by a 30-day washout period. Subjects were also randomized to receive rifampin (600 mg daily, 7 days) and clarithromycin (1000 mg daily, 7 days) as positive controls for P-gp induction and inhibition, respectively. Digoxin (Lanoxin, 0.5 mg) was administered p.o. before and at the end of each supplementation and control period. Serial digoxin plasma concentrations were obtained over 24 h and analyzed by chemiluminescent immunoassay. Comparisons of area under the curve (AUC)((0-3)), AUC((0-24)), C(max,) CL/F, and elimination half-life were used to assess the effects of goldenseal, kava kava, rifampin, and clarithromycin on digoxin pharmacokinetics. Rifampin produced significant reductions (p < 0.01) in AUC((0-3)), AUC((0-24)), CL/F, t(1/2), and C(max), whereas clarithromycin increased these parameters significantly (p < 0.01). With the exception of goldenseal's effect on C(max) (14% increase), no statistically significant effects on digoxin pharmacokinetics were observed following supplementation with either goldenseal or kava kava. When compared with rifampin and clarithromycin, supplementation with these specific formulations of goldenseal or kava kava did not appear to affect digoxin pharmacokinetics, suggesting that these supplements are not potent modulators of P-gp in vivo.

  12. Kava consumption and its health effects.

    PubMed

    Gounder, Ramneek

    2006-09-01

    Sakau or Kava is a psychoactive beverage used ceremonially for thousands of years by Pacificans Kava beverage is made from the root of the pepper plant, Piper methysticum. It contains herbal ingredients for reliving anxiety and tension. The Kava's biological effects is due to a mixture of compounds called kava lactones which are reported to include sedative, anxiolytic, anti-stress, analgesic, local anaesthetic, anticonvulsant and neuroprotective properties. A skin disorder or dermopathy, occurs with prolonged use of large amounts of kava and reversible on reduced intake or cessation. Heavy kava drinkers acquire a reversible ichthyosiform eruption, known as kanikani in Fijian. Rare cases of interactions have occurred with pharmaceutical drugs that share one or more mechanisms of action with the kava lactones Kava was banned in the United Kingdom, after concerns that the product can cause liver toxicity. The US Food and drug Administration is still investigating kava's continued use in United States.

  13. Are mould hepatotoxins responsible for kava hepatotoxicity?

    PubMed

    Rowe, Anthony; Ramzan, Iqbal

    2012-11-01

    Previous studies with kava components such as kavalactones, pipermethystine and flavokavain B have demonstrated hepatotoxicity from these constituents. Regardless, there has recently been speculation that adulterants or impurities such as the mould hepatotoxin aflatoxin are a more likely cause of kava hepatotoxicity, despite a paucity of supporting evidence. Although there is limited similarity between acute kava hepatotoxicity and acute aflatoxicosis, and background levels of aflatoxin have been detected in kava samples, unless epidemiological investigations can uncover direct evidence implicating mould hepatotoxins, it remains more likely that chemical constituents of kava are the cause of the hepatotoxicity from kava.

  14. Analysis of responses to kava kava in the feline pulmonary vascular bed.

    PubMed

    Hoover, Jason M; Kaye, Alan D; Ibrahim, Ikhlass N; Fields, Aaron M; Richards, Todd A

    2006-01-01

    This study was designed to test the hypothesis that kava kava induces a depressor response in the pulmonary vascular bed of the cat and to identify the pathways involved in the mediation or modulation of these effects. In separate experiments, the effects of L-N5-(1-iminoethyl)ornithine hydrochloride (L-NIO), a nitric oxide synthase inhibitor, glibenclamide, an ATP-sensitive K+ channel blocker, meclofenamate, a nonselective cyclooxygenase inhibitor, nicardipine, a calcium channel blocker, bicuculline, a gamma-aminobutyric acid (GABA)A receptor antagonist, and saclofen, a GABAB antagonist, were investigated on pulmonary arterial responses to kava kava (kava), pinacidil, an ATP-sensitive K+ channel activator, bradykinin, an inducer of nitric oxide synthase, 3-aminopropyl(methyl)phosphinic acid hydrochloride (SKF-97541), a GABAB receptor agonist, and muscimol, a GABAA receptor agonist. Lobar arterial perfusion pressure and systemic pressure were continuously monitored, electronically averaged, and recorded. Under elevated tone conditions in the isolated left lower lobe of the feline vascular bed, kava induced a dose-dependent vasodepressor response that was not significantly altered after administration of L-NIO, glibenclamide, meclofenamate, or saclofen. Responses to kava were significantly reduced after administration of either nicardipine or bicuculline. When the calcium channel blocker nicardipine was administered in addition to the GABA blocker bicuculline, there was near complete attenuation of the kava-induced vasodepressor responses. The results of this investigation suggest that kava has potent vasodepressor activity in the feline lung bed and that this response is mediated or modulated by both a calcium channel- and GABA receptor-sensitive pathway.

  15. Kava dermopathy in Fiji: an acquired ichthyosis?

    PubMed

    Hannam, Sarah; Murray, Michael; Romani, Lucia; Tuicakau, Meciusela; J Whitfeld, Margot

    2014-12-01

    Kava dermopathy is a common cutaneous effect of regular or heavy use of Kava, a psychoactive beverage consumed widely throughout the Pacific. In Fiji in 2012, over 1000 study participants underwent full skin examination, and kava dermopathy was a common cutaneous finding. The clinical manifestations of kava dermopathy share similarities with the spectrum of autosomal recessive congenital ichthyoses, predominantly lamellar ichthyosis. The pathogenesis of Kava dermopathy may be associated with a functional defect in one or more cytochrome P450 enzymes implicated in epidermal integrity, thus mimicking the genetic defect as seen in lamellar ichthyosis type 3.

  16. Kava hepatotoxicity--a clinical review.

    PubMed

    Teschke, Rolf

    2010-01-01

    This review critically analyzes the clinical data of patients with suspected kava hepatotoxicity and suggests recommendations for minimizing risk. Kava is a plant (Piper methysticum) of the pepper family Piperaceae, and its rhizome is used for traditional aqueous extracts in the South Pacific Islands and for commercial ethanolic and acetonic medicinal products as anxiolytic herbs in Western countries. A regulatory ban for ethanolic and acetonic kava extracts was issued in 2002 for Germany on the basis of reports connecting liver disease with the use of kava, but the regulatory causality assessment was a matter of international discussions. Based on one positive reexposure test with the kava drug, it was indeed confirmed that kava is potentially hepatotoxic. In subsequent studies using a structured, quantitative and hepatotoxicity specific causality assessment method in 14 patients with liver disease described worldwide, causality for kava +/- comedicated drugs and dietary supplements including herbal ones was highly probable (n = 1), probable (n = 4) or possible (n = 9) regarding aqueous extracts (n = 3), ethanolic extracts (n = 5), acetonic extracts (n = 4), and mixtures containing kava (n = 2). Risk factors included overdose, prolonged treatment, and comedication with synthetic drugs and dietary supplements comprizing herbal ones in most of the 14 patients. Hepatotoxicity occurred independently of the used solvent, suggesting poor kava raw material quality as additional causative factor. In conclusion, in a few individuals kava may be hepatotoxic due to overdose, prolonged treatment, comedication, and probably triggered by an unacceptable quality of the kava raw material; standardization is now required, minimizing thereby hepatotoxic risks.

  17. Proposal for a kava quality standardization code.

    PubMed

    Teschke, Rolf; Lebot, Vincent

    2011-10-01

    Rare cases of hepatotoxicity emerged with the use of kava drugs and dietary supplements prepared from rhizomes and roots of the South Pacific plant kava (Piper methysticum). Their psychoactive, anxiolytic, relaxing, and recreational ingredients are the kavalactones kavain, dihydrokavain, methysticin, dihydromethysticin, yangonin, and desmethoxyyangonin, but there is little evidence that these kavalactones or the non-kavalactones pipermethystine and flavokavain B are the culprits of the adverse hepatic reactions. It rather appears that poor quality of the kava material was responsible for the liver toxicity. Analysis of existing kava quality standardizations with focus on chemical, agricultural, manufacturing, nutritional, regulatory, and legislation backgrounds showed major shortcomings that could easily explain quality problems. We therefore suggest a uniform, internationally accepted device for kava quality standardizations that are in the interest of the consumers because of safety reasons and will meet the expectations of kava farmers, pharmaceutical manufacturers, regulators of agencies, and legislators. The initial step resides in the establishment of Pan-Pacific kava quality legislation as an important part of the proposed Kava Quality Standardization Code. In conclusion, a sophisticated approach to establish kava quality standardizations is needed for safe human use of kava as relaxing traditional beverages, the anxiolytic drugs, and recreational dietary supplements.

  18. Kava hepatotoxicity solution: A six-point plan for new kava standardization.

    PubMed

    Teschke, Rolf; Sarris, Jerome; Lebot, Vincent

    2011-01-15

    Kava-induced liver injury has been demonstrated in a few patients worldwide and appears to be caused by inappropriate quality of the kava raw material. When cases of liver disease in connection with the use of kava emerged, this was an unexpected and challenging event considering the long tradition of safe kava use. In order to prevent kava hepatotoxicity in future, a set of quality specifications as standard is essential for the preparation not only of kava drugs and kava dietary supplements in the Western world but also for traditional kava drinks in the South Pacific Islands. For all these purposes a uniform approach is required, using water based extracts from the peeled rhizomes and roots of a noble cultivar such as Borogu with at least 5 years of age at the time of harvest. Cultivated in Vanuatu for centuries, noble varieties (as defined in the Vanuatu Kava Act of December 2002) are well tolerated traditional cultivars with a good safety record. At present, Vanuatu kava legislation is inadequately enforced to meet quality issues for kava, and further efforts are required in Vanuatu, in addition to similar legislation in other kava producing South Pacific Islands. Future regulatory and commercial strategies should focus not only on the standardization of kava drugs, kava dietary supplements, and traditional kava extracts, but also on thorough surveillance during the manufacturing process to improve kava quality for safe human use. The efficacy of kava extracts to treat patients with anxiety disorders is well supported, but further clinical trials with aqueous kava extracts are necessary. We thereby propose a six-point kava solution plan: (1) use of a noble kava cultivar such as Borogu, at least 5 years old at time of harvest, (2) use of peeled and dried rhizomes and roots, (3) aqueous extraction, (4) dosage recommendation of ≤250mg kavalactones per day (for medicinal use), (5) systematic rigorous future research, and (6) a Pan Pacific quality control system

  19. Liver toxicity and carcinogenicity in F344/N rats and B6C3F1 mice exposed to Kava Kava.

    PubMed

    Behl, Mamta; Nyska, Abraham; Chhabra, Rajendra S; Travlos, Gregory S; Fomby, Laurene M; Sparrow, Barney R; Hejtmancik, Milton R; Chan, Po C

    2011-11-01

    Kava Kava is an herbal supplement used as an alternative to antianxiety drugs. Although some reports suggest an association of Kava Kava with hepatotoxicity , it continues to be used in the United States due to lack of toxicity characterization. In these studies F344/N rats and B6C3F1 mice were administered Kava Kava extract orally by gavage in corn oil for two weeks, thirteen weeks or two years. Results from prechronic studies administered Kava Kava at 0.125 to 2g/kg body weight revealed dose-related increases in liver weights and incidences of hepatocellular hypertrophy. In the chronic studies, there were dose-related increases in the incidences of hepatocellular hypertrophy in rats and mice administered Kava Kava for up to 1g/kg body weight. This was accompanied by significant increases in incidences of centrilobular fatty change. There was no treatment- related increase in carcinogenic activity in the livers of male or female rats in the chronic studies. Male mice showed a significant dose-related increase in the incidence of hepatoblastomas. In female mice, there was a significant increase in the combined incidence of hepatocellular adenoma and carcinoma in the low and mid dose groups but not in the high dose group. These findings were accompanied by several nonneoplastic hepatic lesions.

  20. Toxic hepatitis after consumption of traditional kava preparation.

    PubMed

    Christl, Stefan U; Seifert, Axel; Seeler, Dirk

    2009-01-01

    Liver toxicity from the use of kava dietary supplements has been reported, but little is known about the side effects of traditional kava preparations. We present a case study of a tourist who developed serious toxic liver disease after consumption of kava beverages in traditional Samoan kava ceremonies.

  1. Discriminative-stimulus and time-course effects of kava-kava (Piper methysticum) in rats.

    PubMed

    Bruner, Natalie R; Anderson, Karen G

    2009-04-01

    Kava is a widely available and used herbal medicine that is not regulated in many countries. There are many questions concerning kava's stimulus properties, potential for therapeutic use, and potential for abuse. Although there is evidence that kava may possess some anxiolytic properties, kava's mechanism of action and the extent to which it may serve as an alternative to pharmaceutical anxiolytics are not fully known. The current study was designed to evaluate whether kava shares discriminative-stimulus properties with the anxiolytic chlordiazepoxide (CDP). Effects of different doses of kava extract were evaluated in two groups of rats trained to discriminate either a high or low training dose of CDP (i.p.). In order to assess time-course effects, two tests were conducted/session at 60 (Test One) and 90 (Test Two) min following oral administration of kava, CDP, or d-amphetamine. Dose-dependent substitution of CDP was found in both training groups in both tests. Kava (560 mg/kg, p.o.) occasioned responding indicative of partial substitution in both groups during Test One and only the low-dose group during Test Two. Partial substitution of kava extract for CDP suggests that the herbal compound may share a mechanism of action similar to CDP, but is less potent.

  2. Kava

    MedlinePlus

    ... Differences in dosages used, preparation methods, and study designs have resulted in mixed conclusions about kava’s usefulness. ... hard-of-hearing callers): 1-866-464-3615 Web site: nccih.nih.gov E-mail: info@nccih. ...

  3. KaVA ESTEMA project

    NASA Astrophysics Data System (ADS)

    Oyadomari, Miyako; Imai, Hiroshi; Cho, Se-Hyung; Asaki, Yoshiharu; Choi, Yoon-Kyong; Kim, Jaeheon; Yun, Youngjoo; Matsumoto, Naoko; Min, Cheul-Hong; Oyama, Tomoaki; Yoon, Sung-Chul; Yoon, Dong-Hwan; Kim, Dong-Jin; Dodson, Richard; Rioja, Maria; Burns, Ross; Orosz, Gabor; Nakagawa, Akiharu; Chibueze O, James; Nakashima, Jun-ichi; Sobolev, Andrey

    2016-07-01

    The ESTEMA (Expanded Study on Stellar Masers) project is one of three Large Programs of the KaVA (the combined array of the Korean VLBI Network and Japanese VLBI Exploration of Radio Astrometry), and conducted in 2015-2016. It aims to publish a database of the largest sample of VLBI images of circumstellar water (H2O) and silicon-monoxide (SiO) maser sources towards circumstellar envelopes (CSEs) of 80 evolved stars in late AGB to early post-AGB phase. Here we present the specifications of the ESTEMA observations and the planned scientific goals in order to share the basic information of the ESTEMA with astronomical community and encourage future collaborations with the ESTEMA and future follow-up observations for the targeted stars.

  4. Supplementation with goldenseal (Hydrastis canadensis), but not kava kava (Piper methysticum), inhibits human CYP3A activity in vivo.

    PubMed

    Gurley, B J; Swain, A; Hubbard, M A; Hartsfield, F; Thaden, J; Williams, D K; Gentry, W B; Tong, Y

    2008-01-01

    The effects of goldenseal (Hydrastis canadensis) and kava kava (Piper methysticum) supplementation on human CYP3A activity were evaluated using midazolam (MDZ) as a phenotypic probe. Sixteen healthy volunteers were randomly assigned to receive either goldenseal or kava kava for 14 days. Each supplementation phase was followed by a 30-day washout period. MDZ (8 mg, per os) was administered before and after each phase, and pharmacokinetic parameters were determined using standard non-compartmental methods. Comparisons of pre- and post-supplementation MDZ pharmacokinetic parameters revealed significant inhibition of CYP3A by goldenseal (AUC(0-infinity), 107.9+/-43.3 vs 175.3+/-74.8 ng x h/ml; Cl/F/kg, 1.26+/-0.59 vs 0.81+/-0.45 l/h/kg; T(1/2), 2.01+/-0.42 vs 3.15+/-1.12 h; Cmax, 50.6+/-26.9 vs 71.2+/-50.5 ng/ml). MDZ disposition was not affected by kava kava supplementation. These findings suggest that significant herb-drug interactions may result from the concomitant ingestion of goldenseal and CYP3A substrates.

  5. Kava hepatotoxicity in traditional and modern use: the presumed Pacific kava paradox hypothesis revisited.

    PubMed

    Teschke, Rolf; Sarris, Jerome; Schweitzer, Isaac

    2012-02-01

    Kava, a Pacific herb consumed worldwide for medicinal, recreational and cultural purposes, has been associated with rare hepatotoxicity, and there is currently a critical need to determine this causation. The previously proposed Pacific kava paradox was based on the theory that kava hepatotoxicity was not observed following use of traditional aqueous extracts in the Pacific region, but was restricted to use of Western acetonic and ethanolic extracts. Subsequent cases analyzed by the World Health Organization and published case reports revealed that traditional aqueous extracts used in New Caledonia, Australia, the USA and Germany may also be hepatotoxic; thus, there is no longer a basis to sustain the previously proposed Pacific kava paradox. It appears that the primary cause of toxicity may reside in the time before the preparation of the various kava extracts, possibly attributed to poor quality of the raw material caused by mould hepatotoxins. Rigorous testing of kava raw material is urgently advised, in addition to Pan-Pacific kava manufacturing quality standards. © 2011 The Authors. British Journal of Clinical Pharmacology © 2011 The British Pharmacological Society.

  6. Hepatitis A outbreak associated with kava drinking.

    PubMed

    Parker, Jo-Anne; Kurien, Thomas T; Huppatz, Clare

    2014-03-31

    Hepatitis A is caused by the hepatitis A virus (HAV), with transmission occurring through the faecal-oral route. In May 2013, a case of hepatitis A infection was reported to a Western Australian regional public health unit, with infection acquired in Fiji. Following this, 2 further cases were linked to the index case by kava drinking and 1 further case was a household contact of a secondary case. This outbreak highlights that the preparation of kava drink and/or the use of a common drinking vessel could be a vehicle for the transmission of HAV.

  7. Is kava alcohol?: The myths and the facts.

    PubMed

    Aporosa, S Apo

    2011-03-01

    This paper addresses the misconception that kava is an alcoholic substance. After a brief introduction as to what prompted the writing of this, I follow by discussing kava's cultural importance to Pacific peoples, and then compare kava 'intoxication' with alcohol intoxication. The paper concludes with a discussion of the historical influences that have promoted some of the misconceptions surrounding kava. Ultimately the paper demonstrates that kava and alcohol are entirely different kinds of beverages with different effects, and that lingering misconceptions can be seen as a 'colonial hangover'.

  8. Enhanced cognitive performance and cheerful mood by standardized extracts of Piper methysticum (Kava-kava).

    PubMed

    Thompson, Richard; Ruch, Willibald; Hasenöhrl, Rüdiger U

    2004-06-01

    The acute effects of the herbal anxiolytic Kava-kava (Piper methysticum G. Forster) on emotional reactivity and cognitive performance were investigated in a double-blind randomized placebo-controlled trial involving healthy volunteers. Subjects' reports of mood change were assessed with the state-trait-cheerfulness-inventory, which measures the three concepts of cheerfulness, seriousness and bad mood as both traits and states. Cognitive performance was examined with the Sperling partial report and the Sternberg item recognition task, which were used as an index for visual attention and short-term memory processing. The intake of a single dose of Kava extract (300 mg; p.o.) led to an increase in state cheerfulness, while the phytopharmacon did not influence state seriousness and bad mood. The mood-elevating effects of Kava were most prominent in trait cheerful subjects, indicating that trait cheerfulness moderated the drug-induced increase in cheerful mood. Furthermore, Kava improved the accuracy and the speed of performing the partial report and the item recognition task, indicative of a beneficial effect of the phytopharmacon on visual attention and short-term memory retrieval, respectively. Thus, unlike conventional benzodiazepine-type anxiolytics, which tend to impair cognitive performance and to increase the occurrence of negative affective states, Kava is a potent anxiolytic agent, which, additionally, can facilitate cognitive functioning and can increase positive affectivity related to exhilaration. Copyright 2004 John Wiley & Sons, Ltd.

  9. Reduction in colon cancer risk by consumption of kava or kava fractions in carcinogen-treated rats.

    PubMed

    Triolet, Julie; Shaik, Ahmad Ali; Gallaher, Daniel D; O'Sullivan, Michael G; Xing, Chengguo

    2012-08-01

    Epidemiological studies suggest that kava reduces colon cancer risk. However, no experimental studies of the chemopreventive properties of kava toward colon cancer have been reported. Further, there are concerns regarding hepatotoxicity of kava. The goal of this study was to determine whether kava consumption reduces markers of colon cancer in an animal model and to study the safety of kava. An ethanolic extract and polar and nonpolar fractions of the kava extract were fed to rats for 12 days prior to, during, and after administration of dimethylhydrazine, a colon-specific carcinogen. After 14 wk, rats fed the nonpolar extract had a significant reduction in precancerous lesions [aberrant crypt (AC) foci (ACF)] as well as large (≥ 4 AC/ACF) sialomucin-only expressing foci, an indicator of greater tumorigenic potential, compared to the control group. Groups fed the ethanolic extract and polar kava fraction trended toward reductions in ACF and large sialomucin-only expressing foci. The combined kava groups had significantly fewer total AC, ACF, large ACF, and large sialomucin-only expressing foci compared to the control group. Histological examination found no hepatic lesions in animals consuming the kava diets, suggesting that kava is safe to consume. Our results support that kava may reduce colon cancer risk.

  10. Constituents in kava extracts potentially involved in hepatotoxicity: a review.

    PubMed

    Olsen, Line R; Grillo, Mark P; Skonberg, Christian

    2011-07-18

    Aqueous kava root preparations have been consumed in the South Pacific as an apparently safe ceremonial and cultural drink for centuries. However, several reports of hepatotoxicity have been linked to the consumption of kava extracts in Western countries, where mainly ethanolic or acetonic extracts are used. The mechanism of toxicity has not been established, although several theories have been put forward. The composition of the major constituents, the kava lactones, varies according to preparation method and species of kava plant, and thus, the toxicity of the individual lactones has been tested in order to establish whether a single lactone or a certain composition of lactones may be responsible for the increased prevalence of kava-induced hepatotoxicity in Western countries. However, no such conclusion has been made on the basis of current data. Inhibition or induction of the major metabolizing enzymes, which might result in drug interactions, has also gained attention, but ambiguous results have been reported. On the basis of the chemical structures of kava constituents, the formation of reactive metabolites has also been suggested as an explanation of toxicity. Furthermore, skin rash is a side effect in kava consumers, which may be indicative of the formation of reactive metabolites and covalent binding to skin proteins leading to immune-mediated responses. Reactive metabolites of kava lactones have been identified in vitro as glutathione (GSH) conjugates and in vivo as mercapturates excreted in urine. Addition of GSH to kava extracts has been shown to reduce cytotoxicity in vitro, which suggests the presence of inherently reactive constituents. Only a few studies have investigated the toxicity of the minor constituents present in kava extract, such as pipermethystine and the flavokavains, where some have been shown to display higher in vitro cytotoxicity than the lactones. To date, there remains no indisputable reason for the increased prevalence of kava

  11. Kava and kava hepatotoxicity: requirements for novel experimental, ethnobotanical and clinical studies based on a review of the evidence.

    PubMed

    Teschke, Rolf; Qiu, Samuel X; Xuan, Tran Dang; Lebot, Vincent

    2011-09-01

    Kava hepatotoxicity is a well described disease entity, yet there is uncertainty as to the culprit(s). In particular, there is so far no clear evidence for a causative role of kavalactones and non-kavalactone constituents, such as pipermethystine and flavokavain B, identified from kava. Therefore, novel enzymatic, analytical, toxicological, ethnobotanical and clinical studies are now required. Studies should focus on the identification of further potential hepatotoxic constituents, considering in particular possible adulterants and impurities with special reference to ochratoxin A and aflatoxins (AFs) producing Aspergillus varieties, which should be urgently assessed and published. At present, Aspergillus and other fungus species producing hepatotoxic mycotoxins have not yet been examined thoroughly as possible contaminants of some kava raw materials. Its occurence may be facilitated by high humidity, poor methods for drying procedures and insufficient storage facilities during the time after harvest. Various experimental studies are recommended using aqueous, acetonic and ethanolic kava extracts derived from different plant parts, such as peeled rhizomes and peeled roots including their peelings, and considering both noble and non-noble kava cultivars. In addition, ethnobotanical studies associated with local expertise and surveillance are required to achieve a good quality of kava as the raw material. In clinical trials of patients with anxiety disorders seeking herbal anxiolytic treatment with kava extracts, long-term safety and efficacy should be tested using traditional aqueous extracts obtained from peeled rhizomes and peeled roots of a noble kava cultivar, such as Borogu, to evaluate the risk: benefit ratio. Concomitantly, more research should be conducted on the bioavailability of kavalactones and non-kavalactones derived from aqueous kava extracts. To be on the side of caution and to ensure lack of liver injury, kava consuming inhabitants of the kava

  12. The Health Effects of Kava/Sakau and Betel Nut.

    ERIC Educational Resources Information Center

    Lee, Harvey

    For generations Pacific Islanders have used kava root and betel nut for a variety of cultural, medicinal, and ceremonial purposes: to overcome social barriers and lubricate social interactions; to cure bodily afflictions; and to accompany traditional and religious rituals. Kava, also known as ava, sakau, and yaqona has a long tradition as a…

  13. The Health Effects of Kava/Sakau and Betel Nut.

    ERIC Educational Resources Information Center

    Lee, Harvey

    For generations Pacific Islanders have used kava root and betel nut for a variety of cultural, medicinal, and ceremonial purposes: to overcome social barriers and lubricate social interactions; to cure bodily afflictions; and to accompany traditional and religious rituals. Kava, also known as ava, sakau, and yaqona has a long tradition as a…

  14. Kava in generalized anxiety disorder: three placebo-controlled trials.

    PubMed

    Connor, Kathryn M; Payne, Victoria; Davidson, Jonathan R T

    2006-09-01

    In this study, we evaluated the efficacy and safety of kava kava (Piper methysticum) in generalized anxiety disorder. Data were analyzed from three randomized, double-blind, placebo-controlled trials of kava, including one study with an active comparator (venlafaxine), in adult outpatients with DSM-IV generalized anxiety disorder. The pooled sample (n=64) included the following number of participants: kava, n=28; placebo, n=30; and venlafaxine, n=6. Given the comparability of the study designs, the data comparing kava and placebo were then pooled for further efficacy and safety analyses. No significant differences were observed between the treatment groups in any of the trials. In the pooled analyses, no effects were found for kava, while a significant effect in favor of placebo was observed in participants with higher anxiety at baseline. No evidence of hepatotoxicity was found with kava, and all of the treatments were well tolerated. Findings from these three controlled trials do not support the use of kava in DSM-IV generalized anxiety disorder.

  15. Kava hepatotoxicity: regulatory data selection and causality assessment.

    PubMed

    Teschke, R; Wolff, A

    2009-12-01

    Kava hepatotoxicity in 20 patients from Germany has been debated worldwide following a regulatory ad hoc causality assessment and ban of kava, an anxiolytic herbal remedy obtained from the rhizome of Piper methysticum Forster. We assessed causality with a quantitative structured causality analysis in all 20 cases of patients with liver disease, presented by the German regulatory agency that assumed a causal relationship with the use of kava extracts. The quantitative scale of CIOMS (Council for International Organizations of Medical Sciences) in its updated form was employed for causality assessment and quality evaluation of the regulatory data presentation. The regulatory information is scattered and selective, and items essential for causality assessment, such as exclusion of kava independent causes, were not, or only marginally, considered by the regulator. Quantitative causality assessment for kava was possible (n=2), unlikely (n=12), or excluded (n=6), showing no concordance with the regulatory ad hoc causality evaluation. The regulatory data regarding kava hepatotoxicity is selective and of low quality, not supportive of the regulatory proposed causality; but instead, is an explanation of the overall causality discussions of kava hepatotoxicity. We are proposing that the regulatory agency reports data in full length and reevaluates causality.

  16. Extracts and kavalactones of Piper methysticum G. Forst (kava-kava) inhibit P-glycoprotein in vitro.

    PubMed

    Weiss, Johanna; Sauer, Alexandra; Frank, Andreas; Unger, Matthias

    2005-11-01

    Root extracts from kava-kava (Piper methysticum G. Forst) are clinically used for the treatment of anxiety and restlessness. Due to reported cases of liver toxicity, kava-kava extracts were withdrawn from the market in several countries in 2002. Because the efflux transporter P-glycoprotein (P-gp) is involved in the absorption, distribution, and excretion of many drugs and often participates in drug-drug interactions, we studied the effect of a crude kava extract and the main kavalactones kavain, dihydrokavain, methysticin, dihydromethysticin, yangonin, and desmethoxyyangonin on the P-gp-mediated efflux of calcein-acetoxymethylester in the P-gp-overexpressing cell line P388/dx and the corresponding cell line P388. The crude extract and the kavalactones showed a moderate to potent inhibitory activity with f2) (concentration needed to double baseline fluorescence) values of 170 microg/ml and 17 to 90 microM, respectively. The f2 value of yangonin could not be determined due to its higher lipophilicity. In conclusion, our results for the first time demonstrate P-gp-inhibitory activity of kava-kava and its components in vitro.

  17. Does inflammation play a role in kava hepatotoxicity?

    PubMed

    Zhang, Lillian Yuan; Rowe, Anthony; Ramzan, Iqbal

    2011-04-01

    The pathophysiology of kava hepatotoxicity remains inconclusive. There is circumstantial evidence for the roles of toxic metabolites, inhibition of cyclooxygenase (COX) enzymes and depletion of liver glutathione. Pharmacogenomic effects are likely, particularly for Cytochrome P450 genes. Experimental and clinical cases of hepatotoxicity show evidence of hepatitis. The question remains whether this inflammation is caused by components of kava directly, or indirectly due to the downstream effects.

  18. Driving following Kava Use and Road Traffic Injuries: A Population-Based Case-Control Study in Fiji (TRIP 14)

    PubMed Central

    Wainiqolo, Iris; Kafoa, Berlin; Kool, Bridget; Robinson, Elizabeth; Herman, Josephine; McCaig, Eddie; Ameratunga, Shanthi

    2016-01-01

    Objective To investigate the association between kava use and the risk of four-wheeled motor vehicle crashes in Fiji. Kava is a traditional beverage commonly consumed in many Pacific Island Countries. Herbal anxiolytics containing smaller doses of kava are more widely available. Methods Data for this population-based case-control study were collected from drivers of ‘case’ vehicles involved in serious injury-involved crashes (where at least one road user was killed or admitted to hospital for 12 hours or more) and ‘control’ vehicles representative of ‘driving time’ in the study base. Structured interviewer administered questionnaires collected self-reported participant data on demographic characteristics and a range of risk factors including kava use and potential confounders. Unconditional logistic regression models estimated odds ratios relating to the association between kava use and injury-involved crash risk. Findings Overall, 23% and 4% of drivers of case and control vehicles, respectively, reported consuming kava in the 12 hours prior to the crash or road survey. After controlling for assessed confounders, driving following kava use was associated with a four-fold increase in the odds of crash involvement (Odds ratio: 4.70; 95% CI: 1.90–11.63). The related population attributable risk was 18.37% (95% CI: 13.77–22.72). Acknowledging limited statistical power, we did not find a significant interaction in this association with concurrent alcohol use. Conclusion In this study conducted in a setting where recreational kava consumption is common, driving following the use of kava was associated with a significant excess of serious-injury involved road crashes. The precautionary principle would suggest road safety strategies should explicitly recommend avoiding driving following kava use, particularly in communities where recreational use is common. PMID:26930404

  19. Measuring the Chemical and Cytotoxic Variability of Commercially Available Kava (Piper methysticum G. Forster)

    PubMed Central

    Martin, Amanda C.; Johnston, Ed; Xing, Chengguo; Hegeman, Adrian D.

    2014-01-01

    Formerly used world-wide as a popular botanical medicine to reduce anxiety, reports of hepatotoxicity linked to consuming kava extracts in the late 1990s have resulted in global restrictions on kava use and have hindered kava-related research. Despite its presence on the United States Food and Drug Administration consumer advisory list for the past decade, export data from kava producing countries implies that US kava imports, which are not publicly reported, are both increasing and of a fairly high volume. We have measured the variability in extract chemical composition and cytotoxicity towards human lung adenocarcinoma A549 cancer cells of 25 commercially available kava products. Results reveal a high level of variation in chemical content and cytotoxicity of currently available kava products. As public interest and use of kava products continues to increase in the United States, efforts to characterize products and expedite research of this potentially useful botanical medicine are necessary. PMID:25365244

  20. Measuring the chemical and cytotoxic variability of commercially available kava (Piper methysticum G. Forster).

    PubMed

    Martin, Amanda C; Johnston, Ed; Xing, Chengguo; Hegeman, Adrian D

    2014-01-01

    Formerly used world-wide as a popular botanical medicine to reduce anxiety, reports of hepatotoxicity linked to consuming kava extracts in the late 1990s have resulted in global restrictions on kava use and have hindered kava-related research. Despite its presence on the United States Food and Drug Administration consumer advisory list for the past decade, export data from kava producing countries implies that US kava imports, which are not publicly reported, are both increasing and of a fairly high volume. We have measured the variability in extract chemical composition and cytotoxicity towards human lung adenocarcinoma A549 cancer cells of 25 commercially available kava products. Results reveal a high level of variation in chemical content and cytotoxicity of currently available kava products. As public interest and use of kava products continues to increase in the United States, efforts to characterize products and expedite research of this potentially useful botanical medicine are necessary.

  1. Contaminant hepatotoxins as culprits for kava hepatotoxicity--fact or fiction?

    PubMed

    Teschke, Rolf; Sarris, Jerome; Lebot, Vincent

    2013-03-01

    The culprit of kava hepatotoxicity will continue to remain a mystery in humans, if the underlying reaction is of idiosyncratic, unpredictable, and dose-independent nature due potentially to some metabolic aberration in a few individuals emerging from kava use. In addition, kava hepatotoxicity is presently not reproducible experimentally in preclinical models, as demonstrated by studies showing whole kava extracts are not hepatotoxic. This led us to propose our 'working hypothesis' that contaminant hepatotoxins including moulds might have caused rare kava hepatotoxicity in humans. Further studies are now warranted to proof or disproof our working hypothesis, because kava hepatotoxicity possibly based on contaminant hepatotoxins could be a preventable disease. In the meantime, however, for minimizing toxicity risk in kava users, a pragmatic approach should focus on the medicinal use of an aqueous extract derived from peeled rhizomes and roots of a non-mouldy noble kava cultivar, limited to maximum 250-mg kavalactones daily for acute or intermittent use.

  2. Hepatocellular toxicity of kava leaf and root extracts.

    PubMed

    Lüde, Saskia; Török, Michael; Dieterle, Sandy; Jäggi, René; Büter, Karin Berger; Krähenbühl, Stephan

    2008-01-01

    Kava extracts are used widely for different purposes and were thought to be safe. Recently, several cases of hepatotoxicity have been published. To explore possible mechanisms of kava hepatotoxicity, we prepared and analyzed three different kava extracts (a methanolic and an acetonic root and a methanolic leaf extract), and investigated their toxicity on HepG2 cells and isolated rat liver mitochondria. All three extracts showed cytotoxicity starting at a concentration of 50 microg/ml (lactate dehydrogenase leakage) or 1 microg/ml (MTT test). The mitochondrial membrane potential was decreased (root extracts starting at 50 microg/ml) and the respiratory chain inhibited and uncoupled (root extracts) or only uncoupled (leaf extract) at 150 microg/ml, and mitochondrial beta-oxidation was inhibited by all extracts starting at 100 microg/ml. The ratio oxidized to reduced glutathione was increased in HepG2 cells, whereas the cellular ATP content was maintained. Induction of apoptosis was demonstrated by all extracts at a concentration of 150 microg/ml. These results indicate that the kava extracts are toxic to mitochondria, leading to inhibition of the respiratory chain, increased ROS production, a decrease in the mitochondrial membrane potential and eventually to apoptosis of exposed cells. In predisposed patients, mitochondrial toxicity of kava extract may explain hepatic adverse reactions of this drug.

  3. Kava, the anxiolytic herb: back to basics to prevent liver injury?

    PubMed

    Teschke, Rolf; Sarris, Jerome; Glass, Xaver; Schulze, Johannes

    2011-03-01

    The use of the anxiolytic herb kava has caused toxic liver injury in Western countries and economic problems in South Pacific Islands due to tthe regulatory ban on kava. This analysis shows poor quality of kava raw material as a cause for its toxicity and suggests preventative measures by going back to the traditional use of kava for the sake of the patients and the South Pacific economy.

  4. Gene expression profiling in male B6C3F1 mouse livers exposed to kava identifies--changes in drug metabolizing genes and potential mechanisms linked to kava toxicity.

    PubMed

    Guo, Lei; Shi, Qiang; Dial, Stacey; Xia, Qingsu; Mei, Nan; Li, Quan-zhen; Chan, Po-Chuen; Fu, Peter

    2010-02-01

    The association of kava products with liver-related health risks has prompted regulatory action in many countries. We used a genome-wide gene expression approach to generate global gene expression profiles from the livers of male B6C3F1 mice administered kava extract by gavage for 14 weeks, and identified the differentially expressed drug metabolizing genes in response to kava treatments. Analyses of gene functions and pathways reveal that the levels of significant numbers of genes involving drug metabolism were changed and that the pathways involving xenobiotics metabolism, Nrf2-mediated oxidative stress response, mitochondrial functions and others, were altered. Our results indicate that kava extract can significantly modulate drug metabolizing enzymes, potentially leading to herb-drug interactions and hepatotoxicity.

  5. Identification of methysticin as a potent and non-toxic NF-kappaB inhibitor from kava, potentially responsible for kava's chemopreventive activity.

    PubMed

    Shaik, Ahmad Ali; Hermanson, David Lee; Xing, Chengguo

    2009-10-01

    Nuclear factor-kappaB (NF-kappaB) is a transcription factor that plays an essential role in cancer development. The results of our recent chemopreventive study demonstrate that kava, a beverage in the South Pacific Islands, suppresses NF-kappaB activation in lung adenoma tissues, potentially a mechanism responsible for kava's chemopreventive activity. Methysticin is identified as a potent NF-kappaB inhibitor in kava with minimum toxicity. Other kava constituents, including four kavalactones of similar structures to methysticin, demonstrate minimum activities in inhibiting NF-kappaB.

  6. Chemopreventive effect of kava on 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone plus benzo[a]pyrene-induced lung tumorigenesis in A/J mice.

    PubMed

    Johnson, Thomas E; Kassie, Fekadu; O'Sullivan, M Gerard; Negia, Mesfin; Hanson, Timothy E; Upadhyaya, Pramod; Ruvolo, Peter P; Hecht, Stephen S; Xing, Chengguo

    2008-11-01

    Lung cancer is the leading cause of cancer death, and chemoprevention is a potential strategy to help control this disease. Epidemiologic survey indicates that kava may be chemopreventive for lung cancer, but there is a concern about its potential hepatotoxicity. In this study, we evaluated whether oral kava could prevent 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) plus benzo[a]pyrene (B[a]P)-induced lung tumorigenesis in A/J mice. We also studied the effect of kava to liver. At a dose of 10 mg/g diet, 30-week kava treatment (8 weeks concurrent with NNK and B[a]P treatment followed by 22 weeks post-carcinogen treatment) effectively reduced lung tumor multiplicity by 56%. Kava also reduced lung tumor multiplicity by 47% when administered concurrently with NNK and B[a]P for 8 weeks. Perhaps most importantly, kava reduced lung tumor multiplicity by 49% when administered after the final NNK and B[a]P treatment. These results show for the first time the chemopreventive potential of kava against lung tumorigenesis. Mechanistically, kava inhibited proliferation and enhanced apoptosis in lung tumors, as shown by a reduction in proliferating cell nuclear antigen (PCNA), an increase in caspase-3, and cleavage of poly(ADP-ribose) polymerase (PARP). Kava treatment also inhibited the activation of nuclear factor kappaBNF-kappaB, a potential upstream mechanism of kava chemoprevention. Although not rigorously evaluated in this study, our preliminary data were not suggestive of hepatotoxicity. Based on these results, further studies are warranted to explore the chemopreventive potential and safety of kava.

  7. Tradition and toxicity: evidential cultures in the kava safety debate.

    PubMed

    Baker, Jonathan D

    2011-06-01

    This paper examines the debate about the safety of kava (Piper methysticum Forst. f, Piperaceae), a plant native to Oceania, where it has a long history of traditional use. Kava became popular as an anti-anxiety treatment in Western countries in the late 1990s, but it was subsequently banned in many places due to adverse reports of liver toxicity. This paper focuses on the responses to the bans by scientists involved in kava research, contrasting their evidential culture with that employed by clinicians and regulatory officials. Cultural constructions and social negotiations of risk are shown to be context-specific, and are shaped by professional, disciplinary, and organizational factors, among others. Though the science of hepatotoxicity is uncertain enough to allow for multiple interpretations of the same data, the biomedical/clinical narrative about kava remains dominant. This case study explores the influence of these cultural, social, and political factors on the production of scientific knowledge and the assessment of benefit/risk posed by comestibles.

  8. PCR-DGGE analysis of bacterial community dynamics in kava beverages during refrigeration.

    PubMed

    Dong, J; Kandukuru, P; Huang, A S; Li, Y

    2011-07-01

    Kava beverages are highly perishable even under refrigerated conditions. This study aimed to investigate the bacterial community dynamics in kava beverages during refrigeration.  Four freshly made kava beverages were obtained from kava bars and stored at 4°C. On days 0, 3 and 6, the aerobic plate count (APC), lactic acid bacteria (LAB) count and yeast and mould count (YMC) of the samples were determined. Meanwhile, bacterial DNA was extracted from each sample and subjected to the polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE). Moreover, species-specific PCR assays were employed to identify predominant Pseudomonas spp. involved in kava spoilage. Over the storage period, the APC, LAB count and YMC of the four kava beverages all increased, whereas their pH values decreased. The DGGE profile revealed diverse bacterial populations in the samples. LAB, such as Weissella soli, Lactobacillus spp. and Lactococcus lactis, were found in the kava beverages. Species-specific PCR assays detected Pseudomonas putida and Pseudomonas fluorescens in the samples; Ps. fluorescens became dominant during refrigeration. LAB and Pseudomonas may play a significant role in the spoilage of kava beverages. This study provides important information that may be used to extend the shelf life of kava beverages. © 2011 The Authors. Letters in Applied Microbiology © 2011 The Society for Applied Microbiology.

  9. Quantitative elimination of Flavokavines A and B from Kava Kava (Piper methysticum G. Forst) by isoelectric focused adsorptive bubble separation.

