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Sample records for 28-day repeated oral

  1. Toxicological evaluation of silver nanoparticles and silver nitrate in rats following 28 days of repeated oral exposure.

    PubMed

    Qin, Guangqiu; Tang, Song; Li, Shibin; Lu, Haoliang; Wang, Yanwu; Zhao, Peng; Li, Bin; Zhang, Jiehong; Peng, Liang

    2017-02-01

    The increasing application of silver nanoparticles (AgNPs) has been raising concerns about their potential adverse effects to human and the environment. However, the knowledge on the systemic toxicity of AgNPs in mammalian systems is still limited. The present study investigated the toxicity of PVP-coated AgNPs in rats treated with repeated oral administration, and compared that with equivalent dose of AgNO3 . Specifically, one hundred male and female rats were orally administrated with particulate or ionic forms of silver (Ag) separately at doses of 0.5 and 1 mg kg(-1) body weight daily for 28 days. The results reveal no significant toxic effects of AgNPs and AgNO3 up to 1 mg kg(-1) body weight, with respect to the body weight, organ weight, food intake, and histopathological examination. Ag distribution pattern in organs of rats treated with AgNPs was similar to that of AgNO3 treated rats, showing liver and kidneys are the main target organs followed by testis and spleen. The total Ag contents in organs were significantly lower in the AgNPs treated rats than those in the AgNO3 treated rats. However, the comparisons between AgNPs and AgNO3 treatments further indicated more potent of AgNPs in biochemical and hematological parameters in rats, including red blood cell count (RBC), platelet count (PLT), white blood cell count (WBC) and aspartate transaminase (AST). Results of this study suggested that particulate Ag at least partially contributed to the observed toxicity of AgNPs, and both ionic and particulate Ag should be taken into consideration in toxicological evaluation of AgNPs. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 609-618, 2017.

  2. 28-day repeated dose oral toxicity of human copper-zinc superoxide dismutase from recombinant Pichia pastori in rats.

    PubMed

    Zhu, Liang; Tian, Ying-Juan; Zhu, Si-Ming

    2012-04-01

    Human copper/zinc superoxide dismutase from recombinant Pichia pastori (RH-Cu/Zn-SOD) was orally administered, via gavage, to Sprague-Dawley rats at 500, 1,000, and 2,000 mg/kg body weight/day for 28 days. During the 28-day period, animals were examined for evidence of toxicity; there were no deaths, and in-life physical signs were normal. On day 29, the animals were exsanguinated, examined for gross pathology, and tissues were preserved for histopathology. Although statistical differences were noted in some hematology and clinical chemistry, they were of questionable biological significance. The results of the 28-day oral administration demonstrated a lack of toxicity of RH-Cu/Zn-SOD in rats. There were no treatment-related, toxicologically relevant changes in clinical signs, growth, food consumption, hematology, clinical chemistry, organ weights, or pathology. The no observed adverse effect level was greater than 2,000 mg/kg/day for RH-Cu/Zn-SOD in rats.

  3. Correlation among the toxicity profiling (28-days repeated oral dose toxicity), toxicokinetics and tissue distribution data of ulifloxacin, the active metabolite of prulifloxacin in Wistar albino rats.

    PubMed

    Nandi, Utpal; Roy, Bikash; Das, Anjan Kumar; Pal, Tapan Kumar

    2012-09-01

    This experiment was designed to investigate correlation among 28-days repeated oral dose toxicity, toxicokinetics and tissue distribution data of ulifloxacin (active metabolite of prulifloxacin) in Wistar albino rats. Prulifloxacin was administered for 28-days in rats at 0, 100, 200, 400mg/kg/day followed by 14-days recovery period. Simultaneously different toxicokinetic parameters and tissue distributions of ulifloxacin was examined by LC-MS/MS method. Plasma levels and tissue concentrations of ulifloxacin were increased with dose-related manner. Ulifloxacin was also distributed to many tissues, and concentration in lungs nearly equivalent to the plasma concentration. Based on these results it was concluded that long-term repeated dose of prulifloxacin may produce different blood parameters abnormality, liver damage, stomach ulcer, joint damage and dysfunction of lungs in rats which relates to high tissue distribution and accumulation of ulifloxacin in these tissues. These findings help in management of prulifloxacin induced adverse effects by appropriate dose selection in clinical practice.

  4. Repeated dose 28-days oral toxicity study of Carica papaya L. leaf extract in Sprague Dawley rats.

    PubMed

    Afzan, Adlin; Abdullah, Noor Rain; Halim, Siti Zaleha; Rashid, Badrul Amini; Semail, Raja Hazlini Raja; Abdullah, Noordini; Jantan, Ibrahim; Muhammad, Hussin; Ismail, Zakiah

    2012-04-10

    Carica papaya L. leaves have been used in ethnomedicine for the treatment of fevers and cancers. Despite its benefits, very few studies on their potential toxicity have been described. The aim of the present study was to characterize the chemical composition of the leaf extract from 'Sekaki' C. papaya cultivar by UPLC-TripleTOF-ESI-MS and to investigate the sub-acute oral toxicity in Sprague Dawley rats at doses of 0.01, 0.14 and 2 g/kg by examining the general behavior, clinical signs, hematological parameters, serum biochemistry and histopathology changes. A total of twelve compounds consisting of one piperidine alkaloid, two organic acids, six malic acid derivatives, and four flavonol glycosides were characterized or tentatively identified in the C. papaya leaf extract. In the sub-acute study, the C. papaya extract did not cause mortality nor were treatment-related changes in body weight, food intake, water level, and hematological parameters observed between treatment and control groups. Some biochemical parameters such as the total protein, HDL-cholesterol, AST, ALT and ALP were elevated in a non-dose dependent manner. Histopathological examination of all organs including liver did not reveal morphological alteration. Other parameters showed non-significant differences between treatment and control groups. The present results suggest that C. papaya leaf extract at a dose up to fourteen times the levels employed in practical use in traditional medicine in Malaysia could be considered safe as a medicinal agent.

  5. A repeated 28-day oral dose toxicity study of nonylphenol in rats, based on the 'Enhanced OECD Test Guideline 407' for screening of endocrine-disrupting chemicals.

    PubMed

    Woo, Gye-Hyeong; Shibutani, Makoto; Ichiki, Tsutomu; Hamamura, Masao; Lee, Kyoung-Youl; Inoue, Kaoru; Hirose, Masao

    2007-02-01

    A 28-day repeated oral dose toxicity study of nonylphenol (NP) was performed for an international validation of the 'Enhanced OECD Test Guideline 407' paying particular attention to the sensitivity of individual endocrine-related parameters. Sprague-Dawley rats, each group consisting of ten males and ten females, were administered NP once daily by gavage at doses of 0 (control), 10, 50, or 250 mg/kg body weight. At 250 mg/kg, three females died or became moribund during the experiment. At this dose, hepatic and renal toxicity was evident in both sexes with increase of relative liver and kidney weights as well as histopathological changes, such as centrilobular liver cell hypertrophy and a variety of renal tubular lesions, and alteration of serum biochemical parameters, some of them being evident from 50 mg/kg in females (glucose and inorganic phosphates). Hematologically, development of anemia was evident at 250 mg/kg in both sexes. Regarding endocrine-related effects, increase of thyroid weight in males was detected from 50 mg/kg. At 250 mg/kg, males exhibited reduction of relative weights of the ventral prostate and seminal vesicles, and females developed irregular estrous cyclicity and vaginal mucosal hyperplasia. Although changes in serum hormone levels were detected in both sexes, magnitude of the changes was small to be regarded as a low toxicological significance. In summary, repeated oral doses of NP to rats for 28 days resulted in hepato-renal toxicity from 50 mg/kg and anemia at 250 mg/kg. Effects on the endocrine system were observed from 50 mg/kg, and assessment of weights and histopathology of endocrine-related organs and estrous cyclicity may be valid in a battery for detecting endocrine effects of NP. The no-observed-adverse-effect level of NP was estimated to be 10 mg/kg per day.

  6. Estimation of acute oral toxicity using the No Observed Adverse Effect Level (NOAEL) from the 28 day repeated dose toxicity studies in rats.

    PubMed

    Bulgheroni, Anna; Kinsner-Ovaskainen, Agnieszka; Hoffmann, Sebastian; Hartung, Thomas; Prieto, Pilar

    2009-02-01

    Acute systemic toxicity is one of the areas of particular concern due to the 2009 deadline set by the 7th Amendment of the Cosmetics Directive (76/768/EEC), which introduces a testing and marketing ban of cosmetic products with ingredients tested on animals. The scientific community is putting considerable effort into developing and validating non-animal alternatives in this area. However, it is unlikely that validated and regulatory accepted alternative methods and/or strategies will be available in March 2009. Following the initiatives undertaken in the pharmaceutical industry to waive the acute oral toxicity testing before going to clinical studies by using information from other in vivo studies, we proposed an approach to identify non-toxic compounds (LD50>2000mg/kg) using information from 28 days repeated dose toxicity studies. Taking into account the high prevalence of non-toxic substances (87%) in the New Chemicals Database, it was possible to set a NOAEL threshold of 200mg/kg that allowed the correct identification of 63% of non-toxic compounds, while <1% of harmful compounds were misclassified as non-toxic. Since repeated dose toxicity studies can be performed in vivo until 2013, the proposed approach could have an immediate impact for the testing of cosmetic ingredients.

  7. Liver and kidney damage induced by 4-aminopyridine in a repeated dose (28 days) oral toxicity study in rats: gene expression profile of hybrid cell death.

    PubMed

    Frejo, María Teresa; Del Pino, Javier; Lobo, Margarita; García, Jimena; Capo, Miguel Andrés; Díaz, María Jesús

    2014-03-03

    4-Aminopyridine (4-AP) is an orphan drug indicated for the treatment of neuromuscular disorders. There is a great controversy around the use of this drug because of its narrow safety index and because a large number of adverse effects have been reported. Moreover, it was shown to induce cell death in different cell lines, being reported mainly apoptosis and necrosis as the principal pathways of cell death mediated by blockage of K channels or the Na, K-ATPase, but until now it was not described in vivo cell death induced by 4-aminipyridine. To provide new subchronic toxicity data and specifically, evaluate if 4-AP is able to induce in vivo cell death process and the main pathways related to it, a repeated dose (28 days) oral toxicity study, at therapeutic range of doses, was conducted in rats. The anatomical pathology, the biochemical and hematological parameters were analyzed and a real-time PCR array analysis was developed with an Ingenuity Pathway Analysis (IPA). The leucocytes number, the lactate dehydrogenase (LDH) and aspartate aminotransferase (AST) enzymatic activity were increased at all dose but the erythrocytes number, the hemoglobin concentration, the alkaline phosphatase (FAL) and alanine aminotransferase (ALT) enzymatic activity were increased only at highest dose studied. However, glucose levels decreased at all doses. The biochemical results are indicative of hepatic damage. The anatomy pathology studies showed cell death only on liver and kidney, and the real-time PCR array on liver tissue expressed a gene expression profile of necrotic and apoptotic induced cell death. The present work shows for the first time in vivo cell death on liver and kidney with features of apoptosis and necrosis induced by 4-AP and the gene expression profile shows that the cell death is mediated by necrotic and apoptotic pathways that support this finding.

  8. Acute toxicity and the 28-day repeated dose study of a Siddha medicine Nuna Kadugu in rats

    PubMed Central

    2012-01-01

    Background Nuna Kadugu (NK), a Siddha medicine prepared from leaves and fruits of Morinda Pubescens, used for the treatment of various skin diseases. Though NK has been widely used for several decades, no scientific report was available on its safety. Present study was undertaken to demonstrate the oral toxicity of NK in Sprague Dawley rats. Methods Acute and 28-day repeated oral toxicity studies were performed following OECD test guidelines 423 and 407, respectively, with minor modifications. In acute oral toxicity study, NK was administered at 2000mg/kg b.wt., p.o and animals were observed for toxic signs at 0, 0.5, 1, 4, 24 h and for next 14 days. Gross pathology was performed at the end of the study. In repeated dose, the 28- day oral toxicity study, NK was administered at 300, 600 and 900 mg/kg b.wt./p.o/day. Two satellite groups (control and high dose) were also maintained to determine the delayed onset toxicity of NK. Animals were observed for mortality, morbidity, body weight changes, feed and water intake. Haematology, clinical biochemistry, electrolytes, gross pathology, relative organ weight and histopathological examination were performed. Results In acute toxicity study, no treatment related death or toxic signs were observed with NK administration. In the repeated dose study, no significant differences in body weight changes, food / water intake, haematology, clinical biochemistry and electrolytes content were observed between control and NK groups. No gross pathological findings and difference in relative organ weights were observed between control and NK treated rats. Histopathological examination revealed no abnormalities with NK treatment. Conclusion Acute study reveals that the LD50 of NK is greater than 2000mg/kg, b.wt. in fasted female rats and can be classified as Category 5. 28-day repeated oral toxicity demonstrates that the No Observed Adverse Effect Level of NK is greater than 900 mg/kg b.wt./day, p.o in rats. There were no delayed effects

  9. Evaluation of Genotoxicity and 28-day Oral Dose Toxicity on Freeze-dried Powder of Tenebrio molitor Larvae (Yellow Mealworm).

    PubMed

    Han, So-Ri; Yun, Eun-Young; Kim, Ji-Young; Hwang, Jae Sam; Jeong, Eun Ju; Moon, Kyoung-Sik

    2014-06-01

    The larval form of Tenebrio molitor (T. molitor) has been eaten in many countries and provides benefits as a new food source of protein for humans. However, no information exists regarding its safety for humans. The objective of the present study was to evaluate the genotoxicity and repeated dose oral toxicity of the freeze-dried powder of T. molitor larvae. The genotoxic potential was evaluated by a standard battery testing: bacterial reverse mutation test, in vitro chromosome aberration test, and in vivo micronucleus test. To assess the repeated dose toxicity, the powder was administered once daily by oral gavage to Sprague-Dawley (SD) rats at dose levels of 0, 300, 1000 and 3000 mg/kg/day for 28 days. The parameters which were applied to the study were mortality, clinical signs, body and organ weights, food consumption, ophthalmology, urinalysis, hematology, serum chemistry, gross findings and histopathologic examination. The freezedried powder of T. molitor larvae was not mutagenic or clastogenic based on results of in vitro and in vivo genotoxicity assays. Furthermore, no treatment-related changes or findings were observed in any parameters in rats after 28 days oral administration. In conclusion, the freeze-dried powder of T. molitor larvae was considered to be non-genotoxic and the NOAEL (No Observed Adverse Effect Level) was determined to be 3000 mg/kg/day in both sexes of SD rats under our experimental conditions.

  10. Evaluation of Genotoxicity and 28-day Oral Dose Toxicity on Freeze-dried Powder of Tenebrio molitor Larvae (Yellow Mealworm)

    PubMed Central

    Han, So-Ri; Yun, Eun-Young; Kim, Ji-Young; Hwang, Jae Sam; Jeong, Eun Ju

    2014-01-01

    The larval form of Tenebrio molitor (T. molitor) has been eaten in many countries and provides benefits as a new food source of protein for humans. However, no information exists regarding its safety for humans. The objective of the present study was to evaluate the genotoxicity and repeated dose oral toxicity of the freeze-dried powder of T. molitor larvae. The genotoxic potential was evaluated by a standard battery testing: bacterial reverse mutation test, in vitro chromosome aberration test, and in vivo micronucleus test. To assess the repeated dose toxicity, the powder was administered once daily by oral gavage to Sprague-Dawley (SD) rats at dose levels of 0, 300, 1000 and 3000 mg/kg/day for 28 days. The parameters which were applied to the study were mortality, clinical signs, body and organ weights, food consumption, ophthalmology, urinalysis, hematology, serum chemistry, gross findings and histopathologic examination. The freezedried powder of T. molitor larvae was not mutagenic or clastogenic based on results of in vitro and in vivo genotoxicity assays. Furthermore, no treatment-related changes or findings were observed in any parameters in rats after 28 days oral administration. In conclusion, the freeze-dried powder of T. molitor larvae was considered to be non-genotoxic and the NOAEL (No Observed Adverse Effect Level) was determined to be 3000 mg/kg/day in both sexes of SD rats under our experimental conditions. PMID:25071922

  11. 28-Day repeated dose toxicity study of dried microorganism in rats.

    PubMed

    Kitano, M; Hosoe, K; Fukutomi, N; Hidaka, T; Imai, N; Kawabe, M

    2004-11-01

    Ubidecarenone, also known as CoQ(10), is currently sold as a dietary supplement in the United States, with a majority of these products derived from the fermentation of carbohydrates or tobacco leaf extracts. In addition to its availability in dietary supplements, CoQ(10) is now being considered for use in foods. Accordingly, as part of the process for attaining "Generally Recognized as Safe" status, and to supplement information already available regarding the safety of CoQ(10) per se, a 28-day oral toxicity study in rats was conducted to evaluate the subacute safety of a microorganism biomass used as a new source in CoQ(10) production. Groups of Crj:CD(SD) rats (SPF) (6 males or females per group, 4 groups per sex) received dried microorganism at doses of 0, 500, 1000 or 2000 mg/kg/day via intragastric intubation. Clinical observations were recorded, and body weight, and food and water consumptions measured throughout the study. At the end of the study, aortic blood samples were collected from all animals for analysis of hematological and clinical chemistry parameters, and gross pathologic examination was performed. Histopathologic examination was performed on select tissues from the control and high-dose groups. There were no treatment-related changes that were considered to be of toxicological significance. Since rats treated with 2000 mg/kg of dried microorganism did not demonstrate any treatment-related changes, the no-observable-adverse-effect level (NOAEL) for dried microorganism was estimated to be greater than 2000 mg/kg/day under the present study conditions.

  12. Oral 28-day and developmental toxicity studies of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate

    PubMed Central

    Clarke, Kieran; Tchabanenko, Kirill; Pawlosky, Robert; Carter, Emma; Knight, Nicholas S.; Murray, Andrew J.; Cochlin, Lowri E.; King, M. Todd; Wong, Andrea W.; Roberts, Ashley; Robertson, Jeremy; Veech, Richard L.

    2013-01-01

    (R)-3-Hydroxybutyl (R)-3-hydroxybutyrate (ketone monoester) has been developed as an oral source of ketones, which may be utilized for energy. In a 28-day toxicity study, Crl:WI (Wistar) rats received diets containing, as 30% of the calories, ketone monoester (12 and 15 g/kg body weight/day for male and female rats, respectively). Control groups received either carbohydrate- or fat-based diets. Rats in the test group consumed less feed and gained less weight than control animals; similar findings have been documented in studies of ketogenic diets. Between-group differences were noted in selected hematology, coagulation, and serum chemistry parameters; however, values were within normal physiological ranges and/or were not accompanied by other changes indicative of toxicity. Upon gross and microscopic evaluation, there were no findings associated with the ketone monoester. In a developmental toxicity study, pregnant Crl:WI (Han) rats were administered 2 g/kg body weight/day ketone monoester or water (control) via gavage on days 6 through 20 of gestation. No Caesarean-sectioning or litter parameters were affected by the test article. The overall incidence of fetal alterations was higher in the test group; however, there were no specific alterations attributable to the test substance. The results of these studies support the safety of ketone monoester. PMID:22504461

  13. Evaluation of in vivo genotoxicity by thioacetamide in a 28-day repeated-dose liver micronucleus assay using male young adult rats.

    PubMed

    Sui, Hajime; Matsumoto, Hirotaka; Wako, Yumi; Kawasako, Kazufumi

    2015-03-01

    The repeated-dose liver micronucleus (RDLMN) assay has the potential to detect liver carcinogens and can be integrated into general toxicological studies. In this study, thioacetamide (TAA) was tested in 14- and 28-day RDLMN assays to assess the performance of the assay. The test substance, TAA, was administered orally to 6-week-old male Crl:CD (SD) rats once daily for 14 or 28 days at a dosage of 5, 10 or 20mg/kg/day. Hepatocytes were collected approximately 24h after the last TAA administration, and the incidence of micronuclei was assessed. In this study, bone marrow micronucleus assays were also conducted in the same animals. The 14- and 28-day RDLMN assays indicated that none of the TAA dosages significantly increased the proportion of micronucleated hepatocytes. Bone marrow micronucleus assays with TAA also provided negative results. It is known that TAA is a liver carcinogen in mice and rats. In the previous genotoxic studies, the Ames test and the chromosomal aberration test using CHL/IU cells have yielded negative results [1-4]. The liver micronucleus assay using young adult rats singly dosed with TAA (75 and 150mg/kg) also produced negative results [5]. TAA gave positive results only in the mouse bone marrow micronucleus assays [6,7].

  14. 28-day repeated dose response study of diglycolic acid: Renal and hepatic effects.

    PubMed

    Sprando, Robert L; Mossoba, Miriam E; Black, Thomas; Keltner, Zachary; Vohra, Sanah; Olejnik, Nicholas; Toomer, Howard; Stine, Cynthia; Evans, Eric; Sprando, Jessica L; Ferguson, Martine

    2017-03-25

    The acute oral toxicity of diglycolic acid (DGA) was evaluated. Groups of female rats (n = 8 rats/group) received 28 consecutive daily single doses of 0.3, 1.0, 3.0, 10.0, 30.0, 100.0 or 300.0 mg DGA/kg body weight by gastric intubation. One group of animals served as vehicle control. Tissues and blood serum were collected at necropsy on day 29. Select organs were weighed and fixed in formalin for histopathological analysis. Animals from the 300 mg/kg bw dose group were removed from the study after 5 consecutive days of treatment as a consequence of adverse treatment related effects. The animals in the remaining treatment groups survived the exposure period. No adverse clinical signs were observed throughout the exposure period in the surviving animals. No significant differences from controls were observed for feed and fluid consumption or body weight gain in the surviving animals. Lesions were observed in the kidneys, liver, stomach, intestine, thymus, spleen and bone marrow in animals from the 300 mg/kg dose group and signs of renal tubular regeneration were observed only in the 100 mg/kg dose group. These results suggest that high levels of pure DGA would need to be consumed before renal and other forms of organ toxicity are observed.

  15. Repeated dose (28-day) administration of silver nanoparticles of varied size and coating does not significantly alter the indigenous murine gut microbiome.

    PubMed

    Wilding, Laura A; Bassis, Christine M; Walacavage, Kim; Hashway, Sara; Leroueil, Pascale R; Morishita, Masako; Maynard, Andrew D; Philbert, Martin A; Bergin, Ingrid L

    2016-01-01

    Silver nanoparticles (AgNPs) have been used as antimicrobials in a number of applications, including topical wound dressings and coatings for consumer products and biomedical devices. Ingestion is a relevant route of exposure for AgNPs, whether occurring unintentionally via Ag dissolution from consumer products, or intentionally from dietary supplements. AgNP have also been proposed as substitutes for antibiotics in animal feeds. While oral antibiotics are known to have significant effects on gut bacteria, the antimicrobial effects of ingested AgNPs on the indigenous microbiome or on gut pathogens are unknown. In addition, AgNP size and coating have been postulated as significantly influential towards their biochemical properties and the influence of these properties on antimicrobial efficacy is unknown. We evaluated murine gut microbial communities using culture-independent sequencing of 16S rRNA gene fragments following 28 days of repeated oral dosing of well-characterized AgNPs of two different sizes (20 and 110 nm) and coatings (PVP and Citrate). Irrespective of size or coating, oral administration of AgNPs at 10 mg/kg body weight/day did not alter the membership, structure or diversity of the murine gut microbiome. Thus, in contrast to effects of broad-spectrum antibiotics, repeat dosing of AgNP, at doses equivalent to 2000 times the oral reference dose and 100-400 times the effective in vitro anti-microbial concentration, does not affect the indigenous murine gut microbiome.

  16. Phenolic acid protects of renal damage induced by ochratoxin A in a 28-days-oral treatment in rats.

    PubMed

    Cariddi, L N; Escobar, F M; Sabini, M C; Campra, N A; Bagnis, G; Decote-Ricardo, D; Freire-de-Lima, C G; Mañas, F; Sabini, L I; Dalcero, A M

    2016-04-01

    The present study aimed to characterize the chlorogenic acid (ChlA) capacity to reverse the toxic effects induced by ochratoxin A (OTA) in a subacute toxicity test in rats. Male Wistar rats were fed orally by gavage for 28 days with OTA (0.4mg/kg bw/day), ChlA (5mg/kg bw/day) or the combination OTA (0.4mg/kg bw/day)+ChlA (5mg/kg bw/day). No deaths, no decrease in feed intake or body weight in any experimental group were recorded. The negative control group and the animals treated with ChlA alone showed no changes in any parameters evaluated. In OTA-treated group significant changes such as decrease in urine volume, proteinuria, occult blood, increase in serum creatinine values; decrease in absolute and relative kidney weight and characteristics histopathological lesions that indicated kidney damage were observed. However, limited effect on oxidative stress parameters were detected in kidneys of OTA-treated group. Animals treated with the combination OTA+ChlA were showed as negative control group in the evaluation of several parameters of toxicity. In conclusion, ChlA, at given concentration, improved biochemical parameters altered in urine and serum and pathological damages in kidneys induced by OTA exposure, showing a good protective activity, but not by an apparent antioxidant mechanism.

  17. Acute and 28-Day Subchronic Oral Toxicity of an Ethanol Extract of Zingiber zerumbet (L.) Smith in Rodents

    PubMed Central

    Chang, Chia Ju; Tzeng, Thing-Fong; Liou, Shorong-Shii; Chang, Yuan-Shiun; Liu, I-Min

    2012-01-01

    The objective of this study was to evaluate the acute and subacute toxicity (28 days) of the ethanol extract of Z. zerumbet rhizomes (EEZZ) via the oral route in Wistar rats of both sexes. In the acute toxicity study, Wistar rats were administered a single dose of 15 g kg−1 of body weight by gavage, and were monitored for 14 days. EEZZ did not produce any toxic signs or deaths; the 50% lethal dose must be higher than 15 g kg−1. In the subchronic toxicity study, EEZZ was administered by gavage at doses of 1000, 2000 and 3000 mg/kg daily for 4 weeks to Wistar rats. The subacute treatment with EEZZ did not alter either the body weight gain or the food and water consumption. The hematological and biochemical analysis did not show significant differences in any of the parameters examined in female or male groups. Necropsy and histopathological examination, did not reveal any remarkable and treatment related changes. A no-observed adverse-effect level for EEZZ is 3000 mg kg−1 for rats under the conditions of this study. Hence, consumption of EEZZ for various medicinal purposes is safe. PMID:22536288

  18. 40 CFR 799.9305 - TSCA Repeated dose 28-day oral toxicity study in rodents.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... indication of immunological effects and reproductive organ toxicity. (c) Definitions. The definitions in...—(1) Number and sex of animals. At least 10 animals (five female and five male) should be used at each... should be carefully recorded, preferably using scoring systems, explicitly defined by the...

  19. 40 CFR 799.9305 - TSCA Repeated dose 28-day oral toxicity study in rodents.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... indication of immunological effects and reproductive organ toxicity. (c) Definitions. The definitions in...—(1)Number and sex of animals. At least 10 animals (five female and five male) should be used at each... should be carefully recorded, preferably using scoring systems, explicitly defined by the...

  20. 40 CFR 799.9305 - TSCA Repeated dose 28-day oral toxicity study in rodents.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... indication of immunological effects and reproductive organ toxicity. (c) Definitions. The definitions in...—(1) Number and sex of animals. At least 10 animals (five female and five male) should be used at each... should be carefully recorded, preferably using scoring systems, explicitly defined by the...

  1. 40 CFR 799.9305 - TSCA Repeated dose 28-day oral toxicity study in rodents.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... indication of immunological effects and reproductive organ toxicity. (c) Definitions. The definitions in...—(1)Number and sex of animals. At least 10 animals (five female and five male) should be used at each... should be carefully recorded, preferably using scoring systems, explicitly defined by the...

  2. 40 CFR 799.9305 - TSCA Repeated dose 28-day oral toxicity study in rodents.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... indication of immunological effects and reproductive organ toxicity. (c) Definitions. The definitions in...—(1)Number and sex of animals. At least 10 animals (five female and five male) should be used at each... should be carefully recorded, preferably using scoring systems, explicitly defined by the...

  3. A 28-day repeated dose toxicity study of ultraviolet absorber 2-(2'-hydroxy-3',5'-di-tert-butylphenyl) benzotriazole in rats.

    PubMed

    Hirata-Koizumi, Mutsuko; Watari, Nobuaki; Mukai, Daisuke; Imai, Toshio; Hirose, Akihiko; Kamata, Eiichi; Ema, Makoto

    2007-01-01

    To examine the possible repeated-dose toxicity of an ultraviolet absorber, 2-(2'-hydroxy-3',5'-di-tert-butylphenyl)benzotriazole (HDBB), CD(SD)IGS rats were administered HDBB by gavage at a dose of 0 (vehicle: corn oil), 0.5, 2.5, 12.5, or 62.5 mg kg(-1) day(-1) for 28 days. At the completion of the administration period, a decrease in red blood cells, hemoglobin, and hematocrit was noted only in males at 2.5 mg/kg and more. Blood biochemical changes were noted at 0.5 mg/kg and more in males and at 62.5 mg/kg in females. Histopathologic changes were observed principally in the liver (vacuolar degeneration and hypertrophy of hepatocytes, bile duct proliferation, etc.) and in the heart (degeneration and hypertrophy of myocardium and cell infiltration). These changes were noted at 0.5 mg/kg and more in males and at 12.5 mg/kg and more in females. At higher doses, hypertrophy of tubular epithelium in the kidneys and diffuse follicular cell hyperplasia in the thyroids in both sexes and increased severity of basophilic tubules in the kidneys and extramedullary hematopoiesis in the spleen in males were also detected. After the 14-day recovery period, these changes mostly recovered in females but not in males. Based on these findings, no observed adverse effect level (NOAEL) was concluded to be less than 0.5 mg kg(-1) day(-1) in male rats and 2.5 mg kg(-1) day(-1) in female rats.

  4. 17alpha-methyltestosterone: 28-day oral toxicity study in the rat based on the "Enhanced OECD Test Guideline 407" to detect endocrine effects.

    PubMed

    Wason, Sheila; Pohlmeyer-Esch, Gabriele; Pallen, Catherine; Palazzi, Xavier; Espuña, Gemma; Bars, Remi

    2003-11-05

    A 28-day oral gavage toxicity study in the rat with 17alpha-methyltestosterone was conducted as part of the international validation exercise on the modified Enhanced OECD Test Guideline 407 (Organisation for Economic Co-operation and Development, Paris). Special emphasis was placed on the endocrine mediated effects exerted by 17alpha-methyltestosterone, a potent androgen agonist. The test compound was administered daily by oral gavage for at least 28 days to groups of 7-week-old-Wistar rats. Dose levels were 0, 10, 40 and 200 mg/kg body weight per day for males and 0, 10, 100 and 600 mg/kg body weight per day for females. In addition, and outside the remit of the enhanced protocol, testosterone levels in males, oestradiol levels in females and luteinizing hormone (LH) levels in both sexes were measured, to provide a broader profile on the hormonally mediated effects of 17alpha-methyltestosterone. Furthermore, stage-specific quantification of Terminal deoxynucleotidyl transferase-mediated dUTP Nick-End Labeling (TUNEL)-labeled germ cells (apoptotic germ cells) in the seminiferous tubules was also performed, in an effort to demonstrate the precise stages in the spermatogenic cycle 17alpha-methyltestosterone exerts its effect. In this study, the most critical additional parameters contained in the Enhanced OECD Test Guideline 407 for the detection of endocrine disruption were considered to be the histopathological assessment and organ weight data of endocrine-related tissues. Beyond the scope of this validation exercise, an increase in apoptosis in specific germ cell types was detected using the TUNEL assay in male rats treated at 200 and 40 mg/kg.

  5. Effects of SiO₂, ZrO₂, and BaSO₄ nanomaterials with or without surface functionalization upon 28-day oral exposure to rats.

    PubMed

    Buesen, Roland; Landsiedel, Robert; Sauer, Ursula G; Wohlleben, Wendel; Groeters, Sibylle; Strauss, Volker; Kamp, Hennicke; van Ravenzwaay, Bennard

    2014-10-01

    The effects of seven nanomaterials (four amorphous silicon dioxides with or without surface functionalization, two surface-functionalized zirconium dioxides, and barium sulfate) upon 28-day oral exposure to male or female rats were investigated. The studies were performed as limit tests in accordance with OECD Test Guideline 407 applying 1,000 mg test substance/kg body weight/day. Additionally, the acute phase proteins haptoglobin and α2-macroglobulin as well as cardiac troponin I were determined, and metabolome analysis was performed in plasma samples. There were no test substance-related adverse effects for any of the seven nanomaterials. Moreover, metabolomics changes were below the threshold of effects. Since test substance organ burden was not analyzed, it was not possible to establish whether the lack of findings related to the absence of systemic exposure of the tested nanomaterials or if the substances are devoid of any potential for toxicity. The few published subacute oral or short-term inhalation studies investigating comparable nanomaterials (SiO₂, ZrO₂, and BaSO₄) also do not report the occurrence of pronounced treatment-related findings. Overall, the results of the present survey provide a first indication that the tested nanomaterials neither cause local nor systemic effects upon subacute oral administration under the selected experimental conditions. Further investigations should aim at elucidating the extent of gastrointestinal absorption of surface-functionalized nanomaterials.

  6. Cuprizone decreases intermediate and late-stage progenitor cells in hippocampal neurogenesis of rats in a framework of 28-day oral dose toxicity study

    SciTech Connect

    Abe, Hajime; Tanaka, Takeshi; Kimura, Masayuki; Mizukami, Sayaka; Saito, Fumiyo; Imatanaka, Nobuya; Akahori, Yumi; Yoshida, Toshinori; Shibutani, Makoto

    2015-09-15

    Developmental exposure to cuprizone (CPZ), a demyelinating agent, impairs intermediate-stage neurogenesis in the hippocampal dentate gyrus of rat offspring. To investigate the possibility of alterations in adult neurogenesis following postpubertal exposure to CPZ in a framework of general toxicity studies, CPZ was orally administered to 5-week-old male rats at 0, 120, or 600 mg/kg body weight/day for 28 days. In the subgranular zone (SGZ), 600 mg/kg CPZ increased the number of cleaved caspase-3{sup +} apoptotic cells. At ≥ 120 mg/kg, the number of SGZ cells immunoreactive for TBR2, doublecortin, or PCNA was decreased, while that for SOX2 was increased. In the granule cell layer, CPZ at ≥ 120 mg/kg decreased the number of postmitotic granule cells immunoreactive for NEUN, CHRNA7, ARC or FOS. In the dentate hilus, CPZ at ≥ 120 mg/kg decreased phosphorylated TRKB{sup +} interneurons, although the number of reelin{sup +} interneurons was unchanged. At 600 mg/kg, mRNA levels of Bdnf and Chrna7 were decreased, while those of Casp4, Casp12 and Trib3 were increased in the dentate gyrus. These data suggest that CPZ in a scheme of 28-day toxicity study causes endoplasmic reticulum stress-mediated apoptosis of granule cell lineages, resulting in aberrations of intermediate neurogenesis and late-stage neurogenesis and following suppression of immediate early gene-mediated neuronal plasticity. Suppression of BDNF signals to interneurons caused by decreased cholinergic signaling may play a role in these effects of CPZ. The effects of postpubertal CPZ on neurogenesis were similar to those observed with developmental exposure, except for the lack of reelin response, which may contribute to a greater decrease in SGZ cells. - Highlights: • Effect of 28-day CPZ exposure on hippocampal neurogenesis was examined in rats. • CPZ suppressed intermediate neurogenesis and late-stage neurogenesis in the dentate gyrus. • CPZ suppressed BDNF signals to interneurons by decrease of

  7. Cuprizone decreases intermediate and late-stage progenitor cells in hippocampal neurogenesis of rats in a framework of 28-day oral dose toxicity study.

    PubMed

    Abe, Hajime; Tanaka, Takeshi; Kimura, Masayuki; Mizukami, Sayaka; Saito, Fumiyo; Imatanaka, Nobuya; Akahori, Yumi; Yoshida, Toshinori; Shibutani, Makoto

    2015-09-15

    Developmental exposure to cuprizone (CPZ), a demyelinating agent, impairs intermediate-stage neurogenesis in the hippocampal dentate gyrus of rat offspring. To investigate the possibility of alterations in adult neurogenesis following postpubertal exposure to CPZ in a framework of general toxicity studies, CPZ was orally administered to 5-week-old male rats at 0, 120, or 600mg/kg body weight/day for 28days. In the subgranular zone (SGZ), 600mg/kg CPZ increased the number of cleaved caspase-3(+) apoptotic cells. At ≥120mg/kg, the number of SGZ cells immunoreactive for TBR2, doublecortin, or PCNA was decreased, while that for SOX2 was increased. In the granule cell layer, CPZ at ≥120mg/kg decreased the number of postmitotic granule cells immunoreactive for NEUN, CHRNA7, ARC or FOS. In the dentate hilus, CPZ at ≥120mg/kg decreased phosphorylated TRKB(+) interneurons, although the number of reelin(+) interneurons was unchanged. At 600mg/kg, mRNA levels of Bdnf and Chrna7 were decreased, while those of Casp4, Casp12 and Trib3 were increased in the dentate gyrus. These data suggest that CPZ in a scheme of 28-day toxicity study causes endoplasmic reticulum stress-mediated apoptosis of granule cell lineages, resulting in aberrations of intermediate neurogenesis and late-stage neurogenesis and following suppression of immediate early gene-mediated neuronal plasticity. Suppression of BDNF signals to interneurons caused by decreased cholinergic signaling may play a role in these effects of CPZ. The effects of postpubertal CPZ on neurogenesis were similar to those observed with developmental exposure, except for the lack of reelin response, which may contribute to a greater decrease in SGZ cells.

  8. A 28-day oral toxicity evaluation of small interfering RNAs and a long double-stranded RNA targeting vacuolar ATPase in mice.

    PubMed

    Petrick, Jay S; Moore, William M; Heydens, William F; Koch, Michael S; Sherman, James H; Lemke, Shawna L

    2015-02-01

    New biotechnology-derived crop traits have been developed utilizing the natural process of RNA interference (RNAi). However, plant-produced double stranded RNAs (dsRNAs) are not known to present a hazard to mammals because numerous biological barriers limit uptake and potential for activity. To evaluate this experimentally, dsRNA sequences matching the mouse vATPase gene (an established target for control of corn rootworms) were evaluated in a 28-day toxicity study with mice. Test groups were orally gavaged with escalating doses of either a pool of four 21-mer vATPase small interfering RNAs (siRNAs) or a 218-base pair vATPase dsRNA. There were no treatment-related effects on body weight, food consumption, clinical observations, clinical chemistry, hematology, gross pathology, or histopathology endpoints. The highest dose levels tested were considered to be the no observed adverse effect levels (NOAELs) for the 21-mer siRNAs (48 mg/kg/day) and the 218 bp dsRNA (64 mg/kg/day). As an additional exploratory endpoint, vATPase gene expression, was evaluated in selected gastrointestinal tract and systemic tissues. The results of this assay did not indicate treatment-related suppression of vATPase. The results of this study indicate that orally ingested dsRNAs, even those targeting a gene in the test species, do not produce adverse health effects in mammals.

  9. A 28-day repeat dose toxicity study of steroidal glycoalkaloids, alpha-solanine and alpha-chaconine in the Syrian Golden hamster.

    PubMed

    Langkilde, Søren; Mandimika, Tafadzwa; Schrøder, Malene; Meyer, Otto; Slob, Wout; Peijnenburg, Ad; Poulsen, Morten

    2009-06-01

    Glycoalkaloids alpha-solanine and alpha-chaconine are naturally present toxicants in the potato plant (Solanumtuberosum). Human intake of high doses of glycoalkaloids has led to acute intoxication, in severe cases coma and death. Previous studies have indicated that the ratio of alpha-solanine to alpha-chaconine may determine the degree and nature of the glycoalkaloid toxicity in potatoes, as the toxicity of the two alkaloids act synergistically. The aim of the present study was to investigate whether an altered ratio of alpha-solanine and alpha-chaconine would reduce the toxicity of the glycoalkaloids. The Syrian Golden hamster was given daily doses of alpha-solanine and alpha-chaconine by gavage for 28 days. Doses of up to 33.3 mg total glycoalkaloids/kg body weight were applied in ratios of 1:3.7 and 1:70 (alpha-solanine:alpha-chaconine). Administration of the highest doses of both ratios resulted in distended and fluid filled small intestines and stomach. Animals receiving the ratio with the reduced content of alpha-solanine were less affected compared to those receiving the other ratio. Gene expression profiling experiments were conducted using RNA from epithelial scrapings from the small intestines of the hamsters administered the highest doses of the glycoalkaloid treatments. In general, more differential gene expression was observed in the epithelial scrapings of the hamsters fed the ratio of 1:3.7. Mostly, pathways involved in lipid and energy metabolism were affected by the ratio of 1:3.7.

  10. 28-day oral safety evaluation of extracellular polysaccharopeptides produced in submerged culture from the turkey tail medicinal mushroom Trametes versicolor (L.:Fr.) Pilát LH-1 in mice.

    PubMed

    Lai, Chun-Hong; Teng, Ju-Fang; Hsu, Tai-Hao; Lin, Fang-Yi; Yang, Po-Wen; Lo, Hui-chen

    2011-01-01

    Turkey tail medicinal mushroom, Trametes versicolor (TV), is a species with a variety of pharmacological activities. Its intracellular polysaccharopeptides are widely commercialized. Recently, we found a novel TV strain LH-1 in Taiwan and demonstrated that the extracellular polysaccharopeptide (ePSP) of LH-1 obtained from submerged culture exhibits significant immunomodulatory activity. In this in vivo study, we further evaluated the safety of orally administered LH-1 ePSP using both male and female ICR mice. The LH-1 ePSP was orally administered to mice at levels of 0 (water), 100 (low dose), 500 (medium dose), or 1000 mg/kg/day (high dose) for 28 days. Clinical observations, growth, food consumption, histopathological examination, and clinical biochemical analyses revealed no adverse effects of LH-1 ePSP in mice. There were no significant differences in the results of target organ weights, hematological analyses, and urinalysis examination among groups. However, male mice that ingested high doses of LH-1 ePSP tended to have decreased lung weights and platelet numbers. In conclusion, the results of the present study suggested that oral administration of LH-1 ePSP for 28 days is accompanied by no obvious signs of toxicity. The lack of toxicity supports the potential use of LH-1 ePSP as a food or dietary supplement.

  11. Safety profile and gender specific differences of a methanol extract of Eriosema laurentii (Leguminosae) in acute and subchronic (28 days) oral toxicity studies in Wistar rats.

    PubMed

    Ateba, Sylvin Benjamin; Simo, Rudy Valdès; Mbanya, Jean Claude; Krenn, Liselotte; Njamen, Dieudonné

    2014-03-01

    Despite widespread use of Eriosema laurentii De Wild (Leguminosae) in West and Central Africa as herbal medicine and food additive the toxicity of this plant is unknown. Therefore, we performed the safety evaluation of a methanol extract (AEL). In acute toxicity, single oral administration of 2000mg/kg AEL caused neither toxicological symptoms nor mortality and the LD50 was estimated >5000mg/kg. In the subchronic oral toxicity, AEL induced no phenotypical signs of toxicity during and after treatment. Only a delayed decrease of relative spleen weight in males at the highest dose of 400mg/kg occurred. High density lipoprotein (HDL) increased significantly in females at 200 and 400mg/kg. Non-persistent increases in alanine aminotransferase activity within normal ranges were noted at 200mg/kg in males and at all doses in females. In males, AEL induced a decrease of white blood cell count at 400mg/kg, whereas lymphocytes increased at 200 and 400mg/kg and granulocytes at 400mg/kg. In females, no differences in haematological parameters occurred. Neither differences in bilirubin, creatinine and total protein levels were observed nor histological alterations in organs. The results indicate a broad safety margin for AEL.

  12. A 28-day oral gavage toxicity study of 3-monochloropropane-1,2-diol (3-MCPD) in CB6F1-non-Tg rasH2 mice.

    PubMed

    Lee, Byoung-Seok; Park, Sang-Jin; Kim, Yong-Bum; Han, Ji-Seok; Jeong, Eun-Ju; Moon, Kyoung-Sik; Son, Hwa-Young

    2015-12-01

    3-Monochloro-1,2-propanediol (3-MCPD) is a well-known contaminant of foods containing hydrolyzed vegetable protein. However, limited toxicity data are available for the risk assessment of 3-MCPD and its carcinogenic potential is controversial. To evaluate the potential toxicity and determine the dose levels for a 26-week carcinogenicity test using Tg rasH2 mice, 3-MCPD was administered once daily by oral gavage at doses of 0, 25, 50, and 100 mg/kg body weight (b.w.)/day for 28 days to male and female CB6F1-non-Tg rasH2 mice (N = 5 males and females per dose). The standard toxicological evaluations were conducted during the in-life and post-mortem phase. In the 100 mg/kg b.w./day group, 3 males and 1 female died during the study and showed clinical signs such as thin appearance and subdued behavior accompanied by significant decreases in mean b.w. Microscopy revealed tubular basophilia in the kidneys, exfoliated degenerative germ cells in the lumen of the seminiferous tubule of the testes, vacuolation in the brain, axonal degeneration of the sciatic nerve, and cardiomyopathy in the 100, ≥25, ≥50, 100, and 100 mg/kg b.w./day groups, respectively. In conclusion, 3-MCPD's target organs were the kidneys, testes, brain, sciatic nerve, and heart. The "no-observed-adverse-effect level" (NOAEL) of 3-MCPD was ≤25 and 25 mg/kg b.w./day in males and females, respectively.

  13. Multinational, multicentre, randomised, open-label study evaluating the impact of a 91-day extended regimen combined oral contraceptive, compared with two 28-day traditional combined oral contraceptives, on haemostatic parameters in healthy women

    PubMed Central

    Paoletti, Anna Maria; Volpe, Annibale; Chiovato, Luca; Howard, Brandon; Weiss, Herman; Ricciotti, Nancy

    2014-01-01

    Objectives To evaluate the impact of a 91-day extended regimen combined oral contraceptive (150 μg levonorgestrel [LNG]/30 μg ethinylestradiol [EE] for 84 days, followed by 10 μg EE for seven days [Treatment 1]) compared with two traditional 21/7 regimens (21 days 150 μg LNG/30 μg EE [Treatment 2] or 150 μg desogestrel [DSG]/30 μg EE [Treatment 3], both with seven days’ hormone free), on several coagulation factors and thrombin formation markers. Methods Randomised, open-label, parallel-group comparative study involving healthy women (18–40 years). The primary endpoint was change from baseline in prothrombin fragment 1 + 2 (F1 + 2) levels over six months. Results A total of 187 subjects were included in the primary analysis. In all groups, mean F1 + 2 values were elevated after six months of treatment. Changes were comparable between Treatments 1 and 2 (least squares mean change: 170 pmol/L and 158 pmol/L, respectively) but noticeably larger after Treatment 3 (least squares mean change: 592 pmol/L). The haemostatic effects of Treatment 1 were comparable to those of Treatment 2 and noninferior to those of Treatment 3 (lower limit of 95% confidence interval [− 18.3 pmol/L] > − 130 pmol/L). Conclusions The LNG/EE regimens had similar effects on F1 + 2. Noninferiority was demonstrated between extended regimen LNG/EE and DSG/EE. PMID:24923685

  14. Acute, 28days sub acute and genotoxic profiling of Quercetin-Magnesium complex in Swiss albino mice.

    PubMed

    Ghosh, Nilanjan; Sandur, Rajendra; Ghosh, Deepanwita; Roy, Souvik; Janadri, Suresh

    2017-02-01

    Quercetin-Magnesium complex is one of the youngest alkaline rare earth metal (Magnesium) complexes with flavonoids (Quercetin) in organo-metalic family. Earlier studies describe the details of the complex formation, characterization and antioxidant study of the complex but toxicity profile is still under darkness. The present study was taken up to investigate the oral acute toxicity, 28days repeated oral sub-acute toxicity study and genotoxicity study of Quercetin-Magnesium complex in Swiss albino mice. Quercetin-Magnesium complex showed mortality at a dose of 185mg/kg in the Swiss albino mice. In 28days repeated oral toxicity study, Quercetin-Magnesium complex was administered to both sex of Swiss albino mice at dose levels of 150, 130 and 100mg/kg body weight respectively. Where 150mg/kg dose shows increased levels of white blood cells and changes in total protein, serum creatinine and blood urea nitrogen. Histopathological study of Quercetin-Magnesium complex shows minor structural alteration in kidney at 150mg/kg dose. No observed toxic level found in 130mg/kg or below doses. No genotoxic effect found in any doses of the complex. Therefore 130mg/kg or below dose level could be better for further study.

  15. Problem Solving with Guided Repeated Oral Reading Instruction

    ERIC Educational Resources Information Center

    Conderman, Greg; Strobel, Debra

    2006-01-01

    Many students with disabilities require specialized instructional interventions and frequent progress monitoring in reading. The guided repeated oral reading technique promotes oral reading fluency while providing a reliable data-based monitoring system. This article emphasizes the importance of problem-solving when using this reading approach.

  16. Repeated dosing with oral cocaine in humans: assessment of direct effects, withdrawal, and pharmacokinetics.

    PubMed

    Walsh, Sharon L; Stoops, William W; Moody, David E; Lin, Shen-Nan; Bigelow, George E

    2009-08-01

    Cocaine withdrawal symptoms are thought to play a role in relapse; studies characterizing the symptomatology have yielded mixed findings. This study sought to examine the pharmacodynamic/pharmacokinetic profile of repeated high dose exposure to oral cocaine and characterize acute and protracted withdrawal in cocaine abusers. This study employed a repeated-dosing, single-blind design in which subjects (n = 9), resided for 40 days on a closed ward. They were maintained for two 4-day cocaine exposure periods (Days 1-4 & Days 9-12, cocaine 175 mg, p.o.; 5 hourly doses; 875 mg/day) separated by a 4-day matched placebo exposure period (Days 5-8). After these 12 days, an additional period of 28 days of placebo maintenance followed (Days 13-40). Test sessions were conducted during each phase; measures of mood, drug effects, sleep, pharmacokinetics, and prolactin were collected throughout the study. The dosing regimen produced cocaine plasma concentrations (Cmax of 680 ng/mL) two to threefold higher than typically seen in acute dose studies. Prototypic psychostimulant effects, including subjective ratings of euphoric effects (liking, high, good effects) and significant cardiopressor effects, were sustained during the active dosing periods, corresponding to the rise and fall of plasma cocaine. Withdrawal-like symptoms (i.e., disruptions of sleep, increased ratings of anxiety, irritability, crashing) were observed within 24-hr after cessation of dosing. Cocaine reduced prolactin acutely, but no sustained alterations were observed for this measure or for other signs or symptoms during the 28-day abstinence period. These findings indicate that exposure to controlled high doses of cocaine produces modest symptoms consistent with cocaine withdrawal within hours of cessation of dosing but provide no evidence of symptoms persisting beyond 24 hours.

  17. Biochemical observation during 28 days of space flight

    NASA Technical Reports Server (NTRS)

    Leach, C. S.; Kambaut, P. C.

    1975-01-01

    With the completion of the 28-day flight of Skylab 2, the sum of biochemical data on human reaction to the weightless environment was significantly extended both quantitatively and qualitatively. The biochemical studies were divided into two broad categories. One group included the more routine blood studies similar to those used in everyday medical practice. The second category encompassed those analyses used to investigate more thoroughly the endocrinological and fluid changes first seen in the crewmembers following the Gemini, Apollo, and Soviet missions. Significant biochemical changes were observed that varied in magnitude and direction, but all disappeared shortly after return to earth. Most of changes indicate successful adaptation by the body to the combined stresses of weightlessness. Results of the biochemical observation are presented in the form of data tables and graphs.

  18. Cetirizine in horses: pharmacokinetics and pharmacodynamics following repeated oral administration.

    PubMed

    Olsén, Lena; Bondesson, Ulf; Broström, Hans; Tjälve, Hans; Ingvast-Larsson, Carina

    2008-08-01

    The pharmacokinetics of the histamine H(1)-antagonist cetirizine and its effect on histamine-induced cutaneous wheal formation were studied in six healthy horses following repeated oral administration. After three consecutive administrations of cetirizine (0.2 mg/kg body weight, bw) every 12h, the trough plasma concentration of cetirizine was 16+/-4 ng/mL (mean+/-SD) and the wheal formation was inhibited by 45+/-23%. After four additional administrations of cetirizine (0.4 mg/kg bw) every 12 h, the trough plasma concentration was 48+/-15 ng/mL and the wheal formation was inhibited by 68+/-11%. The terminal half-life was about 5.8 h. A pharmacokinetic/pharmacodynamic link model showed that the maximal inhibition of wheal formation was about 95% and the EC(50) about 18 ng/mL. It is concluded that cetirizine in doses of 0.2-0.4 mg/kg bw administered at 12 h intervals exhibits favourable pharmacokinetic and pharmacodynamic properties without causing visible side effects, and the drug may therefore be a useful antihistamine in equine medicine.

  19. Coenzyme Q10 Abrogated the 28 Days Aluminium Chloride Induced Oxidative Changes in Rat Cerebral Cortex

    PubMed Central

    Majumdar, Anuradha S.; Nirwane, Abhijit; Kamble, Rahul

    2014-01-01

    Objective: The present study was designed to elucidate the impact of oral administration of aluminium chloride for 28 days with respect to oxidative stress in the cerebral cortex of female rats. Further, to investigate the potentials of Coenzyme (Co) Q10 (4, 8, and 12 mg/kg, i.p.) in mitigating the detrimental changes. Materials and Methods: Biochemical estimations of cerebral lipid peroxidation (LPO), reduced glutathione (GSH), vitamin E and activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were carried out after 28 days of aluminium chloride (AlCl3) and Co Q10 exposures along with histopathological examination of cerebral cortex of the rats. Results: Subacute exposure to AlCl3(5 mg/kg) led to significant decrease in levels of GSH, vitamin E and activities of SOD, CAT, GPx, and an increase in LPO of cerebral cortex. These aberrations were restored by Co Q10 (12 mg/kg, i.p.). This protection offered was comparable to that of L-deprenyl (1 mg/kg, i.p.) which served as a reference standard. Histopathological evaluations confirmed that the normal cerebral morphology was maintained by Co Q10. Conclusion: Thus, AlCl3 exposure hampers the activities of various antioxidant enzymes and induces oxidative stress in cerebral cortex of female Wistar rats. Supplementation with intraperitoneal Co Q10 abrogated these deleterious effects of AlCl3. PMID:25253934

  20. Downregulation of immediate-early genes linking to suppression of neuronal plasticity in rats after 28-day exposure to glycidol

    SciTech Connect

    Akane, Hirotoshi; Saito, Fumiyo; Shiraki, Ayako; Takeyoshi, Masahiro; Imatanaka, Nobuya; Itahashi, Megu; Murakami, Tomoaki; Shibutani, Makoto

    2014-09-01

    We previously found that the 28-day oral toxicity study of glycidol at 200 mg/kg/day in rats resulted in axonopathy in both the central and peripheral nervous systems and aberrations in the late-stage of hippocampal neurogenesis targeting the process of neurite extension. To capture the neuronal parameters in response to glycidol toxicity, these animals were subjected to region-specific global gene expression profiling in four regions of cerebral and cerebellar architectures, followed by immunohistochemical analysis of selected gene products. Expression changes of genes related to axonogenesis and synaptic transmission were observed in the hippocampal dentate gyrus, cingulate cortex and cerebellar vermis at 200 mg/kg showing downregulation in most genes. In the corpus callosum, genes related to growth, survival and functions of glial cells fluctuated their expression. Immunohistochemically, neurons expressing gene products of immediate-early genes, i.e., Arc, Fos and Jun, decreased in their number in the dentate granule cell layer, cingulate cortex and cerebellar vermis. We also applied immunohistochemical analysis in rat offspring after developmental exposure to glycidol through maternal drinking water. The results revealed increases of Arc{sup +} neurons at 1000 ppm and Fos{sup +} neurons at ≥ 300 ppm in the dentate granule cell layer of offspring only at the adult stage. These results suggest that glycidol suppressed neuronal plasticity in the brain after 28-day exposure to young adult animals, in contrast to the operation of restoration mechanism to increase neuronal plasticity at the adult stage in response to aberrations in neurogenesis after developmental exposure. - Highlights: • Neuronal toxicity parameters after 28-day glycidol treatment were examined in rats. • Region-specific global gene expression profiling was conducted in brain regions. • Cortical tissues downregulated genes on axonogenesis and synaptic transmission. • Cortical tissues

  1. Corn rootworm-active RNA DvSnf7: Repeat dose oral toxicology assessment in support of human and mammalian safety.

    PubMed

    Petrick, Jay S; Frierdich, Gregory E; Carleton, Stephanie M; Kessenich, Colton R; Silvanovich, Andre; Zhang, Yuanji; Koch, Michael S

    2016-11-01

    Genetically modified (GM) crops have been developed and commercialized that utilize double stranded RNAs (dsRNA) to suppress a target gene(s), producing virus resistance, nutritional and quality traits. MON 87411 is a GM maize variety that leverages dsRNAs to selectively control corn rootworm through production of a 240 base pair (bp) dsRNA fragment targeting for suppression the western corn rootworm (Diabrotica virgifera virgifera) Snf7 gene (DvSnf7). A bioinformatics assessment found that endogenous corn small RNAs matched ∼450 to 2300 unique RNA transcripts that likely code for proteins in rat, mouse, and human, demonstrating safe dsRNA consumption by mammals. Mice were administered DvSnf7 RNA (968 nucleotides, including the 240 bp DvSnf7 dsRNA) at 1, 10, or 100 mg/kg by oral gavage in a 28-day repeat dose toxicity study. No treatment-related effects were observed in body weights, food consumption, clinical observations, clinical chemistry, hematology, gross pathology, or histopathology endpoints. Therefore, the No Observed Adverse Effect Level (NOAEL) for DvSnf7 RNA was 100 mg/kg, the highest dose tested. These results demonstrate that dsRNA for insect control does not produce adverse health effects in mammals at oral doses millions to billions of times higher than anticipated human exposures and therefore poses negligible risk to mammals.

  2. COMPARATIVE METABOLISM OF ARSENIC IN MICE AFTER A SINGLE OR REPEATED ORAL ADMINISTRATION OF ARSENATE

    EPA Science Inventory

    COMPARATIVE METABOLISM OF ARSENIC IN MICE AFTER A SINGLE OR REPEATED ORAL ADMINISTRATION OF ARSENATE
    Michael F. Hughes*1, Elaina M. Kenyon1, Brenda C. Edwards1, Carol T. Mitchell1, Luz Maria Del Razo2 and David J. Thomas1
    1US EPA, ORD, NHEERL, ETD, PKB, Research Triangle Pa...

  3. Induction of hyperchromic microcytic anaemia by repeated oral administration of methotrexate in rats.

    PubMed

    Kojima, Sayuri; Yoshida, Toshinori; Sasaki, Junya; Takahashi, Naofumi; Kuwahara, Maki; Shutoh, Yasufumi; Saka, Machiko; Nakashima, Nobuaki; Kosaka, Tadashi; Harada, Takanori

    2012-01-01

    Anaemia is a significant prognostic factor in cancer patients receiving anticancer drugs such as methotrexate (MTX). This study focuses on the effects of toxicological changes on the hematopoietic systems in male and female Wistar Hannover rats when MTX is orally administered at a dose of 0, 0.05, 0.15, or 0.45 mg/(kg·day) for a period of 28 days. Both male and female rats receiving 0.45 mg/kg MTX showed a decrease in the haemoglobin concentration (Hb), haematocrit, and erythrocyte count. Female rats showed a decrease in mean corpuscular volume (MCV) and an increase in cell mean Hb (CHCM) in total erythrocytes, including the mature erythrocytes. These results indicate that MTX causes the production of small, mature erythrocytes that contain a high concentration of Hb. MTX reduced the number of peripheral reticulocytes but produced the cells with a large size and a high concentration of Hb, as demonstrated by the reticulocyte MCV and CHCM as well as the content of haemoglobin per reticulocyte (CHr). Consistent with these findings, bone marrow haematopoiesis was impaired by MTX, as there was a reduction in erythroid count in rats of both sexes. The number of cells of the myeloid lineage reduced in female rats, followed by a reduction in the total leukocyte and neutrophil counts in peripheral blood. Thrombocytopenia was detected in a small population of rats. These results indicate that MTX induces hyperchromic microcytic anaemia and pancytopenia, and the use of MCV and CHCM in mature erythrocytes and reticulocytes, along with the CHr, gives a better understanding of the development and nature of anaemia.

  4. 28-Day emergency surgical re-admission rates as a clinical indicator of performance.

    PubMed Central

    Courtney, Edward D. J.; Ankrett, Sarah; McCollum, Peter T.

    2003-01-01

    With the introduction of clinical governance, the NHS Executive has identified 28-day emergency re-admission rates as a clinical indicator to be used to assess and compare performance between NHS trusts. We undertook a 3-month retrospective audit of patients identified from the trust computer as having been re-admitted as an emergency within 28 days of discharge from the general surgical division. We wanted to examine reasons for re-admission, possible errors in coding and any preventable factors in these patients subsequently re-admitted acutely. PMID:12648333

  5. The Return Home: Transitioning from a 28-Day Remote Outdoor Education Programme

    ERIC Educational Resources Information Center

    McNatty, Shannon

    2016-01-01

    This article addresses the challenges for students transitioning from the remote Te Kahu (pseudonym) outdoor education programme back into their home and school city environments. Students must develop methods of coping and readjust to society to continue the personal growth and process the learning affected through the 28-day programme. The…

  6. Improving Oral Reading Fluency through Response Opportunities: A Comparison of Phrase Drill Error Correction with Repeated Readings

    ERIC Educational Resources Information Center

    Begeny, John C.; Daly, Edward J., III; Valleley, Rachel J.

    2006-01-01

    The purpose of this study was to compare two oral reading fluency treatments (repeated readings and phrase drill error correction) which differ in the way they prompt student responding. Repeated readings (RR) and phrase drill (PD) error correction were alternated with a baseline and a reward condition within an alternating treatments design with…

  7. Behavioral toxicity and physiological changes from repeated exposure to fluorene administered orally or intraperitoneally to adult male Wistar rats: A dose-response study.

    PubMed

    Peiffer, Julie; Grova, Nathalie; Hidalgo, Sophie; Salquèbre, Guillaume; Rychen, Guido; Bisson, Jean-François; Appenzeller, Brice M R; Schroeder, Henri

    2016-03-01

    Fluorene is one of the most abundant polycyclic aromatic hydrocarbons (PAHs) in the environment by reason of its high volatility. Demonstrated to be a neurotoxicant through inhalation, it was also identified as a contributive PAH to food contamination. Since no data are available on its oral neurotoxicity, the purpose of the present study was to assess the behavioral and physiological toxicity of repeated oral administration of fluorene to adult Wistar male rats. Animals were daily treated with fluorene at 1, 10 or 100mg/kg/day for 28 consecutive days. Administration was intraperitoneal (i.p.) or oral (p.o.) to evaluate the influence of the route of exposure on fluorene toxicity. Following this period of treatment, animals in both groups were subjected to similar cognitive evaluations, namely anxiety (elevated-plus maze), locomotor activity (open-field) and learning and memory abilities (eight-arm maze and avoidance test of an aversive light stimulus), as well as physiological measurements. The behavioral testing occurred from the 28th to the 60th day of the experiment during which fluorene treatment continued uninterrupted. At the end of this period, the concentration levels of fluorene and of three of its monohydroxylated metabolites in blood and brain were determined using a GC-MS/MS method. The results demonstrated a reduction in rat anxiety level at the lowest doses administered (1 and 10mg/kg/day) regardless of the treatment route, whereas locomotor activity and learning abilities remained unchanged. Moreover, a less significant weight gain was noticed in animals i.p.- and p.o.-treated with 100mg/kg/day during the 28-day period of treatment, which, upon comparison with the three other groups, induced a body weight gap that was maintained throughout the experiment. Significant increases in relative liver weight were also observed in a dose-dependent manner in orally treated rats and only in animal treated i.p. with 100mg/kg/day. According to the dose, higher

  8. Pulmonary function and pathology in cats exposed 28 days to diesel exhaust

    SciTech Connect

    Pepelko, W.E.; Mattox, J.K.; Yang, Y.Y.; Moore, W. Jr.

    1980-09-01

    Young adult male cats were exposed 28 days, 20 hrs per day, to a 1:14 dilution of diesel exhaust emissions. Following termination of exposure, the following pulmonary function measurements were carried out: lung volumes, maximum expiratory flow rates (MEF), MEF at 50%, 25% and 10% of vital capacity (VC): forced expiratory volume (FEV) after 0.2, 0.3 and 0.4 sec, dynamic compliance, resistance and helium washout at 25, 50, 75, and 100 breaths per min. The only significant functional change was a decrease in MEF at 10% of VC (P x .02). The lungs of the exposed cats appeared charcoal grey with frequent focal black spots visible on the pleural surface. Pathologic changes in the exposed cats included a predominantly peribronchiolar localization of black-pigmented macrophages within the alveoli producing a focal pneumonitis or alveolitis. In general, evidence of serious lung damage was not observed following the 28-day exposure period.

  9. Comparative toxicity of silicon dioxide, silver and iron oxide nanoparticles after repeated oral administration to rats.

    PubMed

    Yun, Jun-Won; Kim, Seung-Hyun; You, Ji-Ran; Kim, Woo Ho; Jang, Ja-June; Min, Seung-Kee; Kim, Hee Chan; Chung, Doo Hyun; Jeong, Jayoung; Kang, Byeong-Cheol; Che, Jeong-Hwan

    2015-06-01

    Although silicon dioxide (SiO2), silver (Ag) and iron oxide (Fe2O3) nanoparticles are widely used in diverse applications from food to biomedicine, in vivo toxicities of these nanoparticles exposed via the oral route remain highly controversial. To examine the systemic toxicity of these nanoparticles, well-dispersed nanoparticles were orally administered to Sprague-Dawley rats daily over a 13-week period. Based on the results of an acute toxicity and a 14-day repeated toxicity study, 975.9, 1030.5 and 1000 mg kg(-1) were selected as the highest dose of the SiO2 , Ag and Fe2O3 nanoparticles, respectively, for the 13-week repeated oral toxicity study. The SiO2 and Fe2O3 nanoparticles did not induce dose-related changes in a number of parameters associated with the systemic toxicity up to 975.9 and 1000 mg kg(-1) , respectively, whereas the Ag nanoparticles resulted in increases in serum alkaline phosphatase and calcium as well as lymphocyte infiltration in liver and kidney, raising the possibility of liver and kidney toxicity induced by the Ag nanoparticles. Compared with the SiO2 and Fe2O3 nanoparticles showing no systemic distribution in all tissues tested, the Ag concentration in sampled blood and organs in the Ag nanoparticle-treated group significantly increased with a positive and/or dose-related trend, meaning that the systemic toxicity of the Ag nanoparticles, including liver and kidney toxicity, might be explained by extensive systemic distribution of Ag originating from the Ag nanoparticles. Our current results suggest that further study is required to identify that Ag detected outside the gastrointestinal tract were indeed a nanoparticle form or ionized form.

  10. Repeat Brachytherapy for Patients With Residual or Recurrent Tumors of Oral Cavity

    SciTech Connect

    Yoshimura, Ryo-ichi; Shibuya, Hitoshi; Hayashi, Keiji; Nakagawa, Keiko; Toda, Kazuma; Watanabe, Hiroshi; Kaida, Atushi; Miura, Masahiko

    2012-07-15

    Purpose: To analyze data from patients receiving repeat brachytherapy (re-BT) for the treatment of residual or recurrent tumor in the oral cavity. Methods and Materials: Between January 2003 and December 2007, 62 patients who had undergone definitive BT as an initial treatment of oral cancer subsequently underwent re-BT for the treatment of residual or recurrent tumors at the diagnostic radiology and oncology department (Tokyo Medical and Dental University Hospital). Re-BT was performed 0.9-73 months (median, 5.7) after the initial BT. Au-198 grains were used as the re-BT source in all 62 patients, and an area of 0.8-6.3 cm{sup 2} (median, 3.1) was permanently irradiated with 60-110 Gy (median, 83) according to the system of Paterson-Parker. Results: The 2-year local control and overall survival rate was 53% and 66%, respectively, and local control significantly affected overall survival. Both local control and overall survival were affected by the initial tumor characteristics and the macroscopic appearance of the residual or recurrent tumor. Grade 3 or 4 complications were seen in 5 patients. The incidence of mandibular and mucosal complications was significantly related to a biologic effective dose of {alpha}/{beta} of 3 Gy to the surface of the gingiva and mucosa, respectively. Conclusion: Re-BT using Au-198 grains for the treatment of residual or recurrent tumor after definitive BT in the oral cavity is effective and well tolerated.

  11. Effect of oral administration of sodium bicarbonate on surface EMG activity during repeated cycling sprints.

    PubMed

    Matsuura, Ryouta; Arimitsu, Takuma; Kimura, Takehide; Yunoki, Takahiro; Yano, Tokuo

    2007-11-01

    The purpose of this study was to determine the effect of oral administration of sodium bicarbonate (NaHCO3) on surface electromyogram (SEMG) activity from the vastus lateralis (VL) during repeated cycling sprints (RCS). Subjects performed two RCS tests (ten 10-s sprints) interspersed with both 30-s and 360-s recovery periods 1 h after oral administration of either NaHCO3 (RCSAlk) or CaCO3 (RCSPla) in a random counterbalanced order. Recovery periods of 360 s were set before the 5th and 9th sprints. The rate of decrease in plasma HCO3- concentration during RCS was significantly greater in RCSAlk than in RCSPla, but the rates of decline in blood pH during the two RCS tests were similar. There was no difference between change in plasma lactate concentration in RCSAlk and that in RCSPla. Performance during RCSAlk was similar to that during RCSPla. There were no differences in oxygen uptake immediately before each cycling sprint (preVO2) and in SEMG activity between RCSAlk and RCSPla. In conclusion, oral administration of NaHCO3 did not affect SEMG activity from the VL. This suggests that the muscle recruitment strategy during RCS is not determined by only intramuscular pH.

  12. Downregulation of immediate-early genes linking to suppression of neuronal plasticity in rats after 28-day exposure to glycidol.

    PubMed

    Akane, Hirotoshi; Saito, Fumiyo; Shiraki, Ayako; Takeyoshi, Masahiro; Imatanaka, Nobuya; Itahashi, Megu; Murakami, Tomoaki; Shibutani, Makoto

    2014-09-01

    We previously found that the 28-day oral toxicity study of glycidol at 200mg/kg/day in rats resulted in axonopathy in both the central and peripheral nervous systems and aberrations in the late-stage of hippocampal neurogenesis targeting the process of neurite extension. To capture the neuronal parameters in response to glycidol toxicity, these animals were subjected to region-specific global gene expression profiling in four regions of cerebral and cerebellar architectures, followed by immunohistochemical analysis of selected gene products. Expression changes of genes related to axonogenesis and synaptic transmission were observed in the hippocampal dentate gyrus, cingulate cortex and cerebellar vermis at 200mg/kg showing downregulation in most genes. In the corpus callosum, genes related to growth, survival and functions of glial cells fluctuated their expression. Immunohistochemically, neurons expressing gene products of immediate-early genes, i.e., Arc, Fos and Jun, decreased in their number in the dentate granule cell layer, cingulate cortex and cerebellar vermis. We also applied immunohistochemical analysis in rat offspring after developmental exposure to glycidol through maternal drinking water. The results revealed increases of Arc(+) neurons at 1000ppm and Fos(+) neurons at ≥300ppm in the dentate granule cell layer of offspring only at the adult stage. These results suggest that glycidol suppressed neuronal plasticity in the brain after 28-day exposure to young adult animals, in contrast to the operation of restoration mechanism to increase neuronal plasticity at the adult stage in response to aberrations in neurogenesis after developmental exposure.

  13. Pharmacokinetics of grepafloxacin after oral administration of single and repeat doses in healthy young males.

    PubMed

    Efthymiopoulos, C; Bramer, S L; Maroli, A

    1997-01-01

    The pharmacokinetics of grepafloxacin in healthy male subjects following single oral administration of doses ranging from 200 to 1200 mg, and following repeated oral administration of 400 and 800 mg doses are reported. Plasma levels of grepafloxacin reached a peak within 2 hours (on average) following drug administration and then declined bi-exponentially with concentrations being detectable (> 5 micrograms/L) in the plasma for at least up to 72 hours postdose. The high values for the apparent volume of distribution (5 to 8 L/kg) suggested extensive distribution of grepafloxacin in the tissues. Only a small percentage of the administered dose (ranging from 6% to 9.5%) was recovered in the urine as unchanged grepafloxacin, suggesting that metabolism, rather than urinary excretion, is the major elimination route. The half-life of grepafloxacin was about 12 hours after single doses and about 15 hours after repeat doses. The trough levels increased significantly over the first 3 days of repeat administration; thereafter, the changes were small, with steady-state being reached by the fifth day. The area under the concentration-time curve (AUC24 h) values observed on days 7 and 14 of repeat administration, at each dose level, were similar, suggesting that steady-state is maintained. The area values increased more than proportionally after administration of increasing single and repeat doses, suggesting nonlinear kinetics. The elimination half-life and renal clearance did not change with increasing doses. Saturation in the metabolism of grepafloxacin and possibly in the distribution into a peripheral compartment, as suggested by a decrease in the total plasma clearance and in the apparent volume of distribution, could be the origin of the nonlinear kinetics. However, this deviation from linearity is unlikely to be of clinical significance, since it was very small over the recommended range of therapeutic doses (400 to 600 mg once daily). Compared with other quinolones

  14. Same site submucosal tunneling for a repeat per oral endoscopic myotomy: A safe and feasible option

    PubMed Central

    Wehbeh, Antonios N; Mekaroonkamol, Parit; Cai, Qiang

    2016-01-01

    Per oral endoscopic myotomy (POEM) is a novel endoscopic procedure for achalasia treatment. Due to its novelty and high success rates, a repeat procedure is usually not warranted, making the feasibility and safety of such approach unknown. We report the first case of a successful repeat POEM done at the same site of a previously uncompleted POEM. An 84-year-old female with type 2 achalasia presented for a POEM procedure. The procedure was aborted at the end of tunneling and before myotomy due to hypotension, which later resolved spontaneously. POEM was re-attempted at the same site of the original tunnel 1 year afterward, and surprisingly we didn’t encounter any submucosal fibrosis. The procedure felt similar to a native POEM and a myotomy was performed uneventfully. Our case is the first to suggest that submucosal tunneling during a repeat POEM can be done at the same site. Hypotension during POEM is a rare complication that should be recognized as a potential result of tension capnothorax, it can however, be managed with close supportive care. PMID:27803774

  15. A fourteen-day repeated dose oral toxicity study of APFO in rats.

    PubMed

    Iwai, Hiroyuki; Yamashita, Kotaro

    2006-01-01

    Ammonium perfluoroocanoate (APFO) was repeatedly administered orally to male Crj:CD(SD)IGS rats for 14 days. Doses of APFO were 0, 0.5, 5, and 50 mg/kg. Significant increases and increasing tendencies in absolute/relative weight of the liver and no change in weight of the spleen were observed in all groups. Although inductions of mitochondrion- and peroxisome-specific enzymes were increased, no decrease was seen in any hematological parameter of lipid metabolism. Red blood cell count, hemoglobin concentration, and hematocrit or these tendencies showed a significant decrease or a tendency to decrease, but no influence on lymphocyte subsets was noted. Secondary inhibition of immunocompetent cells, previously reported for mice, was not seen in this study of rats.

