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Sample records for acute oral ld50

  1. The acute lethal dose 50 (LD50) of caffeine in albino rats.

    PubMed

    Adamson, Richard H

    2016-10-01

    An acute LD50 is a statistically derived amount of a substance that can be expected to cause death in 50% of the animals when given by a specified route as a single dose and the animals observed for a specified time period. Although conducting routine acute toxicity testing in rodents has been criticized, it can serve useful functions and also have practical implications. Material safety data sheets (MSDS) will reflect the acute toxicity of a substance and may require workers to wear protective gear, if appropriate, based on the LD50. There is no information in the scientific published literature which calculates a mean LD50 and standard deviation for caffeine administered orally to rats, using studies performed under good laboratory practice (GLP) or equivalent. This report does that and should be useful to manufacturers, packagers, transporters and regulators of this material. Using data from studies that are reproducible and reliable, the most accurate estimate of the acute LD50 of caffeine administered orally in male albino rats is hereby reported to be 367/mg/kg.

  2. The acute lethal dose 50 (LD50) of caffeine in albino rats.

    PubMed

    Adamson, Richard H

    2016-10-01

    An acute LD50 is a statistically derived amount of a substance that can be expected to cause death in 50% of the animals when given by a specified route as a single dose and the animals observed for a specified time period. Although conducting routine acute toxicity testing in rodents has been criticized, it can serve useful functions and also have practical implications. Material safety data sheets (MSDS) will reflect the acute toxicity of a substance and may require workers to wear protective gear, if appropriate, based on the LD50. There is no information in the scientific published literature which calculates a mean LD50 and standard deviation for caffeine administered orally to rats, using studies performed under good laboratory practice (GLP) or equivalent. This report does that and should be useful to manufacturers, packagers, transporters and regulators of this material. Using data from studies that are reproducible and reliable, the most accurate estimate of the acute LD50 of caffeine administered orally in male albino rats is hereby reported to be 367/mg/kg. PMID:27461039

  3. Assessment of the predictive capacity of the 3T3 Neutral Red Uptake cytotoxicity test method to identify substances not classified for acute oral toxicity (LD50>2000 mg/kg): results of an ECVAM validation study.

    PubMed

    Prieto, Pilar; Cole, Thomas; Curren, Rodger; Gibson, Rosemary M; Liebsch, Manfred; Raabe, Hans; Tuomainen, Anita M; Whelan, Maurice; Kinsner-Ovaskainen, Agnieszka

    2013-04-01

    Assessing chemicals for acute oral toxicity is a standard information requirement of regulatory testing. However, animal testing is now prohibited in the cosmetics sector in Europe, and strongly discouraged for industrial chemicals. Building on the results of a previous international validation study, a follow up study was organised to assess if the 3T3 Neutral Red Uptake cytotoxicity assay could identify substances not requiring classification as acute oral toxicants under the EU regulations. Fifty-six coded industrial chemicals were tested in three laboratories, each using one of the following protocols: the previously validated protocol, an abbreviated version of the protocol and the protocol adapted for an automation platform. Predictions were very similar among the three laboratories. The assay exhibited high sensitivity (92-96%) but relatively low specificity (40-44%). Three chemicals were under predicted. Assuming that most industrial chemicals are not likely to be acutely toxic, this test method could prove a valuable component of an integrated testing strategy, a read-across argument, or weight-of-evidence approach to identify non toxic chemicals (LD50>2000 mg/kg). However, it is likely to under predict chemicals acting via specific mechanisms of action not captured by the 3T3 test system, or which first require biotransformation in vivo. PMID:23246604

  4. Assessment of the predictive capacity of the 3T3 Neutral Red Uptake cytotoxicity test method to identify substances not classified for acute oral toxicity (LD50>2000 mg/kg): results of an ECVAM validation study.