    PubMed

    Backleh, Marlène; Ekici, Perihan; Leupold, Günther; Parlar, Harun

    2003-08-01

    Adsorptive bubble separation, though still rarely used, is a suitable method for enrichment of surface-active macromolecules such as enzymes and proteins. There is a lack of investigations with small molecules, which can also be separated from complex mixtures by this method. In this work, an aqueous extract of Kava Kava ( Piper methysticum G. Forst) was used as a model system. Enrichment of undesirable Flavokavine A (7) and Flavokavine B (8) in the foam was influenced by the pH value, the amount of saponin as surface active substance, and the flow rate of the foam-forming gas. Efficiency was highest with diluted samples at pH 6.5. Under these conditions, transfer of Kavapyrone (1-6) to the foam was negligible.

  10. [Factors related to smoking and consumption of alcohol and kava in children attending the upper grades of primary schools in Vanuatu].

    PubMed

    Nakaseko, Emi; Matsuda, Nobuko; Kotera, Sayaka

    2014-01-01

    To identify factors related to smoking and consumption of alcohol and kava in children attending the upper grades of primary schools in Vanuatu. We conducted a self-administered survey of 6th, 7th, and 8th grade students attending primary schools in both urban and rural areas of Vanuatu. The main survey items included questions on the personal attribute (sex, age, grade); experience of smoking and consumption of alcohol and kava; food consumption (local food/store-bought food); perceptions of local foods and store-bought foods; attitudes toward smoking and consumption of alcohol and kava; knowledge related to non-communicable diseases; attitudes toward health practices; guardians' health-related parenting attitudes; and family members' use of tobacco, alcohol, and kava.The responses for the main outcome variables (smoking and consumption of alcohol and kava) were dichotomized as 'ever' versus 'never'. Factors related to smoking and consumption of alcohol and kava were examined using logistic regression analysis. The significance level was set at P<0.05. A total of 415 (194 urban and 221 rural) students participated in our study that had total and valid response rates of 100% for both. Of the participants, 8%, 12.4%, and 5.8% had previously smoked, consumed alcohol, or consumed kava, respectively. Students' experience of smoking and consumption of alcohol and kava were mutually associated. Student sex and family members' smoking status were significantly associated with the participants' smoking status. Student grades, attitudes toward drinking, and perceptions of local and store-bought food were significantly associated with alcohol consumption. Lastly, attitudes toward kava and alcohol consumption and perceptions of local food were significantly associated with kava consumption. Our results indicate that the food consumption, attitudes toward smoking and consumption of alcohol and kava, and family members' smoking status were associated with the participants

  11. Immunohistochemical analysis of expressions of hepatic cytochrome P450 in F344 rats following oral treatment with kava extract

    PubMed Central

    Clayton, Natasha P.; Yoshizawa, Katsuhiko; Kissling, Grace E.; Burka, Leo T.; Chan, Po-Chuen; Nyska, Abraham

    2007-01-01

    Kava (Piper methysticum), used for relaxation and pain relief, has been one of the leading dietary supplements and several reports linking hepatic functional disturbances and liver failure to kava have resulted in a ban on sales in Europe and Canada and the issuance of warnings by the US FDA. The National Toxicology Program conducted 14-week rat studies to characterize the toxicology of kava exposure in Fischer 344 rats [National Toxicity Program. 90 day gavage toxicity studies of KAVA KAVA EXTRACT in Fischer rats and B6C3F1 mice. Research Triangle Park, NC; 2005a; National Toxicity Program. Testing status of agents at NTP (KAVA KAVA EXTRACT M990058). Research Triangle Park, NC; 2005b. (http://ntp.niehs.nih.gov/index.cfm?objectid=071516E-C6E1-7AAA-C90C751E23D14C1B)]. Groups of 10 male and 10 female rats were administered kava extract by gavage at 0, 0.125, 0.25, 0.5, 1.0, and 2.0 g/kg/day. Increased γ-glutamyl-transpeptidase (GGT) activities were observed in the 2.0 g/kg males and 1.0 and 2.0 g/kg females, as well as increased serum cholesterol levels in males and females at 0.5 g/kg and higher. Increases in incidence and severity of hepatocellular hypertrophy (HP) were noted in males at 1.0 g/kg and females at 0.5 g/kg and higher, as well as increased liver weights. Immunohistochemical analyses of the expression of cytochrome-P450 (CYP) enzymes in liver of the control and 1.0-and 2.0-g/kg-treated groups indicated decreased expression of CYP2D1 (human CYP2D6 homolog) in 2.0 g/kg females and increased expression of CYP1A2, 2B1, and 3A1 in 1.0 and 2.0 g/kg groups of both sexes. The no observed adverse effect levels were decided as 0.25 g/kg in both genders, based on neurotoxic effects, increases in GGT, cholesterol, liver weight, and HP and decreases in body weight. Kava-induced hepatic functional changes in the F344 rat might be relevant to human clinical cases of hepatotoxicity following exposure. PMID:17059882

  12. Immunohistochemical analysis of expressions of hepatic cytochrome P450 in F344 rats following oral treatment with kava extract.

    PubMed

    Clayton, Natasha P; Yoshizawa, Katsuhiko; Kissling, Grace E; Burka, Leo T; Chan, Po-Chuen; Nyska, Abraham

    2007-01-01

    Kava (Piper methysticum), used for relaxation and pain relief, has been one of the leading dietary supplements and several reports linking hepatic functional disturbances and liver failure to kava have resulted in a ban on sales in Europe and Canada and the issuance of warnings by the US FDA. The National Toxicology Program conducted 14-week rat studies to characterize the toxicology of kava exposure in Fischer 344 rats [National Toxicity Program. 90 day gavage toxicity studies of KAVA KAVA EXTRACT in Fischer rats and B6C3F1 mice. Research Triangle Park, NC; 2005a; National Toxicity Program. Testing status of agents at NTP (KAVA KAVA EXTRACT M990058). Research Triangle Park, NC; 2005b. (http://ntp.niehs.nih.gov/index.cfm?objectid=071516E-C6E1-7AAA-C90C751E23D14C1B)]. Groups of 10 male and 10 female rats were administered kava extract by gavage at 0, 0.125, 0.25, 0.5, 1.0, and 2.0 g/kg/day. Increased gamma-glutamyl-transpeptidase (GGT) activities were observed in the 2.0 g/kg males and 1.0 and 2.0 g/kg females, as well as increased serum cholesterol levels in males and females at 0.5 g/kg and higher. Increases in incidence and severity of hepatocellular hypertrophy (HP) were noted in males at 1.0 g/kg and females at 0.5 g/kg and higher, as well as increased liver weights. Immunohistochemical analyses of the expression of cytochrome-P450 (CYP) enzymes in liver of the control and 1.0- and 2.0-g/kg-treated groups indicated decreased expression of CYP2D1 (human CYP2D6 homolog) in 2.0 g/kg females and increased expression of CYP1A2, 2B1, and 3A1 in 1.0 and 2.0 g/kg groups of both sexes. The no observed adverse effect levels were decided as 0.25 g/kg in both genders, based on neurotoxic effects, increases in GGT, cholesterol, liver weight, and HP and decreases in body weight. Kava-induced hepatic functional changes in the F344 rat might be relevant to human clinical cases of hepatotoxicity following exposure.

  13. Kava feeding in rats does not cause liver injury nor enhance galactosamine-induced hepatitis.

    PubMed

    DiSilvestro, Robert A; Zhang, Wenyi; DiSilvestro, David J

    2007-07-01

    Kava, like a number of herbals, has been associated with causing liver damage based on limited evidence. In contrast, the present study found that in rats, 3 mo feedings of two types of kava extracts (an acetone extract and an ethanol extract of the Samoan kava cultivar Ava Laau) at three different doses (31.25, 62.5 and 133 mg/kg diet) produced no liver injury based on serum markers of liver damage (sorbitol dehydrogenase activities, bile acid concentrations, and beta-glucuronidase activities) and serum lipid peroxide readings. In fact, for some measurements and some kava doses, the injury marker readings were below control values. Moreover, for these same parameters, kava feeding did not enhance the effects of the hepatotoxin galacatosamine (500 mg/kg ip); some kava doses even showed modest protection against liver injury. Liver histology analysis showed no signs of kava causing or enhancing liver injury. Thus, this study does not support the concept that kava produces or aggravates liver injury.

  14. Extract of kava (Piper methysticum) and its methysticin constituents protect brain tissue against ischemic damage in rodents.

    PubMed

    Backhauss, C; Krieglstein, J

    1992-05-14

    The purpose of the present study was to test whether kava extract and its constituents kawain, dihydrokawain, methysticin, dihydromethysticin and yangonin provide protection against ischemic brain damage. To this end, we used a model of focal cerebral ischemia in mice and rats. Ischemia was induced by microbipolar coagulation of the left middle cerebral artery (MCA). To quantify the size of the lesion in mice, the area of the infarct on the brain surface was assessed planimetrically 48 h after MCA occlusion by transcardial perfusion of carbon black. In the rat model infarct volume was determined 48 h after MCA occlusion by planimetric analysis and subsequent integration of the infarct areas on serial coronal slices. Compounds were administered i.p., except the kava extract, which was administered orally. The effects of the kava extract and its constituents were compared with those produced by the typical anticonvulsant, memantine. The kava extract, methysticin and dihydromethysticin produced effects similar to those of the reference substance memantine. The kava extract (150 mg/kg, 1 h before ischemia) diminished the infarct area (P less than 0.05) in mouse brains and the infarct volume (P less than 0.05) in rat brains. Methysticin, dihydromethysticin (both 10 and 30 mg/kg, 15 min before ischemia) and memantine (20 mg/kg, 30 min before ischemia) significantly reduced the infarct area in mouse brains. All other compounds failed to produce a beneficial effect on the infarct area in mouse brains. In conclusion, the kava extract exhibited neuroprotective activity, which was probably mediated by its constituents methysticin and dihydromethysticin.

  15. In vivo effects of goldenseal, kava kava, black cohosh, and valerian on human cytochrome P450 1A2, 2D6, 2E1, and 3A4/5 phenotypes.

    PubMed

    Gurley, Bill J; Gardner, Stephanie F; Hubbard, Martha A; Williams, D Keith; Gentry, W Brooks; Khan, Ikhlas A; Shah, Amit

    2005-05-01

    Phytochemical-mediated modulation of cytochrome P450 (CYP) activity may underlie many herb-drug interactions. Single-time point phenotypic metabolic ratios were used to determine whether long-term supplementation of goldenseal ( Hydrastis canadensis ), black cohosh ( Cimicifuga racemosa ), kava kava ( Piper methysticum ), or valerian ( Valeriana officinalis ) extracts affected CYP1A2, CYP2D6, CYP2E1, or CYP3A4/5 activity. Twelve healthy volunteers (6 women) were randomly assigned to receive goldenseal, black cohosh, kava kava, or valerian for 28 days. For each subject, a 30-day washout period was interposed between each supplementation phase. Probe drug cocktails of midazolam and caffeine, followed 24 hours later by chlorzoxazone and debrisoquin (INN, debrisoquine), were administered before (baseline) and at the end of supplementation. Presupplementation and postsupplementation phenotypic trait measurements were determined for CYP3A4/5, CYP1A2, CYP2E1, and CYP2D6 by use of 1-hydroxymidazolam/midazolam serum ratios (1-hour sample), paraxanthine/caffeine serum ratios (6-hour sample), 6-hydroxychlorzoxazone/chlorzoxazone serum ratios (2-hour sample), and debrisoquin urinary recovery ratios (8-hour collection), respectively. The content of purported "active" phytochemicals was determined for each supplement. Comparisons of presupplementation and postsupplementation phenotypic ratio means revealed significant inhibition (approximately 40%) of CYP2D6 (difference, -0.228; 95% confidence interval [CI], -0.268 to -0.188) and CYP3A4/5 (difference, -1.501; 95% CI, -1.840 to -1.163) activity for goldenseal. Kava produced significant reductions (approximately 40%) in CYP2E1 only (difference, -0.192; 95% CI, -0.325 to -0.060). Black cohosh also exhibited statistically significant inhibition of CYP2D6 (difference, -0.046; 95% CI, -0.085 to -0.007), but the magnitude of the effect (approximately 7%) did not appear to be clinically relevant. No significant changes in phenotypic

  16. In vivo effects of goldenseal, kava kava, black cohosh, and valerian on human cytochrome P450 1A2, 2D6, 2E1, and 3A4 phenotypes

    PubMed Central

    Gardner, Stephanie F.; Hubbard, Martha A.; Williams, D. Keith; Gentry, W. Brooks; Khan, Ikhlas A.; Shah., Amit

    2007-01-01

    Objectives Phytochemical-mediated modulation of cytochrome P-450 activity may underlie many herb-drug interactions. Single time-point, phenotypic metabolic ratios were used to determine whether long-term supplementation of goldenseal (Hydrastis canadensis), black cohosh (Cimicifuga racemosa), kava kava (Piper methysticum), or valerian (Valeriana officinalis) extracts affected CYP1A2, CYP2D6, CYP2E1, or CYP3A4/5 activity. Methods Twelve healthy volunteers (6 females) were randomly assigned to receive goldenseal, black cohosh, kava kava, or valerian for 28 days. For each subject, a 30-day washout period was interposed between each supplementation phase. Probe drug cocktails of midazolam and caffeine, followed 24 hours later by chlorzoxazone and debrisoquine were administered before (baseline) and at the end of supplementation. Pre- and post-supplementation phenotypic trait measurements were determined for CYP3A4/5, CYP1A2, CYP2E1, and CYP2D6 using 1-hydroxymidazolam/midazolam serum ratios (1-hour sample), paraxanthine/caffeine serum ratios (6-hour sample), 6-hydroxychlorzoxazone/chlorzoxazone serum ratios (2-hour sample), and debrisoquine urinary recovery ratios (8-hour collection), respectively. The content of purported “active” phytochemicals was determined for each supplement. Results Comparisons of pre- and post-supplementation phenotypic ratio means revealed significant inhibition (~40%) of CYP2D6 (difference = −0.228; 95% CI = −0.268 to −0.188) and CYP3A4/5 (difference = −1.501; 95% CI = −1.840 to −1.163) activity for goldenseal. Kava produced significant reductions (~40%) in CYP2E1 only (difference = −0.192; 95% CI = −0.325 to −0.060). Black cohosh also exhibited statistically significant inhibition of CYP2D6 (difference = −0.046; 95% CI = −0.085 to −0.007), but the magnitude of the effect (~7%) did not appear clinically relevant. No significant changes in phenotypic ratios were observed for valerian. Conclusions Botanical

  17. Clinical assessment of CYP2D6-mediated herb-drug interactions in humans: Effects of milk thistle, black cohosh, goldenseal, kava kava, St. John's wort, and Echinacea

    PubMed Central

    Gurley, Bill J.; Swain, Ashley; Hubbard, Martha A.; Williams, D. Keith; Barone, Gary; Hartsfield, Faith; Tong, Yudong; Carrier, Danielle J.; Cheboyina, Shreekar; Battu, Sunil K.

    2007-01-01

    Cytochrome P450 2D6 (CYP2D6), an important CYP isoform with regard to drug-drug interactions, accounts for the metabolism of ∼30% of all medications. To date, few studies have assessed the effects of botanical supplementation on human CYP2D6 activity in vivo. Six botanical extracts were evaluated in three separate studies (2 extracts per study), each incorporating 18 healthy volunteers (9 females). Subjects were randomized to receive a standardized botanical extract for 14 days on separate occasions. A 30-day washout period was interposed between each supplementation phase. In study 1, subjects received milk thistle (Silybum marianum) and black cohosh (Cimicifuga racemosa). In study 2, kava kava (Piper methysticum), and goldenseal (Hydrastis canadensis) extracts were administered, and in study 3 subjects received St. John's wort (Hypericum perforatum) and Echinacea (Echinacea purpurea). The CYP2D6 substrate, debrisoquine (5 mg), was administered before and at the end of supplementation. Pre- and post-supplementation phenotypic trait measurements were determined for CYP2D6 using 8-hour debrisoquine urinary recovery ratios (DURR). Comparisons of pre- and post-supplementation DURR revealed significant inhibition (∼50%) of CYP2D6 activity for goldenseal, but not for the other extracts. Accordingly, adverse herb-drug interactions may result with concomitant ingestion of goldenseal supplements and drugs that are CYP2D6 substrates. PMID:18214849

  18. Policy approaches to support local community control over the supply and distribution of kava in the Northern Territory (Australia).

    PubMed

    Clough, Alan R; Jones, Peter J

    2004-03-01

    The health consequences of kava abuse in Arnhem Land Aboriginal populations in the Northern Territory (NT) and the persistence of an illegal kava trade with its associated social harms have been a cause for concern for 20 years. Despite these concerns, some Arnhem Land groups seek to continue using kava and to control its sale, distribution and the profits from the enterprise. In response, policy makers in the NT have embraced principles of harm reduction and created regulatory mechanisms to address broader public concerns and to support local management of kava supply while reinforcing control over the consequences of its use. This paper describes the kava regulatory system now being implemented in the NT which features kava management plans developed in consultation between Aboriginal communities and licensing authorities. It complements the earlier Harm Reduction Digest 9 by McDonald & Jowitt which looked at Kava in the South Pacific.

  19. Herbal hepatotoxicity by kava: update on pipermethystine, flavokavain B, and mould hepatotoxins as primarily assumed culprits.

    PubMed

    Teschke, Rolf; Qiu, Samuel X; Lebot, Vincent

    2011-09-01

    Herbal hepatotoxicity by the anxiolytic kava (Piper methysticum Forst. f.) emerged unexpectedly and was observed in a few patients worldwide. Liver injury occurred after the use of traditional aqueous kava extracts in the South Pacific region and of acetonic and ethanolic extracts in Western countries in rare cases, suggesting that the solvents used play no major causative role. In this review, we discuss actual pathogenetic issues of kava hepatotoxicity with special focus on developments regarding pipermethystine, flavokavain B, and mould hepatotoxins as possible culprits. There is abundant data of in vitro cytotoxicity including apoptosis by pipermethystine and flavokavain B added to the incubation media, yet evidence is lacking of in vivo hepatotoxicity in experimental animals under conditions similar to human kava use. Furthermore, in commercial Western kava extracts, pipermethystine was not detectable and flavokavain B was present as a natural compound in amounts much too low to cause experimental liver injury. There is concern, however, that due to high temperature and humidity in the South Pacific area, kava raw material might have been contaminated by mould hepatotoxins such as aflatoxins after harvest and during storage. Whether kava hepatotoxicity may be due to aflatoxicosis or other mould hepatotoxins, requires further studies.

  20. Re-introduction of kava (Piper methysticum) to the EU: is there a way forward?

    PubMed

    Sarris, Jerome; Teschke, Rolf; Stough, Con; Scholey, Andrew; Schweitzer, Isaac

    2011-01-01

    Kava (Piper methysticum) is an effective anxiolytic that has been withdrawn from various consumer markets in European countries due to concerns over its hepatotoxicity. It is plausible that the reported hepatotoxicity may be due in part to plant substitution, or an incorrect cultivar, or plant parts being used (such as leaves or bark); thus both the plant chemotype and the plant part used may be critical factors. If re-institution of kava in the EU is to occur, more evidence is required to determine its safety and efficacy. Furthermore, according to current evidence, the study of traditional water soluble rhizome extracts using a noble cultivar of kava may be advised. The Kava Anxiety-Lowering Medication (KALM) project is due to start in late 2010 to address these considerations. The KALM project uses an aqueous rhizome extract of a noble cultivar of kava in participants with generalised anxiety and Generalised Anxiety Disorder (GAD). The project comprises of 1) an acute RCT, kava (180 mg of kavalactones) versus oxazepam and placebo in 20 anxious people, testing effects on cognition, mood, anxiety, and driving; 2) an 8-week RCT comparing kava (120 mg kavalactones) versus placebo in 100 patients with GAD. To assess differences between dosages, non-responders at 3 weeks will be titrated to 240 mg of kavalactones. The project will also assess the effects of kava on liver function tests and its side effects profile. A novel component of the project is the pharmacogenomic exploration of phenotypical responses (GABA system and cytochrome P450 markers). The results of the study may be of benefit to sufferers of anxiety and the future economy of the Pacific islands, potentially providing an important step in the way forward with kava.

  1. Enhanced efficacy and reduced side effects of diazepam by kava combination.

    PubMed

    Tawfiq, Rasha A; Nassar, Noha N; El-Eraky, Wafaa I; El-Denshary, Ezzeldein S

    2014-09-01

    The long term use of antiepileptic drugs possesses many unwanted effects; thus, new safe combinations are urgently mandated. Hence, the present study aimed to investigate the anticonvulsant effect of kava alone or in combination with a synthetic anticonvulsant drug, diazepam (DZ). To this end, female Wistar rats were divided into two subsets, each comprising 6 groups as follows: group (i) received 1% Tween 80 p.o. and served as control, while groups (ii) and (iii) received kava at two dose levels (100 and 200 mg/kg, p.o.). The remaining three groups received (iv) DZ alone (10 mg/kg p.o.) or kava in combination with DZ (v) (5 mg/kg, p.o.) or (vi) (10 mg/kg, p.o.). Results of the present study revealed that kava increased the maximal electroshock seizure threshold (MEST) and enhanced the anticonvulsant effect of diazepam following both acute and chronic treatment. Moreover, neither kava nor its combination with DZ impaired motor co-ordination either acutely or chronically. Furthermore, kava ameliorated both the reduction in locomotor activity as well as changes in liver function tests induced by chronic administration of DZ. Moreover, no elevation was shown in the creatinine concentration vs. control group following chronic administration of kava or DZ either alone or in combination with kava. In conclusion, the present study suggests the possibility of combining a low dose DZ with kava to reduce harmful effects and might be recommended for clinical use in patients chronically treated with this synthetic anticonvulsant drug.

  2. Kava extract, an herbal alternative for anxiety relief, potentiates acetaminophen-induced cytotoxicity in rat hepatic cells.

    PubMed

    Yang, Xi; Salminen, William F

    2011-05-15

    The widely used over-the-counter analgesic acetaminophen (APAP) is the leading cause of acute liver failure in the United States and due to this high incidence, a recent FDA Advisory Board recommended lowering the maximum dose of APAP. Kava herbal dietary supplements have been implicated in several human liver failure cases leading to the ban of kava-containing products in several Western countries. In the US, the FDA has issued warnings about the potential adverse effects of kava, but kava dietary supplements are still available to consumers. In this study, we tested the potential of kava extract to potentiate APAP-induced hepatocyte cytotoxicity. In rat primary hepatocytes, co-treatment with kava and APAP caused 100% loss of cell viability, while the treatment of kava or APAP alone caused ∼50% and ∼30% loss of cell viability, respectively. APAP-induced glutathione (GSH) depletion was also potentiated by kava. Co-exposure to kava decreased cellular ATP concentrations, increased the formation of reactive oxygen species, and caused mitochondrial damage as indicated by a decrease in mitochondrial membrane potential. In addition, similar findings were obtained from a cultured rat liver cell line, clone-9. These observations indicate that kava potentiates APAP-induced cytotoxicity by increasing the magnitude of GSH depletion, resulting in oxidative stress and mitochondrial dysfunction, ultimately leading to cell death. These results highlight the potential for drug-dietary supplement interactions even with widely used over-the-counter drugs.

  3. Effects of the heavy usage of kava on physical health: summary of a pilot survey in an aboriginal community.

    PubMed

    Mathews, J D; Riley, M D; Fejo, L; Munoz, E; Milns, N R; Gardner, I D; Powers, J R; Ganygulpa, E; Gununuwawuy, B J

    1988-06-06

    Health status was assessed in 39 kava users and 34 non-users in a coastal Aboriginal community in Arnhem Land. Twenty (27%) respondents were very heavy (mean consumption, 440 g/week) users of kava; 15 (21%) respondents were heavy (310 g/week) users of kava and four (5%) respondents were occasional (100 g/week) users of kava. Kava users were more likely to complain of poor health and a "puffy" face, and were more likely to have a typical scaly rash, and slightly-increased patellar reflexes. Very heavy users of kava were 20% underweight and their levels of gamma-glutamyl transferase were increased greatly. Albumin, plasma protein, urea and bilirubin levels were decreased in kava users, and high-density lipoprotein cholesterol levels were increased. Kava users were more likely to show haematuria, and to have urine which was poorly acidified and of low specific gravity. The use of kava was also associated with an increased red-cell volume, with a decreased platelet volume and with a decreased lymphocyte count. Shortness of breath in kava users was associated with tall P waves on a resting electrocardiogram, which provided suggestive evidence of pulmonary hypertension. In common with other Aboriginal communities, there was evidence of decreased lung volumes, a high carriage rate of hepatitis B surface antigen, and of other morbidity that was unrelated to the use of kava. On the basis of these findings, there is a strong rationale for urgent social action to improve health in Aboriginal communities and, in particular, to reduce the consumption of kava and to improve the nutritional status of kava users.

  4. Pacific island 'Awa (Kava) extracts, but not isolated kavalactones, promote proinflammatory responses in model mast cells.

    PubMed

    Shimoda, Lori M N; Park, Christy; Stokes, Alexander J; Gomes, Henry Halenani; Turner, Helen

    2012-12-01

    Kava ('Awa) is a traditional water-based beverage in Pacific island communities, prepared from the ground root and stems of Piper methysticum. Kava use is associated with an ichthyotic dermatitis and delayed type hypersensitivity reactions. In the current study we collated preparative methodologies from cultural practitioners and recreational kava users in various Pacific communities. We standardized culturally informed aqueous extraction methods and prepared extracts that were subjected to basic physicochemical analysis. Mast cells exposed to these extracts displayed robust intracellular free calcium responses, and concomitant release of proinflammatory mediators. In contrast, mast cells were refractory to single or combinatorial stimulation with kavalactones, including methysticin, dihydromethysticin and kavain. Moreover, we reproduced a traditional modification of the kava preparation methodology, pre-mixing with the mucilage of Hibiscus tiliaceus, and observed its potentiating effect on the activity of aqueous extracts in mast cells. Taken together, these data indicate that water extractable active ingredients may play a role in the physiological and pathophysiological effects of kava, and suggests that mast cell activation may be a mechanistic component of kava-related skin inflammations.

  5. Efficacy of extracting solvents to chemical components of kava (Piper methysticum) roots.

    PubMed

    Xuan, Tran Dang; Fukuta, Masakazu; Wei, Ao Chang; Elzaawely, Abdelnaser Abdelghany; Khanh, Tran Dang; Tawata, Shinkichi

    2008-04-01

    The chemical composition of kava (Piper methysticum) lactones and various phytochemicals obtained following the sonication of ground kava roots extracted in the solvents hexane, chloroform, acetone, ethanol, methanol and water, respectively, was analyzed. Eighteen kava lactones, cinnamic acid bornyl ester and 5,7-dimethoxy-flavanone, known to be present in kava roots, were identified, and seven compounds, including 2,5,8-trimethyl-1-naphthol, 5-methyl-1-phenylhexen-3-yn-5-ol, 8,11-octadecadienoic acid-methyl ester, 5,7-(OH)(2)-4'-one-6,8-dimethylflavanone, pinostrobin chalcone and 7-dimethoxyflavanone-5-hydroxy-4', were identified for the first time. Glutathione (26.3 mg/g) was found in the water extract. Dihydro-5,6-dehydrokavain (DDK) was present at a higher level than methysticin and desmethoxyyagonin, indicating that DDK is also a major constituent of kava roots. Acetone was the most effective solvent in terms of maximum yield and types of kava lactones isolated, followed by water and chloroform, whereas hexane, methanol, and ethanol were less effective as solvents. Total phenolic and antioxidant activity varied among the extracting solvents, with acetone and chloroform producing the highest effects, followed by water, while methanol, ethanol and hexane were less effective.

  6. Phototoxicity of kava - formation of reactive oxygen species leading to lipid peroxidation and DNA damage.

    PubMed

    Xia, Qingsu; Chiang, Hsiu-Mei; Zhou, Yu-Ting; Yin, Jun-Jie; Liu, Fang; Wang, Cheng; Guo, Lei; Fu, Peter P

    2012-01-01

    Kava is one of the most widely sold herbal dietary supplements in the United States. It has been reported that, besides exhibiting hepatotoxicity, kava also possesses photosensitivity and induces dermopathy in humans. In this study, we determined that UVA irradiation of kava in the presence of a lipid, methyl linoleate, generated lipid peroxidation which was mediated by singlet oxygen generated during photoirradiation. The six major kavalactones(yangonin, 7,8-dihydrokawa in, kawain, 7,8-dihydromethysticin, methysticin, and 5,6-dehydrokawain) were also studied in parallel; only 5,6-dehydrokawain and yangonin-induced a low level of lipid peroxidation. UVA irradiation of kava in human HaCaT skin keratinocytes induced cytotoxicity which was mediated by oxidative stress, led to DNA strand cleavage, and produced 8-hydroxy-2'-deoxyguanosine (8-OHdG) adduct. Study by the electron spin resonance (ESR) method revealed that UVA irradiation of kava produced singlet oxygen and carbon-centered radicals. The overall results suggest that kava is photocytotoxic and photogenotoxic, both mediated by free radicals generated during photoirradiation.

  7. In vitro cytotoxicity of nonpolar constituents from different parts of kava plant (Piper methysticum).

    PubMed

    Jhoo, Jin-Woo; Freeman, James P; Heinze, Thomas M; Moody, Joanna D; Schnackenberg, Laura K; Beger, Richard D; Dragull, Klaus; Tang, Chung-Shih; Ang, Catharina Y W

    2006-04-19

    Kava (Piper methysticum), a perennial shrub native to the South Pacific islands, has been used to relieve anxiety. Recently, several cases of severe hepatotoxicity have been reported from the consumption of dietary supplements containing kava. It is unclear whether the kava constituents, kavalactones, are responsible for the associated hepatotoxicity. To investigate the key components responsible for the liver toxicity, bioassay-guided fractionation was carried out in this study. Kava roots, leaves, and stem peelings were extracted with methanol, and the resulting residues were subjected to partition with a different polarity of solvents (hexane, ethyl acetate, n-butanol, and water) for evaluation of their cytotoxicity on HepG2 cells based on the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and lactate dehydrogenase and aspartate aminotransferase enzyme leakage assays. Organic solvent fractions displayed a much stronger cytotoxicity than water fractions for all parts of kava. The hexane fraction of the root exhibited stronger cytotoxic effects than fractions of root extracted with other solvents or extracts from the other parts of kava. Further investigations using bioassay-directed isolation and analysis of the hexane fraction indicated that the compound responsible for the cytotoxicity was flavokavain B. The identity of the compound was confirmed by (1)H and (13) C NMR and MS techniques.

  8. Lung tumorigenesis suppressing effects of a commercial kava extract and its selected compounds in A/J mice.

    PubMed

    Johnson, Thomas E; Hermanson, David; Wang, Lei; Kassie, Fekadu; Upadhyaya, Pramod; O'Sullivan, Michael G; Hecht, Stephen S; Lu, Junxuan; Xing, Chengguo

    2011-01-01

    Lung cancer is the most deadly malignancy in the US. Chemoprevention is potentially a complementary approach to smoking cessation for lung cancer control. Recently, we reported that a commercially available form of kava extract significantly inhibits 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and benzo(a)pyrene (BaP)-induced lung tumorigenesis in A/J mice at a dose of 10 mg per gram diet. In the present study, we examined the dose-dependent lung tumor inhibitory activities of kava and investigated potential active constituent(s). Mice treated with carcinogen alone contained 12.1±5.8 lung adenomas per mouse 22 weeks after final carcinogen administration. Mice that were fed diets containing kava at dosages of 1.25, 2.5, 5, and 10 mg/g of diet had 8.4±3.5, 6.6±3.5, 4.3±2.4, and 3.8±2.3 lung adenomas per mouse, respectively. This corresponds to a reduction of 31%, 46%, 65% and 69% in tumor multiplicity, which were all statistically significant (p < 0.05). Analyses of lung adenoma tissues derived from kava-treated animals revealed that kava significantly inhibited adenoma cell proliferation while it had no detectable effect on cell death, indicating that kava primarily suppressed lung tumorigenesis in A/J mice via inhibition of cell proliferation. Flavokawains A, B, and C, three chalcone-based components from kava, demonstrated greatly reduced chemopreventive efficacies even at concentrations much higher than their natural abundance, suggesting that they alone were unlikely to be responsible for kava's chemopreventive activity. Kava at all dosages and treatment regimens did not induce detectable adverse effects, particularly with respect to liver. Specifically, kava treatment showed no effect on liver integrity indicator enzymes or liver weight, indicating that kava may be potentially safe for long-term chemopreventive application.

  9. Flavokawains a and B in kava, not dihydromethysticin, potentiate acetaminophen-induced hepatotoxicity in C57BL/6 mice.

    PubMed

    Narayanapillai, Sreekanth C; Leitzman, Pablo; O'Sullivan, M Gerard; Xing, Chengguo

    2014-10-20

    Anxiolytic kava products have been associated with rare but severe hepatotoxicity in humans. This adverse potential has never been captured in animal models, and the responsible compound(s) remains to be determined. The lack of such knowledge greatly hinders the preparation of a safer kava product and limits its beneficial applications. In this study we evaluated the toxicity of kava as a single entity or in combination with acetaminophen (APAP) in C57BL/6 mice. Kava alone revealed no adverse effects for long-term usage even at a dose of 500 mg/kg bodyweight. On the contrary a three-day kava pretreatment potentiated APAP-induced hepatotoxicity, resulted in an increase in serum ALT and AST, and increased severity of liver lesions. Chalcone-based flavokawains A (FKA) and B (FKB) in kava recapitulated its hepatotoxic synergism with APAP while dihydromethysticin (DHM, a representative kavalactone and a potential lung cancer chemopreventive agent) had no such effect. These results, for the first time, demonstrate the hepatotoxic risk of kava and its chalcone-based FKA and FKB in vivo and suggest that herb-drug interaction may account for the rare hepatotoxicity associated with anxiolytic kava usage in humans.

  10. Kava for the treatment of generalized anxiety disorder RCT: analysis of adverse reactions, liver function, addiction, and sexual effects.

    PubMed

    Sarris, J; Stough, C; Teschke, R; Wahid, Z T; Bousman, C A; Murray, G; Savage, K M; Mouatt, P; Ng, C; Schweitzer, I

    2013-11-01

    Presently, little is known about a number issues concerning kava (Piper methysticum), including (i) whether kava has any withdrawal or addictive effects; (ii) if genetic polymorphisms of the cytochrome (CYP) P450 2D6 liver enzyme moderates any potential adverse effects; and (iii) if medicinal application of kava has any negative or beneficial effect on sexual function and experience. The study design was a 6-week, double-blind, randomized controlled trial (n = 75) involving chronic administration of kava (one tablet of kava twice per day; 120 mg of kavalactones per day, titrated in non-response to two tablets of kava twice per day; 240 mg of kavalactones) or placebo for participants with generalized anxiety disorder. Results showed no significant differences across groups for liver function tests, nor were there any significant adverse reactions that could be attributed to kava. No differences in withdrawal or addiction were found between groups. Interesting, kava significantly increased female's sexual drive compared to placebo (p = 0.040) on a sub-domain of the Arizona Sexual Experience Scale (ASEX), with no negative effects seen in males. Further, it was found that there was a highly significant correlation between ASEX reduction (improved sexual function and performance) and anxiety reduction in the whole sample.

  11. Hepatotoxicity Induced by “the 3Ks”: Kava, Kratom and Khat

    PubMed Central

    Pantano, Flaminia; Tittarelli, Roberta; Mannocchi, Giulio; Zaami, Simona; Ricci, Serafino; Giorgetti, Raffaele; Terranova, Daniela; Busardò, Francesco P.; Marinelli, Enrico

    2016-01-01

    The 3Ks (kava, kratom and khat) are herbals that can potentially induce liver injuries. On the one hand, growing controversial data have been reported about the hepatotoxicity of kratom, while, on the other hand, even though kava and khat hepatotoxicity has been investigated, the hepatotoxic effects are still not clear. Chronic recreational use of kratom has been associated with rare instances of acute liver injury. Several studies and case reports have suggested that khat is hepatotoxic, leading to deranged liver enzymes and also histopathological evidence of acute hepatocellular degeneration. Numerous reports of severe hepatotoxicity potentially induced by kava have also been highlighted, both in the USA and Europe. The aim of this review is to focus on the different patterns and the mechanisms of hepatotoxicity induced by “the 3Ks”, while trying to clarify the numerous aspects that still need to be addressed. PMID:27092496

  12. Kava in the treatment of generalized anxiety disorder: a double-blind, randomized, placebo-controlled study.

    PubMed

    Sarris, Jerome; Stough, Con; Bousman, Chad A; Wahid, Zahra T; Murray, Greg; Teschke, Rolf; Savage, Karen M; Dowell, Ashley; Ng, Chee; Schweitzer, Isaac

    2013-10-01

    Kava (Piper methysticum) is a plant-based medicine, which has been previously shown to reduce anxiety. To date, however, no placebo-controlled trial assessing kava in the treatment of generalized anxiety disorder (GAD) has been completed. A total of 75 participants with GAD and no comorbid mood disorder were enrolled in a 6-week double-blind trial of an aqueous extract of kava (120/240 mg of kavalactones per day depending on response) versus placebo. γ-Aminobutyric acid (GABA) and noradrenaline transporter polymorphisms were also analyzed as potential pharmacogenetic markers of response. Reduction in anxiety was measured using the Hamilton Anxiety Rating Scale (HAMA) as the primary outcome. Intention-to-treat analysis was performed on 58 participants who met inclusion criteria after an initial 1 week placebo run-in phase. Results revealed a significant reduction in anxiety for the kava group compared with the placebo group with a moderate effect size (P = 0.046, Cohen d = 0.62). Among participants with moderate to severe Diagnostic and Statistical Manual of Mental Disorders-diagnosed GAD, this effect was larger (P = 0.02; d = 0.82). At conclusion of the controlled phase, 26% of the kava group were classified as remitted (HAMA ≤ 7) compared with 6% of the placebo group (P = 0.04). Within the kava group, GABA transporter polymorphisms rs2601126 (P = 0.021) and rs2697153 (P = 0.046) were associated with HAMA reduction. Kava was well tolerated, and aside from more headaches reported in the kava group (P = 0.05), no other significant differences between groups occurred for any other adverse effects, nor for liver function tests. Standardized kava may be a moderately effective short-term option for the treatment of GAD. Furthermore, specific GABA transporter polymorphisms appear to potentially modify anxiolytic response to kava.

  13. Regulatory causality evaluation methods applied in kava hepatotoxicity: are they appropriate?

    PubMed

    Teschke, Rolf; Wolff, Albrecht

    2011-02-01

    Since 1998 liver injury has been assumed in some patients after the use of kava (Piper methysticum G. Forster) as an anxyolytic herbal extract, but the regulatory causality evaluation of these cases was a matter of international and scientific debate. This review critically analyzes the regulatory issues of causality assessments of patients with primarily suspected kava hepatotoxicity and suggests recommendations for minimizing regulatory risks when assessing causality in these and other related cases. The various regulatory causality approaches were based on liver unspecific assessments such as ad hoc evaluations, the WHO scale using the definitions of the WHO Collaborating Centre for International Drug Monitoring, and the Naranjo scale. Due to their liver unspecificity, however, these causality approaches are not suitable for assessing cases of primarily assumed liver related adverse reactions by drugs and herbs including kava. Major problems emerged trough the combination of regulatory inappropriate causality assessment methods with the poor data quality as presented by the regulatory agency when reassessment was done and the resulting data were heavily criticized worldwide within the scientific community. Conversely, causality of cases with primarily assumed kava hepatotoxicity is best assessed by structured, quantitative and liver specific causality algorithms such as the scale of the CIOMS (Council for International Organizations of Medical Sciences) or the main-test as its update. Future strategies should therefore focus on the implementation of structured, quantitative and liver specific causality assessment methods as regulatory standards to improve regulatory causality assessments for liver injury by drugs and herbs including kava. Copyright © 2010 Elsevier Inc. All rights reserved.

  14. Evaluation of commercial kava extracts and kavalactone standards for mutagenicity and toxicity using the mammalian cell gene mutation assay in L5178Y mouse lymphoma cells.

    PubMed

    Whittaker, Paul; Clarke, Jane J; San, Richard H C; Betz, Joseph M; Seifried, Harold E; de Jager, Lowri S; Dunkel, Virginia C

    2008-01-01

    Kava (Piper methysticum) is a member of the pepper family and has been cultivated by South Pacific islanders for centuries and used as a social and ceremonial drink. Traditionally, kava extracts are prepared by grinding or chewing the rhizome and mixing with water and coconut milk. The active constituents of kava are a group of approximately 18 compounds collectively referred to as kavalactones or kava pyrones. Kawain, dihydrokawain, methysticin, dihydromethysticin, yangonin, and desmethoxyyangonin are the six major kavalactones. Kava beverages and other preparations are known to be anxiolytic and are used for anxiety disorders. Dietary supplements containing the root of the kava shrub have been implicated in several cases of liver toxicity in humans, including several who required liver transplants after using kava supplements. In order to study the toxicity and mutagenicity, two commercial samples of kava, Kaviar and KavaPure, and the six pure kavalactones including both D-kawain and DL-kawain, were evaluated in L5178Y mouse lymphoma cells. Neither the kava samples nor the kavalactones induced a mutagenic response in the L5178Y mouse lymphoma mutation assay with the addition of human liver S9 activation.

  15. German Kava Ban Lifted by Court: The Alleged Hepatotoxicity of Kava (Piper methysticum) as a Case of Ill-Defined Herbal Drug Identity, Lacking Quality Control, and Misguided Regulatory Politics.

    PubMed

    Kuchta, Kenny; Schmidt, Mathias; Nahrstedt, Adolf

    2015-12-01

    Kava, the rhizome and roots of Piper methysticum, are one of the most important social pillars of Melanesian societies. They have been used for more than 1000 years in social gatherings for the preparation of beverages with relaxing effects. During the colonial period, extract preparations found their way into Western medicinal systems, with experience especially concerning the treatment of situational anxiety dating back more than 100 years. It therefore came as a surprise when the safety of kava was suddenly questioned based on the observation of a series of case reports of liver toxicity in 1999 and 2000. These case reports ultimately led to a ban of kava products in Europe - a ban that has been contested because of the poor evidence of risks related to kava. Only recently, two German administrative courts decided that the decision of the regulatory authority to ban kava as a measure to ensure consumer safety was inappropriate and even associated with an increased risk due to the higher risk inherent to the therapeutic alternatives. This ruling can be considered as final for at least the German market, as no further appeal has been pursued by the regulatory authorities. However, in order to prevent further misunderstandings, especially in other markets, the current situation calls for a comprehensive presentation of the cardinal facts and misconceptions concerning kava and related drug quality issues.