  16. Orally administered conjugated linoleic acid ameliorates allergic dermatitis induced by repeated applications of oxazolone in mice.

    PubMed

    Nakanishi, Tomonori; Tokunaga, Yuzo; Yamasaki, Masao; Erickson, Laurie; Kawahara, Satoshi

    2016-12-01

    Conjugated linoleic acid (CLA) is one of the constituents of animal products with possible health benefits such as anti-carcinogenic and anti-obesity effects. In this study, we investigated the immunomodulatory effects of CLA using a mouse model of allergic dermatitis. Mice were orally administered either a CLA mixture containing equal amounts of 9c, 11 t-CLA and 10 t, 12c-CLA, or high linoleic acid safflower oil, and allergic dermatitis was induced on the ear by repeated topical applications of oxazolone. Oral administration of the CLA mixture but not the high linoleic safflower oil attenuated the symptoms of allergic dermatitis in both ear weights and clinical scores. This effect was associated with decreased levels of ear interleukin-4 (IL-4) and plasma immunoglobulin E. The immunomodulatory effects of the CLA isomers were compared by an in vitro cytokine production assay. The results showed that 9c, 11 t-CLA, the most predominant isomer in animal products, significantly inhibited IL-4 and interferon-γ production from mouse splenocytes with similar potency to 10 t, 12c-CLA. These findings suggest that CLA, a constituent of animal products, has a potentially beneficial effect for amelioration of allergic dermatitis.

  17. Mineral and nitrogen balance study - Results of metabolic observations on Skylab II 28-day orbital mission

    NASA Technical Reports Server (NTRS)

    Whedon, G. D.; Lutwak, L.; Reid, J.; Rambaut, P.; Whittle, M.; Smith, M.; Leach, C.

    1975-01-01

    The prediction that various stresses of flight, particularly weightlessness, would bring about significant derangements in the metabolism of the musculoskeletal system has been based on various balance-study observations of long-term immobilized or inactive bed rest. The three astronauts of Skylab II consumed a planned dietary intake of major metabolic elements in mixed foods and beverages and provided virtually complete collections of excreta for 31 days preflight, 28 days inflight, and 17 days postflight. Analyses showed that, in varying degree among the crewmen, urinary calcium increased gradually during flight in a pattern similar to that observed in bed-rest studies. Fecal calcium excretion did not change significantly, but calcium balance, owing to the urinary calcium rise, became either negative or less positive than in preflight measurement. Increased excretion and negative nitrogen and phosphorus balances inflight indicated appreciable loss of muscle tissue in all three crewmen. Significant losses also occurred inflight in potassium, sodium, and magnesium. Based on the similarity in pattern and degree between these observations of calcium, phosphorus, and nitrogen loss, musculoskeletal integrity would not be threatened in space flights of up to at least 3 months. However, if similar changes occur in the planed Skylab flights for considerably more than 28 days, concern for capable musculoskeletal function should be serious for flights of very many months' duration.

  18. A 4-week Repeated dose Oral Toxicity Study of Mecasin in Sprague-Dawley Rats to Determine the Appropriate Doses for a 13-week, Repeated Toxicity Test

    PubMed Central

    Cha, Eunhye; Lee, Jongchul; Lee, Seongjin; Park, Manyong; Song, Inja; Son, Ilhong; Song, Bong-Keun; Kim, Dongwoung; Lee, Jongdeok

    2015-01-01

    Objectives: In this study, we investigated the 4-week repeated-dose oral toxicity of gami-jakyak gamcho buja decoction (Mecasin) to develop safe treatments. Methods: In order to investigate the 4-week oral toxicity of Mecasin, we administered Mecasin orally to rats. Sprague-Dawley (SD) rats were divided into four groups of five male and five female animals per group: group 1 being the control group and groups 2, 3, and 4 being the experimental groups. Doses of Mecasin of 500, 1,000, and 2,000 mg/kg of body weight were administered to the experimental groups, and a dose of normal saline solution of 10 mL/kg was administered to the control group. We examined the survival rate, weight, clinical signs, and gross findings for four weeks. This study was conducted under the approval of the Institutional Animal Ethics Committee. Results: No deaths occurred in any of the four groups. No significant changes in weights or food consumption between the control group and the experimental groups were observed. Serum biochemistry revealed that some groups showed significant decrease in inorganic phosphorus (IP) (P < 0.05). During necropsy on the rats, one abnormal macroscopic feature, a slight loss of fur, was observed in the mid dosage (1,000 mg/ kg) male group. No abnormalities were observed in any other rats. In histopathological findings, the tubular basophilia and cast of the kidney and extramedullary hematopoiesis of the spleen were found. However, those changes were minimal and had occurred naturally or sporadically. No other organ abnormalities were observed. Conclusion: During this 4-week, repeated, oral toxicity test of Mecasin in SD rats, no toxicity changes due to Mecasin were observed in any of the male or the female rats in the high dosage group. Thus, we suggest that the doses in a 13-week, repeated test should be 0, 500, 1,000, and 2,000 mg/kg respectively. PMID:26998389

  19. No effects of oral ribose supplementation on repeated maximal exercise and de novo ATP resynthesis.

    PubMed

    Eijnde, B O; Van Leemputte, M; Brouns, F; Van Der Vusse, G J; Labarque, V; Ramaekers, M; Van Schuylenberg, R; Verbessem, P; Wijnen, H; Hespel, P

    2001-11-01

    A double-blind randomized study was performed to evaluate the effect of oral ribose supplementation on repeated maximal exercise and ATP recovery after intermittent maximal muscle contractions. Muscle power output was measured during dynamic knee extensions with the right leg on an isokinetic dynamometer before (pretest) and after (posttest) a 6-day training period in conjunction with ribose (R, 4 doses/day at 4 g/dose, n = 10) or placebo (P, n = 9) intake. The exercise protocol consisted of two bouts (A and B) of maximal contractions, separated by 15 s of rest. Bouts A and B consisted of 15 series of 12 contractions each, separated by a 60-min rest period. During the training period, the subjects performed the same exercise protocol twice per day, with 3-5 h of rest between exercise sessions. Blood samples were collected before and after bouts A and B and 24 h after bout B. Knee-extension power outputs were approximately 10% higher in the posttest than in the pretest but were similar between P and R for all contraction series. The exercise increased blood lactate and plasma ammonia concentrations (P < 0.05), with no significant differences between P and R at any time. After a 6-wk washout period, in a subgroup of subjects (n = 8), needle-biopsy samples were taken from the vastus lateralis before, immediately after, and 24 h after an exercise bout similar to the pretest. ATP and total adenine nucleotide content were decreased by approximately 25 and 20% immediately after and 24 h after exercise in P and R. Oral ribose supplementation with 4-g doses four times a day does not beneficially impact on postexercise muscle ATP recovery and maximal intermittent exercise performance.

  20. Consuming a multi-ingredient thermogenic supplement for 28 days is apparently safe in healthy adults

    PubMed Central

    Vogel, Roxanne M.; Joy, Jordan M.; Falcone, Paul H.; Mosman, Matt M.; Kim, Michael P.; Moon, Jordan R.

    2015-01-01

    Background Thermogenic (TRM) supplements are often used by people seeking to decrease body weight. Many TRM supplements are formulated with multiple ingredients purported to increase energy expenditure and maximize fat loss. However, in the past some TRM ingredients have been deemed unsafe and removed from the market. Therefore, it is important to verify the safety of multi-ingredient TRM supplements with chronic consumption. Objective To assess the safety of daily consumption of a multi-ingredient TRM supplement over a 28-day period in healthy adults. Design Twenty-three recreationally active adults (11M, 12F; 27.1±5.4 years, 171.6±9.6 cm, 76.8±16.1 kg, 26±5 BMI) were randomly assigned either to consume a multi-ingredient TRM supplement (SUP; n=9) or remain unsupplemented (CRL; n=14) for 28 days. Participants maintained their habitual dietary and exercise routines for the duration of the study. Fasting blood samples, resting blood pressure, and heart rate were taken before and after the supplementation period. Samples were analyzed for complete blood counts, comprehensive metabolic, and lipid panels. Results Significant (p<0.05) group by time interactions were present for diastolic BP, creatinine, estimated glomerular filtration rate (eGFR), chloride, CO2, globulin, albumin:globulin (A/G), and high-density lipoprotein (HDL). Dependent t-tests conducted on significant variables revealed significant (p<0.05) within-group differences in SUP for diastolic BP (+6.2±5.3 mmHG), creatinine (+0.09±0.05 mg/dL), eGFR (−11.2±5.8 mL/min/1.73), globulin (−0.29±0.24 g/dL), A/G (+0.27±0.23), and HDL (−5.0±5.5 mg/dL), and in CRL for CO2 (−1.9±1.5 mmol/L) between time points. Each variable remained within the accepted physiological range. Conclusion Results of the present study support the clinical safety of a multi-ingredient TRM containing caffeine, green tea extract, and cayenne powder. Although there were statistically significant (p<0.05) intragroup

  1. A microfluidic culture model of the human reproductive tract and 28-day menstrual cycle

    PubMed Central

    Xiao, Shuo; Coppeta, Jonathan R.; Rogers, Hunter B.; Isenberg, Brett C.; Zhu, Jie; Olalekan, Susan A.; McKinnon, Kelly E.; Dokic, Danijela; Rashedi, Alexandra S.; Haisenleder, Daniel J.; Malpani, Saurabh S.; Arnold-Murray, Chanel A.; Chen, Kuanwei; Jiang, Mingyang; Bai, Lu; Nguyen, Catherine T.; Zhang, Jiyang; Laronda, Monica M.; Hope, Thomas J.; Maniar, Kruti P.; Pavone, Mary Ellen; Avram, Michael J.; Sefton, Elizabeth C.; Getsios, Spiro; Burdette, Joanna E.; Kim, J. Julie; Borenstein, Jeffrey T.; Woodruff, Teresa K.

    2017-01-01

    The endocrine system dynamically controls tissue differentiation and homeostasis, but has not been studied using dynamic tissue culture paradigms. Here we show that a microfluidic system supports murine ovarian follicles to produce the human 28-day menstrual cycle hormone profile, which controls human female reproductive tract and peripheral tissue dynamics in single, dual and multiple unit microfluidic platforms (Solo-MFP, Duet-MFP and Quintet-MPF, respectively). These systems simulate the in vivo female reproductive tract and the endocrine loops between organ modules for the ovary, fallopian tube, uterus, cervix and liver, with a sustained circulating flow between all tissues. The reproductive tract tissues and peripheral organs integrated into a microfluidic platform, termed EVATAR, represents a powerful new in vitro tool that allows organ–organ integration of hormonal signalling as a phenocopy of menstrual cycle and pregnancy-like endocrine loops and has great potential to be used in drug discovery and toxicology studies. PMID:28350383

  2. The effects of oral creatine supplementation on performance in single and repeated sprint swimming.

    PubMed

    Peyrebrune, M C; Nevill, M E; Donaldson, F J; Cosford, D J

    1998-04-01

    We studied the effects of oral creatine supplementation on sprint swimming performance in 14 elite competitive male swimmers. The subjects performed a single sprint (1 x 50 yards [45.72 m]) and repeated sprint set (8 x 50 yards at intervals of 1 min 30 s) before and after a 5 day period of either creatine (9 g creatine + 4.5 g maltodextrin + 4.5 g glucose day(-1)) or placebo (18 g glucose day(-1); double-blind protocol) supplementation. Venous and capillary blood samples were taken for the determination of plasma ammonia, blood pH and lactate. Mean times recorded for the single 50 yard sprint were unchanged as a result of supplementation (creatine vs control, N.S.). During the repeated sprint test, mean times increased (P< 0.01, main effect time) during all trials, but performance was improved as a result of creatine supplementation (sprints 1-8: control pre-, 23.35+/-0.68 to 26.32+/-1.34 s; control post-, 23.59+/-0.66 to 26.19+/-1.48 s; creatine pre-, 23.20+/-0.67 to 26.85+/-0.42 s; creatine post-, 23.39+/-0.54 to 25.73+/-0.26 s; P < 0.03, group x trial interaction). Thus the percentage decline in performance times was reduced after creatine supplementation (control, 12.7+/-5.7% vs 11.0+/-5.5%; creatine, 15.7+/-4.3% vs 10.0+/-2.5%; P< 0.05, group x trial interaction). The metabolic response was similar before and after supplementation, with no differences in the blood lactate or pH response. Plasma ammonia was lower on the second trial (P< 0.05, main effect trial), but this could not be attributed to the effect of supplementation (group x trial interaction, N.S.). A further urinary analysis study supported these findings by demonstrating an approximately 67% (approximately 26 g) retention of the administered creatine in this group of swimmers after an identical supplementation regimen. In summary, our results suggest that ingesting 9 g creatine per day for 5 days can improve swimming performance in elite competitors during repeated sprints, but appears to have no

  3. Toxicity of palytoxin after repeated oral exposure in mice and in vitro effects on cardiomyocytes.

    PubMed

    Del Favero, Giorgia; Beltramo, Dario; Sciancalepore, Marina; Lorenzon, Paola; Coslovich, Tamara; Poli, Mark; Testai, Emanuela; Sosa, Silvio; Tubaro, Aurelia

    2013-12-01

    Palytoxin (PLTX) is a highly toxic hydrophilic polyether detected in several edible marine organisms from intra-tropical areas, where seafood poisoning were reported. Symptoms usually start with gastro-intestinal malaise, often accompanied by myalgia, muscular cramps, dyspnea and, sometimes, arrhythmias. Monitoring programs in the Mediterranean Sea have detected PLTX-like molecules in edible mollusks and echinoderms. Despite the potential exposure of the human population and its high toxic potential, the toxicological profile of the molecule is still an issue. Thus, the effects of repeated oral administration of PLTX in mice were investigated. Seven days of PLTX administration caused lethality and toxic effects at doses ≥ 30 μg/kg/day. A NOAEL was estimated equal to 3 μg/kg/day, indicating a quite steep dose-response curve. This value, due to the limited number of animal tested, is provisional, although represents a sound basis for further testing. Macroscopic alterations at gastrointestinal level (gastric ulcers and intestinal fluid accumulation) were observed in mice dead during the treatment period. Histological analysis highlighted severe inflammation, locally associated with necrosis, at pulmonary level, as well as hyper-eosinophilia and fiber separation in myocardium. A cardiac damage was supported by the in vitro effect of the toxin on cardiomyocytes, indicating a severe and irreversible impairment of their electrical properties: electrophysiological recordings detected a progressive cell depolarization, arrest of action potentials and beating.

  4. Repeated-dose liver micronucleus assay: an investigation with 2-nitropropane, a hepatocarcinogen.

    PubMed

    Kawakami, Satoru; Araki, Tetsuro; Nakajima, Mikio; Kusuoka, Osamu; Uchida, Keisuke; Sato, Norihiro; Tanabe, Yoko; Takahashi, Kaori; Wako, Yumi; Kawasako, Kazufumi; Tsurui, Kazuyuki

    2015-03-01

    The utility of the repeated-dose liver micronucleus (RDLMN) assay in the detection of a genotoxic hepatocarcinogen was evaluated. In this paper, a rat hepatocarcinogen, 2-nitropropane (2-NP), was administered orally to young adult rats for 14 and 28 days without a partial hepatectomy or a mitogen, and the micronucleus induction in liver was examined using a simple method to isolate hepatocytes. In addition, a bone marrow micronucleus assay was conducted concomitantly. The frequency of micronucleated hepatocytes induced by 2-NP increased significantly in both the 14- and 28-day repeated-dose studies, while the bone marrow micronucleus assays were negative in each study. These results indicate that the RDLMN assay is useful for detecting a genotoxic hepatocarcinogen that is negative in bone marrow micronucleus assays and is a suitable in vivo genotoxicity test method for integration into a repeated-dose general toxicity study.

  5. A repeated dose 90-day oral toxicity study of cyflumetofen,a novel acaricide, in rats.

    PubMed

    Yoshida, Toshinori; Ikemi, Naoki; Takeuchi, Yukiko; Ebino, Koichi; Kojima, Sayuri; Chiba, Yuko; Nakashima, Nobuaki; Kawakatsu, Hisao; Saka, Machiko; Harada, Takanori

    2012-02-01

    Cyflumetofen is a novel acaricide which is highly active against phytophagous mites. As a part of safety assessment, a repeated dose 90-day oral toxicity study of cyflumetofen was conducted in Fischer (F344/DuCrj) rats of both sexes. Technical grade cyflumetofen was administered in feed to groups of 10 males and 10 females at dose levels of 0, 100, 300, 1,000, and 3,000 ppm. Prothrombin time was prolonged in males at 3,000 ppm and plasma globulin levels were decreased in females at 1,000 and 3,000 ppm. At necropsy, enlarged and whitish adrenals were observed in females at 3,000 ppm. There were statistically significant increases in relative liver weight (ratio to body weight) in males and relative adrenal weight in females in the 1,000 ppm group; increased relative liver and kidney weights in both sexes at 3,000 ppm, and increased absolute and relative weights of adrenals in females at 3,000 ppm. Increased absolute liver weight was also noted in males at 3,000 ppm. Histopathologically, at 1,000 and 3,000 ppm males had diffuse vacuolation and females had diffuse hypertrophy of adrenal cortical cells. In addition, vacuolation of ovarian interstitial gland cells was noted in females at 1,000 and 3,000 ppm. There were no treatment-related changes in any parameters for either sex in other dose groups. Based on these results, the no-observed-adverse-effect level (NOAEL) of cyflumetofen was judged to be 300 ppm for both sexes (16.5 mg/kg/day for males and 19.0 mg/kg/day for females).

  6. Toxicological evaluation of isopropylparaben and isobutylparaben mixture in Sprague-Dawley rats following 28 days of dermal exposure.

    PubMed

    Kim, Min Ji; Kwack, Seung Jun; Lim, Seong Kwang; Kim, Yeon Joo; Roh, Tae Hyun; Choi, Seul Min; Kim, Hyung Sik; Lee, Byung Mu

    2015-11-01

    The alkyl esters of p-hydroxybenzoic acid (Parabens) have been of concern due to their probable endocrine disrupting property especially in baby consumer products. The safety of parabens for use as a preservative in cosmetics has come into controversy, and thus consumer demand for paraben-free products is ever increasing. Thus, more comprehensive studies are needed to conclusively determine the safety of the multiple prolonged exposure to parabens with cosmetic ingredients. This study was conducted to investigate the potential repeated 28 days dermal toxicity (50, 100, 300, or 600 mg/kg bw/day) of isopropylparaben (IPP), isobutylparaben (IBP), or the mixture of IPP and IBP in rats. There were no significant changes in body and organ weights in any group. However, histopathological examinations showed that weak or moderate skin damages were observed in female rats by macroscopic and microscopic evaluations. In female rats, no observed adverse effect levels (NOAELs) of IPP with no skin lesion and IBP for skin hyperkeratosis, were estimated to be 600 mg/kg bw/day, and 50 mg/kg bw/day, respectively. With regard skin hyperkeratosis, the lowest observed adverse effect level (LOAEL) of the mixture of IPP and IBP was estimated to be 50 mg/kg bw/day. Analysis of six serum hormones (estrogen, testosterone, insulin, T3, TSH, or FSH) in animals showed that only FSH was dose-dependently decreased in the mixture groups of 100 mg/kg bw/day or higher. These data suggest that the mixture of IPP and IBP showed a synergistic dermal toxicity in rats and should be considered for future use in consumer products.

  7. Physiological effects following administration of Citrus aurantium for 28 days in rats

    SciTech Connect

    Hansen, Deborah K.; Pellicore, Linda S.

    2012-06-15

    Background: Since ephedra-containing dietary supplements were banned from the US market, manufacturers changed their formulations by eliminating ephedra and replacing with other botanicals, including Citrus aurantium, or bitter orange. Bitter orange contains, among other compounds, synephrine, a chemical that is chemically similar to ephedrine. Since ephedrine may have cardiovascular effects, the goal of this study was to investigate the cardiovascular effects of various doses of bitter orange extract and pure synephrine in rats. Method: Female Sprague–Dawley rats were dosed daily by gavage for 28 days with synephrine from two different extracts. One extract contained 6% synephrine, and the other extract contained 95% synephrine. Doses were 10 or 50 mg synephrine/kg body weight from each extract. Additionally, caffeine was added to these doses, since many dietary supplements also contain caffeine. Telemetry was utilized to monitor heart rate, blood pressure, body temperature and QT interval in all rats. Results and conclusion: Synephrine, either as the bitter orange extract or as pure synephrine, increased heart rate and blood pressure. Animals treated with 95% synephrine showed minimal effects on heart rate and blood pressure; more significant effects were observed with the bitter orange extract suggesting that other components in the botanical can alter these physiological parameters. The increases in heart rate and blood pressure were more pronounced when caffeine was added. None of the treatments affected uncorrected QT interval in the absence of caffeine.

  8. Identification of hydroxylated metabolites of hexabromocyclododecane in wildlife and 28-days exposed Wistar rats.

    PubMed

    Brandsma, Sicco H; Van der Ven, Leo T M; De Boer, Jacob; Leonards, Pim E G

    2009-08-01

    We studied the presence of hydroxylated metabolites of hexabromocyclododecane (HBCD) in three wildlife species (tern egg, seal, and flounder) and in Wistar rats exposed to 30 and 100 mg HBCD/kg bw/day for 28 days. A nondestructive extraction, fractionation, and cleanup method was developed to separate the hydroxylated HBCD metabolites from the biotic sample matrix. Four different groups of hydroxylated HBCD metabolites were identified in rat adipose, liver, lung, and muscle tissues by liquid and gas chromatography (LC and GC) combined with mass spectrometry (MS): monohydroxy metabolites of HBCD, pentabromocyclododecene (PBCDe), tetrabromocyclododecene (TBCDe), and dihydroxy-HBCD. Dihydroxy-PBCDe was identified by GC-MS but could not be confirmed by LCMS. Debromination of HBCD to PBCDe was another metabolic pathway observed. In tern eggs from the Western Scheldt the monohydroxy-HBCD was found and in the blubber of harbor seal (Wadden Sea) the monohydroxy metabolites of HBCD and PBCDe were found. No hydroxylated metabolites were detected in the tissue of flounder (Wadden Sea). To our knowledge, this is the first study to identify different hydroxylated metabolite groups of HBCD in rat and wildlife samples.

  9. 28-day intraocular pressure reduction with a single dose of brimonidine tartrate-loaded microspheres.

    PubMed

    Fedorchak, Morgan V; Conner, Ian P; Medina, Carlos A; Wingard, Jeremy B; Schuman, Joel S; Little, Steven R

    2014-08-01

    Treatment of glaucoma by intraocular pressure (IOP) reduction is typically accomplished through the administration of eye drops, the difficult and frequent nature of which contributes to extremely low adherence rates. Poor adherence to topical treatment regimens in glaucoma patients can lead to irreversible vision loss and increased treatment costs. Currently there are no approved treatments for glaucoma that address the inherent inefficiencies in drug delivery and patient adherence. Brimonidine tartrate (BT), a common glaucoma medication, requires dosing every 8-12 h, with up to 97% of patients not taking it as prescribed. This study provides proof-of-principle testing of a controlled release BT formulation. BT was encapsulated in poly(lactic-co-glycolic) acid microspheres and drug release was quantified using UV-Vis spectroscopy. For in vivo studies, rabbits were randomized to receive a single subconjunctival injection of blank (no drug) or BT-loaded microspheres or twice daily topical 0.2% BT drops. The microspheres released an average of 2.1 ± 0.37 μg BT/mg microspheres/day in vitro. In vivo, the percent decrease in IOP from baseline was significantly greater in the treated eye for both topical drug and drug-loaded microspheres versus blank microspheres throughout the 4-week study, with no evidence of migration or foreign body response. IOP measurements in the contralateral, untreated eyes also suggested a highly localized effect from the experimental treatment. A treatment designed using the release systems described in this study would represent a vast improvement over the current clinical standard of 56-84 topical doses over 28 days.

  10. Acute and 28-Day Subacute Toxicity Studies of Hexane Extracts of the Roots of Lithospermum erythrorhizon in Sprague-Dawley Rats

    PubMed Central

    Han, Chung-Tack; Kim, Myoung-Jun; Moon, Seol-Hee; Jeon, Yu-Rim; Hwang, Jae-Sik; Nam, Chunja; Park, Chong-Woo; Lee, Sun-Ho; Na, Jae-Bum; Park, Chan-Sung; Park, Hee-Won; Lee, Jung-Min; Jang, Ho-Song; Park, Sun-Hee; Han, Kyoung-Goo; Choi, Young Whan

    2015-01-01

    Lithospermum erythrorhizon has long been used as a traditional oriental medicine. In this study, the acute and 28-day subacute oral dose toxicity studies of hexane extracts of the roots of L. erythrorhizon (LEH) were performed in Sprague-Dawley rats. In the acute toxicity study, LEH was administered once orally to 5 male and 5 female rats at dose levels of 500, 1,000, and 2,000 mg/kg. Mortality, clinical signs, and body weight changes were monitored for 14 days. Salivation, soft stool, soiled perineal region, compound-colored stool, chromaturia and a decrease in body weight were observed in the extract-treated groups, and no deaths occurred during the study. Therefore, the approximate lethal dose (ALD) of LEH in male and female rats was higher than 2,000 mg/kg. In the subacute toxicity study, LEH was administered orally to male and female rats for 28 days at dose levels of 25, 100, and 400 mg/kg/day. There was no LEH-related toxic effect in the body weight, food consumption, ophthalmology, hematology, clinical chemistry and organ weights. Compound-colored (black) stool, chromaturia and increased protein, ketone bodies, bilirubin and occult blood in urine were observed in the male and female rats treated with the test substance. In addition, the necropsy revealed dark red discoloration of the kidneys, and the histopathological examination showed presence of red brown pigment or increased hyaline droplets in the renal tubules of the renal cortex. However, there were no test substance-related toxic effects in the hematology and clinical chemistry, and no morphological changes were observed in the histopathological examination of the kidneys. Therefore, it was determined that there was no significant toxicity because the changes observed were caused by the intrinsic color of the test substance. These results suggest that the no-observed-adverse-effect Level (NOAEL) of LEH is greater than 400 mg/kg/day in both sexes. PMID:26877842

  11. Simulation for clinical repeated-dose pharmacokinetic trials applying a peak-and-trough sampling design to estimate oral clearance.

    PubMed

    Ishida, Kazuya; Kayano, Yuichiro; Taguchi, Masato; Hashimoto, Yukiya

    2007-11-01

    We performed a simulation for the clinical pharmacokinetic study, in which blood was sampled at two time points corresponding to the peak concentration (C(peak)) and trough concentration (C(trough)) following repetitive oral drug administration to subjects. We estimated the approximate oral clearance (CL/F(approx)) as 2.D/(C(peak).tau+C(trough).tau), where D is the dose, and tau is the dosing interval. The CL/F(approx) value was accurate for drugs with a long-elimination half-life, and the estimation error of the CL/F value was slightly increased for drugs with a shorter elimination half-life. The accuracy of CL/F(approx) in each subject was not affected by the magnitude of the interindividual pharmacokinetic variability, but was significantly decreased by the larger measurement error of drug concentrations (or intraindividual pharmacokinetic variability). We further performed several computer simulations to mimic statistical hypothesis testing following the clinical repeated-dose pharmacokinetic trials. The statistical power to detect the difference of oral clearance between two groups was marginally dependent on the measurement error of drug concentration, but was highly dependent on the interindividual pharmacokinetic variability. These findings suggested that the peak-and-trough sampling design to estimate the CL/F(approx) value is useful for clinical repeated-dose pharmacokinetic trials, and that the study design and protocol should be evaluated carefully by computer simulation prior to a real clinical trial.

  12. Oral health behavior patterns among Tanzanian university students: a repeat cross-sectional survey.

    PubMed

    Åstrøm, Anne Nordrehaug; Masalu, Joyce Rose

    2001-01-01

    PURPOSE: This study examines oral health behavioral trends and the development of sociodemographic differences in oral health behaviors among Tanzanian students between 1999 and 2000. METHODS: The population targeted was students attending the Muhimbili University College of Health Sciences (MUCHS) at the University of Dar es Salaam (UDSM), Dar es Salaam, Tanzania. Cross-sectional surveys were conducted and a total of 635 and 981 students, respectively, completed questionnaires in 1999 and 2001. RESULTS: Cross-tabulation analyses revealed that in 1999, the rates of abstinence from tobacco use, and of soft drink consumption, regular dental checkups, and intake of chocolate/candy were 84%, 51%, 48%, and 12%, respectively, among students of urban origin and 83%, 29%, 37%, and 5% among their rural counterparts. The corresponding rates in 2001 were 87%, 56%, 50%, and 9% among urban students and 84%, 44%, 38%, and 4% among rural ones. Multiple logistic regression analyses controlling for sex, age, place of origin, educational level, year of survey, and their interaction terms revealed a significant increase in the rate of soft drink consumption, implementation of oral hygiene measures, and abstinence from tobacco use between 1999 and 2001. Social inequalities observed in 1999, with urban students being more likely than their rural counterparts to take soft drinks and go for regular dental checkups, had leveled off by 2001. CONCLUSION: This study provides initial evidence of oral health behavioral trends, that may be utilized in the planning of preventive programs among university students in Tanzania.

  13. Oral health behavior patterns among Tanzanian university students: a repeat cross-sectional survey

    PubMed Central

    Åstrøm, Anne Nordrehaug; Masalu, Joyce Rose

    2001-01-01

    Purpose This study examines oral health behavioral trends and the development of sociodemographic differences in oral health behaviors among Tanzanian students between 1999 and 2000. Methods The population targeted was students attending the Muhimbili University College of Health Sciences (MUCHS) at the University of Dar es Salaam (UDSM), Dar es Salaam, Tanzania. Cross-sectional surveys were conducted and a total of 635 and 981 students, respectively, completed questionnaires in 1999 and 2001. Results Cross-tabulation analyses revealed that in 1999, the rates of abstinence from tobacco use, and of soft drink consumption, regular dental checkups, and intake of chocolate/candy were 84%, 51%, 48%, and 12%, respectively, among students of urban origin and 83%, 29%, 37%, and 5% among their rural counterparts. The corresponding rates in 2001 were 87%, 56%, 50%, and 9% among urban students and 84%, 44%, 38%, and 4% among rural ones. Multiple logistic regression analyses controlling for sex, age, place of origin, educational level, year of survey, and their interaction terms revealed a significant increase in the rate of soft drink consumption, implementation of oral hygiene measures, and abstinence from tobacco use between 1999 and 2001. Social inequalities observed in 1999, with urban students being more likely than their rural counterparts to take soft drinks and go for regular dental checkups, had leveled off by 2001. Conclusion This study provides initial evidence of oral health behavioral trends, that may be utilized in the planning of preventive programs among university students in Tanzania. PMID:11782294

  14. BEHAVIORAL AND NEUROCHEMICAL OUTCOMES OF REPEATED ORAL ADMINISTRATION OF CHLORPYRIFOS IN POSTNATAL/JUVENILE RATS.

    EPA Science Inventory

    Concern has been raised regarding potential adverse effects on the nervous system following childhood exposure to chlorpyrifos (O,O-diethyl-O-3,5,6-trichloro-2-pyridyl-phosphorothioate). This study examined the outcomes of daily oral dosing with chlorpyrifos, from early postnata...

  15. Metabolite profiles of rats in repeated dose toxicological studies after oral and inhalative exposure.

    PubMed

    Fabian, E; Bordag, N; Herold, M; Kamp, H; Krennrich, G; Looser, R; Ma-Hock, L; Mellert, W; Montoya, G; Peter, E; Prokudin, A; Spitzer, M; Strauss, V; Walk, T; Zbranek, R; van Ravenzwaay, B

    2016-07-25

    The MetaMap(®)-Tox database contains plasma-metabolome and toxicity data of rats obtained from oral administration of 550 reference compounds following a standardized adapted OECD 407 protocol. Here, metabolic profiles for aniline (A), chloroform (CL), ethylbenzene (EB), 2-methoxyethanol (ME), N,N-dimethylformamide (DMF) and tetrahydrofurane (THF), dosed inhalatively for six hours/day, five days a week for 4 weeks were compared to oral dosing performed daily for 4 weeks. To investigate if the oral and inhalative metabolome would be comparable statistical analyses were performed. Best correlations for metabolome changes via both routes of exposure were observed for toxicants that induced profound metabolome changes. e.g. CL and ME. Liver and testes were correctly identified as target organs. In contrast, route of exposure dependent differences in metabolic profiles were noted for low profile strength e.g. female rats dosed inhalatively with A or THF. Taken together, the current investigations demonstrate that plasma metabolome changes are generally comparable for systemic effects after oral and inhalation exposure. Differences may result from kinetics and first pass effects. For compounds inducing only weak changes, the differences between both routes of exposure are visible in the metabolome.

  16. The Effects of Combining Repeated Reading with "Reading Mastery" on First Graders' Oral Reading Fluency

    ERIC Educational Resources Information Center

    Nanda, Alice O.; Fredrick, Laura D.

    2007-01-01

    The present study replicates and extends the work of Frankhauser, Tso, and Martella (2001) using 6 first-grade students in a multiple baseline design across participants to determine if the addition of three repeated readings following "Reading Mastery I and II" (Engelmann & Bruner, 1995) lessons improves student fluency beyond that expected…

  17. Effects of repeated oral corticosterone administration on performance and stress parameters of laying hens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The effects of repeated stress during rearing on performance and physiology of laying hens was studied using a corticosterone (Cort) model. 240 Hisex laying hens were reared in environmentally controlled battery cages. At 7, 11, and 15 wk of age they were exposed for 1 wk to the following treatments...

  18. Using a Repeated Reading Program to Improve Generalization of Oral Reading Fluency

    ERIC Educational Resources Information Center

    Lo, Ya-yu; Cooke, Nancy L.; Starling, A. Leyf Peirce

    2011-01-01

    Three second-grade students at-risk for reading failure participated in an adult-directed repeated reading program that integrated isolated word reading practice, unison reading, error correction, and performance cueing and feedback procedures. During each intervention session, the participants practiced five difficult words key to a first-grade…

  19. Supra-nutritional vitamin E supplementation for 28 days before slaughter maximises muscle vitamin E concentration in finisher pigs.

    PubMed

    Kim, J C; Jose, C G; Trezona, M; Moore, K L; Pluske, J R; Mullan, B P

    2015-12-01

    A 4 × 3 factorial experiment (n=8 pigs per treatment combination) was conducted with 96 female Landrace × Large White pigs to examine the required level of dietary vitamin E and optimum feeding duration before slaughter to maximise muscle vitamin E content in the Longissimus thoracis et lumborum (LTL) muscle. The respective factors were four dietary levels of vitamin E (supplemented as dl-α-tocopheryl acetate; 35, 300, 500, and 700 IU/kg) and three feeding durations (14, 28 and 42 days before slaughter). Vitamin E concentration in the LTL was maximised at 6 mg/kg, which was achieved by feeding a 700 IU vitamin E diet for 28 days before slaughter (P<0.001). There was no further increase in the vitamin E content of the LTL by feeding the high vitamin E diet more than 28 days before slaughter.

  20. Responses in the respiratory tract of rats following exposure to sulphuric acid aerosols for 5 or 28 days.

    PubMed

    Kilgour, Joanne D; Foster, John; Soames, Anthony; Farrar, David G; Hext, Paul M

    2002-01-01

    Sulphuric acid mists have been classified by the International Agency for Research on Cancer as being carcinogenic to humans based on epidemiological findings of respiratory tract tumours. To determine if early changes in the respiratory tract following exposure to sulphuric acid (H(2)SO(4)) aerosols are consistent with the possible development of tumours after extended periods of exposure, groups of female rats were exposed to respirable aerosols of H(2)SO(4) at target concentrations of 0, 0.2, 1.0 or 5.0 mg m(-3) for 6 h per day for either 5 days or for 5 days a week over a 28-day period. Additional groups exposed to 0 or 5.0 mg m(-3) over the 28-day period were retained after exposure for 4 or 8 weeks to assess recovery. Histopathological examinations and quantitative cell proliferation measurements were conducted on the nasal passages, larynx and lung. Achieved concentrations were 0.3, 1.38 and 5.52 mg m(-3) H(2)SO(4). Histological and cell proliferative changes were confined to the larynx and no effects were seen in the nasal passages or lungs. At the two highest concentrations, squamous metaplasia accompanied by significant cell proliferation was apparent after 5 and 28 days of exposure and there was a reduction in the severity of the pathological changes following the recovery periods. No effects were seen at 0.3 mg m(-3) after 5 days of exposure and only minimal metaplastic change was seen after 28 days in a few animals and was not accompanied by cell proliferation. The toxicological relevance of these findings is discussed.

  1. Acute toxicity, twenty-eight days repeated dose toxicity and genotoxicity of vanadyl trehalose in kunming mice.

    PubMed

    Jiang, Pingzhe; Ni, Zaizhong; Wang, Bin; Ma, Baicheng; Duan, Huikun; Li, Xiaodan; Ma, Xiaofeng; Wei, Qian; Ji, Xiangzhen; Liu, Qiqi; Xing, Shuguang; Li, Minggang

    2017-04-01

    A new trend has been developed using vanadium and organic ligands to form novel compounds in order to improve the beneficial actions and reduce the toxicity of vanadium compounds. In present study, vanadyl trehalose was explored the oral acute toxicity, 28 days repeated dose toxicity and genotoxicity in Kunming mice. The Median Lethal Dose (LD50) of vanadyl trehalose was revealed to be 1000 mg/kg body weight in fasted Kunming mice. Stomach and intestine were demonstrated to be the main target organs of vanadyl trehalose through 28 days repeated dose toxicity study. And vanadyl trehalose also showed particular genotoxicity through mouse bone marrow micronucleus and mouse sperm malformation assay. In brief, vanadyl trehalose presented certain, but finite toxicity, which may provide experimental basis for the clinical application.

  2. Toxicity evaluation of zinc aluminium levodopa nanocomposite via oral route in repeated dose study

    NASA Astrophysics Data System (ADS)

    Kura, Aminu Umar; Cheah, Pike-See; Hussein, Mohd Zobir; Hassan, Zurina; Tengku Azmi, Tengku Ibrahim; Hussein, Nor Fuzina; Fakurazi, Sharida

    2014-05-01

    Nanotechnology, through nanomedicine, allowed drugs to be manipulated into nanoscale sizes for delivery to the different parts of the body, at the same time, retaining the valuable pharmacological properties of the drugs. However, efficient drug delivery and excellent release potential of these delivery systems may be hindered by possible untoward side effects. In this study, the sub-acute toxicity of oral zinc aluminium nanocomposite with and without levodopa was assessed using the Organization for Economic Co-operation and Development guidelines. No sign or symptom of toxicity was observed in orally treated rats with the nanocomposite at 5 and 500 mg/kg concentrations. Body weight gain, feeding, water intake, general survival and organosomatic index were not significantly different between control and treatment groups. Aspartate aminotransferase (AST) in 500 mg/kg levodopa nanocomposite (169 ± 30 U/L), 5 mg/kg levodopa nanocomposite (172 ± 49 U/L), and 500 mg/kg layered double hydroxides (LDH) nanocomposite (175 ± 25 U/L) were notably elevated compared to controls (143 ± 05 U/L); but the difference were not significant ( p > 0.05). However, the differences in aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio of 500 mg/kg levodopa nanocomposite (0.32 ± 0.12) and 500 mg/kg LDH nanocomposite (0.34 ± 0.12) were statistically significant ( p < 0.05) compared to the control (0.51 ± 0.07). Histology of the liver, spleen and brain was found to be of similar morphology in both control and experimental groups. The kidneys of 500-mg/kg-treated rats with levodopa nanocomposite and LDH nanocomposite were found to have slight inflammatory changes, notably leukocyte infiltration around the glomeruli. The ultra-structure of the neurons from the substantia nigra of nanocomposite-exposed group was similar to those receiving only normal saline. The observed result has suggested possible liver and renal toxicity in orally administered levodopa intercalated

  3. Toxicity evaluation of zinc aluminium levodopa nanocomposite via oral route in repeated dose study

    PubMed Central

    2014-01-01

    Nanotechnology, through nanomedicine, allowed drugs to be manipulated into nanoscale sizes for delivery to the different parts of the body, at the same time, retaining the valuable pharmacological properties of the drugs. However, efficient drug delivery and excellent release potential of these delivery systems may be hindered by possible untoward side effects. In this study, the sub-acute toxicity of oral zinc aluminium nanocomposite with and without levodopa was assessed using the Organization for Economic Co-operation and Development guidelines. No sign or symptom of toxicity was observed in orally treated rats with the nanocomposite at 5 and 500 mg/kg concentrations. Body weight gain, feeding, water intake, general survival and organosomatic index were not significantly different between control and treatment groups. Aspartate aminotransferase (AST) in 500 mg/kg levodopa nanocomposite (169 ± 30 U/L), 5 mg/kg levodopa nanocomposite (172 ± 49 U/L), and 500 mg/kg layered double hydroxides (LDH) nanocomposite (175 ± 25 U/L) were notably elevated compared to controls (143 ± 05 U/L); but the difference were not significant (p > 0.05). However, the differences in aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio of 500 mg/kg levodopa nanocomposite (0.32 ± 0.12) and 500 mg/kg LDH nanocomposite (0.34 ± 0.12) were statistically significant (p < 0.05) compared to the control (0.51 ± 0.07). Histology of the liver, spleen and brain was found to be of similar morphology in both control and experimental groups. The kidneys of 500-mg/kg-treated rats with levodopa nanocomposite and LDH nanocomposite were found to have slight inflammatory changes, notably leukocyte infiltration around the glomeruli. The ultra-structure of the neurons from the substantia nigra of nanocomposite-exposed group was similar to those receiving only normal saline. The observed result has suggested possible liver and renal toxicity in

  4. Telomeric repeat-binding factor 2: a marker for survival and anti-EGFR efficacy in oral carcinoma

    PubMed Central

    Raybaud, Hélène; Sudaka, Anne; Chamorey, Emmanuel; Brolih, Sanja; Monteverde, Martino; Merlano, Marco; Nigro, Cristiana Lo; Ambrosetti, Damien; Pagès, Gilles

    2016-01-01

    Oral Squamous Cell Carcinoma (OSCC) is the most common oral cancer worldwide. Treatments including surgery, radio- and chemo-therapies mostly result in debilitating side effects. Thus, a more accurate evaluation of patients at risk of recurrence after radio/chemo treatment is important for preserving their quality of life. We assessed whether the Telomeric Repeat-binding Factor 2 (TERF2) influences tumor aggressiveness and treatment response. TERF2 is over-expressed in many cancers but its correlation to patient outcome remains controversial in OSCC. Our retrospective study on sixty-two patients showed that TERF2 overexpression has a negative impact on survival time. TERF2-dependent survival time was independent of tumor size in a multivariate analysis. In vitro, TERF2 knockdown by RNA interference had no effect on cell proliferation, migration, senescence and apoptosis. Instead, TERF2 knockdown increased the expression of cytokines implicated in inflammation and angiogenesis, except for vascular endothelial growth factor. TERF2 knockdown resulted in a decrease vascularization and growth of xenograft tumors. Finally, response to erlotinib/Tarceva and cetuximab/Erbitux treatment was increased in TRF2 knocked-down cells. Hence, TERF2 may represent an independent marker of survival for OSCC and a predictive marker for cetuximab/Erbitux and erlotinib/Tarceva efficacy. PMID:27329590

  5. Toxicity of Smokeless Tobacco Extract after 184-Day Repeated Oral Administration in Rats

    PubMed Central

    Yu, Chenlin; Zhang, Ziteng; Liu, Yangang; Zong, Ying; Chen, Yongchun; Du, Xiuming; Chen, Jikuai; Feng, Shijie; Hu, Jinlian; Cui, Shufang; Lu, Guocai

    2016-01-01

    The use of smokeless tobacco (ST) is growing rapidly and globally. The consumption of ST is associated with an increased risk for developing chronic diseases, such as diabetes, hypercholesterolemia, and myocardial infarction, and has led to many public health problems. It is very important to access the toxicity of ST. This experiment presents data from 184-day toxicology studies in Sprague-Dawley (SD) rats designed to characterize the chronic effects of a smokeless tobacco extract (STE). The control group and treatment groups were matched for a range of nicotine levels. Animals were given STE by oral gavage with doses of 3.75 (low-dose), 7.50 (mid-dose) and 15.00 (high-dose) mg·nicotine/kg body weight/day for 184 days, followed by 30 days for recovery. Variables evaluated included body weights, feed consumption, clinical observations, clinical and anatomic pathology (including organ weights), and histopathology. Decreased body weights and organ weights (heart, liver and kidney) were found in animals in the mid-dose and high-dose groups. STE also showed moderate and reversible toxicity in esophagus, stomach, liver, kidney and lung. PMID:26959038

  6. Evaluation of 2-week repeated oral dose toxicity of 100 nm zinc oxide nanoparticles in rats

    PubMed Central

    Ko, Je-Won; Hong, Eun-Taek; Lee, In-Chul; Park, Sung-Hyeuk; Park, Jong-Il; Seong, Nak-Won; Hong, Jeong-Sup; Yun, Hyo-In

    2015-01-01

    The aim of this study was to verify subacute oral dose toxicity of positively charged 100 nm zinc oxide (ZnOAE100[+]) nanoparticles (NPs) in Sprague-Dawley rats. ZnOAE100[+] NPs were administered to rats of each sex by gavage at 0, 500, 1,000, and 2,000 mg/kg/day for 14 days. During the study period, clinical signs, mortality, body weight, food consumption, hematology, serum biochemistry, gross pathology, organ weight, and histopathology were examined. Increased mortality and clinical signs, decreased body weight, feed consumption, hemoglobin (HB), hematocrit (HCT), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), platelet (PT), and lymphocyte (LYM) and increased white blood cells (WBCs), neutrophils (NEUs), alkaline phosphatase (ALP), and histopathological alterations in the spleen, stomach, and pancreas were observed at 2,000 mg/kg/day. Increased clinical signs, decreased body weight, feed consumption, HB, HCT, MCV, MCH, MCHC, and LYM and increased WBCs, NEUs, ALP, and histopathological alterations in the spleen, stomach, and pancreas were seen at 1,000 mg/kg/day. Increased clinical signs, decreased MCV and MCH and increased histopathological alterations in the stomach and pancreas were found at 500 mg/kg/day. These results suggest that the target organs were the spleen, stomach, and pancreas in rats. The no-observed-adverse-effect level was <500 mg/kg for both sexes. PMID:26472967

  7. A 13-week repeated-dose oral toxicity and bioaccumulation of aluminum oxide nanoparticles in mice.

    PubMed

    Park, Eun-Jung; Sim, Jaehoon; Kim, Younghun; Han, Beom Seok; Yoon, Cheolho; Lee, Somin; Cho, Myung-Haing; Lee, Byoung-Seok; Kim, Jae-Ho

    2015-03-01

    Because of an increase in the commercial applications of manufactured nanoparticles, the issue of potential adverse health effects of nanoparticles following intended or unintended exposure is rapidly gaining attention. In this study, we evaluated the toxicity of aluminum oxide nanoparticles (AlNPs, rod-type, 1.5, 3, and 6 mg/kg) after oral administration to mice for 13 weeks. Compared with the control group, the consumption of diet and drinking water and body weight gain decreased in the group treated with AlNPs. The group treated with 6 mg/kg AlNPs also showed a marked elevation in the count of white blood cells that associated with a significant decrease and increase to the proportion of eosinophils and lymphocytes, respectively. In addition, the secretion of IL-6 and monocyte chemotactic protein-1 increased in a dose-dependent manner in the treated groups. Furthermore, AlNPs showed the highest accumulation in the liver and kidneys compared with the control group, increased the lactate dehydrogenase level in the blood, and induced the development of a pathological lesion in the liver and kidneys. Taken together, we suggest that the target organs of rod-type AlNPs may be the liver, kidneys and the immune system, and the not-observed adverse effect level may be lower than 6 mg/kg.

  8. Effects of 28 days silicon dioxide aerosol exposure on respiratory parameters, blood biochemical variables and lung histopathology in rats.

    PubMed

    Deb, Utsab; Lomash, Vinay; Raghuvanshi, Suchita; Pant, S C; Vijayaraghavan, R

    2012-11-01

    Inhalation toxicity of silicon dioxide aerosol (150, 300 mg/m(3)) daily over a period of 28 days was carried out in rats. The changes in respiratory variables during the period of exposure were monitored using a computer programme that recognizes the modifications of the breathing pattern. Exposure to the aerosol caused a time dependent decrease in tidal volume, with an increase in respiratory frequency compared to the control. Biochemical variables and histopathological observation were noted at 28th day following the start of exposure. Biochemical markers of silica induced lung injury like plasma alkaline phosphatase, lactate dehydrogenase and angiotensine converting enzyme activities increased in a concentration dependent manner compared to control. Increase in the plasma enzymatic activities indicates endothelial lung damage, increased lung membrane permeability. Histopathological observation of the lungs confirmed concentration dependent granulomatous inflammation, fibrosis and proteinacious degeneration. Aggregates of mononuclear cells with entrapped silica particles circumscribed by fibroblast were observed in 300 mg/m(3) silica aerosol exposed group at higher magnification. Decrease in tidal volume and increase in respiratory frequency might be due to the thickening of the alveolar wall leading to a decreased alveolar volume and lowered elasticity of the lung tissue. The trends in histological and biochemical data are in conformity with the respiratory data in the present study. This study reports for the first time, the changes in respiratory variables during silica aerosol exposure over a period of 28 days.

  9. Optimization of Hyalella azteca IQ Toxicity Test{trademark} for prediction of 28-day sediment toxicity tests

    SciTech Connect

    Novotny, A.N.; Ezzard, C.L.; Douglas, W.S.; Home, M.T.

    1995-12-31

    The IQ Toxicity Test, which is a rapid screening toxicity test consisting of the observation of in-vivo inhibition of an enzymatic process using a fluorescent substrate, has proven successful for the determination of 24 and 48-hour EC50`s of D. magna, C. dubia, D. pulex and M. bahia. The application of this concept to utilize the freshwater amphipod Hyalella azteca may be an excellent way in which to reduce the standard 28-day chronic sediment toxicity test to possibly one hour`s time. This study incorporates an additive experimental design to explore the effects of and interactions between five specific variables: size of the amphipod, exposure time to the toxicant, concentration of substrate, exposure time to the substrate, and length of time starved prior to testing. The results of the IQ toxicity test were compared to those of a 28-day chronic sediment toxicity test. Preliminary data indicate that there is an optimal combination of these variables which results in a concise, reproducible toxicity test for use with Hyalella azteca, and would potentially be applicable to other freshwater amphipods in the future.

  10. Serum kinetics, distribution and excretion of silver in rabbits following 28 days after a single intravenous injection of silver nanoparticles.

    PubMed

    Lee, Yeonjin; Kim, Pilje; Yoon, Junheon; Lee, Byoungcheun; Choi, Kyunghee; Kil, Ki-Hyun; Park, Kwangsik

    2013-09-01

    Serum kinetics, tissue distribution, and excretion of citrate-coated silver nanoparticles (AgNPs) were investigated in rabbits (n = 4) up to 28 days after a single intravenous injection. Following a single injection of AgNPs, the AUC(last) was reported to be 3.65 ± 0.68 μg·day/ml in 5 mg/kg-treated group and 0.90 ± 0.16 μg·day/ml in 0.5 mg/kg-treated group, respectively. The accumulation of silver was observed in all the tested organs including liver, kidney, spleen, lung, brain, testis, and thymus at 1 day, 7 day, and 28 day of measurement. The liver and spleen seemed to be the major targets because of high accumulation of silver. Excretion via feces and urine was also monitored during the entire experimental period. Unexpectedly, much more excretion of silver occurred via feces than through urine after an intravenous injection, which suggests biliary excretion of AgNPs. General toxicity was analyzed and histopathological changes were also evaluated.

  11. Impact of iPod Touch-Supported Repeated Reading on the English Oral Reading Fluency of L2 Students with Specific Learning Difficulties

    ERIC Educational Resources Information Center

    Papadima-Sophocleous, Salomi; Charalambous, Marina

    2014-01-01

    In recent years the use of new technologies has been extensively explored in different aspects of language learning pedagogy. The objective of this research was to investigate the impact Repeated Reading activity, supported by iPod Touch could have on the English Oral Reading Fluency (ORF) of second language university students with Special…

  12. Evaluation of 90 day repeated dose oral toxicity and reproductive/developmental toxicity of 3'-hydroxypterostilbene in experimental animals

    PubMed Central

    Majeed, Muhammed; Bani, Sarang; Natarajan, Sankaran; Pandey, Anjali; S, Naveed

    2017-01-01

    3'-Hydroxypterostilbene (3'-HPT) is one of the active constituents of Sphaerophysa salsula and Pterocarpus marsupium. Despite many proposed therapeutic applications, the safety profile of 3'-HPT has not been established. The present work investigated 90 day repeated oral dose and reproductive (developmental) toxicity of 3'-HPT as a test substance in rats as per OECD guidelines. 90 day toxicity was conducted in sixty Sprague Dawley rats of each sex (120 rats), grouped into six dosage groups of 0 (control), 0 (control recovery), 20 (low dose), 80 (mid dose), 200 (high dose) and 200 (high dose recovery) mg/kg bwt/day (body weight/day) respectively. For the reproductive toxicity study forty Wistar rats of each sex (80 rats) divided into four dosage groups received 0 (vehicle control), 20 (low dose), 100 (mid dose) and 200 (high dose) mg/kg bwt/day of 3'-HPT respectively for a period of two weeks while pre-mating, mating, on the day before sacrifice, in females during pregnancy and four days of lactation period. Results showed no significant differences in body weight, food intake, absolute organ weight, haematology, with no adverse effects (toxicity) on biochemical values nor any abnormal clinical signs or behavioural changes were observed in any of the control/treatment groups, including reproductive and developmental parameters, gross and histopathological changes. In conclusion, the results suggested a No-Observed-Adverse-Effect-Level (NOAEL) of 200 mg/kg bwt/day in rats after oral administration, implying 3'-HPT did not exhibit any toxicity under the study conditions employed. PMID:28257483

  13. Evaluation of 90 day repeated dose oral toxicity and reproductive/developmental toxicity of 3'-hydroxypterostilbene in experimental animals.

    PubMed

    Majeed, Muhammed; Bani, Sarang; Natarajan, Sankaran; Pandey, Anjali; S, Naveed

    2017-01-01

    3'-Hydroxypterostilbene (3'-HPT) is one of the active constituents of Sphaerophysa salsula and Pterocarpus marsupium. Despite many proposed therapeutic applications, the safety profile of 3'-HPT has not been established. The present work investigated 90 day repeated oral dose and reproductive (developmental) toxicity of 3'-HPT as a test substance in rats as per OECD guidelines. 90 day toxicity was conducted in sixty Sprague Dawley rats of each sex (120 rats), grouped into six dosage groups of 0 (control), 0 (control recovery), 20 (low dose), 80 (mid dose), 200 (high dose) and 200 (high dose recovery) mg/kg bwt/day (body weight/day) respectively. For the reproductive toxicity study forty Wistar rats of each sex (80 rats) divided into four dosage groups received 0 (vehicle control), 20 (low dose), 100 (mid dose) and 200 (high dose) mg/kg bwt/day of 3'-HPT respectively for a period of two weeks while pre-mating, mating, on the day before sacrifice, in females during pregnancy and four days of lactation period. Results showed no significant differences in body weight, food intake, absolute organ weight, haematology, with no adverse effects (toxicity) on biochemical values nor any abnormal clinical signs or behavioural changes were observed in any of the control/treatment groups, including reproductive and developmental parameters, gross and histopathological changes. In conclusion, the results suggested a No-Observed-Adverse-Effect-Level (NOAEL) of 200 mg/kg bwt/day in rats after oral administration, implying 3'-HPT did not exhibit any toxicity under the study conditions employed.

  14. Utility of models to predict 28-day or 30-day unplanned hospital readmissions: an updated systematic review

    PubMed Central

    Zhou, Huaqiong; Della, Phillip R; Roberts, Pamela; Goh, Louise; Dhaliwal, Satvinder S

    2016-01-01

    Objective To update previous systematic review of predictive models for 28-day or 30-day unplanned hospital readmissions. Design Systematic review. Setting/data source CINAHL, Embase, MEDLINE from 2011 to 2015. Participants All studies of 28-day and 30-day readmission predictive model. Outcome measures Characteristics of the included studies, performance of the identified predictive models and key predictive variables included in the models. Results Of 7310 records, a total of 60 studies with 73 unique predictive models met the inclusion criteria. The utilisation outcome of the models included all-cause readmissions, cardiovascular disease including pneumonia, medical conditions, surgical conditions and mental health condition-related readmissions. Overall, a wide-range C-statistic was reported in 56/60 studies (0.21–0.88). 11 of 13 predictive models for medical condition-related readmissions were found to have consistent moderate discrimination ability (C-statistic ≥0.7). Only two models were designed for the potentially preventable/avoidable readmissions and had C-statistic >0.8. The variables ‘comorbidities’, ‘length of stay’ and ‘previous admissions’ were frequently cited across 73 models. The variables ‘laboratory tests’ and ‘medication’ had more weight in the models for cardiovascular disease and medical condition-related readmissions. Conclusions The predictive models which focused on general medical condition-related unplanned hospital readmissions reported moderate discriminative ability. Two models for potentially preventable/avoidable readmissions showed high discriminative ability. This updated systematic review, however, found inconsistent performance across the included unique 73 risk predictive models. It is critical to define clearly the utilisation outcomes and the type of accessible data source before the selection of the predictive model. Rigorous validation of the predictive models with moderate-to-high discriminative

  15. Tissue distribution of inhaled micro- and nano-sized cerium oxide particles in rats: results from a 28-day exposure study.

    PubMed

    Geraets, Liesbeth; Oomen, Agnes G; Schroeter, Jeffry D; Coleman, Victoria A; Cassee, Flemming R

    2012-06-01

    In order to obtain more insight into the tissue distribution, accumulation, and elimination of cerium oxide nanoparticles after inhalation exposure, blood and tissue kinetics were investigated during and after a 28-day inhalation study in rats with micro- and nanocerium oxide particles (nominal primary particle size: < 5000, 40, and 5-10 nm). Powder aerosolization resulted in comparable mass median aerodynamic diameter (1.40, 1.17, and 1.02 μm). After single exposure, approximately 10% of the inhaled dose was measured in lung tissue, as was also estimated by a multiple path particle dosimetry model (MPPD). Though small differences in pulmonary deposition efficiencies of cerium oxide were observed, no consistent differences in pulmonary deposition between the micro- and nanoparticles were observed. Each cerium oxide sample was also distributed to tissues other than lung after a single 6-h exposure, such as liver, kidney, and spleen and also brain, testis, and epididymis. No clear particle size-dependent effect on extrapulmonary tissue distribution was observed. Repeated exposure to cerium oxide resulted in significant accumulation of the particles in the (extra)pulmonary tissues. In addition, tissue clearance was shown to be slow, and, overall, insignificant amounts of cerium oxide were eliminated from the body at 48- to 72-h post-exposure. In conclusion, no clear effect of the primary particle size or surface area on pulmonary deposition and extrapulmonary tissue distribution could be demonstrated. This is most likely explained by similar aerodynamic diameter of the cerium oxide particles in air because of the formation of aggregates and irrespective possible differences in surface characteristics. The implications of the accumulation of cerium oxide particles for systemic toxicological effects after repeated chronic exposure via ambient air are significant and require further exploration.

  16. Acute and repeated dose toxicity studies of different β-cyclodextrin-based nanosponge formulations.

    PubMed

    Shende, Pravin; Kulkarni, Yogesh A; Gaud, R S; Deshmukh, Kiran; Cavalli, Roberta; Trotta, Francesco; Caldera, Fabrizio

    2015-05-01

    Nanosponges (NS) show promising results in different fields such as medicine, agriculture, water purification, fire engineering and so on. The present study was designed to evaluate toxicity of different NS formulations (namely, S1-S6) synthesized with different cross-linking agents such as carbonyl diimidazole, pyromellitic dianhydride and hexamethylene diisocynate; and preparation methods in experimental animals. Acute and repeated dose toxicity studies of formulations were carried out as per OECD guidelines 423 and 407, respectively. For acute toxicity study, formulations were administered to female rats at doses of 300 and 2000 mg/kg orally. The general behaviour of the rats was continuously monitored for 1 h after dosing, periodically during the first 24 h and daily thereafter for a total of 14 days. On day 14, animals were fasted overnight, weighed, and sacrificed. After sacrification, animals were subjected to necropsy. For repeated dose toxicity study, rats of either sex were orally administered with formulations at the dose of 300 mg/kg per day for a period of 28 days. The maximally tolerated dose of all formulations was found to be 2000 mg/kg. Repeated administration of formulations for 28 days did not show any significant changes in haematological and biochemical parameters in experimental animals. These results indicate that the formulations are safe, when tested in experimental animals.

  17. Effect of the oral thrombin inhibitor dabigatran on allergic lung inflammation induced by repeated house dust mite administration in mice.

    PubMed

    de Boer, Johannes D; Berkhout, Lea C; de Stoppelaar, Sacha F; Yang, Jack; Ottenhoff, Roelof; Meijers, Joost C M; Roelofs, Joris J T H; van't Veer, Cornelis; van der Poll, Tom

    2015-10-15

    Asthma is a chronic disease of the airways; asthma patients are hampered by recurrent symptoms of dyspnoea and wheezing caused by bronchial obstruction. Most asthma patients suffer from chronic allergic lung inflammation triggered by allergens such as house dust mite (HDM). Coagulation activation in the pulmonary compartment is currently recognized as a feature of allergic lung inflammation, and data suggest that coagulation proteases further drive inflammatory mechanisms. Here, we tested whether treatment with the oral thrombin inhibitor dabigatran attenuates allergic lung inflammation in a recently developed HDM-based murine asthma model. Mice were fed dabigatran (10 mg/g) or placebo chow during a 3-wk HDM airway exposure model. Dabigatran treatment caused systemic thrombin inhibitory activity corresponding with dabigatran levels reported in human trials. Surprisingly, dabigatran did not lead to inhibition of HDM-evoked coagulation activation in the lung as measured by levels of thrombin-antithrombin complexes and D-dimer. Repeated HDM administration caused an influx of eosinophils and neutrophils into the lungs, mucus production in the airways, and a T helper 2 response, as reflected by a rise in bronchoalveolar IL-4 and IL-5 levels and a systemic rise in IgE and HDM-IgG1. Dabigatran modestly improved HDM-induced lung pathology (P < 0.05) and decreased IL-4 levels (P < 0.01), without influencing other HDM-induced responses. Considering the limited effects of dabigatran in spite of adequate plasma levels, these results argue against clinical evaluation of dabigatran in patients with asthma.

  18. VO2max and ventilatory threshold of trained cyclists are not affected by 28-day L-arginine supplementation.

    PubMed

    Sunderland, Kyle L; Greer, Felicia; Morales, Jacobo

    2011-03-01

    The ergogenic effect of L-arginine on an endurance-trained population is not well studied. The few studies that have investigated L-arginine on this population have not been conducted in a laboratory setting or measured aerobic variables. The purpose of the current study is to determine if 28 days of L-arginine supplementation in trained male cyclists affects VO2max and ventilatory threshold (VT). Eighteen (18) endurance-trained male cyclists (mean ± SD, age: 36.3 ± 7.9 years; height: 182.4 ± 4.6 cm; and body mass: 79.5 ± 4.7 kg) performed a graded exercise test (GXT; 50 W + 25 W·min) before and after 28 days of supplementation with L-arginine (ARG; 2 × 6 g·d) or placebo (PLA; cornstarch). The GXT was conducted on the subject's own bicycle using the RacerMate CompuTrainer (Seattle, WA, USA). VO2 was continuously recorded using the ParvoMedics TrueOne 2400 metabolic cart (Salt Lake City, UT, USA) and VT was established by plotting the ventilatory equivalent for O2 (VE/VO2) and the ventilatory equivalent for CO2 (VE/VCO2) and identifying the point at which VE/VO2 increases with no substantial changes in VE/VCO2. L-arginine supplementation had no effect from initial VO2max (PL, 58.7 ± 7.1 ml·kg·min; ARG, 63.5 ± 7.3 ml·kg·min) to postsupplement VO2max (PL, 58.9 ± 6.0 ml·kg·min; ARG, 63.2 ± 7.2 ml·kg·min). Also, no effect was seen from initial VT (PL, 75.7 ± 4.6% VO2max; ARG, 76.0 ± 5.3% VO2max) to postsupplement VT (PL, 74.3 ± 8.1% VO2max; ARG, 74.2 ± 6.4% VO2max). These results indicate that L-arginine does not impact VO2max or VT in trained male cyclists.

  19. Integration of Pig-a, micronucleus, chromosome aberration and comet assay endpoints in a 28-day rodent toxicity study with urethane

    PubMed Central

    Stankowski, Leon F.; Aardema, Marilyn J.; Lawlor, Timothy E.; Pant, Kamala; Roy, Shambhu; Xu, Yong; Elbekai, Reem

    2015-01-01

    As part of the international Pig-a validation trials, we examined the induction of Pig-a mutant reticulocytes and red blood cells (RETCD59− and RBCCD59−, respectively) in peripheral blood of male Sprague Dawley® rats treated with urethane (25, 100 and 250mg/kg/day) or saline by oral gavage for 29 days. Additional endpoints integrated into this study were: micronucleated reticulocytes (MN-RET) in peripheral blood; chromosome aberrations (CAb) and DNA damage (%tail intensity via the comet assay) in peripheral blood lymphocytes (PBL); micronucleated polychromatic erythrocytes (MN-PCE) in bone marrow; and DNA damage (comet) in various organs at termination (the 29th dose was added for the comet endpoint at sacrifice). Ethyl methanesulfonate (EMS; 200mg/kg/day on Days 3, 4, 13, 14, 15, 27, 28 and 29) was evaluated as the concurrent positive control (PC). All animals survived to termination and none exhibited overt toxicity, but there were significant differences in body weight and body weight gain in the 250-mg/kg/day urethane group, as compared with the saline control animals. Statistically significant, dose-dependent increases were observed for urethane for: RETCD59− and RBCCD59− (on Days 15 and 29); MN-RET (on Days 4, 15 and 29); and MN-PCE (on Day 29). The comet assay yielded positive results in PBL (Day 15) and liver (Day 29), but negative results for PBL (Days 4 and 29) and brain, kidney and lung (Day 29). No significant increases in PBL CAb were observed at any sample time. Except for PBL CAb (likely due to excessive cytotoxicity), EMS-induced significant increases in all endpoints/tissues. These results compare favorably with earlier in vivo observations and demonstrate the utility and sensitivity of the Pig-a in vivo gene mutation assay, and its ability to be easily integrated, along with other standard genotoxicity endpoints, into 28-day rodent toxicity studies. PMID:25934985

  20. Cellular distribution of cell cycle-related molecules in the renal tubules of rats treated with renal carcinogens for 28 days: relationship between cell cycle aberration and carcinogenesis.

    PubMed

    Taniai, Eriko; Hayashi, Hitomi; Yafune, Atsunori; Watanabe, Maiko; Akane, Hirotoshi; Suzuki, Kazuhiko; Mitsumori, Kunitoshi; Shibutani, Makoto

    2012-09-01

    Some renal carcinogens can induce karyomegaly, which reflects aberrant cell division in the renal tubules, from the early stages of exposure. To clarify the cell cycle-related changes during the early stages of renal carcinogenesis, we performed immunohistochemical analysis of tubular cells in male F344 rats treated with carcinogenic doses of representative renal carcinogens for 28 days. For this purpose, the karyomegaly-inducing carcinogens ochratoxin A (OTA), ferric nitrilotriacetic acid, and monuron, and the non-karyomegaly-inducing carcinogens tris(2-chloroethyl) phosphate and potassium bromate were examined. For comparison, a karyomegaly-inducing non-carcinogen, p-nitrobenzoic acid, and a non-carcinogenic non-karyomegaly-inducing renal toxicant, acetaminophen, were also examined. The outer stripe of the outer medulla (OSOM) and the cortex + OSOM were subjected to morphometric analysis of immunoreactive proximal tubular cells. Renal carcinogens, irrespective of their karyomegaly-inducing potential, increased proximal tubular cell proliferation accompanied by an increase in topoisomerase IIα-immunoreactive cells, suggesting a reflection of cell proliferation. Karyomegaly-inducing carcinogens increased nuclear Cdc2-, γH2AX-, and phosphorylated Chk2-immunoreactive cells in both areas, the former two acting in response to DNA damage and the latter one suggestive of sustained G₂. OTA, an OSOM-targeting carcinogen, could easily be distinguished from untreated controls and non-carcinogens by evaluation of molecules responding to DNA damage and G₂/M transition in the OSOM. Thus, all renal carcinogens examined facilitated proximal tubular proliferation by repeated short-term treatment. Among these, karyomegaly-inducing carcinogens may cause DNA damage and G₂ arrest in the target tubular cells.

  1. Psychomotor performance during a 28 day head-down tilt with and without lower body negative pressure

    NASA Astrophysics Data System (ADS)

    Traon, A. Pavy-le; de Feneyrols, A. Rous; Cornac, A.; Abdeseelam, R.; N'uygen, D.; Lazerges, M.; Güell, A.; Bes, A.

    Several factors may affect psychomotor performance in space: sensory-motor changes, sleep disturbances, psychological modifications induced by the social isolation and confinement. However, psychomotor performance is difficult to assess. A battery of standardized and computerized tests, so-called "Automated Portable Test System" (APTS) was devised to ascertain the cognitive, perceptive and motor abilities and their possible fluctuations according to environmental effects. Antiorthostatic bedrest, often used to simulate weightlessness, (particularly cardiovascular modifications) also constitutes a situation of social confinement and isolation. During two bedrest experiments (with head-down tilt of -6°) of 28 days each, we intended to assess psychomotor performance of 6 males so as to determine whether: —on the one hand, it could be altered by remaining in decubitus; —on the other, the Lower Body Negative Pressure sessions, designed to prevent orthostatic intolerance back on Earth, could improve the performance. To accomplish this, part of the APTS tests as well as an automated perceptive attention test were performed. No downgrading of psychomotor performance was observed. On the contrary, the tasks were more accurately performed over time. In order to assess the experimental conditions on the acquisition phase, the learning curves were modelled. A beneficial effect of the LBNP sessions on simple tests involving the visual-motor coordination and attention faculties can only be regarded as a mere trend. Methods used in this experiment are also discussed.

  2. Comparative hazard identification of nano- and micro-sized cerium oxide particles based on 28-day inhalation studies in rats.

    PubMed

    Gosens, Ilse; Mathijssen, Liesbeth E A M; Bokkers, Bas G H; Muijser, Hans; Cassee, Flemming R

    2014-09-01

    There are many uncertainties regarding the hazard of nanosized particles compared to the bulk material of the parent chemical. Here, the authors assess the comparative hazard of two nanoscale (NM-211 and NM-212) and one microscale (NM-213) cerium oxide materials in 28-day inhalation toxicity studies in rats (according to Organisation for Economic Co-operation and Development technical guidelines). All three materials gave rise to a dose-dependent pulmonary inflammation and lung cell damage but without gross pathological changes immediately after exposure. Following NM-211 and NM-212 exposure, epithelial cell injury was observed in the recovery groups. There was no evidence of systemic inflammation or other haematological changes following exposure of any of the three particle types. The comparative hazard was quantified by application of the benchmark concentration approach. The relative toxicity was explored in terms of three exposure metrics. When exposure levels were expressed as mass concentration, nanosized NM-211 was the most potent material, whereas when expression levels were based on surface area concentration, micro-sized NM-213 material induced the greatest extent of pulmonary inflammation/damage. Particles were equipotent based on particle number concentrations. In conclusion, similar pulmonary toxicity profiles including inflammation are observed for all three materials with little quantitative differences. Systemic effects were virtually absent. There is little evidence for a dominant predicting exposure metric for the observed effects.

  3. Assessing sediment toxicity from navigational pools of the Upper Mississippi River using a 28-day Hyalella azteca test

    USGS Publications Warehouse

    Kemble, N.E.; Brunson, E.L.; Canfield, T.J.; Dwyer, F.J.; Ingersoll, C.G.

    1998-01-01

    To assess the extent of sediment contamination in the Upper Mississippi River (UMR) system after the flood of 1993, sediment samples were collected from 24 of the 26 navigational pools in the river and from one site in the Saint Croix River in the summer of 1994. Whole-sediment tests were conducted with the amphipod Hyalella azteca for 28 days measuring the effects on survival, growth, and sexual maturation. Amphipod survival was significantly reduced in only one sediment (13B) relative to the control and reference sediments. Body length of amphipods was significantly reduced relative to the control and reference sediments in only one sample (26C). Sexual maturation was not significantly reduced in any treatment when compared to the control and reference sediments. No significant correlations were observed between survival, growth, and maturation to either the physical or chemical characteristics of the sediment samples from the river. When highly reliable effect range medians (ERMs) were used to evaluate sediment chemistry, 47 of 49 (96%) of the samples were correctly classified as nontoxic. These results indicate that sediment samples from the Upper Mississippi River are relatively uncontaminated compared to other areas of known contamination in the United States.

  4. Effect of orally administered Hochu-ekki-to, a Japanese herbal medicine, on contact hypersensitivity caused by repeated application of antigen.

    PubMed

    Nakada, Tsutomu; Watanabe, Kenji; Matsumoto, Tsukasa; Santa, Kazuki; Triizuka, Kazuo; Hanawa, Toshihiko

    2002-06-01

    The effects of oral administration of Hochu-ekki-to (HET; bu-zhong-yi-qi-tang in Chinese), a traditional Japanese and Chinese herbal medicine, on chronic contact hypersensitivity were investigated. HET suppressed ear swelling due to chronic contact hypersensitivity caused by repeated application of 2,4,6-trinitro-1-chlorobenzene (TNCB). HET significantly suppressed not only increases in hapten-specific immunoglobulin E (IgE) and IgG1 titer due to repeated application of TNCB, but also total IgE and IgG1 concentration in the serum. Interleukin 4 (IL-4) level in inflamed ear tissue was significantly increased by repeated application of TNCB, and this increase in IL-4 level in the ear was significantly suppressed by oral administration of HET. Interferon gamma (IFN-gamma), IL-2, IL-5, IL-10 and IL-12 levels are not changed as much as IL4 by TNCB and HET did not alter these cytokines as much as IL-4. These results suggest that oral administration of HET suppresses chronic contact hypersensitivity, and it can be assumed that the suppression of serum Ig E and Ig G1 and IL-4 in inflamed ear.

  5. Nutrition Composition and Single, 14-Day and 13-Week Repeated Oral Dose Toxicity Studies of the Leaves and Stems of Rubus coreanus Miquel.

    PubMed

    Om, Ae-Son; Song, Yu-Na; Noh, GeonMin; Kim, HaengRan; Choe, JeongSook

    2016-01-08

    The leaves and stems of the plant Rubus coreanus Miquel (RCMLS) are rich in vitamins, minerals and phytochemicals which have antioxidant, anti-hemolytic, anti-inflammatory, anti-fatigue and anti-cancer effects. However, RCMLS is not included in the Korean Food Standards Codex due to the lack of safety assurance concerning RCMLS. We evaluated single and repeated oral dose toxicity of RCMLS in Sprague-Dawley rats. RCMLS did not induce any significant toxicological changes in both male and female rats at a single doses of 2500 mg/kg/day. Repeated oral dose toxicity studies showed no adverse effects in clinical signs, body weight, food consumption, ophthalmic examination, urinalysis, hematology, serum biochemistry, necropsy findings, organ weight, and histopathology at doses of 625, 1250, and 2500 mg/kg/day. The LD50 and LOAEL of RCMLS might be over 2500 mg/kg body weight/day and no target organs were identified. Therefore, this study revealed that single and repeated oral doses of RCMLS are safe.