    PubMed

    Prieto, Pilar; Cole, Thomas; Curren, Rodger; Gibson, Rosemary M; Liebsch, Manfred; Raabe, Hans; Tuomainen, Anita M; Whelan, Maurice; Kinsner-Ovaskainen, Agnieszka

    2013-04-01

    Assessing chemicals for acute oral toxicity is a standard information requirement of regulatory testing. However, animal testing is now prohibited in the cosmetics sector in Europe, and strongly discouraged for industrial chemicals. Building on the results of a previous international validation study, a follow up study was organised to assess if the 3T3 Neutral Red Uptake cytotoxicity assay could identify substances not requiring classification as acute oral toxicants under the EU regulations. Fifty-six coded industrial chemicals were tested in three laboratories, each using one of the following protocols: the previously validated protocol, an abbreviated version of the protocol and the protocol adapted for an automation platform. Predictions were very similar among the three laboratories. The assay exhibited high sensitivity (92-96%) but relatively low specificity (40-44%). Three chemicals were under predicted. Assuming that most industrial chemicals are not likely to be acutely toxic, this test method could prove a valuable component of an integrated testing strategy, a read-across argument, or weight-of-evidence approach to identify non toxic chemicals (LD50>2000 mg/kg). However, it is likely to under predict chemicals acting via specific mechanisms of action not captured by the 3T3 test system, or which first require biotransformation in vivo.

  5. Comparative study of the assay of Artemia salina L. and the estimate of the medium lethal dose (LD50 value) in mice, to determine oral acute toxicity of plant extracts.

    PubMed

    Logarto Parra, A; Silva Yhebra, R; Guerra Sardiñas, I; Iglesias Buela, L

    2001-09-01

    Artemia salina L. (Artemiidae), the brine shrimp larva, is an invertebrate used in the alternative test to determine toxicity of chemical and natural products. In this study the Medium Lethal Concentrations (LC50 value) of 20 plant extracts, Aloe vera (L.) Burm. F. (Aloeaceae), Artemisia absinthium L. (Asteraceae); Citrus aurantium L. (Rutaceae); Cymbopogon citratus (DC. Ex Nees) Stapf (Poaceae); Datura stramonium L. (Solanaceae); Justicia pectoralis Jacq. (Acanthaceae); Musa x paradisiaca L. (Musaceae); Ocimum basilicum L.; O. gratissimum L.; O. tenuiflorum L. (Lamiaceae); Pimenta dioica (L.) Merr. (Myrtaceae); Piper auritum Kunth (Piperaceae); Plantago major L. (Plantaginaceae); Plectranthus amboinicus (Lour.) Spreng. (Lamiaceae); Ruta graveolens L. (Rutaceae); Senna alata (L.) Roxb. (Fabaceae); Stachytarpheta jamaicensis (L.) Vahl (Verbenaceae); and Thuja occidentalis L. (Cupressaceae), were determined using Artemia salina L. (Artemiidae), with the objective of relating the results to the LD50 values reported in mice (tested at three concentrations: 10, 100, and 1000 microg/mL, for each extract). We found good correlation between the in vivo and the in vitro tests (r = 0.85 p < 0.05), and this method is a useful tool for predicting oral acute toxicity in plant extracts. PMID:11695884

  6. Comparative study of the assay of Artemia salina L. and the estimate of the medium lethal dose (LD50 value) in mice, to determine oral acute toxicity of plant extracts.

    PubMed

    Logarto Parra, A; Silva Yhebra, R; Guerra Sardiñas, I; Iglesias Buela, L

    2001-09-01

    Artemia salina L. (Artemiidae), the brine shrimp larva, is an invertebrate used in the alternative test to determine toxicity of chemical and natural products. In this study the Medium Lethal Concentrations (LC50 value) of 20 plant extracts, Aloe vera (L.) Burm. F. (Aloeaceae), Artemisia absinthium L. (Asteraceae); Citrus aurantium L. (Rutaceae); Cymbopogon citratus (DC. Ex Nees) Stapf (Poaceae); Datura stramonium L. (Solanaceae); Justicia pectoralis Jacq. (Acanthaceae); Musa x paradisiaca L. (Musaceae); Ocimum basilicum L.; O. gratissimum L.; O. tenuiflorum L. (Lamiaceae); Pimenta dioica (L.) Merr. (Myrtaceae); Piper auritum Kunth (Piperaceae); Plantago major L. (Plantaginaceae); Plectranthus amboinicus (Lour.) Spreng. (Lamiaceae); Ruta graveolens L. (Rutaceae); Senna alata (L.) Roxb. (Fabaceae); Stachytarpheta jamaicensis (L.) Vahl (Verbenaceae); and Thuja occidentalis L. (Cupressaceae), were determined using Artemia salina L. (Artemiidae), with the objective of relating the results to the LD50 values reported in mice (tested at three concentrations: 10, 100, and 1000 microg/mL, for each extract). We found good correlation between the in vivo and the in vitro tests (r = 0.85 p < 0.05), and this method is a useful tool for predicting oral acute toxicity in plant extracts.