  16. Pacific island ‘Awa (Kava) extracts, but not isolated kavalactones, promote pro-inflammatory responses in model mast cells

    PubMed Central

    Shimoda, Lori M.N.; Park, Christy; Stokes, Alexander J.; Gomes, Henry Halenani; Turner, Helen

    2013-01-01

    Kava (‘Awa) is a traditional water-based beverage in Pacific island communities, prepared from the ground root and stems of Piper methysticum. Kava use is associated with an ichthyotic dermatitis and delayed type hypersensitivity reactions. In the current study we collated preparative methodologies from cultural practitioners and recreational kava users in various Pacific communities. We standardized culturally-informed aqueous extraction methods and prepared extracts that were subjected to basic physicochemical analysis. Mast cells exposed to these extracts displayed robust intracellular free calcium responses, and concomitant release of pro-inflammatory mediators. In contrast, mast cells were refractory to single or combinatorial stimulation with kavalactones including methysticin, dihydromethysticin and kavain. Moreover, we reproduced a traditional modification of the kava preparation methodology, pre-mixing with the mucilage of Hibiscus taliaceus, and observed its potentiating effect on the activity of aqueous extracts in mast cells. Taken together, these data indicate that water extractable active ingredients may play a role in the physiological and pathophysiological effects of kava, and suggests that mast cell activation may be a mechanistic component of kava-related skin inflammations. PMID:22473598

  17. Kavalactone content and chemotype of kava beverages prepared from roots and rhizomes of Isa and Mahakea varieties and extraction efficiency of kavalactones using different solvents.

    PubMed

    Wang, Jun; Qu, Weiyue; Bittenbender, Harry C; Li, Qing X

    2015-02-01

    The South Pacific islanders have consumed kava beverage for thousands of years. The quality of kava and kava beverage is evaluated through determination of the content of six major kavalactones including methysticin, dihydromethysticin, kavain, dihydrokavain, yangonin and desmethoxyyangonin. In this study, we determined contents of kavalactones in and chemotype of kava beverages prepared from roots and rhizomes of Isa and Mahakea varieties and extraction efficiency of five different solvents including hexane, acetone, methanol, ethanol and ethyl acetate. The six major kavalactones were detected in all kava beverages with these five solvents. Different solvents had different extraction efficiencies for kavalactones from the lyophilized kava preparations. The contents of kavalactones in the extracts with acetone, ethanol, and methanol did not differ significantly. Ethanol had the highest extraction efficiency for the six major kavalactones whereas hexane gave the lowest extraction efficiency.

  18. Melanogenesis stimulation in murine B16 melanoma cells by Kava (Piper methysticum) rhizome extract and kavalactones.

    PubMed

    Matsuda, Hideaki; Hirata, Noriko; Kawaguchi, Yoshiko; Naruto, Shunsuke; Takata, Takanobu; Oyama, Masayoshi; Iinuma, Munekazu; Kubo, Michinori

    2006-04-01

    Melanogenesis stimulation activity of aqueous ethanolic extracts obtained from several different parts of five Piper species, namely Piper longum, P. kadsura, P. methysticum, P. betle, and P. cubeba, were examined by using cultured murine B16 melanoma cells. Among them, the extract of P. methysticum rhizome (Kava) showed potent stimulatory effect on melanogenesis as well as P. nigrum leaf extract. Activity-guided fractionation of Kava extract led to the isolation of two active kavalactones, yangonin (2) and 7,8-epoxyyangonin (5), along with three inactive kavalactones, 5,6-dehydrokawain (1), (+)-kawain (3) and (+)-methysticin (4), and a glucosylsterol, daucosterin (6). 7,8-Epoxyyangonin (5) showed a significant stimulatory effect on melanogenesis in B16 melanoma cells. Yangonin (2) exhibited a weak melanogenesis stimulation activity.

  19. Methysticin and 7,8-dihydromethysticin are two major kavalactones in kava extract to induce CYP1A1.

    PubMed

    Li, Yan; Mei, Hu; Wu, Qiangen; Zhang, Suhui; Fang, Jia-Long; Shi, Leming; Guo, Lei

    2011-12-01

    Kava is a plant traditionally used for making beverages in Pacific Basin countries and has been used for the treatment of nervous disorders in the United States. The pharmacological activity of kava is achieved through kavalactones in kava extract, which include kawain, 7,8-dihydrokawain, yangonin, 5,6-dehydrokawain, methysticin, and 7,8-dihydromethysticin. Recent studies have shown that kava extract induces hepatic CYP1A1 enzyme; however, the mechanisms of CYP1A1 induction have not been elucidated, and the kavalactones responsible for CYP1A1 induction have not yet been identified. Using a combination of biochemical assays and molecular docking tools, we determined the functions of kava extract and kavalactones and delineated the underlying mechanisms involved in CYP1A1 induction. The results showed that kava extract displayed a concentration-dependent effect on CYP1A1 induction. Among the six major kavalactones, methysticin triggered the most profound inducing effect on CYP1A1 followed by 7,8-dihydromethysticin. The other four kavalactones (yangonin, 5,6-dehydrokawain, kawain, and 7,8-dihydrokawain) did not show significant effects on CYP1A1. Consistent with the experimental results, in silico molecular docking studies based on the aryl hydrocarbon receptor (AhR)-ligand binding domain homology model also revealed favorable binding to AhR for methysticin and 7,8-dihydromethysticin compared with the remaining kavalactones. Additionally, results from a luciferase gene reporter assay suggested that kava extract, methysticin, and 7,8-dihydromethysticin were able to activate the AhR signaling pathway. Moreover, kava extract-, methysticin-, and 7,8-dihydromethysticin-mediated CYP1A1 induction was blocked by an AhR antagonist and abolished in AhR-deficient cells. These findings suggest that kava extract induces the expression of CYP1A1 via an AhR-dependent mechanism and that methysticin and 7,8-dihydromethysticin contribute to CYP1A1 induction. The induction of CYP1A1

  20. How does male ritual behavior vary across the lifespan? An examination of Fijian kava ceremonies.

    PubMed

    Shaver, John H; Sosis, Richard

    2014-03-01

    Ritual behaviors of some form exist in every society known to anthropologists. Despite this universality, we have little understanding of how ritual behavior varies within populations or across the lifespan, nor the determinants of this variation. Here we test hypotheses derived from life history theory by using behavioral observations and oral interview data concerning participant variation in Fijian kava-drinking ceremonies. We predicted that substantial variation in the frequency and duration of participation would result from (1) trade-offs with reproduction and (2) the intrinsic status differences between ritual participants. We demonstrate that when controlling for household composition, men with young offspring participated less frequently and exhibited greater variance in their time spent at ceremonies than men without young children. However, men with a larger number of total dependents in their household participated more frequently than those with fewer. Moreover, we found that men's ascribed rank, level of education, and reliance on wage labor all significantly predict their frequency of attendance. We also found that the number of dependents a man has in his household is positively correlated with total food production, and the amount of kava he cultivates. In general, these results suggest that ritual participation is part of an important strategy employed by Fijian men for both achieving status and developing social alliances. Variation in participation in kava ceremonies by Fijian men therefore reflects the constraints of their current life history condition and their inherited rank.

  1. VLBI observations of bright AGN jets with the KVN and VERA Array (KaVA): Evaluation of imaging capability

    NASA Astrophysics Data System (ADS)

    Niinuma, Kotaro; Lee, Sang-Sung; Kino, Motoki; Sohn, Bong Won; Akiyama, Kazunori; Zhao, Guang-Yao; Sawada-Satoh, Satoko; Trippe, Sascha; Hada, Kazuhiro; Jung, Taehyun; Hagiwara, Yoshiaki; Dodson, Richard; Koyama, Shoko; Honma, Mareki; Nagai, Hiroshi; Chung, Aeree; Doi, Akihiro; Fujisawa, Kenta; Han, Myoung-Hee; Kim, Joeng-Sook; Lee, Jeewon; Lee, Jeong Ae; Miyazaki, Atsushi; Oyama, Tomoaki; Sorai, Kazuo; Wajima, Kiyoaki; Bae, Jaehan; Byun, Do-Young; Cho, Se-Hyung; Choi, Yoon Kyung; Chung, Hyunsoo; Chung, Moon-Hee; Han, Seog-Tae; Hirota, Tomoya; Hwang, Jung-Wook; Je, Do-Heung; Jike, Takaaki; Jung, Dong-Kyu; Jung, Jin-Seung; Kang, Ji-Hyun; Kang, Jiman; Kang, Yong-Woo; Kan-ya, Yukitoshi; Kanaguchi, Masahiro; Kawaguchi, Noriyuki; Kim, Bong Gyu; Kim, Hyo Ryoung; Kim, Hyun-Goo; Kim, Jaeheon; Kim, Jongsoo; Kim, Kee-Tae; Kim, Mikyoung; Kobayashi, Hideyuki; Kono, Yusuke; Kurayama, Tomoharu; Lee, Changhoon; Lee, Jung-Won; Lee, Sang Hyun; Minh, Young Chol; Matsumoto, Naoko; Nakagawa, Akiharu; Oh, Chung Sik; Oh, Se-Jin; Park, Sun-Youp; Roh, Duk-Gyoo; Sasao, Tetsuo; Shibata, Katsunori M.; Song, Min-Gyu; Tamura, Yoshiaki; Wi, Seog-Oh; Yeom, Jae-Hwan; Yun, Young Joo

    2014-12-01

    The Korean very-long-baseline interferometry (VLBI) network (KVN) and VLBI Exploration of Radio Astrometry (VERA) Array (KaVA) is the first international VLBI array dedicated to high-frequency (23-43 GHz bands) observations in East Asia. Here, we report the first imaging observations of three bright active galactic nuclei (AGNs) known for their complex morphologies: 4C 39.25, 3C 273, and M 87. This is one of the initial results of KaVA's early operation. Our KaVA images reveal extended outflows with complex substructures such as knots and limb brightening, in agreement with previous Very Long Baseline Array (VLBA) observations. Angular resolutions are better than 1.4 and 0.8 mas at 23 and 43 GHz, respectively. KaVA achieves a high dynamic range of ˜ 1000, more than three times the value achieved by VERA. We conclude that KaVA is a powerful array with a great potential for the study of AGN outflows, at least comparable to the best existing radio interferometric arrays.

  2. The health and social effects of drinking water-based infusions of kava: a review of the evidence.

    PubMed

    Rychetnik, Lucie; Madronio, Christine M

    2011-01-01

    To review the evidence on the health and social effects of drinking kava; a water-based infusion of the roots of the kava plant. Included all empirical studies of the effects of kava published 1987-2008 reporting health and social outcomes. Evidence appraised on study design (level of evidence) and standard epidemiological criteria for causality. Causality indicated: scaly skin rash, weight loss, raised Gamma Glutamyl Transpeptidase liver enzyme levels, nausea, loss of appetite or indigestion; Association indicated but causality unclear: red sore eyes, impotence or loss of sexual drive, self-reported poor health, raised cholesterol, and loss of time and money, low motivation and 'slow/lazy' days following use, reduced alcohol consumption and related violence; Association hypothesised: fits or seizures, Melioidosis, Ischaemic Heart Disease, protective effects for cancer; No association indicated: cognitive performance; No association suggested: cognitive impairment, liver toxicity or permanent liver damage, other pneumonia; No association hypothesised: hallucinations. The health and social implications of chronic kava drinking can be significant for individuals and communities, although most effects of even heavy consumption appear to be reversible when consumption is stopped. An Australia-wide ban on commercial importation of kava has been in place since mid-2007, but there is no published literature to date on the impact of the ban. © 2010 Australasian Professional Society on Alcohol and other Drugs.

  3. Effects of kava alkaloid, pipermethystine, and kavalactones on oxidative stress and cytochrome P450 in F-344 rats.

    PubMed

    Lim, Steven T S; Dragull, Klaus; Tang, Chung-Shih; Bittenbender, Harry C; Efird, Jimmy T; Nerurkar, Pratibha V

    2007-05-01

    Kava-containing products remain popular in the United States and continue to be sold in health food stores and ethnic markets regardless of the fact that it was banned in Western countries such as Germany, France, Switzerland, Australia, and Canada, following reports of alleged hepatotoxicity. It is therefore critical to establish efficacy and verify adverse effects and/or herb-drug interactions for kava-kava (Piper methysticum). We have previously demonstrated that kava alkaloid, pipermethystine (PM), abundant in leaves and stem peelings, induces mitochondrial toxicity in human hepatoma cells, HepG2, as compared with the bioactive components, kavalactones (KL), abundant in the rhizome. The current study compared short-term toxic effects of PM in Fischer-344 (F-344) rats to acetone-water extracts of kava rhizome (KRE). Treatment of F-344 rats with PM (10 mg/kg) and KRE (100 mg/kg) for 2 weeks failed to elicit any significant changes in liver function tests or cause severe hepatic toxicity as measured by lipid peroxidation and apoptosis markers such as malondialdehyde, Bax, and Bcl-2. However, PM-treated rats demonstrated a significant increase in hepatic glutathione, cytosolic superoxide dismutase (Cu/ZnSOD), tumor necrosis factor alpha mRNA expression, and cytochrome P450 (CYP) 2E1 and 1A2, suggesting adaptation to oxidative stress and possible drug-drug interactions.

  4. Analysis of gene expression changes of drug metabolizing enzymes in the livers of F344 rats following oral treatment with kava extract.

    PubMed

    Guo, Lei; Li, Quanzhen; Xia, Qingsu; Dial, Stacey; Chan, Po-Chuen; Fu, Peter

    2009-02-01

    The association of kava product use with liver-related risks has prompted regulatory action in many countries. We studied the changes in gene expression of drug metabolizing enzymes in the livers of Fischer 344 male rats administered kava extract by gavage for 14 weeks. Analysis of 22,226 genes revealed that there were 14, 41, 110, 386, and 916 genes significantly changed in the 0.125, 0.25, 0.5, 1.0, and 2.0 g/kg treatment groups, respectively. There were 16 drug metabolizing genes altered in all three high-dose treatment groups, among which seven genes belong to cytochrome P450 isozymes. While gene expression of Cyp1a1, 1a2, 2c6, 3a1, and 3a3 increased; Cyp 2c23 and 2c40 decreased, all in a dose-dependent manner. Real-time PCR analyses of several genes verified these results. Our results indicate that kava extract can significantly modulate drug metabolizing enzymes, particularly the CYP isozymes, which could cause herb-drug interactions and may potentially lead to hepatotoxicity.

  5. Potential for interaction of kava and St. John's wort with drugs.

    PubMed

    Singh, Yadhu N

    2005-08-22

    The present interest and widespread use of herbal remedies has created the possibility of interaction between them and pharmaceutical drugs if they are used simultaneously. Before the recent reports of apparent hepatotoxicity associated with its use, kava (Piper methysticum Forst. F.), was one of the top 10 selling herbal remedies in Europe and North America. This adverse effect was not previously encountered with the traditional beverage which was prepared as a water infusion in contrast to the commercial products which are extracted with organic solvents. Kavalactones, the active principles in kava, are potent inhibitors of several of the CYP 450 enzymes, suggesting a high potential for causing pharmacokinetic interactions with drugs and other herbs which are metabolized by the same CYP 450 enzymes. Furthermore, some kavalactones have been shown to possess pharmacological effects, such as blockade of GABA receptors and sodium and calcium ion channels, which may lead to pharmacodynamic interactions with other substances which possess similar pharmacological proprieties. St. John's wort (Hypericum perforatum L.), used extensively for the treatment of mild to moderate clinical depression, has long been considered safer than the conventional pharmaceutical agents. However, its ability, through its active constituents hypericin, pseudohypericin and hyperforin, to induce intestinal P-glycoprotein/MRD1 and both intestinal and hepatic CYP3A4 enzyme, could markedly reduce the distribution and disposition of their co-substrates. In addition, St. John's wort is a potent uptake inhibitor of the neurotransmitters serotonin, norepinephrine and dopamine all of which have a role in mood control. Consequently, the very real potential for a pharmacodynamic interaction between the herb and pharmaceutical drugs which share this mechanism of action and, like St. John's wort, are used for mood elevation. However, presently there is very little evidence to substantiate actual

  6. Kava blocks 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced lung tumorigenesis in association with reducing O6-methylguanine DNA adduct in A/J mice.

    PubMed

    Leitzman, Pablo; Narayanapillai, Sreekanth C; Balbo, Silvia; Zhou, Bo; Upadhyaya, Pramod; Shaik, Ahmad Ali; O'Sullivan, M Gerard; Hecht, Stephen S; Lu, Junxuan; Xing, Chengguo

    2014-01-01

    We previously reported the chemopreventive potential of kava against 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)- and benzo(a)pyrene (BaP)-induced lung tumorigenesis in A/J mice during the initiation and postinitiation stages. In this study, we investigated the tumorigenesis-stage specificity of kava, the potential active compounds, and the underlying mechanisms in NNK-induced lung tumorigenesis in A/J mice. In the first experiment, NNK-treated mice were given diets containing kava at a dose of 5 mg/g of diet during different periods. Kava treatments covering the initiation stage reduced the multiplicity of lung adenomas by approximately 99%. A minimum effective dose is yet to be defined because kava at two lower dosages (2.5 and 1.25 mg/g of diet) were equally effective as 5 mg/g of diet in completely inhibiting lung adenoma formation. Daily gavage of kava (one before, during, and after NNK treatment) completely blocked lung adenoma formation as well. Kavalactone-enriched fraction B fully recapitulated kava's chemopreventive efficacy, whereas kavalactone-free fractions A and C were much less effective. Mechanistically, kava and fraction B reduced NNK-induced DNA damage in lung tissues with a unique and preferential reduction in O(6)-methylguanine (O(6)-mG), the highly tumorigenic DNA damage by NNK, correlating and predictive of efficacy on blocking lung adenoma formation. Taken together, these results demonstrate the outstanding efficacy of kava in preventing NNK-induced lung tumorigenesis in A/J mice with high selectivity for the initiation stage in association with the reduction of O(6)-mG adduct in DNA. They also establish the knowledge basis for the identification of the active compound(s) in kava.

  7. Determination of kavalactones in dried kava (Piper methysticum) powder using near-infrared reflectance spectroscopy and partial least-squares regression.

    PubMed

    Gautz, Loren D; Kaufusi, Pakieli; Jackson, Mel C; Bittenbender, Harry C; Tang, Chung-Shih

    2006-08-23

    Kava (Piper methysticum Forst F.), or àwa in the Hawaiian language, has been used for thousands of years by the people of the South Pacific Islands, in particular Fiji, Vanuatu, Tonga, and Samoa, for social and ceremonial occasions. Kava has the unique ability to promote a state of relaxation without the loss of mental alertness. Kava recently became part of the herbal pharmacopoeia throughout the United States and Europe because of its anxiolytic properties. The active compounds are collectively called kavalactones (or kava pyrones). The need for a less time-consuming and costly method to determine the concentration of kavalactones in dried kava is urgent. The combination of near-infrared reflectance spectroscopy (NIRS) and partial least-squares (PLS) methods has been found to be a convenient, versatile, and rapid analytical tool for determination of kavalactones in dried kava powder. Calibration equations were developed based on the analyses of 110 samples with variable physical and chemical properties collected over time from Hawaii kava growers and validated by analyses of a set of 12 samples with unknown kavalactones concentration. All six major kavalactones and the total kavalactones were measured using NIRS with accuracy acceptable for commercial use. The NIRS measurements are reproducible and have a repeatability on a par with HPLC methods.

  8. High dose of commercial products of kava (Piper methysticum) markedly enhanced hepatic cytochrome P450 1A1 mRNA expression with liver enlargement in rats.

    PubMed

    Yamazaki, Yuko; Hashida, Hiroko; Arita, Anna; Hamaguchi, Keiko; Shimura, Fumio

    2008-12-01

    Commercial products containing the kava plant (Piper methysticum), known to have the anxiolytic activity, are banned in several European countries and Canada because of the suspicion of a potential liver toxicity. In some reports, kava and kavalactones (major constituents of kava) inhibited activities of cytochrome P450 (CYP) isoforms including CYP1A2. On the other hand, a few studies showed that administration of kava to rats moderately increased CYP1A2 proteins in the liver. CYP1A isoforms are likely responsible for the metabolic activation of potent carcinogenic environmental toxins such as aflatoxins, benzo[a]pyrene, and others. On these bases, we have investigated the effects of administration of commercial kava products on gene expression of hepatic CYP1A isoforms in rats. A high dose (equivalent to approximately 380mg kavalactones/kg/day; 100 times of the suggested dosage for human use) of two different types of kava products for 8 days significantly increased liver weights. CYP1A2 mRNA expression was moderately increased (2.8-7.3 fold). More importantly, the high dose of kava markedly enhanced CYP1A1 mRNA expression (75-220 fold) as well as ethoxyresorufin O-deethylase activities and CYP1A1 immunoreactivities. Thus, no observed adverse effect levels of kavalactones would be lower than 380mg/kg/day. When the safety factor of kavalactones is assumed to be 100, a value most often used upon the risk analysis of chemicals and designed to account for interspecies and intraspecies variations, a number of kava product users likely ingest more kavalactones than acceptable daily intakes. Based on overall evidence, we should pay considerable attention to the possibility that kava products induce hepatic CYP1A1 expression in human especially in sensitive individuals.

  9. An internet-based randomized, placebo-controlled trial of kava and valerian for anxiety and insomnia.

    PubMed

    Jacobs, Bradly P; Bent, Stephen; Tice, Jeffrey A; Blackwell, Terri; Cummings, Steven R

    2005-07-01

    The herbal extracts kava and valerian are the leading dietary supplements used in the self-management of anxiety and insomnia, respectively. There is limited evidence to support their effectiveness for these common symptoms. The Internet has been used to a limited extent for research, but it is not known whether randomized controlled trials can be conducted entirely using Internet technology. We performed a randomized, double-blind, placebo-controlled trial using a novel Internet-based design to determine if kava is effective for reducing anxiety and if valerian is effective for improving sleep quality. E-mail recruitment letters and banner advertisements on websites were used to recruit a large pool of interested participants (1551) from 45 states over an 8-week period. Participants were first asked to read study information, complete an online informed consent process, and undergo electronic identity verification. In order to be eligible for the study, participants were required to have 1) anxiety as documented by scores of at least 0.5 standard deviations above the mean on the State-Trait Anxiety Inventory State subtest (STAI-State) on 2 separate occasions, and 2) insomnia, defined as a "problem getting to sleep or staying asleep over the past 2 weeks." We randomly assigned 391 eligible participants to 1 of the following 3 groups, and mailed 28 days' supply: kava with valerian placebo (n = 121), valerian with kava placebo (n = 135), or double placebo (n = 135). The primary outcome measures were changes from baseline in anxiety (STAI-State questionnaire) and insomnia (Insomnia Severity Index [ISI]) compared with placebo. Participants receiving placebo had a 14.4 point decrease in anxiety symptoms on the STAI-State score and an 8.3 point decrease in insomnia symptoms on the ISI. Those receiving kava had similar reductions in STAI-State score (2.7 point greater reduction in placebo compared with kava; 95% confidence interval [CI], -0.8 to +6.2). Those receiving

  10. Kava components down-regulate expression of AR and AR splice variants and reduce growth in patient-derived prostate cancer xenografts in mice.

    PubMed

    Li, Xuesen; Liu, Zhongbo; Xu, Xia; Blair, Christopher A; Sun, Zheng; Xie, Jun; Lilly, Michael B; Zi, Xiaolin

    2012-01-01

    Men living in Fiji and drinking kava have low incidence of prostate cancer (PCa). However, the PCa incidence among Fijian men who had migrated to Australia, increased by 5.1-fold. We therefore examined the potential effects of kava root extracts and its active components (kavalactones and flavokawains) on PCa growth and androgen receptor (AR) expression. PCa cell lines (LNCaP, LAPC-4, 22Rv1, C4-2B, DU145 and PC-3) with different AR expression, and a transformed prostate myofibroblast cell line (WPMY-1), were treated with a commercial kava extract, kavalactones (kawain, 5'6'-dehydrokawain, yangonin, methysticin) and flavokawain B. Expression of AR and its target genes (PSA and TMPRSS2) was examined. Two novel patient-derived PCa xenograft models from high grade PCa specimens were established by implanting the specimens into nude mice and passing tumor pieces through subcutaneous injection in nude mice, and then treated with kava extract and flavokawain B to examine their effects on tumor growth, AR expression and serum PSA levels. The kava extract and flavokawain B effectively down-regulated the expression of both the full-length AR and AR splice variants. The kava extract and kavalactones accelerated AR protein degradation, while flavokawain B inhibited AR mRNA transcription via decreasing Sp1 expression and the binding of Sp1 to the AR promoter. The kava root extract and flavokawain B reduce tumor growth, AR expression in tumor tissues and levels of serum PSA in the patient-derived PCa xenograft models. These results suggest a potential usefulness of a safe kava product or its active components for prevention and treatment of advanced PCa by targeting AR.

  11. Kava Components Down-Regulate Expression of AR and AR Splice Variants and Reduce Growth in Patient-Derived Prostate Cancer Xenografts in Mice

    PubMed Central

    Li, Xuesen; Liu, Zhongbo; Xu, Xia; Blair, Christopher A.; Sun, Zheng; Xie, Jun; Lilly, Michael B.; Zi, Xiaolin

    2012-01-01

    Men living in Fiji and drinking kava have low incidence of prostate cancer (PCa). However, the PCa incidence among Fijian men who had migrated to Australia, increased by 5.1-fold. We therefore examined the potential effects of kava root extracts and its active components (kavalactones and flavokawains) on PCa growth and androgen receptor (AR) expression. PCa cell lines (LNCaP, LAPC-4, 22Rv1, C4-2B, DU145 and PC-3) with different AR expression, and a transformed prostate myofibroblast cell line (WPMY-1), were treated with a commercial kava extract, kavalactones (kawain, 5′6′-dehydrokawain, yangonin, methysticin) and flavokawain B. Expression of AR and its target genes (PSA and TMPRSS2) was examined. Two novel patient-derived PCa xenograft models from high grade PCa specimens were established by implanting the specimens into nude mice and passing tumor pieces through subcutaneous injection in nude mice, and then treated with kava extract and flavokawain B to examine their effects on tumor growth, AR expression and serum PSA levels. The kava extract and flavokawain B effectively down-regulated the expression of both the full-length AR and AR splice variants. The kava extract and kavalactones accelerated AR protein degradation, while flavokawain B inhibited AR mRNA transcription via decreasing Sp1 expression and the binding of Sp1 to the AR promoter. The kava root extract and flavokawain B reduce tumor growth, AR expression in tumor tissues and levels of serum PSA in the patient-derived PCa xenograft models. These results suggest a potential usefulness of a safe kava product or its active components for prevention and treatment of advanced PCa by targeting AR. PMID:22347450

  12. Morphological research on radio loud AGN 4C39.25 using KaVA observations

    NASA Astrophysics Data System (ADS)

    Yoo, Hyemin; Sohn, Bong Won; Yi, Sukyoung; KaVA AGN WG members

    2016-01-01

    4C39.25 (0923+392) is a distant radio loud AGN placed at redshift 0.695. Its kilo-parsec scale jet observed by VLBA(Kollgaard et al. 1990) and parsec scale jet observed by VLBA(Kellermann et al. 1998) are misaligned. This might indicate episodic-jet activity which recently turned on. This object currently shows two stationary compact parsec-scale components:a bright jet component on the east and less luminous core on the west. Also, it is known that there have been superluminal jet components which are flowing from the core toward east, and then merging with the bright jet component (Marscher et al. 1991, Alberdi et al. 2000, Lister et al. 2013). Including the detection of broad emission lines(SDSS), its viewing angle was concluded to be small. However, the jet component being more luminous than the core is abnormal for a source with a small viewing angle. Furthermore, it has young radio galaxy-like properties such as non-variation in total flux(Alberdi et al. 1997, 2000, MOJAVE database) and a high frequency peak in the spectral energy distribution(Orienti et al 2007). In this case, it is more reliable to think that viewing angle of 4C39.25 is large. Korean VLBI Network (KVN) and VLBI Exploration of Radio Astronomy (VERA) Array (KaVA) is a cooperated VLBI system of Korea and Japan which provides high-frequency (23GHz and 43GHz) and high spatial resolution(1.2mas and 0.6mas). Their advantages of multi-wavelength and relatively high S/N ratio relative to its number of baseline allow us to discover the central region and dim structures of 4C39.25. We present results of several epochs observed during 2013 to 2014, focusing on morphological changes of 4C39.25 using KaVA images. According to these results, we were able to find a recently emitted counter-jet component for images of first 6 epochs. Also the counter-jet component propagates along a curved trajectory, and it shows an extreme superluminal motion. This might indicate a necessity of relatively large viewing

  13. Effect of kava extract and individual kavapyrones on neurotransmitter levels in the nucleus accumbens of rats.

    PubMed

    Baum, S S; Hill, R; Rommelspacher, H

    1998-10-01

    1. Kavapyrones have well-known psychotropic properties. The most common actions of the extract are relaxation and euphoria, depending on the circumstances of ingestion, whereas higher doses cause sleepiness and skeletal muscle relaxation. Several other actions have been reported such as anticonvulsant properties, neuroprotection and analgesia. No interactions with neuroreceptors have yet been found that would explain the multiple actions. 2. To reveal neuronal functions affected by the kavapyrones the authors studied their actions on the mesolimbic reward system using in vivo microdialysis. 3. A small dose of kava extract (20 mg/kg body weight i.p.) caused changes in rat behaviour and concentrations of dopamine in the nucleus accumbens. Higher doses (120 mg/kg i.p.) increased the levels of dopamine. With respect to the individual compounds, D,L-kawain induced in low doses a decrease in dopamine levels and in higher amounts either an increase or no change in dopamine concentrations. Yangonin resulted in a decrease of dopamine levels to below the detection limit and desmethoxyyangonin in an increase of dopamine levels. Dihydrokawain, methysticin and dihydromethysticin did not produce any significant changes of dopamine levels. D,L-kawain caused a decrease in 5-HT concentrations. Some of the other kavapyrones affected 5-HT levels as well. 4. The results suggest that the relaxing and slightly euphoric actions may be caused by the activation of the mesolimbic dopaminergic neurones. Changes of the activity of 5-HT neurones could explain the sleep-inducing action.

  14. Identification and characterization of Kava-derived compounds mediating TNF-α suppression

    PubMed Central

    Pollastri, Michael P.; Whitty, Adrian; Merrill, Jamie Cassidy; Ashton, Trent D.; Amar, Salomon

    2009-01-01

    There is a substantial unmet need for new classes of drugs that block TNF-α-mediated inflammation, and particularly for small molecule agents that can be taken orally. We have screened a library of natural products against an assay measuring TNF-α secretion in lipopolysaccharide (LPS)-stimulated THP-1 cells, seeking compounds capable of interfering with the TNF-α inducing transcription factor Lipopolysaccharide Induced TNF Alpha Factor (LITAF). Among the active compounds were several produced by the kava plant (Piper mysticum), extracts of which have previously been linked to a range of therapeutic effects. When tested in vivo, a representative of these compounds, kavain, was found to render mice immune to lethal doses of LPS. Kavain displays promising pharmaceutical properties, including good solubility and high cell permeability, but pharmacokinetic experiments in mice showed relatively rapid clearance. A small set of kavain analogs was synthesized, resulting in compounds of similar or greater potency in vitro compared to kavain. Interestingly, a ring-opened analog of kavain inhibited TNF-α secretion in the cell based assay and suppressed LITAF expression in the same cells, whereas the other compounds inhibited TNF-α secretion without affecting LITAF levels, indicating a potential divergence in mechanism of action. PMID:19538508

  15. Flavokawain B, a kava chalcone, induces apoptosis in synovial sarcoma cell lines.

    PubMed

    Sakai, Toshinori; Eskander, Ramez N; Guo, Yi; Kim, Kap Jung; Mefford, Jason; Hopkins, Justin; Bhatia, Nitin N; Zi, Xiaolin; Hoang, Bang H

    2012-07-01

    Synovial sarcomas (SS) are soft tissue sarcomas with poor prognosis, displaying a lack of response to conventional cytotoxic chemotherapy. Although SS cell lines have moderate chemosensitivity to isofamide and doxorubicin therapy, the clinical prognosis is still poor. In this article, we showed that flavokawain B (FKB), a novel chalcone from kava extract, potently inhibits the growth of SS cell lines SYO-I and HS-SY-II through induction of apoptosis. Treatment with FKB increased caspase 8, 9, and 3/7 activity compared to vehicle-treated controls, indicating that both extrinsic and intrinsic apoptotic pathways were activated. Furthermore, FKB treatment of both cell lines resulted in increased mRNA and protein expression of death receptor-5 and the mitochondrial pro-apoptotic proteins Bim and Puma, while down-regulating the expression of an inhibitor of apoptosis, survivin in a dose-dependent manner. Our results suggest the natural compound FKB has a pro-apoptotic effect on SS cell lines. FKB may be a new chemotherapeutic strategy for patients with SS and deserves further investigation as a potential agent in the treatment of this malignancy.

  16. Flavokawain B, the hepatotoxic constituent from kava root, induces GSH-sensitive oxidative stress through modulation of IKK/NF-kappaB and MAPK signaling pathways.

    PubMed

    Zhou, Ping; Gross, Shimon; Liu, Ji-Hua; Yu, Bo-Yang; Feng, Ling-Ling; Nolta, Jan; Sharma, Vijay; Piwnica-Worms, David; Qiu, Samuel X

    2010-12-01

    Kava (Piper methysticum Foster, Piperaceae) organic solvent-extract has been used to treat mild to moderate anxiety, insomnia, and muscle fatigue in Western countries, leading to its emergence as one of the 10 best-selling herbal preparations. However, several reports of severe hepatotoxicity in kava consumers led the U.S. Food and Drug Administration and authorities in Europe to restrict sales of kava-containing products. Herein we demonstrate that flavokawain B (FKB), a chalcone from kava root, is a potent hepatocellular toxin, inducing cell death in HepG2 (LD(50)=15.3 ± 0.2 μM) and L-02 (LD(50)=32 μM) cells. Hepatocellular toxicity of FKB is mediated by induction of oxidative stress, depletion of reduced glutathione (GSH), inhibition of IKK activity leading to NF-κB transcriptional blockade, and constitutive TNF-α-independent activation of mitogen-activated protein kinase (MAPK) signaling pathways, namely, ERK, p38, and JNK. We further demonstrate by noninvasive bioluminescence imaging that oral consumption of FKB leads to inhibition of hepatic NF-κB transcriptional activity in vivo and severe liver damage. Surprisingly, replenishment with exogenous GSH normalizes both TNF-α-dependent NF-κB as well as MAPK signaling and rescues hepatocytes from FKB-induced death. Our data identify FKB as a potent GSH-sensitive hepatotoxin, levels of which should be specifically monitored and controlled in kava-containing herb products.

  17. Case-control study of the association between kava use and pneumonia in eastern Arnhem and Aboriginal communities (Northern Territory, Australia).

    PubMed Central

    Clough, A. R.; Wang, Z.; Bailie, R. S.; Burns, C. B.; Currie, B. J.

    2003-01-01

    Pneumonia causes significant morbidity and mortality in Aboriginal populations in Australia's Northern Territory (NT). Kava, consumed in Arnhem Land since 1982, may be a risk factor for infectious disease including pneumonia. A case-control study (n = 115 cases; n = 415 controls) was conducted in 7001 Aboriginal people (4217 over 15 years). Odds ratios (OR) were calculated by conditional logistic regression with substance use and social factors as confounders. Pneumonia was not associated with kava use. Crude OR = 1.26 (0.74-2.14, P = 0.386), increased after controlling for confounders (OR = 1.98, 0.63-6.23, P = 0.237) but was not significant. Adjusted OR for pneumonia cases involving kava and alcohol users was 1.19 (0.39-3.62, P = 0.756). In communities with longer kava-using histories, adjusted OR was 2.19 (0.67-7.14, P = 0.187). There was no kava dose-response relationship. Crude ORs for associations between pneumonia and cannabis use (OR = 2.27, 1 18-4.37, P = 0.014) and alcohol use (OR = 1.95, 1.07-3.53, P = 0.026) were statistically significant and approached significance for petrol sniffing (OR = 1.98, 0.99-3.95, P = 0.056). PMID:12948361

  18. The risk-benefit profile of commonly used herbal therapies: Ginkgo, St. John's Wort, Ginseng, Echinacea, Saw Palmetto, and Kava.

    PubMed

    Ernst, Edzard

    2002-01-01

    Because use of herbal remedies is increasing, a risk-benefit profile of commonly used herbs is needed. This article provides a clinically oriented overview of the efficacy and safety of ginkgo, St. John's wort, ginseng, echinacea, saw palmetto, and kava. Wherever possible, assessments are based on systematic reviews of randomized clinical trials. Encouraging data support the efficacy of some of these popular herbal medicinal products, and the potential for doing good seems greater than that for doing harm. The published evidence suggests that ginkgo is of questionable use for memory loss and tinnitus but has some effect on dementia and intermittent claudication. St. John's wort is efficacious for mild to moderate depression, but serious concerns exist about its interactions with several conventional drugs. Well-conducted clinical trials do not support the efficacy of ginseng to treat any condition. Echinacea may be helpful in the treatment or prevention of upper respiratory tract infections, but trial data are not fully convincing. Saw palmetto has been shown in short-term trials to be efficacious in reducing the symptoms of benign prostatic hyperplasia. Kava is an efficacious short-term treatment for anxiety. None of these herbal medicines is free of adverse effects. Because the evidence is incomplete, risk-benefit assessments are not completely reliable, and much knowledge is still lacking.

  19. Detection of flavokavins (A, B, C) in cultivars of kava (Piper methysticum) using high performance thin layer chromatography (HPTLC).

    PubMed

    Lebot, V; Do, T K T; Legendre, L

    2014-05-15

    Kava (Piper methysticum) is used to prepare the traditional beverage of the Pacific islands. In Europe, kava has been suspected to cause hepatoxicity with flavokavin B (FKB) considered as a possible factor. The present study describes an HPTLC protocol for rapid screening of samples. The objectives are: to detect the presence of flavokavins in extracts and to compare the FKB levels in different cultivars. Overall, 172 samples originating from four cultivars groups (noble, medicinal, two-days and wichmannii), were analysed. Results indicate that the ratio FKB/kavalactones is much higher in two-days (0.39) and wichmannii (0.32) compared to nobles (0.09) and medicinal cultivars (0.10). For each group, the ratios flavokavins/kavalactones do not change significantly between roots, stumps or basal stems and among clones, indicating that they are genetically controlled. This protocol has good accuracy and is cost efficient for routine analysis. We discuss how it could be used for quality control.

  20. Comparative analysis of genetic variation in kava (Piper methysticum) assessed by SSR and DArT reveals zygotic foundation and clonal diversification.

    PubMed

    Vandenbroucke, Henri; Mournet, Pierre; Malapa, Roger; Glaszmann, Jean-Christophe; Chaïr, Hana; Lebot, Vincent

    2015-01-01

    Kava (Piper methysticum) is a major cash crop in the Pacific. The aim of this study was to assess genetic variation among 103 accessions of kava using SSRs and DArTs. Genetic structure was determined using clustering analyses (WPGMA) and principal coordinate analyses (PCA). Thirteen SSR primers and 75 DArT markers were found polymorphic, and the two types of markers generated similar clustering patterns. Genetic distances ranged from 0 to 0.65 with an average of 0.24 using SSRs and from 0 to 0.64 with an average of 0.24 using DArT. Eleven genotypes were identified with SSR while 28 genotypes were identified with DArT markers. By combining the two sets of markers, a total of only 30 distinct genotypes were observed. In the Vanuatu archipelago, noble cultivars originating from different islands clustered together within a very narrow genetic base despite their diversity of morphotypes. SSR and DArT fingerprints allowed the identification of kava cultivars unsuitable for consumption, so called two-days, and clearly differentiated the wild types classified as P. methysticum var. wichmannii from the cultivars as var. methysticum. Molecular data reveals that all noble cultivars evolved by the predominance of clonal selection. Although they are represented by clearly distinct morphotypes, these cultivars are genetically vulnerable and their potential to adapt to forthcoming changes is limited. These newly developed markers provide high resolution and will be useful for kava diversity analyses and quality assessment.

  1. Coltsfoot as a potential cause of deep vein thrombosis and pulmonary embolism in a patient also consuming kava and blue vervain.

    PubMed

    Freshour, Jessica E; Odle, Brian; Rikhye, Somi; Stewart, David W

    2012-09-01

    To report a case of deep vein thrombosis (DVT) with symptomatic pulmonary embolism (PE) possibly associated with the use of coltsfoot, kava, or blue vervain. A 27-year-old white male presented with leg pain and swelling, tachycardia, and pleuritic chest pain. He had no significant medical history. A medication history revealed extensive herbal medication use including: coltsfoot, passionflower, red poppy flower petals, wild lettuce, blue lily flowers, wild dagga flowers, Diviners Three Burning Blend® (comprised of salvia divinorum, blue lily, and wild dagga), kava-kava, St. John's Wort, blue vervain, and Dreamer's Blend® (comprised of Calea zacatechichi, vervain, Entada rheedii, wild lettuce, and Eschscholzia californica). Lower extremity Doppler ultrasound and computed topography (CT) of the chest revealed DVT and PE. A hypercoagulable work-up was negative. The patient was treated with enoxaparin and warfarin and was discharged home. While no distinct agent can be identified as a sole cause of this venous thromboembolic event, coltsfoot could potentially affect coagulation through its effect on vascular endothelial cells as they regulate nitric oxide. Nitric oxide is a known mediator of platelet activity and coagulation, particularly in the pulmonary vasculature. Kava and vervain have estrogenic properties. Of the medications consumed by this self-proclaimed "herbalist," coltsfoot is a potential cause of venous thromboembolic disease (VTE).

  2. Gene expression signatures associated with suppression of TRAMP prostate carcinogenesis by a kavalactone-rich Kava fraction.

    PubMed

    Tang, Su-Ni; Zhang, Jinhui; Jiang, Peixin; Datta, Palika; Leitzman, Pablo; O'Sullivan, M Gerard; Jiang, Cheng; Xing, Chengguo; Lü, Junxuan

    2016-12-01

    Kava (Piper methysticum Forster) extract and its major kavalactones have been shown to block chemically induced lung tumor initiation in mouse models. Here we evaluated the chemopreventive effect of a kavalactone-rich Kava fraction B (KFB), free of flavokavains, on carcinogenesis in a transgenic adenocarcinoma of mouse prostate (TRAMP) model and characterized the prostate gene expression signatures. Male C57BL/6 TRAMP mice were fed AIN93M diet with or without 0.4% KFB from 8 wk of age. Mice were euthanized at 16 or 28 wk. The growth of the dorsolateral prostate (DLP) lobes in KFB-treated TRAMP mice was inhibited by 66% and 58% at the respective endpoint. Anterior and ventral prostate lobes in KFB-treated TRAMP mice were suppressed by 40% and 49% at 28 wk, respectively. KFB consumption decreased cell proliferation biomarker Ki-67 and epithelial lesion severity in TRAMP DLP, without detectable apoptosis enhancement. Real time qRT-PCR detection of mRNA from DLP at 28 wk showed decreased expression of cell cycle regulatory genes congruent with Ki-67 suppression. Microarray profiling of DLP mRNA indicated that "oncogene-like" genes related to angiogenesis and cell proliferation were suppressed by KFB but tumor suppressor, immunity, muscle/neuro, and metabolism-related genes were upregulated by KFB in both TRAMP and WT DLP. TRAMP mice fed KFB diet developed lower incidence of neuroendocrine carcinomas (NECa) (2 out of 14 mice) than those fed the basal diet (8 out of 14 mice, χ(2)  = 5.6, P < 0.025). KFB may, therefore, inhibit not only TRAMP DLP epithelial lesions involving multiple molecular pathways, but also NECa. © 2016 Wiley Periodicals, Inc.