  6. D-aspartic acid supplementation combined with 28 days of heavy resistance training has no effect on body composition, muscle strength, and serum hormones associated with the hypothalamo-pituitary-gonadal axis in resistance-trained men.

    PubMed

    Willoughby, Darryn S; Leutholtz, Brian

    2013-10-01

    It was hypothesized that D-aspartic acid (D-ASP) supplementation would not increase endogenous testosterone levels or improve muscular performance associated with resistance training. Therefore, body composition, muscle strength, and serum hormone levels associated with the hypothalamo-pituitary-gonadal axis were studied after 28 days of resistance training and D-ASP supplementation. Resistance-trained men resistance trained 4 times/wk for 28 days while orally ingesting either 3 g of placebo or 3 g of D-ASP. Data were analyzed with 2 × 2 analysis of variance (P < .05). Before and after resistance training and supplementation, body composition and muscle strength, serum gonadal hormones, and serum D-ASP and d-aspartate oxidase (DDO) were determined. Body composition and muscle strength were significantly increased in both groups in response to resistance training (P < .05) but not different from one another (P > .05). Total and free testosterone, luteinizing hormone, gonadotropin-releasing hormone, and estradiol were unchanged with resistance training and D-ASP supplementation (P > .05). For serum D-ASP and DDO, D-ASP resulted in a slight increase compared with baseline levels (P > .05). For the D-ASP group, the levels of serum DDO were significantly increased compared with placebo (P < .05). The gonadal hormones were unaffected by 28 days of D-ASP supplementation and not associated with the observed increases in muscle strength and mass. Therefore, at the dose provided, D-ASP supplementation is ineffective in up-regulating the activity of the hypothalamo-pituitary-gonadal axis and has no anabolic or ergogenic effects in skeletal muscle.

  7. Systemic and immunotoxicity of pristine and PEGylated multi-walled carbon nanotubes in an intravenous 28 days repeated dose toxicity study

    PubMed Central

    Zhang, Ting; Tang, Meng; Zhang, Shanshan; Hu, Yuanyuan; Li, Han; Zhang, Tao; Xue, Yuying; Pu, Yuepu

    2017-01-01

    The numerous increasing use of carbon nanotubes (CNTs) derived from nanotechnology has raised concerns about their biosafety and potential toxicity. CNTs cause immunologic dysfunction and limit the application of CNTs in biomedicine. The immunological responses induced by pristine multi-walled carbon nanotubes (p-MWCNTs) and PEGylated multi-walled carbon nanotubes (MWCNTs-PEG) on BALB/c mice via an intravenous administration were investigated. The results reflect that the p-MWCNTs induced significant increases in spleen, thymus, and lung weight. Mice treated with p-MWCNTs showed altered lymphocyte populations (CD3+, CD4+, CD8+, and CD19+) in peripheral blood and increased serum IgM and IgG levels, and splenic macrophage ultrastructure indicated mitochondria swelling. p-MWCNTs inhibited humoral and cellular immunity function and were associated with decreased immune responses against sheep erythrocytes and serum hemolysis level. Natural killer (NK) activity was not modified by two types of MWCNTs. In comparison with two types of MWCNTs, for a same dose, p-MWCNTs caused higher levels of inflammation and immunosuppression than MWCNTs-PEG. The results of immunological function suggested that after intravenous administration with p-MWCNTs caused more damage to systemic immunity than MWCNTs-PEG. Here, we demonstrated that a surface functional modification on MWCNTs reduces their immune perturbations in vivo. The chemistry-modified MWCNTs change their preferred immune response in vivo and reduce the immunotoxicity of p-MWCNTs. PMID:28280324

  8. Systemic and immunotoxicity of pristine and PEGylated multi-walled carbon nanotubes in an intravenous 28 days repeated dose toxicity study.

    PubMed

    Zhang, Ting; Tang, Meng; Zhang, Shanshan; Hu, Yuanyuan; Li, Han; Zhang, Tao; Xue, Yuying; Pu, Yuepu

    2017-01-01

    The numerous increasing use of carbon nanotubes (CNTs) derived from nanotechnology has raised concerns about their biosafety and potential toxicity. CNTs cause immunologic dysfunction and limit the application of CNTs in biomedicine. The immunological responses induced by pristine multi-walled carbon nanotubes (p-MWCNTs) and PEGylated multi-walled carbon nanotubes (MWCNTs-PEG) on BALB/c mice via an intravenous administration were investigated. The results reflect that the p-MWCNTs induced significant increases in spleen, thymus, and lung weight. Mice treated with p-MWCNTs showed altered lymphocyte populations (CD3(+), CD4(+), CD8(+), and CD19(+)) in peripheral blood and increased serum IgM and IgG levels, and splenic macrophage ultrastructure indicated mitochondria swelling. p-MWCNTs inhibited humoral and cellular immunity function and were associated with decreased immune responses against sheep erythrocytes and serum hemolysis level. Natural killer (NK) activity was not modified by two types of MWCNTs. In comparison with two types of MWCNTs, for a same dose, p-MWCNTs caused higher levels of inflammation and immunosuppression than MWCNTs-PEG. The results of immunological function suggested that after intravenous administration with p-MWCNTs caused more damage to systemic immunity than MWCNTs-PEG. Here, we demonstrated that a surface functional modification on MWCNTs reduces their immune perturbations in vivo. The chemistry-modified MWCNTs change their preferred immune response in vivo and reduce the immunotoxicity of p-MWCNTs.

  9. Effects of acute and repeated oral doses of D-tagatose on plasma uric acid in normal and diabetic humans.

    PubMed

    Saunders, J P; Donner, T W; Sadler, J H; Levin, G V; Makris, N G

    1999-04-01

    D-tagatose, a stereoisomer of D-fructose, is a naturally occurring ketohexose proposed for use as a low-calorie bulk sweetener. Ingested D-tagatose appears to be poorly absorbed. The absorbed portion is metabolized in the liver by a pathway similar to that of D-fructose. The main purpose of this study was to determine if acute or repeated oral doses of D-tagatose would cause elevations in plasma uric acid (as is seen with fructose) in normal humans and Type 2 diabetics. In addition, effects of subchronic D-tagatose ingestion on fasting plasma phosphorus, magnesium, lipids, and glucose homeostasis were studied. Eight normal subjects and eight subjects with Type 2 diabetes participated in this two-phase study. Each group was comprised of four males and four females. In the first phase, all subjects were given separate 75 g 3-h oral glucose and D-tagatose tolerance tests. Uric acid, phosphorus, and magnesium were determined in blood samples collected from each subject at 0, 30, 60, 120, and 180 min after dose. In the 8-week phase of the study, the normals were randomly placed into two groups which received 75 g of either D-tagatose or sucrose (25 g with each meal) daily for 8 weeks. The diabetics were randomized into two groups which received either 75 g D-tagatose or no supplements of sugar daily for 8 weeks. Uric acid, phosphorus, magnesium, lipids, glycosylated hemoglobin, glucose, and insulin were determined in fasting blood plasma of all subjects at baseline (time zero) and biweekly over the 8 weeks. The 8-week test did not demonstrate an increase in fasting plasma uric acid in response to the daily intake of D-tagatose. However, a transient increase of plasma uric acid levels was observed after single doses of 75 g of D-tagatose in the tolerance test. Plasma uric acid levels were found to rise and peak at 60 min after such dosing. No clinical relevance was attributed to this treatment-related effect because excursions of plasma uric acid levels above the normal

  10. Effects of 28-day mechanical and chewing stress on content of bound and diffusible ions in muscles of mastication.

    PubMed

    Gedrange, T; Kuhn, U D; Walter, B; Harzer, W; Bauer, R

    2001-06-01

    Type I and type II muscle fibres have different ion concentrations. Muscles adapt to chronic stress by changing of fibre types and remodelling of the myosin heavy chains in the muscle fibres. The present investigation on ionic change during muscular contraction was carried out on 10-week-old pigs (6 treated animals, 6 controls) over a 28-day period. Six pigs received acrylic build-ups to induce mechanical advancement of the lower jaw and chronic chewing stress. Muscle tissue was taken from the masseter (M1, M2, M3), temporal (TP1, TP2), medial pterygoid (PM) and geniohyoid (GH) muscles by a standardized method. Eighty-four muscle samples were used for histological fibre differentiation with mATPase. Energy-dispersive X-ray microanalysis of muscles was carried out in an environmental scanning electron microscope. Endurance stress in the stressed muscles was seen as an increase of type I fibres (P < 0.001). This histological change and ionic alterations were measured in the anterior region of the masseter (M1 and M2) and in the posterior region of the temporal muscle (TP2). Smaller changes were found in the medial pterygoid muscle. We measured in this muscles increases in potassium, sulphur, chloride (P < 0.05) and even larger increases in phosphate (up to 1.5 mmol/g to 2.3 mmol/g, P < 0.001) and sodium (3-fold, P < 0.001). The results reveal the effects of chronic stress on muscle fibres and ion concentration in the muscle. Chronic stress resulted in an increase of type I fibres and increased ion concentration in the same muscle region. These are considered to be indicators of more efficient contraction. The changes in ion concentration are an important factor in muscle contraction.

  11. Characterization of pulmonary protein profiles in response to zinc oxide nanoparticles in mice: a 24-hour and 28-day follow-up study

    PubMed Central

    Pan, Chih-Hong; Chuang, Kai-Jen; Chen, Jen-Kun; Hsiao, Ta-Chih; Lai, Ching-Huang; Jones, Tim P; BéruBé, Kelly A; Hong, Gui-Bing; Ho, Kin-Fai; Chuang, Hsiao-Chi

    2015-01-01

    Although zinc oxide nanoparticles (ZnONPs) are recognized to cause systemic disorders, little is known about the mechanisms that underlie the time-dependent differences that occur after exposure. The objective of this study was to investigate the mechanistic differences at 24 hours and 28 days after the exposure of BALB/c mice to ZnONPs via intratracheal instillation. An isobaric tag for the relative and absolute quantitation coupled with liquid chromatography/tandem mass spectrometry was used to identify the differential protein expression, biological processes, molecular functions, and pathways. A total of 18 and 14 proteins displayed significant changes in the lung tissues at 24 hours and 28 days after exposure, respectively, with the most striking changes being observed for S100-A9 protein. Metabolic processes and catalytic activity were the main biological processes and molecular functions, respectively, in the responses at the 24-hour and 28-day follow-up times. The glycolysis/gluconeogenesis pathway was continuously downregulated from 24 hours to 28 days, whereas detoxification pathways were activated at the 28-day time-point after exposure. A comprehensive understanding of the potential time-dependent effects of exposure to ZnONPs was provided, which highlights the metabolic mechanisms that may be important in the responses to ZnONP. PMID:26251593

  12. Characterization of pulmonary protein profiles in response to zinc oxide nanoparticles in mice: a 24-hour and 28-day follow-up study.

    PubMed

    Pan, Chih-Hong; Chuang, Kai-Jen; Chen, Jen-Kun; Hsiao, Ta-Chih; Lai, Ching-Huang; Jones, Tim P; BéruBé, Kelly A; Hong, Gui-Bing; Ho, Kin-Fai; Chuang, Hsiao-Chi

    2015-01-01

    Although zinc oxide nanoparticles (ZnONPs) are recognized to cause systemic disorders, little is known about the mechanisms that underlie the time-dependent differences that occur after exposure. The objective of this study was to investigate the mechanistic differences at 24 hours and 28 days after the exposure of BALB/c mice to ZnONPs via intratracheal instillation. An isobaric tag for the relative and absolute quantitation coupled with liquid chromatography/tandem mass spectrometry was used to identify the differential protein expression, biological processes, molecular functions, and pathways. A total of 18 and 14 proteins displayed significant changes in the lung tissues at 24 hours and 28 days after exposure, respectively, with the most striking changes being observed for S100-A9 protein. Metabolic processes and catalytic activity were the main biological processes and molecular functions, respectively, in the responses at the 24-hour and 28-day follow-up times. The glycolysis/gluconeogenesis pathway was continuously downregulated from 24 hours to 28 days, whereas detoxification pathways were activated at the 28-day time-point after exposure. A comprehensive understanding of the potential time-dependent effects of exposure to ZnONPs was provided, which highlights the metabolic mechanisms that may be important in the responses to ZnONP.

  13. Additional notes on clinical repeated-dose pharmacokinetic trials applying a peak-and-trough sampling design to estimate oral clearance.

    PubMed

    Takaai, Mari; Kayano, Yuichiro; Shimizu, Takako; Taguchi, Masato; Hashimoto, Yukiya

    2008-01-01

    In the previous study, we performed a simulation of a clinical pharmacokinetic trial, in which blood was sampled at two time points corresponding to the peak concentration (C(peak)) and trough concentration (C(trough)) following repetitive oral administration at the dose, D, and dosing interval, tau. The approximate oral clearance (CL/F(approx)), estimated as 2 x D/(C(peak) x tau+C(trough) x tau), is accurate for drugs with an elimination half-life comparative to or longer than tau; however, it was suggested that we might not use CL/F(approx) for drugs with a considerably short elimination half-life relative to tau. In the present study, we evaluated the accuracy of the alternative oral clearance (CL/F(exp)) estimated by the simple monoexponential model. In contrast to CL/F(approx), CL/F(exp) was accurate for drugs with a short elimination half-life relative to tau. The present finding in conjunction with our previous study suggested that the peak-and-trough sampling design is promising for the clinical repeated-dose pharmacokinetic trial for drugs with not only slow but also rapid elimination from the body. We think that the accuracy and precision of the two analysis methods to estimate oral clearance (CL/F(approx) and CL/F(exp)) for a target drug should be evaluated carefully before and after a real clinical trial.

  14. Cholesterol reduction and lack of genotoxic or toxic effects in mice after repeated 21-day oral intake of lemongrass (Cymbopogon citratus) essential oil.

    PubMed

    Costa, Celso A R A; Bidinotto, Lucas T; Takahira, Regina K; Salvadori, Daisy M F; Barbisan, Luís F; Costa, Mirtes

    2011-09-01

    Cymbopogon citratus (lemongrass) is currently used in traditional folk medicine. Although this species presents widespread use, there are no scientific data on its efficacy or safety after repeated treatments. Therefore, this work investigated the toxicity and genotoxicity of this lemongrass's essential oil (EO) in male Swiss mice. The single LD(50) based on a 24h acute oral toxicity study was found to be around 3500 mg/kg. In a repeated-dose 21-day oral toxicity study, mice were randomly assigned to two control groups, saline- or Tween 80 0.01%-treated groups, or one of the three experimental groups receiving lemongrass EO (1, 10 or 100mg/kg). No significant changes in gross pathology, body weight, absolute or relative organ weights, histology (brain, heart, kidneys, liver, lungs, stomach, spleen and urinary bladder), urinalysis or clinical biochemistry were observed in EO-treated mice relative to the control groups. Additionally, blood cholesterol was reduced after EO-treatment at the highest dose tested. Similarly, data from the comet assay in peripheral blood cells showed no genotoxic effect from the EO. In conclusion, our findings verified the safety of lemongrass intake at the doses used in folk medicine and indicated the beneficial effect of reducing the blood cholesterol level.

  15. Repeated vaginal SHIV challenges in macaques receiving oral or topical Pre-Exposure Prophylaxis induce virus-specific T cell responses

    PubMed Central

    Tsegaye, Theodros Solomon; Butler, Katherine; Luo, Wei; Radzio, Jessica; Srinivasan, Priya; Sharma, Sunita; Aubert, Rachael D.; Hanson, Debra L.; Dobard, Charles; Garcia-Lerma, J. Gerardo; Heneine, Walid; McNicholl, Janet M.; Kersh, Ellen N.

    2015-01-01

    Background Pre-Exposure Prophylaxis (PrEP) for HIV prevention is a novel biomedical prevention method. We have previously modeled PrEP during rectal SHIV exposures in macaques and identified that SHIV-specific T cell responses were induced in the presence of antiretroviral drugs, an observation previously termed T cell chemo-vaccination. This report expands those initial findings by examining a larger group of macaques that were given oral or topical PrEP during repeated vaginal virus exposure. Methods Thirty-six female pigtail macaques received up to 20 repeat low-dose vaginal inoculations with wild type (WT) SHIVSF162P3 (n=24) or a clonal derivative with the tenofovir K65R drug resistant mutation (n=12). PrEP consisted of oral Truvada (n=6, WT), tenofovir vaginal gel (n=6, K65R), or tenofovir intra-vaginal ring (n=6, WT). The remaining animals were PrEP-inexperienced controls (n=12, WT; n=6, K65R). SHIV-specific T cells were identified and characterized using IFNγ ELISPOT and multi-parameter flow cytometry. Results Of nine animals that were on PrEP and remained uninfected during WT SHIV vaginal challenges, eight (88.9%) developed virus-specific T cell responses. T cells were in CD4 and CD8 compartments, reached up to 4,900 IFNγ producing cells per million PBMCs, and primarily pol directed. In contrast, the replication impaired K65R virus did not induce detectable T cell responses, likely reflecting the need for adequate replication. Conclusion Virus-specific T cell responses occur frequently in oral or topical PrEP-protected pigtail macaques after vaginal exposure to WT SHIV virus. The contribution of such immune responses to protection from infection during and following PrEP warrants further investigation. PMID:25886925

  16. 26-week repeated oral dose toxicity study of UP446, a combination of defined extracts of Scutellaria baicalensis and Acacia catechu, in beagle dogs.

    PubMed

    Yimam, Mesfin; Lee, Young Chul; Jia, Qi

    2016-07-01

    The needs for relatively safe botanical alternatives to relieve symptoms associated to arthritis have continued to grow in parallel with the ageing population. UP446, a standardized bioflavonoid composition from the roots of Scutellaria baicalensis and the heartwoods of Acacia catechu, has been used as over the counter joint care dietary supplements and a prescription medical food. Significant safety data have been documented in rodents and human for this composition. Here we evaluated the potential adverse effects of orally administered UP446 in beagle dogs following a 26-week repeated oral dose toxicity study. UP446 at doses of 250, 500 and 1000 mg/kg/day were administered orally to beagle dogs for 26 weeks. A 4-week recovery group from the high dose (1000 mg/kg) and vehicle treated groups were included. No morbidity or mortality was observed for the duration of the study. No significant differences between groups in body weights, food consumption, ophthalmological examinations, electrocardiograms, urinalysis, hematology, clinical chemistry, organ weights, gross pathology and histopathology were documented. Emesis, loose feces and diarrhea were noted in both genders at the 1000 mg/kg treatment groups. These clinical signs were considered to be reversible as they were not evident in the recovery period. In conclusion, the no-observed-adverse-effect-level (NOAEL) of UP446 was considered to be 500 mg/kg/day both in male and female beagle dogs.

  17. Accumulation and effects of nodularin from a single and repeated oral doses of cyanobacterium Nodularia spumigena on flounder (Platichthys flesus L.).

    PubMed

    Vuorinen, Pekka J; Sipiä, Vesa O; Karlsson, Krister; Keinänen, Marja; Furey, Ambrose; Allis, Orla; James, Kevin; Perttilä, Ulla; Rimaila-Pärnänen, Eija; Meriluoto, Jussi A O

    2009-07-01

    Nodularin (NODLN) is a cyclic pentapeptide hepatotoxin produced by the cyanobacterium Nodularia spumigena, which occurs regularly in the Baltic Sea during the summer season. In this study flounder (Platichthys flesus L.) was orally exposed to NODLN either as a single dose or as three repeated doses 3 days apart. Liver and bile samples of the fish were taken 4 days after the last dose. Liver glutathione-S-transferase (GST) activity was also measured and the histopathology of the liver was investigated. The liver of the exposed fish was analyzed by liquid chromatography-mass spectrometry for NODLN concentration. The content of NODLN-like compounds in the bile was analyzed by enzyme-linked immunosorbent assay. NODLN exposure caused slightly incoherent liver architecture and degenerative cell changes in both groups. The mean liver GST activity was significantly higher in the repeatedly dosed flounders than in the singly dosed flounders or in the control. In conclusion, the significantly lower NODLN concentration and the increased GST activity in the liver of the repeatedly dosed flounders compared to the singly dosed flounders suggest that NODLN is rapidly detoxificated. The absence of NODLN glutathione conjugates and the low concentrations of NODLN-like compounds in the bile indicate that detoxification products disintegrate or they are rapidly excreted.

  18. Short-term repeated-dose toxicity profile of archaeosomes administered to mice via intravenous and oral routes.

    PubMed

    Omri, Abdelwahab; Agnew, Brian J; Patel, Girishchandra B

    2003-01-01

    Archaeosomes, liposomes made from polar ether lipids of archaea, show promise for vaccine and drug delivery applications. The potential toxicity of intravenously (14, 70, or 140 mg/kg/day for 5 consecutive days) and orally (gavaged at 55, 275, or 550 mg/kg/day for 10 consecutive days) administered unilamellar archaeosomes, prepared from the total polar lipids (TPLs) extracted from several species of archaea, was assessed in female BALB/c mice. Liposomes prepared from an ester phospholipid composition were included for comparative purposes. Control groups of mice were administered 0.1 ml phosphate-buffered saline (PBS) by either route. Animals were monitored at least once daily for temperature, body weight, and clinical signs of adverse reactions. One day after the last dose, the mice were sacrificed. Blood was collected for selected biochemical/enzyme analyses, and the major organs (heart, lungs, liver, spleen, kidneys) were weighed and examined macroscopically. In addition, the spleens were examined histologically. At the two lower dosages of intravenously administered vesicles, there were no significant indications of toxicity, as compared with the PBS-administered control group. At the highest intravenous dose of 140 mg/kg/day, archaeosomes prepared from the TPL of the extreme halophiles, Halobacterium salinarum and Natronobacterium magadii, indicated potential toxicity, as evidenced by clinical signs (hyperactivity and/or piloerection), drop in body temperature, and loss in body weight. Spleens from mice administered some archaeosomes types, primarily at the highest intravenous dose tested, were enlarged, had increased organ weight, and microscopic examination revealed mild to moderate expansion of the red pulp with increased numbers of hematopoietic cells, but no changes in the white pulp. There were similar clinical signs at one or more of the higher oral doses of the ester liposomes and some of the archaeosome types; however, no other apparent toxicity was

  19. A Bayesian hierarchical model for multi-level repeated ordinal data: analysis of oral practice examinations in a large anaesthesiology training programme.

    PubMed

    Tan, M; Qu, Y; Mascha, E; Schubert, A

    1999-08-15

    Oral practice examinations (OPEs) are used in many anaesthesiology programmes to familiarize anaesthesiology residents with the format of the oral examination administered by the American Board of Anesthesiology. The OPE outcome (final grade) consists of 'Definite Not Pass', 'Probable Not Pass', 'Probable Pass' and 'Definite Pass'. In our study to assess the validity of the OPE, residents took an average of two (ranging from one to six) OPEs, each of which was evaluated by two board certified anaesthesiologists randomly selected from a pool of 12. A key question of interest was to identify factors, for example, the length of training, didactic experience and other characteristics, that most influence OPE outcome. In addition, we were interested in assessing the reliability of the final grade, that is, the covariance parameters are of interest as well. However, estimating variance components in multi-level data with an unequal number of repeated ordinal outcomes presents several statistical challenges, such as how to estimate high dimensional random effects parameters, especially for ordinal outcomes. We propose a Bayesian hierarchical proportional odds model for data with such complexity. The flexibility of such a model allows us to make inference on the association of OPE outcomes with other factors and to estimate the variance components as well.

  20. Oral Administration of Recombinant Lactococcus lactis Expressing HSP65 and Tandemly Repeated P277 Reduces the Incidence of Type I Diabetes in Non-Obese Diabetic Mice

    PubMed Central

    Ma, Yanjun; Liu, Jingjing; Hou, Jing; Dong, Yuankai; Lu, Yong; Jin, Liang; Cao, Rongyue; Li, Taiming; Wu, Jie

    2014-01-01

    Diabetes mellitus type 1 (DM1) is an autoimmune disease that gradually destroys insulin-producing beta-cells. We have previously reported that mucosal administration of fusion protein of HSP65 with tandem repeats of P277 (HSP65-6P277) can reduce the onset of DM1 in non-obese diabetic (NOD) mice. To deliver large amounts of the fusion protein and to enhance long-term immune tolerance effects, in the present study, we investigated the efficacy of using orally administrated L. lactis expressing HSP65-6P277 to reduce the incidence of DM1 in NOD mice. L. lactis strain NZ9000 was engineered to express HSP65-6P277 either constitutively or by nisin induction. After immunization via gavage with the recombinant L. lactis strains to groups of 4-week old female NOD mice for 36 weeks, we observed that oral administration of recombinant L. Lactis resulted in the prevention of hyperglycemia, improved glucose tolerance and reduced insulitis. Immunologic analysis showed that treatment with recombinant L. lactis induced HSP65- and P277- specific T cell immuno-tolerance, as well as antigen-specific proliferation of splenocytes. The results revealed that the DM1-preventing function was in part caused by a reduction in the pro-inflammatory cytokine IFN-γ and an increase in the anti-inflammatory cytokine IL-10. Orally administered recombinant L. lactis delivering HSP65-6P277 may be an effective therapeutic approach in preventing DM1. PMID:25157497

  1. Disposition of Lead (Pb) in Saliva and Blood of Sprague-Dawley Rats Following a Single or Repeated Oral Exposure to Pb-Acetate

    SciTech Connect

    Timchalk, Chuck; Lin, Yuehe; Weitz, Karl K.; Wu, Hong; Gies, Richard A.; Moore, Dean A.; Yantasee, Wassana

    2006-05-01

    Biological monitoring for lead (Pb) is usually based upon a determination of blood Pb concentration; however, saliva has been suggested as a non-invasive biological matrix for assessing exposure. To further evaluate the potential utility of saliva for biomonitoring, the disposition of Pb was evaluated in whole blood (WB), red blood cells (RBC), plasma, parotid gland, bone, and saliva following either a single oral dose of 100 mg Pb-acetate/kg body weight in rats or {approx}1-week after 5 sequential daily oral gavage doses of 1, 10, or 100 mg Pb-acetate/kg/day. Saliva volume, pH, total saliva protein, and ?-amylase activity were also determined. At specified times post-dosing groups of animals were anethetized and administered pilocarpine to induce salivation. Saliva was collected, the animals were humanely sacrificed, and tissue samples were likewise collected, weighed, and processed for Pb analysis. Following a single dose exposure to PB-acetate, Pb was detectable in all samples by 30 min post-dosing. For both the single and repeated dose treatments the concentration of Pb was highest in WB and RBC relative to plasma and saliva. However, the Pb rapidly redistributed (within 5-days post-treatment) from the blood into the bone compartment based on the substantial decrease in WB and RBC Pb concentration, and the concurrent increase in bone Pb following repeated exposure at all dose levels. Although there is clear variability in the observed Pb concentrations in plasma and saliva, there was a reasonable correlation (r2=0.922) between the average Pb concentrations in these biological matrices which was consistent with previous observations. The single oral dose of Pb-acetate resulted in a decrease in salivary pH which recovered by 24 hr post-dosing and a decrease in ?-amylase enzyme activity which did recover within 5-days of ceasing exposure. It is currently unclear what impact these slight functional changes may or may not have on Pb salivary clearance rates. These

  2. Repeated Acute Oral Exposure to Cannabis sativa Impaired Neurocognitive Behaviours and Cortico-hippocampal Architectonics in Wistar Rats.

    PubMed

    Imam, A; Ajao, M S; Akinola, O B; Ajibola, M I; Ibrahim, A; Amin, A; Abdulmajeed, W I; Lawal, Z A; Ali-Oluwafuyi, A

    2017-03-06

    The most abused illicit drug in both the developing and the developed world is Cannabis disposing users to varying forms of personality disorders. However, the effects of cannabis on cortico-hippocampal architecture and cognitive behaviours still remain elusive.  The present study investigated the neuro-cognitive implications of oral cannabis use in rats. Eighteen adult Wistar rats were randomly grouped to three. Saline was administered to the control rats, cannabis (20 mg/kg) to the experimental group I, while Scopolamine (1 mg/kg. ip) was administered to the last group as a standard measure for the cannabis induced cognitive impairment. All treatments lasted for seven consecutive days. Open Field Test (OFT) was used to assess locomotor activities, Elevated Plus Maze (EPM) for anxiety-like behaviour, and Y maze paradigm for spatial memory and data subjected to ANOVA and T test respectively. Thereafter, rats were sacrificed and brains removed for histopathological studies. Cannabis significantly reduced rearing frequencies in the OFT and EPM, and increased freezing period in the OFT. It also reduced percentage alternation similar to scopolamine in the Y maze, and these effects were coupled with alterations in the cortico-hippocampal neuronal architectures. These results point to the detrimental impacts of cannabis on cortico-hippocampal neuronal architecture and morphology, and consequently cognitive deficits.

  3. Modularity of the Oral Jaws Is Linked to Repeated Changes in the Craniofacial Shape of African Cichlids

    PubMed Central

    Parsons, Kevin J.; Cooper, W. James; Albertson, R. Craig

    2011-01-01

    The African cichlids of the East-African rift-lakes provide one of the most dramatic examples of adaptive radiation known. It has long been thought that functional decoupling of the oral and pharyngeal jaws in cichlids has facilitated their explosive evolution. Recent research has also shown that craniofacial evolution from radiations in lakes Victoria, Malawi, and Tanganyika has occurred along a shared primary axis of shape divergence, whereby the preorbital region of the skull changes in a manner that is, relatively independent from other head regions. We predicted that the preorbital region would comprise a variational module and used an extensive dataset from each lake that allowed us to test this prediction using a model selection approach. Our findings supported the presence of a preorbital module across all lakes, within each lake, and for Malawi, within sand and rock-dwelling clades. However, while a preorbital module was consistently present, notable differences were also observed among groups. Of particular interest, a negative association between patterns of variational modularity was observed between the sand and rock-dwelling clades, a patter consistent with character displacement. These findings provide the basis for further experimental research involving the determination of the developmental and genetic bases of these patterns of modularity. PMID:21716745

  4. Incremental effects of 28 days of beta-alanine supplementation on high-intensity cycling performance and blood lactate in masters female cyclists.

    PubMed

    Glenn, J M; Gray, M; Stewart, R; Moyen, N E; Kavouras, S A; DiBrezzo, R; Turner, R; Baum, J

    2015-12-01

    Within the aging population, there exists a subset of individuals termed masters athletes (MA). As masters-level competition increases in popularity, MA must find methods to enhance individual athletic performance. Longitudinal beta-alanine (BA) supplementation is suggested to enhance physical capability during exercise; however, these effects have not been evaluated in MA. To examine the longitudinal effects of BA on time to exhaustion (TTE), total work completed (TWC), and lactate clearance in female MA cyclists. Twenty-two female MA (age = 53.3 ± 1.0) participated in this double-blind design. Subjects were randomly assigned to BA (n = 11; 800 mg BA + 8 g dextrose) or placebo (PLA; n = 11; 8 g dextrose) groups and supplemented 4 doses/day over 28 days. Every 7 days, subjects completed a cycling TTE at 120% VO2max, and TWC was calculated. Blood lactate was measured at baseline, immediate post, and 20-min post each TTE. No significant differences existed between groups for any variable at baseline (p > 0.05). After 28 days supplementation, BA had greater TTE (23 vs 1% change) and TWC (21 vs 2% change) than PLA (p < 0.05). Following the 20-min TTE recovery, lactate was 24% lower in BA compared to PLA (4.35 vs. 5.76 mmol/L, respectively). No differences existed for variables during intermittent weeks. 28 days of BA supplementation increased cycling performance via an enhanced time to exhaustion and total work completed with associated lactate clearance during passive rest in female MA.

  5. Prognostic factors of 28 days survival rate in patients with a first acute myocardial infarction based on gender in Isfahan, Iran (2000-2009)

    PubMed Central

    Mohammadian, Mahdi; Hosseini, Shidokht; Salehiniya, Hamid; Sadeghi, Masoumeh; Sarrafzadegan, Nizal; Roohafza, Hamid Reza; Khazaei, Salman; Soltani, Shahin; Sarrafkia, Ali; Golshahi, Jafar; Mohammadian-Hafshejani, Abdollah

    2015-01-01

    BACKGROUND Determinant prognostic factors of 28 days survival rate in patients with a first acute myocardial infarction (AMI) based on gender in teen year’s period in Isfahan, Iran, was the aim of this study. METHODS This study is a prospective hospital-based study that consisted, all patients with AMI admitted to all hospitals (private and universal hospitals) in Isfahan and Najafabad (Iran) during 2000-2009. To determinant the prognostic factors of 28 days survival rate in patients based on gender, analysis conducted separately for male and female. In analysis, we use of t-test, log Rank tests, Kaplan-Meier method, and univariate and multivariate Cox regression model. RESULTS Short-term (28 days) survival rate was 92.5% in male and 86.7% in female (P < 0.001). The adjusted hazard ratio (HR) of death for age group 80 years and older was 12.7 [95% confidence interval (CI): 5.14-31.3] in male and 8.78 (95% CI: 1.2-63.1) in female. HR for acute transmural MI of the unspecified site in male was 8.9 (95% CI: 4.68-16.97) and in female 9.33 (95% CI: 4.42-19.7). HR for receive of streptokinase in male was 1.11 (95% CI: 0.94-1.31) and in female was 0.69 (95% CI: 0.56-0.84). CONCLUSION Short-term survival rate in male was a higher than female. In male age, anatomic location of MI and hospital status and in female streptokinase use and anatomic location of MI was the most important prognostic factors of survival in-patient with AMI in Isfahan. PMID:26862341

  6. Determination of enrofloxacin stability and in vitro efficacy against Staphylococcus pseudintermedius and Pseudomonas aeruginosa in four ear cleaner solutions over a 28 day period.

    PubMed

    Metry, Catherine A; Maddox, Carol W; Dirikolu, Levent; Johnson, Yvette J; Campbell, Karen L

    2012-02-01

    Chemical stability and in vitro bactericidal efficacy of 0.9% enrofloxacin-compounded solutions were evaluated following storage at room temperature for 28 days. Chemical stability of enrofloxacin was determined by high-performance liquid chromatography (HPLC) in five compounded solutions, including sterile water. Bactericidal efficacy was determined by spiral plating serial 10-fold dilutions of bacteria and solutions followed by colony counts. Tris-EDTA [TrizEDTA(®) (TE)], Tris-EDTA and 0.15% chlorhexidine [TrizChlor(®) (TC)], 2.5% lactic acid, 0.1% salicylic acid and 0.1% parachlorometaxylenol [Epi-Otic (EO)], and 0.1% free salicylic acid, 0.1% parachlorometaxylenol and 0.5% EDTA [Epi-Otic Advanced (EA)] were used. High-performance liquid chromatography was carried out with one-step liquid/liquid extraction to detect and quantify enrofloxacin stability. Mean recoveries for compounded samples run in triplicate at 28 days were 97.7% (TE), 99.9% (TC), 98.1% (EO) and 97.8% (EA). Kruskal-Wallis analysis showed no significant difference in the percentage recovery (H=0.0539, df=3, P=0.9967). American Type Culture Collection strains of Staphylococcus pseudintermedius and Pseudomonas aeruginosa were used to evaluate in vitro efficacy following 30 min incubation on days 0, 14 and 28. Consistent in vitro bactericidal efficacy of all compounded solutions, indicated by killing >2.3×10(7) colony-forming units/mL, was seen; however, bactericidal efficacy decreased for compounded TC on day 14. Pseudomonas aeruginosa was more sensitive to the ear cleaners and enrofloxacin than S. pseudintermedius. The HPLC and in vitro data suggest that 0.9% enrofloxacin compounded with sterile water, TE, EO and EA maintains chemical stability and bactericidal efficacy for 28 days.

  7. Immunotoxicological profile of chloramine in female B6C3F1 mice when administered in the drinking water for 28 days.

    PubMed

    Guo, Tai L; Germolec, Dori R; Collins, Bradley J; Luebke, Robert W; Auttachoat, Wimolnut; Smith, Matthew J; White, Kimber L

    2011-01-01

    Monochloramine has been used to provide a disinfecting residual in water distribution systems where it is difficult to maintain an adequate free-chlorine residual or where disinfection by-product formation is of concern. The goal of this study was to characterize the immunotoxic effects of chloramine in female B(6)C(3)F(1) mice when administered via the drinking water. Mice were exposed to chloramine-containing deionized tap water at 2, 10, 20, 100, or 200 ppm for 28 days. No statistically significant differences in drinking water consumption, body weight, body weight gain, organ weights, or hematological parameters between the exposed and control animals were noted during the experimental period. There were no changes in the percentages and numbers of total B-lymphocytes, T-lymphocytes, CD4(+) and CD8(+) T-lymphocytes, natural killer (NK) cells, and macrophages in the spleen. Exposure to chloramine did not affect the IgM antibody-forming cell response to sheep red blood cells (SRBC) or anti-SRBC IgM antibody production. Minimal effects, judged to be biologically insignificant, were observed in the mixed-leukocyte response and NK activity. In conclusion, chloramine produced no toxicological and immunotoxic effects in female B(6)C(3)F(1) mice when administered for 28 days in the drinking water at concentrations ranging from 2-200 ppm.

  8. Integrating Computer Assisted Language Learning into Out-of-Class Extended Learning: The Impact of iPod Touch-Supported Repeated Reading on the Oral Reading Fluency of English for Specific Academic Purposes Students

    ERIC Educational Resources Information Center

    Papadima-Sophocleous, Salomi

    2015-01-01

    By using the formative experiment, this study investigated how an instructional intervention, consisting of a Repeated Reading (RR) technique and an iPod Touch, helped achieve a valued pedagogical goal, that of enhancing the Oral Reading Fluency (ORF) of sixteen English for Specific Academic Purposes (ESAP) first-year university students. Students…

  9. Benzo[a]pyrene (BP) DNA adduct formation in DNA repair–deficient p53 haploinsufficient [Xpa(−/−)p53(+/−)] and wild-type mice fed BP and BP plus chlorophyllin for 28 days

    PubMed Central

    Poirier, Miriam C.

    2012-01-01

    We have evaluated DNA damage (DNA adduct formation) after feeding benzo[a]pyrene (BP) to wild-type (WT) and cancer-susceptible Xpa(−/−)p53(+/−) mice deficient in nucleotide excision repair and haploinsufficient for the tumor suppressor p53. DNA damage was evaluated by high-performance liquid chromatography/electrospray ionization tandem mass spectrometry (HPLC/ES-MS/MS), which measures r7,t8,t9-trihydroxy-c-10-(N 2-deoxyguanosyl)-7,8,9,10-tetrahydrobenzo[a]pyrene (BPdG), and a chemiluminescence immunoassay (CIA), using anti-r7,t8-dihydroxy-t-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE)–DNA antiserum, which measures both BPdG and the other stable BP-DNA adducts. When mice were fed 100 ppm BP for 28 days, BP-induced DNA damage measured in esophagus, liver and lung was typically higher in Xpa(−/−)p53(+/−) mice, compared with WT mice. This result is consistent with the previously observed tumor susceptibility of Xpa(−/−)p53(+/−) mice. BPdG, the major DNA adduct associated with tumorigenicity, was the primary DNA adduct formed in esophagus (a target tissue in the mouse), whereas total BP-DNA adducts predominated in higher levels in the liver (a non-target tissue in the mouse). In an attempt to lower BP-induced DNA damage, we fed the WT and Xpa(−/−)p53(+/−) mice 0.3% chlorophyllin (CHL) in the BP-containing diet for 28 days. The addition of CHL resulted in an increase of BP–DNA adducts in esophagus, liver and lung of WT mice, a lowering of BPdG in esophagi of WT mice and livers of Xpa(−/−)p53(+/−) mice and an increase of BPdG in livers of WT mice. Therefore, the addition of CHL to a BP-containing diet showed a lack of consistent chemoprotective effect, indicating that oral CHL administration may not reduce PAH–DNA adduct levels consistently in human organs. PMID:22828138

  10. Benzo[a]pyrene (BP) DNA adduct formation in DNA repair-deficient p53 haploinsufficient [Xpa(-/-)p53(+/-)] and wild-type mice fed BP and BP plus chlorophyllin for 28 days.

    PubMed

    John, Kaarthik; Pratt, M Margaret; Beland, Frederick A; Churchwell, Mona I; McMullen, Gail; Olivero, Ofelia A; Pogribny, Igor P; Poirier, Miriam C

    2012-11-01

    We have evaluated DNA damage (DNA adduct formation) after feeding benzo[a]pyrene (BP) to wild-type (WT) and cancer-susceptible Xpa(-/-)p53(+/-) mice deficient in nucleotide excision repair and haploinsufficient for the tumor suppressor p53. DNA damage was evaluated by high-performance liquid chromatography/electrospray ionization tandem mass spectrometry (HPLC/ES-MS/MS), which measures r7,t8,t9-trihydroxy-c-10-(N (2)-deoxyguanosyl)-7,8,9,10-tetrahydrobenzo[a]pyrene (BPdG), and a chemiluminescence immunoassay (CIA), using anti-r7,t8-dihydroxy-t-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE)-DNA antiserum, which measures both BPdG and the other stable BP-DNA adducts. When mice were fed 100 ppm BP for 28 days, BP-induced DNA damage measured in esophagus, liver and lung was typically higher in Xpa(-/-)p53(+/-) mice, compared with WT mice. This result is consistent with the previously observed tumor susceptibility of Xpa(-/-)p53(+/-) mice. BPdG, the major DNA adduct associated with tumorigenicity, was the primary DNA adduct formed in esophagus (a target tissue in the mouse), whereas total BP-DNA adducts predominated in higher levels in the liver (a non-target tissue in the mouse). In an attempt to lower BP-induced DNA damage, we fed the WT and Xpa(-/-)p53(+/-) mice 0.3% chlorophyllin (CHL) in the BP-containing diet for 28 days. The addition of CHL resulted in an increase of BP-DNA adducts in esophagus, liver and lung of WT mice, a lowering of BPdG in esophagi of WT mice and livers of Xpa(-/-)p53(+/-) mice and an increase of BPdG in livers of WT mice. Therefore, the addition of CHL to a BP-containing diet showed a lack of consistent chemoprotective effect, indicating that oral CHL administration may not reduce PAH-DNA adduct levels consistently in human organs.

  11. Comparison of the toxicity of several fumonisin derivatives in a 28-day feeding study with female B6C3F(1) mice.

    PubMed

    Howard, Paul C; Couch, Letha H; Patton, Ralph E; Eppley, Robert M; Doerge, Daniel R; Churchwell, Mona I; Marques, M Matilde; Okerberg, Carlin V

    2002-12-15

    Fumonisinmycotoxins are produced by Fusaria fungi that grow worldwide primarily on corn. Fumonisin B(1), the most predominant form in corn samples, is a renal carcinogen in male F344/N rats and a hepatocarcinogen in female B6C3F(1) mice when fed at concentrations higher than 50 ppm (70 micromol/kg) in the diet for 2 years. We sought to determine the relative toxicities of several naturally occurring fumonisin derivatives when included in the diet of female B6C3F(1) mice. Mice were fed diets containing fumonisin B(1), fumonisin B(2), fumonisin B(3), fumonisin P1, hydrolyzed-fumonisin B(1), N-(acetyl)fumonisin B(1), or N-(carboxymethyl)fumonisin B(1) (approximately 0, 14, 70, and 140 micromol/kg diet) for 28 days. None of the doses used caused a decrease in body weight gain over the 28 days. Serum levels of total bile acids, cholesterol, and alkaline phosphatase were increased only in mice receiving 72 and 143 micromol/kg fumonisin B(1), suggesting that only fumonisin B(1) was hepatotoxic in the mice. Corroborating this observation, the liver weight, relative to body weight, was decreased only in the mice that consumed 143 micromol/kg fumonisin B(1). Consistent with fumonisin B(1) inhibition of ceramide synthase, the liver sphinganine-to-sphingosine ratio was increased and the liver ceramide levels were decreased only in the mice receiving 72 and 143 micromol/kg fumonisin B(1). Increased hepatocellular apoptosis, hepatocellular hypertrophy, Kupffer cell hyperplasia, and macrophage pigmentation were detected in the mice consuming 72 and 143 micromol/kg fumonisin B(1). The other fumonisin derivatives did not alter serum analytes, organ weights, or hepatic structure. These results suggest that, of the naturally occurring fumonisins, fumonisin B(1) is the principal hepatotoxic derivative in the B6C3F(1) mouse.

  12. Renal hemodynamic and morphological changes after 7 and 28 days of leptin treatment: the participation of angiotensin II via the AT1 receptor.

    PubMed

    Thieme, Karina; Oliveira-Souza, Maria

    2015-01-01

    The role of hyperleptinemia in cardiovascular diseases is well known; however, in the renal tissue, the exact site of leptin's action has not been established. This study was conducted to assess the effect of leptin treatment for 7 and 28 days on renal function and morphology and the participation of angiotensin II (Ang II), through its AT1 receptor. Rats were divided into four groups: sham, losartan (10 mg/kg/day, s.c.), leptin (0.5 mg/kg/day for the 7 days group and 0.25 mg/kg/day for the 28 days group) and leptin plus losartan. Plasma leptin, Ang II and endothelin 1 (ET-1) levels were measured using an enzymatic immuno assay. The systolic blood pressure (SBP) was evaluated using the tail-cuff method. The renal plasma flow (RPF) and the glomerular filtration rate (GFR) were determined by p-aminohippuric acid and inulin clearance, respectively. Urinary Na+ and K+ levels were also analyzed. Renal morphological analyses, desmin and ED-1 immunostaining were performed. Proteinuria was analyzed by silver staining. mRNA expression of renin-angiotensin system (RAS) components, TNF-α and collagen type III was analyzed by quantitative PCR. Our results showed that leptin treatment increased Ang II plasma levels and progressively increased the SBP, achieving a pre-hypertension state. Rats treated with leptin 7 days showed a normal RPF and GFR, but increased filtration fraction (FF) and natriuresis. However, rats treated with leptin for 28 showed a decrease in the RPF, an increase in the FF and no changes in the GFR or tubular function. Leptin treatment-induced renal injury was demonstrated by: glomerular hypertrophy, increased desmin staining, macrophage infiltration in the renal tissue, TNF-α and collagen type III mRNA expression and proteinuria. In conclusion, our study demonstrated the progressive renal morphological changes in experimental hyperleptinemia and the interaction between leptin and the RAS on these effects.

  13. 14C-NaVP and 14C-PEV repeated dose study in rat. Pharmacokinetic study in rats after repeated oral administrations of 14C-valproic acid sodium salt and 14C-valproic acid pivaloyl oxymethyl ester.

    PubMed

    Bertolino, M; Acerbi, D; Canali, S; Giachetti, C; Poli, G; Ventura, P; Zanolo, G

    1998-01-01

    The absorption, excretion and tissue distribution of radioactivity after repeated oral equimolar doses of 14C-valproic acid sodium salt (NaVP) or 14C-valproic acid pivaloyl oxymethyl ester (PEV) was investigated in male rats treated once a day for 14 consecutive days. The 14th day plasma time-course of radioactivity after PEV administrations was characterised by a slow absorption rate with a delayed peak (tmax 2 h, Cmax 7.52 +/- 1.35 microg eq./ml), followed by a plateau lasting up to 8 h. After NaVP treatment, the main peak of radioactivity was observed 0.5 h after administration (Cmax 8.30 +/- 1.26 microg eq./ml) followed by a secondary peak due to biliary enterohepatic recycling. Starting from 4 h onwards, radioactivity levels after PEV treatment were higher than those after NaVP (AUCtau = 113.3 h.microg eq./ml after PEV vs 71.9 h.microg eq./ml after NaVP), but concentrations declined with similar terminal half-lives (52.8 h for PEV and 49.7 h for NaVP). Radioactivity recovered (0-432 h interval) in urine accounted for 79.3% (PEV) and 56.1% (NaVP) while, in faeces accounted for 9.1% (PEV) and 26.1% (NaVP) of total administered dose (14 days). The difference is attributable to a higher excretion of radioactivity in the bile for NaVP. The missing fraction in the total radioactivity balance is probably excreted in expired air, as observed in single dose studies. Radioactivity excreted in bile (0-8 h interval of the last 14th day) accounted for 5.1% (NaVP) and 0.23% (PEV) of the total administered dose (14 days). A possible explanation of this difference may be a different metabolism pattern for the two compounds. The negligible biliary excretion observed after PEV administration is probably due to an inhibition of the glucuronation of valproic acid (or other metabolites) caused by the pivalic acid. Due to the presence of the enterohepatic recycle, the radioactivity levels in intestine, 0.5 and 2 h after administration, were higher after NaVP administration

  14. Aryl hydrocarbon receptor knockout rats are insensitive to the pathological effects of repeated oral exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin.

    PubMed

    Harrill, Joshua A; Layko, Debra; Nyska, Abraham; Hukkanen, Renee R; Manno, Rosa Anna; Grassetti, Andrea; Lawson, Marie; Martin, Greg; Budinsky, Robert A; Rowlands, J Craig; Thomas, Russell S

    2016-06-01

    Sustained activation of the aryl hydrocarbon receptor (AHR) is believed to be the initial key event in AHR receptor-mediated tumorigenesis in the rat liver. The role of AHR in mediating pathological changes in the liver prior to tumor formation was investigated in a 4-week, repeated-dose study using adult female wild-type (WT) and AHR knockout (AHR-KO) rats treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Beginning at 8 weeks of age, AHR-KO and WT rats were dosed by oral gavage with varying concentrations of TCDD (0, 3, 22, 100, 300 and 1000 ng kg(-1)  day(-1) ). Lung, liver and thymus histopathology, hematology, serum chemistry and the distribution of TCDD in liver and adipose tissue were examined. Treatment-related increases in the severity of liver and thymus pathology were observed in WT, but not AHR-KO rats. In the liver, these included hepatocellular hypertrophy, bile duct hyperplasia, multinucleated hepatocytes and inflammatory cell foci. A loss of cellularity in the thymic cortex and thymic atrophy was observed. Treatment-related changes in serum chemistry parameters were also observed in WT, but not AHR-KO rats. Finally, dose-dependent accumulation of TCDD was observed primarily in the liver of WT rats and primarily in the adipose tissue of AHR-KO rats. The results suggest that AHR activation is the initial key event underlying the progression of histological effects leading to liver tumorigenesis following TCDD treatment. Copyright © 2015 John Wiley & Sons, Ltd.

  15. Influence of Exercise on the Metabolic Profile Caused by 28 days of Bed Rest with Energy Deficit and Amino Acid Supplementation in Healthy Men

    PubMed Central

    Brooks, Naomi E.; Cadena, Samuel M.; Cloutier, Gregory; Vega-López, Sonia; Roubenoff, Ronenn; Castaneda-Sceppa, Carmen

    2014-01-01

    Objective Muscle loss and metabolic changes occur with disuse [i.e. bed rest (BR)]. We hypothesized that BR would lead to a metabolically unhealthy profile defined by: increased circulating tumor necrosis factor (TNF)-α, decreased circulating insulin-like-growth-factor (IGF)-1, decreased HDL-cholesterol, and decreased muscle density (MD; measured by mid-thigh computerized tomography). Methods We investigated the metabolic profile after 28 days of BR with 8±6% energy deficit in male individuals (30-55 years) randomized to resistance exercise with amino acid supplementation (RT, n=24) or amino acid supplementation alone (EAA, n=7). Upper and lower body exercises were performed in the horizontal position. Blood samples were taken at baseline, after 28 days of BR and 14 days of recovery. Results We found a shift toward a metabolically unfavourable profile after BR [compared to baseline (BLN)] in both groups as shown by decreased HDL-cholesterol levels (EAA: BLN: 39±4 vs. BR: 32±2 mg/dL, RT: BLN: 39±1 vs. BR: 32±1 mg/dL; p<0.001) and Low MD (EAA: BLN: 27±4 vs. BR: 22±3 cm2, RT: BLN: 28±2 vs. BR: 23±2 cm2; p<0.001). A healthier metabolic profile was maintained with exercise, including NormalMD (EAA: BLN: 124±6 vs. BR: 110±5 cm2, RT: BLN: 132±3 vs. BR: 131±4 cm2; p<0.001, time-by-group); although, exercise did not completely alleviate the unfavourable metabolic changes seen with BR. Interestingly, both groups had increased plasma IGF-1 levels (EAA: BLN:168±22 vs. BR 213±20 ng/mL, RT: BLN:180±10 vs. BR: 219±13 ng/mL; p<0.001) and neither group showed TNFα changes (p>0.05). Conclusions We conclude that RT can be incorporated to potentially offset the metabolic complications of BR. PMID:25317071

  16. VS411 Reduced Immune Activation and HIV-1 RNA Levels in 28 Days: Randomized Proof-of-Concept Study for AntiViral-HyperActivation Limiting Therapeutics

    PubMed Central

    Lori, Franco; De Forni, Davide; Katabira, Elly; Baev, Denis; Maserati, Renato; Calarota, Sandra A.; Cahn, Pedro; Testori, Marco; Rakhmanova, Aza; Stevens, Michael R.

    2012-01-01

    Background A new class of antiretrovirals, AntiViral-HyperActivation Limiting Therapeutics (AV-HALTs), has been proposed as a disease-modifying therapy to both reduce Human Immunodeficiency Virus Type 1 (HIV-1) RNA levels and the excessive immune activation now recognized as the major driver of not only the continual loss of CD4+ T cells and progression to Acquired Immunodeficiency Syndrome (AIDS), but also of the emergence of both AIDS-defining and non-AIDS events that negatively impact upon morbidity and mortality despite successful (ie, fully suppressive) therapy. VS411, the first-in-class AV-HALT, combined low-dose, slow-release didanosine with low-dose hydroxycarbamide to accomplish both objectives with a favorable toxicity profile during short-term administration. Five dose combinations were administered as VS411 to test the AV-HALT Proof-of-Concept in HIV-1-infected subjects. Methods Multinational, double-blind, 28-day Phase 2a dose-ranging Proof-of-Concept study of antiviral activity, immunological parameters, safety, and genotypic resistance in 58 evaluable antiretroviral-naïve HIV-1-infected adults. Randomization and allocation to study arms were carried out by a central computer system. Results were analyzed by ANOVA, Kruskal-Wallis, ANCOVA, and two-tailed paired t tests. Results VS411 was well-tolerated, produced significant reductions of HIV-1 RNA levels, increased CD4+ T cell counts, and led to significant, rapid, unprecedented reductions of immune activation markers after 28 days despite incomplete viral suppression and without inhibiting HIV-1-specific immune responses. The didanosine 200 mg/HC 900 mg once-daily formulation demonstrated the greatest antiviral efficacy (HIV-1 RNA: −1.47 log10 copies/mL; CD4+ T cell count: +135 cells/mm3) and fewest adverse events. Conclusions VS411 successfully established the Proof-of-Concept that AV-HALTs can combine antiviral efficacy with rapid, potentially beneficial reductions in the excessive immune system

  17. A 28-day rat inhalation study with an integrated molecular toxicology endpoint demonstrates reduced exposure effects for a prototypic modified risk tobacco product compared with conventional cigarettes.

    PubMed

    Kogel, Ulrike; Schlage, Walter K; Martin, Florian; Xiang, Yang; Ansari, Sam; Leroy, Patrice; Vanscheeuwijck, Patrick; Gebel, Stephan; Buettner, Ansgar; Wyss, Christoph; Esposito, Marco; Hoeng, Julia; Peitsch, Manuel C

    2014-06-01

    Towards a systems toxicology-based risk assessment, we investigated molecular perturbations accompanying histopathological changes in a 28-day rat inhalation study combining transcriptomics with classical histopathology. We demonstrated reduced biological activity of a prototypic modified risk tobacco product (pMRTP) compared with the reference research cigarette 3R4F. Rats were exposed to filtered air or to three concentrations of mainstream smoke (MS) from 3R4F, or to a high concentration of MS from a pMRTP. Histopathology revealed concentration-dependent changes in response to 3R4F that were irritative stress-related in nasal and bronchial epithelium, and inflammation-related in the lung parenchyma. For pMRTP, significant changes were seen in the nasal epithelium only. Transcriptomics data were obtained from nasal and bronchial epithelium and lung parenchyma. Concentration-dependent gene expression changes were observed following 3R4F exposure, with much smaller changes for pMRTP. A computational-modeling approach based on causal models of tissue-specific biological networks identified cell stress, inflammation, proliferation, and senescence as the most perturbed molecular mechanisms. These perturbations correlated with histopathological observations. Only weak perturbations were observed for pMRTP. In conclusion, a correlative evaluation of classical histopathology together with gene expression-based computational network models may facilitate a systems toxicology-based risk assessment, as shown for a pMRTP.

  18. Safety assessment of SDA soybean oil: results of a 28-day gavage study and a 90-day/one generation reproduction feeding study in rats.

    PubMed

    Hammond, Bruce G; Lemen, Joan K; Ahmed, Gulam; Miller, Kathleen D; Kirkpatrick, Jeannie; Fleeman, Tammye

    2008-12-01

    Long chain polyunsaturated fatty acids (LC-PUFAs) in the diet reduce risk of cardiac mortality. Fish oils are a dietary source of LC-PUFAs (EPA, DHA) but intake is low in Western diets. Adding beneficial amounts of LC-PUFAs to foods is limited by their instability and potential to impart off-flavors. Stearidonic acid (SDA), a precursor of EPA in man, is more stable than EPA/DHA in food matrices. SDA is present in fish oils (0.5-4%) and in nutraceuticals (echium, borage oil). Genes for Delta6, Delta15 desaturases were introduced into soybeans that convert linoleic and alpha-linolenic acid to SDA (15-30% fatty acids). Since addition of SDA soybean oil into human foods increases SDA intake, toxicology studies were undertaken to assess its safety. In a 28-day pilot study, rats were gavaged with SDA soybean oil at dosages up to 3g/kg body weight/day; no treatment-related adverse effects were observed. A 90-day/one generation rat reproduction study was subsequently conducted where SDA soybean oil was added to diets to provide daily doses of 1.5 and 4 g/kg body weight. There were no treatment-related adverse effects on parental animals or on reproductive performance and progeny development.

  19. Comparative biodistribution and safety profiling of olmesartan medoxomil oil-in-water oral nanoemulsion.

    PubMed

    Gorain, Bapi; Choudhury, Hira; Tekade, Rakesh Kumar; Karan, Saumen; Jaisankar, P; Pal, Tapan Kumar

    2016-12-01

    Poor aqueous solubility and unfavourable de-esterification of olmesartan medoxomil (a selective angiotensin II receptor blocker), results in low oral bioavailability of less than 26%. Improvement of oral bioavailability with prolonged pharmacodynamics activity of olmesartan in Wistar rats had been approached by nanoemulsification strategy in our previous article [Colloid Surface B, 115, 2014: 286]. In continuation to that work, we herewith report the biodistribution behaviour and 28-day repeated dose sub-chronic toxicity of olmesartan medoxomil nanoemulsion in Wistar rats following oral administration. The levels of olmesartan in collected biological samples were estimated using our validated LC-MS/MS technique. Our biodistribution study showed significantly higher brain concentrations of olmesartan (0.290 ± 0.089 μg/mL, 0.333 ± 0.071 μg/mL and 0.217 ± 0.062 μg/mL at 0.5, 2.0 and 8.0 h post dosing, respectively) when administered orally as nanoemulsion formulation as compared to the aqueous suspension. In addition, the olmesartan nanoemulsion was found to be safe and non-toxic, as it neither produced any lethality nor remarkable haematological, biochemical and structural adverse effects as observed during the 28-days sub-chronic toxicity studies in experimental Wistar rats. It is herewith envisaged that the developed nanoemulsion formulation approach for the delivery of olmesartan medoxomil via oral route can further be explored in memory dysfunction and brain ischemia, for better brain penetration and improved clinical application in stroke patients.

  20. No Increases in Biomarkers of Genetic Damage or Pathological Changes in Heart and Brain Tissues in Male Rats Administered Methylphenidate Hydrochloride (Ritalin) for 28 Days

    PubMed Central

    Witt, Kristine L.; Malarkey, David E.; Hobbs, Cheryl A.; Davis, Jeffrey P.; Kissling, Grace E.; Caspary, William; Travlos, Gregory; Recio, Leslie

    2009-01-01

    Following a 2005 report of chromosomal damage in children with attention deficit/hyperactivity disorder (ADHD) who were treated with the commonly prescribed medication methylphenidate (MPH), numerous studies have been conducted to clarify the risk for MPH-induced genetic damage. Although most of these studies reported no changes in genetic damage endpoints associated with exposure to MPH, one recent study (Andreazza et al. 2007) reported an increase in DNA damage detected by the Comet assay in blood and brain cells of Wistar rats treated by intraperitoneal injection with 1, 2, or 10 mg/kg MPH; no increases in micronucleated lymphocyte frequencies were observed in these rats. To clarify these findings, we treated adult male Wistar Han rats with 0, 2, 10, or 25 mg/kg MPH by gavage once daily for 28 consecutive days and measured micronucleated reticulocyte (MN-RET) frequencies in blood, and DNA damage in blood, brain, and liver cells 4 hr after final dosing. Flow cytometric evaluation of blood revealed no significant increases in MN-RET. Comet assay evaluations of blood leukocytes and cells of the liver, as well as of the striatum, hippocampus, and frontal cortex of the brain showed no increases in DNA damage in MPH-treated rats in any of the three treatment groups. Thus, the previously reported observations of DNA damage in blood and brain tissue of rats exposed to MPH for 28 days were not confirmed in this study. Additionally, no histopathological changes in brain or heart, or elevated serum biomarkers of cardiac injury were observed in these MPH-exposed rats. PMID:19634155

  1. No increases in biomarkers of genetic damage or pathological changes in heart and brain tissues in male rats administered methylphenidate hydrochloride (Ritalin) for 28 days.

    PubMed

    Witt, Kristine L; Malarkey, David E; Hobbs, Cheryl A; Davis, Jeffrey P; Kissling, Grace E; Caspary, William; Travlos, Gregory; Recio, Leslie

    2010-01-01

    Following a 2005 report of chromosomal damage in children with attention deficit/hyperactivity disorder (ADHD) who were treated with the commonly prescribed medication methylphenidate (MPH), numerous studies have been conducted to clarify the risk for MPH-induced genetic damage. Although most of these studies reported no changes in genetic damage endpoints associated with exposure to MPH, one recent study (Andreazza et al. [2007]: Prog Neuropsychopharmacol Biol Psychiatry 31:1282-1288) reported an increase in DNA damage detected by the Comet assay in blood and brain cells of Wistar rats treated by intraperitoneal injection with 1, 2, or 10 mg/kg MPH; no increases in micronucleated lymphocyte frequencies were observed in these rats. To clarify these findings, we treated adult male Wistar Han rats with 0, 2, 10, or 25 mg/kg MPH by gavage once daily for 28 consecutive days and measured micronucleated reticulocyte (MN-RET) frequencies in blood, and DNA damage in blood, brain, and liver cells 4 hr after final dosing. Flow cytometric evaluation of blood revealed no significant increases in MN-RET. Comet assay evaluations of blood leukocytes and cells of the liver, as well as of the striatum, hippocampus, and frontal cortex of the brain showed no increases in DNA damage in MPH-treated rats in any of the three treatment groups. Thus, the previously reported observations of DNA damage in blood and brain tissue of rats exposed to MPH for 28 days were not confirmed in this study. Additionally, no histopathological changes in brain or heart, or elevated serum biomarkers of cardiac injury were observed in these MPH-exposed rats.

  2. The Effect of Repeated Reading Instruction on Oral Reading Fluency and Its Impact on Reading Comprehension of Grade 5 English Language Learners

    ERIC Educational Resources Information Center

    Wang, W. Maria

    2011-01-01

    The Problem. In its meta-analysis on teaching children to read, U.S. National Reading Panel (NICHD & NIH, 2000) found repeated reading to be an effective technique for reading instruction. Specifically, the report determined that repeated reading procedures had a positive impact on word recognition, fluency, and comprehension across a range of…

  3. Toxicologic effects of 28-day dietary exposure to the flame retardant 1,2-dibromo-4-(1,2-dibromoethyl)-cyclohexane (TBECH) in F344 rats.

    PubMed

    Curran, Ivan H A; Liston, Virginia; Nunnikhoven, Andrée; Caldwell, Don; Scuby, Matthew J S; Pantazopoulos, Peter; Rawn, Dorothea F K; Coady, Laurie; Armstrong, Cheryl; Lefebvre, David E; Bondy, Genevieve S

    2017-02-15

    The brominated flame retardant TBECH is used as an additive to delay ignition and inhibit fires in construction materials and consumer goods. Trends in human exposure are not clear, although humans may be exposed to TBECH via indoor dust and air. In birds and fish there is some evidence of disruption in endocrine and reproductive parameters due to TBECH. In vitro studies indicate that TBECH is an androgen receptor agonist. In this study rats were exposed to 0, 10, 50, 250, 1250 or 5000mg/kg technical TBECH for 28days in diet, corresponding to 0, 0.9, 4.2, 21.3, 98.0 or 328.9mg TBECH/kg bw/d in males and 0, 0.8, 3.9, 19.4, 91.7 or 321.4mg TBECH/kg bw/d in females. Dose-dependent increases in α- and β- TBECH were detected in serum, liver and adipose. Rats in the 5000mg/kg group lost weight rapidly and were euthanized after 15-18days. At study termination rats displayed dose-dependent clinical and histopathological changes consistent with mild hepatic and renal inflammation. In male rats, evidence of gender-specific alpha2u-globulin nephropathy was not considered predictive of renal toxicity in humans. Frank immunosuppression or inappropriate immunostimulation were not apparent, nor was there a primary effect of TBECH on adaptive immunity. Some evidence of hormone disruption was observed, including changes in serum testosterone levels in males and changes in serum T3 and T4 levels in females. Apparent increases in thyroid follicular cell hypertrophy and hyperplasia in male and female rats were not statistically significant. Benchmark dose (BMD) modelling indicated that clinical changes indicative of mild nephrotoxicity and increased blood monocyte numbers indicative of inflammation and tissue damage were the most sensitive outcomes of TBECH exposure that could be modelled. Preliminary evidence of hormone disruption supports the need for rodent studies using more sensitive models of growth, development and reproduction.

  4. A Randomized, Double-Blind, Placebo-Controlled, Multicenter, 28-Day, Polysomnographic Study of Gabapentin in Transient Insomnia Induced by Sleep Phase Advance

    PubMed Central

    Furey, Sandy A.; Hull, Steven G.; Leibowitz, Mark T.; Jayawardena, Shyamalie; Roth, Thomas

    2014-01-01

    Study Objective: To evaluate multiple doses of gabapentin 250 mg on polysomnography (PSG) and participant-reported sleep assessments in a 5-h phase advance insomnia model. Methods: Adults reporting occasional disturbed sleep received gabapentin 250 mg (n = 128) or placebo (n = 128). On Days 1 and 28, participants received medication 30 min before bedtime and were in bed from 17:00 to 01:00, ∼5 h before their habitual bedtime. Sleep was assessed by PSG, a post sleep questionnaire, and the Karolinska Sleep Diary. Next-day residual effects and tolerability were evaluated. On Days 2-27, participants took medication at home 30 min before their habitual bedtime. Results: Treatment-group demographics were comparable. Gabapentin resulted in significantly less PSG wake after sleep onset (WASO) compared with placebo on Day 1 (primary endpoint, mean: 107.0 versus 149.1 min, p ≤ 0.001) and Day 28 (113.6 versus 152.3 min, p = 0.002), and significantly greater total sleep time (TST; Day 1: 347.6 versus 283.9 min; Day 28: 335.3 versus 289.1 min) (p ≤ 0.001). Participant-reported WASO and TST also showed significant treatment effects on both days. Gabapentin was associated with less %stage1 on Day 1, and greater %REM on Day 28, versus placebo. During home use, gabapentin resulted in significantly less participant-reported WASO and higher ratings of sleep quality. Gabapentin was well tolerated (most common adverse events: headache, somnolence) with no evidence of next-day impairment. Conclusion: Gabapentin 250 mg resulted in greater PSG and participant-reported sleep duration following a 5-h phase advance on Day 1 and Day 28 of use without evidence of next-day impairment, and greater sleep duration during at-home use. Citation: Furey SA, Hull SG, Leibowitz MT, Jayawardena S, Roth T. A randomized, double-blind, placebo-controlled, multicenter, 28-day, polysomnographic study of gabapentin in transient insomnia induced by sleep phase advance. J Clin Sleep Med 2014

  5. Nitrogen removal and mass balance in newly-formed Myriophyllum aquaticum mesocosm during a single 28-day incubation with swine wastewater treatment.

    PubMed

    Liu, Feng; Zhang, Shunan; Wang, Yi; Li, Yong; Xiao, Runlin; Li, Hongfang; He, Yang; Zhang, Miaomiao; Wang, Di; Li, Xi; Wu, Jinshui

    2016-01-15

    The aim of this research was to assess the applicability of Myriophyllum (M.) aquaticum for swine wastewater treatment. Nitrogen (N) removal processes were investigated in M. aquaticum mesocosms with swine wastewater (SW), 50% diluted swine wastewater (50% SW), and two strengths of synthetic wastewater, 200 mg [Formula: see text] L(-1) (200 [Formula: see text] ) and 400 mg [Formula: see text] L(-1) (400 [Formula: see text] ). During a 28-day incubation period, the average [Formula: see text] and TN removal rates were 99.8% and 94.2% for 50% SW and 99.8% and 93.8% for SW, which were greater than 86.5% and 83.7% for 200 [Formula: see text] , and 73.7% and 74.1% for 400 [Formula: see text] , respectively. A maximum areal total nitrogen (TN) removal rate of 157.8 mg N m(-2) d(-1) was found in M. aquaticum mesocosms with SW. During the incubation period, the observed dynamics of [Formula: see text] concentrations in water and gene copy numbers of ammonia-oxidizing archaea (AOA), ammonia-oxidizing bacteria (AOB), nirK and nirS in soil unraveled strong nitrification and denitrification processes occurring in M. aquaticum mesocosms with swine wastewater. The N mass balance analysis indicated that plant uptake and soil N accumulation accounted for 17.9-42.2% and 18.0-43.8% of the initial TN load, respectively. The coupled nitrification and denitrification process was calculated to account for, on average, 36.8% and 62.8% of TN removal for 50% SW and SW, respectively. These findings demonstrated that the N uptake by M. aquaticum contributed to a considerable proportion of N removal. In particular, the activities of ammonia-oxidizing and denitrification microbes responsible for nitrification and denitrification processes in M. aquaticum mesocosm accelerated [Formula: see text] and TN removal from swine wastewater.

  6. Efficacy and safety of extended dosing schedules of CC-486 (oral azacitidine) in patients with lower-risk myelodysplastic syndromes

    PubMed Central

    Garcia-Manero, G; Gore, S D; Kambhampati, S; Scott, B; Tefferi, A; Cogle, C R; Edenfield, W J; Hetzer, J; Kumar, K; Laille, E; Shi, T; MacBeth, K J; Skikne, B

    2016-01-01

    CC-486, the oral formulation of azacitidine (AZA), is an epigenetic modifier and DNA methyltransferase inhibitor in clinical development for treatment of hematologic malignancies. CC-486 administered for 7 days per 28-day treatment cycle was evaluated in a phase 1 dose-finding study. AZA has a short plasma half-life and DNA incorporation is S-phase-restricted; extending CC-486 exposure may increase the number of AZA-affected diseased target cells and maximize therapeutic effects. Patients with lower-risk myelodysplastic syndromes (MDS) received 300 mg CC-486 once daily for 14 days (n=28) or 21 days (n=27) of repeated 28-day cycles. Median patient age was 72 years (range 31–87) and 75% of patients had International Prognostic Scoring System Intermediate-1 risk MDS. Median number of CC-486 treatment cycles was 7 (range 2–24) for the 14-day dosing schedule and 6 (1–24) for the 21-day schedule. Overall response (complete or partial remission, red blood cell (RBC) or platelet transfusion independence (TI), or hematologic improvement) (International Working Group 2006) was attained by 36% of patients receiving 14-day dosing and 41% receiving 21-day dosing. RBC TI rates were similar with both dosing schedules (31% and 38%, respectively). CC-486 was generally well-tolerated. Extended dosing schedules of oral CC-486 may provide effective long-term treatment for patients with lower-risk MDS. PMID:26442612

  7. Efficacy and safety of extended dosing schedules of CC-486 (oral azacitidine) in patients with lower-risk myelodysplastic syndromes.

    PubMed

    Garcia-Manero, G; Gore, S D; Kambhampati, S; Scott, B; Tefferi, A; Cogle, C R; Edenfield, W J; Hetzer, J; Kumar, K; Laille, E; Shi, T; MacBeth, K J; Skikne, B

    2016-04-01

    CC-486, the oral formulation of azacitidine (AZA), is an epigenetic modifier and DNA methyltransferase inhibitor in clinical development for treatment of hematologic malignancies. CC-486 administered for 7 days per 28-day treatment cycle was evaluated in a phase 1 dose-finding study. AZA has a short plasma half-life and DNA incorporation is S-phase-restricted; extending CC-486 exposure may increase the number of AZA-affected diseased target cells and maximize therapeutic effects. Patients with lower-risk myelodysplastic syndromes (MDS) received 300 mg CC-486 once daily for 14 days (n=28) or 21 days (n=27) of repeated 28-day cycles. Median patient age was 72 years (range 31-87) and 75% of patients had International Prognostic Scoring System Intermediate-1 risk MDS. Median number of CC-486 treatment cycles was 7 (range 2-24) for the 14-day dosing schedule and 6 (1-24) for the 21-day schedule. Overall response (complete or partial remission, red blood cell (RBC) or platelet transfusion independence (TI), or hematologic improvement) (International Working Group 2006) was attained by 36% of patients receiving 14-day dosing and 41% receiving 21-day dosing. RBC TI rates were similar with both dosing schedules (31% and 38%, respectively). CC-486 was generally well-tolerated. Extended dosing schedules of oral CC-486 may provide effective long-term treatment for patients with lower-risk MDS.

  8. Safety Evaluation of Multiple Strains of Lactobacillus plantarum and Pediococcus pentosaceus in Wistar Rats Based on the Ames Test and a 28-Day Feeding Study

    PubMed Central

    Leu, Sew-Fen; Huang, Quan-Rong; Chou, Lan-Chun; Huang, Chun-Chih

    2014-01-01

    Three lactic acid bacterial strains, Lactobacillus plantarum, HK006, and HK109, and Pediococcus pentosaceus PP31 exhibit probiotic potential as antiallergy agents, both in vitro and in vivo. However, the safety of these new strains requires evaluation when isolated from infant faeces or pickled cabbage. Multiple strains (HK006, HK109, and PP31) were subject to a bacterial reverse mutation assay and a short-term oral toxicity study. The powder product exhibited mutagenic potential in Salmonella Typhimurium strains TA98 and TA1535 (with or without metabolic activation). In the short-term oral toxicity study, rats received a normal dosage of 390 mg/kg/d (approximately 9 × 109 CFU/kg/d) or a high dosage of 1950 mg/kg/d (approximately 4.5 × 1010 CFU/kg/d) for 28 d. No adverse effects were observed regarding the general condition, behaviour, growth, feed and water consumption, haematology, clinical chemistry indices, organ weights, or histopathologic analysis of the rats. These studies have demonstrated that the consumption of multiple bacterial strains is not associated with any signs of mutagenicity of S. Typhimurium or toxicity in Wistar rats, even after consuming large quantities of bacteria. PMID:25379552

  9. Repeated nightmares

    MedlinePlus

    ... different from night terrors . Alternative Names Nightmares - repeated; Dream anxiety disorder References American Academy of Family Physicians. Information from your family doctor. Nightmares and night terrors in children. ...