  7. Oral LD50 toxicity modeling and prediction of per- and polyfluorinated chemicals on rat and mouse.

    PubMed

    Bhhatarai, Barun; Gramatica, Paola

    2011-05-01

    Quantitative structure-activity relationship (QSAR) analyses were performed using the LD(50) oral toxicity data of per- and polyfluorinated chemicals (PFCs) on rodents: rat and mouse. PFCs are studied under the EU project CADASTER which uses the available experimental data for prediction and prioritization of toxic chemicals for risk assessment by using the in silico tools. The methodology presented here applies chemometrical analysis on the existing experimental data and predicts the toxicity of new compounds. QSAR analyses were performed on the available 58 mouse and 50 rat LD(50) oral data using multiple linear regression (MLR) based on theoretical molecular descriptors selected by genetic algorithm (GA). Training and prediction sets were prepared a priori from available experimental datasets in terms of structure and response. These sets were used to derive statistically robust and predictive (both internally and externally) models. The structural applicability domain (AD) of the models were verified on 376 per- and polyfluorinated chemicals including those in REACH preregistration list. The rat and mouse endpoints were predicted by each model for the studied compounds, and finally 30 compounds, all perfluorinated, were prioritized as most important for experimental toxicity analysis under the project. In addition, cumulative study on compounds within the AD of all four models, including two earlier published models on LC(50) rodent analysis was studied and the cumulative toxicity trend was observed using principal component analysis (PCA). The similarities and the differences observed in terms of descriptors and chemical/mechanistic meaning encoded by descriptors to prioritize the most toxic compounds are highlighted.

  8. Consensus Modeling of Oral Rat Acute Toxicity

    EPA Science Inventory

    An acute toxicity dataset (oral rat LD50) with about 7400 compounds was compiled from the ChemIDplus database. This dataset was divided into a modeling set and a prediction set. The compounds in the prediction set were selected so that they were present in the modeling set used...

  9. Acute oral and percutaneous toxicity of pesticides to mallards: Correlations with mammalian toxicity data

    USGS Publications Warehouse

    Hudson, R.H.; Haegele, M.A.; Tucker, R.K.

    1979-01-01

    Acute oral (po) and 24-hr percutaneous (perc) LD50 values for 21 common pesticides (19 anticholinesterases, of which 18 were organophosphates, and one was a carbamate; one was an organochlorine central nervous system stimulant; and one was an organonitrogen pneumotoxicant) were determined in mallards (Anas platyrhynchos). Three of the pesticides tested were more toxic percutaneously than orally. An index to the percutaneous hazard of a pesticide, the dermal toxicity index (DTI = po LD50/perc LD50 ? 100), was also calculated for each pesticide. These toxicity values in mallards were compared with toxicity data for rats from the literature. Significant positive correlations were found between log po and log percutaneous LD50 values in mallards (r = 0.65, p 0.10). Variations in percutaneous methodologies are discussed with reference to interspecies variation in toxicity values. It is recommended that a mammalian DTI value approaching 30 be used as a guideline for the initiation of percutaneous toxicity studies in birds, when the po LD50 and/or projected percutaneous LD50 are less than expected field exposure levels.

  10. Acute oral toxicities of wildland fire control chemicals to birds.

    PubMed

    Vyas, Nimish B; Spann, James W; Hill, Elwood F

    2009-03-01

    Wildland fire control chemicals are released into the environment by aerial and ground applications to manage rangeland, grassland, and forest fires. Acute oral 24h median lethal dosages (LD50) for three fire retardants (Fire-Trol GTS-R, Phos-Chek D-75F, and Fire-Trol LCG-R) and two Class A fire suppressant foams (Silv-Ex and Phos-Chek WD881) were estimated for northern bobwhites, Colinus virginianus, American kestrels, Falco sparverius, and red-winged blackbirds, Agelaius phoeniceus. The LD50s of all chemicals for the bobwhites and red-winged blackbirds and for kestrels dosed with Phos-Chek WD881 and Silv-Ex were above the predetermined 2000mg chemical/kg body mass regulatory limit criteria for acute oral toxicity. The LD50s were not quantifiable for kestrels dosed with Fire-Trol GTS-R, Phos-Chek D-75F, and Fire-Trol LCG-R because of the number of birds which regurgitated the dosage. These chemicals appear to be of comparatively low order of acute oral toxicity to the avian species tested.