  3. Kavain, the Major Constituent of the Anxiolytic Kava Extract, Potentiates GABAA Receptors: Functional Characteristics and Molecular Mechanism

    PubMed Central

    Chua, Han Chow; Christensen, Emilie T. H.; Hoestgaard-Jensen, Kirsten; Hartiadi, Leonny Y.; Ramzan, Iqbal; Jensen, Anders A.; Absalom, Nathan L.; Chebib, Mary

    2016-01-01

    Extracts of the pepper plant kava (Piper methysticum) are effective in alleviating anxiety in clinical trials. Despite the long-standing therapeutic interest in kava, the molecular target(s) of the pharmacologically active constituents, kavalactones have not been established. γ-Aminobutyric acid type A receptors (GABAARs) are assumed to be the in vivo molecular target of kavalactones based on data from binding assays, but evidence in support of a direct interaction between kavalactones and GABAARs is scarce and equivocal. In this study, we characterised the functional properties of the major anxiolytic kavalactone, kavain at human recombinant α1β2, β2γ2L, αxβ2γ2L (x = 1, 2, 3 and 5), α1βxγ2L (x = 1, 2 and 3) and α4β2δ GABAARs expressed in Xenopus oocytes using the two-electrode voltage clamp technique. We found that kavain positively modulated all receptors regardless of the subunit composition, but the degree of enhancement was greater at α4β2δ than at α1β2γ2L GABAARs. The modulatory effect of kavain was unaffected by flumazenil, indicating that kavain did not enhance GABAARs via the classical benzodiazepine binding site. The β3N265M point mutation which has been previously shown to profoundly decrease anaesthetic sensitivity, also diminished kavain-mediated potentiation. To our knowledge, this study is the first report of the functional characteristics of a single kavalactone at distinct GABAAR subtypes, and presents the first experimental evidence in support of a direct interaction between a kavalactone and GABAARs. PMID:27332705

  4. Quantification of kavalactones and determination of kava (Piper methysticum) chemotypes using near-infrared reflectance spectroscopy for quality control in vanuatu.

    PubMed

    Lasme, Privat; Davrieux, Fabrice; Montet, Didier; Lebot, Vincent

    2008-07-09

    Kava ( Piper methysticum Forst f., Piperaceae) has anxiolytic properties and the ability to promote a state of relaxation without the loss of mental alertness. The rapid growth of the nutraceutical market between 1998 and 2000 has been stopped by a ban in Europe and Australia because of some suspicion of liver toxicity. It is now important to develop a fast, cheap, and reliable quality test to control kava exports. The aim of this study is to develop a calibration of the near-infrared reflectance spectroscopy (NIRS) using partial least-squares (PLS) regression. Two hundred thirty-six samples of kava roots, stumps, and basal stems were collected from the Vanuatu Agricultural Research and Technical Centre germplasm collection and from four villages. These samples, representing 45 different varieties, were analyzed using NIRS to record their absorption spectra between 400 and 2500 nm. A set of 101 selected samples was analyzed for their kavalactone content using HPLC. The results were used for PLS calibration of the NIRS. The NIRS prediction of the kavalactone content and the dry matter were in agreement with the HPLC results. There were good correlations between these two series of results, and coefficients ( R (2)) were all close to 1. The measurements were reproducible and had repeatability on par with the HPLC method. The NIRS system has been calibrated for the six major kavalactone content measurements, and it is suggested that this method could be used for quality control in Vanuatu.

  5. Inhibition of mitogen activated protein kinases increases the sensitivity of A549 lung cancer cells to the cytotoxicity induced by a kava chalcone analog.

    PubMed

    Warmka, Janel K; Solberg, Eric L; Zeliadt, Nicholette A; Srinivasan, Balasubramanian; Charlson, Aaron T; Xing, Chengguo; Wattenberg, Elizabeth V

    2012-08-03

    We are interested in investigating the biological activity of chalcones, a major class of compounds found in the beverage kava, in order to develop potent and selective chemopreventive candidates. Consumption of kava in the South Pacific Islands is inversely correlated with cancer incidence, even among smokers. Accordingly, chalcones have anti-cancer activities in animal and cell culture models. To investigate signaling pathways that affect chalcone action we studied a potent analog, (E)-3-(3-hydroxy-4-methoxyphenyl)-1-(3,4,5-trimethoxyphenyl)prop-2-en-1-one (chalcone-24). Chalcone-24 was selected from a series of chalcone analogs that were synthesized based on the structures derived from flavokawain compounds found in kava, and screened in A549 lung cancer cells for induction of cytotoxicity and inhibition of NF-κB, a transcription factor associated with cell survival. Incubation of A549 cells with chalcone-24 resulted in a dose-dependent inhibition of cell viability, inhibition of NF-κB, activation of caspases, and activation of extracellular signal regulated kinase 1/2 (ERK1/2) and c-Jun N-terminal kinase (JNK); ERK1/2 and JNK are mitogen activated protein kinases that play central roles in regulating cell fate. Pharmacological inhibitors of ERK1/2 or JNK increased the sensitivity of A549 cells to chalcone-24-induced cytotoxicity, without affecting NF-κB or caspase activity. These results will help refine the synthesis of chalcone analogs to maximize the combination of actions required to prevent and treat cancer.

  6. Kava chalcone, flavokawain A, inhibits urothelial tumorigenesis in the UPII-SV40T transgenic mouse model.

    PubMed

    Liu, Zhongbo; Xu, Xia; Li, Xuesen; Liu, Shuman; Simoneau, Anne R; He, Feng; Wu, Xue-Ru; Zi, Xiaolin

    2013-12-01

    Flavokawain A (FKA) is the predominant chalcone identified from the kava plant. We have previously shown that FKA preferentially inhibits the growth of p53 defective bladder cancer cell lines. Here, we examined whether FKA could inhibit bladder cancer development and progression in vivo in the UPII-SV40T transgenic model that resembles human urothelial cell carcinoma (UCC) with defects in the p53 and the retinoblastoma (Rb) protein pathways. Genotyped UPII-SV40T mice were fed orally with vehicle control (AIN-93M) or FKA (6 g/kg food; 0.6%) for 318 days starting at 28 days of age. More than 64% of the male mice fed with FKA-containing food survived beyond 318 days of age, whereas only about 38% of the male mice fed with vehicle control food survived to that age (P = 0.0383). The mean bladder weights of surviving male transgenic mice with the control diet versus the FKA diet were 234.6 ± 72.5 versus 96.1 ± 69.4 mg (P = 0.0002). FKA was excreted primarily through the urinary tract and concentrated in the urine up to 8.4 μmol/L, averaging about 38 times (males) and 15 times (females) more concentrated than in the plasma (P = 0.0001). FKA treatment inhibited the occurrence of high-grade papillary UCC, a precursor to invasive urothelial cancer, by 42.1%. A decreased expression of Ki67, survivin, and X-linked inhibitor of apoptotic proteins (XIAP) and increased expression of p27 and DR5, and the number of terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-positive apoptotic cells were observed in the urothelial tissue of FKA-fed mice. These results suggest a potential of FKA in preventing the recurrence and progression of non-muscle-invasive UCC.

  7. Effects of the kava chalcone flavokawain A differ in bladder cancer cells with wild-type versus mutant p53.

    PubMed

    Tang, Yaxiong; Simoneau, Anne R; Xie, Jun; Shahandeh, Babbak; Zi, Xiaolin

    2008-11-01

    Flavokawain A is the predominant chalcone from kava extract. We have assessed the mechanisms of flavokawain A's action on cell cycle regulation. In a p53 wild-type, low-grade, and papillary bladder cancer cell line (RT4), flavokawain A increased p21/WAF1 and p27/KIP1, which resulted in a decrease in cyclin-dependent kinase-2 (CDK2) kinase activity and subsequent G(1) arrest. The increase of p21/WAF1 protein corresponded to an increased mRNA level, whereas p27/KIP1 accumulation was associated with the down-regulation of SKP2, which then increased the stability of the p27/KIP1 protein. The accumulation of p21/WAF1 and p27/KIP1 was independent of cell cycle position and thus not a result of the cell cycle arrest. In contrast, flavokawain A induced a G(2)-M arrest in six p53 mutant-type, high-grade bladder cancer cell lines (T24, UMUC3, TCCSUP, 5637, HT1376, and HT1197). Flavokawain A significantly reduced the expression of CDK1-inhibitory kinases, Myt1 and Wee1, and caused cyclin B1 protein accumulation leading to CDK1 activation in T24 cells. Suppression of p53 expression by small interfering RNA in RT4 cells restored Cdc25C expression and down-regulated p21/WAF1 expression, which allowed Cdc25C and CDK1 activation, which then led to a G(2)-M arrest and an enhanced growth-inhibitory effect by flavokawain A. Consistently, flavokawain A also caused a pronounced CDK1 activation and G(2)-M arrest in p53 knockout but not in p53 wild-type HCT116 cells. This selectivity of flavokawain A for inducing a G(2)-M arrest in p53-defective cells deserves further investigation as a new mechanism for the prevention and treatment of bladder cancer.

  8. Pilot KaVA monitoring on the M 87 jet: Confirming the inner jet structure and superluminal motions at sub-pc scales

    NASA Astrophysics Data System (ADS)

    Hada, Kazuhiro; Park, Jong Ho; Kino, Motoki; Niinuma, Kotaro; Sohn, Bong Won; Ro, Hyun Wook; Jung, Taehyun; Algaba, Juan-Carlos; Zhao, Guang-Yao; Lee, Sang-Sung; Akiyama, Kazunori; Trippe, Sascha; Wajima, Kiyoaki; Sawada-Satoh, Satoko; Tazaki, Fumie; Cho, Ilje; Hodgson, Jeffrey; Lee, Jeong Ae; Hagiwara, Yoshiaki; Honma, Mareki; Koyama, Shoko; Oh, Junghwan; Lee, Taeseak; Yoo, Hyemin; Kawaguchi, Noriyuki; Roh, Duk-Gyoo; Oh, Se-Jin; Yeom, Jae-Hwan; Jung, Dong-Kyu; Oh, Chungsik; Kim, Hyo-Ryoung; Hwang, Ju-Yeon; Byun, Do-Young; Cho, Se-Hyung; Kim, Hyun-Goo; Kobayashi, Hideyuki; Shibata, Katsunori M.

    2017-08-01

    We report the initial results of our high-cadence monitoring program on the radio jet in the active galaxy M 87, obtained by the KVN and VERA Array (KaVA) at 22 GHz. This is a pilot study that preceded a larger KaVA-M 87 monitoring program, which is currently ongoing. The pilot monitoring was mostly performed every two to three weeks from 2013 December to 2014 June, at a recording rate of 1 Gbps, obtaining data for a total of ten epochs. We successfully obtained a sequence of good quality radio maps that revealed the rich structure of this jet from ≲1 mas to 20 mas, corresponding to physical scales (projected) of ∼0.1-2 pc (or ∼140-2800 Schwarzschild radii). We detected superluminal motions at these scales, together with a trend of gradual acceleration. The first evidence for such fast motions and acceleration near the jet base were obtained from recent VLBA studies at 43 GHz, and the fact that very similar kinematics are seen at a different frequency and time with a different instrument suggests that these properties are fundamental characteristics of this jet. This pilot program demonstrates that KaVA is a powerful VLBI array for studying the detailed structural evolution of the M 87 jet and also other relativistic jets.

  9. Dihydromethysticin from kava blocks tobacco carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced lung tumorigenesis and differentially reduces DNA damage in A/J mice.

    PubMed

    Narayanapillai, Sreekanth C; Balbo, Silvia; Leitzman, Pablo; Grill, Alex E; Upadhyaya, Pramod; Shaik, Ahmad Ali; Zhou, Bo; O'Sullivan, M Gerard; Peterson, Lisa A; Lu, Junxuan; Hecht, Stephen S; Xing, Chengguo

    2014-10-01

    We have previously shown that kava and its flavokavain-free Fraction B completely blocked 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung tumorigenesis in A/J mice with a preferential reduction in NNK-induced O (6)-methylguanine (O (6)-mG). In this study, we first identified natural (+)-dihydromethysticin (DHM) as a lead compound through evaluating the in vivo efficacy of five major compounds in Fraction B on reducing O (6)-mG in lung tissues. (+)-DHM demonstrated outstanding chemopreventive activity against NNK-induced lung tumorigenesis in A/J mice with 97% reduction of adenoma multiplicity at a dose of 0.05mg/g of diet (50 ppm). Synthetic (±)-DHM was equally effective as the natural (+)-DHM in these bioassays while a structurally similar analog, (+)-dihydrokavain (DHK), was completely inactive, revealing a sharp in vivo structure-activity relationship. Analyses of an expanded panel of NNK-induced DNA adducts revealed that DHM reduced a subset of DNA adducts in lung tissues derived from 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL, the active metabolite of NNK). Preliminary 17-week safety studies of DHM in A/J mice at a dose of 0.5mg/g of diet (at least 10× its minimum effective dose) revealed no adverse effects, suggesting that DHM is likely free of kava's hepatotoxic risk. These results demonstrate the outstanding efficacy and promising safety margin of DHM in preventing NNK-induced lung tumorigenesis in A/J mice, with a unique mechanism of action and high target specificity.

  10. Flavokawain A, a novel chalcone from kava extract, induces apoptosis in bladder cancer cells by involvement of Bax protein-dependent and mitochondria-dependent apoptotic pathway and suppresses tumor growth in mice.

    PubMed

    Zi, Xiaolin; Simoneau, Anne R

    2005-04-15

    Consumption of the traditional kava preparation was reported to correlate with low and uncustomary gender ratios (more cancer in women than men) of cancer incidences in three kava-drinking countries: Fiji, Vanuatu, and Western Samoa. We have identified flavokawain A, B, and C but not the major kavalactone, kawain, in kava extracts as causing strong antiproliferative and apoptotic effect in human bladder cancer cells. Flavokawain A results in a significant loss of mitochondrial membrane potential and release of cytochrome c into the cytosol in an invasive bladder cancer cell line T24. These effects of flavokawain A are accompanied by a time-dependent decrease in Bcl-x(L), a decrease in the association of Bcl-x(L) to Bax, and an increase in the active form of Bax protein. Using the primary mouse embryo fibroblasts Bax knockout and wild-type cells as well as a Bax inhibitor peptide derived from the Bax-binding domain of Ku70, we showed that Bax protein was, at least in part, required for the apoptotic effect of flavokawain A. In addition, flavokawain A down-regulates the expression of X-linked inhibitor of apoptosis and survivin. Because both X-linked inhibitor of apoptosis and survivin are main factors for apoptosis resistance and are overexpressed in bladder tumors, our data suggest that flavokawain A may have a dual efficacy in induction of apoptosis preferentially in bladder tumors. Finally, the anticarcinogenic effect of flavokawain A was evident in its inhibitory growth of bladder tumor cells in a nude mice model (57% of inhibition) and in soft agar.

  11. THE FIRST VERY LONG BASELINE INTERFEROMETRY IMAGE OF A 44 GHz METHANOL MASER WITH THE KVN AND VERA ARRAY (KaVA)

    SciTech Connect

    Matsumoto, Naoko; Hirota, Tomoya; Honma, Mareki; Kameya, Osamu; Sunada, Kazuyoshi; Sugiyama, Koichiro; Motogi, Kazuhito; Kim, Kee-Tae; Kim, Mikyoung; Byun, Do-Young; Jung, Taehyun; Kim, Jongsoo; Lyo, A-Ran; Oh, Chungsik; Bae, Jaehan; Chung, Hyunsoo; Chung, Moon-Hee; Cho, Se-Hyung; Chibueze, James O.; Shino, Nagisa; and others

    2014-07-01

    We have carried out the first very long baseline interferometry (VLBI) imaging of a 44 GHz class I methanol maser (7{sub 0}-6{sub 1} A {sup +}) associated with a millimeter core MM2 in a massive star-forming region IRAS 18151–1208 with KaVA (KVN and VERA Array), which is a newly combined array of KVN (Korean VLBI Network) and VERA (VLBI Exploration of Radio Astrometry). We have succeeded in imaging compact maser features with a synthesized beam size of 2.7 milliarcseconds × 1.5 milliarcseconds (mas). These features are detected at a limited number of baselines within the length of shorter than ≈ 650 km corresponding to 100 Mλ in the uv-coverage. The central velocity and the velocity width of the 44 GHz methanol maser are consistent with those of the quiescent gas rather than the outflow traced by the SiO thermal line. The minimum component size among the maser features is ∼5 mas × 2 mas, which corresponds to the linear size of ∼15 AU × 6 AU assuming a distance of 3 kpc. The brightness temperatures of these features range from ∼3.5 × 10{sup 8} to 1.0 × 10{sup 10} K, which are higher than the estimated lower limit from a previous Very Large Array observation with the highest spatial resolution of ∼50 mas. The 44 GHz class I methanol maser in IRAS 18151–1208 is found to be associated with the MM2 core, which is thought to be less evolved than another millimeter core MM1 associated with the 6.7 GHz class II methanol maser.

  12. Flavokawains A and B from kava (Piper methysticum) activate heat shock and antioxidant responses and protect against hydrogen peroxide-induced cell death in HepG2 hepatocytes.

    PubMed

    Pinner, Keanu D; Wales, Christina T K; Gristock, Rachel A; Vo, Hoa T; So, Nadine; Jacobs, Aaron T

    2016-09-01

    Context Flavokawains are secondary metabolites from the kava plant (Piper methysticum Forst. f., Piperaceae) that have anticancer properties and demonstrated oral efficacy in murine cancer models. However, flavokawains also have suspected roles in rare cases of kava-induced hepatotoxicity. Objective To compare the toxicity flavokawains A and B (FKA, FKB) and monitor the resulting transcriptional responses and cellular adaptation in the human hepatocyte cell line, HepG2. Materials and methods HepG2 were treated with 2-100 μM FKA or FKB for 24-48 h. Cellular viability was measured with calcein-AM and changes in signalling and gene expression were monitored by luciferase reporter assay, real-time PCR and Western blot of both total and nuclear protein extracts. To test for subsequent resistance to oxidative stress, cells were pretreated with 50 μM FKA, 10 μM FKB or 10 μM sulphoraphane (SFN) for 24 h, followed by 0.4-2.8 mM H2O2 for 48 h, and then viability was assessed. Results FKA (≤100 μM) was not toxic to HepG2, whereas FKB caused significant cell death (IC50=23.2 ± 0.8 μM). Both flavokawains activated Nrf2, increasing HMOX1 and GCLC expression and enhancing total glutathione levels over 2-fold (p < 0.05). FKA and FKB also activated HSF1, increasing HSPA1A and DNAJA4 expression. Also, flavokawain pretreatment mitigated cell death after a subsequent challenge with H2O2, with FKA being more effective than FKB, and similar to SFN. Conclusions Flavokawains promote an adaptive cellular response that protects hepatocytes against oxidative stress. We propose that FKA has potential as a chemopreventative or chemotherapeutic agent.

  13. Biotransformation of Flavokawains A, B, and C, Chalcones from Kava (Piper methysticum), by Human Liver Microsomes.

    PubMed

    Zenger, Katharina; Agnolet, Sara; Schneider, Bernd; Kraus, Birgit

    2015-07-22

    The in vitro metabolism of flavokawains A, B, and C (FKA, FKB, FKC), methoxylated chalcones from Piper methysticum, was examined using human liver microsomes. Phase I metabolism and phase II metabolism (glucuronidation) as well as combined phase I+II metabolism were studied. For identification and structure elucidation of microsomal metabolites, LC-HRESIMS and NMR techniques were applied. Major phase I metabolites were generated by demethylation in position C-4 or C-4' and hydroxylation predominantly in position C-4, yielding FKC as phase I metabolite of FKA and FKB, helichrysetin as metabolite of FKA and FKC, and cardamonin as metabolite of FKC. To an even greater extent, flavokawains were metabolized in the presence of uridine diphosphate (UDP) glucuronic acid by microsomal UDP-glucuronosyl transferases. For all flavokawains, monoglucuronides (FKA-2'-O-glucuronide, FKB-2'-O-glucuronide, FKC-2'-O-glucuronide, FKC-4-O-glucuronide) were found as major phase II metabolites. The dominance of generated glucuronides suggests a role of conjugated chalcones as potential active compounds in vivo.

  14. Millimeter VLBI observations of Sgr A* with KaVA and KVN

    NASA Astrophysics Data System (ADS)

    Zhao, G.-Y.; Kino, M.; Cho, I.-J.; Akiyama, K.; Sohn, B. W.; Jung, T.; Algaba, J. C.; Hada, K.; Hagiwara, Y.; Hodgson, J.; Honma, M.; Kawaguchi, N.; Koyama, S.; Lee, J. A.; Lee, T.; Niinuma, K.; Oh, J.; Park, J.-H.; Ro, H.; Sawada-Satoh, S.; Tazaki, F.; Trippe, S.; Wajima, K.; Yoo, H.

    2017-01-01

    We present recent observation results of Sgr A* at millimeter obtained with VLBI arrays in Korea and Japan. 7 mm monitoring of Sgr A* is part of our AGN large project. The results at 7 epochs during 2013-2014, including high resolution maps, flux density and two-dimensional size measurements are presented. The source shows no significant variation in flux and structure related to the G2 encounter in 2014. According to recent MHD simulations by kawashima et al., flux and magnetic field energy can be expected to increase several years after the encounter; We will keep our monitoring in order to test this prediction. Astrometric observations of Sgr A* were performed in 2015 at 7 and 3.5 millimeter simultaneously. Source-frequency phase referencing was applied and a combined ''core-shift'' of Sgr A* and a nearby calibrator was measured. Future observations and analysis are necessary to determine the core-shift in each source.

  15. Food and Food Constituents, Acute Effects on Human Behavior

    DTIC Science & Technology

    2002-12-01

    include the following: individual amino acids; herbal products such as ginkgo biloba , St. John’s wort, kava kava and ginseng; weight loss products, which...for example, melatonin, ginkgo biloba , ephedrine, St. John’s won, and kava kava. Many of these naturally occurring products would be classified as drugs

  16. Differential regulation of calcium signalling pathways by components of Piper methysticum (‘Awa)

    PubMed Central

    Shimoda, L.M.N; Showman, A.; Baker, J.D.; Lange, I.; Koomoa, D.L.; Stokes, A.J.; Borris, R.P.; Turner, H.

    2015-01-01

    Kava is a soporific, anxiolytic and relaxant in widespread ritual and recreational use throughout the Pacific. Traditional uses of kava by indigenous Pacific Island peoples reflect a complex pharmacopeia, centered on GABA-ergic effects of the well-characterized kavalactones. However, peripheral effects of kava suggest active components other than the CNS-targeted kavalactones. We have previously shown that immunocytes exhibit calcium mobilization in response to traditionally-prepared kava extracts, and that the kavalactones do not induce these calcium responses. Here, we characterize the complex calcium-mobilizing activity of traditionally-prepared and partially HPLC-purified kava extracts, noting induction of both calcium entry and store release pathways. Kava components activate intracellular store depletion of thapsigargin-sensitive and –insensitive stores that are coupled to the calcium release activated (CRAC) current, and cause calcium entry through non-store-operated pathways. Together with the pepper-like potency reported by kava users, these studies lead us to hypothesize that kava extracts contain one or more ligands for the transient receptor potential (TRP) family of ion channels. Indeed, TRP-like conductances are observed in kava-treated cells under patch clamp. Thus TRP-mediated cellular effects may be responsible for some of the reported pharmacology of kava. PMID:25640812

  17. Administering Eye Medications.

    ERIC Educational Resources Information Center

    Morris, Sara; Michael, Nancy, Ed.

    This module on administering eye medications is intended for use in inservice or continuing education programs for persons who administer medications in long-term care facilities. Instructor information, including teaching suggestions, and a listing of recommended audiovisual materials and their sources appear first. A brief discussion follows of…

  18. Administering Eye Medications.

    ERIC Educational Resources Information Center

    Morris, Sara; Michael, Nancy, Ed.

    This module on administering eye medications is intended for use in inservice or continuing education programs for persons who administer medications in long-term care facilities. Instructor information, including teaching suggestions, and a listing of recommended audiovisual materials and their sources appear first. A brief discussion follows of…

  19. COMPUTER ADMINISTERED INSTRUCTION VERSUS TRADITIONALLY ADMINISTERED INSTRUCTION, ECONOMICS.

    ERIC Educational Resources Information Center

    KOPSTEIN, FELIX F.; SEIDEL, ROBERT J.

    AN ATTEMPT IS MADE TO ASSESS THE ECONOMICS OF COMPUTER ASSISTED INSTRUCTION (CAI) VERSUS TRADITIONALLY ADMINISTERED INSTRUCTION (TAI) IN CONTROLLING THE STRUCTURE OF THE LEARNER'S STIMULUS ENVIRONMENT IN TEACHING AND TRAINING SITUATIONS. THERE IS A DISCUSSION OF THE NEED FOR A SOUND, OBJECTIVE ECONOMIC APPRAISAL OF THE VALUE TO SOCIETY OF…

  20. Agoraphobia

    MedlinePlus

    ... ready to stop taking medication. Certain dietary and herbal supplements claim to have calming and anti-anxiety benefits. ... health risks in some people. For example, the herbal supplement called kava appeared to be a promising treatment ...

  1. Enlarged Liver

    MedlinePlus

    ... of liver damage. Medicinal herbs. Certain herbs, including comfrey, ma huang and mistletoe, can increase your risk ... herbs to avoid include germander, chaparral, senna, mistletoe, comfrey, ma huang, valerian root, kava, celandine and green ...

  2. Acute Liver Failure

    MedlinePlus

    ... drugs and anticonvulsants, can cause acute liver failure. Herbal supplements. Herbal drugs and supplements, including kava, ephedra, skullcap ... over-the-counter medications do you take? What herbal supplements do you take? Do you use illegal drugs? ...

  3. Anxiety, depression, and insomnia.

    PubMed

    Larzelere, Michele M; Wiseman, Pamela

    2002-06-01

    Evidence for alternative treatments for depression, anxiety, and insomnia are reviewed in this article. Treatment of depression with St. John's wort, L-tryptophan, 5-hydroxytryptophan, S-adenosylmethionine, dehydroepiandosterone, folate, exercise, acupuncture, and meditation are examined. Evidence for the efficacy of kava kava, exercise, relaxation therapies, and acupuncture in treatment anxiety is reviewed. The use of valerian, melatonin, chamomile, passionflower, exercise, acupuncture, and behavioral therapies (i.e., sleep restriction, stimulus control, relaxation, and sleep hygiene) for insomnia is discussed.

  4. 16 CFR 1000.2 - Laws administered.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 16 Commercial Practices 2 2010-01-01 2010-01-01 false Laws administered. 1000.2 Section 1000.2 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION GENERAL COMMISSION ORGANIZATION AND FUNCTIONS § 1000.2 Laws administered. The Commission administers five acts: (a) The Consumer Product Safety Act...

  5. 16 CFR 1000.2 - Laws administered.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 16 Commercial Practices 2 2013-01-01 2013-01-01 false Laws administered. 1000.2 Section 1000.2 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION GENERAL COMMISSION ORGANIZATION AND FUNCTIONS § 1000.2 Laws administered. The Commission administers five acts: (a) The Consumer Product Safety Act...

  6. 16 CFR 1000.2 - Laws administered.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 16 Commercial Practices 2 2012-01-01 2012-01-01 false Laws administered. 1000.2 Section 1000.2 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION GENERAL COMMISSION ORGANIZATION AND FUNCTIONS § 1000.2 Laws administered. The Commission administers five acts: (a) The Consumer Product Safety Act...

  7. 16 CFR 1000.2 - Laws administered.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 16 Commercial Practices 2 2011-01-01 2011-01-01 false Laws administered. 1000.2 Section 1000.2 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION GENERAL COMMISSION ORGANIZATION AND FUNCTIONS § 1000.2 Laws administered. The Commission administers five acts: (a) The Consumer Product Safety Act...

  8. 16 CFR 1000.2 - Laws administered.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 16 Commercial Practices 2 2014-01-01 2014-01-01 false Laws administered. 1000.2 Section 1000.2 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION GENERAL COMMISSION ORGANIZATION AND FUNCTIONS § 1000.2 Laws administered. The Commission administers five acts: (a) The Consumer Product Safety Act...

  9. Relaxation processes in administered-rate pricing

    NASA Astrophysics Data System (ADS)

    Hawkins, Raymond J.; Arnold, Michael R.

    2000-10-01

    We show how the theory of anelasticity unifies the observed dynamics and proposed models of administered-rate products. This theory yields a straightforward approach to rate model construction that we illustrate by simulating the observed relaxation dynamics of two administered rate products. We also demonstrate how the use of this formalism leads to a natural definition of market friction.

  10. 16 CFR 0.4 - Laws administered.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 16 Commercial Practices 1 2010-01-01 2010-01-01 false Laws administered. 0.4 Section 0.4 Commercial Practices FEDERAL TRADE COMMISSION ORGANIZATION, PROCEDURES AND RULES OF PRACTICE ORGANIZATION § 0.4 Laws administered. The Commission exercises enforcement and administrative authority under the...

  11. 16 CFR 0.4 - Laws administered.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 16 Commercial Practices 1 2012-01-01 2012-01-01 false Laws administered. 0.4 Section 0.4 Commercial Practices FEDERAL TRADE COMMISSION ORGANIZATION, PROCEDURES AND RULES OF PRACTICE ORGANIZATION § 0.4 Laws administered. The Commission exercises enforcement and administrative authority under the...

  12. 16 CFR 0.4 - Laws administered.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 16 Commercial Practices 1 2013-01-01 2013-01-01 false Laws administered. 0.4 Section 0.4 Commercial Practices FEDERAL TRADE COMMISSION ORGANIZATION, PROCEDURES AND RULES OF PRACTICE ORGANIZATION § 0.4 Laws administered. The Commission exercises enforcement and administrative authority under the...

  13. 16 CFR 0.4 - Laws administered.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 16 Commercial Practices 1 2014-01-01 2014-01-01 false Laws administered. 0.4 Section 0.4 Commercial Practices FEDERAL TRADE COMMISSION ORGANIZATION, PROCEDURES AND RULES OF PRACTICE ORGANIZATION § 0.4 Laws administered. The Commission exercises enforcement and administrative authority under the...

  14. 22 CFR 196.4 - Administering office.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Administering office. 196.4 Section 196.4 Foreign Relations DEPARTMENT OF STATE INTERNATIONAL COMMERCIAL ARBITRATION THOMAS R. PICKERING FOREIGN AFFAIRS/GRADUATE FOREIGN AFFAIRS FELLOWSHIP PROGRAM § 196.4 Administering office. The Department of State...

  15. 16 CFR 0.4 - Laws administered.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 16 Commercial Practices 1 2011-01-01 2011-01-01 false Laws administered. 0.4 Section 0.4 Commercial Practices FEDERAL TRADE COMMISSION ORGANIZATION, PROCEDURES AND RULES OF PRACTICE ORGANIZATION § 0.4 Laws administered. The Commission exercises enforcement and administrative authority under the...

  16. Herbal medicine for insomnia: A systematic review and meta-analysis.

    PubMed

    Leach, Matthew J; Page, Amy T

    2015-12-01

    Insomnia is a prevalent sleep disorder that can profoundly impact a person's health and wellbeing. Herbal medicine represents one of the most frequently used complementary and alternative treatments of insomnia. However, the safety and efficacy of herbal medicine for the treatment of this disorder is currently uncertain. In order to ascertain the evidence base for herbal medicine for insomnia, we systematically searched seventeen electronic databases and the reference lists of included studies for relevant randomised controlled trials (RCTs). Fourteen RCTs, involving a total of 1602 participants with insomnia, met the inclusion criteria. Four distinct orally administered herbal monopreparations were identified (i.e., valerian, chamomile, kava and wuling). There was no statistically significant difference between any herbal medicine and placebo, or any herbal medicine and active control, for any of the thirteen measures of clinical efficacy. As for safety, a similar or smaller number of adverse events per person were reported with kava, chamomile and wuling when compared with placebo. By contrast, a greater number of events per person were reported with valerian. While there is insufficient evidence to support the use of herbal medicine for insomnia, there is a clear need for further research in this area.

  17. Computer-administered interviews and rating scales.

    PubMed

    Garb, Howard N

    2007-03-01

    To evaluate the value of computer-administered interviews and rating scales, the following topics are reviewed in the present article: (a) strengths and weaknesses of structured and unstructured assessment instruments, (b) advantages and disadvantages of computer administration, and (c) the validity and utility of computer-administered interviews and rating scales. Computer-administered evaluations are more comprehensive and reliable and less biased than evaluations routinely conducted in clinical practice. Also, the use of continuous monitoring systems, which increasingly entail the use of computer administration, has been related to improved treatment outcome. However, the use of computer-administered interviews and rating scales will sometimes lead to false positive diagnoses, and for this reason, it is recommended that computer assessment be combined with clinical judgment. ((c) 2007 APA, all rights reserved).

  18. Identification by methane chemical ionization gas chromatography/mass spectrometry of the products obtained by steam distillation and aqueous acid extraction of commercial Piper methysticum.

    PubMed

    Cheng, D; Lidgard, R O; Duffield, P H; Duffield, A M; Brophy, J J

    1988-11-01

    Bornyl cinnamate has been identified as a constituent of kava resin and of the steam distillate of Piper methysticum. 5-Hydroxydihydrokawain was identified in commercial samples of P. methysticum originating from Vanuatu provided an initial aqueous extraction was employed. Commercial preparations, and fresh samples of the root of this plant from Fiji, lacked this compound. Two previously described N-cinnamoyl pyrrolidine alkaloids were also observed along with stigmasterol in kava resin from Fiji and Vanuatu. The products derived from aqueous 2 M hydrochloric acid extraction of P. methysticum were determined from methane chemical ionization gas chromatography/mass spectrometry analysis which identified a series of hydroxylated compounds (15a-d) derived from formal decarbonylation of the parent kava lactones. The products (13a-c) of dehydration of these compounds were also observed. The efficiency of kava resin extraction from plant material by water (the traditional method of preparation of the kava beverage) was typically 5-10% of that recovered by direct extraction with an organic solvent.

  19. Changes in Medications Administered in Schools

    ERIC Educational Resources Information Center

    McCarthy, Ann Marie; Kelly, Michael W.; Johnson, Shella; Roman, Jaclyn; Zimmerman, M. Bridget

    2006-01-01

    The purpose of this descriptive, cross-sectional study was to determine if there have been changes in the type and number of attention deficit/hyperactivity disorder (AD/HD) medications administered in schools since the introduction of long-acting stimulants. A survey was sent to 1,000 school nurses randomly selected from the National Association…

  20. Teaching Students to Administer the WISC

    ERIC Educational Resources Information Center

    Ritter, Kathleen Yost

    1977-01-01

    A college level psychology course is described in which students were trained by both traditional and experimental methods to administer individual intelligence tests. Comparative analysis of performance by each group indicates that student motivation and performance is not greatly influenced by teaching method and that videotape demonstrations…

  1. 7 CFR 247.3 - Administering agencies.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... Agriculture Regulations of the Department of Agriculture (Continued) FOOD AND NUTRITION SERVICE, DEPARTMENT OF AGRICULTURE CHILD NUTRITION PROGRAMS COMMODITY SUPPLEMENTAL FOOD PROGRAM § 247.3 Administering agencies. (a... Department's Food and Nutrition Service (FNS), which provides commodities, assigns caseload, and...

  2. 7 CFR 247.3 - Administering agencies.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... Agriculture Regulations of the Department of Agriculture (Continued) FOOD AND NUTRITION SERVICE, DEPARTMENT OF AGRICULTURE CHILD NUTRITION PROGRAMS COMMODITY SUPPLEMENTAL FOOD PROGRAM § 247.3 Administering agencies. (a... Department's Food and Nutrition Service (FNS), which provides commodities, assigns caseload, and...

  3. 7 CFR 247.3 - Administering agencies.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Agriculture Regulations of the Department of Agriculture (Continued) FOOD AND NUTRITION SERVICE, DEPARTMENT OF AGRICULTURE CHILD NUTRITION PROGRAMS COMMODITY SUPPLEMENTAL FOOD PROGRAM § 247.3 Administering agencies. (a... Department's Food and Nutrition Service (FNS), which provides commodities, assigns caseload, and...

  4. 7 CFR 247.3 - Administering agencies.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... Agriculture Regulations of the Department of Agriculture (Continued) FOOD AND NUTRITION SERVICE, DEPARTMENT OF AGRICULTURE CHILD NUTRITION PROGRAMS COMMODITY SUPPLEMENTAL FOOD PROGRAM § 247.3 Administering agencies. (a... Department's Food and Nutrition Service (FNS), which provides commodities, assigns caseload, and...

  5. 7 CFR 247.3 - Administering agencies.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Agriculture Regulations of the Department of Agriculture (Continued) FOOD AND NUTRITION SERVICE, DEPARTMENT OF AGRICULTURE CHILD NUTRITION PROGRAMS COMMODITY SUPPLEMENTAL FOOD PROGRAM § 247.3 Administering agencies. (a... Department's Food and Nutrition Service (FNS), which provides commodities, assigns caseload, and...

  6. Teaching Students to Administer the WISC

    ERIC Educational Resources Information Center

    Ritter, Kathleen Yost

    1977-01-01

    A college level psychology course is described in which students were trained by both traditional and experimental methods to administer individual intelligence tests. Comparative analysis of performance by each group indicates that student motivation and performance is not greatly influenced by teaching method and that videotape demonstrations…

  7. On the Interchangeability of Individually Administered and Group Administered Ability Tests

    ERIC Educational Resources Information Center

    Nevo, Baruch; Sela, Roni

    2003-01-01

    This research studied the interchangeability of individually administered and group administered cognitive tests. Seventy undergraduate students took the Hebrew version of the WAIS-R (Wechsler Adult Intelligence Scale-Revised), and their IQs were measured. They also took the IPET (Israeli Psychometric Entrance Test) and their IPET scores were…

  8. Administering social security: challenges yesterday and today.

    PubMed

    Puckett, Carolyn

    2010-01-01

    In 2010, the Social Security Administration (SSA) celebrates the 75th anniversary of the passage of the Social Security Act. In those 75 years, SSA has been responsible for programs providing unemployment insurance, child welfare, and supervision of credit unions, among other duties. This article focuses on the administration of the Old-Age, Survivors, and Disability Insurance program, although it also covers some of the other major programs SSA has been tasked with administering over the years-in particular, Medicare, Black Lung benefits, and Supplemental Security Income. The article depicts some of the challenges that have accompanied administering these programs and the steps that SSA has taken to meet those challenges. Whether implementing complex legislation in short timeframes or coping with natural disasters, SSA has found innovative ways to overcome problems and has evolved to meet society's changing needs.

  9. Transdermally administered fentanyl for pain management.

    PubMed

    Calis, K A; Kohler, D R; Corso, D M

    1992-01-01

    The physicochemical properties, pharmacology, pharmacokinetics, serum concentrations and clinical effects, adverse effects and contraindications, and dosage of transdermally administered fentanyl are described, and clinical studies evaluating the use of a transdermal fentanyl system in the treatment of postoperative pain and chronic cancer-associated pain are reviewed. After application of a transdermal system, fentanyl is absorbed into the skin beneath the patch, where a depot forms in the upper skin layers. Plasma fentanyl concentrations are barely detectable for about two hours after patch placement. Eight to 12 hours after patch placement, concentrations approximate those achieved with equivalent i.v. doses of fentanyl. Some studies comparing transdermally administered fentanyl with placebo in postoperative patients showed that the patients who received fentanyl required fewer supplementary analgesics and reported less pain than the patients who received placebo. However, the overall efficacy and safety of the transdermal fentanyl system for the treatment of postoperative pain have not been adequately evaluated. Studies of cancer patients showed that transdermally administered fentanyl appears to be effective in the management of chronic, cancer-related pain. Dermatological reactions to the fentanyl patch are generally transient and mild. Other adverse effects are those that are commonly associated with narcotic analgesics. The 25-micrograms/hr patch should be used for initial treatment in patients not previously treated with narcotics. The dosage may be gradually increased until effective analgesia is obtained. Although experience with the product is limited, transdermally administered fentanyl appears to be effective for the long-term management of cancer-related pain.

  10. Orally Administered Bioadherent Sustained Release Microencapsulated Vaccines

    DTIC Science & Technology

    1996-09-01

    Bioadherent Sustained Release Microencapsulated Vaccines PRINCIPAL INVESTIGATOR: Dr. G. Duncan Hitchens, Anthony Giletto, Allison Rice-Ficht, Sunitha...Aug 96) 4. TITLE AND SUBTITLE 5. FUNDING NUMBERS Orally Administered Bioadherent Sustained Release Microencapsulated Vaccines DAMD17-95-C-5099 6... microencapsulated vaccine against staphylococcal enterotoxin A (SEA). The research is centered around using a known bioadhesive, vitelline protein B (vpB), to

  11. 40 CFR 63.216 - Who administers this subpart?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... and Information § 63.216 Who administers this subpart? (a) This subpart can be administered by us, the... authority to administer and enforce this subpart. You should contact your EPA Regional Office to find out...

  12. 40 CFR 63.216 - Who administers this subpart?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... and Information § 63.216 Who administers this subpart? (a) This subpart can be administered by us, the... authority to administer and enforce this subpart. You should contact your EPA Regional Office to find out...

  13. 40 CFR 63.5455 - Who administers this subpart?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... § 63.5455 Who administers this subpart? (a) This subpart can be administered by us, the United States... that agency has the primary authority to administer and enforce this subpart. You should contact your...

  14. Ocular toxicity from systemically administered xenobiotics

    PubMed Central

    Gokulgandhi, Mitan R; Vadlapudi, Aswani Dutt; Mitra, Ashim K

    2015-01-01

    Introduction The eye is considered as the most privileged organ because of the blood–ocular barrier that acts as a barrier to systemically administered xenobiotics. However, there has been a significant increase in the number of reports on systemic drug-induced ocular complications. If such complications are left untreated, then it may cause permanent damage to vision. Hence, knowledge of most recent updates on ever-increasing reports of such toxicities has become imperative to develop better therapy while minimizing toxicities. Areas covered The article is mainly divided into anterior and posterior segment manifestations caused by systemically administered drugs. The anterior segment is further elaborated on corneal complications where as the posterior segment is focused on optic nerve, retinal and vitreous complications. Furthermore, this article includes recent updates on acute and chronic ocular predicaments, in addition to discussing various associated symptoms caused by drugs. Expert opinion Direct correlation of ocular toxicities due to systemic drug therapy is evident from current literature. Therefore, it is necessary to have detailed documentation of these complications to improve understanding and predict toxicities. We made an attempt to ensure that the reader is aware of the characteristic ocular complications, the potential for irreversible drug toxicity and indications for cessation. PMID:22803583

  15. 40 CFR 147.1201 - EPA-administered program.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 24 2013-07-01 2013-07-01 false EPA-administered program. 147.1201... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Minnesota § 147.1201 EPA-administered program. (a) Contents. The UIC program for the State of Minnesota is administered...