  10. Biodistribution of PLGA and PLGA/chitosan nanoparticles after repeat-dose oral delivery in F344 rats for 7 days

    PubMed Central

    Navarro, Sara M; Darensbourg, Caleb; Cross, Linda; Stout, Rhett; Coulon, Diana; Astete, Carlos E; Morgan, Timothy; Sabliov, Cristina M

    2015-01-01

    Aim To quantify in vivo the biodistribution of poly(lactic-co-glycolic) acid (PLGA) and PLGA/chitosan nanoparticles (PLGA/Chi NPs) and assess if the positive charge of chitosan significantly enhances nanoparticle absorption in the GI tract. Material & methods PLGA and PLGA/Chi NPs covalently linked to tetramethylrhodamine-5-isothiocyanate (TRITC) were orally administered to F344 rats for 7 days, and the biodistribution of fluorescent NPs was analyzed in different organs. Results The highest amount of particles (% total dose/g) was detected for both treatments in the spleen, followed by intestine and kidney, and then by liver, lung, heart and brain, with no significant difference between PLGA and PLGA/Chi NPs. Conclusion Only a small percentage of orally delivered NPs was detected in the analyzed organs. The positive charge conferred by chitosan was not sufficient to improve the absorption of the PLGA/Chi NPs over that of PLGA NPs. PMID:25491670

  11. Repeated Reading. What Works Clearinghouse Intervention Report

    ERIC Educational Resources Information Center

    What Works Clearinghouse, 2014

    2014-01-01

    "Repeated reading" is an academic practice that aims to increase oral reading fluency. "Repeated reading" can be used with students who have developed initial word reading skills but demonstrate inadequate reading fluency for their grade level. During "repeated reading," a student sits in a quiet location with a…

  12. A 90-day repeated dose oral (gavage) toxicity study of perfluorohexanoic acid (PFHxA) in rats (with functional observational battery and motor activity determinations).

    PubMed

    Chengelis, Christopher P; Kirkpatrick, Jeannie B; Radovsky, Ann; Shinohara, Motoki

    2009-06-01

    Possible toxic effects of perfluorohexanoic acid (PFHxA) were evaluated when administered orally by gavage to rats at levels up to 200mg/kg/day for 90 days. Lower body weight gains were noted in the 10, 50 and 200mg/kg/day group males (not dose-responsive) throughout dosing. Other changes included lower red blood cell parameters, higher reticulocyte counts and lower globulin in the 200mg/kg/day group males and females, higher liver enzymes in males at 50 and 200mg/kg/day, lower total protein and higher albumin/globulin ratio, and lower cholesterol, calcium in males at 200mg/kg/day. Minimal centrilobular hepatocellular hypertrophy was present in 200mg/kg/day group males and correlated with higher liver weights and slightly higher peroxisome beta oxidation activity at the end of the dosing period. Based on liver histopathology and liver weight changes, the no-observed-adverse-effect level (NOAEL) for oral administration was 50mg/kg/day for males and 200mg/kg/day for females.

  13. Discovery of a 3-(4-Pyrimidinyl) Indazole (MLi-2), an Orally Available and Selective Leucine-Rich Repeat Kinase 2 (LRRK2) Inhibitor that Reduces Brain Kinase Activity.

    PubMed

    Scott, Jack D; DeMong, Duane E; Greshock, Thomas J; Basu, Kallol; Dai, Xing; Harris, Joel; Hruza, Alan; Li, Sarah W; Lin, Sue-Ing; Liu, Hong; Macala, Megan K; Hu, Zhiyong; Mei, Hong; Zhang, Honglu; Walsh, Paul; Poirier, Marc; Shi, Zhi-Cai; Xiao, Li; Agnihotri, Gautam; Baptista, Marco A S; Columbus, John; Fell, Matthew J; Hyde, Lynn A; Kuvelkar, Reshma; Lin, Yinghui; Mirescu, Christian; Morrow, John A; Yin, Zhizhang; Zhang, Xiaoping; Zhou, Xiaoping; Chang, Ronald K; Embrey, Mark W; Sanders, John M; Tiscia, Heather E; Drolet, Robert E; Kern, Jonathan T; Sur, Sylvie M; Renger, John J; Bilodeau, Mark T; Kennedy, Matthew E; Parker, Eric M; Stamford, Andrew W; Nargund, Ravi; McCauley, John A; Miller, Michael W

    2017-03-16

    Leucine-rich repeat kinase 2 (LRRK2) is a large, multidomain protein which contains a kinase domain and GTPase domain among other regions. Individuals possessing gain of function mutations in the kinase domain such as the most prevalent G2019S mutation have been associated with an increased risk for the development of Parkinson's disease (PD). Given this genetic validation for inhibition of LRRK2 kinase activity as a potential means of affecting disease progression, our team set out to develop LRRK2 inhibitors to test this hypothesis. A high throughput screen of our compound collection afforded a number of promising indazole leads which were truncated in order to identify a minimum pharmacophore. Further optimization of these indazoles led to the development of MLi-2 (1): a potent, highly selective, orally available, brain-penetrant inhibitor of LRRK2.

  14. Hepatic effects of repeated oral administration of diclofenac to hepatic cytochrome P450 reductase null (HRN™) and wild-type mice.

    PubMed

    Akingbasote, James A; Foster, Alison J; Wilson, Ian; Sarda, Sunil; Jones, Huw B; Kenna, J Gerry

    2016-04-01

    Hepatic NADPH-cytochrome P450 oxidoreductase null (HRN™) mice exhibit normal hepatic and extrahepatic biotransformation enzyme activities when compared to wild-type (WT) mice, but express no functional hepatic cytochrome P450 activities. When incubated in vitro with [(14)C]-diclofenac, liver microsomes from WT mice exhibited extensive biotransformation to oxidative and glucuronide metabolites and covalent binding to proteins was also observed. In contrast, whereas glucuronide conjugates and a quinone-imine metabolite were formed when [(14)C]-diclofenac was incubated with HRN™ mouse liver, only small quantities of P450-derived oxidative metabolites were produced in these samples and covalent binding to proteins was not observed. Livers from vehicle-treated HRN™ mice exhibited enhanced lipid accumulation, bile duct proliferation, hepatocellular degeneration and necrosis and inflammatory cell infiltration, which were not present in livers from WT mice. Elevated liver-derived alanine aminotransferase, glutamate dehydrogenase and alkaline phosphatase activities were also observed in plasma from HRN™ mice. When treated orally with diclofenac for 7 days, at 30 mg/kg/day, the severities of the abnormal liver histopathology and plasma liver enzyme findings in HRN™ mice were reduced markedly. Oral diclofenac administration did not alter the liver histopathology or elevate plasma enzyme activities of WT mice. These findings indicate that HRN™ mice are valuable for exploration of the role played by hepatic P450s in drug biotransformation, but poorly suited to investigations of drug-induced liver toxicity. Nevertheless, studies in HRN™ mice could provide novel insights into the role played by inflammation in liver injury and may aid the evaluation of new strategies for its treatment.

  15. Assessment of the safety of hydrogenated resistant maltodextrin: reverse mutation assay, acute and 90-day subchronic repeated oral toxicity in rats, and acute no-effect level for diarrhea in humans.

    PubMed

    Yoshikawa, Yuko; Kishimoto, Yuka; Tagami, Hiroyuki; Kanahori, Sumiko

    2013-01-01

    A series of safety assessments were performed on hydrogenated resistant maltodextrin prepared by converting the reducing terminal glucose of resistant maltodextrin into sorbitol. The reverse mutation assay did not show mutagenicity. Acute and 90-day subchronic oral toxicity studies in rats showed no death was observed in any groups, including the group receiving the highest single dose of 10 g/kg body weight or the highest dose of 5 g/kg body weight per day for 90 days. Mucous or watery stools were observed in the hydrogenated resistant maltodextrin treatment group on the acute study, which were transient and were associated with the osmotic pressure caused by intake of the high concentrations. Subchronic study showed dose-dependent increases in the weights of cecum alone, cecal contents alone, and cecum with cecal contents as well as hypertrophy of the cecal mucosal epithelium, which are considered to be common physiological responses after intake of indigestible carbohydrates. These results indicated that the no observed adverse effect level (NOAEL) of hydrogenated resistant maltodextrin was 10 g/kg body weight or more on the acute oral toxicity study and 5.0 g/kg body weight/day or more on the 90-day subchronic repeated oral toxicity study in rats. Further study performed in healthy adult humans showed that the acute no-effect level of hydrogenated resistant maltodextrin for diarrhea was 0.8 g/kg body weight for men and more than 1.0 g/kg body weight for women. The results of the current safety assessment studies suggest that hydrogenated resistant maltodextrin is safe for human consumption.

  16. Single- and repeated-dose oral toxicity studies of citicoline free-base (choline cytidine 5'-pyrophosphate) in Sprague-Dawley rats.

    PubMed

    Schauss, A G; Somfai-Relle, S; Financsek, I; Glavits, R; Parent, S C; Endres, J R; Varga, T; Szücs, Z; Clewell, A

    2009-01-01

    The dietary supplement Citicoline free-base (choline cytidine 5'-pyrophosphate) was toxicologically evaluated in Sprague-Dawley rats using oral gavage. In an acute 14-day study, 2000 mg/kg was well tolerated. In a 90-day study, 100, 350, and 1000 mg/kg/day doses resulted in no mortality. In males, slight significant increases in serum creatinine (350 and 1000 mg/kg/day), and decreases in urine volume (all treated groups) were observed. In females, slight significant increases in total white blood cell and absolute lymphocyte counts (1000 mg/kg/day), and blood urea nitrogen (BUN) (100 and 350, but not 1000 mg/kg/day) were noted. A dose-related increase in renal tubular mineralization, without degenerative or inflammatory reaction, was found in females (all treated groups) and two males (1000 mg/kg/day). Renal mineralization in rats (especially females) is influenced by calcium:phosphorus ratios in the diet. A high level of citicoline consumption resulted in increased phosphorus intake in the rats, and likely explains this result.

  17. Evaluation of 90-day Repeated Dose Oral Toxicity, Glycometabolism, Learning and Memory Ability, and Related Enzyme of Chromium Malate Supplementation in Sprague-Dawley Rats.

    PubMed

    Feng, Weiwei; Wu, Huiyu; Li, Qian; Zhou, Zhaoxiang; Chen, Yao; Zhao, Ting; Feng, Yun; Mao, Guanghua; Li, Fang; Yang, Liuqing; Wu, Xiangyang

    2015-11-01

    Our previous study showed that chromium malate improved the regulation of blood glucose in mice with alloxan-induced diabetes. The present study was designed to evaluate the 90-day oral toxicity of chromium malate in Sprague-Dawley rats. The present study inspected the effect of chromium malate on glycometabolism, glycometabolism-related enzymes, lipid metabolism, and learning and memory ability in metabolically healthy Sprague-Dawley rats. The results showed that all rats survived and pathological, toxic, feces, and urine changes were not observed. Chromium malate did not cause measurable damage on liver, brain, and kidney. The fasting blood glucose, serum insulin, insulin resistance index, C-peptide, hepatic glycogen, glucose-6-phosphate dehydrogenase, glucokinase, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglyceride levels of normal rats in chromium malate groups had no significant change when compared with control group and chromium picolinate group under physiologically relevant conditions. The serum and organ content of Cr in chromium malate groups had no significant change compared with control group. No significant changes were found in morris water maze test and superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and true choline esterase (TChE) activity. The results indicated that supplementation with chromium malate did not cause measurable toxicity and has no obvious effect on glycometabolism and related enzymes, learning and memory ability, and related enzymes and lipid metabolism of female and male rats. The results of this study suggest that chromium malate is safe for human consumption.

  18. Presenting symptoms, pre-hospital delay time and 28-day case fatality in patients with peripheral arterial disease and acute myocardial infarction from the MONICA/KORA Myocardial Infarction Registry.

    PubMed

    Kirchberger, Inge; Amann, Ute; Heier, Margit; Kuch, Bernhard; Thilo, Christian; Peters, Annette; Meisinger, Christa

    2017-02-01

    Background Previous studies have indicated that patients with acute myocardial infarction (AMI) who have a history of peripheral arterial disease (PAD) have different characteristics and poorer outcomes than patients without PAD. However, data on short-term mortality are conflicting and it is unclear whether patients with PAD have a different scope of AMI symptoms or differences in pre-hospital delay time (PHDT) compared with patients without PAD. The objective of this study was to determine the associations between a history of PAD and presenting AMI symptoms, PHDT and 28-day case fatality in a population-based sample of patients with AMI. Design This was an observational study. Methods Information on history of PAD was obtained from the patients' medical records and their AMI symptoms were assessed by interviews with patients. Multivariable logistic regression models were used to determine the association of PAD with AMI symptoms and 28-day case fatality. A multivariable linear regression model was developed to examine the relations between PAD and PHDT. Results From the 5848 patients with AMI included in this study, 9.8% had a history of PAD. Patients with PAD were significantly less likely to report chest symptoms (odds ratio (OR) 0.52, 95% confidence interval (CI) 0.41-0.66) or pain in the upper left extremity (OR 0.67, 95% CI 0.54-0.84) than patients without PAD. PAD was significantly related with longer PHDT in patients <69 years of age ( p = 0.0117) and men ( p = 0.0104). A significantly higher 28-day case fatality (OR 2.09, 95% CI 1.47-2.96) was found in patients with PAD compared with patients without PAD. Conclusions Patients with PAD should receive comprehensive education on the possibility of atypical AMI symptoms and the need to call emergency medical services immediately.

  19. Short-term (28 days) prognosis between genders according to the type of coronary event (Q-wave versus non-Q-wave acute myocardial infarction versus unstable angina pectoris).

    PubMed

    Marrugat, Jaume; García, María; Elosua, Roberto; Aldasoro, Elena; Tormo, María José; Zurriaga, Oscar; Arós, Fernando; Masiá, Rafael; Sanz, Ginés; Valle, Vicente; López De Sá, Esteban; Sala, Joan; Segura, Antonio; Rubert, Catalina; Moreno, Concepción; Cabadés, Adolfo; Molina, Lluís; López-Sendón, José Luís; Gil, Miguel

    2004-11-01

    The type of acute coronary syndrome may account for different prognoses between men and women after myocardial infarction. This study assessed gender differences in 28-day mortality rates for first or recurrent Q-wave and non-Q-wave myocardial infarctions and unstable angina by using data from 5 registries that included 20,836 patients (24.8% women). Mortality rates were higher in women with first Q-wave myocardial infarction but not in the other patients after adjusting for confounding variables.

  20. Acute toxicity assessment of choline by inhalation, intraperitoneal and oral routes in Balb/c mice.

    PubMed

    Mehta, Amit Kumar; Arora, Naveen; Gaur, Shailendra Nath; Singh, Bhanu Pratap

    2009-08-01

    Studies suggest that choline has potential to be used as a dietary supplement and a drug for immune inflammatory diseases like asthma and rhinitis. But there are apprehensions regarding adverse effects of choline when given orally in high doses. To address this knowledge gap, toxicity assessment of choline chloride was carried out by intranasal (i.n.), oral and intraperitoneal (i.p.) routes in Balb/c mice for 28days. Body weight, food and water consumption of mice were recorded daily. Hematology and clinical chemistry were assessed to check hepatocellular functions and morphological alterations of the cells. Splenocyte counts were analysed for evaluating cellular immunity. Liver function test was performed by assaying different enzyme systems in serum such as, urea, blood urea nitrogen (BUN), creatinine, alanine aminotransferase (ALT), and aspartate aminotransferase (AST). Body weight, food and water consumption did not differ between mice treated with choline and the saline control group. Hematologic and biochemical variables were not affected with any increase in serum toxicity marker enzymes indicating normal liver functioning. Choline administration did not affect total cholesterol and high density lipoprotein levels as compared to their respective controls. Urea and blood urea nitrogen levels in choline treated mice were not different than controls. Creatinine level was, however, higher than control in i.p. treatment group, but other parameters were normal. In conclusion, the repeated consumption of choline chloride via i.n. and oral or i.p. routes did not cause toxicity in mice in the toxicological endpoints examined.

  1. Citrus aurantium L. essential oil exhibits anxiolytic-like activity mediated by 5-HT1A-receptors and reduces cholesterol after repeated oral treatment

    PubMed Central

    2013-01-01

    Background The current treatments for anxiety disorders and depression have multiple adverse effects in addition to a delayed onset of action, which has prompted efforts to find new substances with potential activity in these disorders. Citrus aurantium was chosen based on ethnopharmacological data because traditional medicine refers to the Citrus genus as useful in diminishing the symptoms of anxiety or insomnia, and C. aurantium has more recently been proposed as an adjuvant for antidepressants. In the present work, we investigated the biological activity underlying the anxiolytic and antidepressant effects of C. aurantium essential oil (EO), the putative mechanism of the anxiolytic-like effect, and the neurochemical changes in specific brain structures of mice after acute treatment. We also monitored the mice for possible signs of toxicity after a 14-day treatment. Methods The anxiolytic-like activity of the EO was investigated in a light/dark box, and the antidepressant activity was investigated in a forced swim test. Flumazenil, a competitive antagonist of benzodiazepine binding, and the selective 5-HT1A receptor antagonist WAY100635 were used in the experimental procedures to determine the mechanism of action of the EO. To exclude false positive results due to motor impairment, the mice were submitted to the rotarod test. Results The data suggest that the anxiolytic-like activity observed in the light/dark box procedure after acute (5 mg/kg) or 14-day repeated (1 mg/kg/day) dosing was mediated by the serotonergic system (5-HT1A receptors). Acute treatment with the EO showed no activity in the forced swim test, which is sensitive to antidepressants. A neurochemical evaluation showed no alterations in neurotransmitter levels in the cortex, the striatum, the pons, and the hypothalamus. Furthermore, no locomotor impairment or signs of toxicity or biochemical changes, except a reduction in cholesterol levels, were observed after treatment with the EO. Conclusion

  2. Effects of 28 days of resistance exercise and consuming a commercially available pre-workout supplement, NO-Shotgun®, on body composition, muscle strength and mass, markers of satellite cell activation, and clinical safety markers in males

    PubMed Central

    Shelmadine, Brian; Cooke, Matt; Buford, Thomas; Hudson, Geoffrey; Redd, Liz; Leutholtz, Brian; Willoughby, Darryn S

    2009-01-01

    Purpose This study determined the effects of 28 days of heavy resistance exercise combined with the nutritional supplement, NO-Shotgun®, on body composition, muscle strength and mass, markers of satellite cell activation, and clinical safety markers. Methods Eighteen non-resistance-trained males participated in a resistance training program (3 × 10-RM) 4 times/wk for 28 days while also ingesting 27 g/day of placebo (PL) or NO-Shotgun® (NO) 30 min prior to exercise. Data were analyzed with separate 2 × 2 ANOVA and t-tests (p < 0.05). Results Total body mass was increased in both groups (p = 0.001), but without any significant increases in total body water (p = 0.77). No significant changes occurred with fat mass (p = 0.62); however fat-free mass did increase with training (p = 0.001), and NO was significantly greater than PL (p = 0.001). Bench press strength for NO was significantly greater than PL (p = 0.003). Myofibrillar protein increased with training (p = 0.001), with NO being significantly greater than PL (p = 0.019). Serum IGF-1 (p = 0.046) and HGF (p = 0.06) were significantly increased with training and for NO HGF was greater than PL (p = 0.002). Muscle phosphorylated c-met was increased with training for both groups (p = 0.019). Total DNA was increased in both groups (p = 0.006), while NO was significantly greater than PL (p = 0.038). For DNA/protein, PL was decreased and NO was not changed (p = 0.014). All of the myogenic regulatory factors were increased with training; however, NO was shown to be significantly greater than PL for Myo-D (p = 0.008) and MRF-4 (p = 0.022). No significant differences were located for any of the whole blood and serum clinical chemistry markers (p > 0.05). Conclusion When combined with heavy resistance training for 28 days, NO-Shotgun® is not associated with any negative side effects, nor does it abnormally impact any of the clinical chemistry markers. Rather, NO-Shotgun® effectively increases muscle strength and mass

  3. Repeated-dose liver micronucleus test of 4,4'-methylenedianiline using young adult rats.

    PubMed

    Sanada, Hisakazu; Koyama, Naomi; Wako, Yumi; Kawasako, Kazufumi; Hamada, Shuichi

    2015-03-01

    Liver micronucleus (MN) tests using partial hepatectomized rats or juvenile rats have been shown to be useful for the detection of hepatic carcinogens. Moreover, Narumi et al. established the repeated-dose liver MN test using young adult rats for integration into general toxicity. In the present study, in order to examine the usefulness of the repeated-dose liver MN test, we investigated MN induction with a 14 or 28 day treatment protocol using young adult rats treated with 4,4′-methylenedianiline (MDA), a known hepatic carcinogen. MDA dose-dependently induced micronuclei in hepatocytes in 14- and 28-day repeated-dose tests. However, although statistically significant increases in micronuclei were observed in bone marrow cells at two dose levels in the 14-day study, there was no dose response and no increases in micronuclei in the 28-day study. These results indicate that the evaluation of genotoxic effects using hepatocytes is effective in cases where chromosomal aberrations are not clearly detectable in bone marrow cells. Moreover, the repeated-dose liver MN test allows evaluation at a dose below the maximum tolerable dose, which is required for the conventional MN test because micronucleated hepatocytes accumulate. The repeated-dose liver MN test employed in the present study can be integrated into the spectrum of general toxicity tests without further procedural modifications.

  4. Oral Transliterating. PEPNet Tipsheet

    ERIC Educational Resources Information Center

    Troiano, Claire A.

    2010-01-01

    An oral transliterator provides communication access to a person who is deaf or hard of hearing and who uses speechreading and speaking as a means of communicating. The oral transliterator, positioned in front of the speechreader, inaudibly repeats the spoken message, making it as speechreadable as possible. This is called Expressive Oral…

  5. Toxicity of aerosols of nicotine and pyruvic acid (separate and combined) in Sprague-Dawley rats in a 28-day OECD 412 inhalation study and assessment of systems toxicology.

    PubMed

    Phillips, Blaine; Esposito, Marco; Verbeeck, Jan; Boué, Stéphanie; Iskandar, Anita; Vuillaume, Gregory; Leroy, Patrice; Krishnan, Subash; Kogel, Ulrike; Utan, Aneli; Schlage, Walter K; Bera, Monali; Veljkovic, Emilija; Hoeng, Julia; Peitsch, Manuel C; Vanscheeuwijck, Patrick

    2015-01-01

    Toxicity of nebulized nicotine (Nic) and nicotine/pyruvic acid mixtures (Nic/Pyr) was characterized in a 28-day Organization for Economic Co-operation and Development 412 inhalation study with additional transcriptomic and lipidomic analyses. Sprague-Dawley rats were nose-only exposed, 6 h/day, 5 days/week to filtered air, saline, nicotine (50 µg/l), sodium pyruvate (NaPyr, 33.9 µg/l) or equimolar Nic/Pyr mixtures (18, 25 and 50 µg nicotine/l). Saline and NaPyr caused no health effects, but rats exposed to nicotine-containing aerosols had decreased body weight gains and concentration-dependent increases in liver weight. Blood neutrophil counts were increased and lymphocyte counts decreased in rats exposed to nicotine; activities of alkaline phosphatase and alanine aminotransferase were increased, and levels of cholesterol and glucose decreased. The only histopathologic finding in non-respiratory tract organs was increased liver vacuolation and glycogen content. Respiratory tract findings upon nicotine exposure (but also some phosphate-buffered saline aerosol effects) were observed only in the larynx and were limited to adaptive changes. Gene expression changes in the lung and liver were very weak. Nic and Nic/Pyr caused few significant changes (including Cyp1a1 gene upregulation). Changes were predominantly related to energy metabolism and fatty acid metabolism but did not indicate an obvious toxicity-related response. Nicotine exposure lowered plasma lipids, including cholesteryl ester (CE) and free cholesterol and, in the liver, phospholipids and sphingolipids. Nic, NaPyr and Nic/Pyr decreased hepatic triacylglycerol and CE. In the lung, Nic and Nic/Pyr increased CE levels. These data suggest that only minor biologic effects related to inhalation of Nic or Nic/Pyr aerosols were observed in this 28-day study.

  6. Identification of epigenetically downregulated Tmem70 and Ube2e2 in rat liver after 28-day treatment with hepatocarcinogenic thioacetamide showing gene product downregulation in hepatocellular preneoplastic and neoplastic lesions produced by tumor promotion.

    PubMed

    Mizukami, Sayaka; Yafune, Atsunori; Watanabe, Yousuke; Nakajima, Kota; Jin, Meilan; Yoshida, Toshinori; Shibutani, Makoto

    2017-01-15

    The present study identified genes showing promoter region hypermethylation by CpG island microarrays in the liver of rats treated with hepatocarcinogen thioacetamide (TAA) for 28days. Among 47 hypermethylated genes, Hist1h2aa, Tmem70, Ube2e2, and Slk were confirmed to show hypermethylation by methylation-specific quantitative polymerase chain reaction (PCR) and pyrosequencing analyses as well as downregulation of transcript levels by real-time reverse transcription-PCR analysis in the livers of rats treated with TAA. All gene products of the 4 selected genes showed decreased immunoreactivity forming negative liver cell foci in a subpopulation of glutathione S-transferase placental form (GST-P)(+) foci in TAA-promoted rat livers in a two-stage hepatocarcinogenesis model. Among them, TMEM70 and UBE2E2 showed increased incidences of negative foci in GST-P(+) foci by promotion of all examined TAA, β-naphthoflavone, piperonyl butoxide, fenbendazole and phenobarbital, while HIST1H2AA and SLK did not respond to all promotive treatments. In the late stage of tumor promotion by TAA, the incidence of GST-P(+) proliferative lesions with downregulation of TMEM70 or UBE2E2 was higher in adenomas and carcinomas than liver cell foci. TMEM70 plays a role in mitochondrial oxidative phosphorylation, and UBE2E2 participates in the stabilization of cell cycle regulatory proteins. Therefore, our results indicate that aberrant epigenetic gene downregulation suggestive of a metabolic shift of cellular respiration from oxidative phosphorylation to glycolysis and aberrant cell cycle regulation facilitating cell proliferation from as early as 28days after hepatocarcinogen treatment contribute to tumor development.

  7. Does oral experience terminate ingestion?

    PubMed

    Swithers, S E; Hall, W G

    1994-10-01

    Using data from studies of ingestive behavior in developing rat pups we demonstrate how oral experience can contribute to the termination of ingestion. In rat pups, repeated oral stimulation with sweet solutions causes a decline in oral responsiveness. The diminished responsiveness is specific to the flavor of the stimulus experienced orally and can persist for several hours. We suggest that this experience-based decrement in responsiveness is best considered "oral habituation" and that oral habituation largely accounts for the onset of satiety. Post-ingestive feedback signals may have their influence through the oral habituation process or act in the context of oral habituation. Oral habituation is also shown to depend on the pattern of stimulus presentation, a phenomenon that adds considerable complexity to assessing the contributions of oral experience to satiety. The concept of oral habituation may be useful in understanding the immediate control of ingestion and the moment-to-moment expression of ingestive behavior in adult animals.

  8. Evaluation of the repeated-dose liver and gastrointestinal tract micronucleus assays with 22 chemicals using young adult rats: summary of the collaborative study by the Collaborative Study Group for the Micronucleus Test (CSGMT)/The Japanese Environmental Mutagen Society (JEMS) - Mammalian Mutagenicity Study Group (MMS).

    PubMed

    Hamada, Shuichi; Ohyama, Wakako; Takashima, Rie; Shimada, Keisuke; Matsumoto, Kazumi; Kawakami, Satoru; Uno, Fuyumi; Sui, Hajime; Shimada, Yasushi; Imamura, Tadashi; Matsumura, Shoji; Sanada, Hisakazu; Inoue, Kenji; Muto, Shigeharu; Ogawa, Izumi; Hayashi, Aya; Takayanagi, Tomomi; Ogiwara, Yosuke; Maeda, Akihisa; Okada, Emiko; Terashima, Yukari; Takasawa, Hironao; Narumi, Kazunori; Wako, Yumi; Kawasako, Kazufumi; Sano, Masaki; Ohashi, Nobuyuki; Morita, Takeshi; Kojima, Hajime; Honma, Masamitsu; Hayashi, Makoto

    2015-03-01

    The repeated-dose liver micronucleus (RDLMN) assay using young adult rats has the potential to detect hepatocarcinogens. We conducted a collaborative study to assess the performance of this assay and to evaluate the possibility of integrating it into general toxicological studies. Twenty-four testing laboratories belonging to the Mammalian Mutagenicity Study Group, a subgroup of the Japanese Environmental Mutagen Society, participated in this trial. Twenty-two model chemicals, including some hepatocarcinogens, were tested in 14- and/or 28-day RDLMN assays. As a result, 14 out of the 16 hepatocarcinogens were positive, including 9 genotoxic hepatocarcinogens, which were reported negative in the bone marrow/peripheral blood micronucleus (MN) assay by a single treatment. These outcomes show the high sensitivity of the RDLMN assay to hepatocarcinogens. Regarding the specificity, 4 out of the 6 non-liver targeted genotoxic carcinogens gave negative responses. This shows the high organ specificity of the RDLMN assay. In addition to the RDLMN assay, we simultaneously conducted gastrointestinal tract MN assays using 6 of the above carcinogens as an optional trial of the collaborative study. The MN assay using the glandular stomach, which is the first contact site of the test chemical when administered by oral gavage, was able to detect chromosomal aberrations with 3 test chemicals including a stomach-targeted carcinogen. The treatment regime was the 14- and/or 28-day repeated-dose, and the regime is sufficiently promising to incorporate these methods into repeated-dose toxicological studies. The outcomes of our collaborative study indicated that the new techniques to detect chromosomal aberrations in vivo in several tissues worked successfully.

  9. In vivo flow cytometric Pig-a and micronucleus assays: highly sensitive discrimination of the carcinogen/noncarcinogen pair benzo(a)pyrene and pyrene using acute and repeated-dose designs.

    PubMed

    Torous, Dorothea K; Phonethepswath, Souk; Avlasevich, Svetlana L; Mereness, Jared; Bryce, Steven M; Bemis, Jeffrey C; Weller, Pamela; Bell, Sara; Gleason, Carol; Custer, Laura L; MacGregor, James T; Dertinger, Stephen D

    2012-07-01

    Combining multiple genetic toxicology endpoints into a single in vivo study, and/or integrating one or more genotoxicity assays into general toxicology studies, is attractive because it reduces animal use and enables comprehensive comparative analysis using toxicity, metabolism, and pharmacokinetic information from the same animal. This laboratory has developed flow cytometric scoring techniques for monitoring two blood-based genotoxicity endpoints-micronucleated reticulocyte frequency and gene mutation at the Pig-a locus-thereby making combination and integration studies practical. The ability to effectively monitor these endpoints in short-term and repeated dosing schedules was investigated with the carcinogen/noncarcinogen pair benzo(a)pyrene (BP) and pyrene (Pyr). Male Sprague-Dawley rats were treated via oral gavage for 3 or 28 consecutive days with several dose levels of Pyr, including maximum tolerated doses. BP exposure was administered by the same route but at one dose level, 250 or 125 mg/kg/day for 3-day and 28-day studies, respectively. Serial blood samples were collected up to Day 45, and were analyzed for Pig-a mutation with a dual labeling method (SYTO 13 in combination with anti-CD59-PE) that facilitated mutant cell frequency measurements in both total erythrocytes and the reticulocyte subpopulation. A mutant cell enrichment step based on immunomagnetic column separation was used to increase the statistical power of the assay. BP induced robust mutant reticulocyte responses by Day 15, and elevated frequencies persisted until study termination. Mutant erythrocyte responses lagged mutant reticulocyte responses, with peak incidences observed on Day 30 of the 3-day study (43-fold increase) and on Day 42 of the 28-day study (171-fold increase). No mutagenic effects were apparent for Pyr. Blood samples collected on Day 4, and Day 29 for the 28-day study, were evaluated for micronucleated reticulocyte frequency. Significant increases in micronucleus

  10. Effect of Beta alanine and sodium bicarbonate supplementation on repeated-sprint performance.

    PubMed

    Ducker, Kagan J; Dawson, Brian; Wallman, Karen E

    2013-12-01

    This study aimed to investigate if combining beta alanine (BA) and sodium bicarbonate (NaHCO3) supplementation could lead to enhanced repeated-sprint performance in team-sport athletes, beyond what is possible with either supplement alone. Participants (n = 24) completed duplicate trials of a repeated-sprint test (3 sets; 6 × 20 m departing every 25 seconds, 4 minutes active recovery between sets) and were then allocated into 4 groups as follows: BA only (n = 6; 28 days BA, acute sodium chloride placebo); NaHCO3 only (n = 6; 28 days glucose placebo, acute NaHCO3); BA/NaHCO3 (n = 6; 28 days BA, acute NaHCO3); placebo only (n = 6; 28 days glucose placebo, acute sodium chloride placebo), then completed duplicate trials postsupplementation. Sodium bicarbonate alone resulted in moderate effect size (d = 0.40-0.71) and "likely" and "very likely" benefit for overall total sprint times (TST) and for each individual set and for first sprint (sets 2 and 3) and best sprint time (sets 2 and 3). Combining BA and NaHCO3 resulted in "possible" to "likely" benefits for overall TST and for sets 2 and 3. First sprint (set 3) and best sprint time (sets 2 and 3) also showed "likely" benefit after this trial. The BA and placebo groups showed no differences in performance after supplementation. In conclusion, these results indicate that supplementation with acute NaHCO3 improved repeated-sprint performance more than either a combination of NaHCO3 and BA or BA alone.

  11. Oral Cancer

    MedlinePlus

    Oral Cancer Basic description Cancer can affect any part of the oral cavity, including the lips, tongue, mouth, and throat. There are 2 kinds of oral cancer: oral cavity cancer and oropharyngeal cancer. The most ...

  12. Murine bone marrow IgA responses to orally administered sheep erythrocytes.

    PubMed

    Alley, C D; Kiyono, H; McGhee, J R

    1986-06-15

    Specific immunization protocols have been established for the induction of murine bone marrow IgA responses to the T cell-dependent (TD) antigen sheep red blood cells (SRBC). Systemic immunization, either i.p. or i.v., followed by a second injection, induced splenic IgM and IgG responses and a bone marrow IgM response. No significant IgA responses were observed in either lymphoid tissue compartment. Oral immunization with SRBC by gastric intubation for 2 days, followed 1 wk later by an i.p. injection of SRBC resulted in a splenic IgA plaque-forming cell (PFC) response, but did not elicit a bone marrow IgA response. Repeated daily gastric intubation of SRBC to C3H/HeN and C3H/HeJ mice led to the previously reported pattern of systemic unresponsiveness in C3H/HeN mice and good anamnestic type IgM, IgG, and IgA splenic anti-SRBC PFC responses in the C3H/HeJ strain upon parenteral challenge. Oral administration of SRBC for 14 days to C3H/HeN mice, followed by systemic SRBC challenge, resulted in diminished splenic PFC responses of all isotypes, whereas gastric intubation of SRBC for 28 days led to complete systemic unresponsiveness to antigen in C3H/HeN mice. Interestingly, the repeated oral administration of SRBC resulted in significant bone marrow IgA PFC responses upon i.p. challenge in both C3H/HeN and C3H/HeJ mouse strains. The bone marrow IgA responses were clearly dependent upon chronic oral exposure to SRBC, because gastric intubation with SRBC for 2 consecutive days/wk for 10 wk also induced bone marrow and splenic IgA anti-SRBC PFC responses in C3H/HeN mice. These results suggest that memory B cells reside in the bone marrow of orally immunized mice and can yield anamnestic-type responses to challenge with the inducing antigen. The memory cells may arise in the Peyer's patches of the gut and migrate to the bone marrow. The possibility that the bone marrow is a component of the common mucosal immune system in mammals is suggested by this study.

  13. Toxicological evaluation of ammonium perfluorobutyrate in rats: Twenty-eight-day and ninety-day oral gavage studies

    EPA Science Inventory

    Sequential 28-day and 90-day oral toxicity studies were performed in male and female rats with ammonium perfluorobutyrate (NH4+PFBA) at doses up to 150 and 30 mg/kg/d, respectively. Ammonium perfluorooctanoate was used as a comparator at a dose of 30 mg/kg/d in the 28-d study. Fe...

  14. URINE MUTAGENICITY AND BIOCHEMICAL EFFECTS OF THE DRINKING WATER MUTAGEN, 3-CHLORO-4-(DICHLOROMETHYL)-5-HYDROX-2[5H]-FURANONE (MX), FOLLOWING REPEATED ORAL ADMINISTRATION TO MICE AND RATS

    EPA Science Inventory

    Mutagenicity analysis of urine from rats treated by oral gavage with MX at a dose of 64 mg/kg for 14 days revealed that only 0.3% of the administered cmpound was excreted in a genotoxically active form. At lower doses, mutagenicity was not detectable. No evidence of micronucleu...

  15. Stability of cilazapril in pediatric oral suspensions prepared from commercially available tablet dosage forms.

    PubMed

    Stanisz, Beata J; Paszun, Sylwia K; Zalewska, Anna

    2014-01-01

    Abstract: Cilazapril is a drug commonly used in management of heart failure in pediatric population. On pharmaceutical market it is available only in inconvenient for pediatric use tablet dosage forms. Until now, no oral liquid formulation containing cilazapril has been evaluated. Therefore, the aim of this study was to prepare easy to made and palatable 1 mg/mL oral liquid formulation with cilazapril (with consideration of original and generic cilazapril tablet and different packages) and subsequent investigation of physicochemical stability of these suspensions. Formulations were compounded using cilazapril obtained from original or generic cilazapril marketed tablet formulations and Ora-Blend" suspending agent. Stability of prepared suspensions stored in closed amber glass or amber plastic PET bottles in the temperature of 298 K was estimated throughout 28 day shelf-life period. Chemical stability was assessed by HPLC cilazapril stability indicating method. Physical stability was evaluated by appearance, taste, smell, pH and theological assessments. Cilazapril oral suspensions at concentration of 1 mg/mL demonstrated satisfactory stability over 28 day long storage at room temperature. Cilazapril concentrations remained within acceptable limit (+/- 10%) stored in closed amber bottles made of glass or PET material. Moreover, suspensions physical properties remained unaffected. Cilazapril - Ora-Blend* pediatric oral liquid is easy to made, palatable and stable when stored at room temperature for 28 days. Stability of cilazapril oral liquid remains unchanged while using cilazapril tablets produced by different manufacturers and bottles made of amber glass or PET material.

  16. Improvement of innate immune responses and defense activity in mitten crab (Eriocheir sinensis) by oral administration of beta-glucan.

    PubMed

    Zhou, Jin; Wang, Yong-Hong; Chu, Ju; Luo, Ling-Zhi

    2008-10-01

    The beta-glucan (BG), extracted from Saccharomyces cerevisiae cell wall, was orally administrated to the mitten crab (Eriocheir sinensis) at 0, 1, 5 and 10 g BG/kg diet for 28 days, followed by a challenge with Vibrio mimicus by intramuscular injection. Growth, phenoloxidase, superoxide dismutase, acid phosphatase and alkaline phosphatase activity were monitored after 14 and 28 days. The results showed an immunomodulatory effect and protection against V. mimicus by dietary supplementation of BG. The recommended concentration is 5 g BG/kg diet.

  17. Oral Cancer

    MedlinePlus

    Oral cancer can form in any part of the mouth. Most oral cancers begin in the flat cells that cover the ... your mouth, tongue, and lips. Anyone can get oral cancer, but the risk is higher if you are ...

  18. Oral Cancer

    MedlinePlus

    ... Are the Signs & Symptoms? Should You Have an Oral Cancer Exam? U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health About Oral Cancer Oral cancer includes cancers of the mouth and ...

  19. Oral Medication

    MedlinePlus

    ... Size: A A A Listen En Español Oral Medication The first treatment for type 2 diabetes blood ... new — even over-the-counter items. Explore: Oral Medication How Much Do Oral Medications Cost? Save money ...

  20. Evaluation of a repeated dose liver micronucleus assay in rats treated with two genotoxic hepatocarcinogens, dimethylnitrosamine and 2-acetylaminofluorene: the possibility of integrating micronucleus tests with multiple tissues into a repeated dose general toxicity study.

    PubMed

    Takashima, Rie; Takasawa, Hironao; Kawasako, Kazufumi; Ohyama, Wakako; Okada, Emiko; Narumi, Kazunori; Fujiishi, Yohei; Wako, Yumi; Yasunaga, Katsuaki; Hattori, Akiko; Kawabata, Masayoshi; Nakadate, Kiyoko; Nakagawa, Munehiro; Hamada, Shuichi

    2015-03-01

    As part of a collaborative study by the Collaborative Study Group for Micronucleus Test (CSGMT) of the Mammalian Mutagenicity Study Group (MMS) in the Japanese Environmental Mutagen Society (JEMS), the present study evaluated the effectiveness of the repeated dose liver micronucleus (RDLMN) assay. Two genotoxic hepatocarcinogens, dimethylnitrosamine (DMN) and 2-acetylaminofluorene (2-AAF), were administered orally to male rats (6 weeks old at the initial dosing) once daily for 14 and 28 days to evaluate the micronucleus (MN) inducibility in the liver. In addition, these chemicals were evaluated for MN inducibility in the bone marrow (BM) and gastrointestinal (GI) tract, i.e. glandular stomach and colon of the same animals used in the RDLMN assay. As a result, both chemicals produced positive results in the liver, although a weak positive response was given by 2-AAF. DMN gave negative results in the tissues other than the liver. 2-AAF produced positive responses in the BM and glandular stomach, and a prominent response was particularly observed in the glandular stomach, which is directly exposed to the test chemicals by gavage. The present results suggest that the RDLMN assay is a useful method for detecting genotoxic hepatocarcinogens, and that it is especially effective for evaluating test chemicals, such as DMN, undetectable by the BM and GI tract MN assay. Moreover, the results in this investigation indicate that the use of multiple tissues in the study integrating the MN tests is more effective than using a single tissue, for detection of the MN induction produced by chemical exposure to rats, and helps to determine the characteristics of the test chemicals.

  1. [Oral ulcers].

    PubMed

    Bascones-Martínez, Antonio; Figuero-Ruiz, Elena; Esparza-Gómez, Germán Carlos

    2005-10-29

    Ulcers commonly occur in the oral cavity, their main symptom being pain. There are different ways to classify oral ulcers. The most widely accepted form divides them into acute ulcers--sudden onset and short lasting--and chronic ulcers--insidious onset and long lasting. Commonest acute oral ulcers include traumatic ulcer, recurrent aphthous stomatitis, viral and bacterial infections and necrotizing sialometaplasia. On the other hand, oral lichen planus, oral cancer, benign mucous membrane pemphigoid, pemphigus and drug-induced ulcers belong to the group of chronic oral ulcers. It is very important to make a proper differential diagnosis in order to establish the appropriate treatment for each pathology.

  2. Effects of Oral Administration of Chitin Nanofiber on Plasma Metabolites and Gut Microorganisms

    PubMed Central

    Azuma, Kazuo; Izumi, Ryotaro; Kawata, Mari; Nagae, Tomone; Osaki, Tomohiro; Murahata, Yusuke; Tsuka, Takeshi; Imagawa, Tomohiro; Ito, Norihiko; Okamoto, Yoshiharu; Morimoto, Minoru; Izawa, Hironori; Saimoto, Hiroyuki; Ifuku, Shinsuke

    2015-01-01

    The aim of this study was to examine the effects of oral administration of chitin nanofibers (CNFs) and surface-deacetylated (SDA) CNFs on plasma metabolites using metabolome analysis. Furthermore, we determined the changes in gut microbiota and fecal organic acid concentrations following oral administrations of CNFs and SDACNFs. Healthy female mice (six-week-old) were fed a normal diet and administered tap water with 0.1% (v/v) CNFs or SDACNFs for 28 days. Oral administration of CNFs increased plasma levels of adenosine triphosphate (ATP), adenosine diphosphate (ADP), and serotonin (5-hydroxytryptamine, 5-HT). Oral administration of SDACNFs affected the metabolisms of acyl-carnitines and fatty acids. The fecal organic level analysis indicated that oral administration of CNFs stimulated and activated the functions of microbiota. These results indicate that oral administration of CNFs increases plasma levels of ATP and 5-HT via activation of gut microbiota. PMID:26378523

  3. Effects of Oral Administration of Chitin Nanofiber on Plasma Metabolites and Gut Microorganisms.

    PubMed

    Azuma, Kazuo; Izumi, Ryotaro; Kawata, Mari; Nagae, Tomone; Osaki, Tomohiro; Murahata, Yusuke; Tsuka, Takeshi; Imagawa, Tomohiro; Ito, Norihiko; Okamoto, Yoshiharu; Morimoto, Minoru; Izawa, Hironori; Saimoto, Hiroyuki; Ifuku, Shinsuke

    2015-09-10

    The aim of this study was to examine the effects of oral administration of chitin nanofibers (CNFs) and surface-deacetylated (SDA) CNFs on plasma metabolites using metabolome analysis. Furthermore, we determined the changes in gut microbiota and fecal organic acid concentrations following oral administrations of CNFs and SDACNFs. Healthy female mice (six-week-old) were fed a normal diet and administered tap water with 0.1% (v/v) CNFs or SDACNFs for 28 days. Oral administration of CNFs increased plasma levels of adenosine triphosphate (ATP), adenosine diphosphate (ADP), and serotonin (5-hydroxytryptamine, 5-HT). Oral administration of SDACNFs affected the metabolisms of acyl-carnitines and fatty acids. The fecal organic level analysis indicated that oral administration of CNFs stimulated and activated the functions of microbiota. These results indicate that oral administration of CNFs increases plasma levels of ATP and 5-HT via activation of gut microbiota.

  4. Efficacy and tolerance of repeated oral doses of tolperisone hydrochloride in the treatment of painful reflex muscle spasm: results of a prospective placebo-controlled double-blind trial.

    PubMed

    Pratzel, H G; Alken, R G; Ramm, S

    1996-10-01

    The efficacy and safety of oral tolperisone hydrochloride (Mydocalm) in the treatment of painful reflex muscle spasm was assessed in a prospective, randomized, double-blind, placebo-controlled trial. A total of 138 patients, aged between 20 and 75 years, with painful reflex muscle spasm associated with diseases of the spinal column or proximal joints were enrolled in eight rehabilitation centers. Patients were randomized to receive either 300 mg tolperisone hydrochloride or placebo for a period of 21 days. Both treatment groups recovered during the 3 weeks rehabilitation program. However, tolperisone hydrochloride proved to be significantly superior to placebo: the change score of the pressure pain threshold as the primary target parameter significantly increased during therapy with tolperisone hydrochloride (P = 0.03, valid-case-analysis) compared to the results obtained on placebo treatment. The overall assessment of efficacy by the patient also demonstrated significant differences in favor of tolperisone hydrochloride. Best results were seen in patients aged between 40 and 60 years with a history of complaints shorter than 1 year and with concomitant physical therapy. The evaluation of safety data, i.e., adverse events, biochemical and hematological laboratory parameters, demonstrated no differences between tolperisone hydrochloride and placebo. As a conclusion tolperisone hydrochloride represents an effective and safe treatment of painful reflex muscle spasm without the typical side effects of centrally active muscle relaxants.

  5. Oral cancer

    MedlinePlus

    Cancer - mouth; Mouth cancer; Head and neck cancer; Squamous cell cancer - mouth; Malignant neoplasm - oral ... Oral cancer most commonly involves the lips or the tongue. It may also occur on the: Cheek lining Floor ...

  6. Oral candidosis.

    PubMed

    McIntyre, G T

    2001-04-01

    Oral candidoses are frequently encountered in the practice of dentistry. Although most oral candidoses are symptomless, the can indicate the presence of an underlying systemic disease, and the persistence of oral candidosis following appropriate conventional management may be one of the first signs of undiagnosed immunosuppression. The opportunistic pathogen Candida albicans is the most commonly isolated species from oral candidal lesions; however, the non-albicans Candida spp. are also implicated in the aetiology of oral candidoses. The effective management of oral candidosis is dependent on an accurate diagnosis, identification and elimination of any predisposing factors (where possible), and the prescription of either topical or systemic antifungal agents. Oral candidosis may have significant implications for the general health of immunosuppressed patients, particularly when caused by the non-albicans spp. and, in cases of severe immunosuppression, systemic candidosis can be life-threatening. This article outlines the clinical presentation and appropriate management for the commonly presenting oral candidal conditions.

  7. A standard picture of healthy oral mucosae by direct oral microscopy

    PubMed Central

    Drogoszewska, Barbara; Michcik, Adam; Polcyn, Adam

    2013-01-01

    Introduction Direct oral microscopy constitutes a novel technique of in vivo oral mucosae examination. The basic principles of this method derive from colposcopy and dermoscopy. The main goal of direct oral microscopy is the earliest possible detection of oral precancerous lesions in order to implement their treatment as quickly as possible and prevent malignant transformation. Aim To establish a standard picture of healthy oral mucosae with direct oral microscopy applying standard colposcopic criteria in order to create a reference point for further diagnosis of precancerous lesions. Material and methods Thirty patients of both genders with clinically unaltered oral mucosae were examined. For every individual, clinical examination with the naked eye was performed, followed by direct oral microscopy with colposcopic assessment criteria. Oral mucosae at various sites (lip, cheek, floor of mouth, ventral and lateral sides of the tongue, alveolar ridge and soft palate) were examined. Results Subepithelial blood vessel patterns, mucosal surface, colour tone and transparency were described for healthy oral mucosae. Moreover, cases with clinically unaltered oral mucosae where direct oral microscopy revealed subclinical alterations were described. Conclusions Direct oral microscopy with colposcopic assessment criteria enables establishment of a repeated picture of unaltered oral mucosae. The standard picture of healthy oral mucosae is an essential reference point for application of this technique to early diagnose potentially malignant oral mucosal lesions as well as apply their early treatment. PMID:24278068

  8. Acute and subchronic oral toxicity studies in rats with nanoscale and pigment grade titanium dioxide particles.

    PubMed

    Warheit, D B; Brown, S C; Donner, E M

    2015-10-01

    Data generated using standardized testing protocols for toxicity studies generally provide reproducible and reliable results for establishing safe levels and formulating risk assessments. The findings of three OECD guideline-type oral toxicity studies of different duration in rats are summarized in this publication; each study evaluated different titanium dioxide (TiO2) particles of varying sizes and surface coatings. Moreover, each study finding demonstrated an absence of any TiO2 -related hazards. To briefly summarize the findings: 1) In a subchronic 90-day study (OECD TG 408), groups of young adult male and female rats were dosed with rutile-type, surface-coated pigment-grade TiO2 test particles (d50 = 145 nm - 21% nanoparticles by particle number criteria) by oral gavage for 90 days. The no-adverse-effect level (NOAEL) for both male and female rats in this study was 1000 mg/kg bw/day, the highest dose tested. The NOAEL was determined based on a lack of TiO2 particle-related adverse effects on any in-life, clinical pathology, or anatomic/microscopic pathology parameters; 2) In a 28-day repeated-dose oral toxicity study (OECD TG 407), groups of young adult male rats were administered daily doses of two rutile-type, uncoated, pigment-grade TiO2 test particles (d50 = 173 nm by number) by daily oral gavage at a dose of 24,000 mg/kg bw/day. There were no adverse effects measured during or following the end of the exposure period; and the NOAEL was determined to be 24,000 mg/kg bw/day; 3) In an acute oral toxicity study (OECD TG 425), female rats were administered a single oral exposure of surface-treated rutile/anatase nanoscale TiO2 particles (d50 = 73 nm by number) with doses up to 5000 mg/kg and evaluated over a 14-day post-exposure period. Under the conditions of this study, the oral LD50 for the test substance was >5000 mg/kg bw. In summary, the results from these three toxicity studies - each with different TiO2 particulate-types, demonstrated an absence of

  9. Facilitating English-Language Learners' Oral Reading Fluency with Digital Pen Technology

    ERIC Educational Resources Information Center

    Chen, Chih-Ming; Tan, Chia-Chen; Lo, Bey-Jane

    2016-01-01

    Oral reading fluency is an indicator of overall reading competence. Many studies have claimed that repeated reading can promote oral reading fluency. Currently, novel Web- or computer-based reading technologies offer interactive digital materials that promote English oral reading fluency using the repeated reading strategy; however, paper-based…

  10. Repeating the Past

    NASA Astrophysics Data System (ADS)

    Moore, John W.

    1998-05-01

    As part of the celebration of the Journal 's 75th year, we are scanning each Journal issue from 25, 50, and 74 years ago. Many of the ideas and practices described are so similar to present-day "innovations" that George Santayana's adage (1) "Those who cannot remember the past are condemned to repeat it" comes to mind. But perhaps "condemned" is too strong - sometimes it may be valuable to repeat something that was done long ago. One example comes from the earliest days of the Division of Chemical Education and of the Journal.

  11. Prolonged Oral Administration of Oleuropein Might Protect Heart against Aconitine-induced Arrhythmia

    PubMed Central

    Esmailidehaj, Mansour; Mirhosseini, Seyed-Jalil; Rezvani, Mohammad Ebrahim; Rasoulian, Bahram; Mosaddeghmehrjardi, Mohammad Hossein; Haghshenas, Damoon

    2012-01-01

    In this study, it was surveyed to know whether an oral single dose of oleuropein could mimic the cardiac preconditioning in rats’ hearts or whether its prolonged oral administration could protect the heart against the aconitine-induced arrhythmia in rats. Eighty male Wistar rats were divided into two series (n = 8 in each group). In the first series, all groups (except the control (Con) group) were given a single oral dose of oleuropein (20 mg/Kg) 1, 3, 24 and 48 h before the infusion of aconitine. In the second series, except the Con group, the other four groups were given oral oleuropein (20 mg/Kg/day) for 3, 7, 14 and 28 days, before the infusion of aconitine. Electrocardiogram was recorded to monitor arrhythmia. Data of the first series showed that the initiation time of arrhythmia, the initiation of ventricular tachycardia (VT), the numbers of reversible ventricular fibrillation (VF) and the death time had no significant difference compared with Con group. In the second series, a significant protection was occurred only in the 28 days group that was evident with increased initiation time of arrhythmia, increased initiation time of VT, and increased the number of reversible VF and death time in compared to the Con group. The findings of this study show that the oral administration of a single dose of oleuropein could not mimic the preconditioning effects in rat hearts, but the prolonged administration of oleuropein for about four weeks could protect the heart against aconitine-induced arrhythmia. PMID:24250560

  12. Duct Leakage Repeatability Testing

    SciTech Connect

    Walker, Iain; Sherman, Max

    2014-01-01

    Duct leakage often needs to be measured to demonstrate compliance with requirements or to determine energy or Indoor Air Quality (IAQ) impacts. Testing is often done using standards such as ASTM E1554 (ASTM 2013) or California Title 24 (California Energy Commission 2013 & 2013b), but there are several choices of methods available within the accepted standards. Determining which method to use or not use requires an evaluation of those methods in the context of the particular needs. Three factors that are important considerations are the cost of the measurement, the accuracy of the measurement and the repeatability of the measurement. The purpose of this report is to evaluate the repeatability of the three most significant measurement techniques using data from the literature and recently obtained field data. We will also briefly discuss the first two factors. The main question to be answered by this study is to determine if differences in the repeatability of these tests methods is sufficient to indicate that any of these methods is so poor that it should be excluded from consideration as an allowed procedure in codes and standards.

  13. Accumulate repeat accumulate codes

    NASA Technical Reports Server (NTRS)

    Abbasfar, Aliazam; Divsalar, Dariush; Yao, Kung

    2004-01-01

    In this paper we propose an innovative channel coding scheme called 'Accumulate Repeat Accumulate codes' (ARA). This class of codes can be viewed as serial turbo-like codes, or as a subclass of Low Density Parity Check (LDPC) codes, thus belief propagation can be used for iterative decoding of ARA codes on a graph. The structure of encoder for this class can be viewed as precoded Repeat Accumulate (RA) code or as precoded Irregular Repeat Accumulate (IRA) code, where simply an accumulator is chosen as a precoder. Thus ARA codes have simple, and very fast encoder structure when they representing LDPC codes. Based on density evolution for LDPC codes through some examples for ARA codes, we show that for maximum variable node degree 5 a minimum bit SNR as low as 0.08 dB from channel capacity for rate 1/2 can be achieved as the block size goes to infinity. Thus based on fixed low maximum variable node degree, its threshold outperforms not only the RA and IRA codes but also the best known LDPC codes with the dame maximum node degree. Furthermore by puncturing the accumulators any desired high rate codes close to code rate 1 can be obtained with thresholds that stay close to the channel capacity thresholds uniformly. Iterative decoding simulation results are provided. The ARA codes also have projected graph or protograph representation that allows for high speed decoder implementation.

  14. Oral Histoplasmosis.

    PubMed

    Folk, Gillian A; Nelson, Brenda L

    2017-02-20

    A 44-year-old female presented to her general dentist with the chief complaint of a painful mouth sore of 2 weeks duration. Clinical examination revealed an irregularly shaped ulcer of the buccal and lingual attached gingiva of the anterior mandible. A biopsy was performed and microscopic evaluation revealed histoplasmosis. Histoplasmosis, caused by Histoplasma capsulate, is the most common fungal infection in the United States. Oral lesions of histoplasmosis are generally associated with the disseminated form of histoplasmosis and may present as a fungating or ulcerative lesion of the oral mucosa. The histologic findings and differential diagnosis for oral histoplasmosis are discussed.

  15. Biomarker-driven trial in metastatic pancreas cancer: feasibility in a multicenter study of saracatinib, an oral Src inhibitor, in previously treated pancreatic cancer.

    PubMed

    Arcaroli, John; Quackenbush, Kevin; Dasari, Arvind; Powell, Rebecca; McManus, Martine; Tan, Aik-Choon; Foster, Nathan R; Picus, Joel; Wright, John; Nallapareddy, Sujatha; Erlichman, Charles; Hidalgo, Manuel; Messersmith, Wells A

    2012-10-01

    Src tyrosine kinases are overexpressed in pancreatic cancers, and the oral Src inhibitor saracatinib has shown antitumor activity in preclinical models of pancreas cancer. We performed a CTEP-sponsored Phase II clinical trial of saracatinib in previously treated pancreas cancer patients, with a primary endpoint of 6-month survival. A Simon MinMax two-stage phase II design was used. Saracatinib (175 mg/day) was administered orally continuously in 28-day cycles. In the unselected portion of the study, 18 patients were evaluable. Only two (11%) patients survived for at least 6 months, and three 6-month survivors were required to move to second stage of study as originally designed. The study was amended as a biomarker-driven trial (leucine rich repeat containing protein 19 [LRRC19] > insulin-like growth factor-binding protein 2 [IGFBP2] "top scoring pairs" polymerase chain reaction [PCR] assay, and PIK3CA mutant) based on preclinical data in a human pancreas tumor explant model. In the biomarker study, archival tumor tissue or fresh tumor biopsies were tested. Biomarker-positive patients were eligible for the study. Only one patient was PIK3CA mutant in a 3' untranslated region (UTR) portion of the gene. This patient was enrolled in the study and failed to meet the 6-month survival endpoint. As the frequency of biomarker-positive patients was very low (<3%), the study was closed. Although we were unable to conclude whether enriching for a subset of second/third line pancreatic cancer patients treated with a Src inhibitor based on a biomarker would improve 6-month survival, we demonstrate that testing pancreatic tumor samples for a biomarker-driven, multicenter study in metastatic pancreas cancer is feasible.

  16. Oral pathology.

    PubMed

    Niemiec, Brook A

    2008-05-01

    Oral disease is exceedingly common in small animal patients. In addition, there is a very wide variety of pathologies that are encountered within the oral cavity. These conditions often cause significant pain and/or localized and systemic infection; however, the majority of these conditions have little to no obvious clinical signs. Therefore, diagnosis is not typically made until late in the disease course. Knowledge of these diseases will better equip the practitioner to effectively treat them. This article covers the more common forms of oral pathology in the dog and cat, excluding periodontal disease, which is covered in its own chapter. The various pathologies are presented in graphic form, and the etiology, clinical signs, recommended diagnostic tests, and treatment options are discussed. Pathologies that are covered include: persistent deciduous teeth, fractured teeth, intrinsically stained teeth, feline tooth resorption, caries, oral neoplasia, eosinophilic granuloma complex, lymphoplasmacytic gingivostomatitis, enamel hypoplasia, and "missing" teeth.

  17. Metabolism of 2,6-dichloro-4-(3,3-dichloroallyloxy)phenyl 3-[5-(trifluoromethyl)-2-pyridyloxy]propyl ether (pyridalyl) in rats after repeated oral administration and a simple physiologically based pharmacokinetic modeling in brown and white adipose tissues.

    PubMed

    Nagahori, Hirohisa; Matsunaga, Haruyuki; Tomigahara, Yoshitaka; Isobe, Naohiko; Kaneko, Hideo

    2010-05-01

    Male and female Sprague-Dawley rats received repeated oral administration of 14C-2,6-dichloro-4-(3,3-dichloroallyloxy)phenyl 3- [5-(trifluoromethyl)-2-pyridyloxy]propyl ether (14C-pyridalyl) at 5 mg/kg/day for 14 consecutive days, and 14C excretion, 14C concentration in tissues, and the metabolic fate were determined. Most 14C was excreted into feces. The 14C concentrations in the blood and tissues attained steady-state levels at days 6 to 10, whereas those in white adipose tissues increased until day 14. Tissue 14C concentrations were highest in brown and white adipose tissue (38.37-57.50 ppm) but were 5.60 ppm or less in all the other tissues. Total 14C residues in blood and tissues on the 27th day after the first administration accounted for 2.6 to 3.2% of the total dose. A major fecal metabolite resulted from O-dealkylation. Analysis of metabolites in tissues revealed that the majority of 14C in perirenal adipose tissue and lungs was pyridalyl, accounting for greater than 90 and 60%, respectively, of the total, whereas a major metabolite in whole blood, kidneys, and liver was a dehalogenated metabolite. The experimental data were simulated with simple physiologically based pharmacokinetics using four-compartment models with assumption of lymphatic absorption and membrane permeability in adipose tissues. The different kinetics in brown and white adipose tissues was reasonably predicted in this model, with large distribution volume in adipose tissues and high hepatic clearance in liver. Sex-related difference of pyridalyl concentration in liver was considered to be a result of different unbound fraction times the hepatic intrinsic clearance (f x CL(int)) of 1.8 and 12 l/h for male and female, respectively.

  18. Duct Leakage Repeatability Testing

    SciTech Connect

    Walker, Iain; Sherman, Max

    2014-08-01

    The purpose of this report is to evaluate the repeatability of the three most significant measurement techniques for duct leakage using data from the literature and recently obtained field data. We will also briefly discuss the first two factors. The main question to be answered by this study is to determine if differences in the repeatability of these tests methods is sufficient to indicate that any of these methods is so poor that it should be excluded from consideration as an allowed procedure in codes and standards. The three duct leak measurement methods assessed in this report are the two duct pressurization methods that are commonly used by many practitioners and the DeltaQ technique. These are methods B, C and A, respectively of the ASTM E1554 standard. Although it would be useful to evaluate other duct leak test methods, this study focused on those test methods that are commonly used and are required in various test standards, such as BPI (2010), RESNET (2014), ASHRAE 62.2 (2013), California Title 24 (CEC 2012), DOE Weatherization and many other energy efficiency programs.

  19. Repeat Customer Success in Extension

    ERIC Educational Resources Information Center

    Bess, Melissa M.; Traub, Sarah M.

    2013-01-01

    Four multi-session research-based programs were offered by two Extension specialist in one rural Missouri county. Eleven participants who came to multiple Extension programs could be called "repeat customers." Based on the total number of participants for all four programs, 25% could be deemed as repeat customers. Repeat customers had…

  20. 78 FR 65594 - Vehicular Repeaters

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-01

    ... changes, and on whether current mobile repeater filter technologies can support reduced frequency... feasibility of adapting SAW filters, or other filter technology, for mobile repeater use. We particularly... mobile repeaters by public safety licensees on certain frequencies in the VHF band. DATES:...

  1. Using Repeated Reading to Improve Reading Speed and Comprehension in Students with Visual Impairments

    ERIC Educational Resources Information Center

    Savaiano, Mackenzie E.; Hatton, Deborah D.

    2013-01-01

    Introduction: This study evaluated whether children with visual impairments who receive repeated reading instruction exhibit an increase in their oral reading rate and comprehension and a decrease in oral reading error rates. Methods: A single-subject, changing-criterion design replicated across three participants was used to demonstrate the…

  2. RepeatsDB: a database of tandem repeat protein structures

    PubMed Central

    Di Domenico, Tomás; Potenza, Emilio; Walsh, Ian; Gonzalo Parra, R.; Giollo, Manuel; Minervini, Giovanni; Piovesan, Damiano; Ihsan, Awais; Ferrari, Carlo; Kajava, Andrey V.; Tosatto, Silvio C.E.

    2014-01-01

    RepeatsDB (http://repeatsdb.bio.unipd.it/) is a database of annotated tandem repeat protein structures. Tandem repeats pose a difficult problem for the analysis of protein structures, as the underlying sequence can be highly degenerate. Several repeat types haven been studied over the years, but their annotation was done in a case-by-case basis, thus making large-scale analysis difficult. We developed RepeatsDB to fill this gap. Using state-of-the-art repeat detection methods and manual curation, we systematically annotated the Protein Data Bank, predicting 10 745 repeat structures. In all, 2797 structures were classified according to a recently proposed classification schema, which was expanded to accommodate new findings. In addition, detailed annotations were performed in a subset of 321 proteins. These annotations feature information on start and end positions for the repeat regions and units. RepeatsDB is an ongoing effort to systematically classify and annotate structural protein repeats in a consistent way. It provides users with the possibility to access and download high-quality datasets either interactively or programmatically through web services. PMID:24311564

  3. Normal Oral Flora and the Oral Ecosystem.

    PubMed

    Samaranayake, Lakshman; Matsubara, Victor H

    2017-04-01

    The oral ecosystem comprises the oral flora, so-called oral microbiome, the different anatomic microniches of the oral cavity, and its bathing fluid, saliva. The oral microbiome comprises a group of organisms and includes bacteria, archaea, fungi, protozoa, and viruses. The oral microbiome exists suspended in saliva as planktonic phase organisms or attached to oral surfaces as a plaque biofilm. Homeostasis of the plaque biofilm and its symbiotic relationship with the host is critical for oral health. Disequilibrium or dysbiosis within the plaque biofilms is the initiating event that leads to major oral diseases, such as caries and periodontal disease.

  4. Intra-oral PTH administration promotes tooth extraction socket healing.

    PubMed

    Kuroshima, S; Kovacic, B L; Kozloff, K M; McCauley, L K; Yamashita, J

    2013-06-01

    Intermittent parathyroid hormone (PTH) administration increases systemic and craniofacial bone mass. However, the effect of PTH therapy on healing of tooth extraction sites is unknown. The aims of this study were to determine the effect of PTH therapy on tooth extraction socket healing and to examine whether PTH intra-oral injection promotes healing. The mandibular first molars were extracted in rats, and subcutaneous PTH was administered intermittently for 7, 14, and 28 days. In a second study, maxillary second molars were extracted, and PTH was administered by either subcutaneous or intra-oral injection to determine the efficacy of intra-oral PTH administration. Healing was assessed by micro-computed tomography and histomorphometric analyses. PTH therapy accelerated the entire healing process and promoted both hard- and soft-tissue healing by increasing bone fill and connective tissue maturation. PTH therapy by intra-oral injection was as effective as subcutaneous injection in promoting tooth extraction socket healing. The findings suggest that PTH therapy promotes tooth extraction socket healing and that intra-oral injections can be used to administer PTH.

  5. Oral myiasis

    PubMed Central

    Pereira, Treville; Tamgadge, Avinash P.; Chande, Mayura S.; Bhalerao, Sudhir; Tamgadge, Sandhya

    2010-01-01

    Myiasis is a relatively rare condition arising from the invasion of body tissues or cavities of living animals or humans by maggots or larvae of certain species of flies. It is an uncommon clinical condition, being more frequent in underdeveloped countries and hot climate regions, and is associated with poor hygiene, suppurative oral lesions; alcoholism and senility. Its diagnosis is made basically by the presence of larvae. The present article reports a case of oral myiasis involving 20 larvae in a patient with neurological deficiency. PMID:22114438

  6. Oral immunogenicity of the plant proteinase bromelain.

    PubMed

    Hale, Laura P; Fitzhugh, David J; Staats, Herman F

    2006-12-20

    Bromelain is a natural mixture of proteolytic enzymes derived from pineapple stem that has been shown to have anti-inflammatory activity when administered orally. Although most proteins given orally without adjuvant (e.g., food) result in tolerance, we previously reported that long-term oral exposure to bromelain stimulated the development of high serum anti-bromelain antibody titers. The purpose of these studies was to further investigate the mechanisms responsible for the immunogenicity of oral bromelain. Results showed that repeated exposure was required for development of anti-bromelain antibodies, with strong antibody responses in all mice that received at least 12 doses of bromelain either orally or intragastrically over 3-6 weeks. Proteolytic activity was required for strong oral immunogenicity in the absence of conventional adjuvant, with strong serum antibody responses generated against proteolytically active bromelain and trypsin, but not against ovalbumin, lysozyme, or inactivated bromelain. Significantly higher anti-bromelain antibody titers were seen in IL-10-deficient versus wild-type mice, suggesting that simultaneous treatments that decrease IL-10 activity may further enhance systemic antibody responses following oral exposure. The antibodies generated did not affect the proteolytic activity of bromelain. The data demonstrate that proteolytically active antigens such as bromelain can stimulate both systemic and mucosal immune responses following repeated oral exposure. Further studies of the mechanisms involved in generation of immune responses following oral exposure to proteolytically active antigens can lead to a better understanding of mechanisms of oral tolerance and to the development of novel adjuvants for oral vaccines.

  7. Oral medications.

    PubMed

    Albretsen, Jay C

    2002-03-01

    Many medications are available today by prescription or in over-the-counter preparations. This article reviews the pharmacokinetics, mechanism of action, toxicity, clinical signs, and management procedures necessary for some oral medications. The medications reviewed include selective serotonin reuptake inhibitors, benzodiazepines, amphetamines or amphetamine like drugs, carprofen, cyclooxygenase-2 inhibitors, pseudoephedrine, calcium channel blockers, and baclofen.

  8. Oral Tumours

    PubMed Central

    Lecavalier, D.R.; Main, J.H.P.

    1988-01-01

    The authors of this article review briefly the anatomy of the oral soft tissues and describe the more common benign and malignant tumours of the mouth, giving emphasis to their clinical features. ImagesFigure 1Figure 2Figure 3Figure 4Figure 5Figure 6Figure 7Figure 8 PMID:21253197

  9. Oral Health and Aging

    MedlinePlus

    ... please turn JavaScript on. Feature: Oral Health and Aging Oral Health and Aging Past Issues / Summer 2016 Table of Contents Jerrold ... they may need. Read More "Oral Health and Aging" Articles Oral Health and Aging / 4 Myths About ...

  10. Effects of Repeated Ropinirole Treatment on Phencyclidine-Induced Hyperlocomotion, Prepulse Inhibition Deficits, and Social Avoidance in Rats.

    PubMed

    Maple, Amanda M; Call, Tanessa; Kimmel, Phylicia C; Hammer, Ronald P

    2017-04-01

    Phencyclidine (PCP), a noncompetitive N-methyl d-aspartate (NMDA) receptor antagonist, provides the most complete pharmacologic model of schizophrenia in humans and animals. Acute PCP causes hyperlocomotion, disrupts prepulse inhibition (PPI), and increases social avoidance in rats. We have previously shown that repeated treatment with the dopamine (DA) D2-like receptor agonists, quinpirole or ropinirole, prevents agonist-induced PPI disruption. In the present study, we examined whether repeated ropinirole treatment similarly attenuates the effects of PCP in a more complete model of schizophrenia symptoms and examined the effect of repeated D2-like agonist treatment on locomotion, PPI, and social interaction after acute PCP challenge. The acute effect of PCP (3.0 or 6.0 mg/kg) on locomotor activity was examined to establish a minimum effective dose. Thereafter, the effect of PCP challenge (3.0 mg/kg) on locomotor activity, PPI, and social interaction was assessed in adult male rats before or 7-10 days after termination of repeated daily treatment with ropinirole (0.1 mg/kg) or saline vehicle (0.1 ml/kg) for 28 days. Repeated ropinirole treatment attenuates PCP-induced hyperlocomotion, PPI deficits, and social avoidance. These findings suggest that repeated ropinirole treatment might affect a final common pathway that is vulnerable to both PCP- and dopamine agonist-induced behavioral disruption, thereby providing an alternative approach to block the effects of PCP.

  11. To Repeat or Not to Repeat a Course

    ERIC Educational Resources Information Center

    Armstrong, Michael J.; Biktimirov, Ernest N.

    2013-01-01

    The difficult transition from high school to university means that many students need to repeat (retake) 1 or more of their university courses. The authors examine the performance of students repeating first-year core courses in an undergraduate business program. They used data from university records for 116 students who took a total of 232…

  12. Subchronic oral toxicity of a standardized white kidney bean (Phaseolus vulgaris) extract in rats.

    PubMed

    Chokshi, Dilip

    2007-01-01

    Dietary supplements containing "starch blockers" are believed to reduce carbohydrate-derived calories by interfering with alpha-amylase, the digestive enzyme responsible for conversion of complex carbohydrates to simple, absorbable sugars. The present paper reports the findings of a 28-day oral toxicity study in rats of Phase 2, a standardized extract derived from the common white kidney bean (Phaseolus vulgaris), which has been shown to have alpha-amylase-inhibiting activity. In order to establish safety, eighty male and female Sprague-Dawley rats (10 animals/sex/group) received Phase 2 via oral gavage at doses of 0, 625, 1250, and 2500 mg/kg (7 days/wk) for a period of 31 (males) or 32 (females) days. There were no mortalities, clinical signs, body weight or nutritional effects, gross alterations, clinical or histopathological alterations that were considered attributable to test substance administration. Under conditions of this study and based on toxicological endpoints evaluated, the no-observed-adverse-effect level (NOAEL) of Phase 2 was judged to be 2500 mg/kg/day in each sex for administration by oral gavage of a standardized white kidney bean extract, Phase 2 for 28 days.

  13. Efficacy of oral moxidectin against benzimidazole-resistant isolates of gastrointestinal nematodes in sheep.

    PubMed

    Kerboeuf, D; Hubert, J; Cardinaud, B; Blond, F

    1995-01-07

    The efficacy of orally administered moxidectin was determined against four benzimidazole-resistant nematode isolates. At the start of the trial, 30 lambs were each infected experimentally with 20,000 third stage larvae (5000 Haemonchus contortus, 7000 Teladorsagia circumcincta, 3000 Trichostrongylus colubriformis and 5000 Cooperia curticei); 28 days later they were allocated randomly to three groups of 10: one untreated group, one group treated orally with fenbendazole (5 mg/kg bodyweight) and one group treated orally with moxidectin (0.2 mg/kg). Samples of faeces were taken five and 10 days after treatment and the lambs were killed 10 days after treatment. Fenbendazole reduced the average number of nematode eggs in faeces by 95 per cent and the average number of worms by 25 to 45 per cent according to the species. The efficacy of moxidectin against these benzimidazole-resistant isolates was 100 per cent. No adverse reactions to either of the drugs were observed.

  14. Oral contraceptives.

    PubMed

    Oesterheld, Jessica R; Cozza, Kelly; Sandson, Neil B

    2008-01-01

    Nearly 50 years ago, the introduction of Enovid (norethynodrel 10 microg and mestranol 150 microg), which provided convenient and reliable contraception, revolutionized birth control. Reports of interactions between oral contraceptives (OCs) and other drugs began to trickle into the literature. At first, these drug interactions appeared to be random and unrelated. Increased understanding of P450 enzymes and phase II reactions of sulfation and glucuronidation has permitted preliminary categorization and assessment of the clinical relevance of these drug interactions.