  11. Acute oral toxicities of wildland fire control chemicals to birds

    USGS Publications Warehouse

    Vyas, N.B.; Spann, J.W.; Hill, E.F.

    2009-01-01

    Wildland fire control chemicals are released into the environment by aerial and ground applications to manage rangeland, grassland, and forest fires. Acute oral 24 h median lethal dosages (LD50) for three fire retardants (Fire-Trol GTS-R?, Phos-Chek D-75F?, and Fire-Trol LCG-R?) and two Class A fire suppressant foams (Silv-Ex? and Phos-Chek WD881?) were estimated for northern bobwhites, Colinus virginianus, American kestrels, Falco sparverius, and red-winged blackbirds, Agelaius phoeniceus. The LD50s of all chemicals for the bobwhites and red-winged blackbirds and for kestrels dosed with Phos-Chek WD881? and Silv-Ex? were above the predetermined 2000 mg chemical/kg body mass regulatory limit criteria for acute oral toxicity. The LD50s were not quantifiable for kestrels dosed with Fire-Trol GTS-R?, Phos-Chek D-75F?, and Fire-Trol LCG-R? because of the number of birds which regurgitated the dosage. These chemicals appear to be of comparatively low order of acute oral toxicity to the avian species tested.

  12. Optimization irradiation conditions for determination of LD50 in pigs.

    PubMed

    Procházka, Z; Hampl, J; Sedlácek, M; Rodák, L

    1975-11-01

    Radiation LD50/30 values were determined in 36 twelve-week-old pigs (with a mean body weigth of 21 kg) exposed to whole-body X-ray irradiation on a revolvable table rotated at a rate of 2.5 rpm using the following conditions: 180 kV, 15 mA, focal distance 79 cm, HVT 0.9 mm Cu, dose rate 2.42 X 10(-3) to 2.68 X 10(-3) C kg-1 min-1 (9.4 to 10.4 R/min) depending upon the animal size. The coefficient of mean irradiation uniformity was 1.4. Under these conditions the LD50/30 for pigs was found to be 5.89 X 10(-2) C kg-1 min-1 (228.3 R) with the biological range of effectiveness being 5.22 X 10(-2) to 6.90 X 10-(2) C kg-1 (202.4 to 267.6 R). Furthermore experiments on 77 pigs showed that LD50 determined in this study had actually the median lethal effect.

  13. Acute and oral subchronic toxicity of D-003 in rats.

    PubMed

    Gámez, R; Mas, R; Noa, M; Menéndez, R; Alemán, C; Acosta, P; García, H; Hernández, C; Amor, A; Pérez, J; Goicochea, E

    2000-12-20

    D-003 is a mixture of higher aliphatic primary acids purified from sugar cane wax (Saccharum officinarum) with cholesterol-lowering and antiplatelet effects experimentally proven. The present work reports the results of two studies investigating the acute and subchronic oral toxicity of D-003 in rats. Oral acute toxicity of D-003 (2000 mg/kg) was investigated according to the Acute Toxic Class (ATC) method (an alternative for the classical LD(50) test), which was performed in Wistar rats. The results obtained in this study defined D-003 oral acute toxicity as unclassified. In the subchronic study, rats of both sexes were orally treated with D-003 at 50, 200 and 1250 mg/kg for 90 days. At this time, animals were sacrificed. No evidence of treatment-related toxicity was detected during the study. Thus, data analysis of body weight gain, food consumption, clinical observations, blood biochemical, haematology, organ weight ratios and histopathological findings did not show significant differences between control and treated groups. It is concluded that D-003 orally administered to rats was safe and that no drug-related toxicity was detected even at the highest doses investigated in both acute (2000 mg/kg) and subchronic (1250 mg/kg) studies.