  16. 40 CFR 147.1201 - EPA-administered program.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 23 2011-07-01 2011-07-01 false EPA-administered program. 147.1201... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Minnesota § 147.1201 EPA-administered program. (a) Contents. The UIC program for the State of Minnesota is administered...

  17. 40 CFR 147.1201 - EPA-administered program.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 23 2014-07-01 2014-07-01 false EPA-administered program. 147.1201... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Minnesota § 147.1201 EPA-administered program. (a) Contents. The UIC program for the State of Minnesota is administered...

  18. 40 CFR 282.74 - Mississippi State-Administered Program.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 26 2010-07-01 2010-07-01 false Mississippi State-Administered Program... Mississippi State-Administered Program. (a) The State of Mississippi is approved to administer and enforce an... administered by the Mississippi Department of Environmental Quality, was approved by EPA pursuant to 42...

  19. 40 CFR 282.74 - Mississippi State-Administered Program.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 27 2014-07-01 2014-07-01 false Mississippi State-Administered Program... Mississippi State-Administered Program. (a) The State of Mississippi is approved to administer and enforce an... administered by the Mississippi Department of Environmental Quality, was approved by EPA pursuant to 42...

  20. 40 CFR 282.74 - Mississippi State-Administered Program.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 28 2013-07-01 2013-07-01 false Mississippi State-Administered Program... Mississippi State-Administered Program. (a) The State of Mississippi is approved to administer and enforce an... administered by the Mississippi Department of Environmental Quality, was approved by EPA pursuant to 42...

  1. 40 CFR 282.74 - Mississippi State-Administered Program.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 27 2011-07-01 2011-07-01 false Mississippi State-Administered Program... Mississippi State-Administered Program. (a) The State of Mississippi is approved to administer and enforce an... administered by the Mississippi Department of Environmental Quality, was approved by EPA pursuant to 42...

  2. 40 CFR 282.74 - Mississippi State-Administered Program.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 28 2012-07-01 2012-07-01 false Mississippi State-Administered Program... Mississippi State-Administered Program. (a) The State of Mississippi is approved to administer and enforce an... administered by the Mississippi Department of Environmental Quality, was approved by EPA pursuant to 42...

  3. Determination of aflatoxins in botanical roots by a modification of AOAC Official Method 991.31: single-laboratory validation.

    PubMed

    Weaver, Carol M; Trucksess, Mary W

    2010-01-01

    AOAC Official Method 991.31 for the determination of aflatoxins (AFs; sum of aflatoxins B1, B2, G1, and G2) in corn, raw peanuts, and peanut butter by using immunoaffinity column cleanup with LC has been modified and applied to the determination of AFs in botanical roots. The modifications were necessary to improve the performance of the method for matrixes beyond corn and peanuts. The extraction solvent was changed from a mixture of methanol and water to acetonitrile and water. The accuracy, repeatability, and reproducibility characteristics of this method were determined. Replicates of 10 test portions of each powdered root (black cohosh, echinacea, ginger, ginseng, kava kava, and valerian) at each spiking level (AFs at 0, 2, 4, 8, and 16 ng/g) were analyzed on 3 separate days. Test portions were extracted with acetonitrile-water (84 + 16, v/v), and the extracts were centrifuged, diluted with phosphate-buffered saline, filtered, and applied to an immunoaffinity column containing antibodies specific for AFs. After the column was washed with water, the toxins were eluted from the column with methanol and quantified by HPLC with fluorescence detection. All test materials except kava kava were found to contain AF at < 0.1 ng/g. Kava kava was naturally contaminated with AFs at 0.5 ng/g. Average within-day and between-days recoveries of AFs from botanical roots ranged from 88 to 112 and from 86 to 118%, respectively. Total RSD values for within-day and between-days repeatability ranged from 1.4 to 15.9%. HorRat values were < 0.4 for all of the matrixes examined. The modified AOAC Official Method 991.31 was found to be applicable to an analysis of the six botanical roots.

  4. Determination of Aflatoxins in Botanical Roots by a Modification of AOAC Official MethodSM 991.31: Single-Laboratory Validation

    PubMed Central

    Weaver, Carol M.; Trucksess, Mary W.

    2010-01-01

    AOAC Official MethodSM 991.31 for the determination of aflatoxins (AFs; sum of aflatoxins B1, B2, G1, and G2) in corn, raw peanuts, and peanut butter by using immunoaffinity column cleanup with LC has been modified and applied to the determination of AFs in botanical roots. The modifications were necessary to improve the performance of the method for matrixes beyond corn and peanuts. The extraction solvent was changed from a mixture of methanol and water to acetonitrile and water. The accuracy, repeatability, and reproducibility characteristics of this method were determined. Replicates of 10 test portions of each powdered root (black cohosh, echinacea, ginger, ginseng, kava kava, and valerian) at each spiking level (AFs at 0, 2, 4, 8, and 16 ng/g) were analyzed on 3 separate days. Test portions were extracted with acetonitrile–water (84 + 16, v/v), and the extracts were centrifuged, diluted with phosphate-buffered saline, filtered, and applied to an immunoaffinity column containing antibodies specific for AFs. After the column was washed with water, the toxins were eluted from the column with methanol and quantified by HPLC with fluorescence detection. All test materials except kava kava were found to contain AF at <0.1 ng/g. Kava kava was naturally contaminated with AFs at 0.5 ng/g. Average within-day and between-days recoveries of AFs from botanical roots ranged from 88 to 112 and from 86 to 118%, respectively. Total RSD values for within-day and between-days repeatability ranged from 1.4 to 15.9%. HorRat values were <0.4 for all of the matrixes examined. The modified AOAC Official Method 991.31 was found to be applicable to an analysis of the six botanical roots. PMID:20334179

  5. The radiation dosimetry of intrathecally administered radionuclides

    SciTech Connect

    Stabin, M.G.; Evans, J.F.

    1999-01-01

    The radiation dose to the spine, spinal cord, marrow, and other organs of the body from intrathecal administration of several radiopharmaceuticals was studied. Anatomic models were developed for the spine, spinal cerebrospinal fluid (CSF), spinal cord, spinal skeleton, cranial skeleton, and cranial CSF. A kinetic model for the transport of CSF was used to determine residence times in the CSF; material leaving the CSF was thereafter assumed to enter the bloodstream and follow the kinetics of the radiopharmaceutical as if intravenously administered. The radiation transport codes MCNP and ALGAMP were used to model the electron and photon transport and energy deposition. The dosimetry of Tc-99m DTPA and HSA, In-111 DTPA, I-131 HSA, and Yb-169 DTPA was studied. Radiation dose profiles for the spinal cord and marrow in the spine were developed and average doses to all other organs were estimated, including dose distributions within the bone and marrow.

  6. Updates on Nutraceutical Sleep Therapeutics and Investigational Research.

    PubMed

    Yurcheshen, Michael; Seehuus, Martin; Pigeon, Wilfred

    2015-01-01

    Approximately 50% of the population will suffer from a sleep disorder over the course of their lifetime. There is increasing interest in nutraceuticals for these conditions. The quality of the evidence for the safety and effectiveness of using these supplements to treat sleep disorders varies substantially. In this review, we discuss the data about the effectiveness and safety of six commonly used plant-based sleep therapeutics: caffeine, chamomile, cherries, kava kava, L-tryptophan, marijuana, and valerian. We explore both historical uses of each substance and the current state of the literature.

  7. Updates on Nutraceutical Sleep Therapeutics and Investigational Research

    PubMed Central

    Yurcheshen, Michael; Seehuus, Martin; Pigeon, Wilfred

    2015-01-01

    Approximately 50% of the population will suffer from a sleep disorder over the course of their lifetime. There is increasing interest in nutraceuticals for these conditions. The quality of the evidence for the safety and effectiveness of using these supplements to treat sleep disorders varies substantially. In this review, we discuss the data about the effectiveness and safety of six commonly used plant-based sleep therapeutics: caffeine, chamomile, cherries, kava kava, L-tryptophan, marijuana, and valerian. We explore both historical uses of each substance and the current state of the literature. PMID:26265921

  8. Treatment of Not-Administered Items on Individually Administered Intelligence Tests

    ERIC Educational Resources Information Center

    He, Wei; Wolfe, Edward W.

    2012-01-01

    In administration of individually administered intelligence tests, items are commonly presented in a sequence of increasing difficulty, and test administration is terminated after a predetermined number of incorrect answers. This practice produces stochastically censored data, a form of nonignorable missing data. By manipulating four factors…

  9. Targeted Lung Delivery of Nasally Administered Aerosols.

    PubMed

    Tian, Geng; Hindle, Michael; Longest, P Worth

    2014-01-01

    Using the nasal route to deliver pharmaceutical aerosols to the lungs has a number of advantages including co-administration during non-invasive ventilation. The objective of this study was to evaluate the growth and deposition characteristics of nasally administered aerosol throughout the conducting airways based on delivery with streamlined interfaces implementing two forms of controlled condensational growth technology. Characteristic conducting airways were considered including a nose-mouth-throat (NMT) geometry, complete upper tracheobronchial (TB) model through the third bifurcation (B3), and stochastic individual path (SIP) model to the terminal bronchioles (B15). Previously developed streamlined nasal cannula interfaces were used for the delivery of submicrometer particles using either enhanced condensational growth (ECG) or excipient enhanced growth (EEG) techniques. Computational fluid dynamics (CFD) simulations predicted aerosol transport, growth and deposition for a control (4.7 μm) and three submicrometer condensational aerosols with budesonide as a model insoluble drug. Depositional losses with condensational aerosols in the cannula and NMT were less than 5% of the initial dose, which represents an order-of-magnitude reduction compared to the control. The condensational growth techniques increased the TB dose by a factor of 1.1-2.6x, delivered at least 70% of the dose to the alveolar region, and produced final aerosol sizes ≥2.5 μm. Compared to multiple commercial orally inhaled products, the nose-to-lung delivery approach increased dose to the biologically important lower TB region by factors as large as 35x. In conclusion, nose-to-lung delivery with streamlined nasal cannulas and condensational aerosols was highly efficient and targeted deposition to the lower TB and alveolar regions.

  10. Targeted Lung Delivery of Nasally Administered Aerosols

    PubMed Central

    Tian, Geng; Hindle, Michael; Longest, P. Worth

    2014-01-01

    Using the nasal route to deliver pharmaceutical aerosols to the lungs has a number of advantages including co-administration during non-invasive ventilation. The objective of this study was to evaluate the growth and deposition characteristics of nasally administered aerosol throughout the conducting airways based on delivery with streamlined interfaces implementing two forms of controlled condensational growth technology. Characteristic conducting airways were considered including a nose-mouth-throat (NMT) geometry, complete upper tracheobronchial (TB) model through the third bifurcation (B3), and stochastic individual path (SIP) model to the terminal bronchioles (B15). Previously developed streamlined nasal cannula interfaces were used for the delivery of submicrometer particles using either enhanced condensational growth (ECG) or excipient enhanced growth (EEG) techniques. Computational fluid dynamics (CFD) simulations predicted aerosol transport, growth and deposition for a control (4.7 μm) and three submicrometer condensational aerosols with budesonide as a model insoluble drug. Depositional losses with condensational aerosols in the cannula and NMT were less than 5% of the initial dose, which represents an order-of-magnitude reduction compared to the control. The condensational growth techniques increased the TB dose by a factor of 1.1–2.6x, delivered at least 70% of the dose to the alveolar region, and produced final aerosol sizes ≥2.5 μm. Compared to multiple commercial orally inhaled products, the nose-to-lung delivery approach increased dose to the biologically important lower TB region by factors as large as 35x. In conclusion, nose-to-lung delivery with streamlined nasal cannulas and condensational aerosols was highly efficient and targeted deposition to the lower TB and alveolar regions. PMID:24932058

  11. Who Should Administer Energy-Efficiency Programs?

    SciTech Connect

    Blumstein, Carl; Goldman, Charles; Barbose, Galen L.

    2003-05-01

    The restructuring of the electric utility industry in the US created a crisis in the administration of ratepayer-funded energy-efficiency programs. Before restructuring, nearly all energy-efficiency programs in the US were administered by utilities and funded from utility rates. Restructuring called these arrangements into question in two ways. First, the separation of generation from transmission and distribution undermined a key rationale for utility administration. This was the Integrated Resource Planning approach in which the vertically integrated utility was given incentives to provide energy services at least cost. Second, questions were raised as to whether funding through utility rates could be sustained in a competitive environment and most states that restructured their electricity industry adopted a system benefits charge. The crisis in administration of energy-efficiency programs produced a variety of responses in the eight years since restructuring in the US began in earn est. These responses have included new rationales for energy-efficiency programs, new mechanisms for funding programs, and new mechanisms for program administration and governance. This paper focuses on issues related to program administration. It describes the administrative functions and some of the options for accomplishing them. Then it discusses criteria for choosing among the options. Examples are given that highlight some of the states that have made successful transitions to new governance and/or administration structures. Attention is also given to California where large-scale energy-efficiency programs have continued to operate, despite the fact that many of the key governance/administration issues remain unresolved. The conclusion attempts to summarize lessons learned.

  12. 40 CFR 282.93 - Texas State-Administered Program.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 26 2010-07-01 2010-07-01 false Texas State-Administered Program. 282... (CONTINUED) APPROVED UNDERGROUND STORAGE TANK PROGRAMS Approved State Programs § 282.93 Texas State-Administered Program. (a) The State of Texas is approved to administer and enforce an underground storage tank...

  13. 40 CFR 147.1900 - State-administered program.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Oregon § 147.1900 State-administered program. The UIC program for all classes of wells in the State of Oregon, except those on Indian lands, is administered by the Oregon Department of Environmental Quality, approved...

  14. 40 CFR 282.87 - Oregon State-Administered Program.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 28 2013-07-01 2013-07-01 false Oregon State-Administered Program. 282... (CONTINUED) APPROVED UNDERGROUND STORAGE TANK PROGRAMS Approved State Programs § 282.87 Oregon State-Administered Program. (a) The State of Oregon is approved to administer and enforce an underground storage...

  15. 40 CFR 147.1900 - State-administered program.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Oregon § 147.1900 State-administered program. The UIC program for all classes of wells in the State of Oregon, except those on Indian lands, is administered by the Oregon Department of Environmental Quality, approved...

  16. 40 CFR 282.87 - Oregon State-Administered Program.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 27 2014-07-01 2014-07-01 false Oregon State-Administered Program. 282... (CONTINUED) APPROVED UNDERGROUND STORAGE TANK PROGRAMS Approved State Programs § 282.87 Oregon State-Administered Program. (a) The State of Oregon is approved to administer and enforce an underground storage...

  17. 40 CFR 147.1900 - State-administered program.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Oregon § 147.1900 State-administered program. The UIC program for all classes of wells in the State of Oregon, except those on Indian lands, is administered by the Oregon Department of Environmental Quality, approved...

  18. 40 CFR 147.1900 - State-administered program.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Oregon § 147.1900 State-administered program. The UIC program for all classes of wells in the State of Oregon, except those on Indian lands, is administered by the Oregon Department of Environmental Quality, approved...

  19. 40 CFR 147.2050 - State-administered program.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS South Carolina § 147.2050 State-administered program. The UIC program for all classes of wells in the State of South Carolina, except for those on Indian lands, is the program administered by the South Carolina Department of...

  20. 40 CFR 282.65 - Iowa State-Administered Program.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 26 2010-07-01 2010-07-01 false Iowa State-Administered Program. 282... (CONTINUED) APPROVED UNDERGROUND STORAGE TANK PROGRAMS Approved State Programs § 282.65 Iowa State-Administered Program. (a) The State of Iowa is approved to administer and enforce an underground storage...

  1. 40 CFR 282.65 - Iowa State-Administered Program.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 28 2012-07-01 2012-07-01 false Iowa State-Administered Program. 282... (CONTINUED) APPROVED UNDERGROUND STORAGE TANK PROGRAMS Approved State Programs § 282.65 Iowa State-Administered Program. (a) The State of Iowa is approved to administer and enforce an underground storage...

  2. 40 CFR 282.65 - Iowa State-Administered Program.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 28 2013-07-01 2013-07-01 false Iowa State-Administered Program. 282... (CONTINUED) APPROVED UNDERGROUND STORAGE TANK PROGRAMS Approved State Programs § 282.65 Iowa State-Administered Program. (a) The State of Iowa is approved to administer and enforce an underground storage...

  3. 40 CFR 282.65 - Iowa State-Administered Program.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 27 2011-07-01 2011-07-01 false Iowa State-Administered Program. 282... (CONTINUED) APPROVED UNDERGROUND STORAGE TANK PROGRAMS Approved State Programs § 282.65 Iowa State-Administered Program. (a) The State of Iowa is approved to administer and enforce an underground storage...

  4. 40 CFR 282.65 - Iowa State-Administered Program.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 27 2014-07-01 2014-07-01 false Iowa State-Administered Program. 282... (CONTINUED) APPROVED UNDERGROUND STORAGE TANK PROGRAMS Approved State Programs § 282.65 Iowa State-Administered Program. (a) The State of Iowa is approved to administer and enforce an underground storage...

  5. 40 CFR 147.1351 - EPA-administered program.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 24 2013-07-01 2013-07-01 false EPA-administered program. 147.1351... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Montana § 147.1351 EPA... within the exterior boundaries of the Fort Peck Indian Reservation, is administered by EPA. This...

  6. 40 CFR 147.1351 - EPA-administered program.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 24 2012-07-01 2012-07-01 false EPA-administered program. 147.1351... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Montana § 147.1351 EPA... within the exterior boundaries of the Fort Peck Indian Reservation, is administered by EPA. This...

  7. 40 CFR 147.3000 - EPA-administered program.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 23 2014-07-01 2014-07-01 false EPA-administered program. 147.3000... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Lands of the Navajo, Ute Mountain Ute, and All Other New Mexico Tribes § 147.3000 EPA-administered program. (a)...

  8. 40 CFR 147.2751 - EPA-administered program.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 24 2013-07-01 2013-07-01 false EPA-administered program. 147.2751... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS American Samoa § 147.2751 EPA-administered program. (a) Contents. The UIC program for American Samoa, including all...

  9. 40 CFR 147.2851 - EPA-administered program.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 24 2013-07-01 2013-07-01 false EPA-administered program. 147.2851... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Trust Territory of the Pacific Islands § 147.2851 EPA-administered program. (a) Contents. The UIC program for Trust Territory...

  10. 40 CFR 147.2151 - EPA-administered program.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 24 2012-07-01 2012-07-01 false EPA-administered program. 147.2151... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Tennessee § 147.2151 EPA-administered program. (a) Contents. The UIC program for the State of Tennessee, including...

  11. 40 CFR 147.801 - EPA-administered program.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 24 2013-07-01 2013-07-01 false EPA-administered program. 147.801... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Iowa § 147.801 EPA... administered by EPA. This program consists of the UIC program requirements of 40 CFR parts 124, 144, 146,...

  12. 40 CFR 147.1151 - EPA-administered program.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 23 2014-07-01 2014-07-01 false EPA-administered program. 147.1151... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Michigan § 147.1151 EPA-administered program. (a) Contents. The UIC program for the State of Michigan, including...

  13. 40 CFR 147.3100 - EPA-administered program.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 24 2013-07-01 2013-07-01 false EPA-administered program. 147.3100... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Lands of Certain Oklahoma Indian Tribes § 147.3100 EPA-administered program. (a) Contents. The UIC program for the...

  14. 40 CFR 147.1951 - EPA-administered program.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 24 2012-07-01 2012-07-01 false EPA-administered program. 147.1951... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Pennsylvania § 147.1951 EPA-administered program. (a) Contents. The UIC program for the State of Pennsylvania,...

  15. 40 CFR 147.1151 - EPA-administered program.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 24 2013-07-01 2013-07-01 false EPA-administered program. 147.1151... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Michigan § 147.1151 EPA-administered program. (a) Contents. The UIC program for the State of Michigan, including...

  16. 40 CFR 147.1351 - EPA-administered program.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 23 2011-07-01 2011-07-01 false EPA-administered program. 147.1351... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Montana § 147.1351 EPA... within the exterior boundaries of the Fort Peck Indian Reservation, is administered by EPA. This...

  17. 40 CFR 147.2751 - EPA-administered program.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 23 2011-07-01 2011-07-01 false EPA-administered program. 147.2751... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS American Samoa § 147.2751 EPA-administered program. (a) Contents. The UIC program for American Samoa, including all...

  18. 40 CFR 147.901 - EPA-administered program.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 24 2013-07-01 2013-07-01 false EPA-administered program. 147.901... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Kentucky § 147.901 EPA... lands, is administered by EPA. This program consists of the UIC program requirements of 40 CFR parts...

  19. 40 CFR 147.2151 - EPA-administered program.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 23 2014-07-01 2014-07-01 false EPA-administered program. 147.2151... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Tennessee § 147.2151 EPA-administered program. (a) Contents. The UIC program for the State of Tennessee, including...

  20. 40 CFR 147.2351 - EPA-administered program.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 23 2011-07-01 2011-07-01 false EPA-administered program. 147.2351... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Virginia § 147.2351 EPA-administered program. (a) Contents. The UIC program for the State of Virginia, including...

  1. 40 CFR 147.2801 - EPA-administered program.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 24 2012-07-01 2012-07-01 false EPA-administered program. 147.2801... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Commonwealth of the Northern Mariana Islands § 147.2801 EPA-administered program. (a) Contents. The UIC program for...

  2. 40 CFR 147.1951 - EPA-administered program.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 24 2013-07-01 2013-07-01 false EPA-administered program. 147.1951... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Pennsylvania § 147.1951 EPA-administered program. (a) Contents. The UIC program for the State of Pennsylvania,...

  3. 40 CFR 147.2751 - EPA-administered program.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 24 2012-07-01 2012-07-01 false EPA-administered program. 147.2751... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS American Samoa § 147.2751 EPA-administered program. (a) Contents. The UIC program for American Samoa, including all...

  4. 40 CFR 147.1951 - EPA-administered program.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 23 2014-07-01 2014-07-01 false EPA-administered program. 147.1951... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Pennsylvania § 147.1951 EPA-administered program. (a) Contents. The UIC program for the State of Pennsylvania,...

  5. 40 CFR 147.2801 - EPA-administered program.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 23 2014-07-01 2014-07-01 false EPA-administered program. 147.2801... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Commonwealth of the Northern Mariana Islands § 147.2801 EPA-administered program. (a) Contents. The UIC program for...

  6. 40 CFR 147.451 - EPA-administered program.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 24 2012-07-01 2012-07-01 false EPA-administered program. 147.451... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS District of Columbia § 147.451 EPA-administered program. (a) Contents. The UIC program for the District of...

  7. 40 CFR 147.3100 - EPA-administered program.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 23 2014-07-01 2014-07-01 false EPA-administered program. 147.3100... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Lands of Certain Oklahoma Indian Tribes § 147.3100 EPA-administered program. (a) Contents. The UIC program for the...

  8. 40 CFR 147.3000 - EPA-administered program.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 23 2011-07-01 2011-07-01 false EPA-administered program. 147.3000... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Lands of the Navajo, Ute Mountain Ute, and All Other New Mexico Tribes § 147.3000 EPA-administered program. (a)...

  9. 40 CFR 147.1951 - EPA-administered program.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 23 2011-07-01 2011-07-01 false EPA-administered program. 147.1951... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Pennsylvania § 147.1951 EPA-administered program. (a) Contents. The UIC program for the State of Pennsylvania,...

  10. 40 CFR 147.2701 - EPA-administered program.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 23 2014-07-01 2014-07-01 false EPA-administered program. 147.2701... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Virgin Islands § 147.2701 EPA-administered program. (a) Contents. The UIC program for the Virgin Islands, including...

  11. 40 CFR 147.2801 - EPA-administered program.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 23 2011-07-01 2011-07-01 false EPA-administered program. 147.2801... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Commonwealth of the Northern Mariana Islands § 147.2801 EPA-administered program. (a) Contents. The UIC program for...

  12. 40 CFR 147.2801 - EPA-administered program.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 24 2013-07-01 2013-07-01 false EPA-administered program. 147.2801... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Commonwealth of the Northern Mariana Islands § 147.2801 EPA-administered program. (a) Contents. The UIC program for...

  13. 40 CFR 147.2351 - EPA-administered program.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 24 2013-07-01 2013-07-01 false EPA-administered program. 147.2351... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Virginia § 147.2351 EPA-administered program. (a) Contents. The UIC program for the State of Virginia, including...

  14. 40 CFR 147.1351 - EPA-administered program.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 22 2010-07-01 2010-07-01 false EPA-administered program. 147.1351... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Montana § 147.1351 EPA... within the exterior boundaries of the Fort Peck Indian Reservation, is administered by EPA. This...

  15. 40 CFR 147.2351 - EPA-administered program.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 23 2014-07-01 2014-07-01 false EPA-administered program. 147.2351... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Virginia § 147.2351 EPA-administered program. (a) Contents. The UIC program for the State of Virginia, including...

  16. 40 CFR 147.2351 - EPA-administered program.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 24 2012-07-01 2012-07-01 false EPA-administered program. 147.2351... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Virginia § 147.2351 EPA-administered program. (a) Contents. The UIC program for the State of Virginia, including...

  17. 40 CFR 147.2801 - EPA-administered program.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 22 2010-07-01 2010-07-01 false EPA-administered program. 147.2801... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Commonwealth of the Northern Mariana Islands § 147.2801 EPA-administered program. (a) Contents. The UIC program for...

  18. 40 CFR 147.2751 - EPA-administered program.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 22 2010-07-01 2010-07-01 false EPA-administered program. 147.2751... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS American Samoa § 147.2751 EPA-administered program. (a) Contents. The UIC program for American Samoa, including all...

  19. 40 CFR 147.2151 - EPA-administered program.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 24 2013-07-01 2013-07-01 false EPA-administered program. 147.2151... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Tennessee § 147.2151 EPA-administered program. (a) Contents. The UIC program for the State of Tennessee, including...

  20. 40 CFR 147.1351 - EPA-administered program.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 23 2014-07-01 2014-07-01 false EPA-administered program. 147.1351... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Montana § 147.1351 EPA... within the exterior boundaries of the Fort Peck Indian Reservation, is administered by EPA. This...

  1. 40 CFR 147.2851 - EPA-administered program.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 22 2010-07-01 2010-07-01 false EPA-administered program. 147.2851... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Trust Territory of the Pacific Islands § 147.2851 EPA-administered program. (a) Contents. The UIC program for Trust Territory...

  2. 40 CFR 147.3000 - EPA-administered program.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 24 2012-07-01 2012-07-01 false EPA-administered program. 147.3000... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Lands of the Navajo, Ute Mountain Ute, and All Other New Mexico Tribes § 147.3000 EPA-administered program. (a)...

  3. 40 CFR 147.901 - EPA-administered program.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 23 2014-07-01 2014-07-01 false EPA-administered program. 147.901... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Kentucky § 147.901 EPA... lands, is administered by EPA. This program consists of the UIC program requirements of 40 CFR parts...

  4. 40 CFR 147.2851 - EPA-administered program.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 23 2014-07-01 2014-07-01 false EPA-administered program. 147.2851... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Trust Territory of the Pacific Islands § 147.2851 EPA-administered program. (a) Contents. The UIC program for Trust Territory...

  5. 40 CFR 147.2851 - EPA-administered program.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 23 2011-07-01 2011-07-01 false EPA-administered program. 147.2851... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Trust Territory of the Pacific Islands § 147.2851 EPA-administered program. (a) Contents. The UIC program for Trust Territory...

  6. 40 CFR 147.3100 - EPA-administered program.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 22 2010-07-01 2010-07-01 false EPA-administered program. 147.3100... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Lands of Certain Oklahoma Indian Tribes § 147.3100 EPA-administered program. (a) Contents. The UIC program for the...

  7. 40 CFR 147.3000 - EPA-administered program.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 24 2013-07-01 2013-07-01 false EPA-administered program. 147.3000... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Lands of the Navajo, Ute Mountain Ute, and All Other New Mexico Tribes § 147.3000 EPA-administered program. (a)...

  8. 40 CFR 147.2751 - EPA-administered program.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 23 2014-07-01 2014-07-01 false EPA-administered program. 147.2751... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS American Samoa § 147.2751 EPA-administered program. (a) Contents. The UIC program for American Samoa, including all...

  9. 40 CFR 147.2851 - EPA-administered program.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 24 2012-07-01 2012-07-01 false EPA-administered program. 147.2851... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Trust Territory of the Pacific Islands § 147.2851 EPA-administered program. (a) Contents. The UIC program for Trust Territory...

  10. 40 CFR 147.2701 - EPA-administered program.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 24 2012-07-01 2012-07-01 false EPA-administered program. 147.2701... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Virgin Islands § 147.2701 EPA-administered program. (a) Contents. The UIC program for the Virgin Islands, including...

  11. 40 CFR 147.3000 - EPA-administered program.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 22 2010-07-01 2010-07-01 false EPA-administered program. 147.3000... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Lands of the Navajo, Ute Mountain Ute, and All Other New Mexico Tribes § 147.3000 EPA-administered program. (a)...

  12. 40 CFR 147.2151 - EPA-administered program.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 23 2011-07-01 2011-07-01 false EPA-administered program. 147.2151... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Tennessee § 147.2151 EPA-administered program. (a) Contents. The UIC program for the State of Tennessee, including...

  13. 24 CFR 982.51 - PHA authority to administer program.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 24 Housing and Urban Development 4 2013-04-01 2013-04-01 false PHA authority to administer program... PHA Plan for Administration of Program § 982.51 PHA authority to administer program. (a) The PHA must have authority to administer the program. The PHA must provide evidence, satisfactory to HUD, of its...

  14. 24 CFR 982.51 - PHA authority to administer program.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 24 Housing and Urban Development 4 2014-04-01 2014-04-01 false PHA authority to administer program... PHA Plan for Administration of Program § 982.51 PHA authority to administer program. (a) The PHA must have authority to administer the program. The PHA must provide evidence, satisfactory to HUD, of its...

  15. 24 CFR 982.51 - PHA authority to administer program.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 24 Housing and Urban Development 4 2012-04-01 2012-04-01 false PHA authority to administer program... PHA Plan for Administration of Program § 982.51 PHA authority to administer program. (a) The PHA must have authority to administer the program. The PHA must provide evidence, satisfactory to HUD, of its...

  16. 24 CFR 982.51 - PHA authority to administer program.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 24 Housing and Urban Development 4 2011-04-01 2011-04-01 false PHA authority to administer program... PHA Plan for Administration of Program § 982.51 PHA authority to administer program. (a) The PHA must have authority to administer the program. The PHA must provide evidence, satisfactory to HUD, of its...

  17. 24 CFR 982.51 - PHA authority to administer program.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 24 Housing and Urban Development 4 2010-04-01 2010-04-01 false PHA authority to administer program... PHA Plan for Administration of Program § 982.51 PHA authority to administer program. (a) The PHA must have authority to administer the program. The PHA must provide evidence, satisfactory to HUD, of its...

  18. 40 CFR 282.95 - Vermont State-Administered Program.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 27 2011-07-01 2011-07-01 false Vermont State-Administered Program... WASTES (CONTINUED) APPROVED UNDERGROUND STORAGE TANK PROGRAMS Approved State Programs § 282.95 Vermont State-Administered Program. (a) The State of Vermont is approved to administer and enforce an...

  19. 40 CFR 282.95 - Vermont State-Administered Program.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 28 2013-07-01 2013-07-01 false Vermont State-Administered Program... WASTES (CONTINUED) APPROVED UNDERGROUND STORAGE TANK PROGRAMS Approved State Programs § 282.95 Vermont State-Administered Program. (a) The State of Vermont is approved to administer and enforce an...

  20. 40 CFR 282.95 - Vermont State-Administered Program.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 28 2012-07-01 2012-07-01 false Vermont State-Administered Program... WASTES (CONTINUED) APPROVED UNDERGROUND STORAGE TANK PROGRAMS Approved State Programs § 282.95 Vermont State-Administered Program. (a) The State of Vermont is approved to administer and enforce an...

  1. 40 CFR 282.95 - Vermont State-Administered Program.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 27 2014-07-01 2014-07-01 false Vermont State-Administered Program... WASTES (CONTINUED) APPROVED UNDERGROUND STORAGE TANK PROGRAMS Approved State Programs § 282.95 Vermont State-Administered Program. (a) The State of Vermont is approved to administer and enforce an...

  2. 40 CFR 282.92 - Tennessee State-Administered Program.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 28 2013-07-01 2013-07-01 false Tennessee State-Administered Program... WASTES (CONTINUED) APPROVED UNDERGROUND STORAGE TANK PROGRAMS Approved State Programs § 282.92 Tennessee State-Administered Program. (a) The State of Tennessee is approved to administer and enforce a petroleum...

  3. 40 CFR 282.92 - Tennessee State-Administered Program.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 28 2012-07-01 2012-07-01 false Tennessee State-Administered Program... WASTES (CONTINUED) APPROVED UNDERGROUND STORAGE TANK PROGRAMS Approved State Programs § 282.92 Tennessee State-Administered Program. (a) The State of Tennessee is approved to administer and enforce a petroleum...

  4. 40 CFR 282.92 - Tennessee State-Administered Program.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 27 2011-07-01 2011-07-01 false Tennessee State-Administered Program... WASTES (CONTINUED) APPROVED UNDERGROUND STORAGE TANK PROGRAMS Approved State Programs § 282.92 Tennessee State-Administered Program. (a) The State of Tennessee is approved to administer and enforce a petroleum...

  5. 40 CFR 282.92 - Tennessee State-Administered Program.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 27 2014-07-01 2014-07-01 false Tennessee State-Administered Program... WASTES (CONTINUED) APPROVED UNDERGROUND STORAGE TANK PROGRAMS Approved State Programs § 282.92 Tennessee State-Administered Program. (a) The State of Tennessee is approved to administer and enforce a petroleum...

  6. 40 CFR 147.1550 - State-administered program.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS New Jersey § 147.1550 State-administered program. The UIC program for all classes of wells in the State of New Jersey, except those on Indian lands, is the program administered by the New Jersey Department of...

  7. 40 CFR 147.1550 - State-administered program.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS New Jersey § 147.1550 State-administered program. The UIC program for all classes of wells in the State of New Jersey, except those on Indian lands, is the program administered by the New Jersey Department of...

  8. 40 CFR 147.1550 - State-administered program.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS New Jersey § 147.1550 State-administered program. The UIC program for all classes of wells in the State of New Jersey, except those on Indian lands, is the program administered by the New Jersey Department of...

  9. 40 CFR 147.1550 - State-administered program.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS New Jersey § 147.1550 State-administered program. The UIC program for all classes of wells in the State of New Jersey, except those on Indian lands, is the program administered by the New Jersey Department of...

  10. 40 CFR 282.86 - Oklahoma State-Administered Program.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 28 2013-07-01 2013-07-01 false Oklahoma State-Administered Program... WASTES (CONTINUED) APPROVED UNDERGROUND STORAGE TANK PROGRAMS Approved State Programs § 282.86 Oklahoma State-Administered Program. (a) The State of Oklahoma is approved to administer and enforce an...

  11. 40 CFR 282.86 - Oklahoma State-Administered Program.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 28 2012-07-01 2012-07-01 false Oklahoma State-Administered Program... WASTES (CONTINUED) APPROVED UNDERGROUND STORAGE TANK PROGRAMS Approved State Programs § 282.86 Oklahoma State-Administered Program. (a) The State of Oklahoma is approved to administer and enforce an...

  12. 40 CFR 282.86 - Oklahoma State-Administered Program.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 27 2011-07-01 2011-07-01 false Oklahoma State-Administered Program... WASTES (CONTINUED) APPROVED UNDERGROUND STORAGE TANK PROGRAMS Approved State Programs § 282.86 Oklahoma State-Administered Program. (a) The State of Oklahoma is approved to administer and enforce an...

  13. 40 CFR 282.86 - Oklahoma State-Administered Program.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 27 2014-07-01 2014-07-01 false Oklahoma State-Administered Program... WASTES (CONTINUED) APPROVED UNDERGROUND STORAGE TANK PROGRAMS Approved State Programs § 282.86 Oklahoma State-Administered Program. (a) The State of Oklahoma is approved to administer and enforce an...

  14. 40 CFR 282.78 - Nevada State-Administered Program.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 28 2013-07-01 2013-07-01 false Nevada State-Administered Program. 282... (CONTINUED) APPROVED UNDERGROUND STORAGE TANK PROGRAMS Approved State Programs § 282.78 Nevada State-Administered Program. (a) The State of Nevada is approved to administer and enforce an underground storage...

  15. 40 CFR 282.78 - Nevada State-Administered Program.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 27 2011-07-01 2011-07-01 false Nevada State-Administered Program. 282... (CONTINUED) APPROVED UNDERGROUND STORAGE TANK PROGRAMS Approved State Programs § 282.78 Nevada State-Administered Program. (a) The State of Nevada is approved to administer and enforce an underground storage...

  16. 40 CFR 282.78 - Nevada State-Administered Program.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 28 2012-07-01 2012-07-01 false Nevada State-Administered Program. 282... (CONTINUED) APPROVED UNDERGROUND STORAGE TANK PROGRAMS Approved State Programs § 282.78 Nevada State-Administered Program. (a) The State of Nevada is approved to administer and enforce an underground storage...

  17. 40 CFR 282.78 - Nevada State-Administered Program.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 27 2014-07-01 2014-07-01 false Nevada State-Administered Program. 282... (CONTINUED) APPROVED UNDERGROUND STORAGE TANK PROGRAMS Approved State Programs § 282.78 Nevada State-Administered Program. (a) The State of Nevada is approved to administer and enforce an underground storage...

  18. 40 CFR 282.78 - Nevada State-Administered Program.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 26 2010-07-01 2010-07-01 false Nevada State-Administered Program. 282... (CONTINUED) APPROVED UNDERGROUND STORAGE TANK PROGRAMS Approved State Programs § 282.78 Nevada State-Administered Program. (a) The State of Nevada is approved to administer and enforce an underground storage...

  19. Noninvasive Imaging of Administered Progenitor Cells

    SciTech Connect

    Steven R Bergmann, M.D., Ph.D.

    2012-12-03

    -99% pure population of leukocytes. Viability was assessed using Trypan blue histological analysis. We successfully isolated and labeled ~25-30 x 10{sup 7} CD34+ lymphocytes in cytokine mobilized progenitor cell apharesis harvests. Cells were also subjected to a stat gram stain to look for bacterial contamination, stat endotoxin LAL to look for endotoxin contamination, flow cytometry for evaluation of the purity of the cells and 14-day sterility culture. Colony forming assays confirm the capacity of these cells to proliferate and function ex-vivo with CFU-GM values of 26 colonies/ 1 x 10{sup 4} cells plated and 97% viability in cytokine augmented methylcellulose at 10-14 days in CO{sub 2} incubation. We developed a closed-processing system for the product labeling prior to infusion to maintain autologous cell integrity and sterility. Release criteria for the labeled product were documented for viability, cell count and differential, and measured radiolabel. We were successful in labeling the cells with up to 500 uCi/10{sup 8} cells, with viability of >98%. However, due to delays in getting the protocol approved by the FDA, the cells were not infused in humans in this location (although we did successfully use CD34+ cells in humans in a study in Australia). The approach developed should permit labeling of progenitor cells that can be administered to human subjects for tracking. The labeling approach should be useful for all progenitor cell types, although this would need to be verified since different cell lines may have differential radiosensitivity.

  20. An overview of herbal supplement utilization with particular emphasis on possible interactions with dental drugs and oral manifestations.

    PubMed

    Abebe, Worku

    2003-01-01

    Herbal medication in the United States is a popular form of therapy. This paper provides an overview of the utilization of herbal supplements with particular emphasis on possible interactions with oral health drugs and oral manifestations. Herbal supplements are regulated by the Dietary Supplement Health and Education Act (DSHEA), which limits their regulation by the U.S Food and Drug Administration (FDA). A number of studies indicate that there is a progressive increase in the utilization of herbal supplements. The majority of consumers of these products are white, middle-aged women who have some college education. Many of the consumers use pharmaceutical drugs concurrently, but most do not inform their health-care providers about their use of herbal supplements. Various herbal supplements have been reported or are suspected to interact with certain oral health drugs, the most important one being 1) bromelain, cayenne, chamomile, feverfew, dong quai, eleuthro/Seberian ginseng, garlic, ginkgo, ginger, ginseng and licorice interacting with aspirin; 2) aloe latex, ephedra, ginseng, rhubarb, cascara sagrada, licorice, and senna interacting with corticosteriods; 3) kava, St. John's wort, chamomile, and valerian interacting with central nervous system (CNS) depressant drugs; and 4) herbs acting on the gastrointestinal system, altering the absorption of several orally administered drugs. Further, the use of some herbal supplements has been reported to be associated with oral manifestations, including aphthous ulcers, lip and tongue irritation, and swelling with feverfew; gingival bleeding with feverfew and ginkgo; tongue numbness with echinacea; xerostomia with St. John's wort; oral and lingual dyskinesia with kava; and salivation with yohimbe. These potential effects of herbal supplements in conjunction with factors related to regulation restrictions suggest that the use of these products may be associated with various adverse reactions that can affect oral health and

  1. 8 CFR 337.8 - Oath administered by the courts.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 8 Aliens and Nationality 1 2012-01-01 2012-01-01 false Oath administered by the courts. 337.8... ALLEGIANCE § 337.8 Oath administered by the courts. (a) Notification of election. An applicant for naturalization not subject to the exclusive jurisdiction of 8 CFR 310.2(d) must notify USCIS at the time of the...

  2. 40 CFR 147.2701 - EPA-administered program.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Virgin Islands § 147.2701 EPA-administered program. (a) Contents. The UIC program for the Virgin Islands, including all... effective date of the UIC program for non-Indian lands in the Virgin Islands is December 30, 1984. The...

  3. 40 CFR 147.2701 - EPA-administered program.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Virgin Islands § 147.2701 EPA-administered program. (a) Contents. The UIC program for the Virgin Islands, including all... effective date of the UIC program for non-Indian lands in the Virgin Islands is December 30, 1984. The...

  4. 40 CFR 147.2700 - State-administered program. [Reserved

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 23 2011-07-01 2011-07-01 false State-administered program. 147.2700 Section 147.2700 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Virgin Islands § 147...

  5. 40 CFR 147.2700 - State-administered program. [Reserved

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 24 2013-07-01 2013-07-01 false State-administered program. 147.2700 Section 147.2700 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Virgin Islands § 147...

  6. 40 CFR 147.2700 - State-administered program. [Reserved

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 22 2010-07-01 2010-07-01 false State-administered program. 147.2700 Section 147.2700 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Virgin Islands § 147...

  7. 40 CFR 147.151 - EPA-administered program.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Arizona § 147.151 EPA-administered program. (a) Contents. The UIC program that applies to all injection activities in Arizona... in Arizona, except for the lands of the Navajo Indians, is June 25, 1984. The effective date for the...

  8. 40 CFR 147.150 - State-administered program. [Reserved

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 23 2011-07-01 2011-07-01 false State-administered program. 147.150 Section 147.150 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Arizona § 147.150...