  15. Nifty Nines and Repeating Decimals

    ERIC Educational Resources Information Center

    Brown, Scott A.

    2016-01-01

    The traditional technique for converting repeating decimals to common fractions can be found in nearly every algebra textbook that has been published, as well as in many precalculus texts. However, students generally encounter repeating decimal numerals earlier than high school when they study rational numbers in prealgebra classes. Therefore, how…

  16. All-photonic quantum repeaters

    NASA Astrophysics Data System (ADS)

    Azuma, Koji; Tamaki, Kiyoshi; Lo, Hoi-Kwong

    2015-04-01

    Quantum communication holds promise for unconditionally secure transmission of secret messages and faithful transfer of unknown quantum states. Photons appear to be the medium of choice for quantum communication. Owing to photon losses, robust quantum communication over long lossy channels requires quantum repeaters. It is widely believed that a necessary and highly demanding requirement for quantum repeaters is the existence of matter quantum memories. Here we show that such a requirement is, in fact, unnecessary by introducing the concept of all-photonic quantum repeaters based on flying qubits. In particular, we present a protocol based on photonic cluster-state machine guns and a loss-tolerant measurement equipped with local high-speed active feedforwards. We show that, with such all-photonic quantum repeaters, the communication efficiency scales polynomially with the channel distance. Our result paves a new route towards quantum repeaters with efficient single-photon sources rather than matter quantum memories.

  17. Oral contraceptives.

    PubMed

    Ellsworth, A J; Leversee, J H

    1990-09-01

    Management of oral contraception requires an understanding of the relationships between the method's effectiveness, noncontraceptive benefits, and hormonal adverse effects. The new multiphasic combinations or OCs containing 35 micrograms of ethinyl estradiol and 0.5-1.0 mg of norethindrone or equivalent result in a maximum combination of efficacy and safety for the patient with minimal annoying problems for the patient and the prescriber. Patient education regarding early warning symptoms of adverse effects, breakthrough bleeding, and lack of withdrawal bleeding adds an additional margin of safety and reduces patient questions and uncertainties.

  18. Oral contraceptives.

    PubMed

    Maclennan, A H

    1987-12-01

    Over 60 million women use highly efficient and safe modern combined oral contraceptives (OCs) every day. A women who takes the oral contraceptive for 5 years before the age of 30 will actually live 12 days longer, although a woman taking the pill for the 1st time for 5 years after the age of 30 will have her life span reduced on the average by 80 days. OC related morbidity and mortality mostly occur in women over 35 who smoke. Combined low dose OCs are safe for women who do not smoke, at least to 45 years of age and probably to the menopause. The prescription of OCs is also safe to the young adolescent. The pill does not interfere with maturation of the hypothalamic-pituitary ovarian axis and does not increase the incidence of amenorrhoea, oligomenorrhoea or infertility in later life. Patients with contraindications to estrogen therapy are excluded from OC use (history of thromboembolism, major heart disease, liver disease, breast cancer). Low-dose (30-35 mcg estrogen-containing monophasic or triphasic) pills are recommended. Combined oral contraceptives contain either ethinyl estradiol (1.7 to 2 times more potent) or mestranol. After absorption the progestagens, norethisterone acetate, ethynodiol diacetate and lynoestrenol are all metabolized to norethisterone. The progestagen-only pill has about a 2% failure rate and poorer cycle control than the combined pill, but it lacks estrogenic, progestagenic and androgenic side effects. This pill is suitable for the lactating mother, for smokers over 35, for hypertensive patients, and for those with a history of thrombosis. The efficacy of the progestagen-only pill is restored in 3 days of pill taking. Postcoital contraception is an alternative: treatment can be given for at least 72 hours after intercourse. The Yuzpe method calls for the patient to take 2 combined oral contraceptive tablets containing levonorgestrel and ethinyl estradiol (Eugynon or Ovral) followed by a further 2 tablets 12 hours later. This regimen

  19. Quantum repeaters: fundamental and future

    NASA Astrophysics Data System (ADS)

    Li, Yue; Hua, Sha; Liu, Yu; Ye, Jun; Zhou, Quan

    2007-04-01

    An overview of the Quantum Repeater techniques based on Entanglement Distillation and Swapping is provided. Beginning with a brief history and the basic concepts of the quantum repeaters, the article primarily focuses on the communication model based on the quantum repeater techniques, which mainly consists of two fundamental modules --- the Entanglement Distillation module and the Swapping module. The realizations of Entanglement Distillation are discussed, including the Bernstein's Procrustean method, the Entanglement Concentration and the CNOT-purification method, etc. The schemes of implementing Swapping, which include the Swapping based on Bell-state measurement and the Swapping in Cavity QED, are also introduced. Then a comparison between these realizations and evaluations on them are presented. At last, the article discusses the experimental schemes of quantum repeaters at present, documents some remaining problems and emerging trends in this field.

  20. Repeatability in redundant manipulator systems

    NASA Astrophysics Data System (ADS)

    Mukherjee, Ranjan

    1994-02-01

    Terrestrial manipulators with more DOF than the dimension of the workspace and space manipulators with as many manipulator DOF as the dimension of the workspace are both redundant systems. An interesting problem of such redundant systems has been the repeatability problem due to the presence of nonholonomic constraints. We show, contrary to the existing belief, that integrability of the nonholonomic constraints is not a necessary condition for the repeatability of the configuration variables. There exist certain trajectories in the independent configuration variable space that are like 'holonomic loops' along which the redundant manipulators exhibit repeatable motion. We present a simple method based on optimization techniques for designing repeatable trajectories for free-flying space manipulators and terrestrial manipulators under pseudoinverse control.

  1. Protein Repeats from First Principles.

    PubMed

    Turjanski, Pablo; Parra, R Gonzalo; Espada, Rocío; Becher, Verónica; Ferreiro, Diego U

    2016-04-05

    Some natural proteins display recurrent structural patterns. Despite being highly similar at the tertiary structure level, repeating patterns within a single repeat protein can be extremely variable at the sequence level. We use a mathematical definition of a repetition and investigate the occurrences of these in sequences of different protein families. We found that long stretches of perfect repetitions are infrequent in individual natural proteins, even for those which are known to fold into structures of recurrent structural motifs. We found that natural repeat proteins are indeed repetitive in their families, exhibiting abundant stretches of 6 amino acids or longer that are perfect repetitions in the reference family. We provide a systematic quantification for this repetitiveness. We show that this form of repetitiveness is not exclusive of repeat proteins, but also occurs in globular domains. A by-product of this work is a fast quantification of the likelihood of a protein to belong to a family.

  2. Protein Repeats from First Principles

    PubMed Central

    Turjanski, Pablo; Parra, R. Gonzalo; Espada, Rocío; Becher, Verónica; Ferreiro, Diego U.

    2016-01-01

    Some natural proteins display recurrent structural patterns. Despite being highly similar at the tertiary structure level, repeating patterns within a single repeat protein can be extremely variable at the sequence level. We use a mathematical definition of a repetition and investigate the occurrences of these in sequences of different protein families. We found that long stretches of perfect repetitions are infrequent in individual natural proteins, even for those which are known to fold into structures of recurrent structural motifs. We found that natural repeat proteins are indeed repetitive in their families, exhibiting abundant stretches of 6 amino acids or longer that are perfect repetitions in the reference family. We provide a systematic quantification for this repetitiveness. We show that this form of repetitiveness is not exclusive of repeat proteins, but also occurs in globular domains. A by-product of this work is a fast quantification of the likelihood of a protein to belong to a family. PMID:27044676

  3. Nanospring behaviour of ankyrin repeats.

    PubMed

    Lee, Gwangrog; Abdi, Khadar; Jiang, Yong; Michaely, Peter; Bennett, Vann; Marszalek, Piotr E

    2006-03-09

    Ankyrin repeats are an amino-acid motif believed to function in protein recognition; they are present in tandem copies in diverse proteins in nearly all phyla. Ankyrin repeats contain antiparallel alpha-helices that can stack to form a superhelical spiral. Visual inspection of the extrapolated structure of 24 ankyrin-R repeats indicates the possibility of spring-like behaviour of the putative superhelix. Moreover, stacks of 17-29 ankyrin repeats in the cytoplasmic domains of transient receptor potential (TRP) channels have been identified as candidates for a spring that gates mechanoreceptors in hair cells as well as in Drosophila bristles. Here we report that tandem ankyrin repeats exhibit tertiary-structure-based elasticity and behave as a linear and fully reversible spring in single-molecule measurements by atomic force microscopy. We also observe an unexpected ability of unfolded repeats to generate force during refolding, and report the first direct measurement of the refolding force of a protein domain. Thus, we show that one of the most common amino-acid motifs has spring properties that could be important in mechanotransduction and in the design of nanodevices.

  4. Evaluation of renal function in rhesus monkeys and comparison to beagle dogs following oral administration of the organic acid triclopyr (3,5,6-trichloro-2-pyridinyloxyacetic acid).

    PubMed

    Timchalk, C; Finco, D R; Quast, J F

    1997-03-01

    The current study evaluated the effects of triclopyr (3,5, 6-trichloro-2-pyridinyloxyacetic acid) on renal function following oral administration in the beagle dog and rhesus monkey. Male rhesus monkeys were orally administered triclopyr by gavage at a dose of 5 mg/kg/day, 7 days/week for 28 days, after which the dosage was increased to 20 mg/kg/day for 102 consecutive days. Groups of male dogs were administered either a single oral dose of 5 mg/kg triclopyr or were fed a diet spiked with triclopyr at a dose of 5 mg/kg/day for 47 consecutive days. The following functional and clinical chemistry parameters were evaluated: exogenous phenolsulfonphthalein (PSP) excretion, inulin and para-aminohippurate (PAH) clearance (monkeys only), endogenous serum creatinine, and blood urea nitrogen (BUN) at multiple time points during the study. Creatinine, BUN, and inulin clearance were within the normal range from both species following triclopyr administration which indicates that repeated administration of triclopyr in the dog and monkey had no effect on glomerular filtration rate (GFR). In monkeys, the percentage excretion of PSP and PAH appeared to increase following triclopyr administration (20 mg/kg/day), suggesting that these weak organic acids may be competing for the same plasma protein-binding site enhancing their clearance. More importantly, these data strongly suggest that triclopyr is not competing with PSP or PAH for the active secretory site within the monkey kidney proximal tubules. In contrast, PSP clearance studies in dogs clearly demonstrated that triclopyr administration (5 mg/kg) can significantly decrease the percentage PSP excretion even following a single dose administration. The decrease in percentage PSP was reversible and inversely related to the plasma triclopyr concentration. Overall, these data clearly indicate that triclopyr effectively competes with PSP for the active secretory site within the dog kidney proximal tubules. In contrast, the monkey

  5. Oral Cancer Foundation

    MedlinePlus

    ... Today! Limited Edition T-Shirt Buy Today! The Oral Cancer Foundation The Oral Cancer Foundation is a national ... trustworthy health information: verify here. Social Networks The Oral Cancer Foundation 3419 Via Lido #205 Newport Beach Ca ...

  6. Oral Lichen Planus

    MedlinePlus

    Oral lichen planus Overview By Mayo Clinic Staff Oral lichen planus (LIE-kun PLAY-nus) is an ongoing (chronic) ... that affects mucous membranes inside your mouth. Oral lichen planus may appear as white, lacy patches; red, ...

  7. A Post-hoc Comparison of Paliperidone Palmitate to Oral Risperidone During Initiation of Long-acting Risperidone Injection in Patients with Acute Schizophrenia

    PubMed Central

    Pandina, Gahan; Lane, Rosanne; Nuamah, Isaac; Remmerie, Bart; Coppola, Danielle; Hough, David

    2011-01-01

    Objective: First-month data of a 13-week acute schizophrenia study were used to compare paliperidone palmitate to oral risperidone during initiation of long-acting injectable risperidone. Design: Double-blind, randomized study. Setting: Outpatient or inpatient. Participants: Adults with established (≥1 year) schizophrenia. Those assigned to risperidone long-acting injectable (n=460) received 25mg on Days 8 and 22 with oral risperidone (l–6mg) supplementation for the first 28 days. The paliperidone palmitate group (n=453) received 150mg eq. on Day 1, l00mg eq. on Day 8, and oral placebo supplementation for the first 28 days. Measurements: Positive and Negative Syndrome Scale, Personal and Social Performance Scale, Clinical Global Impression-Severity score, and responder rate (percentage of patients with ≥30% reduction in PANSS total score). An analysis of covariance model estimated least-square mean differences between treatment groups. A post-hoc analysis of efficacy data for the period of interest, i.e., at the time points before and after the first 28 days, was conducted. Results: Positive and Negative Syndrome Scale, Personal and Social Performance Scale, Clinical global Impression-Severity scores showed similar efficacy between the treatment groups during the first weeks of treatment, corresponding to the risperidone long-acting injection initiation period. Mean Positive and Negative Syndrome Scale total score at baseline was 84.7 for paliperidone palmitate and 84.4 for oral risperidone, on Day 22 was 73.6 and 74.1, respectively, and on Day 36 was 71.8 and 72.8, respectively. Overall incidence of adverse events in the first 28 days was generally similar (45% for paliperidone palmitate vs. 35% for oral risperidone), except for injection site pain (4.6% vs. 0.7%). Similar active moiety plasma concentrations were obtained during this period. Conclusion: During the first month, paliperidone palmitate without oral supplementation has similar efficacy and

  8. Toxicokinetics of short-chain chlorinated paraffins in Sprague-Dawley rats following single oral administration.

    PubMed

    Geng, Ningbo; Zhang, Haijun; Xing, Liguo; Gao, Yuan; Zhang, Baoqin; Wang, Feidi; Ren, Xiaoqian; Chen, Jiping

    2016-02-01

    Short-chain chlorinated paraffins (SCCPs) have attracted considerable attention for their characteristic of persistent organic pollutants. However, very limited information is available for their toxicokinetic characteristics, limiting the evaluation of their health risks. In this study, we performed a toxicokinetics study to explore the absorption and excretion processes of SCCPs (a mixture of C10-, C11-, C12- and C13-CPs) after a single oral administration to the Sprague-Dawley rats. The toxicokinetic results showed that peak blood concentration of total SCCPs was attained at 2.8 day with Cmax value of 2.3 mg L(-1). The half-lives of total SCCPs in blood for the absorption t1/2 (ka), distribution t1/2 (α) and elimination phases t1/2 (β) were calculated to be 1.0, 1.7 and 6.6 days, respectively. During the 28 days post-dosing, about 27.9% and 3.5% of orally administrated SCCPs were excreted through feces and urine without metabolism, respectively. Congener group abundance profiles indicate a relative increase of Cl5-SCCPs in blood and urine in the elimination stage, and a higher accumulation of Cl8-10-SCCPs in feces. The distribution discrepancies of SCCPs congener groups in blood and excreta were more dependent on chlorine contents than on carbon chain lengths.

  9. Limitations on quantum key repeaters.

    PubMed

    Bäuml, Stefan; Christandl, Matthias; Horodecki, Karol; Winter, Andreas

    2015-04-23

    A major application of quantum communication is the distribution of entangled particles for use in quantum key distribution. Owing to noise in the communication line, quantum key distribution is, in practice, limited to a distance of a few hundred kilometres, and can only be extended to longer distances by use of a quantum repeater, a device that performs entanglement distillation and quantum teleportation. The existence of noisy entangled states that are undistillable but nevertheless useful for quantum key distribution raises the question of the feasibility of a quantum key repeater, which would work beyond the limits of entanglement distillation, hence possibly tolerating higher noise levels than existing protocols. Here we exhibit fundamental limits on such a device in the form of bounds on the rate at which it may extract secure key. As a consequence, we give examples of states suitable for quantum key distribution but unsuitable for the most general quantum key repeater protocol.

  10. Magnetars as soft gamma repeaters

    NASA Astrophysics Data System (ADS)

    O'Meara, Karen

    1999-05-01

    The source of non-periodic, repeating, gamma-ray bursts located within our galaxy and near supernova remnants has been a mystery. A new theory by Christopher Thompson and Robert Duncan, postulating the existence of young neutron stars with intense magnetic fields (1E14 Gauss or more) offers an explanation. The intense magnetic fields of these "magnetars" suffice to create the phenomena detected from soft gamma-ray repeaters. The poles of a magnetar are hot enough to emit steady, low level x-ray emissions. Stresses on the star's crust due to the drifting of the magnetic field through the superfluid core create seismic activity and "starquakes," which release enormous bursts of energy. Data collected from recent soft gamma-ray repeater bursts appear to be strong evidence in support of this exciting new theory.

  11. Limitations on quantum key repeaters

    NASA Astrophysics Data System (ADS)

    Bäuml, Stefan; Christandl, Matthias; Horodecki, Karol; Winter, Andreas

    2015-04-01

    A major application of quantum communication is the distribution of entangled particles for use in quantum key distribution. Owing to noise in the communication line, quantum key distribution is, in practice, limited to a distance of a few hundred kilometres, and can only be extended to longer distances by use of a quantum repeater, a device that performs entanglement distillation and quantum teleportation. The existence of noisy entangled states that are undistillable but nevertheless useful for quantum key distribution raises the question of the feasibility of a quantum key repeater, which would work beyond the limits of entanglement distillation, hence possibly tolerating higher noise levels than existing protocols. Here we exhibit fundamental limits on such a device in the form of bounds on the rate at which it may extract secure key. As a consequence, we give examples of states suitable for quantum key distribution but unsuitable for the most general quantum key repeater protocol.

  12. Hysteresis of magnetostructural transitions: Repeatable and non-repeatable processes

    NASA Astrophysics Data System (ADS)

    Provenzano, Virgil; Della Torre, Edward; Bennett, Lawrence H.; ElBidweihy, Hatem

    2014-02-01

    The Gd5Ge2Si2 alloy and the off-stoichiometric Ni50Mn35In15 Heusler alloy belong to a special class of metallic materials that exhibit first-order magnetostructural transitions near room temperature. The magnetic properties of this class of materials have been extensively studied due to their interesting magnetic behavior and their potential for a number of technological applications such as refrigerants for near-room-temperature magnetic refrigeration. The thermally driven first-order transitions in these materials can be field-induced in the reverse order by applying a strong enough field. The field-induced transitions are typically accompanied by the presence of large magnetic hysteresis, the characteristics of which are a complicated function of temperature, field, and magneto-thermal history. In this study we show that the virgin curve, the major loop, and sequentially measured MH loops are the results of both repeatable and non-repeatable processes, in which the starting magnetostructural state, prior to the cycling of field, plays a major role. Using the Gd5Ge2Si2 and Ni50Mn35In15 alloys, as model materials, we show that a starting single phase state results in fully repeatable processes and large magnetic hysteresis, whereas a mixed phase starting state results in non-repeatable processes and smaller hysteresis.

  13. Respiratory distress associated with heterotopic gastrointestinal cysts of the oral cavity: A case report.

    PubMed

    Méndez Sáenz, Marco Antonio; de Jesús Villegas González, Mario; Ponce Camacho, Marco A; Cavazos Cavazos, Lucia M; Ibarra, Bárbara Sáenz; Esquivel García, Blanca I; Treviño González, José Luis

    2016-12-01

    Heterotopic gastrointestinal cysts of the oral cavity are benign lesions usually discovered during infancy. Their pathogenesis is not very clear. They are rare congenital anomalies that result from remnants of foregut-derived epithelium in the head, neck, thorax or abdomen during embryonic development. The majority of these lesions occur in the anterior ventral surface of the tongue and extend to the floor of the mouth. They are confused clinically by surgeons in cases of head and neck masses in children as ranulas, dermoid and thyroglossal cysts, and lymphangioma. We report the case of a 28-day newborn with a 3.6 cm oval mass on the floor of the mouth causing difficulty eating and cyanosis during crying. Complete surgical excision was performed by an oral approach under general anesthesia. Microscopic examination revealed gastric epithelium with tall columnar mucous cells on the surface and numerous short closed crypts, resembling fundal glands and mature gastric epithelium.

  14. Do Twelfths Terminate or Repeat?

    ERIC Educational Resources Information Center

    Ambrose, Rebecca; Burnison, Erica

    2015-01-01

    When finding the decimal equivalent of a fraction with 12 in the denominator, will it terminate or repeat? This question came from a seventh grader in author Erica Burnison's class as the student was pondering a poster generated by one of her classmates. Not only was the question intriguing, but it also affirmed the belief in the power of…

  15. Mechanical Anisotropy of Ankyrin Repeats

    PubMed Central

    Lee, Whasil; Zeng, Xiancheng; Rotolo, Kristina; Yang, Ming; Schofield, Christopher J.; Bennett, Vann; Yang, Weitao; Marszalek, Piotr E.

    2012-01-01

    Red blood cells are frequently deformed and their cytoskeletal proteins such as spectrin and ankyrin-R are repeatedly subjected to mechanical forces. While the mechanics of spectrin was thoroughly investigated in vitro and in vivo, little is known about the mechanical behavior of ankyrin-R. In this study, we combine coarse-grained steered molecular dynamics simulations and atomic force spectroscopy to examine the mechanical response of ankyrin repeats (ARs) in a model synthetic AR protein NI6C, and in the D34 fragment of native ankyrin-R when these proteins are subjected to various stretching geometry conditions. Our steered molecular dynamics results, supported by AFM measurements, reveal an unusual mechanical anisotropy of ARs: their mechanical stability is greater when their unfolding is forced to propagate from the N-terminus toward the C-terminus (repeats unfold at ∼60 pN), as compared to the unfolding in the opposite direction (unfolding force ∼ 30 pN). This anisotropy is also reflected in the complex refolding behavior of ARs. The origin of this unfolding and refolding anisotropy is in the various numbers of native contacts that are broken and formed at the interfaces between neighboring repeats depending on the unfolding/refolding propagation directions. Finally, we discuss how these complex mechanical properties of ARs in D34 may affect its behavior in vivo. PMID:22404934

  16. Pentapeptide Repeat Proteins and Cyanobacteria

    SciTech Connect

    Buchko, Garry W.

    2009-10-16

    Cyanobacteria are unique in many ways and one unusual feature is the presence of a suite of proteins that contain at least one domain with a minimum of eight tandem repeated five-residues (Rfr) of the general consensus sequence A[N/D]LXX. The function of such pentapeptide repeat proteins (PRPs) are still unknown, however, their prevalence in cyanobacteria suggests that they may play some role in the unique biological activities of cyanobacteria. As part of an inter-disciplinary Membrane Biology Grand Challenge at the Environmental Molecular Sciences Laboratory (Pacific Northwest National Laboratory) and Washington University in St. Louis, the genome of Cyanothece 51142 was sequenced and its molecular biology studied with relation to circadian rhythms. The genome of Cyanothece encodes for 35 proteins that contain at least one PRP domain. These proteins range in size from 105 (Cce_3102) to 930 (Cce_2929) kDa with the PRP domains ranging in predicted size from 12 (Cce_1545) to 62 (cce_3979) tandem pentapeptide repeats. Transcriptomic studies with 29 out of the 35 genes showed that at least three of the PRPs in Cyanothece 51142 (cce_0029, cce_3083, and cce_3272) oscillated with repeated periods of light and dark, further supporting a biological function for PRPs. Using X-ray diffraction crystallography, the structure for two pentapeptide repeat proteins from Cyanothece 51142 were determined, cce_1272 (aka Rfr32) and cce_4529 (aka Rfr23). Analysis of their molecular structures suggests that all PRP may share the same structural motif, a novel type of right-handed quadrilateral β-helix, or Rfr-fold, reminiscent of a square tower with four distinct faces. Each pentapeptide repeat occupies one face of the Rfr-fold with four consecutive pentapeptide repeats completing a coil that, in turn, stack upon each other to form “protein skyscrapers”. Details of the structural features of the Rfr-fold are reviewed here together with a discussion for the possible role of end

  17. [Prevention of oral diseases].

    PubMed

    Vodanović, Marin

    2013-06-01

    Oral health is essential to general health and quality of life. Ever more people are affected with oral diseases. Dental caries, gingivitis and periodontitis are the most common oral diseases and they can be prevented. Oral health promotion and oral disease prevention programs should be incorporated in national health strategies. Inability to understand health information can be a profound disadvantage to patients when asked to take responsibility for their health. Increasing the level of oral health literacy and improvement of communication between patients and dentists by avoiding the usage of professional dental terminology should be included in each oral prevention program.

  18. Methodology of oral sensory tests.

    PubMed

    Jacobs, R; Wu, C-H; Van Loven, K; Desnyder, M; Kolenaar, B; Van Steenberghed, D

    2002-08-01

    Different methods of oral sensory tests including light touch sensation, two-point discrimination, vibrotactile function and thermal sensation were compared. Healthy subjects were tested to assess the results obtained from two psychophysical approaches, namely the staircase and the ascending & descending method of limits for light touch sensation and two-point discrimination. Both methods appeared to be reliable for examining oral sensory function. The effect of topical anaesthesia was also evaluated but no conclusion could be drawn as too few subjects were involved. Newly developed simple testing tools for two-point discrimination and thermal sensation in a clinical situation were developed prior to this study and tested for their reproducibility. Thermal sensation could be reliably detected in repeated trials. Although the hand-held instruments have some drawbacks, the outcome of these instruments in a clinical environment is suitable for assessing oral sensory function. Three different frequencies (32, 128 and 256 Hz) were used to estimate the vibrotactile function. Different threshold levels were found at different frequencies.

  19. Dominant short repeated sequences in bacterial genomes.

    PubMed

    Avershina, Ekaterina; Rudi, Knut

    2015-03-01

    We use a novel multidimensional searching approach to present the first exhaustive search for all possible repeated sequences in 166 genomes selected to cover the bacterial domain. We found an overrepresentation of repeated sequences in all but one of the genomes. The most prevalent repeats by far were related to interspaced short palindromic repeats (CRISPRs)—conferring bacterial adaptive immunity. We identified a deep branching clade of thermophilic Firmicutes containing the highest number of CRISPR repeats. We also identified a high prevalence of tandem repeated heptamers. In addition, we identified GC-rich repeats that could potentially be involved in recombination events. Finally, we identified repeats in a 16322 amino acid mega protein (involved in biofilm formation) and inverted repeats flanking miniature transposable elements (MITEs). In conclusion, the exhaustive search for repeated sequences identified new elements and distribution of these, which has implications for understanding both the ecology and evolution of bacteria.

  20. Observations of Soft Gamma Repeaters

    NASA Technical Reports Server (NTRS)

    Kouveliotou, Chryssa

    2004-01-01

    Magnetars (Soft Gamma Repeaters and Anomalous X-ray Pulsars) are a subclass of neutron stars characterized by their recurrent X-ray bursts. While in an active (bursting) state (lasting anywhere between days and years), they are emit&ng hundreds of predominantly soft (kT=30 kev), short (0.1-100 ms long) events. Their quiescent source x-ray light ewes exhibit puhlions rotational period rate changes (spin-down) indicate that their magnetic fields are extremely high, of the order of 10^14- 10^l5 G. Such high B-field objects, dubbed "magnetars", had been predicted to exist in 1992, but the first concrete observational evidence were obtained in 1998 for two of these sources. I will discuss here the history of Soft Gamma Repeaters, and their spectral, timing and flux characteristics both in the persistent and their burst emission.

  1. Comparing the Efficiency of Repeated Reading and Listening-While-Reading to Improve Fluency and Comprehension

    ERIC Educational Resources Information Center

    Hawkins, Renee O.; Marsicano, Richard; Schmitt, Ara J.; McCallum, Elizabeth; Musti-Rao, Shobana

    2015-01-01

    An alternating treatments design was used to compare the effects of two reading fluency interventions on the oral reading fluency and maze accuracy of four fourth-grade students. Also, by taking into account time spent in intervention, the efficiency of the two interventions was compared. In the adult-mediated repeated reading (RR) condition,…

  2. The Effects of Repeated Readings on the Development of Lower Identification Skills of FL Readers.

    ERIC Educational Resources Information Center

    Taguchi, Etsuo

    1997-01-01

    Investigates the effects of repeated readings of a passage in a foreign language (English) on the ability of slow beginning readers at a Japanese university to increase their oral and silent reading rates. Results indicate that, for practice passages, silent reading rates increased significantly. This transfer of practice effects to a new passage…

  3. A repeating fast radio burst

    NASA Astrophysics Data System (ADS)

    Spitler, L. G.; Scholz, P.; Hessels, J. W. T.; Bogdanov, S.; Brazier, A.; Camilo, F.; Chatterjee, S.; Cordes, J. M.; Crawford, F.; Deneva, J.; Ferdman, R. D.; Freire, P. C. C.; Kaspi, V. M.; Lazarus, P.; Lynch, R.; Madsen, E. C.; McLaughlin, M. A.; Patel, C.; Ransom, S. M.; Seymour, A.; Stairs, I. H.; Stappers, B. W.; van Leeuwen, J.; Zhu, W. W.

    2016-03-01

    Fast radio bursts are millisecond-duration astronomical radio pulses of unknown physical origin that appear to come from extragalactic distances. Previous follow-up observations have failed to find additional bursts at the same dispersion measure (that is, the integrated column density of free electrons between source and telescope) and sky position as the original detections. The apparent non-repeating nature of these bursts has led to the suggestion that they originate in cataclysmic events. Here we report observations of ten additional bursts from the direction of the fast radio burst FRB 121102. These bursts have dispersion measures and sky positions consistent with the original burst. This unambiguously identifies FRB 121102 as repeating and demonstrates that its source survives the energetic events that cause the bursts. Additionally, the bursts from FRB 121102 show a wide range of spectral shapes that appear to be predominantly intrinsic to the source and which vary on timescales of minutes or less. Although there may be multiple physical origins for the population of fast radio bursts, these repeat bursts with high dispersion measure and variable spectra specifically seen from the direction of FRB 121102 support an origin in a young, highly magnetized, extragalactic neutron star.

  4. A repeating fast radio burst.

    PubMed

    Spitler, L G; Scholz, P; Hessels, J W T; Bogdanov, S; Brazier, A; Camilo, F; Chatterjee, S; Cordes, J M; Crawford, F; Deneva, J; Ferdman, R D; Freire, P C C; Kaspi, V M; Lazarus, P; Lynch, R; Madsen, E C; McLaughlin, M A; Patel, C; Ransom, S M; Seymour, A; Stairs, I H; Stappers, B W; van Leeuwen, J; Zhu, W W

    2016-03-10

    Fast radio bursts are millisecond-duration astronomical radio pulses of unknown physical origin that appear to come from extragalactic distances. Previous follow-up observations have failed to find additional bursts at the same dispersion measure (that is, the integrated column density of free electrons between source and telescope) and sky position as the original detections. The apparent non-repeating nature of these bursts has led to the suggestion that they originate in cataclysmic events. Here we report observations of ten additional bursts from the direction of the fast radio burst FRB 121102. These bursts have dispersion measures and sky positions consistent with the original burst. This unambiguously identifies FRB 121102 as repeating and demonstrates that its source survives the energetic events that cause the bursts. Additionally, the bursts from FRB 121102 show a wide range of spectral shapes that appear to be predominantly intrinsic to the source and which vary on timescales of minutes or less. Although there may be multiple physical origins for the population of fast radio bursts, these repeat bursts with high dispersion measure and variable spectra specifically seen from the direction of FRB 121102 support an origin in a young, highly magnetized, extragalactic neutron star.

  5. Peptides in oral diseases.

    PubMed

    Lucchese, Alberta; Guida, Agostino; Petruzzi, Massimo; Capone, Giovanni; Laino, Luigi; Serpico, Rosario

    2012-01-01

    The oral cavity is home to numerous viruses and micro-organisms recognized as having a role in various oral diseases as well as in infections in other parts of the body. Indeed, in general a microbial infection underlies or is believed to underlie the ample spectrum of oral diseases, from tooth enamel decay to periodontal lesions, from candidiasis to virus-induced oral squamous cell carcinomas, and bullous autoimmune oral disorders. This clinico-pathological context stresses the need of targeted therapies to specifically kill infectious agents in a complex environment such as the oral cavity, and explains the current interest in exploring peptide-based therapeutic approaches in oral and dental research. Here, we review the therapeutic potential of antimicrobial peptides such as LL-37, beta defensins, adrenomedullin, histatins, and of various peptides modulating gene expression and immuno-biological interaction(s) in oral diseases.

  6. Accumulate Repeat Accumulate Coded Modulation

    NASA Technical Reports Server (NTRS)

    Abbasfar, Aliazam; Divsalar, Dariush; Yao, Kung

    2004-01-01

    In this paper we propose an innovative coded modulation scheme called 'Accumulate Repeat Accumulate Coded Modulation' (ARA coded modulation). This class of codes can be viewed as serial turbo-like codes, or as a subclass of Low Density Parity Check (LDPC) codes that are combined with high level modulation. Thus at the decoder belief propagation can be used for iterative decoding of ARA coded modulation on a graph, provided a demapper transforms the received in-phase and quadrature samples to reliability of the bits.

  7. HAD Oral History Project

    NASA Astrophysics Data System (ADS)

    Holbrook, Jarita

    2014-01-01

    The Historical Astronomy Division is the recipient of an American Institute of Physics Neils Bohr Library Grant for Oral History. HAD has assembled a team of volunteers to conduct oral history interviews since May 2013. Each oral history interview varies in length between two and six hours. This presentation is an introduction to the HAD Oral History Project and the activities of the team during the first six months of the grant.

  8. Oral Steroids for Dermatitis.

    PubMed

    Fisher, Andrew D; Clarke, Jesse; Williams, Timothy K

    2015-01-01

    Contact/allergic dermatitis is frequently treated inappropriately with lower-than-recommended doses or inadequate duration of treatment with oral and intramuscular glucocorticoids. This article highlights a case of dermatitis in a Ranger Assessment and Selection Program student who was improperly treated over 2 weeks with oral steroids after being bit by Cimex lectularius, commonly known as bed bugs. The article also highlights the pitfalls of improper oral steroid dosing and provides reasoning for longer-duration oral steroid treatment.

  9. Subacute and Reproductive Oral Toxicity Assessment of the Hydroethanolic Extract of Jacaranda decurrens Roots in Adult Male Rats.

    PubMed

    Santos, Joyce Alencar; Arruda, Aline; Cardoso, Claudia Andrea Lima; Vieira, Maria do Carmo; Piccinelli, Ana Cláudia; Figueiredo de Santana Aquino, Diana; Kassuya, Cândida Aparecida Leite; Arena, Arielle Cristina

    2013-01-01

    Jacaranda decurrens subsp. symmetrifoliolata Farias & Proença (Bignoniaceae) is a species traditionally used for the treatment of inflammatory and infectious diseases. Previous findings from our group reported scientifically that J. decurrens has anti-inflammatory efficacy. However, more toxicological studies are needed to support and ensure its safe use. The present study was carried out to evaluate the toxic effects of a prolonged treatment with hydroethanolic root extract of J. decurrens (EJD) on hematological, biochemical, and reproductive parameters in adult male rats. The animals received by oral gavage 0; 250; 500; or 1000 mg/kg body weight of EJD for 28 days. After the treatment, biochemical, hematological, histopathological, and reproductive parameters were analyzed. The EJD treatment did not cause adverse effects on body weight gain, feed and water consumption, hematological and biochemical profiles, or histopathological analysis of liver and kidney. Similarly, there were no statistically significant differences in reproductive parameters, such as sperm production, number of sperm in the epididymis, and sperm morphology. These results demonstrate the absence of subacute toxicity as a result of the oral treatment with EJD for 28 days in adult male rats. However, other studies should be performed to evaluate the total safety of this plant.

  10. Effect of oral methyl-t-butyl ether (MTBE) on the male mouse reproductive tract and oxidative stress in liver.

    PubMed

    de Peyster, Ann; Rodriguez, Yvonne; Shuto, Rika; Goldberg, Beck; Gonzales, Frank; Pu, Xinzhu; Klaunig, James E

    2008-01-01

    MTBE is found in water supplies used for drinking and other purposes. These experiments follow up on earlier reports of reproductive tract alterations in male mice exposed orally to MTBE and explored oxidative stress as a mode of action. CD-1 mice were gavaged with 400-2000 mg/kg MTBE on days 1, 3, and 5, injected i.p. with hCG (2.5 IU/g) on day 6, and necropsied on day 7. No effect was seen in testis histology or testosterone levels. Using a similar dosing protocol, others had initially reported disruption of seminiferous tubules in MTBE-gavaged mice, although later conclusions published were consistent with our findings. Another group had also reported testicular and other reproductive system abnormalities in male BALB/c mice exposed for 28 days to 80-8000 microg/ml MTBE in drinking water. We gave these MTBE concentrations to adult mice for 28 days and juvenile mice for 51 days through PND 77. Evidence of oxidative stress was examined in liver homogenates from the juvenile study using MDA, TEAC and 8OH2hG as endpoints. MTBE exposures at the levels examined indicated no significant changes in the male mouse reproductive tract and no signs of hepatic oxidative stress. This appears to be the first oral MTBE exposure of juvenile animals, and also the first to examine potential for MTBE to cause oxidative stress in vivo using a typical route of human exposure.

  11. Oral Communication K-9.

    ERIC Educational Resources Information Center

    Cottrell, June, Ed.

    This speech communication curriculum guide is designed to provide a comprehensive oral language curriculum, to suggest ways for integrating oral activities into other curriculum areas, and to stimulate ideas for using oral language in a holistic rather than a fragmentary learning environment. Following an introductory chapter on "creating the…

  12. Understanding Oral Learners

    ERIC Educational Resources Information Center

    Moon, W. Jay

    2012-01-01

    A five-year research project of seminary students from various cultural backgrounds revealed that the slight majority of contemporary seminary students studied are oral learners. Oral learners learn best and have their lives most transformed when professors utilize oral teaching and assessment methods. After explaining several preferences of oral…

  13. Head, Neck, and Oral Cancer

    MedlinePlus

    ... find out more. Head, Neck and Oral Pathology Head, Neck and Oral Pathology Close to 49,750 Americans ... find out more. Head, Neck and Oral Pathology Head, Neck and Oral Pathology Close to 49,750 Americans ...

  14. Effect of oral contraceptives and doxycycline on endometrial MMP-2 AND MMP-9 activity

    PubMed Central

    Kaneshiro, Bliss; Edelman, Alison; Dash, Chandravanu; Pandhare, Jui; Soli, Faapisa M.; Jensen, Jeffrey T.

    2015-01-01

    Objectives To describe the effect of combined oral contraceptives (COC) on Matrix Metalloproteinase (MMP) -2 and -9 activity and compare MMP activity in women taking aCOC with or without doxycycline. Study Design Subjects (n=20) underwent endometrial biopsies1) in the late luteal phase of a baseline cycle prior to initiating COCs, 2) on day 19 to 21 while taking COCs in a standard 28-day cycle (7-day hormone free interval), 3) on day 26 to 28 while taking active COCs continuously for a 28 day cycle. During the continuous COC cycle, they were randomized to receive daily sub-antimicrobial dose doxycycline 40 mg or placebo. Results Compared to baseline, COC treatment increased MMP-2 (p<0.001) and -9(p<0.001). MMP activity was lower in subjects taking a COC with doxycycline compared to those receiving placebo, although only significantly lower for MMP-2LF (p=0.002). Conclusions Unscheduled bleeding with COCs may be the result of increased endometrial MMPs. Sample size limitations prevent us from determining how doxycycline affects MMP activity in COC-users. PMID:26408375

  15. Crowding by a repeating pattern

    PubMed Central

    Rosen, Sarah; Pelli, Denis G.

    2015-01-01

    Theinability to recognize a peripheral target among flankers is called crowding. For a foveal target, crowding can be distinguished from overlap masking by its sparing of detection, linear scaling with eccentricity, and invariance with target size.Crowding depends on the proximity and similarity of the flankers to the target. Flankers that are far from or dissimilar to the target do not crowd it. On a gray page, text whose neighboring letters have different colors, alternately black and white, has enough dissimilarity that it might escape crowding. Since reading speed is normally limited by crowding, escape from crowding should allow faster reading. Yet reading speed is unchanged (Chung & Mansfield, 2009). Why? A recent vernier study found that using alternating-color flankers produces strong crowding (Manassi, Sayim, & Herzog, 2012). Might that effect occur with letters and reading? Critical spacing is the minimum center-to-center target–flanker spacing needed to correctly identify the target. We measure it for a target letter surrounded by several equidistant flanker letters of the same polarity, opposite polarity, or mixed polarity: alternately white and black. We find strong crowding in the alternating condition, even though each flanker letter is beyond its own critical spacing (as measured in a separate condition). Thus a periodic repeating pattern can produce crowding even when the individual elements do not. Further, in all conditions we find that, once a periodic pattern repeats (two cycles), further repetition does not affect critical spacing of the innermost flanker. PMID:26024457

  16. Crowding by a repeating pattern.

    PubMed

    Rosen, Sarah; Pelli, Denis G

    2015-01-01

    Theinability to recognize a peripheral target among flankers is called crowding. For a foveal target, crowding can be distinguished from overlap masking by its sparing of detection, linear scaling with eccentricity, and invariance with target size.Crowding depends on the proximity and similarity of the flankers to the target. Flankers that are far from or dissimilar to the target do not crowd it. On a gray page, text whose neighboring letters have different colors, alternately black and white, has enough dissimilarity that it might escape crowding. Since reading speed is normally limited by crowding, escape from crowding should allow faster reading. Yet reading speed is unchanged (Chung & Mansfield, 2009). Why? A recent vernier study found that using alternating-color flankers produces strong crowding (Manassi, Sayim, & Herzog, 2012). Might that effect occur with letters and reading? Critical spacing is the minimum center-to-center target-flanker spacing needed to correctly identify the target. We measure it for a target letter surrounded by several equidistant flanker letters of the same polarity, opposite polarity, or mixed polarity: alternately white and black. We find strong crowding in the alternating condition, even though each flanker letter is beyond its own critical spacing (as measured in a separate condition). Thus a periodic repeating pattern can produce crowding even when the individual elements do not. Further, in all conditions we find that, once a periodic pattern repeats (two cycles), further repetition does not affect critical spacing of the innermost flanker.

  17. Influence of repeated ochratoxin A ingestion on milk production and its carry-over into the milk, blood and tissues of lactating cows.

    PubMed

    Hashimoto, Yasushi; Katsunuma, Yu; Nunokawa, Masahiro; Minato, Hajime; Yonemochi, Chisato

    2016-04-01

    An experiment was conducted to investigate the influence of repeated ingestion of ochratoxin A (OTA) on milk production of lactating Holstein cows over 28 days, and the carry-over of OTA from the diets into the milk and tissues of the cows. Nine cows were divided into three groups, labeled OTA5, OTA50 and OTA100, and fed a diet containing 5, 50 and 100 µg OTA/kg of dry matter, respectively. Body weight, feed intake and daily milk yield in cows were not different among the three groups during the OTA-intake period. OTA residues were neither detected in the tissues, such as liver, kidney, muscles, fat and jejunoileum, nor in the milk of any cows in the OTA intake groups. In contrast, a small amount of OTA (0.1 µg/kg) was detected in the blood plasma of one sample in the OTA50 group and multiple samples in the OTA100 group. The results of this study show that the ingestion of diets containing up to 100 µg/kg of OTA over 28 days does not affect feed intake or milk production of cows, and the dietary OTA is not carried over into milk and edible tissues such as the liver, muscles and fat.

  18. Oral steroid contraception.

    PubMed

    Sech, Laura A; Mishell, Daniel R

    2015-11-01

    Oral steroid contraception is a popular method of family planning worldwide. Over the past several decades, this method of contraception has changed significantly by decreasing the estrogen dose, changing the progestin component, and reducing the hormone free interval. Despite the popularity of oral steroid contraception, there has been much criticism regarding the associated risks of venous thromboembolism and stroke. Despite these established, yet uncommon risks, oral steroid contraception has many important health benefits. This review highlights the available formulations of oral contraceptives along with their evidence-based associated risks and benefits. Highlights regarding future directions for development of novel oral contraceptives are also addressed.

  19. Essentials of oral cancer.

    PubMed

    Rivera, César

    2015-01-01

    Oral cancer is one of the 10 most common cancers in the world, with a delayed clinical detection, poor prognosis, without specific biomarkers for the disease and expensive therapeutic alternatives. This review aims to present the fundamental aspects of this cancer, focused on squamous cell carcinoma of the oral cavity (OSCC), moving from its definition and epidemiological aspects, addressing the oral carcinogenesis, oral potentially malignant disorders, epithelial precursor lesions and experimental methods for its study, therapies and future challenges. Oral cancer is a preventable disease, risk factors and natural history is already being known, where biomedical sciences and dentistry in particular are likely to improve their poor clinical indicators.

  20. Essentials of oral cancer

    PubMed Central

    Rivera, César

    2015-01-01

    Oral cancer is one of the 10 most common cancers in the world, with a delayed clinical detection, poor prognosis, without specific biomarkers for the disease and expensive therapeutic alternatives. This review aims to present the fundamental aspects of this cancer, focused on squamous cell carcinoma of the oral cavity (OSCC), moving from its definition and epidemiological aspects, addressing the oral carcinogenesis, oral potentially malignant disorders, epithelial precursor lesions and experimental methods for its study, therapies and future challenges. Oral cancer is a preventable disease, risk factors and natural history is already being known, where biomedical sciences and dentistry in particular are likely to improve their poor clinical indicators. PMID:26617944

  1. Evolution of Protein Domain Repeats in Metazoa

    PubMed Central

    Schüler, Andreas; Bornberg-Bauer, Erich

    2016-01-01

    Repeats are ubiquitous elements of proteins and they play important roles for cellular function and during evolution. Repeats are, however, also notoriously difficult to capture computationally and large scale studies so far had difficulties in linking genetic causes, structural properties and evolutionary trajectories of protein repeats. Here we apply recently developed methods for repeat detection and analysis to a large dataset comprising over hundred metazoan genomes. We find that repeats in larger protein families experience generally very few insertions or deletions (indels) of repeat units but there is also a significant fraction of noteworthy volatile outliers with very high indel rates. Analysis of structural data indicates that repeats with an open structure and independently folding units are more volatile and more likely to be intrinsically disordered. Such disordered repeats are also significantly enriched in sites with a high functional potential such as linear motifs. Furthermore, the most volatile repeats have a high sequence similarity between their units. Since many volatile repeats also show signs of recombination, we conclude they are often shaped by concerted evolution. Intriguingly, many of these conserved yet volatile repeats are involved in host-pathogen interactions where they might foster fast but subtle adaptation in biological arms races. Key Words: protein evolution, domain rearrangements, protein repeats, concerted evolution. PMID:27671125

  2. Pharmacokinetics and pharmacodynamics of oral testosterone enanthate plus dutasteride for 4 weeks in normal men: implications for male hormonal contraception.

    PubMed

    Amory, John K; Kalhorn, Thomas F; Page, Stephanie T

    2008-01-01

    Oral administration of testosterone enanthate (TE) and dutasteride increases serum testosterone and might be useful for male hormonal contraception. To ascertain the contraceptive potential of oral TE and dutasteride by determining the degree of gonadotropin suppression mediated by 4 weeks of oral TE plus dutasteride, 20 healthy young men were randomly assigned to 4 weeks of either 400 mg oral TE twice daily or 800 mg oral TE once daily in a double-blinded, controlled fashion at a single site. All men received 0.5 mg dutasteride daily. Blood for measurement of serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, dihydrotesterone (DHT), and estradiol was obtained prior to treatment, weekly during treatment, and 1, 2, 4, 8, 12, 13, 14, 16, 20, and 24 hours after the morning dose on the last day of treatment. FSH was significantly suppressed throughout treatment with 800 mg TE once daily and after 4 weeks of treatment with 400 mg TE twice daily. LH was significantly suppressed after 2 weeks of treatment with 800 mg TE, but not with 400 mg TE. Serum DHT was suppressed and serum estradiol increased during treatment in both groups. High-density lipoprotein cholesterol was suppresed during treatment, but liver function tests, hematocrit, creatinine, mood, and sexual function were unaffected. The administration of 800 mg oral TE daily combined with dutasteride for 28 days significantly suppresses gonadotropins without untoward side effects and might have utility as part of a male hormonal contraceptive regimen.

  3. Two-dimensional quantum repeaters

    NASA Astrophysics Data System (ADS)

    Wallnöfer, J.; Zwerger, M.; Muschik, C.; Sangouard, N.; Dür, W.

    2016-11-01

    The endeavor to develop quantum networks gave rise to a rapidly developing field with far-reaching applications such as secure communication and the realization of distributed computing tasks. This ultimately calls for the creation of flexible multiuser structures that allow for quantum communication between arbitrary pairs of parties in the network and facilitate also multiuser applications. To address this challenge, we propose a two-dimensional quantum repeater architecture to establish long-distance entanglement shared between multiple communication partners in the presence of channel noise and imperfect local control operations. The scheme is based on the creation of self-similar multiqubit entanglement structures at growing scale, where variants of entanglement swapping and multiparty entanglement purification are combined to create high-fidelity entangled states. We show how such networks can be implemented using trapped ions in cavities.

  4. Linear Synchronous Motor Repeatability Tests

    SciTech Connect

    Ward, C.R.

    2002-10-18

    A cart system using linear synchronous motors was being considered for the Plutonium Immobilization Plant (PIP). One of the applications in the PIP was the movement of a stack of furnace trays, filled with the waste form (pucks) from a stacking/unstacking station to several bottom loaded furnaces. A system was ordered to perform this function in the PIP Ceramic Prototype Test Facility (CPTF). This system was installed and started up in SRTC prior to being installed in the CPTF. The PIP was suspended and then canceled after the linear synchronous motor system was started up. This system was used to determine repeatability of a linear synchronous motor cart system for the Modern Pit Facility.

  5. Repeat instability: mechanisms of dynamic mutations.

    PubMed

    Pearson, Christopher E; Nichol Edamura, Kerrie; Cleary, John D

    2005-10-01

    Disease-causing repeat instability is an important and unique form of mutation that is linked to more than 40 neurological, neurodegenerative and neuromuscular disorders. DNA repeat expansion mutations are dynamic and ongoing within tissues and across generations. The patterns of inherited and tissue-specific instability are determined by both gene-specific cis-elements and trans-acting DNA metabolic proteins. Repeat instability probably involves the formation of unusual DNA structures during DNA replication, repair and recombination. Experimental advances towards explaining the mechanisms of repeat instability have broadened our understanding of this mutational process. They have revealed surprising ways in which metabolic pathways can drive or protect from repeat instability.

  6. 40 CFR 795.228 - Oral/dermal pharmacokinetics.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... radioactivity following oral or dermal administration and total excretion following intravenous administration... repeated dosing study, shall be terminated at 7 days or after at least 90 percent of the radioactivity has... skin surface. Both the covering and the washing shall be assayed to recover residual radioactivity....

  7. 40 CFR 795.228 - Oral/dermal pharmacokinetics.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... radioactivity following oral or dermal administration and total excretion following intravenous administration... repeated dosing study, shall be terminated at 7 days or after at least 90 percent of the radioactivity has... skin surface. Both the covering and the washing shall be assayed to recover residual radioactivity....

  8. 40 CFR 795.228 - Oral/dermal pharmacokinetics.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... radioactivity following oral or dermal administration and total excretion following intravenous administration... repeated dosing study, shall be terminated at 7 days or after at least 90 percent of the radioactivity has... skin surface. Both the covering and the washing shall be assayed to recover residual radioactivity....

  9. Reproducibility and validity of oral visual inspection by trained health workers in the detection of oral precancer and cancer.

    PubMed Central

    Mathew, B.; Sankaranarayanan, R.; Sunilkumar, K. B.; Kuruvila, B.; Pisani, P.; Nair, M. K.

    1997-01-01

    A randomized intervention trial is in progress in Kerala, India, to evaluate the effectiveness of oral visual inspection by trained health workers (HWs) in the prevention of oral cancer. Fourteen health workers with college graduation as the basic qualification were trained in oral visual inspection to identify oral cancers and precancers among the participants of the screening trial and to refer them for further confirmation and management. The aim of the present study was to evaluate the reproducibility and validity of the screening test provided by the health worker against the reference oral visual findings of three physicians. A total of 2069 subjects who had already been examined were re-examined by the health workers and physicians. The sensitivity and the specificity of the oral visual inspection were 94.3% and 99.3% respectively. There was moderate agreement between the findings of the initial and the repeat mouth examinations carried out by the health workers, which were on average 6 months apart. There was almost perfect agreement (kappa = 0.85) between the findings of the health workers and the physicians in identifying the different types of oral precancerous lesions. The findings of our study indicate that it is possible to train resource persons to perform the oral cancer screening test as accurately as doctors, although experience appears to be a crucial component of health workers' accuracy. The efficacy of such an approach to reduce the incidence of and mortality from oral cancer, however, remains to be proven. PMID:9252209

  10. Relationship between brain accumulation of manganese and aberration of hippocampal adult neurogenesis after oral exposure to manganese chloride in mice.

    PubMed

    Kikuchihara, Yoh; Abe, Hajime; Tanaka, Takeshi; Kato, Mizuho; Wang, Liyun; Ikarashi, Yoshiaki; Yoshida, Toshinori; Shibutani, Makoto

    2015-05-04

    We previously found persistent aberration of hippocampal adult neurogenesis, along with brain manganese (Mn) accumulation, in mouse offspring after developmental exposure to 800-ppm dietary Mn. Reduction of parvalbumin (Pvalb)(+) γ-aminobutyric acid (GABA)-ergic interneurons in the hilus of the dentate gyrus along with promoter region hypermethylation are thought to be responsible for this aberrant neurogenesis. The present study was conducted to examine the relationship between the induction of aberrant neurogenesis and brain Mn accumulation after oral Mn exposure as well as the responsible mechanism in young adult animals. We used two groups of mice with 28- or 56-day exposure periods to oral MnCl2·xH2O at 800 ppm as Mn, a dose sufficient to lead to aberrant neurogenesis after developmental exposure. A third group of mice received intravenous injections of Mn at 5-mg/kg body weight once weekly for 28 days. The 28-day oral Mn exposure did not cause aberrations in neurogenesis. In contrast, 56-day oral exposure caused aberrations in neurogenesis suggestive of reductions in type 2b and type 3 progenitor cells and immature granule cells in the dentate subgranular zone. Brain Mn accumulation in 56-day exposed cases, as well as in directly Mn-injected cases occurred in parallel with reduction of Pvalb(+) GABAergic interneurons in the dentate hilus, suggesting that this may be responsible for aberrant neurogenesis. For reduction of Pvalb(+) interneurons, suppression of brain-derived neurotrophic factor-mediated signaling of mature granule cells may occur via suppression of c-Fos-mediated neuronal plasticity due to direct Mn-toxicity rather than promoter region hypermethylation of Pvalb.

  11. Unfolding a linker between helical repeats.

    PubMed

    Ortiz, Vanessa; Nielsen, Steven O; Klein, Michael L; Discher, Dennis E

    2005-06-10

    In many multi-repeat proteins, linkers between repeats have little secondary structure and place few constraints on folding or unfolding. However, the large family of spectrin-like proteins, including alpha-actinin, spectrin, and dystrophin, share three-helix bundle, spectrin repeats that appear in crystal structures to be linked by long helices. All of these proteins are regularly subjected to mechanical stress. Recent single molecule atomic force microscopy (AFM) experiments demonstrate not only forced unfolding but also simultaneous unfolding of tandem repeats at finite frequency, which suggests that the contiguous helix between spectrin repeats can propagate a cooperative helix-to-coil transition. Here, we address what happens atomistically to the linker under stress by steered molecular dynamics simulations of tandem spectrin repeats in explicit water. The results for alpha-actinin repeats reveal rate-dependent pathways, with one pathway showing that the linker between repeats unfolds, which may explain the single-repeat unfolding pathway observed in AFM experiments. A second pathway preserves the structural integrity of the linker, which explains the tandem-repeat unfolding event. Unfolding of the linker begins with a splay distortion of proximal loops away from hydrophobic contacts with the linker. This is followed by linker destabilization and unwinding with increased hydration of the backbone. The end result is an unfolded helix that mechanically decouples tandem repeats. Molecularly detailed insights obtained here aid in understanding the mechanical coupling of domain stability in spectrin family proteins.

  12. A Semiparametric Bayesian Model for Repeatedly Repeated Binary Outcomes

    PubMed Central

    Quintana, Fernando A.; Müller, Peter; Rosner, Gary L.; Relling, Mary V.

    2009-01-01

    Summary We discuss the analysis of data from single nucleotide polymorphism (SNP) arrays comparing tumor and normal tissues. The data consist of sequences of indicators for loss of heterozygosity (LOH) and involve three nested levels of repetition: chromosomes for a given patient, regions within chromosomes, and SNPs nested within regions. We propose to analyze these data using a semiparametric model for multi-level repeated binary data. At the top level of the hierarchy we assume a sampling model for the observed binary LOH sequences that arises from a partial exchangeability argument. This implies a mixture of Markov chains model. The mixture is defined with respect to the Markov transition probabilities. We assume a nonparametric prior for the random mixing measure. The resulting model takes the form of a semiparametric random effects model with the matrix of transition probabilities being the random effects. The model includes appropriate dependence assumptions for the two remaining levels of the hierarchy, i.e., for regions within chromosomes and for chromosomes within patient. We use the model to identify regions of increased LOH in a dataset coming from a study of treatment-related leukemia in children with an initial cancer diagnostic. The model successfully identifies the desired regions and performs well compared to other available alternatives. PMID:19746193

  13. Solid oral forms availability in children: a cost saving investigation

    PubMed Central

    Lajoinie, Audrey; Henin, Emilie; Kassai, Behrouz; Terry, David

    2014-01-01

    Aim To assess the suitability and potential cost savings, from both the hospital and community perspective, of prescribed oral liquid medicine substitution with acceptable solid forms for children over 2 years. Method Oral liquid medicines dispensed from a paediatric hospital (UK) in 1 week were assessed by screening for existence of the solid form alternative and evaluating the acceptability of the available solid form, firstly related to the prescribed dose and secondly to acceptable size depending on the child's age. Costs were calculated based on providing treatment for 28 days or prescribed duration for short term treatments. Results Over 90% (440/476) of liquid formulations were available as a marketed solid form. Considering dosage acceptability (maximum of 10% deviation from prescribed dosage or 0% for narrow therapeutic range drugs, maximum tablet divisions into quarters) 80% of liquids could be substituted with a solid form. The main limitation for liquid substitution would be solid form size. However, two-thirds of prescribed liquids could have been substituted with a suitable solid form for dosage and size, with estimated savings being of £5K and £8K in 1 week, respectively based on hospital and community costs, corresponding to a projected annual saving of £238K and £410K (single institution). Conclusion Whilst not all children over 2 years will be able to swallow tablets, drug cost savings if oral liquid formulations were substituted with suitable solid dosage forms would be considerable. Given the numerous advantages of solid forms compared with liquids, this study may provide a theoretical basis for investing in supporting children to swallow tablets/capsules. PMID:24965935

  14. Radiation Induced Oral Mucositis

    PubMed Central

    PS, Satheesh Kumar; Balan, Anita; Sankar, Arun; Bose, Tinky

    2009-01-01

    Patients receiving radiotherapy or chemotherapy will receive some degree of oral mucositis The incidence of oral mucositis was especially high in patients: (i) With primary tumors in the oral cavity, oropharynx, or nasopharynx; (ii) who also received concomitant chemotherapy; (iii) who received a total dose over 5,000 cGy; and (iv) who were treated with altered fractionation radiation schedules. Radiation-induced oral mucositis affects the quality of life of the patients and the family concerned. The present day management of oral mucositis is mostly palliative and or supportive care. The newer guidelines are suggesting Palifermin, which is the first active mucositis drug as well as Amifostine, for radiation protection and cryotherapy. The current management should focus more on palliative measures, such as pain management, nutritional support, and maintenance, of good oral hygiene PMID:20668585

  15. Acute and Subacute Oral Toxicity Evaluation of Eriobotrya japonica Leaf Triterpene Acids in ICR Mice

    PubMed Central

    Shi, Xianai

    2017-01-01

    The interest focusing on Eriobotrya japonica leaf triterpene acid (ELTA) has increased recently because of its beneficial effects on health. However, there has been a lack of experimental data on its toxicity. The present study therefore was conducted to evaluate its toxicity in ICR mice. The results showed that ELTA produced neither mortality nor toxicity of the main organs in ICR male and female mice in both acute (0.30, 0.65, 1.39, and 3.00 g·kg−1 body weight) and subacute (150, 300, and 600 mg·kg−1 BW) 28-day toxicity studies. Because of lacking apparently adverse effects found in the hematology, clinical biochemistry, and histopathology evaluation, results of the present study together with the beneficial effects make ELTA as a promising dietary supplement and indicated that ELTA administered orally might have a large safety margin for human.

  16. Modeling Repeatedly Flaring δ Sunspots

    NASA Astrophysics Data System (ADS)

    Chatterjee, Piyali; Hansteen, Viggo; Carlsson, Mats

    2016-03-01

    Active regions (ARs) appearing on the surface of the Sun are classified into α , β , γ , and δ by the rules of the Mount Wilson Observatory, California on the basis of their topological complexity. Amongst these, the δ sunspots are known to be superactive and produce the most x-ray flares. Here, we present results from a simulation of the Sun by mimicking the upper layers and the corona, but starting at a more primitive stage than any earlier treatment. We find that this initial state consisting of only a thin subphotospheric magnetic sheet breaks into multiple flux tubes which evolve into a colliding-merging system of spots of opposite polarity upon surface emergence, similar to those often seen on the Sun. The simulation goes on to produce many exotic δ sunspot associated phenomena: repeated flaring in the range of typical solar flare energy release and ejective helical flux ropes with embedded cool-dense plasma filaments resembling solar coronal mass ejections.

  17. Modeling Repeatedly Flaring δ Sunspots.

    PubMed

    Chatterjee, Piyali; Hansteen, Viggo; Carlsson, Mats

    2016-03-11

    Active regions (ARs) appearing on the surface of the Sun are classified into α, β, γ, and δ by the rules of the Mount Wilson Observatory, California on the basis of their topological complexity. Amongst these, the δ sunspots are known to be superactive and produce the most x-ray flares. Here, we present results from a simulation of the Sun by mimicking the upper layers and the corona, but starting at a more primitive stage than any earlier treatment. We find that this initial state consisting of only a thin subphotospheric magnetic sheet breaks into multiple flux tubes which evolve into a colliding-merging system of spots of opposite polarity upon surface emergence, similar to those often seen on the Sun. The simulation goes on to produce many exotic δ sunspot associated phenomena: repeated flaring in the range of typical solar flare energy release and ejective helical flux ropes with embedded cool-dense plasma filaments resembling solar coronal mass ejections.

  18. Trinucleotide Repeats: A Structural Perspective

    PubMed Central

    Almeida, Bruno; Fernandes, Sara; Abreu, Isabel A.; Macedo-Ribeiro, Sandra

    2013-01-01

    Trinucleotide repeat (TNR) expansions are present in a wide range of genes involved in several neurological disorders, being directly involved in the molecular mechanisms underlying pathogenesis through modulation of gene expression and/or the function of the RNA or protein it encodes. Structural and functional information on the role of TNR sequences in RNA and protein is crucial to understand the effect of TNR expansions in neurodegeneration. Therefore, this review intends to provide to the reader a structural and functional view of TNR and encoded homopeptide expansions, with a particular emphasis on polyQ expansions and its role at inducing the self-assembly, aggregation and functional alterations of the carrier protein, which culminates in neuronal toxicity and cell death. Detail will be given to the Machado-Joseph Disease-causative and polyQ-containing protein, ataxin-3, providing clues for the impact of polyQ expansion and its flanking regions in the modulation of ataxin-3 molecular interactions, function, and aggregation. PMID:23801983

  19. [Oral precancer and cancer].

    PubMed

    López-López, José; Omaña-Cepeda, Carlos; Jané-Salas, Enric

    2015-11-06

    We reviewed the concept of oral precancerous lesions, oral cancer, and the possibility of early diagnosis. With the keywords: premalignant oral lesions prevention, a search was performed over the past 10 years. Also clinical trials are searched from January 2011 until today with the keywords: oral cancer prevention AND dentistry. It is emphasized that there can be no significant changes related to the concept of precancerous lesions and cancer, and those relating to the early diagnosis. Despite the numerous described methods of screening, biopsy remains the most useful test, and therefore it is essential, mainly if we consider the new possibilities of molecular studies.

  20. Towards understanding oral health.

    PubMed

    Zaura, Egija; ten Cate, Jacob M

    2015-01-01

    During the last century, dental research has focused on unraveling the mechanisms behind various oral pathologies, while oral health was typically described as the mere absence of oral diseases. The term 'oral microbial homeostasis' is used to describe the capacity of the oral ecosystem to maintain microbial community stability in health. However, the oral ecosystem itself is not stable: throughout life an individual undergoes multiple physiological changes while progressing through infancy, childhood, adolescence, adulthood and old age. Recent discussions on the definition of general health have led to the proposal that health is the ability of the individual to adapt to physiological changes, a condition known as allostasis. In this paper the allostasis principle is applied to the oral ecosystem. The multidimensionality of the host factors contributing to allostasis in the oral cavity is illustrated with an example on changes occurring in puberty. The complex phenomenon of oral health and the processes that prevent the ecosystem from collapsing during allostatic changes in the entire body are far from being understood. As yet individual components (e.g. hard tissues, microbiome, saliva, host response) have been investigated, while only by consolidating these and assessing their multidimensional interactions should we be able to obtain a comprehensive understanding of the ecosystem, which in turn could serve to develop rational schemes to maintain health. Adapting such a 'system approach' comes with major practical challenges for the entire research field and will require vast resources and large-scale multidisciplinary collaborations.

  1. [Perspective of predictive toxicity assessment of in vivo repeated dose toxicity using structural activity relationship].

    PubMed

    Ono, Atsushi

    2010-01-01

    Tens of thousands of existing chemicals have been widely used for manufacture, agriculture, household and other purposes in worldwide. Only approximately 10% of chemicals have been assessed for human health hazard. The health hazard assessment of residual large number of chemicals for which little or no information of their toxicity is available is urgently needed for public health. However, the conduct of traditional toxicity tests which involves using animals for all of these chemicals would be economically impractical and ethically unacceptable. (Quantitative) Structure-Activity Relationships [(Q)SARs] are expected as method to have the potential to estimate hazards of chemicals from their structure, while reducing time, cost and animal testing currently needed. Therefore, our studies have been focused on evaluation of available (Q)SAR systems for estimating in vivo repeated toxicity on the liver. The results from our preliminary analysis showed the distribution for LogP of the chemicals which have potential to induce liver toxicity was bell-shape and indicating the possibility to estimate liver toxicity of chemicals from their physicochemical property. We have developed (Q)SAR models to in vivo liver toxicity using three commercially available systems (DEREK, ADMEWorks and MultiCASE) as well as combinatorial use of publically available chemoinformatic tools (CDK, MOSS and WEKA). Distinct data-sets of the 28-day repeated dose toxicity test of new and existing chemicals evaluated in Japan were used for model development and performance test. The results that concordances of commercial systems and public tools were almost same which below 70% may suggest currently attainable knowledge of in silico estimation of complex biological process, though it possible to obtain complementary and enhanced performance by combining predictions from different programs. In future, the combinatorial application of in silico and in vitro tests might provide more accurate

  2. Competition impedes the recovery of Daphnia magna from repeated insecticide pulses.

    PubMed

    Dolciotti, Ida; Foit, Kaarina; Herkelrath, Anna; Liess, Matthias

    2014-02-01

    The effects of multiple insecticide pulses on non-target organisms have rarely been investigated in combination with relevant biotic interactions, such as competition. In this study, we examined the effects of two repeated pulses of the insecticide pirimicarb (3, 10, 24 μg/L) on populations of Daphnia magna with or without competition. To investigate the influence of competition, half of the test systems were supplemented with the pirimicarb-insensitive species Culex pipiens. The pesticide pulses were followed by a recovery period of 28 days, which corresponded to approximately three generation times for D. magna. The one-species setup with the Daphnia populations and the two-species setup with both the Daphnia and Culex populations had a precontamination period of 30 days so that intra- and interspecific competitions were present prior to the insecticide pulse. Short-term effects on the survival of the Daphnia population were observed in both setups immediately after each insecticide pulse at the highest concentration level. In the one-species setup, the short-term effects on population survival were increased by intraspecific competition. However, the Daphnia populations in the one-species setup recovered and reached the control level within approximately two weeks after each insecticide pulse. In contrast, in the two-species setup at the highest concentration, we observed culmination of insecticide effects: the Daphnia populations did not recover and their abundance was below the control level until the end of the observation time. Their recovery was impeded by the presence of the competing species C. pipiens for at least four weeks. At low concentrations, no culmination of effects was observed. We conclude that repeated toxicant pulses on populations that are challenged with interspecific competition may result in a multigenerational culmination of toxicant effects.

  3. Low-dose gamma irradiation of food protein increases its allergenicity in a chronic oral challenge.

    PubMed

    Vaz, A F M; Souza, M P; Medeiros, P L; Melo, A M M A; Silva-Lucca, R A; Santana, L A; Oliva, M L V; Perez, K R; Cuccovia, I M; Correia, M T S

    2013-01-01

    Few chronic food protein models have described the relationship between allergenicity and the molecular structure of food protein after physical processing. The effect of γ-radiation on the structure of food protein was measured by fluorescence, circular dichroism and microcalorimetry. BALB/c mice were intraperitoneally sensitized and then given non-irradiated and irradiated Con-A by daily gavage for 28days. The tendency to form insoluble amorphous aggregates and partially unfolded species was observed after irradiation. The administration of non-irradiated and irradiated samples at low-dose significantly increased weight loss as well as plasma levels of eotaxin in animals repeatedly exposed to Con-A. Significant lymphocytic infiltrate filling completely the stroma of microvilli and tubular glands was observed in the small intestinal of the group given Con-A irradiated at a low dose. This phenotype was not observed in animals treated with Con-A irradiated at a high dose.

  4. TRDB—The Tandem Repeats Database

    PubMed Central

    Gelfand, Yevgeniy; Rodriguez, Alfredo; Benson, Gary

    2007-01-01

    Tandem repeats in DNA have been under intensive study for many years, first, as a consequence of their usefulness as genomic markers and DNA fingerprints and more recently as their role in human disease and regulatory processes has become apparent. The Tandem Repeats Database (TRDB) is a public repository of information on tandem repeats in genomic DNA. It contains a variety of tools for repeat analysis, including the Tandem Repeats Finder program, query and filtering capabilities, repeat clustering, polymorphism prediction, PCR primer selection, data visualization and data download in a variety of formats. In addition, TRDB serves as a centralized research workbench. It provides user storage space and permits collaborators to privately share their data and analysis. TRDB is available at . PMID:17175540

  5. Oral contraception following abortion

    PubMed Central

    Che, Yan; Liu, Xiaoting; Zhang, Bin; Cheng, Linan

    2016-01-01

    Abstract Oral contraceptives (OCs) following induced abortion offer a reliable method to avoid repeated abortion. However, limited data exist supporting the effective use of OCs postabortion. We conducted this systematic review and meta-analysis in the present study reported immediate administration of OCs or combined OCs postabortion may reduce vaginal bleeding time and amount, shorten the menstruation recovery period, increase endometrial thickness 2 to 3 weeks after abortion, and reduce the risk of complications and unintended pregnancies. A total of 8 major authorized Chinese and English databases were screened from January 1960 to November 2014. Randomized controlled trials in which patients had undergone medical or surgical abortions were included. Chinese studies that met the inclusion criteria were divided into 3 groups: administration of OC postmedical abortion (group I; n = 1712), administration of OC postsurgical abortion (group II; n = 8788), and administration of OC in combination with traditional Chinese medicine postsurgical abortion (group III; n = 19,707). In total, 119 of 6160 publications were included in this analysis. Significant difference was observed in group I for vaginal bleeding time (P = 0.0001), the amount of vaginal bleeding (P = 0.03), and menstruation recovery period (P < 0.00001) compared with the control groups. Group II demonstrated a significant difference in vaginal bleeding time (P < 0.00001), the amount of vaginal bleeding (P = 0.0002), menstruation recovery period (P < 0.00001), and endometrial thickness at 2 (P = 0.003) and 3 (P < 0.00001) weeks postabortion compared with the control group. Similarly, a significant difference was observed in group III for reducing vaginal bleeding time (P < 0.00001) and the amount of vaginal bleeding (P < 0.00001), shortening the menstruation recovery period (P < 0.00001), and increasing endometrial thickness 2 and 3 weeks after surgical abortion (P < 0

  6. Adolescents and oral contraceptives.

    PubMed

    Sanfilippo, J S

    1991-01-01

    Oral contraceptive (OC) options for adolescents are provides. Clarification for those desiring a birth control method is necessary and the benefits of decreased acne and dysmenorrhea with low dose OCs should be stressed along with the importance of compliance. A community effort is suggested to communicate the sexual and contraceptive alternatives, including abstinence and outercourse (sexual stimulation to orgasm without intercourse). Attention is given to concerns associated with teenage sexual activity, prevention of adolescent pregnancy, contraceptive options for the adolescent patient, adolescent attitudes toward birth control OCs, management of the adolescent OC user, manipulation of steroid components of OCs to respond to adolescent concerns, and other hormonal contraceptive options such as minipills or abstinence. The text is supplemented with tables: the % of US women by single years of age for 1971, 1976, 1979, and 1982; comparative pregnancy and abortion rates for the US and 5 other countries; federal cost for teen childbearing; adolescent nonhormonal contraceptive methods (advantages, disadvantages, and retail cost); checklist to identify those at risk for noncompliance with OCs; hormonal side effects of OCs; risks from OCs to adolescents; and benefits of OCs. Concern about adolescent pregnancy dates back to Aristotle. A modern profile shows girls form single-parent families are sexually active at an earlier age, adolescent mothers produce offspring who repeat the cycle, victims of sexual abuse are more likely to be sexually active, and teenagers in foster care are 4 times more likely to be sexually active and 8 times more likely to become pregnant. Prevention involves a multifaceted approach. OCs are the most appropriate contraceptive choice for adolescents. Frequency of intercourse is closely associated with OC use after approximately 15 months of unprotected sexual activity. At risk for noncompliance variables are scales of personality development

  7. Visual Scan Adaptation During Repeated Visual Search

    DTIC Science & Technology

    2010-01-01

    repeated distractor –target configurations both require environmental stability. For stable distractor – target configurations, Chun and Jiang (1998) have...demon- strated search time savings from repeating distractor –target configurations, and Song and Jiang (2005) demonstrated that as little as 25% of the...search environment (i.e., two distractor locations and the target location out of 12 total locations per trial) repeated from trial to trial resulted

  8. Short Tandem Repeat DNA Internet Database

    National Institute of Standards and Technology Data Gateway

    SRD 130 Short Tandem Repeat DNA Internet Database (Web, free access)   Short Tandem Repeat DNA Internet Database is intended to benefit research and application of short tandem repeat DNA markers for human identity testing. Facts and sequence information on each STR system, population data, commonly used multiplex STR systems, PCR primers and conditions, and a review of various technologies for analysis of STR alleles have been included.

  9. Oral administration of Enterococcus faecalis FK-23 suppresses Th17 cell development and attenuates allergic airway responses in mice.