  14. Determination of acute oral toxicity of flumethrin in honey bees.

    PubMed

    Oruc, H H; Hranitz, J M; Sorucu, A; Duell, M; Cakmak, I; Aydin, L; Orman, A

    2012-12-01

    Flumethrin is one of many pesticides used for the control and treatment of varroatosis in honey bees and for the control of mosquitoes and ticks in the environment. For the control of varroatosis, flumethrin is applied to hives formulated as a plastic strip for several weeks. During this time, honey bees are treated topically with flumethrin, and hive products may accumulate the pesticide. Honey bees may indirectly ingest flumethrin through hygienic behaviors during the application period and receive low doses of flumethrin through comb wax remodeling after the application period. The goal of our study was to determine the acute oral toxicity of flumethrin and observe the acute effects on motor coordination in honey bees (Apis mellifera anatoliaca). Six doses (between 0.125 and 4.000 microg per bee) in a geometric series were studied. The acute oral LD50 of flumethrin was determined to be 0.527 and 0.178 microg per bee (n = 210, 95% CI) for 24 and 48 h, respectively. Orally administered flumethrin is highly toxic to honey bees. Oral flumethrin disrupted the motor coordination of honey bees. Honey bees that ingested flumethrin exhibited convulsions in the antennae, legs, and wings at low doses. At higher doses, partial and total paralysis in the antennae, legs, wings, proboscises, bodies, and twitches in the antennae and legs were observed.

  15. Acute toxicity of some synthetic cyanogens in rats and their response to oral treatment with alpha-ketoglutarate.

    PubMed

    Bhattacharya, R; Satpute, R M; Hariharakrishnan, J; Tripathi, H; Saxena, P B

    2009-09-01

    Oral toxicity of several cyanogens and their reversal by alpha-ketoglutarate (A-KG; oral) were studied in rats. LD(50) of acetonitrile (ATCN), acrylonitrile (ACN), malononitrile (MCN), propionitrile (PCN), sodium nitroprusside (SNP), and succinonitrile (SCN) was 4891, 143.3, 69.8, 122.9, 69.8 and 488.7 mg/kg, respectively while the protection index of A-KG (ratio of LD(50) of cyanogens in the presence or absence of A-KG) was>2.0 against MCN (7.6), PCN (2.7) and SNP (3.6) only. We further studied the efficacy of A-KG against acute toxicity of these three cyanogens (0.75 LD(50)) on various hematological and biochemical variables in blood and soft tissues 24h post-exposure. We observed increase in white blood cells (SNP), plasma alanine (PCN, SNP) and aspartate (PCN) aminotransferase, lactate dehydrogenase (MCN, PCN, SNP), Na(+) (MCN, PCN) and cyanide (PCN), and decrease in K(+) (MCN, SNP) accompanied by an increase in brain, kidney and liver malondialdehyde (PCN), decrease in brain glutathione peroxidase, glutathione reductase (PCN, SNP), reduced glutathione (MCN, PCN, SNP) and cytochrome oxidase (PCN), liver rhodanese (PCN, SNP), and kidney cytochrome oxidase (PCN). The study indicates that (i) PCN was most toxic among all the cyanogens and (ii) beside cyanide, A-KG could be considered as an effective antidote for cyanogens.

  16. Acute toxicity of four anticholinesterase insecticides to American kestrels, eastern screech-owls and northern bobwhites

    USGS Publications Warehouse

    Wiemeyer, Stanley N.; Sparling, D.W.

    1991-01-01

    American kestrels (Falco sparverius), eastern screech-owls (Otus asio), and northern bobwhites (Colinus virginianus) were given single acute oral doses of four widely diverse anticholinesterase pesticides: EPN, fenthion, carbofuran, and monocrotophos. LD50s, based on birds that died within 5 d of dosage, were computed for each chemical in each species. Sex differences in the sensitivity of northern bobwhites in reproductive condition were examined. American kestrels were highly sensitive to all chemicals tested (LD50s 0.6--4.0 mg/kg). Eastern screech-owls were highly tolerant to EPN (LD50 274 mg/kg) but sensitive to the remaining chemicals (LD50s 1.5-3.9 mg/kg). Northern bobwhites were highly sensitive to monocrotophos (LD50 0.8 mg/kg) and less sensitive to the remaining chemicals (LD50s 4.6--31 mg/kg). Female bobwhites (LD50 3.1 mg/kg) were more sensitive to fenthion than males (LD50 7.0 mg/kg). Mean percent depression of brain cho[inesterase (ChE) of birds that died on the day of dosing exceeded 65% for all chemicals in all species. The response of one species to a given pesticide should not be used to predict the sensitivity of other species to the same pesticide. The need for research on several topics is discussed

  17. Assessment of Acute Oral and Dermal Toxicity of 2 Ethyl-Carbamates with Activity against Rhipicephalus microplus in Rats