  9. 40 CFR 147.151 - EPA-administered program.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Arizona § 147.151 EPA-administered program. (a) Contents. The UIC program that applies to all injection activities in Arizona... in Arizona, except for the lands of the Navajo Indians, is June 25, 1984. The effective date for the...

  10. 40 CFR 147.150 - State-administered program. [Reserved

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 22 2010-07-01 2010-07-01 false State-administered program. 147.150 Section 147.150 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Arizona § 147.150...

  11. 40 CFR 147.151 - EPA-administered program.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Arizona § 147.151 EPA-administered program. (a) Contents. The UIC program that applies to all injection activities in Arizona... in Arizona, except for the lands of the Navajo Indians, is June 25, 1984. The effective date for the...

  12. 40 CFR 147.150 - State-administered program. [Reserved

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 24 2012-07-01 2012-07-01 false State-administered program. 147.150 Section 147.150 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Arizona § 147.150...

  13. 40 CFR 147.751 - EPA-administered program.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... requirements set forth in the remainder of this subpart. Injection well owners and operators, and EPA shall... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Indiana § 147.751 EPA-administered program. (a) Contents. The UIC program for all classes of wells on Indian lands, and for Class I...

  14. 40 CFR 147.751 - EPA-administered program.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... requirements set forth in the remainder of this subpart. Injection well owners and operators, and EPA shall... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Indiana § 147.751 EPA-administered program. (a) Contents. The UIC program for all classes of wells on Indian lands, and for Class I...

  15. 40 CFR 147.101 - EPA-administered program.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... remainder of this subpart. Injection well owners and operators, and EPA shall comply with these requirements... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Alaska § 147.101 EPA-administered program. (a) Contents. The UIC program in the State of Alaska for Class I, III, IV, and V wells...

  16. 40 CFR 147.101 - EPA-administered program.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... remainder of this subpart. Injection well owners and operators, and EPA shall comply with these requirements... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Alaska § 147.101 EPA-administered program. (a) Contents. The UIC program in the State of Alaska for Class I, III, IV, and V wells...

  17. 40 CFR 147.751 - EPA-administered program.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... requirements set forth in the remainder of this subpart. Injection well owners and operators, and EPA shall... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Indiana § 147.751 EPA-administered program. (a) Contents. The UIC program for all classes of wells on Indian lands, and for Class I...

  18. 40 CFR 147.101 - EPA-administered program.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... remainder of this subpart. Injection well owners and operators, and EPA shall comply with these requirements... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Alaska § 147.101 EPA-administered program. (a) Contents. The UIC program in the State of Alaska for Class I, III, IV, and V wells...

  19. 40 CFR 147.751 - EPA-administered program.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... requirements set forth in the remainder of this subpart. Injection well owners and operators, and EPA shall... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Indiana § 147.751 EPA-administered program. (a) Contents. The UIC program for all classes of wells on Indian lands, and for Class I...

  20. 40 CFR 147.751 - EPA-administered program.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... requirements set forth in the remainder of this subpart. Injection well owners and operators, and EPA shall... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Indiana § 147.751 EPA-administered program. (a) Contents. The UIC program for all classes of wells on Indian lands, and for Class I...

  1. 40 CFR 147.101 - EPA-administered program.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... remainder of this subpart. Injection well owners and operators, and EPA shall comply with these requirements... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Alaska § 147.101 EPA-administered program. (a) Contents. The UIC program in the State of Alaska for Class I, III, IV, and V wells...

  2. 40 CFR 147.800 - State-administered program. [Reserved

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 24 2013-07-01 2013-07-01 false State-administered program. 147.800 Section 147.800 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Iowa § 147.800...

  3. 40 CFR 147.800 - State-administered program. [Reserved

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 22 2010-07-01 2010-07-01 false State-administered program. 147.800 Section 147.800 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Iowa § 147.800...

  4. 40 CFR 147.800 - State-administered program. [Reserved

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 24 2012-07-01 2012-07-01 false State-administered program. 147.800 Section 147.800 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Iowa § 147.800...

  5. 40 CFR 147.800 - State-administered program. [Reserved

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 23 2014-07-01 2014-07-01 false State-administered program. 147.800 Section 147.800 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Iowa § 147.800...

  6. 40 CFR 147.800 - State-administered program. [Reserved

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 23 2011-07-01 2011-07-01 false State-administered program. 147.800 Section 147.800 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Iowa § 147.800...

  7. 40 CFR 282.61 - Hawaii State-Administered Program.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 27 2014-07-01 2014-07-01 false Hawaii State-Administered Program. 282... (CONTINUED) APPROVED UNDERGROUND STORAGE TANK PROGRAMS Approved State Programs § 282.61 Hawaii State-Administered Program. (a) The State of Hawaii's underground storage tank program is approved in lieu of the...

  8. 40 CFR 282.61 - Hawaii State-Administered Program.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 27 2011-07-01 2011-07-01 false Hawaii State-Administered Program. 282... (CONTINUED) APPROVED UNDERGROUND STORAGE TANK PROGRAMS Approved State Programs § 282.61 Hawaii State-Administered Program. (a) The State of Hawaii's underground storage tank program is approved in lieu of the...

  9. 40 CFR 282.61 - Hawaii State-Administered Program.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 26 2010-07-01 2010-07-01 false Hawaii State-Administered Program. 282... (CONTINUED) APPROVED UNDERGROUND STORAGE TANK PROGRAMS Approved State Programs § 282.61 Hawaii State-Administered Program. (a) The State of Hawaii's underground storage tank program is approved in lieu of the...

  10. 40 CFR 147.600 - State-administered program. [Reserved

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 23 2011-07-01 2011-07-01 false State-administered program. 147.600 Section 147.600 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Hawaii § 147.600 State...

  11. 40 CFR 147.600 - State-administered program. [Reserved

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 22 2010-07-01 2010-07-01 false State-administered program. 147.600 Section 147.600 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Hawaii § 147.600 State...

  12. 40 CFR 282.61 - Hawaii State-Administered Program.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 28 2013-07-01 2013-07-01 false Hawaii State-Administered Program. 282... (CONTINUED) APPROVED UNDERGROUND STORAGE TANK PROGRAMS Approved State Programs § 282.61 Hawaii State-Administered Program. (a) The State of Hawaii's underground storage tank program is approved in lieu of the...

  13. 40 CFR 282.61 - Hawaii State-Administered Program.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 28 2012-07-01 2012-07-01 false Hawaii State-Administered Program. 282... (CONTINUED) APPROVED UNDERGROUND STORAGE TANK PROGRAMS Approved State Programs § 282.61 Hawaii State-Administered Program. (a) The State of Hawaii's underground storage tank program is approved in lieu of the...

  14. 8 CFR 337.8 - Oath administered by the courts.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 8 Aliens and Nationality 1 2010-01-01 2010-01-01 false Oath administered by the courts. 337.8 Section 337.8 Aliens and Nationality DEPARTMENT OF HOMELAND SECURITY NATIONALITY REGULATIONS OATH OF ALLEGIANCE § 337.8 Oath administered by the courts. (a) Notification of election. An applicant for...

  15. 47 CFR 97.509 - Administering VE requirements.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... SERVICES AMATEUR RADIO SERVICE Qualifying Examination Systems § 97.509 Administering VE requirements. (a) Each examination for an amateur operator license must be administered by a team of at least 3 VEs at an... person who holds an amateur operator license of the class specified below: (i) Amateur Extra, Advanced or...

  16. 47 CFR 97.509 - Administering VE requirements.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... SERVICES AMATEUR RADIO SERVICE Qualifying Examination Systems § 97.509 Administering VE requirements. (a) Each examination for an amateur operator license must be administered by a team of at least 3 VEs at an... person who holds an amateur operator license of the class specified below: (i) Amateur Extra, Advanced or...

  17. 47 CFR 97.509 - Administering VE requirements.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... SERVICES AMATEUR RADIO SERVICE Qualifying Examination Systems § 97.509 Administering VE requirements. (a) Each examination for an amateur operator license must be administered by a team of at least 3 VEs at an... person who holds an amateur operator license of the class specified below: (i) Amateur Extra, Advanced or...

  18. 47 CFR 97.509 - Administering VE requirements.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... SERVICES AMATEUR RADIO SERVICE Qualifying Examination Systems § 97.509 Administering VE requirements. (a) Each examination for an amateur operator license must be administered by a team of at least 3 VEs at an... person who holds an amateur operator license of the class specified below: (i) Amateur Extra, Advanced or...

  19. 47 CFR 97.509 - Administering VE requirements.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... SERVICES AMATEUR RADIO SERVICE Qualifying Examination Systems § 97.509 Administering VE requirements. (a) Each examination for an amateur operator license must be administered by a team of at least 3 VEs at an... person who holds an amateur operator license of the class specified below: (i) Amateur Extra, Advanced or...

  20. 40 CFR 147.151 - EPA-administered program.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 24 2013-07-01 2013-07-01 false EPA-administered program. 147.151... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Arizona § 147.151 EPA..., including those on Indian lands, except for Class II wells on Navajo Indian lands for which EPA has...

  1. 40 CFR 147.151 - EPA-administered program.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 23 2014-07-01 2014-07-01 false EPA-administered program. 147.151... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Arizona § 147.151 EPA..., including those on Indian lands, except for Class II wells on Navajo Indian lands for which EPA has...

  2. 24 CFR 960.605 - How PHA administers service requirements.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 24 Housing and Urban Development 4 2012-04-01 2012-04-01 false How PHA administers service... Service Activities or Self-Sufficiency Work Activities § 960.605 How PHA administers service requirements. (a) PHA policy. Each PHA must develop a local policy for administration of the community service and...

  3. 24 CFR 960.605 - How PHA administers service requirements.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 24 Housing and Urban Development 4 2011-04-01 2011-04-01 false How PHA administers service... Service Activities or Self-Sufficiency Work Activities § 960.605 How PHA administers service requirements. (a) PHA policy. Each PHA must develop a local policy for administration of the community service and...

  4. 24 CFR 960.605 - How PHA administers service requirements.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 24 Housing and Urban Development 4 2014-04-01 2014-04-01 false How PHA administers service... Service Activities or Self-Sufficiency Work Activities § 960.605 How PHA administers service requirements. (a) PHA policy. Each PHA must develop a local policy for administration of the community service and...

  5. 24 CFR 960.605 - How PHA administers service requirements.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 24 Housing and Urban Development 4 2010-04-01 2010-04-01 false How PHA administers service... Service Activities or Self-Sufficiency Work Activities § 960.605 How PHA administers service requirements. (a) PHA policy. Each PHA must develop a local policy for administration of the community service and...

  6. 24 CFR 960.605 - How PHA administers service requirements.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 24 Housing and Urban Development 4 2013-04-01 2013-04-01 false How PHA administers service... Service Activities or Self-Sufficiency Work Activities § 960.605 How PHA administers service requirements. (a) PHA policy. Each PHA must develop a local policy for administration of the community service and...

  7. 40 CFR 147.2150 - State-administered program. [Reserved

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 23 2011-07-01 2011-07-01 false State-administered program. 147.2150 Section 147.2150 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Tennessee § 147.2150...

  8. 40 CFR 147.2150 - State-administered program. [Reserved

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 22 2010-07-01 2010-07-01 false State-administered program. 147.2150 Section 147.2150 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Tennessee § 147.2150...

  9. 40 CFR 147.2150 - State-administered program. [Reserved

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 23 2014-07-01 2014-07-01 false State-administered program. 147.2150 Section 147.2150 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Tennessee § 147.2150...

  10. 40 CFR 282.94 - Utah State-Administered Program.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ....94 Section 282.94 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED) APPROVED UNDERGROUND STORAGE TANK PROGRAMS Approved State Programs § 282.94 Utah State-Administered Program. (a) The State of Utah is approved to administer and enforce an underground storage tank...

  11. 40 CFR 147.1450 - State-administered program.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 22 2010-07-01 2010-07-01 false State-administered program. 147.1450 Section 147.1450 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS... of Nevada, other than those on Indian lands, is the program administered by the Nevada Division...

  12. 40 CFR 147.1450 - State-administered program.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Nevada § 147.1450... of Nevada, other than those on Indian lands, is the program administered by the Nevada Division of... program under the SDWA for the State of Nevada. This incorporation by reference was approved by the...

  13. 39 CFR 222.1 - Authority to administer postal affairs.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 39 Postal Service 1 2011-07-01 2011-07-01 false Authority to administer postal affairs. 222.1 Section 222.1 Postal Service UNITED STATES POSTAL SERVICE ORGANIZATION AND ADMINISTRATION DELEGATIONS OF AUTHORITY § 222.1 Authority to administer postal affairs. (a) The Postmaster General. The postmaster...

  14. 39 CFR 222.1 - Authority to administer postal affairs.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 39 Postal Service 1 2013-07-01 2013-07-01 false Authority to administer postal affairs. 222.1 Section 222.1 Postal Service UNITED STATES POSTAL SERVICE ORGANIZATION AND ADMINISTRATION DELEGATIONS OF AUTHORITY § 222.1 Authority to administer postal affairs. (a) The Postmaster General. The postmaster...

  15. 40 CFR 147.3100 - EPA-administered program.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Oklahoma Indian Tribes § 147.3100 EPA-administered program. (a) Contents. The UIC program for the Indian lands in Oklahoma, except for that covering the Class II wells of the Five Civilized Tribes, is administered by EPA. The UIC program for all wells on Indian lands in Oklahoma, except Class II wells on the...

  16. 40 CFR 147.3100 - EPA-administered program.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Oklahoma Indian Tribes § 147.3100 EPA-administered program. (a) Contents. The UIC program for the Indian lands in Oklahoma, except for that covering the Class II wells of the Five Civilized Tribes, is administered by EPA. The UIC program for all wells on Indian lands in Oklahoma, except Class II wells on the...

  17. 40 CFR 147.101 - EPA-administered program.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 22 2010-07-01 2010-07-01 false EPA-administered program. 147.101 Section 147.101 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS...-administered program. (a) Contents. The UIC program in the State of Alaska for Class I, III, IV, and V...

  18. 40 CFR 147.1450 - State-administered program.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Nevada § 147.1450... of Nevada, other than those on Indian lands, is the program administered by the Nevada Division of... program under the SDWA for the State of Nevada. This incorporation by reference was approved by...

  19. 40 CFR 147.1450 - State-administered program.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Nevada § 147.1450... of Nevada, other than those on Indian lands, is the program administered by the Nevada Division of... program under the SDWA for the State of Nevada. This incorporation by reference was approved by...

  20. In Vivo Anti-Tumor Effects of Flavokawain A in 4T1 Breast Cancer Cell-Challenged Mice.

    PubMed

    Abu, Nadiah; Mohamed, Nurul Elyani; Yeap, Swee Keong; Lim, Kian Lam; Akhtar, M Nadeem; Zulfadli, Aimi Jamil; Kee, Beh Boon; Abdullah, Mohd Puad; Omar, Abdul Rahman; Alitheen, Noorjahan Banu

    2015-01-01

    Flavokawain A is a chalcone that can be found in the kava-kava plant (Piper methsyticum) extract. The kava-kava plant has been reported to possess anti-cancer, anti-inflammatory and antinociceptive activities. The state of the immune system, and the inflammatory process play vital roles in the progression of cancer. The immunomodulatary effects and the anti-inflammatory effects of flavokawain A in a breast cancer murine model have not been studied yet. Thus, this study aimed to elucidate the basic mechanism as to how flavokawain A regulates and enhance the immune system as well as impeding the inflammatory process in breast cancer-challenged mice. Based on our study, it is interesting to note that flavokawain A increased the T cell population; both Th1 cells and CTLs, aside from the natural killer cells. The levels of IFN-γ and IL-2 were also elevated in the serum of flavokawain A-treated mice. Apart from that, flavokawain A also decreased the weight and volume of the tumor, and managed to induce apoptosis in them. In terms of inflammation, flavokawain A-treated mice had reduced level of major pro-inflammatory mediators; NO, iNOS, NF-KB, ICAM and COX-2. Overall, flavokawain A has the potential to not only enhance antitumor immunity, but also prevents the inflammatory process in a cancer-prone microenvironment.

  1. Burkholderia pseudomallei Data Gap Analysis

    DTIC Science & Technology

    2015-11-01

    alcoholics, kava users (Australia), chronic drug users, or diabetic . However, HIV does not seem to be a factor. Table 2-1. Published melioidosis... Diabetic rats are also common since they are acutely susceptible to B. pseudomallei and often die within 48hrs [Patel, 2011]. Non-human primate (NHP

  2. Evaluation of Genomic Instability in the Abnormal Prostate

    DTIC Science & Technology

    2008-12-01

    186. 9. Rabbani F, Stroumbakis N, Kava BR, Cookson MS, Fair WR. Incidence and clinical significance of false-negative sextant prostate biopsies. The...Journal of urology 1998;159(4):1247-1250. 10. Stamey TA. Making the most out of six systematic sextant biopsies. Urology 1995;45(1):2-12. 11

  3. Lipid peroxidation and cyclooxygenase enzyme inhibitory activities of acidic aqueous extracts of some dietary supplements.

    PubMed

    Raman, Priyadarshini; Dewitt, David L; Nair, Muraleedharan G

    2008-02-01

    The botanical supplement market is growing at a fast pace with more and more people resorting to them for maintaining good health. Echinacea, garlic, ginkgo, ginseng, Siberian ginseng, grape seed extract, kava kava, saw palmetto and St John's wort are some of the popular supplements used for a variety of health benefits. These supplements are associated with various product claims, which suggest that they possess cyclooxygenase (COX) enzyme and lipid s inhibitory activities. COX enzymes are found to be at elevated levels in inflamed and cancerous cells. To test some of the product claims, selected supplements were analysed for their ability to inhibit COX-1 and -2 enzymes and lipid peroxidation in vitro. The supplements were extracted with acidified water (pH 2) at 37 degrees C to simulate the gastric environment. The supplements tested demonstrated varying degrees of COX enzyme inhibition (5-85% for COX-1 and 13-28% for COX-2). Interestingly, extracts of garlic (Meijer), ginkgo (Solaray), ginseng (Nature's Way), Siberian ginseng (GNC, Nutrilite, Solaray, Natrol), kava kava (GNC, Sundown, Solaray) and St John's wort (Nutrilite) selectively inhibited COX-2 enzyme. These supplements also inhibited lipid peroxidation in vitro (5-99%). The results indicated that the consumption of these botanical supplements studied possess health benefits.

  4. 40 CFR 147.350 - State-administered program.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Connecticut § 147.350...: http://www.archives.gov/federal_register/code_of_federal_regulations/ibr_locations.html. (1...

  5. 40 CFR 147.1300 - State-administered program.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Missouri § 147.1300...); (2) Missouri Code of State Regulations, title 10, division 50, chapters 1 and 2 (June 1984); (3...

  6. 40 CFR 147.1700 - State-administered program.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... and Records Administration (NARA). For information on the availability of this material at NARA, call...-administered program: (1) N.C. ADMIN. CODE, Title 15, r. 02L.0100 et seq. Groundwater Classification...

  7. 40 CFR 147.801 - EPA-administered program.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ..., and any additional requirements set forth in the remainder of this subpart. Injection well owners and... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Iowa § 147.801 EPA...

  8. 40 CFR 147.801 - EPA-administered program.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ..., and any additional requirements set forth in the remainder of this subpart. Injection well owners and... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Iowa § 147.801 EPA...

  9. 40 CFR 147.801 - EPA-administered program.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ..., and any additional requirements set forth in the remainder of this subpart. Injection well owners and... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Iowa § 147.801 EPA...

  10. 40 CFR 147.601 - EPA-administered program.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ..., and any additional requirements set forth in the remainder of this subpart. Injection well owners and... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Hawaii § 147.601 EPA...

  11. 40 CFR 147.1151 - EPA-administered program.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    .... Injection well owners and operators, and EPA shall comply with these requirements. (b) Effective dates. The... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Michigan § 147.1151...

  12. 40 CFR 147.451 - EPA-administered program.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... this subpart. Injection well owners and operators, and EPA shall comply with these requirements. (b... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS District of Columbia...

  13. 40 CFR 147.1951 - EPA-administered program.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... subpart. Injection well owners and operators, and EPA shall comply with these requirements. (b) Effective... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Pennsylvania § 147...

  14. 40 CFR 147.1151 - EPA-administered program.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    .... Injection well owners and operators, and EPA shall comply with these requirements. (b) Effective dates. The... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Michigan § 147.1151...

  15. 40 CFR 147.2351 - EPA-administered program.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    .... Injection well owners and operators, and EPA shall comply with these requirements. (b) Effective dates. The... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Virginia § 147.2351...

  16. 40 CFR 147.1151 - EPA-administered program.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    .... Injection well owners and operators, and EPA shall comply with these requirements. (b) Effective dates. The... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Michigan § 147.1151...

  17. 40 CFR 147.601 - EPA-administered program.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ..., and any additional requirements set forth in the remainder of this subpart. Injection well owners and... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Hawaii § 147.601 EPA...

  18. 40 CFR 147.2701 - EPA-administered program.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    .... Injection well owners and operators, and EPA shall comply with these requirements. (b) Effective dates. The... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Virgin Islands § 147...

  19. 40 CFR 147.1201 - EPA-administered program.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... additional requirements set forth in the remainder of this subpart. Injection well owners and operators, and... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Minnesota § 147.1201...

  20. 40 CFR 147.451 - EPA-administered program.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... this subpart. Injection well owners and operators, and EPA shall comply with these requirements. (b... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS District of Columbia...

  1. 40 CFR 147.1201 - EPA-administered program.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... additional requirements set forth in the remainder of this subpart. Injection well owners and operators, and... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Minnesota § 147.1201...

  2. 40 CFR 147.451 - EPA-administered program.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... this subpart. Injection well owners and operators, and EPA shall comply with these requirements. (b... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS District of Columbia...

  3. 40 CFR 147.601 - EPA-administered program.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ..., and any additional requirements set forth in the remainder of this subpart. Injection well owners and... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Hawaii § 147.601 EPA...

  4. 40 CFR 147.601 - EPA-administered program.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ..., and any additional requirements set forth in the remainder of this subpart. Injection well owners and... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Hawaii § 147.601 EPA...

  5. 40 CFR 147.801 - EPA-administered program.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ..., and any additional requirements set forth in the remainder of this subpart. Injection well owners and... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Iowa § 147.801 EPA...

  6. 40 CFR 147.601 - EPA-administered program.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ..., and any additional requirements set forth in the remainder of this subpart. Injection well owners and... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Hawaii § 147.601 EPA...

  7. 40 CFR 147.451 - EPA-administered program.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... this subpart. Injection well owners and operators, and EPA shall comply with these requirements. (b... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS District of Columbia...

  8. 40 CFR 147.2151 - EPA-administered program.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    .... Injection well owners and operators, and EPA shall comply with these requirements. (b) Effective dates... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Tennessee § 147.2151...

  9. Findings from Survey Administered to Weatherization Training Centers

    SciTech Connect

    Conlon, Brian; Tonn, Bruce Edward

    2015-03-01

    This report summarizes results of a survey administered to directors of weatherization training centers that receive funding from the U.S. Department of Energy. The survey presents results related to questions on training offered and future plans.

  10. 40 CFR 147.2500 - State-administered program.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Disposal of Liquid Industrial Wastes and By-Products, Wisconsin Administrative Code §§ 214.03 and 214.08... State-administered program: (1) Chapter 144, Water, Sewage, Refuse, Mining and Air Pollution,...

  11. Systemic Effects of Vaginally Administered Estrogen Therapy: A Review

    PubMed Central

    Krause, Megan; Wheeler, Thomas L.; Richter, Holly E.; Snyder, Thomas E.

    2015-01-01

    Hormone Therapy (HT) was considered the standard of care prior to the publication of the Women’s Health Initiative (WHI). After the study was published, the use of systemic HT dramatically decreased resulting in an increased incidence of menopausal symptoms such as hot flashes, vaginal dryness and dyspareunia experienced by women. Use of vaginal estrogen offers women a unique alternative for relief of these symptoms. This article reviews the systemic effects of vaginally administered estrogen. Effects on serum hormone levels, vasomotor symptoms, lipid profiles and use in women with breast cancer are reviewed. An accompanying review examines the local effects of vaginally administered estrogen. PMID:22453284

  12. 32 CFR 637.11 - Authority to administer oaths.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 32 National Defense 4 2014-07-01 2013-07-01 true Authority to administer oaths. 637.11 Section 637.11 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY (CONTINUED) LAW ENFORCEMENT AND CRIMINAL INVESTIGATIONS MILITARY POLICE INVESTIGATION Investigations § 637.11 Authority to...

  13. 32 CFR 637.11 - Authority to administer oaths.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 4 2010-07-01 2010-07-01 true Authority to administer oaths. 637.11 Section 637.11 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY (CONTINUED) LAW ENFORCEMENT AND CRIMINAL INVESTIGATIONS MILITARY POLICE INVESTIGATION Investigations § 637.11 Authority to...

  14. 32 CFR 637.11 - Authority to administer oaths.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 32 National Defense 4 2012-07-01 2011-07-01 true Authority to administer oaths. 637.11 Section 637.11 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY (CONTINUED) LAW ENFORCEMENT AND CRIMINAL INVESTIGATIONS MILITARY POLICE INVESTIGATION Investigations § 637.11 Authority to...

  15. 32 CFR 637.11 - Authority to administer oaths.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 32 National Defense 4 2013-07-01 2013-07-01 false Authority to administer oaths. 637.11 Section 637.11 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY (CONTINUED) LAW ENFORCEMENT AND CRIMINAL INVESTIGATIONS MILITARY POLICE INVESTIGATION Investigations § 637.11 Authority to...

  16. 32 CFR 637.11 - Authority to administer oaths.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 32 National Defense 4 2011-07-01 2011-07-01 false Authority to administer oaths. 637.11 Section 637.11 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY (CONTINUED) LAW ENFORCEMENT AND CRIMINAL INVESTIGATIONS MILITARY POLICE INVESTIGATION Investigations § 637.11 Authority to...

  17. A Mobile Platform for Administering Questionnaires and Synchronizing Their Answers

    ERIC Educational Resources Information Center

    Ginardi, Maria Germana; Lanzola, Giordano

    2013-01-01

    This paper describes a platform for administering questionnaires on smart-phones and tablets. The project arises from the need of acquiring data for monitoring the outcomes of different homecare interventions. First a model has been defined for representing questionnaires, able to support adaptivity in the dialog with the user and enforce some…

  18. 40 CFR 147.400 - State-administered program.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Delaware § 147.400....archives.gov/federal_register/code_of_federal_regulations/ibr_locations.html. (1) Delaware Environmental Protection Act, (Environmental Control) 7 Delaware Code Annotated, Chapter 60, Sections 6001-6060 (Revised...

  19. 40 CFR 147.1100 - State-administered program.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Massachusetts § 147..., sections 27, 43, and 44 (West 1981); (2) Code of Massachusetts Regulations, title 310, sections 23.01-23.11.... (c) Statement of legal authority. “Underground Injection Control Program—Attorney General's Statement...

  20. 40 CFR 147.1550 - State-administered program.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS New Jersey § 147.1550... Annotated sections 58:10A-1 through 58:10A-20 (West 1982 and Supp. 1990); (2) New Jersey Administrative Code... Protection, “Re: New Jersey Pollutant Discharge Elimination System—Underground Injection Control,” February 9...

  1. 40 CFR 147.2600 - State-administered program.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Guam § 147.2600 State..., 1984. (1) Water Resources Conservation Act, Government Code of Guam sections 57021-57025, Public Law 9... (December 30, 1974); (2) Water Pollution Control Act, Government Code of Guam sections 57042 and 57045...

  2. Molecular Mechanisms of Taste Disorder in Oxaliplatin-administered Rats.

    PubMed

    Nishida, Kentaro

    2016-01-01

    Taste disorder is one of the adverse effects of cancer chemotherapy resulting in a loss of appetite, leading to malnutrition and a decrease in the quality of life of the patient. Oxaliplatin, a platinum anticancer drug, has a critical role in colon cancer chemotherapy and is known to induce taste disorder. Here, we evaluated the taste functions in oxaliplatin-administered rats. Among the taste receptors, expression levels of T1R2, one of the sweet receptor subunits, increased in the circumvallate papillae of the oxaliplatin-administered rats. In a brief-access test, i.e., behavioral analysis of the taste response, oxaliplatin-administered rats showed a decreased response to sweet taste. However, we did not detect any differences in the plasma levels of zinc, number of taste cells, or morphology of taste buds between control and oxaliplatin-administered rats. In conclusion, the decreased response to sweet taste by oxaliplatin administration may be due to the upregulation of T1R2 expression.

  3. 40 CFR 282.53 - Arkansas State-Administered Program.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... administered by the Arkansas Department of Pollution Control and Ecology, was approved by EPA pursuant to 42 U... Pollution Control and Ecology, 8001 National Drive, Little Rock, AR 72219-8913. (1) State statutes and... include: (1) Arkansas Department of Pollution Control and Ecology Regulation Number 12—Storage Tank...

  4. 40 CFR 282.53 - Arkansas State-Administered Program.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... administered by the Arkansas Department of Pollution Control and Ecology, was approved by EPA pursuant to 42 U... Pollution Control and Ecology, 8001 National Drive, Little Rock, AR 72219-8913. (1) State statutes and... include: (1) Arkansas Department of Pollution Control and Ecology Regulation Number 12—Storage Tank...

  5. 40 CFR 282.53 - Arkansas State-Administered Program.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... administered by the Arkansas Department of Pollution Control and Ecology, was approved by EPA pursuant to 42 U... Pollution Control and Ecology, 8001 National Drive, Little Rock, AR 72219-8913. (1) State statutes and... include: (1) Arkansas Department of Pollution Control and Ecology Regulation Number 12—Storage Tank...

  6. 40 CFR 282.53 - Arkansas State-Administered Program.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... administered by the Arkansas Department of Pollution Control and Ecology, was approved by EPA pursuant to 42 U... Pollution Control and Ecology, 8001 National Drive, Little Rock, AR 72219-8913. (1) State statutes and... include: (1) Arkansas Department of Pollution Control and Ecology Regulation Number 12—Storage Tank...

  7. 40 CFR 282.53 - Arkansas State-Administered Program.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... administered by the Arkansas Department of Pollution Control and Ecology, was approved by EPA pursuant to 42 U... Pollution Control and Ecology, 8001 National Drive, Little Rock, AR 72219-8913. (1) State statutes and... include: (1) Arkansas Department of Pollution Control and Ecology Regulation Number 12—Storage Tank...

  8. 40 CFR 282.71 - Massachusetts State-Administered Program.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 28 2012-07-01 2012-07-01 false Massachusetts State-Administered Program. 282.71 Section 282.71 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID... do not relate to underground storage tanks and with respect to underground storage tanks insofar...

  9. 40 CFR 147.2500 - State-administered program.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Statutes Annotated (West 1974 and Supp. 1983); (3) Chapter 162, Pure Drinking Water, Wisconsin Statutes... Section 147.2500 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS... State-administered program: (1) Chapter 144, Water, Sewage, Refuse, Mining and Air Pollution,...

  10. 40 CFR 147.2500 - State-administered program.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Statutes Annotated (West 1974 and Supp. 1983); (3) Chapter 162, Pure Drinking Water, Wisconsin Statutes... Section 147.2500 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS... State-administered program: (1) Chapter 144, Water, Sewage, Refuse, Mining and Air Pollution,...

  11. 40 CFR 147.1500 - State-administered program.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Environmental Services, approved by the EPA pursuant to section 1422 of the SDWA. Notice of this approval was... 40 Protection of Environment 23 2011-07-01 2011-07-01 false State-administered program. 147.1500 Section 147.1500 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS...

  12. 40 CFR 147.1500 - State-administered program.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Environmental Services, approved by the EPA pursuant to section 1422 of the SDWA. Notice of this approval was... 40 Protection of Environment 22 2010-07-01 2010-07-01 false State-administered program. 147.1500 Section 147.1500 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS...

  13. 40 CFR 147.1651 - EPA-administered program.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    .... Injection well owners and operators, and EPA shall comply with these requirements. (b) Effective dates. The effective date of the UIC program for New York for all injection activities except those on lands of the... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS New York § 147.1651...

  14. 40 CFR 147.901 - EPA-administered program.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Kentucky § 147.901 EPA..., 144, 146, 148, and any additional requirements set forth in the remainder of this subpart. Injection well owners and operators, and EPA shall comply with these requirements. (b) Effective dates. The...

  15. 40 CFR 147.1651 - EPA-administered program.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    .... Injection well owners and operators, and EPA shall comply with these requirements. (b) Effective dates. The effective date of the UIC program for New York for all injection activities except those on lands of the... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS New York § 147.1651...

  16. 40 CFR 147.901 - EPA-administered program.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Kentucky § 147.901 EPA..., 144, 146, 148, and any additional requirements set forth in the remainder of this subpart. Injection well owners and operators, and EPA shall comply with these requirements. (b) Effective dates. The...

  17. 40 CFR 147.1651 - EPA-administered program.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    .... Injection well owners and operators, and EPA shall comply with these requirements. (b) Effective dates. The effective date of the UIC program for New York for all injection activities except those on lands of the... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS New York § 147.1651...

  18. 40 CFR 147.1651 - EPA-administered program.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    .... Injection well owners and operators, and EPA shall comply with these requirements. (b) Effective dates. The effective date of the UIC program for New York for all injection activities except those on lands of the... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS New York § 147.1651...

  19. 40 CFR 147.901 - EPA-administered program.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Kentucky § 147.901 EPA..., 144, 146, 148, and any additional requirements set forth in the remainder of this subpart. Injection well owners and operators, and EPA shall comply with these requirements. (b) Effective dates. The...

  20. 40 CFR 147.1651 - EPA-administered program.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    .... Injection well owners and operators, and EPA shall comply with these requirements. (b) Effective dates. The effective date of the UIC program for New York for all injection activities except those on lands of the... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS New York § 147.1651...

  1. Administering the School Library Media Center. Third Edition.

    ERIC Educational Resources Information Center

    Morris, Betty J.; And Others

    This guide brings together all aspects of administration of a school media center in light of the new qualitative standards in "Information Power: Guidelines for School Library Media Programs." The book focuses on practical considerations within a single school as reflected in the new developments in organizing and administering the…

  2. Teaching Auction Strategy Using Experiments Administered Via the Internet

    ERIC Educational Resources Information Center

    Asker, John; Grosskopf, Brit; McKinney, C. Nicholas; Niederle, Muriel; Roth, Alvin E.; Weizsacker, Georg

    2004-01-01

    The authors present an experimental design used to teach concepts in the economics of auctions and implications for e-Business procurement. The experiment is easily administered and can be adapted to many different treatments. The chief innovation is that it does not require the use of a lab or class time. Instead, the design can be implemented on…

  3. Systemically Administered, Target Organ-Specific Therapies for Regenerative Medicine

    PubMed Central

    Järvinen, Tero A. H.; May, Ulrike; Prince, Stuart

    2015-01-01

    Growth factors and other agents that could potentially enhance tissue regeneration have been identified, but their therapeutic value in clinical medicine has been limited for reasons such as difficulty to maintain bioactivity of locally applied therapeutics in the protease-rich environment of regenerating tissues. Although human diseases are treated with systemically administered drugs in general, all current efforts aimed at enhancing tissue repair with biological drugs have been based on their local application. The systemic administration of growth factors has been ruled out due to concerns about their safety. These concerns are warranted. In addition, only a small proportion of systemically administered drugs reach their intended target. Selective delivery of the drug to the target tissue and use of functional protein domains capable of penetrating cells and tissues could alleviate these problems in certain circumstances. We will present in this review a novel approach utilizing unique molecular fingerprints (“Zip/postal codes”) in the vasculature of regenerating tissues that allows target organ-specific delivery of systemically administered therapeutic molecules by affinity-based physical targeting (using peptides or antibodies as an “address tag”) to injured tissues undergoing repair. The desired outcome of targeted therapies is increased local accumulation and lower systemic concentration of the therapeutic payload. We believe that the physical targeting of systemically administered therapeutic molecules could be rapidly adapted in the field of regenerative medicine. PMID:26437400

  4. Evaluation of coagulation via thromboelastography in healthy horses administered dexamethasone

    PubMed Central

    Woodman, Jenna; Wagg, Catherine R.; Boysen, Søren R.; Leguillette, Renaud; Mizen, Kyle; Roy, Marie-France

    2015-01-01

    Dexamethasone was administered to healthy horses daily for 7 days. Blood samples were collected at 3 time points from both treatment and non-treatment groups, and analyzed via thromboelastography (TEG). There were no significant differences in TEG parameters between treated and untreated horses, or within treatment groups over time. PMID:26677262

  5. 40 CFR 282.50 - Alabama State-Administered Program.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 26 2010-07-01 2010-07-01 false Alabama State-Administered Program. 282.50 Section 282.50 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID... establish and protect wellhead areas from contaminants. (C) Alabama Department of Environmental...

  6. 40 CFR 282.50 - Alabama State-Administered Program.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 28 2013-07-01 2013-07-01 false Alabama State-Administered Program. 282.50 Section 282.50 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID... establish and protect wellhead areas from contaminants. (C) Alabama Department of Environmental...

  7. 40 CFR 282.50 - Alabama State-Administered Program.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 27 2011-07-01 2011-07-01 false Alabama State-Administered Program. 282.50 Section 282.50 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID... establish and protect wellhead areas from contaminants. (C) Alabama Department of Environmental...

  8. 40 CFR 282.50 - Alabama State-Administered Program.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 28 2012-07-01 2012-07-01 false Alabama State-Administered Program. 282.50 Section 282.50 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID... establish and protect wellhead areas from contaminants. (C) Alabama Department of Environmental...

  9. 40 CFR 282.50 - Alabama State-Administered Program.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 27 2014-07-01 2014-07-01 false Alabama State-Administered Program. 282.50 Section 282.50 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID... establish and protect wellhead areas from contaminants. (C) Alabama Department of Environmental...

  10. 40 CFR 282.88 - Pennsylvania State-Administered Program.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ..., Bureau of Land Recycling and Waste Management, Storage Tank Program, Rachel Carson State Office Building... WASTES (CONTINUED) APPROVED UNDERGROUND STORAGE TANK PROGRAMS Approved State Programs § 282.88 Pennsylvania State-Administered Program. (a) The Commonwealth of Pennsylvania's underground storage tank...

  11. 24 CFR 511.51 - State-administered program.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... URBAN DEVELOPMENT SLUM CLEARANCE AND URBAN RENEWAL RENTAL REHABILITATION GRANT PROGRAM State Program... 24 Housing and Urban Development 3 2013-04-01 2013-04-01 false State-administered program. 511.51 Section 511.51 Housing and Urban Development Regulations Relating to Housing and Urban...

  12. 24 CFR 511.51 - State-administered program.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... URBAN DEVELOPMENT SLUM CLEARANCE AND URBAN RENEWAL RENTAL REHABILITATON GRANT PROGRAM State Program... 24 Housing and Urban Development 3 2011-04-01 2010-04-01 true State-administered program. 511.51 Section 511.51 Housing and Urban Development Regulations Relating to Housing and Urban...

  13. 24 CFR 511.51 - State-administered program.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... URBAN DEVELOPMENT SLUM CLEARANCE AND URBAN RENEWAL RENTAL REHABILITATON GRANT PROGRAM State Program... 24 Housing and Urban Development 3 2010-04-01 2010-04-01 false State-administered program. 511.51 Section 511.51 Housing and Urban Development Regulations Relating to Housing and Urban...

  14. 24 CFR 511.51 - State-administered program.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... URBAN DEVELOPMENT SLUM CLEARANCE AND URBAN RENEWAL RENTAL REHABILITATION GRANT PROGRAM State Program... 24 Housing and Urban Development 3 2012-04-01 2012-04-01 false State-administered program. 511.51 Section 511.51 Housing and Urban Development Regulations Relating to Housing and Urban...

  15. 24 CFR 511.51 - State-administered program.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... URBAN DEVELOPMENT SLUM CLEARANCE AND URBAN RENEWAL RENTAL REHABILITATION GRANT PROGRAM State Program... 24 Housing and Urban Development 3 2014-04-01 2013-04-01 true State-administered program. 511.51 Section 511.51 Housing and Urban Development Regulations Relating to Housing and Urban...

  16. 25 CFR 170.471 - How are projects administered?

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... PROGRAM Planning, Design, and Construction of Indian Reservation Roads Program Facilities Construction and Construction Monitoring § 170.471 How are projects administered? (a) When a tribe carries out an IRR project... substantial changes in the scope of a construction project in coordination with the affected tribe. (d) The...

  17. 25 CFR 170.471 - How are projects administered?

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... PROGRAM Planning, Design, and Construction of Indian Reservation Roads Program Facilities Construction and Construction Monitoring § 170.471 How are projects administered? (a) When a tribe carries out an IRR project... substantial changes in the scope of a construction project in coordination with the affected tribe. (d) The...

  18. 25 CFR 170.471 - How are projects administered?

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... substantial changes in the scope of a construction project in coordination with the affected tribe. (d) The... PROGRAM Planning, Design, and Construction of Indian Reservation Roads Program Facilities Construction and Construction Monitoring § 170.471 How are projects administered? (a) When a tribe carries out an IRR project...

  19. 25 CFR 170.471 - How are projects administered?

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... substantial changes in the scope of a construction project in coordination with the affected tribe. (d) The... PROGRAM Planning, Design, and Construction of Indian Reservation Roads Program Facilities Construction and Construction Monitoring § 170.471 How are projects administered? (a) When a tribe carries out an IRR project...

  20. 25 CFR 170.471 - How are projects administered?

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 25 Indians 1 2010-04-01 2010-04-01 false How are projects administered? 170.471 Section 170.471 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR LAND AND WATER INDIAN RESERVATION ROADS PROGRAM Planning, Design, and Construction of Indian Reservation Roads Program Facilities Construction and...

  1. Challenges of Administering Teacher Education Programme in Kenyan Universities

    ERIC Educational Resources Information Center

    Genvieve, Nasimiyu

    2017-01-01

    Proper management of logistical issues in Teacher education programme tends to promote the quality of preparation of school teachers. The main objective of the study was to investigate challenges of administering teacher education programmes in Kenyan universities. The theoretical framework of the study was adopted as used by Koehler and Mishra's…

  2. 7 CFR 634.30 - Appeals in USDA administered projects.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 6 2010-01-01 2010-01-01 false Appeals in USDA administered projects. 634.30 Section 634.30 Agriculture Regulations of the Department of Agriculture (Continued) NATURAL RESOURCES CONSERVATION SERVICE, DEPARTMENT OF AGRICULTURE LONG TERM CONTRACTING RURAL CLEAN WATER PROGRAM Participant...

  3. 7 CFR 634.30 - Appeals in USDA administered projects.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 6 2012-01-01 2012-01-01 false Appeals in USDA administered projects. 634.30 Section 634.30 Agriculture Regulations of the Department of Agriculture (Continued) NATURAL RESOURCES CONSERVATION SERVICE, DEPARTMENT OF AGRICULTURE LONG TERM CONTRACTING RURAL CLEAN WATER PROGRAM Participant...