    PubMed

    Zhang, Bei; An, Jun; Shimada, Takashi; Liu, Shuang; Maeyama, Kazutaka

    2012-08-01

    Evidence is increasing that oral administration of probiotics can attenuate asthmatic responses both in murine models and clinical trials. T-helper 17 (Th17) cells, a subset of CD4+ T cells have been implicated as having an important role in the development of several allergic disorders, but the relationship between oral administration of probiotics and Th17 development has not been well studied. BALB/c mice were given lysed Enterococcus faecalis FK-23 (LFK) orally for 28 days. After sensitization by subcutaneous injection of ovalbumin (OVA) on Days 14 and 21 and 1% OVA inhalation on Days 25, 26 and 27, they were challenged with a 5% OVA aerosol on Day 28. Twenty-four hours later, airway resistance and accumulation of inflammatory cells in bronchoalveolar lavage fluid (BALF) and lung tissues were determined. Ιnterleukin (IL)-17-expressing CD4+ lymphocytes isolated from lung, spleen and lamina propria of the intestine were detected by flow cytometry. The expression of IL-6 and TGF-β mRNA was assessed by real-time PCR. Increases in airway hyperresponsiveness, and numbers of total leukocytes and mast cells in BALF induced by OVA challenge were significantly suppressed by oral administration of LFK. The increased percentage of IL-17-expressing CD4+ cells from lung, spleen and intestine in OVA-challenged mice was reduced following LFK treatment. We conclude that the oral administration of LFK suppresses the asthmatic response and that this is associated with attenuation of Th17 cell development.

  10. Lambda Exonuclease Digestion of CGG Trinucleotide Repeats

    PubMed Central

    Conroy, R.S.; Koretsky, A.P.; Moreland, J.

    2011-01-01

    Fragile X syndrome and other triplet repeat diseases are characterized by an elongation of a repeating DNA triplet. The ensemble-averaged lambda exonuclease digestion rate of different substrates, including one with an elongated FMR1 gene containing 120 CGG repeats, was measured using absorption and fluorescence spectroscopy. Using magnetic tweezers sequence-dependent digestion rates and pausing was measured for individual lambda exonucleases. Within the triplet repeats a lower average and narrower distribution of rates and a higher frequency of pausing was observed. PMID:19562332

  11. Oral pulsatile delivery: rationale and chronopharmaceutical formulations.

    PubMed

    Maroni, Alessandra; Zema, Lucia; Del Curto, Maria Dorly; Loreti, Giulia; Gazzaniga, Andrea

    2010-10-15

    Oral pulsatile/delayed delivery systems are designed to elicit programmable lag phases preceding a prompt and quantitative, repeated or prolonged release of drugs. Accordingly, they draw increasing interest because of the inherent suitability for accomplishing chronotherapeutic goals, which have recently been highlighted in connection with a number of widespread chronic diseases with typical night or early-morning recurrence of symptoms (e.g. bronchial asthma, cardiovascular disease, rheumatoid arthritis, early-morning awakening). In addition, time-based colonic release can be attained when pulsatile delivery systems are properly adapted to overcome unpredictable gastric emptying and provide delay phases that would approximately match the small intestinal transit time. Oral pulsatile delivery is pursued by means of a variety of release platforms, namely reservoir, capsular and osmotic devices. The aim of the present review is to outline the rationale and main formulation strategies behind delayed-release dosage forms intended for the pharmacological treatment of chronopathologies.

  12. Oral contraceptives in migraine.

    PubMed

    Allais, Gianni; Gabellari, Ilaria Castagnoli; De Lorenzo, Cristina; Mana, Ornella; Benedetto, Chiara

    2009-03-01

    Combined oral contraceptives are a safe and highly effective method of birth control, but they can also raise problems of clinical tolerability and/or safety in migraine patients. It is now commonly accepted that, in migraine with aura, the use of combined oral contraceptives is always contraindicated, and that their intake must also be suspended by patients suffering from migraine without aura if aura symptoms appear. The newest combined oral contraceptive formulations are generally well tolerated in migraine without aura, and the majority of migraine without aura sufferers do not show any problems with their use; nevertheless, the last International Classification of Headache Disorders identifies at least two entities evidently related to the use of combined oral contraceptives: exogenous hormone-induced headache and estrogen-withdrawal headache. As regards the safety, even if both migraine and combined oral contraceptive intake are associated with an increased risk of ischemic stroke, migraine without aura per se is not a contraindication for combined oral contraceptive use. Other risk factors (tobacco use, hypertension, hyperlipidemia, obesity and diabetes) must be carefully considered when prescribing combined oral contraceptives in migraine without aura patients, in particular in women aged over 35 years. Furthermore, the exclusion of a hereditary thrombophilia and of alterations of coagulative parameters should precede any decision of combined oral contraceptive prescription in migraine patients.

  13. Oral surgery. Basic techniques.

    PubMed

    Ross, D L; Goldstein, G S

    1986-09-01

    Some of the clinical problems most frequently seen in veterinary dentistry and their surgical solutions are discussed. Extraction of teeth, surgical repositioning of teeth, tooth transplant, oral abscesses of tooth origin, impaction of teeth, repair of maxillary canine oronasal fistula, and simple techniques for oral wiring are among the issues considered.

  14. Oral environment and cancer.

    PubMed

    Kudo, Yasusei; Tada, Hidesuke; Fujiwara, Natsumi; Tada, Yoshiko; Tsunematsu, Takaaki; Miyake, Yoichiro; Ishimaru, Naozumi

    2016-01-01

    Cancer is now the leading cause of death in Japan. A rapid increase in cancer mortality is expected as Japan is facing a super-aged society. Many causes of cancer are known to be closely linked to life style factors, such as smoking, drinking, and diet. The oral environment is known to be involved in the pathogenesis and development of various diseases such as bronchitis, pneumonia, diabetes, heart disease, and dementia. Because the oral cavity acts as the bodily entrance for air and food, it is constantly exposed to foreign substances, including bacteria and viruses. A large number of bacteria are endemic to the oral cavity, and indigenous oral flora act to prevent the settlement of foreign bacteria. The oral environment is influenced by local factors, including dental plaque, tartar, teeth alignment, occlusion, an incompatible prosthesis, and bad lifestyle habits, and systemic factors, including smoking, consumption of alcohol, irregular lifestyle and eating habits, obesity, stress, hormones, and heredity. It has recently been revealed that the oral environment is associated with cancer. In particular, commensal bacteria in the oral cavity are involved in the development of cancer. Moreover, Candida, human papilloma virus and Epstein-Barr virus as well as commensal bacteria have been reported to be associated with the pathogenesis of cancer. In this review, we introduce recent findings of the correlation between the oral environment and cancer.

  15. ORAL AMELANOTIC MELANOMA

    PubMed Central

    Adisa, A.O.; Olawole, W.O.; Sigbeku, O.F.

    2012-01-01

    Malignant melanomas of the mucosal regions of the head and neck are extremely rare neoplasms accounting for less than 1% of all melanomas. Approximately half of all head and neck melanomas occur in the oral cavity. Less than 2% of all melanomas lack pigmentation, in the oral mucosa however, up to 75% of cases are amelanotic. No etiologic factors or risk factors have been recognized for oral melanomas. Some authors have suggested that oral habits and selfmedication may be of etiological significance. Oral melanoma is rare but it is relatively frequent in countries like Japan, Uganda, and India. It is rarely identified under the age of 20 years. In Australia where cutaneous melanomas are relatively common primary melanoma of the oral mucosa is rare. The surface architecture of oral melanomas ranges from macular to ulcerated and nodular. The lesion is said to be asymptomatic in the early stages but may become ulcerated and painful in advanced lesions. The diagnosis of amelanotic melanoma is more difficult than that of pigmented lesions. The neoplasm consists of spindle-shaped cells with many mitotic figures and no cytoplasmic melanin pigmentation. Immunohistochemistry using S-100, HMB-45, Melan-A and MART-1 will help in establishing the correct diagnosis. Radical surgery with ample margins and adjuvant chemotherapy are appropriate management protocol for malignant melanoma. Oral melanoma is associated with poor prognosis but its amelanotic variant has even worse prognosis because it exhibits a more aggressive biology and because of difficulty in diagnosis which leads to delayed treatment. PMID:25161399

  16. Epilepsy and oral care.

    PubMed

    Fiske, Janice; Boyle, Carole

    2002-05-01

    Epilepsy is a common symptom of an underlying neurological disorder. The seizures can take a variety of forms. Both the condition and its medical management can affect oral health. Prevention of oral disease and carefully planned dental treatment are essential to the well-being of people with epilepsy.

  17. Migraine and oral contraceptives.

    PubMed

    Mousa, G Y

    1982-10-01

    Migraine is a common complaint in optometric practice. Three cases of migrainous patients taking oral contraceptives are presented in this report. The role of oral contraceptives in triggering a migraine attack and possibly elevating the risk of a stroke in a patient with migraine is discussed. The counseling an optometrist can provide in such cases in discussed.

  18. The Efficacy of an Oral Elemental Diet in Patients Undergoing Hematopoietic Stem Cell Transplantation

    PubMed Central

    Morishita, Takanobu; Tsushita, Natsuko; Imai, Kanae; Sakai, Toshiyasu; Miyao, Kotaro; Sakemura, Reona; Kato, Tomonori; Niimi, Keiko; Ono, Yoshitaka; Sawa, Masashi

    2016-01-01

    Objective Conditioning regimens for hematopoietic stem cell transplantation (HSCT) are well known to cause severe gastrointestinal toxicities that often disturb the oral intake of the patients followed by poor nutrition and life-threatening infection. An oral elemental diet (ED) is an easily consumed and assimilated form of liquid nutrients mainly composed of amino acids. It alleviates the digestive loading from the intestine and is mainly used for enteral nutritional support in patients with Crohn's disease. We herein report, for the first time, the efficacy of ED for patients undergoing HSCT. Methods We evaluated the efficacy of ED in a prospective cohort study. The primary endpoint for this study was the hospitalization period. The secondary endpoint was the occurrence of oral mucositis, nausea, diarrhea and fever. Patients A total of 73 patients were consecutively enrolled between March 2011 and March 2013. Twenty-three patients underwent autologous HSCT and 50 patients underwent allogeneic HSCT. The first 21 patients did not receive ED (non-ED group; NEG) while in the successive 52 patients (ED group; EG), oral ED was started before conditioning and was continued until 28 days after transplantation. Results The patient characteristics were similar between the two groups. The mean duration of ED administration for EG was 28.7 days (range, 3-37 days), and the mean total-dose of ED administration was 1904 g (range, 240-2,960 g). The median hospitalization period was significantly shorter in EG compared to NEG, (34 days vs. 50 days; p=0.007). Grade 3-4 oral mucositis occurred less in EG than NEG (25% vs. 48%; p=0.06). Conclusion Oral ED may promote an early mucosal recovery and thereby shorten the duration of hospitalization. PMID:27980254

  19. Oral lichen planus and lichenoid mucositis.

    PubMed

    De Rossi, Scott S; Ciarrocca, Katharine

    2014-04-01

    Oral lichen planus (OLP) is commonly found in middle-aged women. Although the cause is unknown, research points to several complex immunologic events and cells that are responsible for the inflammatory destruction and chronicity of these lesions. Biopsy for histologic diagnosis is recommended. The mainstay of treatment remains topical corticosteroids; however, newer therapies such as immunomodulating agents are available for recalcitrant lesions. In cases of lichenoid mucositis or reactions, treatment should be directed at identifying and removing the presumed cause. Given the apparent risk of squamous cell carcinoma in these patients, frequent follow-up and repeat biopsy are vital.

  20. [Oral fluid bacteriocidal activity in complex diagnostics of oral disbiosis].

    PubMed

    Rabinovich, O F; Abramova, E S

    2012-01-01

    The possibility of examination of oral fluid bacteriocidal activity in complex diagnostics of oral mucosa disbiosis was evaluated. Thirty-seven patients were included in complex clinical and laboratory studies. The patients were divided in two groups: main group (30 patients exhibiting various grades of oral mucosa disbiosis) and control group (7 patients with no signs of oral disbiosis). The oral fluid bacteriocidal activity was examined by means of laser flow cytometry. Study results proved oral fluid bacteriocidal activity increase to correlate with the grade of oral mucosa disbiosis thus confirming the usefulness of the method in complex diagnostics of oral disbiosis.

  1. Oral contraceptives: current status.

    PubMed

    Burkman, R T

    2001-03-01

    During the past four decades, oral contraceptives have remained a safe and effective method of birth control. Reductions in the estrogen and progestin dosages have significantly decreased the incidence of cardiovascular complications. The association between oral contraceptives and breast cancer appears to be primarily because of detection bias or possibly a promotional effect. Despite the changes in formulation, the problems related to side effects have not been totally solved. Because compliance and successful use is strongly affected by side effects, improvement in this area is probably the biggest challenge faced by developers of oral contraceptives. It is also clear that there are a growing number of significant noncontraceptive benefits that accrue in oral contraceptive users. Unfortunately, many women do not know about these benefits. Thus, one of the issues that providers need to continue to address is how to provide better information about oral contraceptives and contraception in general to patients.

  2. Oral Contraceptive Pill and PCOS

    MedlinePlus

    ... Health Gynecology Medical Conditions Nutrition & Fitness Emotional Health PCOS: The Oral Contraceptive Pill Posted under Health Guides . ... of oral contraceptive pills for young women with PCOS? Regular and Lighter Periods: Oral contraceptive pills can ...

  3. Oral hydration during growth hormone stimulation with clonidine.

    PubMed

    May, Melissa; Rose, Susan R

    2007-10-01

    The arginine-clonidine growth hormone (GH) stimulation test causes hypotension, requiring intravenous fluids to stabilize blood pressure (BP) and delaying departure from clinic. We hypothesized that oral hydration during the stimulation test would decrease need for intravenous fluids and shorten clinic stay. Children drank a diet electrolyte drink (10 ml/kg) on arrival to the test, which was repeated after clonidine. Fifteen children (7 girls) were tested without oral hydration, and 23 (6 girls) were tested with oral hydration (age range, 2-15 years). Compared with no oral hydration, intake of >13 ml/kg rarely required intravenous fluids, improved diastolic BP, and permitted discharge at the end of the GH test, with a higher BP.

  4. Optical diagnostics in the oral cavity: an overview

    PubMed Central

    Wilder-Smith, P; Holtzman, J; Epstein, J; Le, A

    2014-01-01

    As the emphasis shifts from damage mitigation to disease prevention or reversal of early disease in the oral cavity, the need for sensitive and accurate detection and diagnostic tools become more important. Many novel and emergent optical diagnostic modalities for the oral cavity are becoming available to clinicians with a variety of desirable attributes including: (i) non-invasiveness, (ii) absence of ionizing radiation, (iii) patient-friendliness, (iv) real-time information (v) repeatability, and (vi) high-resolution surface and subsurface images. In this article, the principles behind optical diagnostic approaches, their feasibility and applicability for imaging soft and hard tissues, and their potential usefulness as a tool in the diagnosis of oral mucosal lesions, dental pathologies, and other dental applications will be reviewed. The clinical applications of light-based imaging technologies in the oral cavity and of their derivative devices will be discussed to provide the reader with a comprehensive understanding of emergent diagnostic modalities. PMID:20561224

  5. All repeats are not equal: a module-based approach to guide repeat protein design.

    PubMed

    Sawyer, Nicholas; Chen, Jieming; Regan, Lynne

    2013-05-27

    Repeat proteins composed of tandem arrays of a short structural motif often mediate protein-protein interactions. Past efforts to design repeat protein-based molecular recognition tools have focused on the creation of templates from the consensus of individual repeats, regardless of their natural context. Such an approach assumes that all repeats are essentially equivalent. In this study, we present the results of a "module-based" approach in which modules composed of tandem repeats are aligned to identify repeat-specific features. Using this approach to analyze tetratricopeptide repeat modules that contain three tandem repeats (3TPRs), we identify two classes of 3TPR modules with distinct structural signatures that are correlated with different sets of functional residues. Our analyses also reveal a high degree of correlation between positions across the entire ligand-binding surface, indicative of a coordinated, coevolving binding surface. Extension of our analyses to different repeat protein modules reveals more examples of repeat-specific features, especially in armadillo repeat modules. In summary, the module-based analyses that we present effectively capture key repeat-specific features that will be important to include in future repeat protein design templates.

  6. Literatura Oral Hispanica (Hispanic Oral Literature).

    ERIC Educational Resources Information Center

    McAlpine, Dave

    As part of a class in Hispanic Oral Literature, students collected pieces of folklore from various Hispanic residents in the region known as "Siouxland" in Iowa. Consisting of some of the folklore recorded from the residents, this paper includes 18 "cuentos y leyendas" (tales and legends), 48 "refranes" (proverbs), 17…

  7. Oral Toxicity Study and Skin Sensitization Test of a Cricket

    PubMed Central

    Ryu, Hyeon Yeol; Lee, Somin; Ahn, Kyu Sup; Kim, Hye Jin; Lee, Sang Sik; Ko, Hyuk Ju; Lee, Jin Kyu; Cho, Myung-Haing; Ahn, Mi Young; Kim, Eun Mi; Lim, Jeong Ho; Song, Kyung Seuk

    2016-01-01

    Crickets have been attracting considerable interest in the field of nutrition and toxicology due to the global exhaustion of food resulting from a growing population. The cricket is normally eaten in several countries after roasting, similar to the grasshopper; however, safety evaluation data on cricket powder is limited. Here, we performed general toxicity studies of cricket powder including a single, 2-week repeated dose range evaluation test, a 13-week repeated oral dose toxicity test in Sprague-Dawley rats, a single oral dose toxicity test in Beagle dogs, and a skin sensitization test in guinea pigs following the Organization for Economic Cooperation and Development test guidelines 406 and 408 in addition to Good Laboratory Practice. To investigate the NOAEL and target organs of cricket powder, Sprague-Dawley rats were allocated to 4 groups: vehicle control, 1,250 mg/kg, 2,500 mg/kg, 5,000 mg/kg dose test groups and cricket powder was administered over 13 weeks after single dose and dose range finding studies in rats based on the results of the single oral administration toxicity study in rats and Beagle dogs. The results of the study showed that the NOAEL of cricket powder was over 5,000 mg/kg for both sexes of rats without adverse effects in a 13-week repeated oral toxicity study and there was no skin hypersensitivity reaction. Therefore, our results reveal that crickets can be widely used as a new substitute food or nutrient resource. PMID:27123167

  8. Oral immunization of mice with live Pneumocystis murina protects against Pneumocystis pneumonia

    PubMed Central

    Samuelson, Derrick R.; de la Rua, Nicholas M.; Charles, Tysheena P.; Ruan, Sanbao; Taylor, Christopher M.; Blanchard, Eugene E.; Luo, Meng; Ramsay, Alistair J.; Shellito, Judd E.; Welsh, David A.

    2016-01-01

    Pneumocystis pneumonia is a major cause of morbidity and mortality in immunocompromised patients; particularly those infected with human immunodeficiency virus. In this study, we evaluated the potential of oral immunization with live Pneumocystis to elicit protection against respiratory infection with Pneumocystis murina. C57BL/6 mice vaccinated with live P. murina using a prime-boost vaccination strategy were protected from a subsequent lung challenge with P. murina at 2, 7, 14, and 28 days post infection even after CD4+ T cell depletion. Specifically, vaccinated immunocompetent mice had significantly faster clearance than unvaccinated immunocompetent mice and unvaccinated CD4-depleted mice remained persistently infected with P. murina. Vaccination also increased numbers of CD4+ T cells, CD8+ T cells, CD19+ B cells, and CD11b+ macrophages in the lungs following respiratory infection. In addition, levels of lung, serum, and fecal P. murina-specific IgG and IgA were increased in vaccinated animals. Further, administration of serum from vaccinated mice significantly reduced Pneumocystis lung burden in infected animals compared to control serum. We also found that the diversity of the intestinal microbial community was altered by oral immunization with P. murina. Our data demonstrate for the first time that an oral vaccination strategy prevents Pneumocystis infection. PMID:26864029

  9. Apple pectin affects the efficacy of epigallocatechin gallate on oral sucrose tolerance test in adult mice.

    PubMed

    Tamura, M; Hori, S

    2011-11-01

    Epigallocatechin gallate (EGCg), a dietary polyphenol and a major tea catechin, is a known sucrase inhibitor. Since dietary pectin is known to modulate some of the functions of the gastrointestinal tract, we investigated whether it could specifically affect the efficacy of EGCg on an oral sucrose tolerance test in mice. Male Crj:CD-1 (ICR) mice (seven weeks old) were randomly divided into two groups and fed a 5 % apple pectin (PE) or 5 % cellulose (CE) diet (control diet) for 28 days. After the experimental diet period, all mice were fasted overnight. A volume of 0.2 mL EGCg (20 mg/mL) was orally administered to all the mice by stainless steel feeding needle via injection syringe and a sucrose tolerance test was performed. The blood glucose levels were measured in blood collected from the tail vein using the OneTouch® Ultra® blood glucose monitoring system. Blood glucose levels at 30 minutes and 60 minutes after sucrose loading in the PE group were significantly higher than initial blood glucose levels. However, blood glucose levels at 30 minutes, 60 minutes, and 120 minutes after sucrose loading in the CE group were not significantly higher than initial blood glucose levels. After laparotomy, plasma lipids were also measured. Plasma triglyceride concentrations were significantly greater in the PE group than in the CE (control) group. This demonstrates that dietary pectin can affect the efficacy of EGCg on the oral sucrose tolerance test in mice.

  10. Examining the association between oral health and oral HPV infection.

    PubMed

    Bui, Thanh Cong; Markham, Christine M; Ross, Michael Wallis; Mullen, Patricia Dolan

    2013-09-01

    Oral human papillomavirus (HPV) infection is the cause of 40% to 80% of oropharyngeal cancers; yet, no published study has examined the role of oral health in oral HPV infection, either independently or in conjunction with other risk factors. This study examined the relation between oral health and oral HPV infection and the interactive effects of oral health, smoking, and oral sex on oral HPV infection. Our analyses comprised 3,439 participants ages 30 to 69 years for whom data on oral HPV and oral health were available from the nationally representative 2009-2010 National Health and Nutrition Examination Survey. Results showed that higher unadjusted prevalence of oral HPV infection was associated with four measures of oral health, including self-rated oral health as poor-to-fair [prevalence ratio (PR) = 1.56; 95% confidence interval (CI), 1.25-1.95], indicated the possibility of gum disease (PR = 1.51; 95% CI, 1.13-2.01), reported use of mouthwash to treat dental problems in the past week (PR = 1.28; 95% CI, 1.07-1.52), and higher number of teeth lost (Ptrend = 0.035). In multivariable logistic regression models, oral HPV infection had a statistically significant association with self-rated overall oral health (OR = 1.55; 95% CI, 1.15-2.09), independent of smoking and oral sex. In conclusion, poor oral health was an independent risk factor of oral HPV infection, irrespective of smoking and oral sex practices. Public health interventions may aim to promote oral hygiene and oral health as an additional measure to prevent HPV-related oral cancers.

  11. A Comparison of DWI Repeaters and Non-repeaters Who Attended a Level I Rehabilitation Program.

    ERIC Educational Resources Information Center

    Landrum, James W.; Windham, Gerald O.

    1981-01-01

    Compares behavioral and demographic characteristics of drunk drivers with repeated arrests and drivers not having repeated arrests, after attending an alcohol education program. Previous public drunkeness and previous drunk driving arrests were strong predictors of repeat arrests and were judged useful in screening offenders for rehabilitation…

  12. Repeated Testing Produces Superior Transfer of Learning Relative to Repeated Studying

    ERIC Educational Resources Information Center

    Butler, Andrew C.

    2010-01-01

    The present research investigated whether test-enhanced learning can be used to promote transfer. More specifically, 4 experiments examined how repeated testing and repeated studying affected retention and transfer of facts and concepts. Subjects studied prose passages and then either repeatedly restudied or took tests on the material. One week…

  13. Repeated dose pharmacokinetics of pancopride in human volunteers.

    PubMed

    Salva, P; Costa, J; Pérez-Campos, A; Martínez-Tobed, A

    1994-11-01

    The aim of this study was to assess the pharmacokinetic profile of pancopride after repeated oral dose administration of 20 mg pancopride in tablet form once a day for 5 d in 12 healthy male volunteers. Plasma levels were measured by HPLC using a solid phase extraction method and automated injection. The minimum quantification limit of pancopride in plasma was 2 ng mL-1. The maximum plasma concentration (mean +/- SD) after the first dose was 92.5 +/- 41.5 ng ML-1 and tmax was 1.7 +/- 0.9 h. The elimination half-life (t1/2) was 14.3 +/- 6.9 h. The area under the concentration-time curve from zero to infinity (AUC) was 997 +/- 396 ng h mL-1. The maximum plasma concentration (mean +/- SD) at steady state (day 5) was 101.8 +/- 36.9 ng mL-1 and tmax was 2.2 +/- 1.2 h. The elimination half-life (t1/2) was 16.3 +/- 2.7 h and the minimum plasma concentration (Cssmin) was 16.6 +/- 6.9 ng mL-1. The area under the concentration-time curve during the dosing interval (AUCss tau) was 995 +/- 389 ng h mL-1. The average plasma concentration at steady state (Cssav) was 43.3 +/- 16.1 ng mL-1 and the experimental accumulation ratio (RAUC) was 1.34 +/- 0.19, whereas the mean theoretical value (R) was 1.40 +/- 0.29. The results obtained showed a good correlation between the experimental plasma levels and the expected values calculated using a repeated dose two-compartment model assessed by means of the Akaike value. It is concluded that the pharmacokinetics of pancopride are not modified after repeated dose administration.(ABSTRACT TRUNCATED AT 250 WORDS)

  14. The second time around: accounting for retest effects on oral examinations.

    PubMed

    Raymond, Mark R; Luciw-Dubas, Ulana A

    2010-09-01

    Years of research with high-stakes written tests indicates that although repeat examinees typically experience score gains between their first and subsequent attempts, their pass rates remain considerably lower than pass rates for first-time examinees. This outcome is consistent with expectations. Comparable studies of the performance of repeat examinees on oral examinations are lacking. The current research evaluated pass rates for more than 50,000 examinees on written and oral exams administered by six medical specialty boards for several recent years. Pass rates for first-time examinees were similar for both written and oral exams, averaging about 84% across all boards. Pass rates for repeat examinees on written exams were expectedly lower, ranging from 22% to 51%, with an average of 36%. However, pass rates for repeat examinees on oral exams were markedly higher than for written exams, ranging from 53% to 77%, with an average of 65%. Four explanations for the elevated repeat pass rates on oral exams are proposed, including an increase in examinee proficiency, construct-irrelevant variance, measurement error (score unreliability), and memorization of test content. Simulated data are used to demonstrate that roughly one third of the score increase can be explained by measurement error alone. The authors suggest that a substantial portion of the score increase can also likely be attributed to construct-irrelevant variance. Results are discussed in terms of their implications for making pass-fail decisions when retesting is allowed. The article concludes by identifying areas for future research.

  15. [Schizophrenia and oral health].

    PubMed

    Moullan, M; Denis, F

    2017-03-24

    Mental health is an essential component of general health. Schizophrenia is a severe and chronic mental illness that affects higher brain functions. It is characterized by the presence of a mental dissociation, dampened or inappropriate affects, hallucinations and delirium. Schizophrenia has also a negative impact on oral health. As schizophrenia affects 1% of the population, every practitioner concerned with oral sphere will be confronted one day or another with a patient suffering from this disease. It is therefore important to acquire essential notions. The aim of our work was to make an update about factors that may affect oral health in patients with schizophrenia.

  16. Oral Lesions in Neonates

    PubMed Central

    Rao, Roopa S; Majumdar, Barnali; Jafer, Mohammed; Maralingannavar, Mahesh; Sukumaran, Anil

    2016-01-01

    ABSTRACT Oral lesions in neonates represent a wide range of diseases often creating apprehension and anxiety among parents. Early examination and prompt diagnosis can aid in prudent management and serve as baseline against the future course of the disease. The present review aims to enlist and describe the diagnostic features of commonly encountered oral lesions in neonates. How to cite this article: Patil S, Rao RS, Majumdar B, Jafer M, Maralingannavar M, Sukumaran A. Oral Lesions in Neonates. Int J Clin Pediatr Dent 2016;9(2):131-138. PMID:27365934

  17. Etiology of oral habits.

    PubMed

    Bayardo, R E; Mejia, J J; Orozco, S; Montoya, K

    1996-01-01

    The pedodontic admission histories of 1600 Mexican children were analyzed, to determine general epidemiologic factors or oral habits, as well as their relationship with identifiable biopsychosociologic factors. Fifty-six percent of the children gave evidence of an oral habit, with significant predisposition among female patients, single children, subjects in poor physical health (particularly from allergies), as well as children with histories of chronic health problems. Oral habits should be considered a major health hazard because of their high incidence. Successful treatment requires a multidisciplinary approach to the basic cause of the problem.

  18. Probiotics and Oral Health

    PubMed Central

    Haukioja, Anna

    2010-01-01

    The number of products containing probiotics, viable bacteria with proven health benefits, entering the market is increasing. Traditionally, probiotics have been associated with gut health, and most clinical interest has been focused on their use for prevention or treatment of gastrointestinal infections and diseases; however, during the last decade several investigators have also suggested the use of probiotics for oral health purposes. The aim of this review is to examine potential mechanisms of probiotic bacteria in the oral cavity and summarize observed effects of probiotics with respect to oral health. The review focuses on probiotic lactobacilli and bifidobacteria, genera that are most used in various probiotic products. PMID:20613927

  19. Research and Teaching: Think before (and after) You Speak: Practice and Self-Reflection Bolster Oral Communication Skills

    ERIC Educational Resources Information Center

    Sterling, Eleanor; Bravo, Adriana; Porzecanski, Ana Luz; Burks, Romi L.; Linder, Joshua; Langen, Tom; Fernandez, Denny; Ruby, Douglas; Bynum, Nora

    2016-01-01

    In this study, conservation biology faculty and practitioners from across the United States designed classroom exercises and teaching interventions intended to bolster oral communication skills. Through repeated oral presentation assignments integrated into course requirements, the authors examined individual student learning gains via…

  20. Effects of repeated anthelmintic treatment on Enterobius vermicularis infection in chimpanzees.

    PubMed

    Nakano, Tadao; Fukui, Daisuke; Ikeda, Yatsukaho; Hasegawa, Hideo

    2005-06-01

    Effects of repeated treatment with pyrantel pamoate on Enterobius vermicularis infection in chimpanzees were assessed by observing worms discharged in the feces after administration of anthelmintic treatment. Three of 9 chimpanzees reared in a zoological garden in Japan were subjected to fecal worm count and morphometric observation, and all were given oral pyrantel pamoate 6 times at 10-day intervals simultaneously. Following the first and second treatments, more than 30,000 pinworms were discharged from 1 chimpanzee. The number of discharged worms abruptly decreased after the third treatment, and only a few worms were recovered after the fifth treatment, indicating that repeated treatment at short intervals was very effective. Complete eradication was not achieved, however, presumably because of reinfection. The female proportion among discharged worms tended to increase as the treatment was repeated.

  1. Phase II study of S-1, a novel oral fluorouracil, in advanced non-small-cell lung cancer

    PubMed Central

    Kawahara, M; Furuse, K; Segawa, Y; Yoshimori, K; Matsui, K; Kudoh, S; Hasegawa, K; Niitani, H

    2001-01-01

    The purpose of this study was to evaluate the efficacy and safety of a novel oral anticancer fluoropyrimidine derivative, S-1, in patients receiving initial chemotherapy for unresectable, advanced non-small-cell lung cancer (NSCLC). Between June 1996 and July 1998, 62 patients with NSCLC who had not received previous chemotherapy for advanced disease were enrolled in this study. 59 patients (22 stage IIIB and 37 stage IV) were eligible for the evaluation of efficacy and safety. S-1 was administered orally, twice daily, after meals. 3 dosages of S-1 were prescribed according to body surface area (BSA) so that they would be approximately equivalent to 80 mg m−2day−1: BSA < 1.25 m2, 40 mg b.i.d.; BSA≥1.25 but <1.5 m2; 50 mg b.i.d., and BSA≥1.5 m2: 60 mg b.i.d. One cycle consisted of consecutive administration of S-1 for 28 days followed by a 2-week rest period, and cycles were repeated up to 4 times. The partial response (PR) rate of the eligible patients was 22.0% (13/59); (95% confidence interval: 12.3–34.7%). A PR was observed in 22.7% (5/22) of the stage IIIB patients and 21.6% (8/37) of the stage IV patients. The median response duration was 3.4 months (1.1–13.7 months or longer). Grade 4 neutropenia was observed in one of the 59 patients (1.7%). The grade 3 or 4 toxicities consisted of decreased haemoglobin level in 1.7% of patients (1/59), neutropenia in 6.8% (4/59), thrombocytopenia in 1.7% (1/59), anorexia in 10.2% (6/59), diarrhoea in 8.5% (5/59), stomatitis in 1.7% (1/59), and malaise in 6.8% (4/59), and their incidences were relatively low. There were no irreversible, severe or unexpected toxicities. The median survival time (MST) of all patients was 10.2 months (95% confidence interval: 7.7–14.5 months), and the one-year survival rate was 41.1%. The MST of the stage IIIB patients was 7.9 months, and that of the stage IV patients was 11.1 months. The one-year survival rates of the stage IIIB and IV patients were 30.7% and 47

  2. Characterization of a Mouse Model of Oral Potassium Cyanide Intoxication.

    PubMed

    Sabourin, Patrick J; Kobs, Christina L; Gibbs, Seth T; Hong, Peter; Matthews, Claire M; Patton, Kristen M; Sabourin, Carol L; Wakayama, Edgar J

    2016-09-01

    Potassium cyanide (KCN) is an inhibitor of cytochrome C oxidase causing rapid death due to hypoxia. A well-characterized model of oral KCN intoxication is needed to test new therapeutics under the Food and Drug Administration Animal Rule. Clinical signs, plasma pH and lactate concentrations, biomarkers, histopathology, and cyanide and thiocyanate toxicokinetics were used to characterize the pathology of KCN intoxication in adult and juvenile mice. The acute oral LD50s were determined to be 11.8, 11.0, 10.9, and 9.9 mg/kg in water for adult male, adult female, juvenile male, and juvenile female mice, respectively. The time to death was rapid and dose dependent; juvenile mice had a shorter mean time to death. Juvenile mice displayed a more rapid onset and higher incidence of seizures. The time to observance of respiratory signs and prostration was rapid, but mice surviving beyond 2 hours generally recovered fully within 8 hours. At doses up to the LD50, there were no gross necropsy or microscopic findings clearly attributed to administration of KCN in juvenile or adult CD-1 mice from 24 hours to 28 days post-KCN challenge. Toxicokinetic analysis indicated rapid uptake, metabolism, and clearance of plasma cyanide. Potassium cyanide caused a rapid, dose-related decrease in blood pH and increase in serum lactate concentration. An increase in fatty acid-binding protein 3 was observed at 11.5 mg/kg KCN in adult but not in juvenile mice. These studies provide a characterization of KCN intoxication in adult and juvenile mice that can be used to screen or conduct preclinical efficacy studies of potential countermeasures.

  3. Budesonide Oral Inhalation

    MedlinePlus

    Budesonide is used to prevent difficulty breathing, chest tightness, wheezing, and coughing caused by asthma. Budesonide powder for oral inhalation (Pulmicort Flexhaler) is used in adults and children 6 ...

  4. Albuterol Oral Inhalation

    MedlinePlus

    Albuterol is used to prevent and treat difficulty breathing, wheezing, shortness of breath, coughing, and chest tightness ... for oral inhalation is also used to prevent breathing difficulties during exercise. Albuterol inhalation aerosol (Proair HFA, ...

  5. Oral Cancer Screening

    MedlinePlus

    ... the thin, flat cells that line the lips, oral cavity, and oropharynx. Cancer that forms in squamous cells is called squamous cell carcinoma . See the following PDQ summaries for more information ...

  6. Ipratropium Oral Inhalation

    MedlinePlus

    Ipratropium oral inhalation is used to prevent wheezing, shortness of breath, coughing, and chest tightness in people ... damage to the air sacs in the lungs). Ipratropium is in a class of medications called bronchodilators. ...

  7. Beclomethasone Oral Inhalation

    MedlinePlus

    ... other medical conditions, such as asthma, arthritis, or eczema (a skin disease), they may worsen when your oral steroid dose is decreased. Tell your doctor if this happens or if you experience any ...

  8. Mometasone Oral Inhalation

    MedlinePlus

    ... other medical conditions, such as asthma, arthritis, or eczema (a skin disease), they may worsen when your oral steroid dose is decreased. Tell your doctor if this happens or if you experience any ...

  9. Oral compound nevus.

    PubMed

    Cardoso, Lyzete Berriel; Consalaro, Alberto; da Silva Santos, Paulo Sérgio; da Silva Sampieri, Marcelo Bonifácio; Tinoco-Araújo, José Endrigo

    2014-02-18

    The melanocytic nevus is a benign and focal proliferation of nevus cells that can be congenital or acquired. Intraoral lesions are uncommon, and the etiology and pathogenesis are poorly understood. The occurrence rate of oral compound nevus is about 5.9% to 16.5% of all oral melanocytic nevi. A 22-year-old male patient presented with a dark brown macule on the buccal mucosa of the maxilla in the region of tooth 26. The lesion was elliptical, 0.7 x 0.5 cm, well circumscribed, asymptomatic, and the evolution time was unknown. An excisional biopsy was performed and microscopic analysis revealed nests of nevus cells in the epithelium and underlying connective tissue that were compatible with melanocytic compound nevus. Owing to the clinical similarity between oral melanocytic nevus and oral melanoma, a histopathological analysis is mandatory for definitive diagnosis.

  10. Oral and esophageal disorders.

    PubMed

    Noyer, C M; Simon, D

    1997-06-01

    This article focused on the approach to oral and esophageal disorders in patients with AIDS. Most of these disorders respond to various therapeutic regimens. Some of the oral complications can be prevented with dental prophylaxis, whereas recurrent esophageal disease in some patients may require long-term suppressive therapy. As patients with AIDS live longer with lower CD4 counts, gastroenterologists need to become familiar with the approach to and management of the more common lesions of the mouth and esophagus.

  11. Oral vs. salivary diagnostics

    NASA Astrophysics Data System (ADS)

    Marques, Joana; Corby, Patricia M.; Barber, Cheryl A.; Abrams, William R.; Malamud, Daniel

    2015-05-01

    The field of "salivary diagnostics" includes studies utilizing samples obtained from a variety of sources within the oral cavity. These samples include; whole unstimulated saliva, stimulated whole saliva, duct saliva collected directly from the parotid, submandibular/sublingual glands or minor salivary glands, swabs of the buccal mucosa, tongue or tonsils, and gingival crevicular fluid. Many publications state "we collected saliva from subjects" without fully describing the process or source of the oral fluid. Factors that need to be documented in any study include the time of day of the collection, the method used to stimulate and collect the fluid, and how much fluid is being collected and for how long. The handling of the oral fluid during and post-collection is also critical and may include addition of protease or nuclease inhibitors, centrifugation, and cold or frozen storage prior to assay. In an effort to create a standard protocol for determining a biomarker's origin we carried out a pilot study collecting oral fluid from 5 different sites in the mouth and monitoring the concentrations of pro- and anti-inflammatory cytokines detected using MesoScaleDiscovery (MSD) electrochemiluminesence assays. Our data suggested that 3 of the cytokines are primarily derived from the submandibular gland, while 7 of the cytokines come from a source other than the major salivary glands such as the minor salivary glands or cells in the oral mucosae. Here we review the literature on monitoring biomarkers in oral samples and stress the need for determining the blood/saliva ratio when a quantitative determination is needed and suggest that the term oral diagnostic be used if the source of an analyte in the oral cavity is unknown.

  12. Maintaining women's oral health.

    PubMed

    McCann, A L; Bonci, L

    2001-07-01

    Women must adopt health-promoting strategies for both general health and the oral cavity, because the health of a woman's body and oral cavity are bidirectional. For general health-maintenance strategies, dental practitioners should actively advise women to minimize alcohol use, abstain from or cease smoking, stay physically active, and choose the right foods to nourish both the body and mind. For oral health-maintenance strategies, dental practitioners should advise women on how to prevent or control oral infections, particularly dental caries and periodontal diseases. Specifically, women need to know how to remove plaque from the teeth mechanically, use appropriate chemotherapeutic agents and dentifrices, use oral irrigation, and control halitosis. Dental practitioners also need to stress the importance of regular maintenance visits for disease prevention. Adolescent women are more prone to gingivitis and aphthous ulcers when they begin their menstrual cycles and need advice about cessation of tobacco use, mouth protection during athletic activities, cleaning orthodontic appliances, developing good dietary habits, and avoiding eating disorders. Women in early to middle adulthood may be pregnant or using oral contraceptives with concomitant changes in oral tissues. Dental practitioners need to advise them how to take care of the oral cavity during these changes and how to promote the health of their infants, including good nutrition. Older women experience the onset of menopause and increased vulnerability to osteoporosis. They may also experience xerostomia and burning mouth syndrome. Dental practitioners need to help women alleviate these symptoms and encourage them to continue good infection control and diet practices.

  13. Oral pigmentation: A review.

    PubMed

    Sreeja, C; Ramakrishnan, K; Vijayalakshmi, D; Devi, M; Aesha, I; Vijayabanu, B

    2015-08-01

    Pigmentations are commonly found in the mouth. They represent in various clinical patterns that can range from just physiologic changes to oral manifestations of systemic diseases and malignancies. Color changes in the oral mucosa can be attributed to the deposition of either endogenous or exogenous pigments as a result of various mucosal diseases. The various pigmentations can be in the form of blue/purple vascular lesions, brown melanotic lesions, brown heme-associated lesions, gray/black pigmentations.

  14. Oral contraception and sexuality.

    PubMed

    Dennerstein, L; Burrows, G

    1976-05-22

    A search of the literature has been carried out to determined how oral contraceptives affect sexuality in women. Some studies featured a high incidence of loss of libido. This could perhaps be attributed to preparations containing progestational compounds. However, no adequate double-blind trial has confirmed this observation. Some psychological and pharmacological aspects of contraceptions are discussed. More research is needed to ascertain why women often lose their sexual interest when taking oral contraceptives.

  15. Oral pigmentation: A review

    PubMed Central

    Sreeja, C.; Ramakrishnan, K.; Vijayalakshmi, D.; Devi, M.; Aesha, I.; Vijayabanu, B.

    2015-01-01

    Pigmentations are commonly found in the mouth. They represent in various clinical patterns that can range from just physiologic changes to oral manifestations of systemic diseases and malignancies. Color changes in the oral mucosa can be attributed to the deposition of either endogenous or exogenous pigments as a result of various mucosal diseases. The various pigmentations can be in the form of blue/purple vascular lesions, brown melanotic lesions, brown heme-associated lesions, gray/black pigmentations. PMID:26538887

  16. Oral and systemic photoprotection.

    PubMed

    Chen, Andrew C; Damian, Diona L; Halliday, Gary M

    2014-01-01

    Photoprotection can be provided not only by ultraviolet (UV) blockers but also by oral substances. Epidemiologically identified associations between foods and skin cancer and interventional experiments have discovered mechanisms of UV skin damage. These approaches have identified oral substances that are photoprotective in humans. UV inhibits adenosine triphosphate (ATP) production causing an energy crisis, which prevents optimal skin immunity and DNA repair. Enhancing ATP production with oral nicotinamide protects from UV immunosuppression, enhances DNA repair and reduces skin cancer in humans. Reactive oxygen species also contribute to photodamage. Nontoxic substances consumed in the diet, or available as oral supplements, can protect the skin by multiple potential mechanisms. These substances include polyphenols in fruit, vegetables, wine, tea and caffeine-containing foods. UV-induced prostaglandin E2 (PGE2 ) contributes to photodamage. Nonsteroidal anti-inflammatory drugs and food substances reduce production of this lipid mediator. Fish oils are photoprotective, at least partially by reducing PGE2 . Orally consumed substances, either in the diet or as supplements, can influence cutaneous responses to UV. A current research goal is to develop an oral supplement that could be used in conjunction with other sun protective strategies in order to provide improved protection from sunlight.

  17. Melatonin and Oral Cavity

    PubMed Central

    Cengiz, Murat İnanç; Cengiz, Seda; Wang, Hom-Lay

    2012-01-01

    While initially the oral cavity was considered to be mainly a source of various bacteria, their toxins and antigens, recent studies showed that it may also be a location of oxidative stress and periodontal inflammation. Accordingly, this paper focuses on the involvement of melatonin in oxidative stress diseases of oral cavity as well as on potential therapeutic implications of melatonin in dental disorders. Melatonin has immunomodulatory and antioxidant activities, stimulates the proliferation of collagen and osseous tissue, and acts as a protector against cellular degeneration associated with aging and toxin exposure. Arising out of its antioxidant actions, melatonin protects against inflammatory processes and cellular damage caused by the toxic derivates of oxygen. As a result of these actions, melatonin may be useful as a coadjuvant in the treatment of certain conditions of the oral cavity. However, the most important effect of melatonin seems to result from its potent antioxidant, immunomodulatory, protective, and anticancer properties. Thus, melatonin could be used therapeutically for instance, locally, in the oral cavity damage of mechanical, bacterial, fungal, or viral origin, in postsurgical wounds caused by tooth extractions and other oral surgeries. Additionally, it can help bone formation in various autoimmunological disorders such as Sjorgen syndrome, in periodontal diseases, in toxic effects of dental materials, in dental implants, and in oral cancers. PMID:22792106

  18. Effects of Four Weeks of β-Alanine Supplementation on Repeated Sprint Ability in Water Polo Players.

    PubMed

    Brisola, Gabriel Motta Pinheiro; Artioli, Guilherme Giannini; Papoti, Marcelo; Zagatto, Alessandro Moura

    2016-01-01

    The purpose of this study was to investigate the effect of four weeks of β-alanine supplementation on repeated sprint ability in water polo players. Twenty-two male water polo players participated in the study, divided randomly into two homogeneous groups (placebo and β-alanine groups). The study design was double-blind, parallel and placebo controlled. Before and after the supplementation period (28 days), the athletes performed two specific repeated sprint ability tests interspaced by a 30-minute swimming test. Participants received 4.8g∙day-1 of the supplement (dextrose or β-alanine) on the first 10 days and 6.4g∙day-1 on the final 18 days. There was no significant group-time interaction for any variable. The qualitative inference for substantial changes demonstrated a likely beneficial effect in the β-alanine group (β-alanine vs placebo) for mean time (6.6±0.4s vs 6.7±0.4s; 81% likely beneficial), worst time (6.9±0.5s vs 7.1±0.5s; 78% likely beneficial) and total time (39.3±2.5s vs 40.4±2.5s; 81% likely beneficial) in the first repeated sprint ability set and for worst time (7.2±0.6s vs 7.5±0.6s; 57% possible beneficial) in the second repeated sprint ability set. Further, was found substantial change for total time for both repeated sprint ability tests (80.8±5.7s vs 83.4±5.6s; 52% possible beneficial). To conclude, four weeks of β-alanine supplementation had a likely beneficial effect in the first set of repeated sprint ability tests and a possible beneficial effect for worst time in the second set performed in a specific protocol in water polo players.

  19. Effects of Four Weeks of β-Alanine Supplementation on Repeated Sprint Ability in Water Polo Players

    PubMed Central

    Brisola, Gabriel Motta Pinheiro; Artioli, Guilherme Giannini; Papoti, Marcelo; Zagatto, Alessandro Moura

    2016-01-01

    The purpose of this study was to investigate the effect of four weeks of β-alanine supplementation on repeated sprint ability in water polo players. Twenty-two male water polo players participated in the study, divided randomly into two homogeneous groups (placebo and β-alanine groups). The study design was double-blind, parallel and placebo controlled. Before and after the supplementation period (28 days), the athletes performed two specific repeated sprint ability tests interspaced by a 30-minute swimming test. Participants received 4.8g∙day-1 of the supplement (dextrose or β-alanine) on the first 10 days and 6.4g∙day-1 on the final 18 days. There was no significant group-time interaction for any variable. The qualitative inference for substantial changes demonstrated a likely beneficial effect in the β-alanine group (β-alanine vs placebo) for mean time (6.6±0.4s vs 6.7±0.4s; 81% likely beneficial), worst time (6.9±0.5s vs 7.1±0.5s; 78% likely beneficial) and total time (39.3±2.5s vs 40.4±2.5s; 81% likely beneficial) in the first repeated sprint ability set and for worst time (7.2±0.6s vs 7.5±0.6s; 57% possible beneficial) in the second repeated sprint ability set. Further, was found substantial change for total time for both repeated sprint ability tests (80.8±5.7s vs 83.4±5.6s; 52% possible beneficial). To conclude, four weeks of β-alanine supplementation had a likely beneficial effect in the first set of repeated sprint ability tests and a possible beneficial effect for worst time in the second set performed in a specific protocol in water polo players. PMID:27930743

  20. Epigenetics and Triplet-Repeat Neurological Diseases.

    PubMed

    Nageshwaran, Sathiji; Festenstein, Richard

    2015-01-01

    The term "junk DNA" has been reconsidered following the delineation of the functional significance of repetitive DNA regions. Typically associated with centromeres and telomeres, DNA repeats are found in nearly all organisms throughout their genomes. Repetitive regions are frequently heterochromatinized resulting in silencing of intrinsic and nearby genes. However, this is not a uniform rule, with several genes known to require such an environment to permit transcription. Repetitive regions frequently exist as dinucleotide, trinucleotide, and tetranucleotide repeats. The association between repetitive regions and disease was emphasized following the discovery of abnormal trinucleotide repeats underlying spinal and bulbar muscular atrophy (Kennedy's disease) and fragile X syndrome of mental retardation (FRAXA) in 1991. In this review, we provide a brief overview of epigenetic mechanisms and then focus on several diseases caused by DNA triplet-repeat expansions, which exhibit diverse epigenetic effects. It is clear that the emerging field of epigenetics is already generating novel potential therapeutic avenues for this group of largely incurable diseases.

  1. DNA Triplet Repeat Expansion and Mismatch Repair

    PubMed Central

    Iyer, Ravi R.; Pluciennik, Anna; Napierala, Marek; Wells, Robert D.

    2016-01-01

    DNA mismatch repair is a conserved antimutagenic pathway that maintains genomic stability through rectification of DNA replication errors and attenuation of chromosomal rearrangements. Paradoxically, mutagenic action of mismatch repair has been implicated as a cause of triplet repeat expansions that cause neurological diseases such as Huntington disease and myotonic dystrophy. This mutagenic process requires the mismatch recognition factor MutSβ and the MutLα (and/or possibly MutLγ) endonuclease, and is thought to be triggered by the transient formation of unusual DNA structures within the expanded triplet repeat element. This review summarizes the current knowledge of DNA mismatch repair involvement in triplet repeat expansion, which encompasses in vitro biochemical findings, cellular studies, and various in vivo transgenic animal model experiments. We present current mechanistic hypotheses regarding mismatch repair protein function in mediating triplet repeat expansions and discuss potential therapeutic approaches targeting the mismatch repair pathway. PMID:25580529

  2. HPV-associated oral warts.

    PubMed

    Feller, L; Khammissa, R A G; Wood, N H; Marnewick, J C; Meyerov, R; Lemmer, J

    2011-03-01

    Human papillomavirus (HPV) is strictly epitheliotropic, infecting stratified squamous cutaneous and mucosal epithelial cells. Oral HPV infection may be subclinical or putatively associated with benign or malignant oral neoplasms. The benign HPV-associated oral lesions, focal epithelial hyperplasia (Heck disease), oral squamous cell papilloma, oral verruca vulgaris (common wart) and oral condyloma acuminatum, are collectively referred to as oral warts. Oral warts are usually asymptomatic, may be persistent or uncommonly, may regress spontaneously. HPV-associated oral warts have a prevalence of 0.5% in the general population, occur in up to 5% of HIV-seropositive subjects, and in up to 23% of HIV-seropositive subjects on highly active antiretroviral therapy. This paper is a clinico-pathological review of HPV-associated oral warts.

  3. Cumulative Effect of Repeated Brief Cerebral Ischemia

    DTIC Science & Technology

    1993-05-31

    KL, Pohost GM and Conger KA, Correlating EEG and Lactate Kinetics During Repeated Brief Cerebral Ischemia, Proceedings of the American Heart Association 1993...Cornelating EEG and Lactate Kinetics During Repeated Brief Cerebral Ischemia, Proceedings of the American Heart Association 1993. 4) HP Hetherington...thes Bernhard Foundation. ass- 134 󈧑&.1 n5. 9# American Heart Association 026085 66th Scientific Sessions Abstract Form Medical Research Nursing

  4. Newly arisen DNA repeats in primate phylogeny.

    PubMed

    Ryan, S C; Dugaiczyk, A

    1989-12-01

    We discovered the presence of an Alu and an Xba repetitive DNA element within introns 4 and 7, respectively, of the human alpha-fetoprotein (AFP) gene; these elements are absent from the same gene in the gorilla. The Alu element is flanked by 12-base-pair direct repeats, AGGATGTTGTGG ... (Alu) ... AGGATGTTGTGG, which presumably arose by way of duplication of the intronic target site AGGATGTTGTGG at the time of the Alu insertion. In the gorilla, only a single copy of the unoccupied target site is present, which is identical to the terminal repeat flanking the human Alu element. There are two copies of an Xba repeat in the human AFP gene, apparently the only two in the genome. Xba1 and Xba2, located within introns 8 and 7, respectively, differ from each other at 3 of 303 positions. Xba1 is referred to as the old (ancestral) repeat because it lacks direct repeats. The new (derived) Xba2 is flanked by direct repeats, TTTCTTTTT ... (Xba) ... TTTCTTCTT, and is thought to have arisen as a result of transposition of Xba1. The ancestral Xba1 and a single copy of the Xba2 target site are present at orthologous positions in the gorilla, but the new Xba2 is absent. We conclude that the Alu and Xba DNA repeats emerged in the human genome at a time postdating the human-gorilla divergence and became established as genetic novelties in the human lineage. We submit that the chronology of divergence of primate lines of evolution can be correlated with the timing of insertion of new DNA repeats into the genomes of those primates.

  5. Repeat radiosurgery for cerebral arteriovenous malformations

    PubMed Central

    Stapleton, Christopher J.; Ding, Dale; Leed, Cheng-Chia; Loeffler, Jay S.

    2015-01-01

    We perform a systematic review of repeated radiosurgery for cerebral arteriovenous malformations (AVM) with an emphasis on lesion obliteration rates and complications. Radiosurgery is an accepted treatment modality for AVM located in eloquent cortex or deep brain structures. For residual or persistent lesions, repeated radiosurgery can be considered if sufficient time has passed to allow for a full appreciation of treatment effects, usually at least 3 years. A systematic review was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. References for this review were identified by searches of MEDLINE, Web of Science and Google Scholar databases. A total of 14 studies comprising 733 patients met the review criteria and were included. For series that reported target dose at both first and repeat treatments, the weighted means were 19.42 Gy and 19.06 Gy, respectively. The mean and median obliteration rate for the repeat radiosurgery treatments were 61% (95% confidence interval 51.9–71.7%) and 61.5%, respectively. The median follow up following radiosurgery ranged from 19.5 to 80 months. Time to complete obliteration after the repeat treatment ranged from 21 to 40.8 months. The most common complications of repeated radiosurgery for AVM included hemorrhage (7.6%) and radiation-induced changes (7.4%). Repeat radiosurgery can be used to treat incompletely obliterated AVM with an obliteration rate of 61%. Complications are related to treatment effect latency (hemorrhage risk) as well as radiation-induced changes. Repeat radiosurgery can be performed at three years following the initial treatment, allowing for full realization of effects from the initial treatment prior to commencing therapy. PMID:25913746

  6. Jet Fuel Kerosene is not Immunosuppressive in Mice or Rats Following Inhalation for 28 Days

    PubMed Central

    White, Kimber L.; DeLorme, Michael P.; Beatty, Patrick W.; Smith, Matthew J.; Peachee, Vanessa L.

    2013-01-01

    Previous reports indicated that inhalation of JP-8 aviation turbine fuel is immunosuppressive. However, in some of those studies, the exposure concentrations were underestimated, and percent of test article as vapor or aerosol was not determined. Furthermore, it is unknown whether the observed effects are attributable to the base hydrocarbon fuel (jet fuel kerosene) or to the various fuel additives in jet fuels. The present studies were conducted, in compliance with Good Laboratory Practice (GLP) regulations, to evaluate the effects of jet fuel kerosene on the immune system, in conjunction with an accurate, quantitative characterization of the aerosol and vapor exposure concentrations. Two female rodent species (B6C3F1 mice and Crl:CD rats) were exposed by nose-only inhalation to jet fuel kerosene at targeted concentrations of 0, 500, 1000, or 2000 mg/m3 for 6 h daily for 28 d. Humoral, cell-mediated, and innate immune functions were subsequently evaluated. No marked effects were observed in either species on body weights, spleen or thymus weights, the T-dependent antibody-forming cell response (plaque assay), or the delayed-type hypersensitivity (DTH) response. With a few exceptions, spleen cell numbers and phenotypes were also unaffected. Natural killer (NK) cell activity in mice was unaffected, while the NK assessment in rats was not usable due to an unusually low response in all groups. These studies demonstrate that inhalation of jet fuel kerosene for 28 d at levels up to 2000 mg/m3 did not adversely affect the functional immune responses of female mice and rats. PMID:24028664

  7. Tenderness of pasture versus grain fed beef aged 14 and 28 days

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Consumer interest in pasture versus grain fed beef has been on the rise in recent years. This interest could be sparked by the public’s concerns of beef management techniques and processing impacts on the nutrition and safety of their food, as well as the environmental impact of each management type...

  8. Toxicologic evaluation of tungsten: 28-day inhalation study of tungsten blue oxide in rats.

    PubMed

    Rajendran, Narayanan; Hu, Shu-Chieh; Sullivan, Dennis; Muzzio, Miguel; Detrisac, Carol J; Venezia, Carmen

    2012-12-01

    The toxicity and toxicokinetics of tungsten blue oxide (TBO) were examined. TBO is an intermediate in the production of tungsten powder, and has shown the potential to cause cellular damage in in vitro studies. However, in vivo evidence seems to indicate a lack of adverse effects. The present study was undertaken to address the dearth of longer-term inhalation toxicity studies of tungsten oxides by investigating the biological responses induced by TBO when administered via nose-only inhalation to rats at levels of 0.08, 0.325, and 0.65 mg TBO/L of air for 6 h/day for 28 consecutive days, followed by a 14-day recovery period. Inhaled TBO was absorbed systemically and blood levels of tungsten increased as inhaled concentration increased. Among the tissues analyzed for tungsten levels, lung, femur and kidney showed increased levels, with lung at least an order of magnitude greater than kidney or femur. By exposure day 14, tungsten concentration in tissues had reached steady-state. Increased lung weight was noted for both terminal and recovery animals and was attributed to deposition of TBO in the lungs, inducing a macrophage influx. Microscopic evaluation of tissues revealed a dose-related increase in alveolar pigmented macrophages, alveolar foreign material and individual alveolar foamy macrophages in lung. After a recovery period there was a slight reduction in the incidence and severity of histopathological findings. Based on the absence of other adverse effects, the increased lung weights and the microscopic findings were interpreted as nonadverse response to exposure and were not considered a specific reaction to TBO.

  9. Perfluorooctanoic acid exposure for 28 days affects glucose homeostasis and induces insulin hypersensitivity in mice

    NASA Astrophysics Data System (ADS)

    Yan, Shengmin; Zhang, Hongxia; Zheng, Fei; Sheng, Nan; Guo, Xuejiang; Dai, Jiayin

    2015-06-01

    Perfluoroalkyl acids (PFAAs) are widely used in many applications due to their unique physical and chemical characteristics. Because of the increasing prevalence of metabolic syndromes, including obesity, dyslipidemia and insulin resistance, concern has arisen about the roles of environmental pollutants in such diseases. Earlier epidemiologic studies showed a potential association between perfluorooctanoic acid (PFOA) and glucose metabolism, but how PFOA influences glucose homeostasis is still unknown. Here, we report on the modulation of the phosphatidylinositol 3-kinase-serine/threonine protein kinase (PI3K-AKT) signaling pathway in the livers of mice after 28 d of exposure to PFOA. Compared with normal mice, PFOA exposure significantly decreased the expression of the phosphatase and tensin homologue (PTEN) protein and affected the PI3K-AKT signaling pathway in the liver. Tolerance tests further indicated that PFOA exposure induced higher insulin sensitivity and glucose tolerance in mice. Biochemical analysis revealed that PFOA exposure reduced hepatic glycogen synthesis, which might be attributed to gluconeogenesis inhibition. The levels of several circulating proteins were altered after PFOA exposure, including proteins potentially related to diabetes and liver disease. Our results suggest that PFOA affected glucose metabolism and induced insulin hypersensitivity in mice.

  10. Relative toxicity of bifenthrin to Hyalella azteca in 10 day versus 28 day exposures.

    PubMed

    Anderson, Brian S; Phillips, Bryn M; Voorhees, Jennifer P; Petersen, Megan A; Jennings, Lydia L; Fojut, Tessa L; Vasquez, Martice E; Siegler, Catherine; Tjeerdema, Ronald S

    2015-04-01

    Many watersheds in the Central Valley region of California are listed as impaired due to pyrethroid-associated sediment toxicity. The Central Valley Regional Water Quality Control Board is developing numeric sediment quality criteria for pyrethroids, beginning with bifenthrin. Criteria are being developed using existing data, along with data from 10 d and 28 d toxicity tests with Hyalella azteca conducted as part of the current study. A single range-finder and 2 definitive tests were conducted for each test duration. Median lethal concentrations (LC50s), as well as LC20s and inhibition concentrations (IC20s) were calculated based on measured whole sediment bifenthrin concentrations and interstitial water concentrations. Sediment LC50s were also corrected for organic C content. Average LC50s were not significantly different in 10 d versus 28 d tests with H. azteca: 9.1 and 9.6 ng/g bifenthrin for 10 d and 28 d tests, respectively. Average LC20 values were also similar with concentrations at 7.1 and 7.0 for 10 d and 28 d tests, respectively. Bifenthrin inhibition concentrations (IC20s) based on amphipod growth were variable, particularly in the 28 d tests, where a clear dose-response relationship was observed in only 1 of the definitive experiments. Average amphipod growth IC20s were 3.9 and 9.0 ng/g for 10 d and 28 d tests, respectively. Amphipod growth calculated as biomass resulted in IC20s of 4.1 and 6.3 ng/g for the 10 d and 28 d tests, respectively. Lack of a clear growth effect in the longer term test may be related to the lack of food adjustment to account for amphipod mortality in whole sediment exposures. The average C-corrected LC50s were 1.03 and 1.09 μg/g OC for the 10 d and 28 d tests, respectively. Interstitial water LC50s were determined as the measured dissolved concentration of bifenthrin relative to interstitial water dissolved organic carbon. The average LC50s for dissolved interstitial water bifenthrin were 4.23 and 4.28 ng/L for the 10 d and 28 d tests, respectively. In addition, a set of 10 d and 28 d tests were conducted at 15 °C to assess the relative toxicity of bifenthrin at a lower temperature than the standard 23 °C test temperature. These results showed that bifenthrin was more toxic at the lower temperature, with LC50s of 5.1 and 3.4 ng/g bifenthrin in 10 d and 28 d tests, respectively. Amphipod growth at 15 °C after a 28 d exposure resulted in the lowest effect concentration of all experiments conducted (IC20 = 0.61 ng/g). This article discusses how bifenthrin dose-response data from 10 d and 28 d exposures inform development of sediment quality criteria for this pesticide for California Central Valley watersheds.

  11. Digital repeat analysis; setup and operation.

    PubMed

    Nol, J; Isouard, G; Mirecki, J

    2006-06-01

    Since the emergence of digital imaging, there have been questions about the necessity of continuing reject analysis programs in imaging departments to evaluate performance and quality. As a marketing strategy, most suppliers of digital technology focus on the supremacy of the technology and its ability to reduce the number of repeats, resulting in less radiation doses given to patients and increased productivity in the department. On the other hand, quality assurance radiographers and radiologists believe that repeats are mainly related to positioning skills, and repeat analysis is the main tool to plan training needs to up-skill radiographers. A comparative study between conventional and digital imaging was undertaken to compare outcomes and evaluate the need for reject analysis. However, digital technology still being at its early development stages, setting a credible reject analysis program became the major task of the study. It took the department, with the help of the suppliers of the computed radiography reader and the picture archiving and communication system, over 2 years of software enhancement to build a reliable digital repeat analysis system. The results were supportive of both philosophies; the number of repeats as a result of exposure factors was reduced dramatically; however, the percentage of repeats as a result of positioning skills was slightly on the increase for the simple reason that some rejects in the conventional system qualifying for both exposure and positioning errors were classified as exposure error. The ability of digitally adjusting dark or light images reclassified some of those images as positioning errors.

  12. Dynamic combinatorial libraries of artificial repeat proteins.

    PubMed

    Eisenberg, Margarita; Shumacher, Inbal; Cohen-Luria, Rivka; Ashkenasy, Gonen

    2013-06-15

    Repeat proteins are found in almost all cellular systems, where they are involved in diverse molecular recognition processes. Recent studies have suggested that de novo designed repeat proteins may serve as universal binders, and might potentially be used as practical alternative to antibodies. We describe here a novel chemical methodology for producing small libraries of repeat proteins, and screening in parallel the ligand binding of library members. The first stage of this research involved the total synthesis of a consensus-based three-repeat tetratricopeptide (TPR) protein (~14 kDa), via sequential attachment of the respective peptides. Despite the effectiveness of the synthesis and ligation steps, this method was found to be too demanding for the production of proteins containing variable number of repeats. Additionally, the analysis of binding of the individual proteins was time consuming. Therefore, we designed and prepared novel dynamic combinatorial libraries (DCLs), and show that their equilibration can facilitate the formation of TPR proteins containing up to eight repeating units. Interestingly, equilibration of the library building blocks in the presence of the biologically relevant ligands, Hsp90 and Hsp70, induced their oligomerization into forming more of the proteins with large recognition surfaces. We suggest that this work presents a novel simple and rapid tool for the simultaneous screening of protein mixtures with variable binding surfaces, and for identifying new binders for ligands of interest.

  13. Proliferating cell nuclear antigen prevents trinucleotide repeat expansions by promoting repeat deletion and hairpin removal

    PubMed Central

    Beaver, Jill M.; Lai, Yanhao; Rolle, Shantell J.; Liu, Yuan

    2017-01-01

    DNA base lesions and base excision repair (BER) within trinucleotide repeat (TNR) tracts modulate repeat instability through the coordination among the key BER enzymes DNA polymerase β, flap endonuclease 1 (FEN1) and DNA ligase I (LIG I). However, it remains unknown whether BER cofactors can also alter TNR stability. In this study, we discovered that proliferating cell nuclear antigen (PCNA), a cofactor of BER, promoted CAG repeat deletion and removal of a CAG repeat hairpin during BER in a duplex CAG repeat tract and CAG hairpin loop, respectively. We showed that PCNA stimulated LIG I activity on a nick across a small template loop during BER in a duplex (CAG)20 repeat tract promoting small repeat deletions. Surprisingly, we found that during BER in a hairpin loop, PCNA promoted reannealing of the upstream flap of a double-flap intermediate, thereby facilitating the formation of a downstream flap and stimulating FEN1 cleavage activity and hairpin removal. Our results indicate that PCNA plays a critical role in preventing CAG repeat expansions by modulating the structures of dynamic DNA via cooperation with BER enzymes. We provide the first evidence that PCNA prevents CAG repeat expansions during BER by promoting CAG repeat deletion and removal of a TNR hairpin. PMID:27793507

  14. Population Pharmacokinetic Modeling After Repeated Administrations of RBP-6000, a New, Subcutaneously Injectable, Long-Acting, Sustained-Release Formulation of Buprenorphine, for the Treatment of Opioid Use Disorder.

    PubMed

    Laffont, Celine M; Gomeni, Roberto; Heidbreder, Christian; Jones, J P; Nasser, Azmi F

    2016-07-01

    RBP-6000 is a novel sustained-release formulation of buprenorphine for the treatment of opioid use disorder, which has been designed for once-monthly (28 days) subcutaneous (SC) injections. A population pharmacokinetic (PK) model was developed to describe the time course of buprenorphine plasma concentrations after repeated SC injections of RBP-6000 at 50 mg, 100 mg, 200 mg, or 300 mg in treatment-seeking opioid-dependent subjects previously on sublingual buprenorphine (Subutex(®) ) treatment. The μ-opioid receptor occupancy was predicted using a previously developed PK/PD Emax model. The results of the population PK analysis jointly with the predicted level of μ-opioid receptor occupancy provided quantitative criteria for clinical dose selection for RBP-6000: the dose of 300 mg every 28 days seems appropriate for immediately achieving an effective exposure after the first SC injection and to maintain effective levels of exposure during chronic treatment. Furthermore, simulations conducted to evaluate the potential impact of a holiday in drug intake indicated that in the unexpected event of a 2-week holiday, levels of μ-opioid receptor occupancy remained consistently above 70% with no significant loss of drug efficacy. This analysis indicated that RBP-6000 has the potential for becoming an effective treatment for opioid-dependent subjects by addressing compliance issues associated with the current once-a-day treatments.

  15. [Twenty-eight-day repeated dose toxicity test for tetrachlorvinphos in Wistar rat].

    PubMed

    Ogawa, Y; Suzuki, S; Takada, K; Sai, K; Kamata, E; Umemura, T; Kaneko, T; Kurokawa, Y

    1990-01-01

    A 28-day oral toxicity test of tetrachlorvinphos (TCV) was conducted in male and female Slc: Wistar rats by gavage at dose levels of 0, 10, 100 or 1000 mg/kg/day. The male and female rats showed dose-related inhibition of serum cholinesterase activity and erythrocyte acetylcholinesterase activity. At a dose of 1000 mg/kg, body weight gain was decreased in males, and there were 6 deaths in females. Adrenal gland, liver, kidney and thyroid gland weights were increased. The adrenal lesions were characterized by vacuolization and swelling of the cortex cells. The hepatic lesions consisted of vacuolization and necrosis of the hepatocytes. The renal lesions consisted of regeneration and necrosis of the tubular epithelial cells. These lesions were mostly observed at a dose of 1000 mg/kg. After a 14-day recovery period in the 1000 mg/kg group, the changes of cholinesterase, total cholesterol, gamma-glutamyltransferase, alkaline phosphatase, aspartate aminotransferase and blood urea nitrogen in serum were restored or showed a tendency toward recovery. However, the lesions in the kidney and adrenal remained. More than 14 days are therefore considered to be needed for recovery. At doses of more than 10 mg/kg, significant inhibition of the serum cholinesterase activity in both sexes, erythrocyte acetylcholinesterase activity in males, and lesions of the adrenal gland in females were observed. Target organs for TCV-treated rats were the adrenal, liver and kidney. It was concluded that the NOEL under this experimental condition is less than 10 mg/kg/day.

  16. Oral triazolam pretreatment for intravenous sedation.

    PubMed Central

    Stopperich, P. S.; Moore, P. A.; Finder, R. L.; McGirl, B. E.; Weyant, R. J.

    1993-01-01

    This double-blind, controlled clinical trial assessed the anxiety relief provided by oral triazolam given before intravenous sedation. Twenty-two healthy adults undergoing third-molar surgery with intravenous sedation were enrolled in this study. Subjects were randomly assigned to receive either 0.25 mg of triazolam p.o. or an identically appearing placebo 45 to 60 min before venipuncture. Immediately before test drug administration, subjects completed the Corah Anxiety Scale, a Visual Analog Scale (VAS) assessing state anxiety, and the Interval Scale of Anxiety Response (ISAR). The VAS and ISAR were repeated immediately before venipuncture. Intravenous sedation medications consisted of fentanyl, midazolam, and methohexital. At 24 hr, assessments of the venipuncture and global experience were obtained. Results indicated that the characteristics of the triazolam and placebo patients were similar at baseline. With triazolam pretreatment, both the VAS and ISAR scores decreased significantly. Dose requirements for conscious sedation medications were decreased in the triazolam group. Patients rated the venipuncture experience significantly less unpleasant when pretreated with triazolam, and global ratings of the overall surgical experience favored triazolam. An oral-intravenous combination sedation technique using 0.25 mg of triazolam may have a significant therapeutic advantage for outpatient oral surgery. PMID:7943920

  17. An Investigation of the Influence of the Theory of Automaticity and the Impact of Repeated Reading on the Fluency and Comprehension Skills of Eighth Grade Students with and without Learning Disabilities

    ERIC Educational Resources Information Center

    Moyer, Rodney Michael

    2012-01-01

    This mixed method study examined the use of repeated reading with eighteen, eighth grade special education and regular education students. The purpose was to study use of repeated reading's structured, systematic, oral reading intervention while also seeking to further analyze LaBerge and Samuels' "Theory of Automaticity"…

  18. Efficacy of oral Bifidobacterium bifidum ATCC 29521 on microflora and antioxidant in mice.

    PubMed

    Wang, Bao-gui; Xu, Hai-bo; Xu, Feng; Zeng, Zhe-ling; Wei, Hua

    2016-03-01

    This study aimed to examine whether Bifidobacterium bifidum ATCC 29521, a species of colonic microflora in humans, is involved in the intestinal tract of mice. This study was also conducted to determine the antioxidant activity of this species by evaluating different microbial populations and reactive oxygen species isolated from feces and intestinal contents for 28 days of oral administration. Microbial diversities were assessed through bacterial culture techniques, PCR-DGGE, and real-time PCR. This study showed that the intake of B. bifidum ATCC 29521 significantly (p < 0.05) improved the ecosystem of the intestinal tract of BALB/c mice by increasing the amount of probiotics (Lactobacillus intestinalis and Lactobacillus crispatus) and by reducing unwanted bacterial populations (Enterobacter, Escherichia coli). Antioxidative activities of incubated cell-free extracts were evaluated through various assays, including the scavenging ability of DPPH radical (64.5% and 67.54% (p < 0.05), respectively, at 21 days in nutrients and 28 days in MRS broth), superoxide anion, and hydroxyl radical (85% and 61.5% (p < 0.05), respectively, at intestinal contents in nutrients and 21 days in MRS broth). Total reducing power (231.5 μmol/L (p < 0.05), 14 days in MRS broth) and mRNA level of genes related to oxidative stress were also determined. Results indicated that B. bifidum ATCC 29521 elicits a beneficial effect on murine gut microbiota and antioxidant activities compared with the control samples. This species can be considered as a potential bioresource antioxidant to promote health. Bifidobacterium bifidum ATCC 29521 may also be used as a promising material in microbiological and food applications.

  19. Automated genotyping of dinucleotide repeat markers

    SciTech Connect

    Perlin, M.W.; Hoffman, E.P. |

    1994-09-01

    The dinucleotide repeats (i.e., microsatellites) such as CA-repeats are a highly polymorphic, highly abundant class of PCR-amplifiable markers that have greatly streamlined genetic mapping experimentation. It is expected that over 30,000 such markers (including tri- and tetranucleotide repeats) will be characterized for routine use in the next few years. Since only size determination, and not sequencing, is required to determine alleles, in principle, dinucleotide repeat genotyping is easily performed on electrophoretic gels, and can be automated using DNA sequencers. Unfortunately, PCR stuttering with these markers generates not one band for each allele, but a pattern of bands. Since closely spaced alleles must be disambiguated by human scoring, this poses a key obstacle to full automation. We have developed methods that overcome this obstacle. Our model is that the observed data is generated by arithmetic superposition (i.e., convolution) of multiple allele patterns. By quantitatively measuring the size of each component band, and exploiting the unique stutter pattern associated with each marker, closely spaced alleles can be deconvolved; this unambiguously reconstructs the {open_quotes}true{close_quotes} allele bands, with stutter artifact removed. We used this approach in a system for automated diagnosis of (X-linked) Duchenne muscular dystrophy; four multiplexed CA-repeats within the dystrophin gene were assayed on a DNA sequencer. Our method accurately detected small variations in gel migration that shifted the allele size estimate. In 167 nonmutated alleles, 89% (149/167) showed no size variation, 9% (15/167) showed 1 bp variation, and 2% (3/167) showed 2 bp variation. We are currently developing a library of dinucleotide repeat patterns; together with our deconvolution methods, this library will enable fully automated genotyping of dinucleotide repeats from sizing data.