    PubMed Central

    Prado-Ochoa, María Guadalupe; Gutiérrez-Amezquita, Ricardo Alfonso; Abrego-Reyes, Víctor Hugo; Velázquez-Sánchez, Ana María; Muñoz-Guzmán, Marco Antonio; Ramírez-Noguera, Patricia; Angeles, Enrique; Alba-Hurtado, Fernando

    2014-01-01

    The acute oral and dermal toxicity of two new ethyl-carbamates (ethyl-4-bromophenyl-carbamate and ethyl-4-chlorophenyl-carbamate) with ixodicide activity was determined in rats. The oral LD50 of each carbamate was 300 to 2000 mg/kg, and the dermal LD50 of each carbamate was >5000 mg/kg. Clinically, the surviving rats that had received oral doses of each carbamate showed decreased weight gain (P < 0.05) and had slight nervous system manifestations. These clinical signs were evident from the 300 mg/kg dose and were reversible, whereas the 2000 mg/kg dose caused severe damage and either caused their death or was motive for euthanasia. At necropsy, these rats had dilated stomachs and cecums with diffuse congestion, as well as moderate congestion of the liver. Histologically, the liver showed slight degenerative lesions, binucleated hepatocytes, focal coagulative necrosis, and congestion areas; the severity of the lesions increased with dosage. Furthermore, an slight increase in gamma-glutamyltransferase, lactate dehydrogenase, and creatinine was observed in the plasma. The dermal application of the maximum dose (5000 mg/kg) of each carbamate did not cause clinical manifestations or liver and skin alterations. This finding demonstrates that the carbamates under study have a low oral hazard and low acute dermal toxicity. PMID:24883331

  18. Emerging toxicity of 5,6-methylenedioxy-2-aminoindane (MDAI): Pharmacokinetics, behaviour, thermoregulation and LD50 in rats.

    PubMed

    Páleníček, Tomáš; Lhotková, Eva; Žídková, Monika; Balíková, Marie; Kuchař, Martin; Himl, Michal; Mikšátková, Petra; Čegan, Martin; Valeš, Karel; Tylš, Filip; Horsley, Rachel R

    2016-08-01

    MDAI (5,6-Methylenedioxy-2-aminoindane) has a reputation as a non-neurotoxic ecstasy replacement amongst recreational users, however the drug has been implicated in some severe and lethal intoxications. Due to this, and the fact that the drug is almost unexplored scientifically we investigated a broad range of effects of acute MDAI administration: pharmacokinetics (in sera, brain, liver and lung); behaviour (open field; prepulse inhibition, PPI); acute effects on thermoregulation (in group-/individually-housed rats); and systemic toxicity (median lethal dose, LD50) in Wistar rats. Pharmacokinetics of MDAI was rapid, maximum median concentration in serum and brain was attained 30min and almost returned to zero 6h after subcutaneous (sc.) administration of 10mg/kg MDAI; brain/serum ratio was ~4. MDAI particularly accumulated in lung tissue. In the open field, MDAI (5, 10, 20 and 40mg/kg sc.) increased exploratory activity, induced signs of behavioural serotonin syndrome and reduced locomotor habituation, although by 60min some effects had diminished. All doses of MDAI significantly disrupted PPI and the effect was present during the onset of its action as well as 60min after treatment. Unexpectedly, 40mg/kg MDAI killed 90% of animals in the first behavioural test, hence LD50 tests were conducted which yielded 28.33mg/kg sc. and 35mg/kg intravenous but was not established up to 40mg/kg after gastric administration. Disseminated intravascular coagulopathy (DIC) with brain oedema was concluded as a direct cause of death in sc. treated animals. Finally, MDAI (10, 20mg/kg sc.) caused hyperthermia and perspiration in group-housed rats. In conclusion, the drug had fast pharmacokinetics and accumulated in lipohilic tissues. Behavioural findings were consistent with mild, transient stimulation with anxiolysis and disruption of sensorimotor processing. Together with hyperthermia, the drug had a similar profile to related entactogens, especially 3