  4. 7 CFR 634.30 - Appeals in USDA administered projects.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 6 2011-01-01 2011-01-01 false Appeals in USDA administered projects. 634.30 Section 634.30 Agriculture Regulations of the Department of Agriculture (Continued) NATURAL RESOURCES CONSERVATION SERVICE, DEPARTMENT OF AGRICULTURE LONG TERM CONTRACTING RURAL CLEAN WATER PROGRAM Participant...

  5. 7 CFR 634.30 - Appeals in USDA administered projects.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 6 2013-01-01 2013-01-01 false Appeals in USDA administered projects. 634.30 Section 634.30 Agriculture Regulations of the Department of Agriculture (Continued) NATURAL RESOURCES CONSERVATION SERVICE, DEPARTMENT OF AGRICULTURE LONG TERM CONTRACTING RURAL CLEAN WATER PROGRAM Participant...

  6. 7 CFR 634.30 - Appeals in USDA administered projects.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 6 2014-01-01 2014-01-01 false Appeals in USDA administered projects. 634.30 Section 634.30 Agriculture Regulations of the Department of Agriculture (Continued) NATURAL RESOURCES CONSERVATION SERVICE, DEPARTMENT OF AGRICULTURE LONG TERM CONTRACTING RURAL CLEAN WATER PROGRAM Participant...

  7. 40 CFR 282.60 - Georgia State-Administered Program.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... administered by the Georgia Department of Natural Resources, Environmental Protection Division, was approved by..., Georgia Environmental Protection Division, 4244 International Parkway, Suite 100, Atlanta, GA 30354. (1... Regulatory Requirements Applicable to the Underground Storage Tank Program, 1995. (ii) The following statutes...

  8. Identifying Students' Errors in Administering the WAIS-R.

    ERIC Educational Resources Information Center

    Slate, John R.; Jones, Craig H.

    1990-01-01

    Investigated specific problem caused by traditional method of teaching students to administer Wechsler Adult Intelligence Scale-Revised. Analysis of 180 protocols by 26 graduate students revealed average of 8.8 mistakes per protocol. When errors were corrected, 81 percent of Full Scale intelligence quotients were changed. Students' performance…

  9. 40 CFR 147.2300 - State-administered program.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... was approved by the Director of the Federal Register July 6, 1984. (1) Vt. Stat. Ann. tit. 10... are part of the approved State-administered program: (1) Vt. Stat. Ann. tit. 10, sections 1251 through 1283 (1973 and Supp. 1981). (2) Vt. Stat. Ann. tit. 10, sections 901 through 911 (1973 and Supp....

  10. 40 CFR 147.2300 - State-administered program.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... was approved by the Director of the Federal Register July 6, 1984. (1) Vt. Stat. Ann. tit. 10... are part of the approved State-administered program: (1) Vt. Stat. Ann. tit. 10, sections 1251 through 1283 (1973 and Supp. 1981). (2) Vt. Stat. Ann. tit. 10, sections 901 through 911 (1973 and Supp....

  11. 40 CFR 147.2300 - State-administered program.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... was approved by the Director of the Federal Register July 6, 1984. (1) Vt. Stat. Ann. tit. 10... are part of the approved State-administered program: (1) Vt. Stat. Ann. tit. 10, sections 1251 through 1283 (1973 and Supp. 1981). (2) Vt. Stat. Ann. tit. 10, sections 901 through 911 (1973 and Supp....

  12. 40 CFR 147.2300 - State-administered program.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... was approved by the Director of the Federal Register July 6, 1984. (1) Vt. Stat. Ann. tit. 10... are part of the approved State-administered program: (1) Vt. Stat. Ann. tit. 10, sections 1251 through 1283 (1973 and Supp. 1981). (2) Vt. Stat. Ann. tit. 10, sections 901 through 911 (1973 and Supp....

  13. 40 CFR 147.2300 - State-administered program.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... was approved by the Director of the Federal Register July 6, 1984. (1) Vt. Stat. Ann. tit. 10... are part of the approved State-administered program: (1) Vt. Stat. Ann. tit. 10, sections 1251 through 1283 (1973 and Supp. 1981). (2) Vt. Stat. Ann. tit. 10, sections 901 through 911 (1973 and Supp....

  14. Intravenously administered nanoparticles increase survival following blast trauma.

    PubMed

    Lashof-Sullivan, Margaret M; Shoffstall, Erin; Atkins, Kristyn T; Keane, Nickolas; Bir, Cynthia; VandeVord, Pamela; Lavik, Erin B

    2014-07-15

    Explosions account for 79% of combat-related injuries, leading to multiorgan hemorrhage and uncontrolled bleeding. Uncontrolled bleeding is the leading cause of death in battlefield traumas as well as in civilian life. We need to stop the bleeding quickly to save lives, but, shockingly, there are no treatments to stop internal bleeding. A therapy that halts bleeding in a site-specific manner and is safe, stable at room temperature, and easily administered is critical for the advancement of trauma care. To address this need, we have developed hemostatic nanoparticles that are administered intravenously. When tested in a model of blast trauma with multiorgan hemorrhaging, i.v. administration of the hemostatic nanoparticles led to a significant improvement in survival over the short term (1 h postblast). No complications from this treatment were apparent out to 3 wk. This work demonstrates that these particles have the potential to save lives and fundamentally change trauma care.

  15. A tracer study with systemically and locally administered dinitrophenylated osteopontin.

    PubMed

    Nanci, Antonio; Wazen, Rima M; Zalzal, Sylvia F; Fortin, Micheline; Goldberg, Harvey A; Hunter, Graeme K; Ghitescu, Dorin-Lucian

    2004-12-01

    Osteopontin (OPN), a major non-collagenous matrix protein of bone, is also found in tissue fluids and in the circulation. It is still not clear whether circulating OPN contributes to bone formation. To elucidate this question, rat OPN was tagged with dinitrophenol groups and administered to rats either intravenously or by infusion with an osmotic minipump through a "surgical window" in the bone of the hemimandible. Dinitrophenylated rat albumin (ALB) was used as a control. The presence and distribution of tagged proteins were revealed by immunogold labeling on sections of tibia and alveolar bone. Tagged molecules of OPN were found in mineralization foci, surfaces and interfaces, and matrix accumulations among calcified collagen fibrils. Even though dinitrophenylated ALB was administered at several-fold higher concentrations, it did not accumulate in these sites. These results show that circulating OPN can be incorporated into specific compartments of forming bone and suggest that such molecules may play a more important role than previously suspected.

  16. Hemodynamic effects of calcium gluconate administered to conscious horses.

    PubMed

    Grubb, T L; Foreman, J H; Benson, G J; Thurmon, J C; Tranquilli, W J; Constable, P D; Olson, W O; Davis, L E

    1996-01-01

    Calcium gluconate was administered to conscious horses at 3 different rates (0.1, 0.2, and 0.4 mg/kg/min for 15 minutes each). Serum calcium concentrations and parameters of cardiovascular function were evaluated. All 3 calcium administration rates caused marked increases in both ionized and total calcium concentrations, cardiac index, stroke index, and cardiac contractility (dP/dtmax). Mean arterial pressure and right atrial pressure were unchanged; heart rate decreased markedly during calcium administration. Ionized calcium concentration remained between 54% and 57% of total calcium concentration throughout the study. We conclude that calcium gluconate can safely be administered to conscious horses at 0.1 to 0.4 mg/kg/min and that administration will result in improved cardiac function.

  17. Translocation of (133)Cs administered to Cryptomeria japonica wood.

    PubMed

    Aoki, Dan; Asai, Ryutaro; Tomioka, Rie; Matsushita, Yasuyuki; Asakura, Hiroyuki; Tabuchi, Masao; Fukushima, Kazuhiko

    2017-04-15

    To reveal the in planta behaviour of caesium (Cs), the stable isotope (133)Cs was administered into 3-year-old Cryptomeria japonica seedlings by the application of (133)CsCl aqueous solution to the bark surface. The administered (133)Cs was quantified by ICP-MS measurements, which showed transportation of (133)Cs in an ascending direction in the stem. Distribution of (133)Cs was visualized using freeze-fixed C. japonica woody stem samples and cryo-time-of-flight secondary ion mass spectrometry/scanning electron microscopy (cryo-TOF-SIMS/SEM) analysis. Cryo-TOF-SIMS/SEM visualization suggested that (133)Cs was rapidly transported radially by ray parenchyma cells followed by axial transportation by pith and axial parenchyma cells. Adsorption experiments using powdered C. japonica wood samples and X-ray absorption fine structure (XAFS) analysis suggested that (133)Cs was in the hydrated state following its deposition into tracheid cell walls.

  18. [Pharmacokinetics of sulphonamides administered in combination with trimethoprim].

    PubMed

    Klimowicz, A

    1992-01-01

    Pharmacokinetic properties of sulfametrole, sulfamoxole, sulphamerazine, sulphadiazine, sulphamethoxazole and sulfamethopyrazine, i.e. the sulphonamides administered in combination with trimethoprim have been compared. From the pharmacokinetic point of view sulphadiazine seems to be the most optimal sulphonamide to apply jointly with trimethoprim. Some of long-acting sulphonamides like sulfamethopyrazine and sulfadimethoxine, used as components of above mentioned combinations, possess comparable clinical efficacy in spite of differences of their and trimethoprim half-lives.

  19. Supervising nursing students administering medication: a perspective from registered nurses.

    PubMed

    Reid-Searl, Kerry; Happell, Brenda

    2012-07-01

    To explore the attitudes, experiences and opinions of registered nurses regarding supervision of undergraduate nursing students while administering medication in the healthcare setting. Medication errors present a considerable risk to safety in the healthcare setting. By virtue of their role in the administration of medication, registered nurses are considered as major contributors to this problem. Undergraduate nursing students administer medication in the clinical setting, but little attention has been paid to the implications for patient safety. This research was conducted using exploratory qualitative methodology. Focus group interviews were conducted with 13 registered nurses. The participants were asked to describe their experiences and opinions regarding the supervision of undergraduate nursing students. Data were analysed using the framework approach. Three main themes from this work are presented in this paper: 'standard of supervision', 'a beneficial experience' and 'preparation'. The participants regarded supervision as an important process in fostering student learning and ensuring safety. Preparation on the part of the healthcare facility, students and the university were essential to maximise the benefits for all concerned. Relevance to clinical practice.  The ability to administer medication safely is an important skill for all registered nurses. Nursing students need the opportunity to develop these skills as part of their undergraduate educational programme. Registered nurses must supervise students in a rigorous and supportive manner to enhance learning and to promote quality care. © 2012 Blackwell Publishing Ltd.

  20. Whole body autoradiographic distribution of exogenously administered renin in mice

    SciTech Connect

    Iwao, H.; Nakamura, N.; Ikemoto, F.; Yamamoto, K.

    1983-06-01

    The distribution of exogenously administered renin was investigated using whole body autoradiography. Purified renin from mouse submaxillary gland (SR) was labeled with radioactive iodine (/sup 125/I). This labeled renin (/sup 125/I-SR) and Na/sup 125/I were administered into the tail vein of male ddY mice, in doses of 10.2 and 16.4 mu Ci/30 g body weight, respectively. Mice were killed by an overdose of ether, and autoradiography was performed on whole body sections. To separate free /sup 125/I liberated from /sup 125/I-SR, sections were treated with perchloric acid. A major accumulation of /sup 125/I-SR, acid-insoluble, was evident in the renal cortex, whereas the hepatic accumulation of /sup 125/I-SR was minor. Radioactivity in the thyroid and submaxillary glands, in the stomach, and in urine was also apparent, but disappeared after acid treatment, except in the thyroid glands. Radioactivity in the brain, intestinal content, spleen, and adrenal glands was nil. These autoradiograms provide the first evidence that exogenously administered renin is mainly distributed in the renal cortex.

  1. The route of liquids administered to calves by esophageal feeder.

    PubMed Central

    Chapman, H W; Butler, D G; Newell, M

    1986-01-01

    An esophageal feeder and a rubber nasoesophageal tube were used to administer fluids to calves. Radio-opaque fluids were given and their destination determined by fluoroscopy and radiography. Fluids containing glucose and xylose were also given and plasma glucose and xylose concentrations measured. In at least 93% of calves, the radio-opaque fluids entered the reticulum, indicating that the reticular groove did not close. Oral administration of sodium bicarbonate, copper sulfate and guanidine HCl did not influence groove closure in calves that received fluids through an esophageal feeder. As administration of the fluids continued, overflow to the abomasum occurred after about 400 mL had been given. When 2.0 L of glucose and electrolyte solution was given by esophageal feeder, plasma glucose levels rose significantly (p less than 0.01), showing that absorption had occurred. Plasma xylose levels rose in seven out of eight calves 30 minutes after a second 2.0 L dose (containing xylose) had been administered. Thus, even though esophageal feeders do not cause reticular groove closure, they can be used to administer fluids for enteric absorption, provided large quantities are given. PMID:3742363

  2. Absorption sites of orally administered drugs in the small intestine.

    PubMed

    Murakami, Teruo

    2017-09-17

    In pharmacotherapy, drugs are mostly taken orally to be absorbed systemically from the small intestine, and some drugs are known to have preferential absorption sites in the small intestine. It would therefore be valuable to know the absorption sites of orally administered drugs and the influencing factors. Areas covered:In this review, the author summarizes the reported absorption sites of orally administered drugs, as well as, influencing factors and experimental techniques. Information on the main absorption sites and influencing factors can help to develop ideal drug delivery systems and more effective pharmacotherapies. Expert opinion: Various factors including: the solubility, lipophilicity, luminal concentration, pKa value, transporter substrate specificity, transporter expression, luminal fluid pH, gastrointestinal transit time, and intestinal metabolism determine the site-dependent intestinal absorption. However, most of the dissolved fraction of orally administered drugs including substrates for ABC and SLC transporters, except for some weakly basic drugs with higher pKa values, are considered to be absorbed sequentially from the proximal small intestine. Securing the solubility and stability of drugs prior to reaching to the main absorption sites and appropriate delivery rates of drugs at absorption sites are important goals for achieving effective pharmacotherapy.

  3. Administering an epoch initiated for remote memory access

    DOEpatents

    Blocksome, Michael A; Miller, Douglas R

    2012-10-23

    Methods, systems, and products are disclosed for administering an epoch initiated for remote memory access that include: initiating, by an origin application messaging module on an origin compute node, one or more data transfers to a target compute node for the epoch; initiating, by the origin application messaging module after initiating the data transfers, a closing stage for the epoch, including rejecting any new data transfers after initiating the closing stage for the epoch; determining, by the origin application messaging module, whether the data transfers have completed; and closing, by the origin application messaging module, the epoch if the data transfers have completed.

  4. Administering an epoch initiated for remote memory access

    DOEpatents

    Blocksome, Michael A; Miller, Douglas R

    2014-03-18

    Methods, systems, and products are disclosed for administering an epoch initiated for remote memory access that include: initiating, by an origin application messaging module on an origin compute node, one or more data transfers to a target compute node for the epoch; initiating, by the origin application messaging module after initiating the data transfers, a closing stage for the epoch, including rejecting any new data transfers after initiating the closing stage for the epoch; determining, by the origin application messaging module, whether the data transfers have completed; and closing, by the origin application messaging module, the epoch if the data transfers have completed.

  5. Administering an epoch initiated for remote memory access

    DOEpatents

    Blocksome, Michael A.; Miller, Douglas R.

    2013-01-01

    Methods, systems, and products are disclosed for administering an epoch initiated for remote memory access that include: initiating, by an origin application messaging module on an origin compute node, one or more data transfers to a target compute node for the epoch; initiating, by the origin application messaging module after initiating the data transfers, a closing stage for the epoch, including rejecting any new data transfers after initiating the closing stage for the epoch; determining, by the origin application messaging module, whether the data transfers have completed; and closing, by the origin application messaging module, the epoch if the data transfers have completed.

  6. Disposition of disodium cromoglycate administered in three particle sizes.

    PubMed Central

    Curry, S H; Taylor, A J; Evans, S; Godfrey, S; Zeidifard, E

    1975-01-01

    1 Disodium cromoglycate (DSCG) was administered in three particle sizes to five human subjects. 2 Urinary excretion of DSCG, as a proportion of the dose, was highest following small particles; the lower values recorded following intermediate-sized and large particles were similar. 3 DSCG deposited in the mouth was highest following large particles; the lower values recorded following intermediate-sized and small particles were similar. 4 The data were examined in relation to the recent observation that the protective effect of small particles of DSCG is dramatically superior to that of large particles. PMID:825134

  7. Effect of Calcium Carbonate on Bioavailability of Orally Administered Gemifloxacin

    PubMed Central

    Pletz, M. W.; Petzold, P.; Allen, A.; Burkhardt, O.; Lode, H.

    2003-01-01

    We investigated the effect of calcium carbonate on the oral bioavailability of gemifloxacin. Gemifloxacin was administered alone, 2 h before, simultaneously, or 2 h after calcium carbonate in 16 volunteers. Data for 320 mg of gemifloxacin alone were as follows: maximum concentration of drug in serum (Cmax),13 μg/ml; half-life, 7.33 h; and area under the concentration-time curve from 0 h to infinity (AUC∞), 6.79 μg · h/ml. Only simultaneous coadministration of calcium carbonate reduced Cmax (−17%) and AUC∞ (−21%) significantly. PMID:12821462

  8. Urinary metabolites of daidzin orally administered in rats.

    PubMed

    Yasuda, T; Ohsawa, K

    1998-09-01

    In a study on the metabolism of flavonoids, the isoflavone glycoside daidzin was orally administered to rats. Urine samples were collected and treated with beta-glucuronidase and arylsulfatase. Aglycone daidzein (M3) and other three metabolites, 3',4',7-trihydroxyisoflavone (M1), 4',7-dihydroxyisoflavanone (M2) and 4',7-dihydroxyisoflavan (M4) were isolated from the urine following treatment with enzymes. The structures of M1, M2 and M4 were determined on the basis of chemical and spectral data.

  9. Electroencephalographic and autonomic effects of centrally administered dermorphin in rabbits.

    PubMed

    Tartara, A; Maurelli, M; Marchioni, E

    1985-01-01

    Dermorphin, administered into the third ventricle of conscious rabbits, induces an increase of the total power density spectrum of the cortex and a decrease of the total power of the hippocampus. The electrocortical pattern is similar to that found with other opiates and reported as specific of mu agonists. Simultaneously the peptide causes respiratory depression, bradycardia and hypothermia. Naloxone (0.5 mg/kg IV) quickly and completely inverts all these effects. The activity of serotoninergic, Gabaergic, catecholaminergic and cholinergic systems does not seem to be required for these dermorphin actions. Thus, the hypothesis that dermorphin acts directly in modifying cerebral electrical activity is put forward.

  10. A screening program for dancers administered by dancers.

    PubMed

    Wilson, Margaret; Deckert, Jennifer L

    2009-01-01

    Students enrolled in a dance kinesiology class were trained to administer a screening protocol on younger dancers in the same department. The dance kinesiology students gained experience assessing alignment and functional symmetry in their peers, and then recommended exercises for gaining awareness and developing balanced patterns of movement. This "low stakes" assessment created both dialogue and peer support centered on helping the screened dancers understand and effectively work with their individual capacities and limitations. The project was designed to contribute to a culture of wellness and education within the dance department.

  11. Rats self-administer carbachol directly into the nucleus accumbens.

    PubMed

    Ikemoto, S; Glazier, B S; Murphy, J M; McBride, W J

    1998-03-01

    The potential reinforcing effect of the muscarinic cholinergic agonist carbachol within the nucleus accumbens (ACB) was examined in female Wistar rats by using the technique of intracranial self-administration. Rats dose dependently self-administered solutions of 0.0-6.6 mM (in a volume of 100 nL per injection) directly into the ACB. Rats self-administered the 3.3 and 6.6 mM doses significantly more than the group given only vehicle. The caudate putamen did not support reliable self-administration of the 6.6-mM dose. Rats exhibited preference for the lever that produced infusions of 3.3 and 6.6 mM carbachol into the ACB over the lever that had no consequence. The self-infusion of the 6.6-mM dose into the ACB was inhibited by the coadministration of the muscarinic antagonist scopolamine (0.25 mM), but not by the nicotinic antagonist mecamylamine (6.6 mM). The present results suggest that direct activation of muscarinic receptors within the ACB supports self-administration and could result from reinforcement or from elicitation of a novel stimulus.

  12. Caregiver-Administered Neuropsychiatric Inventory (CGA-NPI).

    PubMed

    Kang, Sue J; Choi, Seong H; Lee, Byung Hwa; Jeong, Yong; Hahm, Dong Seok; Han, Il Woo; Cummings, Jeffrey L; Na, Duk L

    2004-03-01

    The Neuropsychiatric Inventory (NPI) is used to assess neuropsychiatric symptoms in dementia patients. To reduce clinicians' time taken to administer the NPI, the authors studied a caregiver-administered NPI (CGA-NPI), in which caregivers completed the written form of the NPI worksheet. After a brief presupervision session, the caregivers of 61 dementia patients completed the CGA-NPI by reading through the worksheet. This was followed by a postsupervision session to check if the caregivers had completed the form appropriately. The correlation between the prevalence rates of each neuropsychiatric symptom obtained by the CGA-NPI and those obtained by the NPI was fair to good (kappa = 0.57-0.90) in all domains. All frequency, severity, and caregivers' distress scores of the CGA-NPI correlated significantly with those of the NPI (r> 0.6, P<.001). Total CGA-NPI scores also correlated highly with total NPI scores (r= 0.86, P<.001). These results suggest that the CGA-NPI can substitute for the NPI, saving administration time.

  13. 40 CFR 282.91 - South Dakota State-Administered Program.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 27 2011-07-01 2011-07-01 false South Dakota State-Administered... Dakota State-Administered Program. (a) The State of South Dakota is approved to administer and enforce an... administered by the South Dakota Department of Environment and Natural Resources, was approved by EPA pursuant...

  14. 40 CFR 282.91 - South Dakota State-Administered Program.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 27 2014-07-01 2014-07-01 false South Dakota State-Administered... Dakota State-Administered Program. (a) The State of South Dakota is approved to administer and enforce an... administered by the South Dakota Department of Environment and Natural Resources, was approved by EPA pursuant...

  15. 40 CFR 282.84 - North Dakota State-Administered Program.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 27 2014-07-01 2014-07-01 false North Dakota State-Administered... Dakota State-Administered Program. (a) The State of North Dakota is approved to administer and enforce an... administered by the North Dakota Department of Health and Consolidated Laboratories, was approved by EPA...

  16. 40 CFR 282.84 - North Dakota State-Administered Program.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 28 2013-07-01 2013-07-01 false North Dakota State-Administered... Dakota State-Administered Program. (a) The State of North Dakota is approved to administer and enforce an... administered by the North Dakota Department of Health and Consolidated Laboratories, was approved by EPA...

  17. 40 CFR 282.84 - North Dakota State-Administered Program.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 28 2012-07-01 2012-07-01 false North Dakota State-Administered... Dakota State-Administered Program. (a) The State of North Dakota is approved to administer and enforce an... administered by the North Dakota Department of Health and Consolidated Laboratories, was approved by EPA...

  18. 40 CFR 282.84 - North Dakota State-Administered Program.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 27 2011-07-01 2011-07-01 false North Dakota State-Administered... Dakota State-Administered Program. (a) The State of North Dakota is approved to administer and enforce an... administered by the North Dakota Department of Health and Consolidated Laboratories, was approved by EPA...

  19. 40 CFR 282.91 - South Dakota State-Administered Program.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 28 2013-07-01 2013-07-01 false South Dakota State-Administered... Dakota State-Administered Program. (a) The State of South Dakota is approved to administer and enforce an... administered by the South Dakota Department of Environment and Natural Resources, was approved by EPA pursuant...

  20. 40 CFR 282.102 - Puerto Rico State-Administered Program.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 27 2014-07-01 2014-07-01 false Puerto Rico State-Administered Program... Rico State-Administered Program. (a) The Commonwealth of Puerto Rico is approved to administer and...'s program, as administered by the Commonwealth of Puerto Rico Environmental Quality Board, is...

  1. 40 CFR 282.102 - Puerto Rico State-Administered Program.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 28 2013-07-01 2013-07-01 false Puerto Rico State-Administered Program... Rico State-Administered Program. (a) The Commonwealth of Puerto Rico is approved to administer and...'s program, as administered by the Commonwealth of Puerto Rico Environmental Quality Board, is...

  2. 40 CFR 282.102 - Puerto Rico State-Administered Program.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 27 2011-07-01 2011-07-01 false Puerto Rico State-Administered Program... Rico State-Administered Program. (a) The Commonwealth of Puerto Rico is approved to administer and...'s program, as administered by the Commonwealth of Puerto Rico Environmental Quality Board, is...

  3. 40 CFR 282.89 - Rhode Island State-Administered Program.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 28 2013-07-01 2013-07-01 false Rhode Island State-Administered... Island State-Administered Program. (a) The State of Rhode Island is approved to administer and enforce an... administered by the Rhode Island Department of Environmental Management, was approved by EPA pursuant to 42 U.S...

  4. 40 CFR 282.89 - Rhode Island State-Administered Program.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 27 2011-07-01 2011-07-01 false Rhode Island State-Administered... Island State-Administered Program. (a) The State of Rhode Island is approved to administer and enforce an... administered by the Rhode Island Department of Environmental Management, was approved by EPA pursuant to 42 U.S...

  5. 40 CFR 282.89 - Rhode Island State-Administered Program.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 27 2014-07-01 2014-07-01 false Rhode Island State-Administered... Island State-Administered Program. (a) The State of Rhode Island is approved to administer and enforce an... administered by the Rhode Island Department of Environmental Management, was approved by EPA pursuant to 42 U.S...

  6. 40 CFR 282.89 - Rhode Island State-Administered Program.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 28 2012-07-01 2012-07-01 false Rhode Island State-Administered... Island State-Administered Program. (a) The State of Rhode Island is approved to administer and enforce an... administered by the Rhode Island Department of Environmental Management, was approved by EPA pursuant to 42 U.S...

  7. 40 CFR 282.89 - Rhode Island State-Administered Program.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 26 2010-07-01 2010-07-01 false Rhode Island State-Administered... Island State-Administered Program. (a) The State of Rhode Island is approved to administer and enforce an... administered by the Rhode Island Department of Environmental Management, was approved by EPA pursuant to 42 U.S...

  8. A Controlled Study to Assess the Clinical Efficacy of Totally Self-Administered Systematic Desensitization

    ERIC Educational Resources Information Center

    Rosen, Gerald M.; And Others

    1976-01-01

    Highly anxious self-referred snake phobics received either (a) therapist-administered desensitization, (b) self-administered desensitization with weekly therapist phone calls, (c) totally self-administered desensitization, (d) self-administered double-blind placebo control, or (e) no treatment. Pretreatment to posttreatment measures revealed…

  9. A Controlled Study to Assess the Clinical Efficacy of Totally Self-Administered Systematic Desensitization

    ERIC Educational Resources Information Center

    Rosen, Gerald M.; And Others

    1976-01-01

    Highly anxious self-referred snake phobics received either (a) therapist-administered desensitization, (b) self-administered desensitization with weekly therapist phone calls, (c) totally self-administered desensitization, (d) self-administered double-blind placebo control, or (e) no treatment. Pretreatment to posttreatment measures revealed…

  10. Administering truncated receive functions in a parallel messaging interface

    DOEpatents

    Archer, Charles J; Blocksome, Michael A; Ratterman, Joseph D; Smith, Brian E

    2014-12-09

    Administering truncated receive functions in a parallel messaging interface (`PMI`) of a parallel computer comprising a plurality of compute nodes coupled for data communications through the PMI and through a data communications network, including: sending, through the PMI on a source compute node, a quantity of data from the source compute node to a destination compute node; specifying, by an application on the destination compute node, a portion of the quantity of data to be received by the application on the destination compute node and a portion of the quantity of data to be discarded; receiving, by the PMI on the destination compute node, all of the quantity of data; providing, by the PMI on the destination compute node to the application on the destination compute node, only the portion of the quantity of data to be received by the application; and discarding, by the PMI on the destination compute node, the portion of the quantity of data to be discarded.

  11. [Hypokalemic effect of salbutamol administered intravenously in the preoperative period].

    PubMed

    Fábregas, N; Taurá, P; Castillo, J; Tomás, A; Planella, V L; Naldá, M A

    1989-01-01

    In 8 healthy patients (ASA I-II) there was analyzed the effect of salbutamol over serum levels of potassium, glucose, insulin, AMPc and GMPc. Also were determined the arterial blood pressure and heart rate. The drug was administered intravenously, as bronchodilator, during the preoperative period. There was a significant decrease in kaliemia (p less than 0.001 immediately after receiving the salbutamol infusion and p less than 0.05 at 60 min). Their plasma potassium levels dropped from 4.03 +/- 25 to 3.45 +/- 0.16 mEq.l-1. The plasma levels of glucose and insulin increased with a significance of p less than 0.001 post salbutamol perfusion. There were no changes in the plasmatic AMPc and GMPc. Heart rate increased from 67 +/- 10.8 to 80.5 +/- 13.7 (p less than 0.01) post perfusion, returning afterwards to their basal values. Arterial blood pressure was unmodified.

  12. Myocardial toxicity in a group of greyhounds administered ractopamine.

    PubMed

    Yaeger, M J; Mullin, K; Ensley, S M; Ware, W A; Slavin, R E

    2012-05-01

    Ractopamine, a synthetic β(2)-adrenoceptor agonist, is widely used as a feed additive in the United States to promote a reduction in body fat and enhance muscle growth in cattle, pigs, and turkeys. It has the potential for illegal use in show and racing animals because it may affect performance via its β-adrenergic agonist properties or anabolic activities. Nine greyhounds were orally administered 1 mg/kg of ractopamine to investigate the ability to detect the drug in urine. Postdosing, 7 of 9 dogs developed cardiac arrhythmias and had elevated troponin levels indicating myocardial damage. One dog necropsied 4 days postdosing had massive myocardial necrosis, mild to focally moderate skeletal muscle necrosis, and widespread segmental arterial mediolysis. A second dog necropsied 17 days postdosing had mild myocardial necrosis and fibrosis. Scattered arteries exhibited segmental medial and perimedial fibromuscular dysplasia. This is the first reported case of arterial, cardiac, and skeletal muscle damage associated with ractopamine.

  13. Web administered pre/post assessment: reliability, compliance and security

    NASA Astrophysics Data System (ADS)

    Bonham, Scott W.

    2006-12-01

    Pre/post assessment measures learning by comparing assessment performance before and after instruction. Usually it is administered on paper during class, needing to be distributed, collected, graded and analyzed. Administration on the web outside class frees up class time and automates many steps. However, this switch to unproctored web administration raises questions. Will the results be as reliable? Will students take it? Will test questions leak to fraternity files? An experiment using two different assessments pre/post test was carried out in introductory astronomy classes. Each section took one assessment on line and one in class. Comparing performance on paper vs. web provides information on reliability. Numbers of students completing in each mode give information on compliance and factors influencing it. Browser events that could indicate copying, saving or printing of questions were recorded to identify possible loss of security.

  14. Metabolism of tellurium, antimony and germanium simultaneously administered to rats.

    PubMed

    Kobayashi, Akihiro; Ogra, Yasumitsu

    2009-06-01

    Recently, tellurium (Te), antimony (Sb) and germanium (Ge) have been used as an alloy in phase-change optical magnetic disks, such as digital versatile disk-random access memory (DVD-RAM) and DVD-recordable disk (DVD-RW). Although these metalloids, the so-called "exotic" elements, are known to be non-essential and harmful, little is known about their toxic effects and metabolism. Metalloid compounds, tellurite, antimonite and germanium dioxide, were simultaneously administered to rats. Their distributions metabolites were determined and identified by speciation. Te and Sb accumulated in red blood cells (RBCs): Te accumulated in RBCs in the dimethylated form, while Sb accumulated in the inorganic/non-methylated form. In addition, trimethyltelluronium (TMTe) was the urinary metabolite of Te, whereas Sb in urine was not methylated but oxidized. Ge was also not methylated in rats. These results suggest that each metalloid is metabolized via a unique pathway.

  15. Peripherally administered orexin improves survival of mice with endotoxin shock

    PubMed Central

    Ogawa, Yasuhiro; Irukayama-Tomobe, Yoko; Murakoshi, Nobuyuki; Kiyama, Maiko; Ishikawa, Yui; Hosokawa, Naoto; Tominaga, Hiromu; Uchida, Shuntaro; Kimura, Saki; Kanuka, Mika; Morita, Miho; Hamada, Michito; Takahashi, Satoru; Hayashi, Yu; Yanagisawa, Masashi

    2016-01-01

    Sepsis is a systemic inflammatory response to infection, accounting for the most common cause of death in intensive care units. Here, we report that peripheral administration of the hypothalamic neuropeptide orexin improves the survival of mice with lipopolysaccharide (LPS) induced endotoxin shock, a well-studied septic shock model. The effect is accompanied by a suppression of excessive cytokine production and an increase of catecholamines and corticosterone. We found that peripherally administered orexin penetrates the blood-brain barrier under endotoxin shock, and that central administration of orexin also suppresses the cytokine production and improves the survival, indicating orexin’s direct action in the central nervous system (CNS). Orexin helps restore body temperature and potentiates cardiovascular function in LPS-injected mice. Pleiotropic modulation of inflammatory response by orexin through the CNS may constitute a novel therapeutic approach for septic shock. DOI: http://dx.doi.org/10.7554/eLife.21055.001 PMID:28035899

  16. Interactions of conjugate vaccines and co-administered vaccines

    PubMed Central

    Findlow, H; Borrow, R

    2016-01-01

    Conjugate vaccines play an important role in the prevention of infectious diseases such as those caused by the bacteria Haemophilus influenzae (Hi) type b (Hib), Neisseria meningitidis, and Streptococcus pneumoniae. Vaccines developed against these 3 pathogens utilize 3 main carrier proteins, non-toxic mutant of diphtheria toxin (CRM197), diphtheria toxoid (DT) and tetanus toxoid (TT). Current pediatric immunisation schedules include the administration of several vaccines simultaneously, therefore increasing the potential for immune interference (both positively and negatively) to the antigens administered. Knowledge of vaccine interactions is principally derived from clinical trials, these are reviewed here to explore immune interference which may result of from carrier-specific T-cell helper interactions, bystander interference and carrier induced epitopic suppression. PMID:26619353

  17. Evaluation of a Self-Administered Oral Glucose Tolerance Test

    PubMed Central

    Bethel, M. Angelyn; Price, Hermione C.; Sourij, Harald; White, Sarah; Coleman, Ruth L.; Ring, Arne; Kennedy, Irene E.C.; Tucker, Lynne; Holman, Rury R.

    2013-01-01

    OBJECTIVE To assess the feasibility of using a disposable, self-administered, capillary blood sampling oral glucose tolerance test (OGTT) device in a community setting. RESEARCH DESIGN AND METHODS Eighteen healthy and 12 type 2 diabetic volunteers underwent six 75-g OGTTs using a prototype device in the following three settings: unaided at home (twice); unaided but observed in clinic (twice); and performed by a nurse with simultaneous laboratory glucose assays of 0- and 120-min venous plasma samples (twice). The device displayed no results. A detachable data recorder returned to the clinic provided plasma-equivalent 0- and 120-min glucose values and key parameters, including test date, start and end times, and time taken to consume the glucose drink. RESULTS The device was universally popular with participants and was perceived as easy to use, and the ability to test at home was well liked. Device failures meant that 0- and 120-min glucose values were obtained for only 141 (78%) of the 180 OGTTs performed, independent of setting. Device glucose measurements showed a mean bias compared with laboratory-measured values of +0.9 at 5.0 mmol/L increasing to +4.4 at 15.0 mmol/L. Paired device glucose values were equally reproducible across settings, with repeat testing showing no training effect regardless of setting order. CONCLUSIONS Self-administered OGTTs can be performed successfully by untrained individuals in a community setting. With improved device reliability and appropriate calibration, this novel technology could be used in routine practice to screen people who might need a formal OGTT to confirm the presence of impaired glucose tolerance or diabetes. PMID:23321216

  18. Evaluation of a self-administered oral glucose tolerance test.

    PubMed

    Bethel, M Angelyn; Price, Hermione C; Sourij, Harald; White, Sarah; Coleman, Ruth L; Ring, Arne; Kennedy, Irene E C; Tucker, Lynne; Holman, Rury R

    2013-06-01

    To assess the feasibility of using a disposable, self-administered, capillary blood sampling oral glucose tolerance test (OGTT) device in a community setting. Eighteen healthy and 12 type 2 diabetic volunteers underwent six 75-g OGTTs using a prototype device in the following three settings: unaided at home (twice); unaided but observed in clinic (twice); and performed by a nurse with simultaneous laboratory glucose assays of 0- and 120-min venous plasma samples (twice). The device displayed no results. A detachable data recorder returned to the clinic provided plasma-equivalent 0- and 120-min glucose values and key parameters, including test date, start and end times, and time taken to consume the glucose drink. The device was universally popular with participants and was perceived as easy to use, and the ability to test at home was well liked. Device failures meant that 0- and 120-min glucose values were obtained for only 141 (78%) of the 180 OGTTs performed, independent of setting. Device glucose measurements showed a mean bias compared with laboratory-measured values of +0.9 at 5.0 mmol/L increasing to +4.4 at 15.0 mmol/L. Paired device glucose values were equally reproducible across settings, with repeat testing showing no training effect regardless of setting order. Self-administered OGTTs can be performed successfully by untrained individuals in a community setting. With improved device reliability and appropriate calibration, this novel technology could be used in routine practice to screen people who might need a formal OGTT to confirm the presence of impaired glucose tolerance or diabetes.

  19. Safety of florfenicol administered in feed to tilapia (Oreochromis sp.)

    USGS Publications Warehouse

    Gaikowski, Mark P.; Wolf, Jeffrey C.; Schleis, Susan M.; Tuomari, Darrell; Endris, Richard G.

    2013-01-01

    The safety of Aquaflor® (50% w/w florfenicol [FFC]) incorporated in feed then administered to tilapia for 20 days (2x the recommended duration) at 0, 15, 45, or 75 mg/kg body weight/day (0, 1, 3, or 5x the recommended dose of 15 mg FFC/kg BW/d) was investigated. Mortality, behavioral change, feed consumption, body size, and gross and microscopic lesions were determined. Estimated delivered doses were >96.9% of target. Three unscheduled mortalities occurred but were considered incidental since FFC-related findings were not identified. Feed consumption was only affected during the last 10 dosing days when the 45 and 75 mg/kg groups consumed only 62.5% and 55.3% of the feed offered, respectively. There were significant, dose-dependent reductions in body size in the FFC-dose groups relative to the controls. Treatment-related histopathological findings included increased severity of lamellar epithelial hyperplasia, increased incidence of lamellar adhesions, decreased incidence of lamellar telangiectasis in the gills, increased glycogen-type and lipid-type hepatocellular vacuolation in the liver, decreased lymphocytes, increased blast cells, and increased individual cell necrosis in the anterior kidney, and tubular epithelial degeneration and mineralization in the posterior kidney. These changes are likely to be of minimal clinical relevance, given the lack of mortality or morbidity observed. This study has shown that FFC, when administered in feed to tilapia at the recommended dose (15 mg FFC/kg BW/day) for 10 days would be well tolerated.

  20. Opponent process properties of self-administered cocaine.

    PubMed

    Ettenberg, Aaron

    2004-01-01

    Over the past decade, data collected in our laboratory have demonstrated that self-administered cocaine produces Opponent-Process-like behavioral effects. Animals running a straight alley once each day for IV cocaine develop over trials an approach-avoidance conflict about re-entering the goal box. This conflict behavior is characterized by a stop in forward locomotion (usually at the very mouth of the goal box) followed by a turn and 'retreat' back toward the goal box. The results of a series of studies conducted over the past decade collectively suggest that the behavioral ambivalence exemplified by rats running the alley for IV cocaine stems from concurrent and opponent positive (rewarding) and negative (anxiogenic) properties of the drug--both of which are associated with the goal box. These opponent properties of cocaine have been shown to result from temporally distinct affective states. Using a conditioned place preference test, we have been able to demonstrate that while the initial immediate effects of IV cocaine are reinforcing, the state present 15 min post-injection is aversive. In our most recent work, the co-administration of IV cocaine with either oral ethanol or IV heroin was found to greatly diminish the development and occurrence of retreat behaviors in the runway. It may therefore be that the high incidence of co-abuse of cocaine with either ethanol or heroin, stems from the users' motivation to alleviate some of the negative side effects of cocaine. It would seem then that the Opponent Process Theory has provided a useful conceptual framework for the study of the behavioral consequences of self-administered cocaine including the notion that both positive and negative reinforcement mechanisms are involved in the development and maintenance of cocaine abuse.

  1. Self-administered pain-relieving manoeuvres in primary headaches.

    PubMed

    Zanchin, G; Maggioni, F; Granella, F; Rossi, P; Falco, L; Manzoni, G C

    2001-09-01

    We investigated the use of self-administered pain-relieving manoeuvres on a sample of 400 patients with primary headaches--represented by an even distribution of migraine without aura (MO), migraine with aura (MA), episodic tension-type headache (TH), and cluster headache (CH)--consecutively seen at Padua and Parma Headache Centres. Manoeuvres on various regions of the head were used by 258 patients (65% of the cases). The most applied procedures were: compression (114 out of 382 manoeuvres; 30%), application of cold (27%), massage (25%) and application of heat (8%). A significant (P < 0.001) relationship was found between headache diagnoses and type of manoeuvre. In MO patients the application of cold (38% of the manoeuvres) and compression (36%), used mainly on the forehead and temples, prevailed; compression, mainly on the temples, was the most frequent procedure (44%) in MA patients. Massage on the temples and nape was the predominant manoeuvre (43%) in TH patients, whereas in the CH group, which more often required heterogeneous procedures, none of the above-mentioned manoeuvres was prevalent. Compression, as a diagnostic criterion for MO, had a sensitivity of 33% and a specificity of 86%; for the application of cold the figures were 36% and 84%, respectively. Massage had a sensitivity of 33% and a specificity of 80% for TH. The efficacy of the self-administered manoeuvres in reducing pain was scarce. Only 8% of the manoeuvres, in fact, resulted in a good or excellent pain control. Moreover, the efficacy of the manoeuvre was often momentary, wearing off when the manoeuvre stopped. In spite of this, 46% of the subjects used the manoeuvres constantly, at each attack.

  2. Validity and reliability of nutrition screening administered by nurses.

    PubMed

    Lim, Su Lin; Ang, Emily; Foo, Yet Li; Ng, Lian Ye; Tong, Chung Yan; Ferguson, Maree; Daniels, Lynne

    2013-12-01

    Nutrition screening is usually administered by nurses. However, most studies on nutrition screening tools have not used nurses to validate the tools. The 3-Minute Nutrition Screening (3-MinNS) assesses weight loss, dietary intake, and muscle wastage, with the composite score of each used to determine risk of malnutrition. The aim of the study was to determine the validity and reliability of 3-MinNS administered by nurses, who are the intended assessors. In this cross-sectional study, 3 ward-based nurses screened 121 patients aged 21 years and over using 3-MinNS in 3 wards within 24 hours of admission. A dietitian then assessed patients' nutrition status using Subjective Global Assessment within 48 hours of admission, while blinded to the results of the screening. To assess the reliability of 3-MinNS, 37 patients screened by the first nurse were rescreened by a second nurse within 24 hours, who was blinded to the results of the first nurse. The sensitivity, specificity, and best cutoff score for 3-MinNS were determined using the receiver operator characteristics curve. The best cutoff score to identify all patients at risk of malnutrition using 3-MinNS was 3, with sensitivity of 89% and specificity of 88%. This cutoff point also identified all (100%) severely malnourished patients. There was strong correlation between 3-MinNS and SGA (r = .78, P < .001). The agreement between 2 nurses conducting the 3-MinNS tool was 78.3%. The 3-MinNS is a valid and reliable tool for nurses to identify patients at risk of malnutrition.