  20. Oral Insulin Reloaded

    PubMed Central

    Heinemann, Lutz; Plum-Mörschel, Leona

    2014-01-01

    Optimal coverage of insulin needs is the paramount aim of insulin replacement therapy in patients with diabetes mellitus. To apply insulin without breaking the skin barrier by a needle and/or to allow a more physiological provision of insulin are the main reasons triggering the continuous search for alternative routes of insulin administration. Despite numerous attempts over the past 9 decades to develop an insulin pill, no insulin for oral dosing is commercially available. By way of a structured approach, we aim to provide a systematic update on the most recent developments toward an orally available insulin formulation with a clear focus on data from clinical-experimental and clinical studies. Thirteen companies that claim to be working on oral insulin formulations were identified. However, only 6 of these companies published new clinical trial results within the past 5 years. Interestingly, these clinical data reports make up a mere 4% of the considerably high total number of publications on the development of oral insulin formulations within this time period. While this picture clearly reflects the rising research interest in orally bioavailable insulin formulations, it also highlights the fact that the lion’s share of research efforts is still allocated to the preclinical stages. PMID:24876606

  1. Salivary markers of oxidative stress in oral diseases

    PubMed Central

    Tóthová, L'ubomíra; Kamodyová, Natália; Červenka, Tomáš; Celec, Peter

    2015-01-01

    Saliva is an interesting alternative diagnostic body fluid with several specific advantages over blood. These include non-invasive and easy collection and related possibility to do repeated sampling. One of the obstacles that hinders the wider use of saliva for diagnosis and monitoring of systemic diseases is its composition, which is affected by local oral status. However, this issue makes saliva very interesting for clinical biochemistry of oral diseases. Periodontitis, caries, oral precancerosis, and other local oral pathologies are associated with oxidative stress. Several markers of lipid peroxidation, protein oxidation and DNA damage induced by reactive oxygen species can be measured in saliva. Clinical studies have shown an association with oral pathologies at least for some of the established salivary markers of oxidative stress. This association is currently limited to the population level and none of the widely used markers can be applied for individual diagnostics. Oxidative stress seems to be of local oral origin, but it is currently unclear whether it is caused by an overproduction of reactive oxygen species due to inflammation or by the lack of antioxidants. Interventional studies, both, in experimental animals as well as humans indicate that antioxidant treatment could prevent or slow-down the progress of periodontitis. This makes the potential clinical use of salivary markers of oxidative stress even more attractive. This review summarizes basic information on the most commonly used salivary markers of oxidative damage, antioxidant status, and carbonyl stress and the studies analyzing these markers in patients with caries or periodontitis. PMID:26539412

  2. A review of biodegradable polymeric systems for oral insulin delivery.

    PubMed

    Luo, Yue Yuan; Xiong, Xiang Yuan; Tian, Yuan; Li, Zi Ling; Gong, Yan Chun; Li, Yu Ping

    2016-07-01

    Currently, repeated routine subcutaneous injections of insulin are the standard treatment for insulin-dependent diabetic patients. However, patients' poor compliance for injections often fails to achieve the stable concentration of blood glucose. As a protein drug, the oral bioavailability of insulin is low due to many physiological reasons. Several carriers, such as macromolecules and liposomes have been used to deliver drugs in vivo. In this review article, the gastrointestinal barriers of oral insulin administration are described. Strategies for increasing the bioavailability of oral insulin, such absorption enhancers, enzyme inhibitors, enteric coatings are also introduced. The potential absorption mechanisms of insulin-loaded nanoparticles across the intestinal epithelium, including intestinal lymphatic route, transcellular route and paracellular route are discussed in this review. Natural polymers, such as chitosan and its derivates, alginate derivatives, γ-PGA-based materials and starch-based nanoparticles have been exploited for oral insulin delivery; synthetic polymers, such as PLGA, PLA, PCL and PEA have also been developed for oral administration of insulin. This review focuses on recent advances in using biodegradable natural and synthetic polymers for oral insulin delivery along with their future prospects.

  3. Preferential induction of the AhR gene battery in HepaRG cells after a single or repeated exposure to heterocyclic aromatic amines

    SciTech Connect

    Dumont, Julie Josse, Rozenn Lambert, Carine Antherieu, Sebastien Laurent, Veronique Loyer, Pascal Robin, Marie-Anne Guillouzo, Andre

    2010-11-15

    2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) are two of the most common heterocyclic aromatic amines (HAA) produced during cooking of meat, fish and poultry. Both HAA produce different tumor profiles in rodents and are suspected to be carcinogenic in humans. In order to better understand the molecular basis of HAA toxicity, we have analyzed gene expression profiles in the metabolically competent human HepaRG cells using pangenomic oligonucleotide microarrays, after either a single (24-h) or a repeated (28-day) exposure to 10 {mu}M PhIP or MeIQx. The most responsive genes to both HAA were downstream targets of the arylhydrocarbon receptor (AhR): CYP1A1 and CYP1A2 after both time points and CYP1B1 and ALDH3A1 after 28 days. Accordingly, CYP1A1/1A2 induction in HAA-treated HepaRG cells was prevented by chemical inhibition or small interference RNA-mediated down-regulation of the AhR. Consistently, HAA induced activity of the CYP1A1 promoter, which contains a consensus AhR-related xenobiotic-responsive element (XRE). In addition, several other genes exhibited both time-dependent and compound-specific expression changes with, however, a smaller magnitude than previously reported for the prototypical AhR target genes. These changes concerned genes mainly related to cell growth and proliferation, apoptosis, and cancer. In conclusion, these results identify the AhR gene battery as the preferential target of PhIP and MeIQx in HepaRG cells and further support the hypothesis that intake of HAA in diet might increase human cancer risk.

  4. [MICROFLORA AND ORAL DISEASE].

    PubMed

    Khavkin, A I; Ippolitov, Y A; Aleshina, E O; Komarova O N

    2015-01-01

    Acid-producing microorganisms are base etiological agents of lesions of tooth enamel and destruction of dentin. The process start by specific microflora of tooth deposit--Streptococcus mutans, Lactobacteria and Actinomycetis viscosus which ferment food carbogydrate to form acids. High titre of them in oral cavity may be considered like a marker of carbohydrate food. But the pathogenic bacteria don't have aggression to host organism until they will have virulent factors which help to get over protection of host organism. At the same time, microflora of oral cavity is involved to form pellicula. Pellicula is a biofilm which to protect tooth enamel and dentin. Understanding relationships between safety factors of host and pathogenic microflora of oral cavity will give to create effective methods of prevention and treatment.

  5. Role of memory errors in quantum repeaters

    NASA Astrophysics Data System (ADS)

    Hartmann, L.; Kraus, B.; Briegel, H.-J.; Dür, W.

    2007-03-01

    We investigate the influence of memory errors in the quantum repeater scheme for long-range quantum communication. We show that the communication distance is limited in standard operation mode due to memory errors resulting from unavoidable waiting times for classical signals. We show how to overcome these limitations by (i) improving local memory and (ii) introducing two operational modes of the quantum repeater. In both operational modes, the repeater is run blindly, i.e., without waiting for classical signals to arrive. In the first scheme, entanglement purification protocols based on one-way classical communication are used allowing to communicate over arbitrary distances. However, the error thresholds for noise in local control operations are very stringent. The second scheme makes use of entanglement purification protocols with two-way classical communication and inherits the favorable error thresholds of the repeater run in standard mode. One can increase the possible communication distance by an order of magnitude with reasonable overhead in physical resources. We outline the architecture of a quantum repeater that can possibly ensure intercontinental quantum communication.

  6. Spectrin repeat proteins in the nucleus.

    PubMed

    Young, Kevin G; Kothary, Rashmi

    2005-02-01

    Spectrin repeat sequences are among the more common repeat elements identified in proteins, typically occurring in large structural proteins. Examples of spectrin repeat-containing proteins include dystrophin, alpha-actinin and spectrin itself--all proteins with well-demonstrated roles of establishing and maintaining cell structure. Over the past decade, it has become clear that, although these proteins display a cytoplasmic and plasma membrane distribution, several are also found both at the nuclear envelope, and within the intranuclear space. In this review, we provide an overview of recent work regarding various spectrin repeat-containing structural proteins in the nucleus. As well, we hypothesize about the regulation of their nuclear localization and possible nuclear functions based on domain architecture, known interacting proteins and evolutionary relationships. Given their large size, and their potential for interacting with multiple proteins and with chromatin, spectrin repeat-containing proteins represent strong candidates for important organizational proteins within the nucleus. Supplementary material for this article can be found on the BioEssays website (http://www.interscience.wiley.com/jpages/0265-9247/suppmat/index.html).

  7. Clinical efficacy and safety of chelation treatment with typical penicillamine in cross combination with DMPS repeatedly for Wilson's disease.

    PubMed

    Xu, San-qing; Li, Xu-fang; Zhu, Hui-yun; Liu, Yan; Fang, Feng; Chen, Ling

    2013-10-01

    The aim of this study was to assess the clinical efficacy and safety of chelation treatment with penicillamine (PCA) in cross combination with sodium 2, 3-dimercapto-1-propane sulfonate (DMPS) repeatedly in patients with Wilson's disease (WD). Thirty-five patients with WD were enrolled. They were administrated intravenous DMPS in cross combination with oral PCA alternately which was practiced repeatedly, all with Zinc in the meantime. During the treatment, clinical observations and 24-h urine copper excretion as well as adverse effects of medicines were recorded and analyzed. Although the incidence of adverse effects was not significantly different after either intravenous DMPS or oral PCA treatment, levels of 24-h urine copper tended to be higher after short-term intravenous DMPS than that of oral PCA. Adverse effects in the course of intravenous DMPS were mainly neutropenia, thrombocytopenia, allergic reaction and bleeding tendency. As compared with oral PCA alone or intravenous DMPS alone, such repeated cross combination treatment could as much as possible avoid continued drug adverse effects or poor curative effect and had less chance to stop treatment in WD patients. Improved or recovered liver function in 71% of the patients, alleviated neurologic symptoms in 50% of the patients, and disappeared hematuria in 70% of the patients could be observed during the follow-up period of 6 months to 5 years after such combined chelation regimen. Chelation treatment repeatedly with oral penicillamine in cross combination with intravenous DMPS alternately could be more beneficial for WD patients to relieve symptoms, avoid continued drug adverse effects and maintain lifelong therapy.

  8. Oral contraceptives: a reassessment.

    PubMed

    Derman, R

    1989-09-01

    Cardiovascular risks attributable to oral contraceptive use may now be subdivided into those that appear to be secondary to the estrogen component, i.e., venous thrombosis, pulmonary embolism, and those linked to the progestin component, i.e., small vessel disease including myocardial infarction and cerebrovascular accident. It appears that venous risk is attributable to subtle changes in clotting factors, while arterial risk may be secondary to changes in glucose and lipid metabolism. In order to determine which women are at greatest risk from oral contraceptive use, Spellacy et al. has developed a risk scoring form that aids in the screening process. After excluding women with an absolute contraindication to pill use, women at greatest risk for cardiovascular disease related to oral contraceptive use are those with a family history of hyperlipidemia, gestational or overt diabetics, hypertensives, and smokers over the age of 35. The gradual reduction by manufacturers of the steroid content of oral contraceptives appears to have lessened the incidence of adverse effects. Our current knowledge of risk factors permits the clinician to reduce exposure to oral contraceptive-related mortality by as much as 86 per cent. As we continue to search for ways to reduce risk among oral contraceptive users, it is important to note that more than 25 per cent of women are still taking formulations containing 50 micrograms of estrogen. It becomes the responsibility of the practicing physician to "step-down" these patients to lower-dose preparations such as the multiphasics. Such preparations also represent optimal therapy for first-time pill users.

  9. Maintaining oral health after stroke.

    PubMed

    Dickinson, Hazel

    Oral care is essential to maintain oral health and prevent complications such as tooth loss, gingivitis and periodontitis. Poor oral hygiene in dependent, hospitalised patients could lead to serious complications such as chest infection, pneumonia, poor nutritional intake and increased length of hospital stay. Patients who have had a stroke may have physical and cognitive problems that make them dependent on others for their personal care, including oral care. It is essential that nurses and carers understand why maintaining oral hygiene is important following stroke and the consequences of poor oral care.

  10. Oral inflammation in small animals.

    PubMed

    Lommer, Milinda J

    2013-05-01

    The oral cavity can be affected by a wide variety of disorders characterized by inflammation of the gingiva and/or oral mucosa. In dogs and cats, differential diagnoses for generalized oral inflammatory disorders include plaque-reactive mucositis, chronic gingivostomatitis, eosinophilic granuloma complex, pemphigus and pemphigoid disorders, erythema multiforme, and systemic lupus erythematosus. In addition, endodontic or periodontal abscesses, infectious conditions, reactive lesions, and neoplastic conditions may initially present with localized or generalized inflammation of the oral mucosa. Determination of the underlying cause of an oral inflammatory condition relies on a thorough history, complete physical and oral examination, and incisional biopsy and histopathologic examination of lesions.

  11. Per-oral cholangioscopy

    PubMed Central

    Monga, Amitabh; Ramchandani, Mohan

    2011-01-01

    Direct endoscopic views of bile duct have been described in literature since the 1970s. Since then rapid strides have been made with the advent of technologically advanced systems with better image quality and maneuverability. The single operator semi-disposable per-oral cholangioscope and other novel methods such as the cholangioscopy access balloon are likely to revolutionize this field. Even though cholangioscopy is currently used primarily for characterization of indeterminate strictures and management of large bile duct stones, the diagnostic and therapeutic indications are likely to expand in future. The following is an overview of the currently available per-oral cholangioscopy equipments, indications for use and future directions. PMID:21776429

  12. Oral myiasis in children.

    PubMed

    Reddy, M H Raghunath; Das, Nagarajappa; Vivekananda, M R

    2012-04-01

    Oral myiasis is a rare condition in humans and is associated with poor oral hygiene, severe halitosis, mouth breathing during sleep, mental handicap, cerebral palsy, epilepsy, anterior open bite, incompetent lips, and other conditions. In this report, a 14 year-old boy who had an orofacial trauma in the maxillary dentoalveolar region,which was neglected, has been described. There was a deep lacerated wound on the upper vestibule which was infected and maggots were found on the same wound. The clinical features, management, treatment are discussed and relevant literature is reviewed.

  13. Trial of Repeated Analgesia with Kangaroo Mother Care (TRAKC Trial)

    PubMed Central

    2013-01-01

    Background Skin-to-skin contact (SSC) between mother and infant, commonly referred to as Kangaroo Mother Care (KMC), is recommended as an intervention for procedural pain. Evidence demonstrates its consistent efficacy in reducing pain for a single painful procedure. The purpose of this study is to examine the sustained efficacy of KMC, provided during all routine painful procedures for the duration of Neonatal Intensive Care Unit (NICU) hospitalization, in diminishing behavioral pain response in preterm neonates. The efficacy of KMC alone will be compared to standard care of 24% oral sucrose, as well as the combination of KMC and 24% oral sucrose. Methods/design Infants admitted to the NICU who are less than 36 6/7 weeks gestational age (according to early ultrasound), that are stable enough to be held in KMC, will be considered eligible (N = 258). Using a single-blinded randomized parallel group design, participants will be assigned to one of three possible interventions: 1) KMC, 2) combined KMC and sucrose, and 3) sucrose alone, when they undergo any routine painful procedure (heel lance, venipuncture, intravenous, oro/nasogastric insertion). The primary outcome is infant’s pain intensity, which will be assessed using the Premature Infant Pain Profile (PIPP). The secondary outcome will be maturity of neurobehavioral functioning, as measured by the Neurobehavioral Assessment of the Preterm Infant (NAPI). Gestational age, cumulative exposure to KMC provided during non-pain contexts, and maternal cortisol levels will be considered in the analysis. Clinical feasibility will be accounted for from nurse and maternal questionnaires. Discussion This will be the first study to examine the repeated use of KMC for managing procedural pain in preterm neonates. It is also the first to compare KMC to sucrose, or the interventions in combination, across time. Based on the theoretical framework of the brain opioid theory of attachment, it is expected that KMC will be a

  14. Oral microbiome and oral and gastrointestinal cancer risk.

    PubMed

    Ahn, Jiyoung; Chen, Calvin Y; Hayes, Richard B

    2012-03-01

    A growing body of evidence implicates human oral bacteria in the etiology of oral and gastrointestinal cancers. Epidemiological studies consistently report increased risks of these cancers in men and women with periodontal disease or tooth loss, conditions caused by oral bacteria. More than 700 bacterial species inhabit the oral cavity, including at least 11 bacterial phyla and 70 genera. Oral bacteria may activate alcohol and smoking-related carcinogens locally or act systemically, through chronic inflammation. High-throughput genetic-based assays now make it possible to comprehensively survey the human oral microbiome, the totality of bacteria in the oral cavity. Establishing the association of the oral microbiome with cancer risk may lead to significant advances in understanding of cancer etiology, potentially opening a new research paradigm for cancer prevention.

  15. Rate analysis for a hybrid quantum repeater

    SciTech Connect

    Bernardes, Nadja K.; Loock, Peter van

    2011-01-15

    We present a detailed rate analysis for a hybrid quantum repeater assuming perfect memories and using optimal probabilistic entanglement generation and deterministic swapping routines. The hybrid quantum repeater protocol is based on atomic qubit-entanglement distribution through optical coherent-state communication. An exact, analytical formula for the rates of entanglement generation in quantum repeaters is derived, including a study on the impacts of entanglement purification and multiplexing strategies. More specifically, we consider scenarios with as little purification as possible and we show that for sufficiently low local losses, such purifications are still more powerful than multiplexing. In a possible experimental scenario, our hybrid system can create near-maximally entangled (F=0.98) pairs over a distance of 1280 km at rates of the order of 100 Hz.

  16. Hematuria home screening: repeat testing results.

    PubMed

    Messing, E M; Young, T B; Hunt, V B; Newton, M A; Bram, L L; Vaillancourt, A; Hisgen, W J; Greenberg, E B; Kuglitsch, M E; Wegenke, J D

    1995-07-01

    To determine at what interval screening should be repeated to detect bladder cancer before it becomes muscle invasive 856 men who had 14 negative daily home tests for hematuria with a chemical reagent strip 9 months previously performed repeat tests. Of these men 50 (5.8%) had at least 1 positive test during the second 14-day screening period and 38 were evaluated, 15 of whom (39.5%) had significant urological pathological conditions, including 8 with malignancies. Bladder cancer was noted in 7 men, with no tumor invading the muscularis propria. The finding of 7 bladder cancers in 856 men (0.82%) who had a negative test 9 months previously indicates that bladder cancer has a brief preclinical duration and that testing must be repeated at least annually for screening to detect bladder cancer consistently before invasion occurs.

  17. Some characteristics of repeated sickness absence

    PubMed Central

    Ferguson, David

    1972-01-01

    Ferguson, D. (1972).Brit. J. industr. Med.,29, 420-431. Some characteristics of repeated sickness absence. Several studies have shown that frequency of absence attributed to sickness is not distributed randomly but tends to follow the negative binomial distribution, and this has been taken to support the concept of `proneness' to such absence. Thus, the distribution of sickness absence resembles that of minor injury at work demonstrated over 50 years ago. Because the investigation of proneness to absence does not appear to have been reported by others in Australia, the opportunity was taken, during a wider study of health among telegraphists in a large communications undertaking, to analyse some characteristics of repeated sickness absence. The records of medically certified and uncertified sickness absence of all 769 telegraphists continuously employed in all State capitals over a two-and-a-half-year period were compared with those of 411 clerks and 415 mechanics and, in Sydney, 380 mail sorters and 80 of their supervisors. All telegraphists in Sydney, Melbourne, and Brisbane, and all mail sorters in Sydney, who were available and willing were later medically examined. From their absence pattern repeaters (employees who had had eight or more certified absences in two and a half years) were separated into three types based on a presumptive origin in chance, recurrent disease and symptomatic non-specific disorder. The observed distribution of individual frequency of certified absence over the full two-and-a-half-year period of study followed that expected from the univariate negative binomial, using maximum likelihood estimators, rather than the poisson distribution, in three of the four occupational groups in Sydney. Limited correlational and bivariate analysis supported the interpretation of proneness ascribed to the univariate fit. In the two groups studied, frequency of uncertified absence could not be fitted by the negative binomial, although the numbers of

  18. Do gamma-ray burst sources repeat?

    NASA Technical Reports Server (NTRS)

    Meegan, Charles A.; Hartmann, Dieter H.; Brainerd, J. J.; Briggs, Michael S.; Paciesas, William S.; Pendleton, Geoffrey; Kouveliotou, Chryssa; Fishman, Gerald; Blumenthal, George; Brock, Martin

    1995-01-01

    The demonstration of repeated gamma-ray bursts from an individual source would severely constrain burst source models. Recent reports (Quashnock and Lamb, 1993; Wang and Lingenfelter, 1993) of evidence for repetition in the first BATSE burst catalog have generated renewed interest in this issue. Here, we analyze the angular distribution of 585 bursts of the second BATSE catalog (Meegan et al., 1994). We search for evidence of burst recurrence using the nearest and farthest neighbor statistic and the two-point angular correlation function. We find the data to be consistent with the hypothesis that burst sources do not repeat; however, a repeater fraction of up to about 20% of the observed bursts cannot be excluded.

  19. Formation of the Arabidopsis pentatricopeptide repeat family.

    PubMed

    Rivals, Eric; Bruyère, Clémence; Toffano-Nioche, Claire; Lecharny, Alain

    2006-07-01

    In Arabidopsis (Arabidopsis thaliana) the 466 pentatricopeptide repeat (PPR) proteins are putative RNA-binding proteins with essential roles in organelles. Roughly half of the PPR proteins form the plant combinatorial and modular protein (PCMP) subfamily, which is land-plant specific. PCMPs exhibit a large and variable tandem repeat of a standard pattern of three PPR variant motifs. The association or not of this repeat with three non-PPR motifs at their C terminus defines four distinct classes of PCMPs. The highly structured arrangement of these motifs and the similar repartition of these arrangements in the four classes suggest precise relationships between motif organization and substrate specificity. This study is an attempt to reconstruct an evolutionary scenario of the PCMP family. We developed an innovative approach based on comparisons of the proteins at two levels: namely the succession of motifs along the protein and the amino acid sequence of the motifs. It enabled us to infer evolutionary relationships between proteins as well as between the inter- and intraprotein repeats. First, we observed a polarized elongation of the repeat from the C terminus toward the N-terminal region, suggesting local recombinations of motifs. Second, the most N-terminal PPR triple motif proved to evolve under different constraints than the remaining repeat. Altogether, the evidence indicates different evolution for the PPR region and the C-terminal one in PCMPs, which points to distinct functions for these regions. Moreover, local sequence homogeneity observed across PCMP classes may be due to interclass shuffling of motifs, or to deletions/insertions of non-PPR motifs at the C terminus.

  20. Repeat Gamma Knife Radiosurgery for Trigeminal Neuralgia

    SciTech Connect

    Aubuchon, Adam C.; Chan, Michael D.; Lovato, James F.; Balamucki, Christopher J.; Ellis, Thomas L.; Tatter, Stephen B.; McMullen, Kevin P.; Munley, Michael T.; Deguzman, Allan F.; Ekstrand, Kenneth E.; Bourland, J. Daniel; Shaw, Edward G.

    2011-11-15

    Purpose: Repeat gamma knife stereotactic radiosurgery (GKRS) for recurrent or persistent trigeminal neuralgia induces an additional response but at the expense of an increased incidence of facial numbness. The present series summarized the results of a repeat treatment series at Wake Forest University Baptist Medical Center, including a multivariate analysis of the data to identify the prognostic factors for treatment success and toxicity. Methods and Materials: Between January 1999 and December 2007, 37 patients underwent a second GKRS application because of treatment failure after a first GKRS treatment. The mean initial dose in the series was 87.3 Gy (range, 80-90). The mean retreatment dose was 84.4 Gy (range, 60-90). The dosimetric variables recorded included the dorsal root entry zone dose, pons surface dose, and dose to the distal nerve. Results: Of the 37 patients, 81% achieved a >50% pain relief response to repeat GKRS, and 57% experienced some form of trigeminal dysfunction after repeat GKRS. Two patients (5%) experienced clinically significant toxicity: one with bothersome numbness and one with corneal dryness requiring tarsorraphy. A dorsal root entry zone dose at repeat treatment of >26.6 Gy predicted for treatment success (61% vs. 32%, p = .0716). A cumulative dorsal root entry zone dose of >84.3 Gy (72% vs. 44%, p = .091) and a cumulative pons surface dose of >108.5 Gy (78% vs. 44%, p = .018) predicted for post-GKRS numbness. The presence of any post-GKRS numbness predicted for a >50% decrease in pain intensity (100% vs. 60%, p = .0015). Conclusion: Repeat GKRS is a viable treatment option for recurrent trigeminal neuralgia, although the patient assumes a greater risk of nerve dysfunction to achieve maximal pain relief.

  1. The puzzle of the triple repeats

    SciTech Connect

    Morell, V.

    1993-06-04

    Two years ago, when researchers discovered the gene that causes a hereditary form of mental retardation known as fragile-X syndrome, they also turned up a mutation so unexpected geneticists are still scratching their heads over it. The defect, which makes genes balloon in size by adding extra copies of a three base-pair repeated sequence of DNA, was the first of its kind. Despite decades of study, nothing like it had ever been seen in any of the species that laid the foundations for modern genetics: bacteria, the fruit fly Drosophila melanogaster, and the mouse. The mutations caused by these expanding trinucleotide repeats turned out be common causes of human disease. In the past 2 years, they have been fingered as the culprits in three hereditary disorders besides fragile-X syndrome: myotronic dystrophy, spinobullar muscular atrophy (also known as Kennedy's disease), and just this March-Huntington's disease. The FMR-1 gene, which is the one at fault in fragile-X syndrome, shows just how much the trinucleotide repeats can expand. The normal gene carries at most 50 copies of the CGG trinucleotide. But in children who inherit the gene from these carriers and actually develop mental retardation and the other fragile-X symptoms, the FMR-1 gene may have hundreds to thousands of CGG repeats. Huge expansions of another trinucleotide repeat (CTG) can also occur from one generation to the next in the gene that causes myotonic dystrophy (DM), while smaller, although no less devastating, expansions in the CAG trinucleotide repeat lead to Huntington's and Kennedy's diseases.

  2. Safety of Repeated Yttrium-90 Radioembolization

    SciTech Connect

    Lam, Marnix G. E. H.; Louie, John D.; Iagaru, Andrei H.; Goris, Michael L.; Sze, Daniel Y.

    2013-10-15

    Purpose: Repeated radioembolization (RE) treatments carry theoretically higher risk of radiation-induced hepatic injury because of the liver's cumulative memory of previous exposure. We performed a retrospective safety analysis on patients who underwent repeated RE. Methods: From 2004 to 2011, a total of 247 patients were treated by RE. Eight patients (5 men, 3 women, age range 51-71 years) underwent repeated treatment of a targeted territory, all with resin microspheres (SIR-Spheres; Sirtex, Lane Cove, Australia). Adverse events were graded during a standardized follow-up. In addition, the correlation between the occurrence of RE-induced liver disease (REILD) and multiple variables was investigated in univariate and multivariate analyses in all 247 patients who received RE. Results: Two patients died shortly after the second treatment (at 84 and 107 days) with signs and symptoms of REILD. Both patients underwent whole liver treatment twice (cumulative doses 3.08 and 2.66 GBq). The other 6 patients demonstrated only minor toxicities after receiving cumulative doses ranging from 2.41 to 3.88 GBq. All patients experienced objective tumor responses. In the whole population, multifactorial analysis identified three risk factors associated with REILD: repeated RE (p = 0.036), baseline serum total bilirubin (p = 0.048), and baseline serum aspartate aminotransferase (p = 0.043). Repeated RE proved to be the only independent risk factor for REILD in multivariate analysis (odds ratio 9.6; p = 0.002). Additionally, the administered activity per target volume (in GBq/L) was found to be an independent risk factor for REILD, but only in whole liver treatments (p = 0.033). Conclusion: The risk of REILD appears to be elevated for repeated RE. Objective tumor responses were observed, but establishment of safety limits will require improvement in dosimetric measurement and prediction.

  3. Evaluation of Arecoline Hydrobromide Toxicity after a 14-Day Repeated Oral Administration in Wistar Rats

    PubMed Central

    Niu, Jianrong; Zhou, Xuzheng; Li, Jianyong; Li, Bing

    2015-01-01

    A subchronic toxicity test was conducted in rats on the basis of a previous acute toxicity test to evaluate the safety of arecoline hydrobromide (Ah), to systematically study its pharmacological effects and to provide experimental support for a safe clinical dose. Eighty rats were randomly divided into four groups: a high-dose group (1000 mg/kg), medium-dose group (200 mg/kg), low-dose group (100mg/kg) and blank control group. The doses were administered daily via gastric lavage for 14 consecutive days. There were no significant differences in the low-dose Ah group compared to the control group (P>0.05) with regard to body weight, organ coefficients, hematological parameters and histopathological changes. The high-dose of Ah influenced some of these parameters, which requires further study. The results of this study indicated that a long-term, continuous high dose of Ah was toxic. However, it is safe to use Ah according to the clinically recommended dosing parameters. The level of Ah at which no adverse effects were observed was 100 mg/kg/day under the present study conditions. PMID:25880067

  4. Therapeutics development for triplet repeat expansion diseases.

    PubMed

    Di Prospero, Nicholas A; Fischbeck, Kenneth H

    2005-10-01

    The underlying genetic mutations for many inherited neurodegenerative disorders have been identified in recent years. One frequent type of mutation is trinucleotide repeat expansion. Depending on the location of the repeat expansion, the mutation might result in a loss of function of the disease gene, a toxic gain of function or both. Disease gene identification has led to the development of model systems for investigating disease mechanisms and evaluating treatments. Examination of experimental findings reveals similarities in disease mechanisms as well as possibilities for treatment.

  5. A robust method for assessing chemically induced mutagenic effects in the oral cavity of transgenic Big Blue® rats.

    PubMed

    Young, Robert R; Thompson, Chad M; Dinesdurage, Harshini R; Elbekai, Reem H; Suh, Mina; Rohr, Annette C; Proctor, Deborah M

    2015-08-01

    The Big Blue® (BB) in vivo mutation assay uses transgenic rodents to measure treatment-induced mutations in virtually any tissue. The BB assay can be conducted in rats or mice and is ideal for investigating tissue-specific mutagenic mode of action of tumor induction. Some tissues such as oral mucosa have not been thoroughly studied. Due to the small quantity and cartilaginous nature of oral cavity tissues, development of special prosection and DNA isolation methods was required to permit robust analysis of mutations in these tissues. Improved surgical methods permitted collection of adequate and reproducible quantities of tissue (∼45 mg gingiva/buccal and ∼30 mg gingiva/palate). Optimized DNA isolation methods included use of liquid nitrogen pulverization, homogenization, nuclei pelleting, digestion, and phenol/chloroform extraction, to yield sufficient quantities of DNA from these tissues. In preliminary optimization work, mutant frequency (MF) in tongue and gingiva was increased in rats exposed to the promutagen, benzo[a]pyrene, and the direct mutagen, N-ethyl-N-nitrosourea. The oral cavity carcinogen, 4-nitroquinoline-1-oxide (4-NQO; 10 ppm in drinking water; 28 days), was qualified as a positive control for mutagenesis in oral tissues since it caused significant increases in cII MFs in gingiva/palate (50.2-fold) and gingiva/buccal tissues (21.3-fold), but not in liver or bone marrow (0.9- and 1.4-fold, respectively). These results are consistent with the observation that 4-NQO primarily induces tumors in oral cavity. Results also demonstrate the utility of the BB rat mutation assay and optimized methods for investigation of oral cavity mutagenicity, and by extension, analysis of other small and cartilaginous tissues.

  6. Oral clofarabine for relapsed/refractory non-Hodgkin lymphomas: results of a phase 1 study.

    PubMed

    Abramson, Jeremy S; Takvorian, Ronald W; Fisher, David C; Feng, Yang; Jacobsen, Eric D; Brown, Jennifer R; Barnes, Jeffrey A; Neuberg, Donna S; Hochberg, Ephraim P

    2013-09-01

    We conducted a phase 1 trial evaluating the oral nucleoside analog clofarabine in patients with relapsed/refractory non-Hodgkin lymphoma. Patients were treated once daily on days 1 through 21 of a 28-day cycle for a maximum of six cycles. The study was conducted with a 3 + 3 design with 10 additional patients treated at the recommended phase 2 dose. Thirty patients were enrolled including indolent B-cell lymphomas (n = 21), mantle cell lymphoma (n = 6) and diffuse large B-cell lymphoma (n = 3). The primary toxicities were hematologic including grade 3-4 neutropenia (53%) and thrombocytopenia (27%). Three milligrams was determined to be the recommended phase 2 dose. Tumor volume was reduced in 70% of patients, and the overall response rate was 47% including 27% complete remissions. Responses were seen in indolent B-cell lymphomas and mantle cell lymphoma. At a median follow-up of 17 months, 68% of responding patients remain in ongoing remission. Oral clofarabine was well tolerated with encouraging efficacy in indolent B-cell lymphomas and mantle cell lymphomas, warranting further investigation.

  7. Subacute oral toxicity investigation of nanoparticulate and ionic silver in rats.

    PubMed

    Hadrup, Niels; Loeschner, Katrin; Bergström, Anders; Wilcks, Andrea; Gao, Xueyun; Vogel, Ulla; Frandsen, Henrik L; Larsen, Erik H; Lam, Henrik R; Mortensen, Alicja

    2012-04-01

    Subacute toxicity of 14 nm nanoparticulate silver (Ag-NP) stabilised with polyvinylpyrrolidone and ionic silver in the form of silver acetate (Ag-acetate) was investigated in four-week-old Wistar rats. Animals received orally by gavage the following: vehicle control (10 ♀, 6 ♂); Ag-NP at doses: 2.25 (8 ♀), 4.5 (8 ♀) or 9 mg/kg bw/day (10 ♀, 6 ♂); or Ag-acetate 9 mg silver/kg bw/day (8 ♀) for 28 days. Clinical, haematolological and biochemical parameters, organ weights, macro- and microscopic pathological changes were investigated. Caecal bacterial phyla and their silver resistance genes were quantified. For the Ag-NP groups, no toxicological effects were recorded. For Ag-acetate, lower body weight gain (day 4-7, 11-14, 14-16, P < 0.05; overall, day 1-28, P < 0.01), increased plasma alkaline phosphatase (P < 0.05), decreased plasma urea (P < 0.05) and lower absolute (P < 0.01) and relative (P < 0.05) thymus weight were recorded. In conclusion, these findings indicate toxicity of 9 mg/kg bw/day ionic silver but not of an equimolar Ag-NP dose. This is in accordance with previously reported data showing that oral Ag-acetate, in comparison with an equimolar dose of Ag-NP, resulted in higher silver plasma and organ concentrations.

  8. Safety assessment of dietary bamboo charcoal powder: a 90-day subchronic oral toxicity and mutagenicity studies.

    PubMed

    Zhenchao, Jia; Yuting, Zhong; Jiuming, Yan; Yedan, Lu; Yang, Song; Jinyao, Chen; Lishi, Zhang

    2015-01-01

    Vegetable carbon has been used as food additive in EU (E153) and China for many years; however, no experimental data have been available on its dietary safety. This study was designed to evaluate the subchronic toxicity and genotoxicity of bamboo charcoal powder (BCP). In the study of subchronic oral toxicity, BCP was administered orally at doses of 2.81, 5.62, and 11.24 g/kg BW for 90 days to SD rats. Additional satellite groups from the control group and high dose group were observed for a 28-day recovery period. At the end of the treatment and recovery periods, animals were sacrificed, and their organs were weighed and blood samples were collected. The toxicological endpoints observed included clinical signs, food consumption, body and organ weights, hematological and biochemical parameters, macroscopic and microscopic examinations. The results showed no significant differences between the BCP treated groups and control group. The genotoxicity of BCP was assessed with the Salmonella typhimurium mutagenicity assay (Ames test) and a combination of comet assay and mammalian erythrocyte micronucleus protocol. The results did not reveal any genotoxicity of BCP. Based on our study, the no-observed-adverse-effect level (NOAEL) for BCP is 11.24 g/kg BW/day.

  9. Experimental study of antiangiogenic gene therapy targeting VEGF in oral cancer.

    PubMed

    Okada, Yasuo; Ueno, Hikaru; Katagiri, Masataka; Oneyama, Takahiro; Shimomura, Kana; Sakurai, Satoshi; Mataga, Izumi; Moride, Michiko; Hasegawa, Hitoshi

    2010-02-01

    It is well known that tumor angiogenesis plays an important role in local growth and metastasis of oral cancer; therefore, inhibiting angiogenesis is considered to be effective for treating oral cancer. This study aimed to investigate the effectiveness of systemically available antiangiogenic gene therapy targeting vascular endothelial growth factor (VEGF), which is one of the most important angiogenesis accelerators. We administered a soluble form of VEGF receptor-expressing gene incorporated into adenovirus (AdVEGF-ExR) intraperitoneally to nude mice to which oral cancer cell lines (SAS, HSC-3, and Ca9-22) had been transplanted subcutaneously in vivo to inhibit angiogenesis and tumor proliferation. Then, we measured tumor volumes over time, and tumors were enucleated and examined histopathologically and immunohistologically at 28 days after AdVEGF-ExR administration. Compared to the controls to which we administered AdLacZ or saline, significant antiproliferative effects were observed (P < 0.05) in the AdVEGF-ExR administration group, and extensive tumor necrosis was found histopathologically. Immunohistochemical analysis with CD34 (NU-4A1) revealed tumor angiogenesis was suppressed significantly (P < 0.05), and that with ssDNA revealed apoptosis induction was significantly high (P < 0.05) in the AdVEGF-ExR group. However, analysis with Ki-67 (MIB-1) revealed tumor proliferative capacity was not significantly different between the groups. Consequently, we consider that AdVEGF-ExR administration achieved tumor growth suppression by inhibiting angiogenesis and inducing apoptosis, but not by inhibiting the proliferative capacity of tumor cells. Neither topical administration of a soluble form of VEGF receptor (sVEGFR) to the tumor nor a megadose was needed to achieve this inhibition effect. These results suggest gene therapy via sVEGFR would be an effective oral cancer therapy and benefit future clinical applications.

  10. Metabolomic Studies of Oral Biofilm, Oral Cancer, and Beyond.

    PubMed

    Washio, Jumpei; Takahashi, Nobuhiro

    2016-06-02

    Oral diseases are known to be closely associated with oral biofilm metabolism, while cancer tissue is reported to possess specific metabolism such as the 'Warburg effect'. Metabolomics might be a useful method for clarifying the whole metabolic systems that operate in oral biofilm and oral cancer, however, technical limitations have hampered such research. Fortunately, metabolomics techniques have developed rapidly in the past decade, which has helped to solve these difficulties. In vivo metabolomic analyses of the oral biofilm have produced various findings. Some of these findings agreed with the in vitro results obtained in conventional metabolic studies using representative oral bacteria, while others differed markedly from them. Metabolomic analyses of oral cancer tissue not only revealed differences between metabolomic profiles of cancer and normal tissue, but have also suggested a specific metabolic system operates in oral cancer tissue. Saliva contains a variety of metabolites, some of which might be associated with oral or systemic disease; therefore, metabolomics analysis of saliva could be useful for identifying disease-specific biomarkers. Metabolomic analyses of the oral biofilm, oral cancer, and saliva could contribute to the development of accurate diagnostic, techniques, safe and effective treatments, and preventive strategies for oral and systemic diseases.

  11. Curriculum Guidelines for Predoctoral Oral Diagnosis/Oral Medicine.

    ERIC Educational Resources Information Center

    Journal of Dental Education, 1987

    1987-01-01

    Oral diagnosis is the area of dental practice that deals with gathering, recording, and evaluating information contributing to the identification of abnormalities of the head and neck region. A statement of general curricular goals in oral diagnosis/oral medicine is presented. (MLW)

  12. The New Orality: Oral Characteristics of Computer-Mediated Communication.

    ERIC Educational Resources Information Center

    Ferris, Sharmila Pixy; Montgomery, Maureen

    1996-01-01

    Considers the characteristics of orality and literacy developed in the work of scholars such as Walter Ong to consider computer-mediated communication (CMC) as the potential site of a "new orality" which is neither purely oral or literate. Notes that the medium of CMC is writing, which has traditionally represented the…

  13. Effect of Repeated Evaluation and Repeated Exposure on Acceptability Ratings of Sentences

    ERIC Educational Resources Information Center

    Zervakis, Jennifer; Mazuka, Reiko

    2013-01-01

    This study investigated the effect of repeated evaluation and repeated exposure on grammatical acceptability ratings for both acceptable and unacceptable sentence types. In Experiment 1, subjects in the Experimental group rated multiple examples of two ungrammatical sentence types (ungrammatical binding and double object with dative-only verb),…

  14. Oral Communication in Reading.

    ERIC Educational Resources Information Center

    Ediger, Marlow

    Noting that oral communication skills need continuous refinement, this document outlines various methods of practicing these skills, such as literature circles in reading; a reader's theater; presentations of book reports; story telling; a poetry reading club; and choral reading. The document describes literature circles as small groups of readers…

  15. History of oral contraception.

    PubMed

    Dhont, Marc

    2010-12-01

    On the 50th birthday of the pill, it is appropriate to recall the milestones which have led to its development and evolution during the last five decades. The main contraceptive effect of the pill being inhibition of ovulation, it may be called a small miracle that this drug was developed long before the complex regulation of ovulation and the menstrual cycle was elucidated. Another stumbling block on its way was the hostile climate with regard to contraception that prevailed at the time. Animal experiments on the effect of sex steroids on ovulation, and the synthesis of sex steroids and orally active analogues were the necessary preliminaries. We owe the development of oral contraceptives to a handful of persons: two determined feminists, Margaret Sanger and Katherine McCormick; a biologist, Gregory Pincus; and a gynaecologist, John Rock. Soon after the introduction of the first pills, some nasty and life-threatening side effects emerged, which were due to the high doses of sex steroids. This led to the development of new preparations with reduced oestrogen content, progestins with more specific action, and alternative administration routes. Almost every decade we have witnessed a breakthrough in oral contraception. Social and moral objections to birth control have gradually disappeared and, notwithstanding some pill scares, oral contraceptives are now one of the most used methods of contraception. Finally, all's well that ends well: recent reports have substantiated the multiple noncontraceptive health benefits paving the way for a bright future for this 50-year-old product.

  16. WRITING ORAL DRILLS.

    ERIC Educational Resources Information Center

    NEY, JAMES W.

    ALL ORAL LANGUAGE DRILLS MAY BE SEPARATED INTO TWO TYPES--(1) MIM-MEM OR MIMICRY MEMORIZATION DRILLS OR (2) PATTERN PRACTICE DRILLS. THESE TWO LARGER CATEGORIES CAN BE SUB-DIVIDED INTO A NUMBER OF OTHER TYPES, SUCH AS TRANSFORMATION AND SUBSTITUTION DRILLS. THE USE OF ANY PARTICULAR TYPE DEPENDS ON THE PURPOSE TO WHICH THE DRILL IS PUT. IN ANY…

  17. Oral focal epithelial hyperplasia.

    PubMed

    Bassioukas, K; Danielides, V; Georgiou, I; Photos, E; Zagorianakou, P; Skevas, A

    2000-01-01

    Focal epithelial hyperplasia (FEH) or Heck disease, is a rare viral infection of the oral mucosa caused by HPV 13 or HPV 32. In Caucasians there have been only a few cases reported. We present the first case in Greece in a young Caucasian girl in which HPV 13 was detected with PCR analysis. The patient was successfully treated with CO2 laser.

  18. Oral Language Continuum.

    ERIC Educational Resources Information Center

    Fresno County Dept. of Education, Fresno, CA.

    An oral language continuum designed to help elementary students develop techniques for a variety of speech situations, learn to listen, and learn to be aware of the responsibility of the speaker is presented. The continuum is divided into four sections. Student needs, implications for teaching, and suggested activities are arranged sequentially.…

  19. AAS Oral History Project

    NASA Astrophysics Data System (ADS)

    Buxner, Sanlyn; Holbrook, Jarita; AAS Oral History Team

    2016-06-01

    Now in its fourth year, the AAS Oral History Project has interviewed over 80 astronomers from all over the world. Led by the AAS Historical Astronomy Division (HAD) and partially funded by the American Institute of Physics Niels Bohr Library and ongoing support from the AAS, volunteers have collected oral histories from astronomers at professional meetings starting in 2015, including AAS, DPS, and the IAU general assembly. Each interview lasts one and a half to two hours and focuses on interviewees’ personal and professional lives. Questions include those about one’s family, childhood, strong influences on one’s scientific career, career path, successes and challenges, perspectives on how astronomy is changing as a field, and advice to the next generation. Each interview is audio recorded and transcribed, the content of which is checked with each interviewee. Once complete, interview transcripts are posted online as part of a larger oral history library at https://www.aip.org/history-programs/niels-bohr-library/oral-histories. Future analysis will reveal a rich story of astronomers and will help the community address issues of diversity, controversies, and the changing landscape of science. We are still recruiting individuals to be interviewed from all stages of career from undergraduate students to retired and emeritus astronomers. Contact Jarita Holbrook to schedule an interview or to find out more information about the project (astroholbrook@gmail.com). Also, contact Jarita Holbrook if you would like to become an interviewer for the project.

  20. The novel oral anticoagulants.

    PubMed

    Rojas-Hernandez, Cristhiam M; Garcia, David A

    2013-03-01

    After the introduction of warfarin, long-term oral anticoagulation treatment remained unchanged for more than 50 years. Most recently, with the development and approval of new oral anticoagulants, the treatment of medical conditions that require thrombosis prophylaxis and long-term anticoagulation has become more complex. In the case of venous thromboembolism (VTE) prevention after orthopedic surgery, the new oral agents will be less costly than the parenteral alternative. In other settings (such as atrial fibrillation or treatment of acute VTE), the new agents will offer additional convenience at higher cost, but the degree to which they will reduce clinically important events such as thrombosis or bleeding will be limited, especially for patients on optimally controlled warfarin. As the use of the new oral anticoagulants becomes more widespread, it will be important for all clinicians to have a basic understanding of their pharmacology, advantages, and limitations. Although the need to measure or reverse the effect of these drugs will arise infrequently, clinicians--especially hematologists--will desire evidence-based recommendations about how to manage such scenarios, which will require research studies.

  1. Oral Anticoagulant Therapy

    PubMed Central

    Gallus, Alexander S.; Wittkowsky, Ann; Crowther, Mark; Hylek, Elaine M.; Palareti, Gualtiero

    2012-01-01

    Background: The objective of this article is to summarize the published literature concerning the pharmacokinetics and pharmacodynamics of oral anticoagulant drugs that are currently available for clinical use and other aspects related to their management. Methods: We carried out a standard review of published articles focusing on the laboratory and clinical characteristics of the vitamin K antagonists; the direct thrombin inhibitor, dabigatran etexilate; and the direct factor Xa inhibitor, rivaroxaban Results: The antithrombotic effect of each oral anticoagulant drug, the interactions, and the monitoring of anticoagulation intensity are described in detail and discussed without providing specific recommendations. Moreover, we describe and discuss the clinical applications and optimal dosages of oral anticoagulant therapies, practical issues related to their initiation and monitoring, adverse events such as bleeding and other potential side effects, and available strategies for reversal. Conclusions: There is a large amount of evidence on laboratory and clinical characteristics of vitamin K antagonists. A growing body of evidence is becoming available on the first new oral anticoagulant drugs available for clinical use, dabigatran and rivaroxaban. PMID:22315269

  2. Research in Oral Language.

    ERIC Educational Resources Information Center

    Petty, Walter T., Ed.

    This collection of six articles on oral language is a product of the cooperative efforts of the National Conference on Research in English, the Association for Supervision and Curriculum Development, the International Reading Association, the Association for Childhood Education International, and the National Council of Teachers of English. It is…

  3. Lakota Oral Literature.

    ERIC Educational Resources Information Center

    One Feather, Vivian

    Course objectives for the three credit hour Lakota Oral Literature (college level English) course presented in this publication are to: perceive through the reading and hearing of Lakota legends a better understanding of the known world of the Lakota people which existed prior to white contact; understand the origin of the laws which the Lakota…

  4. Antibiotics and oral contraceptives.

    PubMed

    DeRossi, Scott S; Hersh, Elliot V

    2002-10-01

    With the exception of rifampin-like drugs, there is a lack of scientific evidence supporting the ability of commonly prescribed antibiotics, including all those routinely employed in outpatient dentistry, to either reduce blood levels and/or the effectiveness of oral contraceptives. To date, all clinical trials studying the effects of concomitant antibiotic therapy (with the exception of rifampin and rifabutin) have failed to demonstrate an interaction. Like all drugs, oral contraceptives are not 100% effective with the failure rate in the typical United States population reported to be as high as 3%. It is thus possible that the case reports of unintended pregnancies during antibiotic therapy may simply represent the normal failure rate of these drugs. Considering that both drug classes are prescribed frequently to women of childbearing potential, one would expect a much higher rate of oral contraceptive failure in this group of patients if a true drug:drug interaction existed. On the other hand, if the interaction does exist but is a relatively rare event, occurring in, say, 1 in 5000 women, clinical studies such as those described in this article would not detect the interaction. The pharmacokinetic studies of simultaneous antibiotic and oral contraceptive ingestion, and the retrospective studies of pregnancy rates among oral contraceptive users exposed to antibiotics, all suffer from one potential common weakness, i.e., their relatively small sample size. Sample sizes in the pharmacokinetic trials ranged from 7 to 24 participants, whereas the largest retrospective study of pregnancy rates still evaluated less than 800 total contraceptive users. Still, the incidence of such a rare interaction would not differ from the accepted normal failure rate of oral contraceptive therapy. The medico-legal ramifications of what looks like at best a rare interaction remains somewhat "murky." On one hand, we have medico-legal experts advising the profession to exercise caution

  5. Assessment of the mutagenic potential of Cr(VI) in the oral mucosa of Big Blue® transgenic F344 rats.

    PubMed

    Thompson, Chad M; Young, Robert R; Suh, Mina; Dinesdurage, Harshini R; Elbekai, Reem H; Harris, Mark A; Rohr, Annette C; Proctor, Deborah M

    2015-08-01

    Exposure to high concentrations of hexavalent chromium [Cr(VI)] in drinking water was associated with an increased incidence of oral tumors in F344 rats in a 2-year cancer bioassay conducted by the National Toxicology Program. These tumors primarily occurred at 180 ppm Cr(VI) and appeared to originate from the gingival mucosa surrounding the upper molar teeth. To investigate whether these tumors could have resulted from a mutagenic mode of action (MOA), a transgenic mutation assay based on OECD Test Guideline 488 was conducted in Big Blue(®) TgF344 rats. The mutagenic oral carcinogen 4-nitroquinoline-1-oxide (4-NQO) served as a positive control. Mutant frequency was measured in the inner gingiva with adjacent palate, and outer gingiva with adjacent buccal tissue. Exposure to 10 ppm 4-NQO in drinking water for 28 days increased mutant frequency in the cII transgene significantly, from 39.1 ± 7.5 × 10(-6) to 688 ± 250 × 10(-6) in the gingival/buccal region, and from 49.8 ± 17.8 × 10(-6) to 1818 ± 362 × 10(-6) in the gingival/palate region. Exposure to 180 ppm Cr(VI) in drinking water for 28 days did not significantly increase the mutant frequency in the gingival/buccal (44.4 ± 25.4 × 10(-6)) or the gingival/palate (57.8 ± 9.1 × 10(-6)) regions relative to controls. These data indicate that high (∼180,000 times expected human exposure), tumorigenic concentrations of Cr(VI) did not significantly increase mutations in the gingival epithelium, and suggest that Cr(VI) does not act by a mutagenic MOA in the rat oral cavity.

  6. AGG interspersions within the FMR1 CGG repeat: Mechanisms and models of triplet repeat instability

    SciTech Connect

    Eichler, E.E.; Nelson, D.L.

    1994-09-01

    Fragile X syndrome CGG repeat alleles are typically classified as normal, premutation, or full mutation based on the length of the repeat in the 5{prime} UTR of the FMR1 gene. The distinction between high-end normals and low-end premutation alleles, however, is not always clear since repeats of similar size differ markedly in their intergenerational stability. This fact suggest that differences in sequence content may play a key role in determining an allele`s predisposition to instability. It has been postulated that the loss of AGG interruptions within the CGG tract may trigger this instability. To test this model, we have developed a simple indirect method to determine the presence or absence of internal AGGs within the FMR1 CGG repeat tract. Analysis of 84 human X chromosomes for the presence of interrupting AGG trinucleotides revealed that most alleles possess two interspersed AGGs at a periodicity of 9 or 10 CGGs. The longest tract of uninterrupted CGG repeats is usually found at the 3{prime} end indicating that variation in the length of the repeat is polar. Alleles containing between 34 and 55 repeats, with documented unstable transmissions, were shown to have lost one or both AGG interruptions when compared to stable alleles of similar length. These comparisons define an instability threshold between 34 and 38 uninterrupted CGG repeats. Analysis of premutation alleles in fragile X syndrome carriers reveals that 70% of these alleles contain a single AGG interruption. Population studies confirm that such highly punctuated FMR1 CGG repeats are virtually static in terms of length variation. These data suggest that the loss of an AGG is an important mutational event in the generation of unstable alleles predisposed to the fragile X syndrome. Loss of AGG trinucleotides and polarized variability support Okazaki fragment slippage as a model for CGG repeat instability and hyperexpansion.

  7. Structures of designed armadillo-repeat proteins show propagation of inter-repeat interface effects

    PubMed Central

    Reichen, Christian; Madhurantakam, Chaithanya; Hansen, Simon; Grütter, Markus G.; Plückthun, Andreas; Mittl, Peer R. E.

    2016-01-01

    The armadillo repeat serves as a scaffold for the development of modular peptide-recognition modules. In order to develop such a system, three crystal structures of designed armadillo-repeat proteins with third-generation N-caps (YIII-type), four or five internal repeats (M-type) and second-generation C-caps (AII-type) were determined at 1.8 Å (His-YIIIM4AII), 2.0 Å (His-YIIIM5AII) and 1.95 Å (YIIIM5AII) resolution and compared with those of variants with third-generation C-caps. All constructs are full consensus designs in which the internal repeats have exactly the same sequence, and hence identical conformations of the internal repeats are expected. The N-cap and internal repeats M1 to M3 are indeed extremely similar, but the comparison reveals structural differences in internal repeats M4 and M5 and the C-cap. These differences are caused by long-range effects of the C-cap, contacting molecules in the crystal, and the intrinsic design of the repeat. Unfortunately, the rigid-body movement of the C-terminal part impairs the regular arrangement of internal repeats that forms the putative peptide-binding site. The second-generation C-cap improves the packing of buried residues and thereby the stability of the protein. These considerations are useful for future improvements of an armadillo-repeat-based peptide-recognition system. PMID:26894544

  8. Prevention of status epilepticus-induced brain edema and neuronal cell loss by repeated treatment with high-dose levetiracetam.

    PubMed

    Itoh, Kouichi; Inamine, Moriyoshi; Oshima, Wataru; Kotani, Masaharu; Chiba, Yoichi; Ueno, Masaki; Ishihara, Yasuhiro

    2015-05-22

    The management of status epilepticus (SE) is important to prevent mortality and the development of post-SE symptomatic epilepsy. Acquired epilepsy after an initial brain insult by SE can be experimentally reproduced in the murine model of SE induced by pilocarpine. In the present study, we evaluated the possibility of treatment with a high-dose of levetiracetam in this model. Repeated treatment with high-dose levetiracetam after termination of SE by diazepam significantly prevented the incidence of spontaneous recurrent seizures and mortality for at least 28 days. To determine the brain alterations after SE, magnetic resonance imaging was performed. Both T2-weighted imaging and diffusion-weighted imaging showed changes in the limbic regions. These changes in the limbic regions demonstrated the development of cytotoxic edema three hours after SE, followed by the development of vasogenic edema two days after SE. In the pilocarpine-SE model, the incidence of spontaneous recurrent seizures after SE was strongly associated with neuronal damage within a few hours to days after SE by the development of vasogenic edema via the breakdown of the blood-brain barrier in the limbic regions. High-dose levetiracetam significantly suppressed the parameters in the limbic areas. These data indicate that repeated treatment with high-dose levetiracetam for at least two days after SE termination by diazepam is important for controlling the neuronal damage by preventing brain edema. Therefore, these findings suggest that early treatment with high-dose levetiracetam after SE termination by diazepam may protect against adverse sequelae via the inhibition of neurotoxicity induced by brain edema events.

  9. Oral Manifestations of Vitiligo

    PubMed Central

    Nagarajan, Anitha; Masthan, Mahaboob Kader; Sankar, Leena Sankari; Narayanasamy, Aravindha Babu; Elumalai, Rajesh

    2015-01-01

    Background: Vitiligo is one of the disorder that has social impact. Both skin and mucous membrane show depigmentation in vitiligo. Depigmentation in oral cavity can be more easily observed and the patient can be given awareness regarding the condition if they are unaware of vitiligo elsewhere in their body and can be guided for treatment. Aim and objectives: The aim of this study is to determine the frequency of occurrence of oral mucosal vitiligo in vitiligo patients and to determine the most commonly involved oral mucosal site. Materials and methods: The study sample included 100 vitiligo patients. The patients of all age groups and both genders were included. Vitiligo patients associated with systemic conditions such as thyroid disorders, juvenile diabetes mellitus, pernicious anemia, Addison's disease were excluded in this study. Results: Out of 100 vitiligo patients 44 % male and 56% were female. The oral presentation of vitiligo in this study showed depigmentation of buccal mucosa in 5% of patients, labial mucosa in 5% of patients, palate in 8% of patients, gingiva in 2% of patients and alveolar mucosa 1%. Depigmentation of lip was seen in 42% of patients. Lip involvement refers to depigmentation of both the lips or either lip. Also vermilion border involvement was noted in majority of cases. In some cases, the depigmentation of lip extended to the facial skin also. Conclusion: In this study 55 patients out of 100 patients showed depigmentation in the oral cavity. Lip involvement was most common in this study showing about 42% of patients. Intraoral mucosal involvement was found in 21% of patients. Among intraoral mucosal site palate was common followed by buccal and labial mucosa, gingiva. Two patients had lip pigmentation as the only manifestation without any depigmentation in the skin. PMID:25657420

  10. [Oral manifestations in systemic diseases].

    PubMed

    Pedersen, Anne Marie Lynge; Jensen, Siri Beier

    2010-11-01

    Systemic diseases may affect the oral tissues, i.e. oral mucosa, salivary glands, teeth or bone, and oral manifestations will frequently present early, i.e. in association with (non-fulminant) systemic disease. Thus, recognition and proper diagnosis is essential to initiate appropriate treatment schedules. Key examples of systemic disease groups with oral manifestations include dermatological, inflammatory connective tissue diseases, haematological and inflammatory gastrointestinal diseases, as well as neurological and endocrine diseases.

  11. Lithium chloride administration prevents spatial learning and memory impairment in repeated cerebral ischemia-reperfusion mice by depressing apoptosis and increasing BDNF expression in hippocampus.

    PubMed

    Fan, Mingyue; Jin, Wei; Zhao, Haifeng; Xiao, Yining; Jia, Yanqiu; Yin, Yu; Jiang, Xin; Xu, Jing; Meng, Nan; Lv, Peiyuan

    2015-09-15

    Lithium has been reported to have neuroprotective effects, but the preventive and treated role on cognition impairment and the underlying mechanisms have not been determined. In the present study, C57Bl/6 mice were subjected to repeated bilateral common carotid artery occlusion to induce the learning and memory deficits. 2 mmol/kg or 5 mmol/kg of lithium chloride (LiCl) was injected intraperitoneally per day before (for 7 days) or post (for 28 days) the operation. This repeated cerebral ischemia-reperfusion (IR) induced dynamic overexpression of ratio of Bcl-2/Bax and BDNF in hippocampus of mice. LiCl pretreatment and treatment significantly decreased the escape latency and increased the percentage of time that the mice spent in the target quadrant in Morris water maze. 2 mmol/kg LiCl evidently reversed the morphologic changes, up-regulated the survival neuron count and increased the BDNF gene and protein expression. 5 mmol/kg pre-LiCl significantly increased IR-stimulated reduce of Bcl-2/Bax and p-CREB/CREB. These results described suggest that pre-Li and Li treatment may induce a pronounced prevention on cognitive impairment. These effects may relay on the inhibition of apoptosis and increasing BDNF and p-CREB expression.

  12. Triggering of repeating earthquakes in central California

    USGS Publications Warehouse

    Wu, Chunquan; Gomberg, Joan; Ben-Naim, Eli; Johnson, Paul

    2014-01-01

    Dynamic stresses carried by transient seismic waves have been found capable of triggering earthquakes instantly in various tectonic settings. Delayed triggering may be even more common, but the mechanisms are not well understood. Catalogs of repeating earthquakes, earthquakes that recur repeatedly at the same location, provide ideal data sets to test the effects of transient dynamic perturbations on the timing of earthquake occurrence. Here we employ a catalog of 165 families containing ~2500 total repeating earthquakes to test whether dynamic perturbations from local, regional, and teleseismic earthquakes change recurrence intervals. The distance to the earthquake generating the perturbing waves is a proxy for the relative potential contributions of static and dynamic deformations, because static deformations decay more rapidly with distance. Clear changes followed the nearby 2004 Mw6 Parkfield earthquake, so we study only repeaters prior to its origin time. We apply a Monte Carlo approach to compare the observed number of shortened recurrence intervals following dynamic perturbations with the distribution of this number estimated for randomized perturbation times. We examine the comparison for a series of dynamic stress peak amplitude and distance thresholds. The results suggest a weak correlation between dynamic perturbations in excess of ~20 kPa and shortened recurrence intervals, for both nearby and remote perturbations.

  13. Chlorinated hydrocarbons in women with repeated miscarriages.

    PubMed Central

    Gerhard, I; Daniel, V; Link, S; Monga, B; Runnebaum, B

    1998-01-01

    This study was conducted to investigate a possible etiological role of chlorinated hydrocarbons in the pathogenesis of repeated miscarriages. The blood levels of chlorinated hydrocarbons [CHCs: pentachlorophenol, hexachlorocyclohexane, hexachlorobenzene, the dichlorodiphenyltrichloroethane (DDT) group, polychlorinated biphenyls] were determined in 89 women with repeated miscarriages, who were referred to the University Hospital of Obstetrics and Gynecology of Heidelberg for investigations between 1989 and 1993, and compared to a previously investigated reference population. In more than 20% of the women, at least one of the CHC levels exceeded the reference range. CHC levels did not differ significantly between women with primary or secondary and early or late miscarriages; neither did they differ between women with hormonal or immunological disorders as causes of repeated miscarriages or women with idiopathic repeated miscarriages. No significant associations were detected between CHC levels and further conceptions or the outcome of further pregnancies. As significant associations were found between increasing CHC blood concentrations and immunological and hormonal changes, CHCs may have an impact on the pregnancy course in certain cases. PMID:9755145

  14. Is Retrieval Mediated after Repeated Testing?

    ERIC Educational Resources Information Center

    Kole, James A.; Healy, Alice F.

    2013-01-01

    In 2 main experiments, the mediated priming effect was used to determine whether retrieval continues to be mediated after repeated testing. In each experiment, participants used the keyword method to learn French vocabulary, then completed a modified lexical decision task in which they first translated a French word, and then made a lexical…

  15. Repeater For A Digital-Communication Bus

    NASA Technical Reports Server (NTRS)

    Torres-Guzman, Esteban; Olson, Stephen; Heaps, Tim

    1993-01-01

    Digital repeater circuit designed to extend range of communication on MIL-STD-1553 bus beyond original maximum allowable length of 300 ft. Circuit provides two-way communication, one way at time, and conforms to specifications of MIL-STD-1553. Crosstalk and instability eliminated.

  16. Rectourethral fistula after repeat transrectal prostate biopsy.

    PubMed

    Loran, Oleg B; Veliev, Evgeny I; Sokolov, Egor A; Dadashev, Elmar O; Guspanov, Renat I

    2013-09-01

    Transrectal prostate biopsy is considered a relatively safe procedure, with a quite small number of complications. We report a patient with a rectourethral fistula after a repeat transrectal prostate biopsy. To our knowledge, this is the first incident in the published literature.

  17. Repeated Random Sampling in Year 5

    ERIC Educational Resources Information Center

    Watson, Jane M.; English, Lyn D.

    2016-01-01

    As an extension to an activity introducing Year 5 students to the practice of statistics, the software "TinkerPlots" made it possible to collect repeated random samples from a finite population to informally explore students' capacity to begin reasoning with a distribution of sample statistics. This article provides background for the…

  18. [Preventive maintenance of repeated ischemic insults].

    PubMed

    Gavrilenko, A V; Kuklin, A V; Kravchenko, A A; Agafonov, I N

    2008-01-01

    In the review we offer analysis of the effectiveness of carotid endarterectomy in treatment of post-functional apoplexy or stroke patients. Published results of the researches specify possible efficiency of carotid endarterectomy in preventive maintenance against repeated apoplectic attack or strokes. Yet the criteria of usage and execution of the carotid endarterectomy are still to be discussed.

  19. Epigenetics and Triplet-Repeat Neurological Diseases

    PubMed Central

    Nageshwaran, Sathiji; Festenstein, Richard

    2015-01-01

    The term “junk DNA” has been reconsidered following the delineation of the functional significance of repetitive DNA regions. Typically associated with centromeres and telomeres, DNA repeats are found in nearly all organisms throughout their genomes. Repetitive regions are frequently heterochromatinized resulting in silencing of intrinsic and nearby genes. However, this is not a uniform rule, with several genes known to require such an environment to permit transcription. Repetitive regions frequently exist as dinucleotide, trinucleotide, and tetranucleotide repeats. The association between repetitive regions and disease was emphasized following the discovery of abnormal trinucleotide repeats underlying spinal and bulbar muscular atrophy (Kennedy’s disease) and fragile X syndrome of mental retardation (FRAXA) in 1991. In this review, we provide a brief overview of epigenetic mechanisms and then focus on several diseases caused by DNA triplet-repeat expansions, which exhibit diverse epigenetic effects. It is clear that the emerging field of epigenetics is already generating novel potential therapeutic avenues for this group of largely incurable diseases. PMID:26733936

  20. Testing Multiple Outcomes in Repeated Measures Designs

    ERIC Educational Resources Information Center

    Lix, Lisa M.; Sajobi, Tolulope

    2010-01-01

    This study investigates procedures for controlling the familywise error rate (FWR) when testing hypotheses about multiple, correlated outcome variables in repeated measures (RM) designs. A content analysis of RM research articles published in 4 psychology journals revealed that 3 quarters of studies tested hypotheses about 2 or more outcome…

  1. Y Se Repite = And It Repeats Itself

    ERIC Educational Resources Information Center

    Katzew, Adriana

    2010-01-01

    In this article, the author discusses Y Se Repite [And It Repeats Itself], a project she conceptualized due to the growing number of Latino/a Mexican migrant workers in dairy farms in the state of Vermont. In 2006, approximately 2,000 Latinos/as--most of them undocumented Mexican migrant workers--worked throughout the state's dairy farms, yet…

  2. Longer-baseline telescopes using quantum repeaters.

    PubMed

    Gottesman, Daniel; Jennewein, Thomas; Croke, Sarah

    2012-08-17

    We present an approach to building interferometric telescopes using ideas of quantum information. Current optical interferometers have limited baseline lengths, and thus limited resolution, because of noise and loss of signal due to the transmission of photons between the telescopes. The technology of quantum repeaters has the potential to eliminate this limit, allowing in principle interferometers with arbitrarily long baselines.

  3. The Effect of Repeaters on Equating

    ERIC Educational Resources Information Center

    Kim, HeeKyoung; Kolen, Michael J.

    2010-01-01

    Test equating might be affected by including in the equating analyses examinees who have taken the test previously. This study evaluated the effect of including such repeaters on Medical College Admission Test (MCAT) equating using a population invariance approach. Three-parameter logistic (3-PL) item response theory (IRT) true score and…

  4. A History of Oral Interpretation.

    ERIC Educational Resources Information Center

    Bahn, Eugene; Bahn, Margaret L.

    This historical account of the oral interpretation of literature establishes a chain of events comprehending 25 centuries of verbal tradition from the Homeric Age through 20th Century America. It deals in each era with the viewpoints and contributions of major historical figures to oral interpretation, as well as with oral interpretation's…

  5. Oral and perioral piercing complications.

    PubMed

    Escudero-Castaño, N; Perea-García, M A; Campo-Trapero, J; Cano-Sánchez; Bascones-Martínez, A

    2008-12-04

    BACKGROUND.: The oral an perioral piercing has a long history as part of religious, tribal,cultural or sexual symbolism and nowdays there is a high incidence of oral and perioral piercing in the adolescent population. This practice has a long history as part of religious, tribal, cultural or sexual symbolism. This article reviews current knowledge on injuries or diseases that might be produced by piercing in the oral cavity. We propose a classification to diagnosed the pathologies related to oral an perioral piercing METHODS.: A search was conducted of articles in PubMed, Scielo published between 1997 and 2007, using the key words ;;oral and perioral, piercing , ;;oral, piercing and disease", ;;recessions and oral piercing . It has reviewed about twentythree articles 17 were narrative reviews and 6 case series RESULTS.: A review was carried out on the origins of oral and perioral body piercing and its local implications, classifying the different alterations like recessions, systemic implications that it can produce in the oral and perioral cavity. CONCLUSION.: Patients with oral and perioral piercing should be regularly followed up because of the possible development of different types of adverse effects. CLINICAL IMPLICATIONS.: Adverse effects of oral and perioral piercing can be systemic, with transmission of infectious diseases such as hepatitis B or C, or can be local, with alteration of oral mucosae or even of dental structures.

  6. Oral Manifestations and Molecular Basis of Oral Genodermatoses: A Review

    PubMed Central

    Shilpasree, A.S.; Chaudhary, Meenakshi

    2016-01-01

    Genodermatoses refers to group of inherited monogenic disorders with skin manifestations. Many of these disorders are rare and also have oral manifestations, called oral genodermatoses. This article provides a focused review of molecular basis of important genodermatoses that affects the oral cavity and also have prominent associated dermatologic features. In several conditions discussed here, the oral findings are distinct and may provide the first clue of an underlying genetic diagnosis. The article also emphasises on the prenatal diagnosis, genetic counselling and the treatment oral genodermatoses. PMID:27437377

  7. Acute and Subacute Oral Toxicity Evaluation of Crude Antifungal Compounds Produced by Lactobacillus plantarum HD1 in Rats

    PubMed Central

    Son, Hee-Kyoung; Chang, Hae-Choon; Lee, Jae-Joon

    2015-01-01

    The aim of this study was to investigate the acute and subacute oral toxicity of crude antifungal compounds produced by Lactobacillus plantarum HD1 in Sprague-Dawley rats. In the acute toxicity study, the crude antifungal compounds (0.625, 1.25, 2.5, and 5.0 g/kg) did not produce mortality, significant changes in general behavior, or changes in the gross appearance of the organs. In the subacute toxicity study, the crude antifungal compounds were administered orally to rats at doses of 0, 0.5, 1.0, and 2.0 g/kg daily for 28 days. There were no test article-related deaths, abnormal clinical signs, or body weight changes. The study also showed no significant differences between the control and treated groups in hematological and serum biochemical parameters, histopathological examination, or any other findings. These results suggest that acute or subacute oral administration of crude antifungal compounds from L. plantarum HD1 is not toxic in rats. PMID:26451356

  8. Repeated sprint training in normobaric hypoxia.

    PubMed

    Galvin, Harvey M; Cooke, Karl; Sumners, David P; Mileva, Katya N; Bowtell, Joanna L

    2013-12-01

    Repeated sprint ability (RSA) is a critical success factor for intermittent sport performance. Repeated sprint training has been shown to improve RSA, we hypothesised that hypoxia would augment these training adaptations. Thirty male well-trained academy rugby union and rugby league players (18.4 ± 1.5 years, 1.83 ± 0.07 m, 88.1 ± 8.9 kg) participated in this single-blind repeated sprint training study. Participants completed 12 sessions of repeated sprint training (10 × 6 s, 30 s recovery) over 4 weeks in either hypoxia (13% FiO₂) or normoxia (21% FiO₂). Pretraining and post-training, participants completed sports specific endurance and sprint field tests and a 10 × 6 s RSA test on a non-motorised treadmill while measuring speed, heart rate, capillary blood lactate, muscle and cerebral deoxygenation and respiratory measures. Yo-Yo Intermittent Recovery Level 1 test performance improved after RS training in both groups, but gains were significantly greater in the hypoxic (33 ± 12%) than the normoxic group (14 ± 10%, p<0.05). During the 10 × 6 s RS test there was a tendency for greater increases in oxygen consumption in the hypoxic group (hypoxic 6.9 ± 9%, normoxic (-0.3 ± 8.8%, p=0.06) and reductions in cerebral deoxygenation (% changes for both groups, p=0.09) after hypoxic than normoxic training. Twelve RS training sessions in hypoxia resulted in twofold greater improvements in capacity to perform repeated aerobic high intensity workout than an equivalent normoxic training. Performance gains are evident in the short term (4 weeks), a period similar to a preseason training block.

  9. Repeated sprint training in normobaric hypoxia

    PubMed Central

    Galvin, Harvey M; Cooke, Karl; Sumners, David P; Mileva, Katya N; Bowtell, Joanna L

    2013-01-01

    Repeated sprint ability (RSA) is a critical success factor for intermittent sport performance. Repeated sprint training has been shown to improve RSA, we hypothesised that hypoxia would augment these training adaptations. Thirty male well-trained academy rugby union and rugby league players (18.4±1.5 years, 1.83±0.07 m, 88.1±8.9 kg) participated in this single-blind repeated sprint training study. Participants completed 12 sessions of repeated sprint training (10×6 s, 30 s recovery) over 4 weeks in either hypoxia (13% FiO2) or normoxia (21% FiO2). Pretraining and post-training, participants completed sports specific endurance and sprint field tests and a 10×6 s RSA test on a non-motorised treadmill while measuring speed, heart rate, capillary blood lactate, muscle and cerebral deoxygenation and respiratory measures. Yo-Yo Intermittent Recovery Level 1 test performance improved after RS training in both groups, but gains were significantly greater in the hypoxic (33±12%) than the normoxic group (14±10%, p<0.05). During the 10×6 s RS test there was a tendency for greater increases in oxygen consumption in the hypoxic group (hypoxic 6.9±9%, normoxic (−0.3±8.8%, p=0.06) and reductions in cerebral deoxygenation (% changes for both groups, p=0.09) after hypoxic than normoxic training. Twelve RS training sessions in hypoxia resulted in twofold greater improvements in capacity to perform repeated aerobic high intensity workout than an equivalent normoxic training. Performance gains are evident in the short term (4 weeks), a period similar to a preseason training block. PMID:24282212

  10. RepeatsDB 2.0: improved annotation, classification, search and visualization of repeat protein structures

    PubMed Central

    Paladin, Lisanna; Hirsh, Layla; Piovesan, Damiano; Andrade-Navarro, Miguel A.; Kajava, Andrey V.; Tosatto, Silvio C.E.