  3. Human metabolism of orally administered radioactive cobalt chloride.

    PubMed

    Holstein, H; Ranebo, Y; Rääf, C L

    2015-05-01

    This study investigated the human gastrointestinal uptake (f1) and subsequent whole-body retention of orally administered inorganic radioactive cobalt. Of eight adult volunteers aged between 24 and 68 years, seven were given solutions of (57)Co (T1/2 = 272 d) containing a stable cobalt carrier, and six were given carrier-free (58)Co (T1/2 = 71 d). The administered activities ranged between 25 and 103 kBq. The observed mean f1, based on 6 days accumulated urinary excretion sampling and whole-body counting, was 0.028 ± 0.0048 for carrier-free (58)Co, and 0.016 ± 0.0021 for carrier-associated (57)Co. These values were in reasonable agreement with values reported from previous studies involving a single intake of inorganic cobalt. The time pattern of the total retention (including residual cobalt in the GI tract) included a short-term component with a biological half-time of 0.71 ± 0.03 d (average ± 1 standard error of the mean for the two nuclides), an intermediate component with a mean half-time of 32 ± 8.5 d, and a long-term component (observed in two volunteers) with half-times ranging from 80 to 720 d for the two isotopes. From the present data we conclude that for the short-lived (57)Co and (58)Co, more than 95% of the internal absorbed dose was delivered within 7 days following oral intake, with a high individual variation influenced by the transit time of the unabsorbed cobalt through the gastro-intestinal tract.

  4. Balanced propofol sedation administered by nonanesthesiologists: The first Italian experience

    PubMed Central

    Repici, Alessandro; Pagano, Nico; Hassan, Cesare; Carlino, Alessandra; Rando, Giacomo; Strangio, Giuseppe; Romeo, Fabio; Zullo, Angelo; Ferrara, Elisa; Vitetta, Eva; Ferreira, Daniel de Paula Pessoa; Danese, Silvio; Arosio, Massimo; Malesci, Alberto

    2011-01-01

    AIM: To assess the efficacy and safety of a balanced approach using midazolam in combination with propofol, administered by non-anesthesiologists, in a large series of diagnostic colonoscopies. METHODS: Consecutive patients undergoing diagnostic colonoscopy were sedated with a single dose of midazolam (0.05 mg/kg) and low-dose propofol (starter bolus of 0.5 mg/kg and repeated boluses of 10 to 20 mg). Induction time and deepest level of sedation, adverse and serious adverse events, as well as recovery times, were prospectively assessed. Cecal intubation and adenoma detection rates were also collected. RESULTS: Overall, 1593 eligible patients were included. The median dose of propofol administered was 70 mg (range: 40-120 mg), and the median dose of midazolam was 2.3 mg (range: 2-4 mg). Median induction time of sedation was 3 min (range: 1-4 min), and median recovery time was 23 min (range: 10-40 min). A moderate level of sedation was achieved in 1561 (98%) patients, whilst a deep sedation occurred in 32 (2%) cases. Transient oxygen desaturation requiring further oxygen supplementation occurred in 8 (0.46%; 95% CI: 0.2%-0.8%) patients. No serious adverse event was observed. Cecal intubation and adenoma detection rates were 93.5% and 23.4% (27.8% for male and 18.5% for female, subjects), respectively. CONCLUSION: A balanced sedation protocol provided a minimalization of the dose of propofol needed to target a moderate sedation for colonoscopy, resulting in a high safety profile for non-anesthesiologist propofol sedation. PMID:21987624

  5. Determination of oxytocin in milk of cows administered oxytocin.

    PubMed

    Prakash, B S; Paul, Vijay; Kliem, Heike; Kulozik, Ulrich; Meyer, Heinrich H D

    2009-03-16

    To address people's concerns of exogenous oxytocin (OT) administration to lactating bovines, a study was undertaken to (a) establish an enzyme immunoassay (EIA) for OT determination in milk, (b) quantify OT in milk of cows administered OT, and (c) study influence of pasteurization on OT stability in milk. A sensitive EIA validated according to the criteria of European Union-Decision 2002/657/EC was developed for OT in skim milk in an analytical range of 10-250pgmL(-1) with a decision limit (CCalpha) of 30pgmL(-1) and detection capability (CCbeta) of 41.5pgmL(-1). Milk samples collected from cows (n=38) administered either 25 or 50IU OT prior to milking were investigated for the presence of OT. There was no significant difference among both groups with the mean concentrations of OT being 15.8 and 14.9pgmL(-1) for cows subjected to 25 and 50IU OT administration, respectively. The OT levels in skim milk of control cows (n=30; untreated) were basal (around 10pgmL(-1)). All the analyzed milk samples were below the CCalpha value of 30pgmL(-1). Pasteurization of OT spiked milk samples at different temperature and sample holding conditions reduced the immunological activity of OT to 43% at 110 degrees C. However, no further decline occurred in the immunological activity with increased pasteurization temperature and time. It was concluded that the milk OT concentrations after OT administrations were minimal and below the assay decision limit. However, OT was quite stable to pasteurization in OT spiked milk.

  6. Efficacy and safety of intravenous fentanyl administered by ambulance personnel.

    PubMed

    Friesgaard, K D; Nikolajsen, L; Giebner, M; Rasmussen, C-H; Riddervold, I S; Kirkegaard, H; Christensen, E F

    2016-04-01

    Management of pain in the pre-hospital setting is often inadequate. In 2011, ambulance personnel were authorized to administer intravenous fentanyl in the Central Denmark Region. The aim of this study was to evaluate the efficacy and safety of intravenous fentanyl administered by ambulance personnel. Pre-hospital medical charts from 2348 adults treated with intravenous fentanyl by ambulance personnel during a 6-month period were reviewed. The primary outcome was the change in pain intensity on a numeric rating scale (NRS) from before fentanyl treatment to hospital arrival. Secondary outcomes included the number of patients with reduction in pain intensity during transport (NRS ≥ 2), the number of patients with NRS > 3 at hospital arrival, and potential fentanyl-related side effects. Fentanyl reduced pain from before treatment (8, IQR 7-9) to hospital arrival (4, IQR 3-6) (NRS reduction: 3, IQR 2-5; P = 0.001), 79.3% of all patients had a reduction in > 2 on the NRS during transport, and 58.4% of patients experienced pain at hospital arrival (NRS > 3). Twenty-one patients (0.9%) had oxygen saturation < 90%. A decrease in Glasgow Coma Scale was seen in 31 patients (1.3%) and hypotension observed in 71 patients (3.0%). Intravenous fentanyl caused clinically meaningful pain reduction in most patients and was safe in the hands of ambulance personnel. Many patients had moderate to severe pain at hospital arrival. As the protocol allowed higher doses of fentanyl, feedback on effect and safety should be part of continuous education of ambulance personnel. © 2015 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  7. Adolescent substance use screening in primary care: validity of computer self-administered vs. clinician-administered screening

    PubMed Central

    Harris, Sion Kim; Knight, John R; Van Hook, Shari; Sherritt, Lon; Brooks, Traci; Kulig, John W; Nordt, Christina; Saitz, Richard

    2015-01-01

    Background Computer self-administration may help busy pediatricians’ offices increase adolescent substance use screening rates efficiently and effectively, if proven to yield valid responses. The CRAFFT screening protocol for adolescents has demonstrated validity as an interview, but a computer self-entry approach needs validity testing. The aim of this study was to evaluate the criterion validity and time efficiency of a computerized adolescent substance use screening protocol implemented by self-administration or clinician-administration. Methods 12- to 17-year-old patients coming for routine care at three primary care clinics completed the computerized screen by both self-administration and clinician-administration during their visit. To account for order effects, we randomly assigned participants to self-administer the screen either before or after seeing their clinician. Both were conducted using a tablet computer and included identical items (any past-12-month use of tobacco, alcohol, drugs; past-3-months frequency of each; and six CRAFFT items). The criterion measure for substance use was the Timeline Follow-Back, and for alcohol/drug use disorder, the Adolescent Diagnostic Interview, both conducted by confidential research assistant-interview after the visit. Tobacco dependence risk was assessed with the self-administered Hooked on Nicotine Checklist (HONC). Analyses accounted for the multi-site cluster sampling design. Results Among 136 participants, mean age was 15.0±1.5 yrs, 54% were girls, 53% were Black or Hispanic, and 67% had ≥3 prior visits with their clinician. Twenty-seven percent reported any substance use (including tobacco) in the past 12 months, 7% met criteria for an alcohol or cannabis use disorder, and 4% were HONC-positive. Sensitivity/specificity of the screener were high for detecting past-12-month use or disorder and did not differ between computer and clinician. Mean completion time was 49 seconds (95%CI 44-54) for computer and 74

  8. Prenatally administered dexamethasone impairs folliculogenesis in spiny mouse offspring.

    PubMed

    Hułas-Stasiak, Monika; Dobrowolski, Piotr; Tomaszewska, Ewa

    2015-01-07

    This study was designed to determine whether prenatal dexamethasone treatment has an effect on follicular development and atresia in the ovary of spiny mouse (Acomys cahirinus) offspring. Dexamethasone (125µg kg-1 bodyweight per day) was administered to pregnant spiny mice from Day 20 of gestation to parturition. The processes of follicle loss were analysed using classical markers of apoptosis (terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling reaction, active caspase-3) and autophagy (Lamp1). The present study indicated that dexamethasone reduced the pool of healthy primordial follicles. Moreover, the oocytes from these follicles showed intensive caspase-3 and Lamp1 staining. Surprisingly, dexamethasone caused an increase in the number of secondary follicles; however, most of these follicles were characterised by extensive degeneration of the oocyte and caspase-3 and Lamp1 labelling. Western-blot analysis indicated that the glucocorticoid receptor as well as apoptosis and autophagy markers were more strongly expressed in the DEX-treated group than in the control. On the basis of these findings, we have concluded that dexamethasone impairs spiny mouse folliculogenesis and enhances follicular atresia through induction of autophagy or combined autophagy and apoptosis.

  9. Clinical Pharmacology of Intravenously Administered Trimethoprim-Sulfamethoxazole

    PubMed Central

    Grose, William E.; Bodey, Gerald P.; Loo, Ti Li

    1979-01-01

    Pharmacokinetic studies of intravenously administered trimethoprim-sulfamethoxazole (TMP-SMX) were conducted in 11 patients with cancer while they received therapy with this drug combination for infection. Each patient received 160 mg of TMP and 800 mg of SMX every 8 h. The highest plasma concentrations of both agents were attained at the end of a 1-h infusion period, and the levels were maintained above 38 μg of free SMX and 2 μg of TMP per ml for 2 to 4 h on day 1. On day 4, these concentrations were exceeded at all time intervals of blood sampling. High concentrations of TMP and free SMX were recovered in the urine during the 8-h period. The plasma half-lives of TMP and free SMX, as determined during the first 8-h period, were 7.6 and 8.6 h, respectively. Compared with SMX, TMP had an approximately 2.5 times higher volume of distribution. This drug combination was well tolerated by the patients and unaccompanied by drug-related toxicity. PMID:464572

  10. Effects of antitussive agents administered before bronchoalveolar lavage in horses.

    PubMed

    Westermann, Cornélie M; Laan, Tamarinde T; van Nieuwstadt, Roel A; Bull, Sarah; Fink-Gremmels, Johanna

    2005-08-01

    To determine whether treatment of horses with antitussive agents before bronchoalveolar lavage (BAL) reduces the frequency and intensity of the cough reflex during BAL. 8 healthy horses. Standard BAL was performed on each horse weekly for 6 weeks. Detomidine was used as a general sedative, and various antitussive agents were evaluated for their suitability to suppress undesirable coughing. Treatments administered prior to BAL consisted of saline (0.9% NaCl) solution (control treatment), codeine, butorphanol tartrate, glycopyrrolate, lidocaine hydrochloride (final concentration, 0.33%), and lidocaine hydrochloride at a final concentration of 0.66% (lidocaine 0.66%). Frequency and intensity of coughing were digitally recorded throughout the BAL procedure. The volume of BAL fluid collected was measured, and the fluid was cytologically examined to assess potential effects of the medications on composition. Coughing frequency was significantly reduced after intratracheal administration of lidocaine 0.66%. Moreover, intratracheal administration of lidocaine 0.66% or IV administration of butorphanol resulted in a significant reduction in the intensity of coughing episodes. All other treatments failed to significantly suppress coughing frequency and intensity, compared with results for the saline treatment. Glycopyrrolate caused obvious adverse clinical effects. Treatments did not influence the volume of BAL fluid collected nor composition of the fluid. Intratracheal administration of lidocaine (final concentration, 0.66%) proved to be the most reliable method to reduce frequency and intensity of coughing in horses during BAL.

  11. Recovery of cholinesterase activity in mallard ducklings administered organophosphorus pesticides

    USGS Publications Warehouse

    Fleming, W.J.; Bradbury, S.P.

    1981-01-01

    Oral doses of the organophosphorus pesticides acephate, dicrotophos, fensulfothion, fonofos, malathion, and parathion were administered to mallard ducklings (Anas platyrhynchos), and brain and plasma cholinesterase (ChE) activities were determined for up to 77 d after dosing. In vivo recovery of brain ChE activity to within 2 standard deviations of the mean activity of undosed birds occurred within 8 d, after being depressed an average of 25-58% at 24 h after dosing. In vivo recovery of plasma ChE appeared as fast as or faster than that of brain, but the pattern of recovery was more erratic and therefore statistical comparison with brain ChE recovery was not attempted. In vitro tests indicated that the potential for dephosphorylation to contribute to in vivo recovery of inhibited brain ChE differed among chemical treatments. Some ducklings died as a result of organophosphate dosing. In an experiment in which ducklings within each treatment group received the same dose (mg/kg), the brain ChE activity in birds that died was less than that in birds that survived. Brain ChE activities in ducklings that died were significantly different among pesticide treatments: fensulfothion > parathion> acephate > malathion (p < 0.05).

  12. Regression of oral hairy leukoplakia after orally administered acyclovir therapy.

    PubMed

    Resnick, L; Herbst, J S; Ablashi, D V; Atherton, S; Frank, B; Rosen, L; Horwitz, S N

    1988-01-15

    To define the role of Epstein-Barr virus (EBV) in the pathogenesis of oral hairy leukoplakia, 13 human immunodeficiency virus-seropositive men with clinical and histologic evidence of oral hairy leukoplakia were enrolled in an open-label trial of orally administered acyclovir therapy (3.2 g/d for 20 days). Of six patients who received therapy, five exhibited clinical regression. Once therapy was discontinued, recurrences occurred in all responders. Among seven patients who refused therapy, no spontaneous remissions occurred. Before therapy, EBV replication within the leukoplakia was demonstrated by immunofluorescence tissue staining or electron microscopy in five patients who were studied. Human papillomavirus was not detected by immunocytochemistry or electron microscopy from tissue specimens of six patients. After therapy, biopsy specimens from two patients with complete responses revealed a normalization of histologic abnormalities and an inability to detect EBV in previously involved mucosa by immunofluorescence or in situ DNA hybridization assays. It was concluded that EBV replication within the epithelial cells of the tongue is necessary for the development of oral hairy leukoplakia.

  13. Macroscopic and microscopic biodistribution of intravenously administered iron oxide nanoparticles

    NASA Astrophysics Data System (ADS)

    Misra, Adwiteeya; Petryk, Alicia A.; Strawbridge, Rendall R.; Hoopes, P. Jack

    2015-03-01

    Iron oxide nanoparticles (IONP) are being developed for use as a cancer treatment. They have demonstrated efficacy when used either as a monotherapy or in conjunction with conventional chemotherapy and radiation. The success of IONP as a therapeutic tool depends on the delivery of a safe and controlled cytotoxic thermal dose to tumor tissue following activation with an alternating magnetic field (AMF). Prior to clinical approval, knowledge of IONP toxicity, biodistribution and physiological clearance is essential. This preliminary time-course study determines the acute toxicity and biodistribution of 110 nm dextran-coated IONP (iron) in mice, 7 days post systemic, at doses of 0.4, 0.6, and 1.0 mg Fe/ g mouse bodyweight. Acute toxicity, manifested as changes in the behavior of mice, was only observed temporarily at 1.0 mg Fe/ g mouse bodyweight, the highest dose administered. Regardless of dose, mass spectrometry and histological analysis demonstrated over 3 mg Fe/g tissue in organs within the reticuloendotheilial system (i.e. liver, spleen, and lymph nodes). Other organs (brain, heart, lungs, and kidney) had less than 0.5 mg Fe/g tissue with iron predominantly confined to the organ vasculature.

  14. Antinociceptive profiles and mechanisms of orally administered coumarin in mice.

    PubMed

    Park, Soo-Hyun; Sim, Yun-Beom; Kang, Yu-Jung; Kim, Sung-Su; Kim, Chea-Ha; Kim, Su-Jin; Lim, Su-Min; Suh, Hong-Won

    2013-01-01

    In the present study, the antinociceptive profiles of coumarin were examined in ICR mice. Coumarin administered orally (from 1 to 10 mg/kg) showed an antinociceptive effect in a dose-dependent manner as measured in the acetic acid-induced writhing test. Duration of antinociceptive action of coumarin maintained at least for 60 min. But, the cumulative response time of nociceptive behaviors induced by a subcutaneous (s.c.) formalin injection, intrathecal (i.t.) substance P (0.7 µg) or glutamate (20 µg) injection was not affected by coumarin. In addition, intracerebroventricular (i.c.v.) or intrathecal (i.t.) administration with coumarin (10-40 µg) attenuated acetic acid-induced writhing response in a dose dependent manner. Intraperitoneal (i.p.) pretreatment with naloxone (an opioid receptor antagonist) attenuated antinociceptive effect induced by coumarin in the writhing test. Furthermore, i.c.v. or i.t. pretreatment with naloxone (5 µg) reversed the decreased acetic acid-induced writhing response. However, methysergide (a 5-HT serotonergic receptor antagonist) or yohimbine (an α2-adrenergic receptor antagonist) did not affect antinociception induced by coumarin in the writhing test. Our results suggest that coumarin exerts a selective antinociceptive property in the acetic acid-induced visceral-derived pain model. Furthermore, the antinociceptive effect of coumarin may be mediated by activation of central opioid receptors, but not serotonergic and adrenergic receptors.

  15. Effects of Systemically Administered Hydrocortisone on the Human Immunome.

    PubMed

    Olnes, Matthew J; Kotliarov, Yuri; Biancotto, Angélique; Cheung, Foo; Chen, Jinguo; Shi, Rongye; Zhou, Huizhi; Wang, Ena; Tsang, John S; Nussenblatt, Robert

    2016-03-14

    Corticosteroids have been used for decades to modulate inflammation therapeutically, yet there is a paucity of data on their effects in humans. We examined the changes in cellular and molecular immune system parameters, or "immunome", in healthy humans after systemic corticosteroid administration. We used multiplexed techniques to query the immunome in 20 volunteers at baseline, and after intravenous hydrocortisone (HC) administered at moderate (250 mg) and low (50 mg) doses, to provide insight into how corticosteroids exert their effects. We performed comprehensive phenotyping of 120 lymphocyte subsets by high dimensional flow cytometry, and observed a decline in circulating specific B and T cell subsets, which reached their nadir 4-8 hours after administration of HC. However, B and T cells rebounded above baseline 24 hours after HC infusion, while NK cell numbers remained stable. Whole transcriptome profiling revealed down regulation of NF-κB signaling, apoptosis, and cell death signaling transcripts that preceded lymphocyte population changes, with activation of NK cell and glucocorticoid receptor signaling transcripts. Our study is the first to systematically characterize the effects of corticosteroids on the human immunome, and we demonstrate that HC exerts differential effects on B and T lymphocytes and natural killer cells in humans.

  16. Developing a self-administered CKD symptom assessment instrument.

    PubMed

    Agarwal, Rajiv

    2010-01-01

    Current disease-centred therapies for CKD focus on preserving the GFR but often ignore patient-reported symptoms. This purpose of this report is to describe the development of an instrument to measure the presence and severity of a wide range of symptoms commonly attributable to CKD. A 37-item questionnaire was administered along with the Kidney Disease Quality of Life instrument to 92 patients with CKD not on dialysis (24% black, 5% women, mean age 68 years, 68% with diabetes mellitus). To discover groups of symptoms, agglomerative cluster analysis followed by exploratory common factor analysis was performed. Construct validity, internal reliability, convergent and discriminant validity, test-retest reliability and finally the association of various symptom domains with objective measurements such as estimated GFR and haemoglobin were tested. The top five symptoms of at least moderate severity in decreasing order of prevalence were 'tire easily', limited physical activity, nocturia, joint pain and 'stop and rest often'. Four common factors emerged that could be broadly classified into neuropsychiatric, cardiovascular, uraemia and anaemia symptoms accounting for 73% of the total variance in the sample. The coefficient alpha for each of these factors approached 0.9. The test-retest reliability in 41 patients over 8 weeks was likewise high. There was good convergent and divergent validity. However, there was little relationship between estimated GFR and symptom scores. The assessment of symptom burden among patients with CKD may be facilitated by incorporating this instrument in routine practice and clinical trials.

  17. Toxicity and biodistribution of orally administered casein nanoparticles.

    PubMed

    Gil, Ana Gloria; Irache, Juan Manuel; Peñuelas, Iván; González Navarro, Carlos Javier; López de Cerain, Adela

    2017-08-01

    In the last years, casein nanoparticles have been proposed as carriers for the oral delivery of biologically active compounds. However, till now, no information about their possible specific hazards in vivo was available. The aim of this work was to assess the safety of casein nanoparticles when administered orally to animals through a 90 days dose-repeated toxicity study (OECD guideline 408), that was performed in Wistar rats under GLP conditions. After 90 days, no evidences of significant alterations in animals treated daily with 50, 150 or 500 mg/kg bw of nanoparticles were found. This safety agrees well with the fact that nanoparticles were not absorbed and remained within the gut as observed by radiolabelling in the biodistribution study. After 28 days, there was a generalized hyperchloremia in males and females treated with the highest dose of 500 mg/kg bw, that was coupled with hypernatremia in the females. These effects were related to the presence of mannitol which was used as excipient in the formulation of casein nanoparticles. According to these results, the No Observed Adverse Effect Level (NOAEL) could be established in 150 mg/kg bw/day and the Lowest Observed Effect Level (LOEL) could be established in 500 mg/kg bw/day. Copyright © 2017. Published by Elsevier Ltd.

  18. Nicotine elicits methamphetamine-seeking in rats previously administered nicotine.

    PubMed

    Neugebauer, N M; Harrod, S B; Bardo, M T

    2010-01-01

    Research has indicated a high correlation between psychostimulant use and tobacco cigarette smoking in human substance abusers. The objective of the current study was to examine the effects of acute and repeated nicotine administration on responding for intravenous methamphetamine (0.03 mg/kg/infusion) in a rodent model of self-administration, as well as the potential of nicotine to induce reinstatement of previously extinguished drug-taking behavior in male Sprague-Dawley rats. In addition, it was assessed whether nicotine-induced reinstatement of methamphetamine-seeking behavior and nicotine-induced locomotor sensitization require that nicotine be temporally paired with the methamphetamine self-administration session or the locomotor activity chamber. Nicotine acutely decreased methamphetamine self-administration, but did not persistently alter responding during the maintenance of methamphetamine self-administration. However, following extinction of methamphetamine self-administration, nicotine administration reinstated methamphetamine-seeking behavior only in rats that had previously been administered nicotine. Nicotine-induced reinstatement and expression of locomotor sensitization were not dependent on a temporal pairing of nicotine with either the methamphetamine self-administration session or the locomotor activity chamber, respectively. These results indicate that nicotine may be acting, at least in part, through a non-associative mechanism to reinstate methamphetamine-seeking behavior. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

  19. Nicotine Elicits Methamphetamine-Seeking in Rats Previously Administered Nicotine

    PubMed Central

    Neugebauer, N. M.; Harrod, S. B.; Bardo, M. T.

    2009-01-01

    Research has indicated a high correlation between psychostimulant use and tobacco cigarette smoking in human substance abusers. The objective of the current study was to examine the effects of acute and repeated nicotine administration on responding for intravenous methamphetamine (0.03 mg/kg/infusion) in a rodent model of self-administration, as well as the potential of nicotine to induce reinstatement of previously extinguished drug-taking behavior in male Sprague-Dawley rats. In addition, it was assessed whether nicotine-induced reinstatement of methamphetamine-seeking behavior and nicotine-induced locomotor sensitization require that nicotine be temporally paired with the methamphetamine self-administration session or the locomotor activity chamber. Nicotine acutely decreased methamphetamine self-administration, but did not persistently alter responding during the maintenance of methamphetamine self-administration. However, following extinction of methamphetamine self-administration, nicotine administration reinstated methamphetamine-seeking behavior only in rats that had previously been administered nicotine. Nicotine-induced reinstatement and expression of locomotor sensitization were not dependent on a temporal pairing of nicotine with either the methamphetamine self-administration session or the locomotor activity chamber, respectively. These results indicate that nicotine may be acting, at least in part, through a non-associative mechanism to reinstate methamphetamine-seeking behavior. PMID:19733448

  20. Administering and Detecting Protein Marks on Arthropods for Dispersal Research.

    PubMed

    Hagler, James R; Machtley, Scott A

    2016-01-28

    Monitoring arthropod movement is often required to better understand associated population dynamics, dispersal patterns, host plant preferences, and other ecological interactions. Arthropods are usually tracked in nature by tagging them with a unique mark and then re-collecting them over time and space to determine their dispersal capabilities. In addition to actual physical tags, such as colored dust or paint, various types of proteins have proven very effective for marking arthropods for ecological research. Proteins can be administered internally and/or externally. The proteins can then be detected on recaptured arthropods with a protein-specific enzyme-linked immunosorbent assay (ELISA). Here we describe protocols for externally and internally tagging arthropods with protein. Two simple experimental examples are demonstrated: (1) an internal protein mark introduced to an insect by providing a protein-enriched diet and (2) an external protein mark topically applied to an insect using a medical nebulizer. We then relate a step-by-step guide of the sandwich and indirect ELISA methods used to detect protein marks on the insects. In this demonstration, various aspects of the acquisition and detection of protein markers on arthropods for mark-release-recapture, mark-capture, and self-mark-capture types of research are discussed, along with the various ways that the immunomarking procedure has been adapted to suit a wide variety of research objectives.

  1. Pregnane X receptor and natural products: beyond drug-drug interactions.

    PubMed

    Staudinger, Jeff L; Ding, Xunshan; Lichti, Kristin

    2006-12-01

    The pregnane X receptor (PXR, NR1I2) is a member of the nuclear receptor superfamily that is activated by a myriad of compounds and natural products in clinical use. Activation of PXR represents the basis for several clinically important drug-drug interactions. Although PXR activation has undesirable effects in patients on combination therapy, it also mediates the hepatoprotective effects exhibited by some herbal remedies. This review focuses on PXR activation by natural products and the potential therapeutic opportunities presented. In particular, the biological effects of St. John's Wort, gugulipid, kava kava, Coleus forskolii, Hypoxis, Sutherlandia, qing hao, wu wei zi, gan cao and other natural products are discussed. The impact of these natural products on drug metabolism and hepatoprotection is highlighted in the context of activation and antagonism of PXR.

  2. Phytomedicine research in Germany.

    PubMed Central

    Wagner, H

    1999-01-01

    In Germany since 1980, more than 300 clinical studies have been carried out with standardized phytopharmaceuticals, including Crataegus, Silybum, Ginkgo, Hypericum, Sabal, Urtica, Kava-Kava, Allium sativum, Valeriana, Aesculus, Echinacea, and Viscum drugs. These studies assessed the efficacy of phytopharmaceuticals for the treatment of moderate or moderately severe diseases and prevention. Several comparative clinical trials showed that these phytopharmaceuticals had full therapeutic equivalence with chemotherapeutics and had the simultaneous advantage of being devoid of any adverse effects. The mechanism of action of herbal drugs and their extract preparations, which differ in many respects from that of synthetic drugs or mono substances, can be characterized as a polyvalent action and interpreted as additive or, in some cases, potentiating. Currently, a rationale for the observed reversal effects and optimal effects with very low doses after a long-term application has not been developed, but is under investigation by systematic research at the molecular level. PMID:10504142

  3. Pregnane X receptor and natural products: beyond drug–drug interactions

    PubMed Central

    Staudinger, Jeff L; Ding, Xunshan; Lichti, Kristin

    2010-01-01

    The pregnane X receptor (PXR, NR1I2) is a member of the nuclear receptor superfamily that is activated by a myriad of compounds and natural products in clinical use. Activation of PXR represents the basis for several clinically important drug–drug interactions. Although PXR activation has undesirable effects in patients on combination therapy, it also mediates the hepatoprotective effects exhibited by some herbal remedies. This review focuses on PXR activation by natural products and the potential therapeutic opportunities presented. In particular, the biological effects of St. John’s Wort, gugulipid, kava kava, Coleus forskolii, Hypoxis, Sutherlandia, qing hao, wu wei zi, gan cao and other natural products are discussed. The impact of these natural products on drug metabolism and hepatoprotection is highlighted in the context of activation and antagonism of PXR. PMID:17125405

  4. 20 CFR 408.1220 - How do we pay Federally administered State recognition payments?

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... amount of a State recognition payment that SSA will administer on behalf of a State. (c) Minimum amount. SSA will not administer State recognition payments in amounts less than $1 per month. Hence...

  5. 20 CFR 408.1220 - How do we pay Federally administered State recognition payments?

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... amount of a State recognition payment that SSA will administer on behalf of a State. (c) Minimum amount. SSA will not administer State recognition payments in amounts less than $1 per month. Hence...

  6. 20 CFR 408.1220 - How do we pay Federally administered State recognition payments?

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... amount of a State recognition payment that SSA will administer on behalf of a State. (c) Minimum amount. SSA will not administer State recognition payments in amounts less than $1 per month. Hence...

  7. 40 CFR 147.1252 - EPA-administered program-Indian lands.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Mississippi... on Indian lands in the State of Mississippi is administered by EPA. This program consists of the...

  8. 40 CFR 147.1252 - EPA-administered program-Indian lands.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Mississippi... on Indian lands in the State of Mississippi is administered by EPA. This program consists of the...

  9. 40 CFR 147.1852 - EPA-administered program-Indian lands.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Oklahoma... lands in Oklahoma, except Class II wells on the lands of the Five Civilized Tribes, is administered by...

  10. 40 CFR 147.1852 - EPA-administered program-Indian lands.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Oklahoma... lands in Oklahoma, except Class II wells on the lands of the Five Civilized Tribes, is administered by...

  11. 40 CFR 147.1852 - EPA-administered program-Indian lands.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Oklahoma... lands in Oklahoma, except Class II wells on the lands of the Five Civilized Tribes, is administered by...

  12. Safety of ceftiofur sodium administered intramuscularly in horses.

    PubMed

    Mahrt, C R

    1992-11-01

    Ceftiofur sodium, a broad-spectrum cephalosporin antibiotic, was evaluated for safe use in horses. Male or female horses were allotted to groups and were given either saline solution (control), or 2.2, 6.6, or 11 mg of an aqueous solution of ceftiofur sodium/kg of body weight/d, IM, for 30 or 31 days. These dosages are expressed in terms of the ceftiofur free acid, and represent 1 to 5 times the proposed therapeutic dosage (2.2 mg/kg/d) administered for 3 times the maximal recommended duration of 10 days. Some of the horses were euthanatized and necropsied on day 31 or 32. The other horses were evaluated for an additional 30 days, and some were euthanatized and necropsied on day 60. The following types of data were collected: clinical observation; physical examination; pelleted food consumption; body weight; hematologic, serum biochemical, and urinalysis findings; organ weight; gross necropsy observations; and histopathologic findings. Ceftiofur sodium was generally well tolerated at the exaggerated doses and treatment durations used in these safety studies. Slight to mild decrease in pelleted food consumption was detected in horses given 6.6 or 11 mg of ceftiofur sodium/kg/d. Decreased food consumption began on day 2 and lasted for approximately 9 to 12 days. Generally, mild skeletal muscle irritation was detected by gross and microscopic examination of the injection sites of horses given ceftiofur sodium. Prevalence and severity of the muscle irritation tended to increase with increasing concentration of the dosing solution.(ABSTRACT TRUNCATED AT 250 WORDS)

  13. Orally administered epigallocatechin gallate attenuates light-induced photoreceptor damage.

    PubMed

    Costa, Belmira Lara da Silveira Andrade da; Fawcett, Rebecca; Li, Guang-Yu; Safa, Rukhsana; Osborne, Neville N

    2008-07-01

    EGCG, a major component of green tea, has a number of properties which includes it being a powerful antioxidant. The purpose of this investigation was to deduce whether inclusion of EGCG in the drinking water of albino rats attenuates the effect of a light insult (2200lx, for 24h) to the retina. TUNEL-positive cells were detected in the outer nuclear layer of the retina, indicating the efficacy of the light insult in inducing photoreceptor degeneration. Moreover, Ret-P1 and the mRNA for rhodopsin located at photoreceptors were also significantly reduced as well as the amplitude of both the a- and b-waves of the electroretinogram was also reduced showing that photoreceptors in particular are affected by light. An increase in protein/mRNA of GFAP located primarily to Müller cells caused by light shows that other retinal components are also influenced by the light insult. However, antigens associated with bipolar (alpha-PKC), ganglion (Thy-1) and amacrine (GABA) cells, in contrast, appeared unaffected. The light insult also caused a change in the content of various proteins (caspase-3, caspase-8, PARP, Bad, and Bcl-2) involved in apoptosis. A number of the changes to the retina caused by a light insult were significantly attenuated when EGCG was in the drinking water. The reduction of the a- and b-waves and photoreceptor specific mRNAs/protein caused by light were significantly less. In addition, EGCG attenuated the changes caused by light to certain apoptotic proteins (especially at after 2 days) but did not appear to significantly influence the light-induced up-regulation of GFAP protein/mRNA. It is concluded that orally administered EGCG blunts the detrimental effect of light to the retina of albino rats where the photoreceptors are primarily affected.

  14. Aqueous penetration of orally and topically administered moxifloxacin.

    PubMed

    Sharma, Trisha; Kamath, M Manjunath; Kamath, M Gurudutt; Nayak, Rajesh R; Bairy, K L; Musmade, Prashant B

    2015-09-01

    To assess the intraocular penetration of 0.5% moxifloxacin hydrochloride into aqueous humour after oral and topical administration. A prospective, interventional study of 42 patients scheduled to undergo cataract surgery was carried out. Out of the 42 subjects, 21 were randomly categorised into Group I and received one drop of 0.5% topical moxifloxacin four times, at 15 min intervals starting 75 min before the surgery. Another 21 subjects were categorised into Group II and all subjects in this group were administered a single tablet of 400 mg of moxifloxacin, 12 h before the surgery. Estimation of moxifloxacin in aqueous samples was carried out using high-performance liquid chromatography. Results were analysed using Student unpaired 't' test and analysis of variance. The value of p<0.05 was considered to be significant. Mean aqueous concentration of moxifloxacin attained in the oral group (n=21) was 0.504±0.30 μg/mL while that in the topical group (n=21) was 2.04±0.72 μg/mL, and this difference in levels was statistically significant (p<0.005). The levels attained by both the groups well exceeded the MIC90 (minimum inhibitory concentration of antibiotic required to inhibit growth of 90% of bacteria strains) levels for most of the organisms causing endophthalmitis. Penetration of moxifloxacin in aqueous in both the groups was not affected by gender, intraocular pressure or comorbidities significantly. However, aqueous levels were found to be higher among the younger subjects within the topical group. Moxifloxacin has an impressive spectrum of coverage and this pharmacokinetic study reinforces its potential as a prophylactic drug against intraocular infections, given the high aqueous levels post topical administration. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  15. Maternal Satisfaction with Administering Infant Interventions in the NICU

    PubMed Central

    Holditch-Davis, Diane; White-Traut, Rosemary; Levy, Janet; Williams, Kristi L.; Ryan, Donna; Vonderheid, Susan

    2015-01-01

    Objective To examine mothers’ satisfaction with administering interventions for their preterm infants and with the helpfulness of the study nurse by comparing the ATVV intervention (massage with auditory, tactile, visual, and vestibular stimulation), kangaroo care, and education about equipment needed at home. Secondarily, to explore whether mother and infant characteristics affected maternal satisfaction ratings. Design Three-group experimental design. Setting Four NICUs (two in North Carolina, two in Illinois). Participants 208 preterm infants and their mothers. Methods When the infant was no longer critically ill, mother-infant dyads were randomly assigned to ATVV, kangaroo care, or the education group, all taught by study nurses. At discharge and 2 months corrected age, mothers completed questionnaires. Results All groups were satisfied with the intervention and with nurse helpfulness, and the degree of satisfaction did not differ among them. Intervention satisfaction, but not nurse helpfulness, was related to recruitment site. Older, married, and minority mothers were less satisfied with the intervention but only at 2 months. Higher anxiety was related to lower intervention satisfaction at discharge and lower ratings of nurse helpfulness at discharge and 2 months. More depressive symptoms were related to lower nurse helpfulness ratings at 2 months. Conclusions Mothers were satisfied with providing interventions for their infants regardless of the intervention performed. Maternal satisfaction with the intervention was related to recruitment site, maternal demographic characteristics, and maternal psychological distress, especially at 2 months. Thus, nursing interventions that provide mothers with a role to play in the infant’s care during hospitalization are particularly likely to be appreciated by mothers. PMID:25803213

  16. Review of the integrity of a Self Administered Motivational Instrument.

    PubMed

    Duffy, Tim; McCaig, Marie; McGrandles, Amanda; Rimmer, Russell; Martin, Colin R

    2014-04-01

    Motivational interviewing (MI) was developed by Miller and Rollnick as an evidence-based counselling approach for use in supporting people with alcohol problems. Over the years the principles and spirit of MI have been reviewed and fine-tuned and the approach has been embraced by practitioners worldwide and across fields. Since 2001 a number of instruments have been designed to evaluate the fidelity of MI practice. For the purposes of this study, one such instrument is used to assess a self-administered motivational instrument, known as the SAMI, which takes the interviewer role. The SAMI is evaluated against the MITI 3.1.1, which is designed to assess the extent to which MI interventions perform on five global dimensions. These are evocation, collaboration, autonomy/support, direction and empathy. The SAMI was assembled based on the principles and spirit of MI, problem solving and goal-setting. The targeted behaviour changes were student learning styles and approaches to study. The SAMI was distributed, completed and submitted electronically via the university virtual learning environment. Thirty three mature students of a university which delivered online nursing programme were invited to complete the SAMI. Of these, 25 submitted completed transcripts. Transcripts of a sample of six completed SAMIs were assessed by a group of teachers and researchers with experience in the use and evaluation of MI, using five-point Likert scales to assess the SAMI on the five dimensions. Overall, an average score exceeding 4.5 was attained across the five dimensions. Conventionally, such a score is recognised as competency in MI. However, on one dimension (empathy), the rating was three. This current research confirms that global principles have been observed in the online delivery of MI using the SAMI to probe approaches to study. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. Safety of Intravitreally Administered Recombinant Erythropoietin (An AOS Thesis)

    PubMed Central

    Tsai, James C.

    2008-01-01

    Purpose This study investigated the safety and potential retinal toxicity of intravitreally administered erythropoietin (EPO) in a rodent animal model. Methods Forty-two healthy Sprague-Dawley rats were divided into one of 7 groups (N = 6 per group): control, sham injection, vehicle injection, and EPO injections of 50 ng (5 U), 100 ng (10 U), 250 ng (25 U), and 625 ng (62.5 U). Only the right eye was treated in each animal. Standard full-field dark- and light-adapted electroretinography (ERG) was obtained at 1 day prior to injection and then on postinjection days 3, 7, 14, and 21. Intraocular pressure (IOP) was measured at the conclusion of each ERG recording. Animals were sacrificed and the eyes underwent histologic examination with light microscopy and hematoxylin-eosin staining. Results Rod peak, scotopic, and photopic responses (amplitude and latency) were not statistically different in the animals receiving 50 to 100 ng EPO. In the 250-ng group, the photopic b-wave amplitude at day 21 was elevated (P <.05), whereas in the 625-ng group, the scotopic OP3 latency ratio was higher at baseline (P <.05). No significant histologic abnormalities were noted except for one animal (625-ng group) with qualitative differences in retinal layer thickness and cellular density. Conclusions Intravitreal administration of EPO (at doses up to 625 ng) does not cause adverse effects on retinal function as assessed by ERG. Moreover, single intravitreal dosing does not appear to elicit retinal neovascularization. Further investigation is warranted to assess fully the potential of this neuroprotective cytokine as a treatment for glaucoma. PMID:19277250

  18. Bioequivalence in dogs of a meloxicam formulation administered as a transmucosal oral mist with an orally administered pioneer suspension product.

    PubMed

    Lees, P; Cheng, Z; Keefe, T J; Weich, E; Bryd, J; Cedergren, R; Cozzi, E

    2013-02-01

    A mucosal mist formulation of meloxicam, administered as a spray into the mouth (test article), was compared for bioequivalence to a pioneer meloxicam suspension for oral administration (reference article). Pharmacokinetic profiles and average bioequivalence were investigated in 20 dogs. The study design comprised a two-period, two-sequence, two-treatment cross-over design, with maximum concentration (C(max)) and area under plasma concentration-time curve to last sampling time (AUC(last)) used as pivotal bioequivalence variables. Bioequivalence of the products was confirmed, based on relative ratios of geometric mean concentrations (and 90% confidence intervals within the range 0.80-1.25) for C(max) of 101.9 (97.99-106.0) and for AUC(last) of 97.24 (94.44-100.1). The initial absorption of meloxicam was more rapid for the test article, despite virtually identical C(max) values for the two products. Mean elimination half-lives were 29.6 h (test article) and 30.0 h (reference article). The meloxicam plasma concentration-time profiles were considered in relation to published data on the inhibition of the cyclooxygenase-1 (COX-1) and COX-2 isoenzymes by meloxicam.

  19. 32 CFR 37.125 - May I award or administer TIAs if I am authorized to award or administer other assistance...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 1 2010-07-01 2010-07-01 false May I award or administer TIAs if I am authorized to award or administer other assistance instruments? 37.125 Section 37.125 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE DoD GRANT AND AGREEMENT REGULATIONS...

  20. 32 CFR 37.125 - May I award or administer TIAs if I am authorized to award or administer other assistance...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 32 National Defense 1 2014-07-01 2014-07-01 false May I award or administer TIAs if I am authorized to award or administer other assistance instruments? 37.125 Section 37.125 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE DoD GRANT AND AGREEMENT REGULATIONS...