    2017-01-01

    RepeatsDB 2.0 (URL: http://repeatsdb.bio.unipd.it/) is an update of the database of annotated tandem repeat protein structures. Repeat proteins are a widespread class of non-globular proteins carrying heterogeneous functions involved in several diseases. Here we provide a new version of RepeatsDB with an improved classification schema including high quality annotations for ∼5400 protein structures. RepeatsDB 2.0 features information on start and end positions for the repeat regions and units for all entries. The extensive growth of repeat unit characterization was possible by applying the novel ReUPred annotation method over the entire Protein Data Bank, with data quality is guaranteed by an extensive manual validation for >60% of the entries. The updated web interface includes a new search engine for complex queries and a fully re-designed entry page for a better overview of structural data. It is now possible to compare unit positions, together with secondary structure, fold information and Pfam domains. Moreover, a new classification level has been introduced on top of the existing scheme as an independent layer for sequence similarity relationships at 40%, 60% and 90% identity. PMID:27899671

  11. Vectorette PCR isolation of microsatellite repeat sequences using anchored dinucleotide repeat primers.

    PubMed Central

    Lench, N J; Norris, A; Bailey, A; Booth, A; Markham, A F

    1996-01-01

    We have developed a vectorette PCR approach to provide an improved method for isolation of microsatellite repeats. The modified procedure relies on PCR amplification using a vectorette-specific primer in combination with one of a panel of anchored dinucleotide repeat primers. The target DNA to be screened for microsatellite sequences can be from YAC, P1, cosmid, bacteriophage or plasmid clones. We have used this technique to isolate novel, polymorphic microsatellite repeats from clones containing the amelogenin gene (AMGX) located on human chromosome Xp22.3. PMID:8668553

  12. Oral, subcutaneous, and intravenous pharmacokinetics of ondansetron in healthy cats.

    PubMed

    Quimby, J M; Lake, R C; Hansen, R J; Lunghofer, P J; Gustafson, D L

    2014-08-01

    Ondansetron is a 5-HT3 receptor antagonist that is an effective anti-emetic in cats. The purpose of this study was to evaluate the pharmacokinetics of ondansetron in healthy cats. Six cats with normal complete blood count, serum biochemistry, and urinalysis received 2 mg oral (mean 0.43 mg/kg), subcutaneous (mean 0.4 mg/kg), and intravenous (mean 0.4 mg/kg) ondansetron in a cross-over manner with a 5-day wash out. Serum was collected prior to, and at 0.25, 0.5, 1, 2, 4, 8, 12, 18, and 24 h after administration of ondansetron. Ondansetron concentrations were measured using liquid chromatography coupled to tandem mass spectrometry. Noncompartmental pharmacokinetic modeling and dose interval modeling were performed. Repeated measures anova was used to compare parameters between administration routes. Bioavailability of ondansetron was 32% (oral) and 75% (subcutaneous). Calculated elimination half-life of ondansetron was 1.84 ± 0.58 h (intravenous), 1.18 ± 0.27 h (oral) and 3.17 ± 0.53 h (subcutaneous). The calculated elimination half-life of subcutaneous ondansetron was significantly longer (P < 0.05) than oral or intravenous administration. Subcutaneous administration of ondansetron to healthy cats is more bioavailable and results in a more prolonged exposure than oral administration. This information will aid management of emesis in feline patients.

  13. Experimental oral and nasal transmission of rabies virus in mice.

    PubMed

    Charlton, K M; Casey, G A

    1979-01-01

    Weanling female white Swiss mice were exposed to challenge virus standard rabies virus and street virus isolates from various domestic and wild animals. Virus was given free choice as suspension or as infected mouse brain by stomach tube, by single injection of suspension into the oral cavity of unanesthetized mice, by repeated injection into the oral cavity of anesthetized mice and by single application to the external nares of anesthetized mice. Challenge virus standard virus in mouse brain suspension and a suspension of skunk salivary glands infected with street virus (titers greater than or equal to 10(6)MICLD50/0.03 ml) consistently produced high rates of infection in mice exposed intranasally, low to high rates of infection in mice exposed by forced feeding and other artificial methods of oral exposure and very low rates of infection when given free choice. Street virus isolates passaged intracerebrally in mice had titers less than or equal to 10(4.5) MICLD50/0.03 ml and rarely caused rabies in mice exposed orally or nasally by any method. The results indicate that with the isolates used, virus of high titer (greater than or equal to 10(6)MICLD50/0.03 ml) is required to consistently produce infection in mice by the nasal route and that the mucosa of the nasal cavity probably is the chief route of infection even after oral administration.

  14. Experimental oral and nasal transmission of rabies virus in mice.

    PubMed Central

    Charlton, K M; Casey, G A

    1979-01-01

    Weanling female white Swiss mice were exposed to challenge virus standard rabies virus and street virus isolates from various domestic and wild animals. Virus was given free choice as suspension or as infected mouse brain by stomach tube, by single injection of suspension into the oral cavity of unanesthetized mice, by repeated injection into the oral cavity of anesthetized mice and by single application to the external nares of anesthetized mice. Challenge virus standard virus in mouse brain suspension and a suspension of skunk salivary glands infected with street virus (titers greater than or equal to 10(6)MICLD50/0.03 ml) consistently produced high rates of infection in mice exposed intranasally, low to high rates of infection in mice exposed by forced feeding and other artificial methods of oral exposure and very low rates of infection when given free choice. Street virus isolates passaged intracerebrally in mice had titers less than or equal to 10(4.5) MICLD50/0.03 ml and rarely caused rabies in mice exposed orally or nasally by any method. The results indicate that with the isolates used, virus of high titer (greater than or equal to 10(6)MICLD50/0.03 ml) is required to consistently produce infection in mice by the nasal route and that the mucosa of the nasal cavity probably is the chief route of infection even after oral administration. PMID:427634

  15. Oral manifestations of hyperoxaluria.

    PubMed

    Guerra, Eliete Neves da Silva; Vianna, Leonora; Sobreira, Maria Nazareth; de Araújo, Flavio Nader Gross; de Melo, Nilce Santos

    2011-11-01

    Primary hyperoxaluria is a rare, inherited autosomal recessive disease caused by defects in the metabolism of glyoxylate. Oral manifestations of hyperoxaluria are rare. However, bone and tooth resorption may be the result of chronic inflammation and the presence of osteoclastic cells surrounding the oxalate crystal deposit. A deposit of calcium oxalate in the periodontium was identified in a patient with end-stage renal disease. Dental radiographs indicated bone loss and external tooth resorption. Radiolucent image in the inferior incisor region was observed and removed. The tissue showed granulomatous inflammation with foreign body reaction and associated crystalline deposits. When viewed in polarized light, these deposits are green and presented a birefringent aspect, which were interpreted as calcium oxalate crystals compatible with oxaluria. Oral manifestations of hyperoxaluria are of particular interest because of the unusual location of the oxalate crystal deposition, resulting in aggressive tooth resorption and alveolar bone loss, which may be misdiagnosed.

  16. Damaging Oral Habits

    PubMed Central

    Kamdar, Rajesh J; Al-Shahrani, Ibrahim

    2015-01-01

    Oral habits, if persist beyond certain developmental age, can pose great harm to the developing teeth, occlusion, and surrounding oral tissues. In the formative years, almost all children engage in some non-nutritive sucking habits. Clinicians, by proper differential diagnosis and thorough understanding of natural growth and developmental processes, should take a decision for intervening. This article describes case series reports of thumb sucking, finger sucking, and tongue thrusting habits, which have been successfully treated by both removable and fixed orthodontic appliances. The cases shown are ranging from the age group of 9-19 years presenting combination of both mixed and permanent dentition development. All cases show satisfactory correction of habits and stable results. PMID:25954079

  17. Immunologically mediated oral diseases

    PubMed Central

    Jimson, Sudha; Balachader, N.; Anita, N.; Babu, R.

    2015-01-01

    Immune mediated diseases of oral cavity are uncommon. The lesions may be self-limiting and undergo remission spontaneously. Among the immune mediated oral lesions the most important are lichen planus, pemphigus, erythema multiformi, epidermolysis bullosa, systemic lupus erythematosis. Cellular and humoral mediated immunity play a major role directed against epithelial and connective tissue in chronic and recurrent patterns. Confirmatory diagnosis can be made by biopsy, direct and indirect immunoflouresence, immune precipitation and immunoblotting. Therapeutic agents should be selected after thorough evaluation of immune status through a variety of tests and after determining any aggravating or provoking factors. Early and appropriate diagnosis is important for proper treatment planning contributing to better prognosis and better quality of life of patient. PMID:26015713

  18. Oral chemotherapy in tinnitus.

    PubMed

    Kay, N J

    1981-05-01

    A double-blind triple cross-over trial was designed for 21 patients suffering from tinnitus; mexiletine, diazapam, betahistine and placebo were taken each for a month sequentially during which time the patients recorded their tinnitus loudness subjectively on a visual analogue scale. The results showed that these medications did not influence the tinnitus loudness. Since mexiletine is an oral analogue of lignocaine and a cardiovascular drug, any untoward cardiovascular history and clinical finding disqualified such patients from the trial. Twenty-one such patients were rejected from an original group of 42 patients. In a volunteer trial mexiletine unrelated to this, it was reported that a vasovagal attack was suffered by someone who had just consumed 400 mg mexiletine orally. After ethical considerations the tinnitus trial was stopped. Eleven patients completed the cycle of medications, 10 did not. The dangers of using a cardiovascular drug for a non-cardiovascular condition is thus exposed.

  19. Lasers in oral surgery

    NASA Astrophysics Data System (ADS)

    Keller, Ulrich; Hibst, Raimund

    1994-12-01

    The indications of lasers in oral surgery are defined by the laser-tissue interaction types. These are mainly thermal effects depending especially on the absorption of laser light in varying biological tissues. In histological sections different laser effects are demonstrated on oral mucosa, bone and cartilage, which have a great influence on wound healing and subsequently on clinical indications of the different wavelengths. On the one hand the good coagulation effect of the Nd:YAG laser is wanted for hemostasis in soft tissue surgery. On the other hand, for the treatment of precancerous dysplasias or neoplasias an effective cutting with a coagulation effect like using the CO2 laser is necessary. However, the excision of benign mucosal lesions as well as performing osteotomies or shaping of cartilage should be undertaken with the Er:YAG laser without greater coagulation and consequently without any delay of wound healing.

  20. Oral health & HIV/AIDS.

    PubMed

    Gennaro, Susan; Naidoo, Sudeshi; Berthold, Peter

    2008-01-01

    Oral lesions are common in women and children with HIV/AIDS and may decrease the overall quality of life in these patients because of pain, dry mouth, and difficulty in eating. An oral cavity screening is an easy, noninvasive, quick, and inexpensive procedure that provides nurses with invaluable information about the need for referral, treatment, and health education. Nurses can use the information obtained from a careful oral screening to decrease the symptoms experienced with oral lesions and optimize a patient's ability to chew and enjoy food. Common oral manifestations of HIV infection include fungal, viral, and bacterial infections, although neoplasms, periodontal disease, salivary gland disease, and lesions of uncertain origin are also seen. Oral lesions such as candidiasis, oral hairy leukoplakia, herpetic ulcers, and Kaposi's sarcoma are often among the first symptoms of HIV infection.

  1. Good Oral Health and Diet

    PubMed Central

    Scardina, G. A.; Messina, P.

    2012-01-01

    An unhealthy diet has been implicated as risk factors for several chronic diseases that are known to be associated with oral diseases. Studies investigating the relationship between oral diseases and diet are limited. Therefore, this study was conducted to describe the relationship between healthy eating habits and oral health status. The dentistry has an important role in the diagnosis of oral diseases correlated with diet. Consistent nutrition guidelines are essential to improve health. A poor diet was significantly associated with increased odds of oral disease. Dietary advice for the prevention of oral diseases has to be a part of routine patient education practices. Inconsistencies in dietary advice may be linked to inadequate training of professionals. Literature suggests that the nutrition training of dentists and oral health training of dietitians and nutritionists is limited. PMID:22363174

  2. Fluoride and Oral Health.

    PubMed

    O'Mullane, D M; Baez, R J; Jones, S; Lennon, M A; Petersen, P E; Rugg-Gunn, A J; Whelton, H; Whitford, G M

    2016-06-01

    The discovery during the first half of the 20th century of the link between natural fluoride, adjusted fluoride levels in drinking water and reduced dental caries prevalence proved to be a stimulus for worldwide on-going research into the role of fluoride in improving oral health. Epidemiological studies of fluoridation programmes have confirmed their safety and their effectiveness in controlling dental caries. Major advances in our knowledge of how fluoride impacts the caries process have led to the development, assessment of effectiveness and promotion of other fluoride vehicles including salt, milk, tablets, toothpaste, gels and varnishes. In 1993, the World Health Organization convened an Expert Committee to provide authoritative information on the role of fluorides in the promotion of oral health throughout the world (WHO TRS 846, 1994). This present publication is a revision of the original 1994 document, again using the expertise of researchers from the extensive fields of knowledge required to successfully implement complex interventions such as the use of fluorides to improve dental and oral health. Financial support for research into the development of these new fluoride strategies has come from many sources including government health departments as well as international and national grant agencies. In addition, the unique role which industry has played in the development, formulation, assessment of effectiveness and promotion of the various fluoride vehicles and strategies is noteworthy. This updated version of 'Fluoride and Oral Health' has adopted an evidence-based approach to its commentary on the different fluoride vehicles and strategies and also to its recommendations. In this regard, full account is taken of the many recent systematic reviews published in peer reviewed literature.

  3. [Reiter's syndrome oral manifestations].

    PubMed

    Fotiou, G; Laskaris, G

    1988-01-01

    Reiter's syndrome is characterized by arthritis, non-gonococcal urethritis, conjunctivitis and mucocutaneous lesions. Oral lesions occur in 20-40% of the cases. They appear as papules and ulcerations on the buccal mucosa, gingiva and lips. Lesions on the tongue resemple "geographic tongue". One case of Reiter's syndrome is described. The significance of the clinical lesions, their microscopic appearance and the differential diagnosis are discussed.

  4. Skylab oral health studies

    NASA Technical Reports Server (NTRS)

    Brown, L. R.; Frome, W. J.; Handler, S.; Wheatcroft, M. G.; Rider, L. J.

    1977-01-01

    Evaluation of Skylab crewmembers for mission related effects on oral health in relation to possible dental injuries provided the following distinctive changes: (1) increased counts of specific anaerobic and streptococcal components; (2) elevations in levels of secretory IgA concurrent with diminutions of salivary lysozyme; and (3) increases in dental calculus and gingival inflammations. The clinical changes are considered to be more influenced by the preexisting state of dental health than by any mission related effects.

  5. Milk and oral health.

    PubMed

    Johansson, Ingegerd; Lif Holgerson, Pernilla

    2011-01-01

    Oral health includes freedom from disease in the gums, the mucosa and the teeth. There has been a striking reduction in dental caries and periodontitis in industrialized countries, although the proportion with severe disease has remained at 10-15%, and the prevalence increases in less developed countries. If left untreated, these diseases may lead to pain, and impaired quality of life and nutritional status. Prevention and treatment need, besides traditional implementation of proper oral hygiene, sugar restriction and use of fluoride, newer cost-effective strategies. Non-sweetened dairy products, which are proven non-cariogenic, or specific bioactive components from alike sources might prove to be part of such strategies. Thus, milk proteins, such as bovine and human caseins and lactoferrin, inhibit initial attachment of cariogenic mutans streptococci to hydroxyapatite coated with saliva or purified saliva host ligands. In contrast, both bovine and human milk coated on hydroxyapatite promotes attachment of commensal Actinomyces naeslundii and other streptococci in vitro, and phosphorylated milk-derived peptides promote maintenance of tooth minerals, as shown for the β-casein-derived caseino-phosphate peptide. Observational studies are promising, but randomized clinical trials are needed to reveal if dairy products could be a complementary treatment for oral health.

  6. Stability of dental waxes following repeated heatings.

    PubMed

    Kotsiomiti, E; McCabe, J F

    1995-02-01

    The flow and strength properties of dental waxes were examined following excessive and repeated heatings of the materials. For one product, the flow at 40 +/- 0.5 degrees C was reduced by 25.3% following heating above 200 degrees C. A decrease of the elastic modulus at 20 +/- 1 degree C by approximately 66% was observed in some cases after the heating temperature had been increased to 300 degrees C. Property variations were related to compositional changes, which were investigated by infrared spectoscopy and thermal analysis. Exposure of dental waxes to temperatures higher than 200 degrees C, particularly if it is repeated, may affect the composition and properties, resulting in inferior materials.

  7. Overcoming fixation with repeated memory suppression.

    PubMed

    Angello, Genna; Storm, Benjamin C; Smith, Steven M

    2015-01-01

    Fixation (blocks to memories or ideas) can be alleviated not only by encouraging productive work towards a solution, but, as the present experiments show, by reducing counterproductive work. Two experiments examined relief from fixation in a word-fragment completion task. Blockers, orthographically similar negative primes (e.g., ANALOGY), blocked solutions to word fragments (e.g., A_L_ _GY) in both experiments. After priming, but before the fragment completion test, participants repeatedly suppressed half of the blockers using the Think/No-Think paradigm, which results in memory inhibition. Inhibiting blockers did not alleviate fixation in Experiment 1 when conscious recollection of negative primes was not encouraged on the fragment completion test. In Experiment 2, however, when participants were encouraged to remember negative primes at fragment completion, relief from fixation was observed. Repeated suppression may nullify fixation effects, and promote creative thinking, particularly when fixation is caused by conscious recollection of counterproductive information.

  8. Mutagenic inverted repeat assisted genome engineering (MIRAGE).

    PubMed

    Nair, Nikhil U; Zhao, Huimin

    2009-01-01

    Here we describe a one-step method to create precise modifications in the genome of Saccharomyces cerevisiae as a tool for synthetic biology, metabolic engineering, systems biology and genetic studies. Through homologous recombination, a mutagenesis cassette containing an inverted repeat of selection marker(s) is integrated into the genome. Due to its inherent instability in genomic DNA, the inverted repeat catalyzes spontaneous self-excision, resulting in precise genome modification. Since this excision occurs at very high frequencies, selection for the integration event can be followed immediately by counterselection, without the need for growth in permissive conditions. This is the first time a truly one-step method has been described for genome modification in any organism.

  9. Accumulate-Repeat-Accumulate-Accumulate Codes

    NASA Technical Reports Server (NTRS)

    Divsalar, Dariush; Dolinar, Samuel; Thorpe, Jeremy

    2007-01-01

    Accumulate-repeat-accumulate-accumulate (ARAA) codes have been proposed, inspired by the recently proposed accumulate-repeat-accumulate (ARA) codes. These are error-correcting codes suitable for use in a variety of wireless data-communication systems that include noisy channels. ARAA codes can be regarded as serial turbolike codes or as a subclass of low-density parity-check (LDPC) codes, and, like ARA codes they have projected graph or protograph representations; these characteristics make it possible to design high-speed iterative decoders that utilize belief-propagation algorithms. The objective in proposing ARAA codes as a subclass of ARA codes was to enhance the error-floor performance of ARA codes while maintaining simple encoding structures and low maximum variable node degree.

  10. Repeat-PPM Super-Symbol Synchronization

    NASA Astrophysics Data System (ADS)

    Connelly, J.

    2016-11-01

    To attain a wider range of data rates in pulse position modulation (PPM) schemes with constrained pulse durations, the sender can repeat a PPM symbol multiple times, forming a super-symbol. In addition to the slot and symbol synchronization typically required for PPM, the receiver must also properly align the noisy super-symbols. We present a low-complexity approximation of the maximum-likelihood method for performing super-symbol synchronization without use of synchronization sequences. We provide simulation results demonstrating performance advantage when PPM symbols are spread by a pseudo-noise sequence, as opposed to simply repeating. Additionally, the results suggest that this super-symbol synchronization technique requires signal levels below those required for reliable communication. This validates that the PPM spreading approach proposed to CCSDS can work properly as part of the overall scheme.

  11. Repeated interactions in open quantum systems

    SciTech Connect

    Bruneau, Laurent; Joye, Alain; Merkli, Marco

    2014-07-15

    Analyzing the dynamics of open quantum systems has a long history in mathematics and physics. Depending on the system at hand, basic physical phenomena that one would like to explain are, for example, convergence to equilibrium, the dynamics of quantum coherences (decoherence) and quantum correlations (entanglement), or the emergence of heat and particle fluxes in non-equilibrium situations. From the mathematical physics perspective, one of the main challenges is to derive the irreversible dynamics of the open system, starting from a unitary dynamics of the system and its environment. The repeated interactions systems considered in these notes are models of non-equilibrium quantum statistical mechanics. They are relevant in quantum optics, and more generally, serve as a relatively well treatable approximation of a more difficult quantum dynamics. In particular, the repeated interaction models allow to determine the large time (stationary) asymptotics of quantum systems out of equilibrium.

  12. Nucleosome repeat lengths and columnar chromatin structure.

    PubMed

    Trifonov, Edward N

    2016-06-01

    Thorough quantitative study of nucleosome repeat length (NRL) distributions, conducted in 1992 by J. Widom, resulted in a striking observation that the linker lengths between the nucleosomes are quantized. Comparison of the NRL average values with the MNase cut distances predicted from the hypothetical columnar structure of chromatin (this work) shows a close correspondence between the two. This strongly suggests that the NRL distribution, actually, reflects the dominant role of columnar chromatin structure common for all eukaryotes.

  13. Identical repeated backbone of the human genome

    PubMed Central

    2010-01-01

    Background Identical sequences with a minimal length of about 300 base pairs (bp) have been involved in the generation of various meiotic/mitotic genomic rearrangements through non-allelic homologous recombination (NAHR) events. Genomic disorders and structural variation, together with gene remodelling processes have been associated with many of these rearrangements. Based on these observations, we identified and integrated all the 100% identical repeats of at least 300 bp in the NCBI version 36.2 human genome reference assembly into non-overlapping regions, thus defining the Identical Repeated Backbone (IRB) of the reference human genome. Results The IRB sequences are distributed all over the genome in 66,600 regions, which correspond to ~2% of the total NCBI human genome reference assembly. Important structural and functional elements such as common repeats, segmental duplications, and genes are contained in the IRB. About 80% of the IRB bp overlap with known copy-number variants (CNVs). By analyzing the genes embedded in the IRB, we were able to detect some identical genes not previously included in the Ensembl release 50 annotation of human genes. In addition, we found evidence of IRB gene copy-number polymorphisms in raw sequence reads of two diploid sequenced genomes. Conclusions In general, the IRB offers new insight into the complex organization of the identical repeated sequences of the human genome. It provides an accurate map of potential NAHR sites which could be used in targeting the study of novel CNVs, predicting DNA copy-number variation in newly sequenced genomes, and improve genome annotation. PMID:20096123

  14. Repeatability of Response to Asthma Medications

    PubMed Central

    Wu, Ann; Tantisira, Kelan; Li, Lingling; Schuemann, Brooke; Weiss, Scott

    2010-01-01

    Background Pharmacogenetic studies of drug response in asthma assume that patients respond consistently to a treatment but that treatment response varies across patients, however, no formal studies have demonstrated this. Objective To determine the repeatability of commonly used outcomes for treatment response to asthma medications: bronchodilator response, forced expiratory volume in 1 second (FEV1), and provocative concentration of methacholine producing a 20% decline in FEV1 (PC20). Methods The Childhood Asthma Management Program (CAMP) was a multi-center clinical trial of children randomized to receiving budesonide, nedocromil, or placebo. We determined the intraclass correlation coefficient (ICC) for each outcome over repeated visits over four years in CAMP using mixed effects regression models. We adjusted for the covariates: age, race/ethnicity, height, family income, parental education, and symptom score. We incorporated each outcome for each child as repeated outcome measurements and stratified by treatment group. Results The ICC for bronchodilator response was 0.31 in the budesonide group, 0.35 in the nedocromil group, and 0.40 in the placebo group, after adjusting for covariates. The ICC for FEV1 was 0.71 in the budesonide group, 0.60 in the nedocromil group, and 0.69 in the placebo group, after adjusting for covariates. The ICC for PC20 was 0.67 in the budesonide and placebo groups and 0.73 in the nedocromil group, after adjusting for covariates. Conclusion The within treatment group repeatability of FEV1 and PC20 are high; thus these phenotypes are heritable. FEV1 and PC20 may be better phenotypes than bronchodilator response for studies of treatment response in asthma. PMID:19064281

  15. 2D Metals by Repeated Size Reduction.

    PubMed

    Liu, Hanwen; Tang, Hao; Fang, Minghao; Si, Wenjie; Zhang, Qinghua; Huang, Zhaohui; Gu, Lin; Pan, Wei; Yao, Jie; Nan, Cewen; Wu, Hui

    2016-10-01

    A general and convenient strategy for manufacturing freestanding metal nanolayers is developed on large scale. By the simple process of repeatedly folding and calendering stacked metal sheets followed by chemical etching, free-standing 2D metal (e.g., Ag, Au, Fe, Cu, and Ni) nanosheets are obtained with thicknesses as small as 1 nm and with sizes of the order of several micrometers.

  16. Automatic-repeat-request error control schemes

    NASA Technical Reports Server (NTRS)

    Lin, S.; Costello, D. J., Jr.; Miller, M. J.

    1983-01-01

    Error detection incorporated with automatic-repeat-request (ARQ) is widely used for error control in data communication systems. This method of error control is simple and provides high system reliability. If a properly chosen code is used for error detection, virtually error-free data transmission can be attained. Various types of ARQ and hybrid ARQ schemes, and error detection using linear block codes are surveyed.

  17. 40 CFR 799.9310 - TSCA 90-day oral toxicity in rodents.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... target organs, body weight changes, effects on mortality and any other general or specific toxic effects... REQUIREMENTS Health Effects Test Guidelines § 799.9310 TSCA 90-day oral toxicity in rodents. (a) Scope. This... no-observed-effects level (NOEL) and toxic effects associated with continuous or repeated exposure...

  18. 40 CFR 799.9310 - TSCA 90-day oral toxicity in rodents.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... target organs, body weight changes, effects on mortality and any other general or specific toxic effects... REQUIREMENTS Health Effects Test Guidelines § 799.9310 TSCA 90-day oral toxicity in rodents. (a) Scope. This... no-observed-effects level (NOEL) and toxic effects associated with continuous or repeated exposure...

  19. Effects of Manipulating Task Complexity on Self-Repairs during L2 Oral Production

    ERIC Educational Resources Information Center

    Gilabert, Roger

    2007-01-01

    This paper analyses the effects of manipulating the cognitive complexity of L2 oral tasks on language production. It specifically focuses on self-repairs, which are taken as a measure of accuracy since they denote both attention to form and an attempt at being accurate. By means of a repeated measures design, 42 lower-intermediate students were…

  20. Programming for Generalization of Oral Reading Fluency Using Computer-Assisted Instruction and Changing Fluency Criteria

    ERIC Educational Resources Information Center

    Keyes, Starr E.; Cartledge, Gwendolyn; Gibson, Lenwood, Jr.; Robinson-Ervin, Porsha

    2016-01-01

    This study examined the effectiveness of a supplemental repeated reading intervention delivered through a computer-assisted instruction (CAI) program on the oral reading fluency (ORF), comprehension, and generalization of second graders who were at risk for reading failure. Six students received the Read Naturally Software Edition (RNSE) treatment…

  1. Orally disintegrating systems: innovations in formulation and technology.

    PubMed

    Goel, Honey; Rai, Parshuram; Rana, Vikas; Tiwary, Ashok K

    2008-01-01

    Orally disintegrating systems have carved a niche amongst the oral drug delivery systems due to the highest component of compliance they enjoy in patients especially the geriatrics and pediatrics. In addition, patients suffering from dysphagia, motion sickness, repeated emesis and mental disorders prefer these medications because they cannot swallow large quantity of water. Further, drugs exhibiting satisfactory absorption from the oral mucosa or intended for immediate pharmacological action can be advantageously formulated in these dosage forms. However, the requirements of formulating these dosage forms with mechanical strength sufficient to with stand the rigors of handling and capable of disintegrating within a few seconds on contact with saliva are inextricable. Therefore, research in developing orally disintegrating systems has been aimed at investigating different excipients as well as techniques to meet these challenges. A variety of dosage forms like tablets, films, wafers, chewing gums, microparticles, nanoparticles etc. have been developed for enhancing the performance attributes in the orally disintegrating systems. Advancements in the technology arena for manufacturing these systems include the use of freeze drying, cotton candy, melt extrusion, sublimation, direct compression besides the classical wet granulation processes. Taste masking of active ingredients becomes essential in these systems because the drug is entirely released in the mouth. Fluid bed coating, agglomeration, pelletization and infusion methods have proven useful for this purpose. It is important to note that although, freeze dried and effervescent disintegrating systems rapidly disintegrate in contact with fluids, they do not generally exhibit the required mechanical strength. Similarly, the candy process cannot be used for thermolabile drugs. In the light of the paradoxical nature of the attributes desired in orally disintegrating systems (high mechanical strength and rapid

  2. Genomic Repeat Abundances Contain Phylogenetic Signal

    PubMed Central

    Dodsworth, Steven; Chase, Mark W.; Kelly, Laura J.; Leitch, Ilia J.; Macas, Jiří; Novák, Petr; Piednoël, Mathieu; Weiss-Schneeweiss, Hanna; Leitch, Andrew R.

    2015-01-01

    A large proportion of genomic information, particularly repetitive elements, is usually ignored when researchers are using next-generation sequencing. Here we demonstrate the usefulness of this repetitive fraction in phylogenetic analyses, utilizing comparative graph-based clustering of next-generation sequence reads, which results in abundance estimates of different classes of genomic repeats. Phylogenetic trees are then inferred based on the genome-wide abundance of different repeat types treated as continuously varying characters; such repeats are scattered across chromosomes and in angiosperms can constitute a majority of nuclear genomic DNA. In six diverse examples, five angiosperms and one insect, this method provides generally well-supported relationships at interspecific and intergeneric levels that agree with results from more standard phylogenetic analyses of commonly used markers. We propose that this methodology may prove especially useful in groups where there is little genetic differentiation in standard phylogenetic markers. At the same time as providing data for phylogenetic inference, this method additionally yields a wealth of data for comparative studies of genome evolution. PMID:25261464

  3. Landauer's Principle in Repeated Interaction Systems

    NASA Astrophysics Data System (ADS)

    Hanson, Eric P.; Joye, Alain; Pautrat, Yan; Raquépas, Renaud

    2017-01-01

    We study Landauer's Principle for Repeated Interaction Systems (RIS) consisting of a reference quantum system S in contact with a structured environment E made of a chain of independent quantum probes; S interacts with each probe, for a fixed duration, in sequence. We first adapt Landauer's lower bound, which relates the energy variation of the environment E to a decrease of entropy of the system S during the evolution, to the peculiar discrete time dynamics of RIS. Then we consider RIS with a structured environment E displaying small variations of order {T^{-1}} between the successive probes encountered by S, after {n ˜eq T} interactions, in keeping with adiabatic scaling. We establish a discrete time non-unitary adiabatic theorem to approximate the reduced dynamics of S in this regime, in order to tackle the adiabatic limit of Landauer's bound. We find that saturation of Landauer's bound is related to a detailed balance condition on the repeated interaction system, reflecting the non-equilibrium nature of the repeated interaction system dynamics. This is to be contrasted with the generic saturation of Landauer's bound known to hold for continuous time evolution of an open quantum system interacting with a single thermal reservoir in the adiabatic regime.

  4. Agreement and repeatability of an infrared thermometer.

    PubMed

    Kelechi, Teresa J; Good, Angela; Mueller, Martina

    2011-01-01

    Recently, manufacturers have devised thermometers for home use by patients, such as the TempTouch Infrared Thermometer (TTIR; Diabetica Solutions, San Antonio, TX), which is designed with a long handle that can be used for self-monitoring localized skin temperature of the feet and legs. This study assessed the level of agreement and repeatability of the TTIR compared to a thermistor-type thermometer (TT; PeriFlux, 5020 Temperature Unit, Perimed, Stockholm, Sweden), the reference standard. In 17 healthy subjects, localized skin temperature was measured 8 cm above the right medial malleolus at baseline (Time 1), after a 10-minute rest period (Time 2), and after 10 minutes of cold provocation (Time 3) with a cryotherapy gel wrap placed around the lower legs using the TTIR and TT for temperature measurement. Scatter plots and correlation coefficients showed strong positive relationships between the two measurement methods at all three time points (Time 1: r = 0.95; Time 2: r = 0.97; and, Time 3: r = 0.87). Results showed a reasonable level of agreement between the two methods at Times 1 and 2 but not after cold provocation. Agreement between the methods appears to be better than repeatability within each method. Results for repeatability from both the TT and TTIR were very similar suggesting that there was a systematic bias with increasing temperatures between Time 1 and Time 2.

  5. Repeated-sprint ability: where are we?

    PubMed

    Dawson, Brian

    2012-09-01

    Repeated-sprint ability (RSA) is now well accepted as an important fitness component in team-sport performance. It is broadly described as the ability to perform repeated short (~3-4 s, 20-30 m) sprints with only brief (~10-30 s) recovery between bouts. Over the past 25 y a plethora of RSA tests have been trialed and reported in the literature. These range from a single set of ~6-10 short sprints, departing every 20-30 s, to team-sport game simulations involving repeating cycles of walk-jog-stride-sprint movements over 45-90 min. Such a wide range of RSA tests has not assisted the synthesis of research findings in this area, and questions remain regarding the optimal methods of training to best improve RSA. In addition, how RSA test scores relate to player "work rate," match performance, or both requires further investigation to improve the application of RSA testing and training to elite team-sport athletes.

  6. Accumulate-Repeat-Accumulate-Accumulate-Codes

    NASA Technical Reports Server (NTRS)

    Divsalar, Dariush; Dolinar, Sam; Thorpe, Jeremy

    2004-01-01

    Inspired by recently proposed Accumulate-Repeat-Accumulate (ARA) codes [15], in this paper we propose a channel coding scheme called Accumulate-Repeat-Accumulate-Accumulate (ARAA) codes. These codes can be seen as serial turbo-like codes or as a subclass of Low Density Parity Check (LDPC) codes, and they have a projected graph or protograph representation; this allows for a high-speed iterative decoder implementation using belief propagation. An ARAA code can be viewed as a precoded Repeat-and-Accumulate (RA) code with puncturing in concatenation with another accumulator, where simply an accumulator is chosen as the precoder; thus ARAA codes have a very fast encoder structure. Using density evolution on their associated protographs, we find examples of rate-lJ2 ARAA codes with maximum variable node degree 4 for which a minimum bit-SNR as low as 0.21 dB from the channel capacity limit can be achieved as the block size goes to infinity. Such a low threshold cannot be achieved by RA or Irregular RA (IRA) or unstructured irregular LDPC codes with the same constraint on the maximum variable node degree. Furthermore by puncturing the accumulators we can construct families of higher rate ARAA codes with thresholds that stay close to their respective channel capacity thresholds uniformly. Iterative decoding simulation results show comparable performance with the best-known LDPC codes but with very low error floor even at moderate block sizes.

  7. Orthologous repeats and mammalian phylogenetic inference

    PubMed Central

    Bashir, Ali; Ye, Chun; Price, Alkes L.; Bafna, Vineet

    2005-01-01

    Determining phylogenetic relationships between species is a difficult problem, and many phylogenetic relationships remain unresolved, even among eutherian mammals. Repetitive elements provide excellent markers for phylogenetic analysis, because their mode of evolution is predominantly homoplasy-free and unidirectional. Historically, phylogenetic studies using repetitive elements have relied on biological methods such as PCR analysis, and computational inference is limited to a few isolated repeats. Here, we present a novel computational method for inferring phylogenetic relationships from partial sequence data using orthologous repeats. We apply our method to reconstructing the phylogeny of 28 mammals, using more than 1000 orthologous repeats obtained from sequence data available from the NISC Comparative Sequencing Program. The resulting phylogeny has robust bootstrap numbers, and broadly matches results from previous studies which were obtained using entirely different data and methods. In addition, we shed light on some of the debatable aspects of the phylogeny. With rapid expansion of available partial sequence data, computational analysis of repetitive elements holds great promise for the future of phylogenetic inference. PMID:15998912

  8. Repeat Stereotactic Radiosurgery for Acoustic Neuromas

    SciTech Connect

    Kano, Hideyuki; Kondziolka, Douglas; Niranjan, Ajay M.Ch.; Flannery, Thomas J.; Flickinger, John C.; Lunsford, L. Dade

    2010-02-01

    Purpose: To evaluate the outcome of repeat stereotactic radiosurgery (SRS) for acoustic neuromas, we assessed tumor control, clinical outcomes, and the risk of adverse radiation effects in patients whose tumors progressed after initial management. Methods and Materials: During a 21-year experience at our center, 1,352 patients underwent SRS as management for their acoustic neuromas. We retrospectively identified 6 patients who underwent SRS twice for the same tumor. The median patient age was 47 years (range, 35-71 years). All patients had imaging evidence of tumor progression despite initial SRS. One patient also had incomplete surgical resection after initial SRS. All patients were deaf at the time of the second SRS. The median radiosurgery target volume at the time of the initial SRS was 0.5 cc and was 2.1 cc at the time of the second SRS. The median margin dose at the time of the initial SRS was 13 Gy and was 11 Gy at the time of the second SRS. The median interval between initial SRS and repeat SRS was 63 months (range, 25-169 months). Results: At a median follow-up of 29 months after the second SRS (range, 13-71 months), tumor control or regression was achieved in all 6 patients. No patient developed symptomatic adverse radiation effects or new neurological symptoms after the second SRS. Conclusions: With this limited experience, we found that repeat SRS for a persistently enlarging acoustic neuroma can be performed safely and effectively.

  9. A Unified Model for Repeating and Non-repeating Fast Radio Bursts

    NASA Astrophysics Data System (ADS)

    Bagchi, Manjari

    2017-04-01

    The model that fast radio bursts (FRBs) are caused by plunges of asteroids onto neutron stars can explain both repeating and non-repeating bursts. If a neutron star passes through an asteroid belt around another star, there would be a series of bursts caused by a series of asteroid impacts. Moreover, the neutron star would cross the same belt repetitively if it were in a binary with the star hosting the asteroid belt, leading to a repeated series of bursts. I explore the properties of neutron star binaries that could lead to the only known repeating FRB so far (FRB121102). In this model, the next two epochs of bursts are expected around 2017 February 27 and 2017 December 18. On the other hand, if the asteroid belt is located around the neutron star itself, then a chance fall of an asteroid from that belt onto the neutron star would lead to a non-repeating burst. Even a neutron star grazing an asteroid belt can lead to a non-repeating burst caused by just one asteroid plunge during the grazing. This is possible even when the neutron star is in a binary with the asteroid-hosting star, if the belt and the neutron star orbit are non-coplanar.

  10. Betel nut chewing, oral premalignant lesions, and the oral microbiome.

    PubMed

    Hernandez, Brenda Y; Zhu, Xuemei; Goodman, Marc T; Gatewood, Robert; Mendiola, Paul; Quinata, Katrina; Paulino, Yvette C

    2017-01-01

    Oral cancers are attributed to a number of causal agents including tobacco, alcohol, human papillomavirus (HPV), and areca (betel) nut. Although betel nut chewing has been established as an independent cause of oral cancer, the mechanisms of carcinogenesis are poorly understood. An investigation was undertaken to evaluate the influence of betel nut chewing on the oral microbiome and oral premalignant lesions. Study participants were recruited from a dental clinic in Guam. Structured interviews and oral examinations were performed. Oral swabbing and saliva samples were evaluated by 454 pyrosequencing of the V3- V5 region of the 16S rRNA bacterial gene and genotyped for HPV. One hundred twenty-two adults were enrolled including 64 current betel nut chewers, 37 former chewers, and 21 with no history of betel nut use. Oral premalignant lesions, including leukoplakia and submucous fibrosis, were observed in 10 chewers. Within-sample bacterial diversity was significantly lower in long-term (≥10 years) chewers vs. never chewers and in current chewers with oral lesions vs. individuals without lesions. Between-sample bacterial diversity based on Unifrac distances significantly differed by chewing status and oral lesion status. Current chewers had significantly elevated levels of Streptococcus infantis and higher and lower levels of distinct taxa of the Actinomyces and Streptococcus genera. Long-term chewers had reduced levels of Parascardovia and Streptococcus. Chewers with oral lesions had significantly elevated levels of Oribacterium, Actinomyces, and Streptococcus, including Streptococcus anginosus. In multivariate analyses, controlling for smoking, oral HPV, S.anginosus, and S. infantis levels, current betel nut chewing remained the only predictor of oral premalignant lesions. Our study provides evidence that betel nut chewing alters the oral bacterial microbiome including that of chewers who develop oral premalignant lesions. Nonetheless, whether microbial changes

  11. Betel nut chewing, oral premalignant lesions, and the oral microbiome

    PubMed Central

    Hernandez, Brenda Y.; Zhu, Xuemei; Goodman, Marc T.; Gatewood, Robert; Mendiola, Paul; Quinata, Katrina; Paulino, Yvette C.

    2017-01-01

    Oral cancers are attributed to a number of causal agents including tobacco, alcohol, human papillomavirus (HPV), and areca (betel) nut. Although betel nut chewing has been established as an independent cause of oral cancer, the mechanisms of carcinogenesis are poorly understood. An investigation was undertaken to evaluate the influence of betel nut chewing on the oral microbiome and oral premalignant lesions. Study participants were recruited from a dental clinic in Guam. Structured interviews and oral examinations were performed. Oral swabbing and saliva samples were evaluated by 454 pyrosequencing of the V3- V5 region of the 16S rRNA bacterial gene and genotyped for HPV. One hundred twenty-two adults were enrolled including 64 current betel nut chewers, 37 former chewers, and 21 with no history of betel nut use. Oral premalignant lesions, including leukoplakia and submucous fibrosis, were observed in 10 chewers. Within-sample bacterial diversity was significantly lower in long-term (≥10 years) chewers vs. never chewers and in current chewers with oral lesions vs. individuals without lesions. Between-sample bacterial diversity based on Unifrac distances significantly differed by chewing status and oral lesion status. Current chewers had significantly elevated levels of Streptococcus infantis and higher and lower levels of distinct taxa of the Actinomyces and Streptococcus genera. Long-term chewers had reduced levels of Parascardovia and Streptococcus. Chewers with oral lesions had significantly elevated levels of Oribacterium, Actinomyces, and Streptococcus, including Streptococcus anginosus. In multivariate analyses, controlling for smoking, oral HPV, S.anginosus, and S. infantis levels, current betel nut chewing remained the only predictor of oral premalignant lesions. Our study provides evidence that betel nut chewing alters the oral bacterial microbiome including that of chewers who develop oral premalignant lesions. Nonetheless, whether microbial changes

  12. Oral yeast colonization throughout pregnancy

    PubMed Central

    Rio, Rute; Simões-Silva, Liliana; Garro, Sofia; Silva, Mário-Jorge; Azevedo, Álvaro

    2017-01-01

    Background Recent studies suggest that placenta may harbour a unique microbiome that may have origin in maternal oral microbiome. Although the major physiological and hormonal adjustments observed in pregnant women lead to biochemical and microbiological modifications of the oral environment, very few studies evaluated the changes suffered by the oral microbiota throughout pregnancy. So, the aim of our study was to evaluate oral yeast colonization throughout pregnancy and to compare it with non-pregnant women. Material and Methods The oral yeast colonization was assessed in saliva of 30 pregnant and non-pregnant women longitudinally over a 6-months period. Demographic information was collected, a non-invasive intra-oral examination was performed and saliva flow and pH were determined. Results Pregnant and non-pregnant groups were similar regarding age and level of education. Saliva flow rate did not differ, but saliva pH was lower in pregnant than in non-pregnant women. Oral yeast prevalence was higher in pregnant than in non-pregnant women, either in the first or in the third trimester, but did not attain statistical significance. In individuals colonized with yeast, the total yeast quantification (Log10CFU/mL) increase from the 1st to the 3rd trimester in pregnant women, but not in non-pregnant women. Conclusions Pregnancy may favour oral yeast growth that may be associated with an acidic oral environment. Key words:Oral yeast, fungi, pregnancy, saliva pH. PMID:28160578

  13. Oral health problems and mortality

    PubMed Central

    Kim, Jung Ki; Baker, Lindsey A.; Davarian, Shieva; Crimmins, Eileen

    2013-01-01

    Background/purpose Previous studies have shown the relationship between individual oral health conditions and mortality; however, the relationship between mortality and multiple oral health conditions has not been examined. This study investigates the link between individual oral health problems and oral comorbidity and mortality risk. Materials and methods Data are derived from the National Health and Nutrition Examination Survey 1999–2004, which is linked to the National Death Index for mortality follow-up through 2006. We estimated the risk of mortality among people with three individual oral health conditions—tooth loss, root caries, and periodontitis as well as with oral comorbidity—or having all three conditions. Results Significant tooth loss, root caries, and periodontal disease were associated with increased odds of dying. The relationship between oral health conditions and mortality disappeared when controlling for sociodemographic, health, and/or health behavioral indicators. Having multiple oral health problems was associated with an even higher rate of mortality. Conclusion Individual oral health conditions—tooth loss, root caries, and periodontal disease—were not related to mortality when sociodemographic, health, and/or health behavioral factors were considered, and there was no differential pattern between the three conditions. Multiple oral health problems were associated with a higher risk of dying. PMID:24416472

  14. Oral hygiene, dentition, sexual habits and risk of oral cancer

    PubMed Central

    Talamini, R; Vaccarella, S; Barbone, F; Tavani, A; Vecchia, C La; Herrero, R; Muñoz, N; Franceschi, S

    2000-01-01

    In an Italian case-control study of oral cancer, number of missing teeth and other aspects of dental care were similar, but the general condition of the mouth, as indicated by gum bleeding, tartar deposits and mucosal irritation, was worse among oral cancer cases than controls. No differences were detected in sexual practices (including oral sex) and (previous) sexually transmitted infections. © 2000 Cancer Research Campaign PMID:11027440

  15. Oral sucrose and pain relief for preterm infants.

    PubMed

    Mitchell, Anita; Waltman, Patricia A

    2003-06-01

    The frequency of painful procedures performed on preterm infants in the neonatal intensive care unit (NICU) presents a challenge to nurses who are attempting to provide effective pain relief, and to the infants themselves who may suffer adverse consequences in response to repeated painful procedures. One new pain relief intervention under study is the administration of oral sucrose, which may activate endogenous opioid systems within the body. Studies with preterm infants that have examined the use of oral sucrose as an analgesic during heelsticks and venipunctures have shown that sucrose is effective in reducing pain. Sucrose may also be combined with nonnutritive sucking to provide significant pain relief. The use of oral sucrose is now recommended with a wide range of painful procedures in the NICU. Promising results have been observed in studies with both term and preterm infants, but less research has occurred with preterm infants. Additional research is warranted to determine the most effective approaches for the administration of sucrose, to examine the effectiveness of sucrose with additional types of painful procedures, and to examine the effects of long-term repeated use of sucrose.

  16. Systematic Review of the Toxicity of Long-Course Oral Corticosteroids in Children

    PubMed Central

    Choonara, Imti; Conroy, Sharon

    2017-01-01

    Background Long courses of oral corticosteroids are commonly used in children in the management of chronic conditions. Various adverse drug reactions (ADRs) are known to occur with their use. This systematic review aimed to identify the most common and serious ADRs and to determine their relative risk levels. Methods A literature search of Embase, Medline, International Pharmaceutical Abstracts, CINAHL, Cochrane Library and PubMed was performed with no language restrictions in order to identify studies where oral corticosteroids were administered to patients aged 28 days to 18 years of age for at least 15 days of treatment. Each database was searched from their earliest dates to January 2016. All studies providing clear information on ADRs were included. Results One hundred and one studies including 33 prospective cohort studies; 21 randomised controlled trials; 21 case series and 26 case reports met the inclusion criteria. These involved 6817 children and reported 4321 ADRs. The three ADRs experienced by the highest number of patients were weight gain, growth retardation and Cushingoid features with respective incidence rates of 21.1%, 18.1% and 19.4% of patients assessed for these ADRs. 21.5% of patients measured showed decreased bone density and 0.8% of patients showed osteoporosis. Biochemical HPA axis suppression was detected in 269 of 487 patients where it was measured. Infection was the most serious ADR, with twenty one deaths. Varicella zoster was the most frequent infection (9 deaths). Conclusions Weight gain, growth retardation and Cushingoid features were the most frequent ADRs seen when long-course oral corticosteroids were given to children. Increased susceptibility to infection was the most serious ADR. PMID:28125632

  17. Subchronic oral toxicity study of decitabine in combination with tetrahydrouridine in CD-1 mice.

    PubMed

    Terse, Pramod; Engelke, Kory; Chan, Kenneth; Ling, Yonghua; Sharpnack, Douglas; Saunthararajah, Yogen; Covey, Joseph M

    2014-01-01

    Decitabine (5-aza-2'-deoxycytidine; DAC) in combination with tetrahydrouridine (THU) is a potential oral therapy for sickle cell disease and β-thalassemia. A study was conducted in mice to assess safety of this combination therapy using oral gavage of DAC and THU administered 1 hour prior to DAC on 2 consecutive days/week for up to 9 weeks followed by a 28-day recovery to support its clinical trials up to 9-week duration. Tetrahydrouridine, a competitive inhibitor of cytidine deaminase, was used in the combination to improve oral bioavailability of DAC. Doses were 167 mg/kg THU followed by 0, 0.2, 0.4, or 1.0 mg/kg DAC; THU vehicle followed by 1.0 mg/kg DAC; or vehicle alone. End points evaluated were clinical observations, body weights, food consumption, clinical pathology, gross/histopathology, bone marrow micronuclei, and toxicokinetics. There were no treatment-related effects noticed on body weight, food consumption, serum chemistry, or urinalysis parameters. Dose- and gender-dependent changes in plasma DAC levels were observed with a Cmax within 1 hour. At the 1 mg/kg dose tested, THU increased DAC plasma concentration (∼ 10-fold) as compared to DAC alone. Severe toxicity occurred in females receiving high-dose 1 mg/kg DAC + THU, requiring treatment discontinuation at week 5. Severity and incidence of microscopic findings increased in a dose-dependent fashion; findings included bone marrow hypocellularity (with corresponding hematologic changes and decreases in white blood cells, red blood cells, hemoglobin, hematocrit, reticulocytes, neutrophils, and lymphocytes), thymic/lymphoid depletion, intestinal epithelial apoptosis, and testicular degeneration. Bone marrow micronucleus analysis confirmed bone marrow cytotoxicity, suppression of erythropoiesis, and genotoxicity. Following the recovery period, a complete or trend toward resolution of these effects was observed. In conclusion, the combination therapy resulted in an increased sensitivity to DAC toxicity

  18. Influence of transdermal rotigotine on ovulation suppression by a combined oral contraceptive

    PubMed Central

    Braun, Marina; Elshoff, Jan-Peer; Andreas, Jens-Otto; Müller, Louise Ischen; Horstmann, Rolf

    2009-01-01

    AIMS To assess the influence of the transdermally applied dopamine agonist rotigotine on ovulation suppression by a combined oral contraceptive (0.03 mg ethinyloestradiol and 0.15 mg levonorgestrel) in a randomized, double-blind crossover study in 40 healthy females. METHODS Treatment A consisted of the combined oral contraceptive for 28 days plus rotigotine for the first 13 days (2 mg (24 h)−1 on days 1–3, 3 mg (24 h)−1 maintenance dose thereafter). During treatment B, subjects received matching placebo patches instead of rotigotine. Pharmacodynamic parameters (progesterone, oestradiol, luteinizing hormone, and follicle stimulating hormone serum concentrations), pharmacokinetic parameters for ethinyloestradiol/levonorgestrel and rotigotine, and safety and tolerability of the treatment were assessed. RESULTS Progesterone serum concentrations remained below 2 ng ml−1 in all subjects during the luteal phase. Median serum concentrations of all other pharmacodynamic parameters were similar during both treatments. Pharmacokinetic parameters Cmax,ss and AUC(0,24 h)ss at steady state were similar with or without co-administration of rotigotine for both ethinyloestradiol and levonorgestrel with geometric mean ratios close to 1 and 90% confidence intervals within the acceptance range of bioequivalence (0.8, 1.25): Cmax,ss 1.05 (0.93, 1.19), AUC(0,24 h)ss 1.05 (0.9, 1.22) for ethinyloestradiol; Cmax,ss 1.01 (0.96, 1.06), AUC(0,24 h)ss 0.98 (0.95, 1.01) for levonorgestrel. Mean plasma concentrations of unconjugated rotigotine remained stable throughout the patch-on period (day 13). CONCLUSIONS Concomitant administration of 3 mg (24 h)−1 transdermal rotigotine had no impact on the pharmacodynamics and pharmacokinetics of a combined oral contraceptive containing 0.03 mg ethinyloestradiol and 0.15 mg levonorgestrel, suggesting that the dopamine agonist does not influence contraception efficacy. PMID:19740396

  19. Intestinal absorption and biological effects of orally administered amorphous silica particles

    PubMed Central

    2014-01-01

    Although amorphous silica nanoparticles are widely used in the production of food products (e.g., as anticaking agents), there is little information available about their absorption and biological effects after oral exposure. Here, we examined the in vitro intestinal absorption and in vivo biological effects in mice of orally administered amorphous silica particles with diameters of 70, 300, and 1,000 nm (nSP70, mSP300, and mSP1000, respectively) and of nSP70 that had been surface-modified with carboxyl or amine groups (nSP70-C and nSP70-N, respectively). Analysis of intestinal absorption by means of the everted gut sac method combined with an inductively coupled plasma optical emission spectrometer showed that the intestinal absorption of nSP70-C was significantly greater than that of nSP70. The absorption of nSP70-N tended to be greater than that of nSP70; however, the results were not statistically significant. Our results indicate that silica nanoparticles can be absorbed through the intestine and that particle diameter and surface properties are major determinants of the degree of absorption. We also examined the biological effects of the silica particles after 28-day oral exposure in mice. Hematological, histopathological, and biochemical analyses showed no significant differences between control mice and mice treated with the silica particles, suggesting that the silica nanoparticles evaluated in this study are safe for use in food production. PMID:25288919

  20. Tissue distribution of tungsten in mice following oral exposure to sodium tungstate.

    PubMed

    Guandalini, Gustavo S; Zhang, Lingsu; Fornero, Elisa; Centeno, Jose A; Mokashi, Vishwesh P; Ortiz, Pedro A; Stockelman, Michael D; Osterburg, Andrew R; Chapman, Gail G

    2011-04-18

    Heavy metal tungsten alloys have replaced lead and depleted uranium in many munitions applications, due to public perception of these elements as environmentally unsafe. Tungsten materials left in the environment may become bioaccessible as tungstate, which might lead to population exposure through water and soil contamination. Although tungsten had been considered a relatively inert and toxicologically safe material, recent research findings have raised concerns about possible deleterious health effects after acute and chronic exposure to this metal. This investigation describes tissue distribution of tungsten in mice following oral exposure to sodium tungstate. Twenty-four 6-9 weeks-old C57BL/6 laboratory mice were exposed to different oral doses of sodium tungstate (0, 62.5, 125, and 200 mg/kg/d) for 28 days, and after one day, six organs were harvested for trace element analysis with inductively coupled plasma mass spectrometry (ICP-MS). Kidney, liver, colon, bone, brain, and spleen were analyzed by sector-field high-resolution ICP-MS. The results showed increasing tungsten levels in all organs with increased dose of exposure, with the highest concentration found in the bones and the lowest concentration found in brain tissue. Gender differences were noticed only in the spleen (higher concentration of tungsten in female animals), and increasing tungsten levels in this organ were correlated with increased iron levels, something that was not observed for any other organ or either of the two other metals analyzed (nickel and cobalt). These findings confirmed most of what has been published on tungsten tissue distribution; they also showed that the brain is relatively protected from oral exposure. Further studies are necessary to clarify the findings in splenic tissue, focusing on possible immunological effects of tungsten exposure.

  1. Oral Lesions and Lymphoproliferative Disorders

    PubMed Central

    Castellarin, P.; Pozzato, G.; Tirelli, G.; Di Lenarda, R.; Biasotto, M.

    2010-01-01

    Lymphoproliferative disorders are heterogeneous malignancy characterized by the expansion of a lymphoid clone more or less differentiated. At the level of the oral cavity, the lymphoproliferative disorder can occur in various ways, most commonly as lymphoid lesions with extranodal externalization, but sometimes, oral lesions may represent a localization of a disease spread. With regard to the primary localizations of lymphoproliferative disorders, a careful examination of the head and neck, oral, and oropharyngeal area is necessary in order to identify suspicious lesions, and their early detection results in a better prognosis for the patient. Numerous complications have been described and frequently found at oral level, due to pathology or different therapeutic strategies. These complications require precise diagnosis and measures to oral health care. In all this, oral pathologists, as well as dental practitioners, have a central role in the treatment and long-term monitoring of these patients. PMID:20871659

  2. Oral manifestations in transplant patients

    PubMed Central

    Nappalli, Deepika; Lingappa, Ashok

    2015-01-01

    Organ transplantation is a widely undertaken procedure and has become an important alternative for the treatment of different end-stage organ diseases that previously had a poor prognosis. The field of organ transplant and hematopoietic stem cell transplant is developing rapidly. The increase in the number of transplant recipients also has an impact on oral and dental services. Most of the oral problems develop as a direct consequence of drug-induced immunosuppression or the procedure itself. These patients may present with oral complaints due to infections or mucosal lesions. Such lesions should be identified, diagnosed, and treated. New treatment strategies permit continuous adaptation of oral care regimens to the changing scope of oral complications. The aim of this review is to analyze those oral manifestations and to discuss the related literature. PMID:26005458

  3. Oral sex and oropharyngeal cancer

    PubMed Central

    Nguyen, Nam P.; Nguyen, Ly M.; Thomas, Sroka; Hong-Ly, Bevan; Chi, Alexander; Vos, Paul; Karlsson, Ulf; Vinh-Hung, Vincent

    2016-01-01

    Abstract Background: We aimed to study the prevalence of oral sex and its possible association with human papillomavirus (HPV) 16 infection in the development of oropharyngeal cancer in the US population for possible prevention. Methods: We conduct a systemic review on the prevalence of oral sex among Americans among different age groups, the prevalence of HPV 16 infection reported in oropharyngeal cancer, and correlation between oral sex and oropharyngeal cancer. Results: Oral sex is prevalent among adolescents and sexually active adults. Sixty percent of oropharyngeal cancer reported in the United States is associated with HPV 16 infections. Individuals who practiced oral sex with multiple partners are at risk for developing oropharyngeal cancer and need to be informed about practicing safe sex or getting vaccination. Conclusion: Family physicians will play a key role in prevention and educating the public about the risk of oral sex. PMID:27428229

  4. Oral tuberculosis: unusual radiographic findings.

    PubMed

    Sansare, K; Gupta, A; Khanna, V; Karjodkar, F

    2011-05-01

    Oral tuberculosis and its radiographic findings are not commonly encountered in an oral and maxillofacial radiology practice. Literature has occasional mention of the radiographic findings of oral tuberculosis, which are still ambiguous. When affected, it is manifested majorly in the oral mucosa and rarely in the jaw bones. Here, we report certain unusual radiographic findings of oral tuberculosis which have been rarely mentioned in the literature. Four illustrative cases describe bony resorption, condylar resorption, resorption of the inferior border of the mandible and rarefaction of the alveolar bone as radiographic findings of oral tuberculosis. Follow up of the first case demonstrated regeneration of the condylar head after anti-Kochs therapy was completed, a hitherto unreported phenomenon. The importance of including tuberculosis in the differential diagnosis of some of the unusual radiographic manifestations is emphasized.

  5. Design of the randomized, Phase III, QUAZAR AML Maintenance trial of CC-486 (oral azacitidine) maintenance therapy in acute myeloid leukemia.

    PubMed

    Roboz, Gail J; Montesinos, Pau; Selleslag, Dominik; Wei, Andrew; Jang, Jun-Ho; Falantes, Jose; Voso, Maria T; Sayar, Hamid; Porkka, Kimmo; Marlton, Paula; Almeida, Antonio; Mohan, Sanjay; Ravandi, Farhad; Garcia-Manero, Guillermo; Skikne, Barry; Kantarjian, Hagop

    2016-02-01

    Older patients with acute myeloid leukemia (AML) have worse rates of complete remission and shorter overall survival than younger patients. The epigenetic modifier CC-486 is an oral formulation of azacitidine with promising clinical activity in patients with AML in Phase I studies. The Phase III, randomized, double-blind, placebo-controlled QUAZAR AML Maintenance trial (CC-486-AML-001) examines CC-486 maintenance therapy (300 mg/day for 14 days of 28-day treatment cycles) for patients aged ≥55 years with AML in first complete remission. The primary end point is overall survival. Secondary end points include relapse-free survival, safety, health-related quality of life and healthcare resource utilization. This trial will investigate whether CC-486 maintenance can prolong remission and improve survival for older patients with AML.

  6. Oral epithelioid hemangioendothelioma

    PubMed Central

    Bhattacharya, Preeti Tomar; Guledgud, Mahima V.; Patil, Karthikeya

    2015-01-01

    Epithelioid hemangioendothelioma (HE) is an intermediate malignant potential vascular neoplasm with uncertain clinical behavior, wide variations in microscopic findings, and prognosis. According to the World Health Organization (2002) classification, epithelioid HE has been considered under malignant tumors which rarely metastasize. The epithelioid variant, the most aggressive one, has similar gender predilection and sporadic occurrence in children. The patients usually present with an asymptomatic oral mass whereas few cases may report with the painful bleeding lesion. We attempt to present a case in an adolescent male with previously never described biological behavior, diverse histopathological features, and immunohistochemistry findings. PMID:26681871

  7. Oral verruciform xanthoma

    PubMed Central

    Harris, Lydia; Staines, Konrad; Pring, Miranda

    2015-01-01

    Verruciform xanthoma (VX) of the oral cavity is a benign mucosal growth that often presents as a pink, yellow or grey raised plaque or papule with granular, papillary or verrucous surface morphology. Intraorally this often presents on the masticatory mucosa and extraorally often involves the skin and anogenital mucosa. There are several proposed aetiological factors and the clinical features of VX can be misleading; clinically it can resemble malignancy. Histopathological diagnosis is a key for the correct management of this lesion. Excision of this lesion is curative. PMID:25819830

  8. Improving the Oral Health of Residents with Intellectual and Developmental Disabilities: An Oral Health Strategy and Pilot Study

    PubMed Central

    Binkley, Catherine J.; Johnson, Knowlton W.; Abadi, Melissa; Thompson, Kirsten; Shamblen, Stephen R.; Young, Linda; Zaksek, Brigit

    2014-01-01

    This article presents an oral health (OH) strategy and pilot study focusing on individuals with intellectual and/or developmental disabilities (IDD) living in group homes. The strategy consists of four components: (1) planned action in the form of the behavioral contract and caregiver OH action planning; (2) capacity building through didactic and observation learning training; (3) environmental adaptations consisting of additional oral heath devices and strategies to create a calm atmosphere; and (4) reinforcement by post-training coaching. A pilot study was conducted consisting of pre- and post-assessment data collected one week before and one week after implementing a one-month OH strategy. The study sample comprised 11 group homes with 21 caregivers and 25 residents with IDD from one service organization in a Midwestern city. A process evaluation found high-quality implementation of the OH strategy as measured by dosage, fidelity, and caregiver reactions to implementing the strategy. Using repeated cross-sectional and repeated measures analyses, we found statistically significant positive changes in OH status and oral hygiene practices of residents. Caregiver self-efficacy as a mechanism of change was not adequately evaluated; however, positive change was found in some but not all types of caregiver OH support that were assessed. Lessons learned from implementing the pilot study intervention and evaluation are discussed, as are the next steps in conducting an efficacy study of the OH strategy. PMID:25137553

  9. Oral complications in cancer patients

    SciTech Connect

    Carl, W.

    1983-02-01

    Ionizing radiation used in treating the head and neck area produces oral side effects such as mucositis, salivary changes, trismus and radiation caries. Sequelae of cancer chemotherapy often include oral stomatitis, myelosuppression and immunosuppression. Infections of dental origin in compromised patients are potentially lethal. Specific programs to eliminate dental pathology before radiation and chemotherapy, and to maintain oral hygiene during and after therapy, will minimize these complications.

  10. Repeated administration of a mild acute toxic dose of di-n-butyltin dichloride at intervals of 3 weeks induces severe lesions in pancreas and liver of rats.

    PubMed

    Merkord, J; Weber, H; Kröning, G; Hennighausen, G

    2001-08-01

    Di-n-butyltin dichloride (DBTC) induced thymus atrophy, bile duct lesions, pancreatitis, and liver lesions in rats. Depending on dose [6 and 8 mg/kg intravenous (i.v.) DBTC] and time (1-24 weeks), the lesions in pancreas developed to a pancreatic fibrosis and the lesions in liver to liver cirrhosis. A single i.v. administration of 4 mg/kg DBTC induces a mild interstitial pancreatitis after 2-4 days followed by a restitutio ad integrum after 21-28 days. In the present study, the lesions of biliopancreatic duct, pancreas, and liver of rats after repeated administration of 4 mg/kg DBTC i.v. at intervals of 3 weeks have been investigated. The histopathological changes of pancreas and liver were examined by light microscopy 1,4, and 7 days and 2,3,4,6,9, and 12 weeks after administration of DBTC. Furthermore, pathobiochemical parameters of pancreatitis (amylase and lipase activity in serum), liver lesions (alkaline phosphatase activity and bilirubin in serum), and of fibrosis (hyaluronic acid in serum) were studied. Repeated administration of rats with DBTC (4 mg/kg i.v.) at intervals of 3 weeks induced an acute interstitial pancreatitis and after 9-12 weeks, a pancreatic fibrosis and liver lesions (intrahepatic bile duct hyperplasia, inflammation in periportal tract, and necrosis). In serum, elevated levels of alkaline phosphatase, bilirubin, and hyaluronic acid were found. This study demonstrates that the organotin compound induces toxic effects on pancreas and liver of rats by repeated administration of lower doses at long intervals. The risk of exposure to organotin at long intervals should be considered.

  11. Repeatability of a running heat tolerance test.

    PubMed

    Mee, Jessica A; Doust, Jo; Maxwell, Neil S

    2015-01-01

    At present there is no standardised heat tolerance test (HTT) procedure adopting a running mode of exercise. Current HTTs may misdiagnose a runner's susceptibility to a hyperthermic state due to differences in exercise intensity. The current study aimed to establish the repeatability of a practical running test to evaluate individual's ability to tolerate exercise heat stress. Sixteen (8M, 8F) participants performed the running HTT (RHTT) (30 min, 9 km h(-1), 2% elevation) on two separate occasions in a hot environment (40 °C and 40% relative humidity). There were no differences in peak rectal temperature (RHTT1: 38.82 ± 0.47 °C, RHTT2: 38.86 ± 0.49 °C, Intra-class correlation coefficient (ICC)=0.93, typical error of measure (TEM) = 0.13 °C), peak skin temperature (RHTT1: 38.12 ± 0.45, RHTT2: 38.11 ± 0.45 °C, ICC = 0.79, TEM = 0.30 °C), peak heart rate (RHTT1: 182 ± 15 beats min(-1), RHTT2: 183 ± 15 beats min(-1), ICC = 0.99, TEM = 2 beats min(-1)), nor sweat rate (1721 ± 675 g h(-1), 1716 ± 745 g h(-1), ICC = 0.95, TEM = 162 g h(-1)) between RHTT1 and RHTT2 (p>0.05). Results demonstrate good agreement, strong correlations and small differences between repeated trials, and the TEM values suggest low within-participant variability. The RHTT was effective in differentiating between individuals physiological responses; supporting a heat tolerance continuum. The findings suggest the RHTT is a repeatable measure of physiological strain in the heat and may be used to assess the effectiveness of acute and chronic heat alleviating procedures.

  12. [Oral transmission of Chagas' disease].

    PubMed

    Toso M, Alberto; Vial U, Felipe; Galanti, Norbel

    2011-02-01

    The traditional transmission pathways of Chagas' disease are vectorial, transfusional, transplacental and organ transplantation. However, oral transmission is gaining importance. The first evidence of oral transmission was reported in Brazil in 1965. Nowadays the oral route is the transmission mode in 50% of cases in the Amazon river zone. Oral infection is produced by the ingestion of infected triatomine bugs or their feces, undercooked meat from infested host animals and food contaminated with urine or anal secretion of infected marsupials. Therefore travelers to those zones should be advised about care to be taken with ingested food. In Chile, this new mode of transmission should be considered in public health policies.

  13. Complications of equine oral surgery.

    PubMed

    Dixon, Padraic M; Hawkes, Claire; Townsend, Neil

    2008-12-01

    The vast majority of equine oral procedures are dental-related and, unless great care is taken, almost all such procedures have the potential to cause marked short- or long-term damage to other oral structures. This review of the more common complications of oral surgery begins at the rostral oral cavity with procedures of the incisors, and then moves caudally to deal with complications related to procedures of wolf teeth and cheek teeth, including salivary duct disruption and dental sinusitis. Finally, complications associated with maxillary and mandibular fractures are discussed.

  14. Improving oral hygiene for patients.

    PubMed

    Bonetti, Debbie; Hampson, Victoria; Queen, Kerry; Kirk, Donna; Clarkson, Jan; Young, Linda

    2015-01-13

    Systematic reviews and patient safety initiatives recommend that oral hygiene should be part of routine patient care. However, evidence suggests it is often neglected in hospitals and care homes. Research recommends encouraging beliefs that support oral hygiene, and teaching nurses appropriate skills, as necessary prerequisites to implementing best practice in hospital wards. This article describes a pilot study of an educational workshop on oral hygiene. Results from the pilot study suggest that this workshop is a feasible intervention for a service-wide trial. The literature suggests that other interventions are required to complement this approach if nurses are to make oral hygiene a priority in daily patient care.

  15. Are all repeats created equal? Understanding DNA repeats at an individual level.

    PubMed

    Yang, Jinpu; Li, Fei

    2017-02-01

    Repetitive DNA sequences, comprising up to 50 % of the genome in all eukaryotes, play important roles in a wide range of cellular functions, such as transcriptional regulation, genome stability, and cellular differentiation. However, due to technical difficulties in differentiating their sequences, DNA repeats remain one of the most mysterious parts of eukaryotic genomes. Key questions, such as how repetitive entities behave at individual level and how the internal architecture of these repeats is organized, are still poorly understood. Recent advances from our group reveal unexpected position-dependent variation within tandem DNA repeats in fission yeast. Despite sharing identical DNA sequences, the peri-centromeric repeats are organized into diverse epigenetic states and chromatin structures. We demonstrate that this position-dependent variation requires key heterochromatin factors and condensin. Our works further suggest that the peri-centromeric repeats are organized into distinct higher order structures that ensure a proper positioning of CENP-A, the centromere-specific histone H3 variant, to centromeres. These most recent developments offer insights into the mechanisms underlying the position effect within tandem DNA arrays, and have broad implications in the field of epigenetics and chromatin biology.

  16. Adult Dental Health Survey 2009: implications of findings for clinical practice and oral health policy.

    PubMed

    Watt, R G; Steele, J G; Treasure, E T; White, D A; Pitts, N B; Murray, J J

    2013-01-01

    This is the final paper in a series reporting on the results of the 2009 Adult Dental Health Survey. Since 1968 national adult surveys have been repeated every decade with broadly similar methods providing a unique overview of trends in oral health over a 40-year period. This paper aims to explore the implications for dentists and oral health policy of the key results from the Adult Dental Health Survey 2009. Although repeat, cross-sectional, epidemiological surveys provide very valuable data on trends in disease patterns, they do not provide answers to test causal relationships and therefore cannot identify the causes for the significant improvements in oral health over the last 40 years. Evidence would indicate, however, that broad societal shifts in population norms and behaviours, combined with changes in clinical diagnostic criteria, treatment planning and clinical procedures are the main reasons for the changes that have taken place. Key implications of the survey results include the need to monitor, support and maintain the good state of oral health of the increasing proportion of younger adults with relatively simple treatment needs. A smaller number of young and middle aged adults but a significant proportion of older adults will have far more complex treatment needs requiring advanced restorative and periodontal care. Future oral health policy will need to address oral health inequalities, encourage skill mix and promote and facilitate the dental profession to deliver appropriate and high quality care relevant to the needs of their local population.

  17. Pharmacokinetics of cimetidine in dogs after oral administration of cimetidine tablets.

    PubMed

    Le Traon, G; Burgaud, S; Horspool, L J I

    2009-06-01

    Long-term oral treatment with cimetidine is recommended to reduce vomiting in dogs with chronic gastritis. Despite this, few studies have specifically examined the plasma disposition and pharmacokinetics of cimetidine in dogs, particularly following repeated oral administration. The pharmacokinetics of cimetidine following oral administration as tablets was investigated in healthy dogs. Cimetidine was absorbed rapidly post-treatment (t(max) = 0.5 h). A mean absolute bioavailability of 75% was calculated following a single oral administration of 5 mg cimetidine/kg body weight. After intravenous administration, a plasma half-life of 1.6 h was calculated. Repeated oral administration at the recommended dose rate and regime (5 mg/kg body weight three times daily) for 30 consecutive days did not lead to any accumulation of cimetidine in plasma. Food intake concomitant with oral administration of cimetidine delayed (t(max) = 2.25 h) and decreased the rate and extent of absorption (AUC) by about 40%. Cimetidine was well absorbed in fasted dogs. Administration of food decreased the bioavailability of cimetidine by 40%. Cimetidine does not accumulate over time in plasma when administered long term to dogs.

  18. Repeats identification using improved suffix trees.

    PubMed

    Huo, Hongwei; Wang, Xiaowu; Stojkovic, Vojislav

    2009-01-01

    The suffix tree data structure plays an important role in the efficient implementations of some querying algorithms. This paper presents the fast Rep(eats)Seeker algorithm for repeats identification based on the improvements of suffix tree construction. The leaf nodes and the branch nodes are numbered in different ways during the construction of a suffix tree and extra information is added to the branch nodes. The experimental results show that improvements reduce the running time of the RepSeeker algorithm without losing the accuracy. The experimental results coincide with the theoretical expectations.

  19. Distillation by repeated measurements: Continuous spectrum case

    SciTech Connect

    Bellomo, Bruno; Compagno, Giuseppe; Nakazato, Hiromichi; Yuasa, Kazuya

    2010-12-15

    Repeated measurements on one part of a bipartite system strongly affect the other part that is not measured, the dynamics of which is regulated by an effective contracted evolution operator. When the spectrum of this operator is discrete, the nonmeasured system is driven into a pure state, irrespective of the initial state, provided that the spectrum satisfies certain conditions. We show here that, even in the case of continuous spectrum, an effective distillation can occur under rather general conditions. We confirm it by applying our formalism to a simple model.

  20. Platelet peripheral benzodiazepine receptors in repeated stress

    SciTech Connect

    Dar, D.E.; Bidder, M.; Gavish, M. ); Weizman, A.; Karp, L.; Tyano, S. ); Grinshpoon, A.; Bleich, A.

    1991-01-01

    ({sup 3}H)PK 11195 binding to platelet membranes and plasma stress hormones were studied in soldiers at the beginning of a parachute training course, following 6 days of preparatory exercises, and after the fourth actual parachute jump. A slight reduction (15%; NS) in the number of peripheral benzodiazepine receptors (PBR) was detected at the end of the exercise period, prior to the first jump. Reduced density of PBR was observed immediately after the repeated actual jumps. Equilibrium dissociation constants were not affected by the stressful situation. Plasma cortisol and prolactin levels remained unaltered during the entire study period.