  19. Acute Oral Toxicity and Histopathological Study of Combination of Endosulfan and Cypermethrin in Wistar Rats

    PubMed Central

    Raj, Jaya; Mohineesh; Ray, Ruma; Dogra, T. D.; Raina, Anupuma

    2013-01-01

    Background: Endosulfan, a neurotoxic organochlorine insecticide and cypermethrin, a synthetic pyrethroid insecticide used to control pests in domestic, industrial, and agricultural situations. Materials and Methods: The present study was carried out to investigate the acute oral toxicity, behavioral and histopathological changes of combination of endosulfan and cypermethrin in albino rats. According to Miller and Tainter analysis method, at 48 h, LD50 value of combination of endosulfan and cypermethrin (ratio 1:1) in rats was found to be 691.83 mg/kg bw by oral gavage. Results: When combination of both these pesticides was administered orally at concentration of 103.72 mg/kg bw, 172.95 mg/kg bw and 207.50 mg/kg bw, respectively, as a single dose, no significant changes in behavior of rats was observed, neither in dosed nor in control group of rats. Combination of endosulfan- and cypermethrin-treated rats showed mild histopathological changes in liver and kidney in group IV (207.50 mg/kg BW) as compared to the control. However, no significant changes were observed in brain and small intestine at either dose of combination of endosulfan and cypermethrin with respect to control. Conclusion: Thus, the present study, first of its kind in India, demonstrated the oral toxicity, behavioral, and histo-architectual alterations after induction of combination of endosulfan and cypermethrin at acute doses in Wistar rats. PMID:23833440

  20. Acute oral toxicity of sodium cyanide in birds

    USGS Publications Warehouse

    Wiemeyer, Stanley N.; Hill, E.F.; Carpenter, J.W.; Krynitsky, A.J.

    1986-01-01

    Sensitivities of six avian species, black vulture (Coragyps atratus), American kestrel (Falco sparverius), Japanese quail (Coturnix japonica), domestic chicken (Gallus domesticus), eastern screech-owl (Otus asio), and European starling (Sturnus vulgaris), to acute poisoning by sodium cyanide (NaCN) were compared by single dose LD50's. Three species, domestic chickens, black vultures, and turkey vultures (Cathartes aura), were dosed with NaCN to determine cyanide residues in those that died and also in survivors, in addition to postmortem fate. Three flesh-eating species (black vulture, American kestrel, and eastern screech-owl; LD50's 4.0-8.6 mg/kg) were more sensitive to NaCN than three species (Japanese quail, domestic chicken, and European starling; LD50's 9.4-21 mg/kg) that fed predominantly on plant material. Elevated concentrations of cyanide were found in the blood of birds that died of cyanide poisoning; however, concentrations in birds that died overlapped those in survivors. Blood was superior to liver as the tissue of choice for detecting cyanide exposure. No gross pathological changes related to dosing were observed at necropsy.

  1. Sensitivity of species to chemicals: dose-response characteristics for various test types (LC(50), LR(50) and LD(50)) and modes of action.

    PubMed

    Hendriks, A Jan; Awkerman, Jill A; de Zwart, Dick; Huijbregts, Mark A J

    2013-11-01

    While variable sensitivity of model species to common toxicants has been addressed in previous studies, a systematic analysis of inter-species variability for different test types, modes of action and species is as of yet lacking. Hence, the aim of the present study was to identify similarities and differences in contaminant levels affecting cold-blooded and warm-blooded species administered via different routes. To that end, data on lethal water concentrations LC50, tissue residues LR50 and oral doses LD50 were collected from databases, each representing the largest of its kind. LC50 data were multiplied by a bioconcentration factor (BCF) to convert them to internal concentrations that allow for comparison among species. For each endpoint data set, we calculated the mean and standard deviation of species' lethal level per compound. Next, the means and standard deviations were averaged by mode of action. Both the means and standard deviations calculated depended on the number of species tested, which is at odds with quality standard setting procedures. Means calculated from (BCF) LC50, LR50 and LD50 were largely similar, suggesting that different administration routes roughly yield similar internal levels. Levels for compounds interfering biochemically with elementary life processes were about one order of magnitude below that of narcotics disturbing membranes, and neurotoxic pesticides and dioxins induced death in even lower amounts. Standard deviations for LD50 data were similar across modes of action, while variability of LC50 values was lower for narcotics than for substances with a specific mode of action. The study indicates several directions to go for efficient use of available data in risk assessment and reduction of species testing.

  2. Sensitivity of species to chemicals: dose-response characteristics for various test types (LC(50), LR(50) and LD(50)) and modes of action.

    PubMed

    Hendriks, A Jan; Awkerman, Jill A; de Zwart, Dick; Huijbregts, Mark A J

    2013-11-01

    While variable sensitivity of model species to common toxicants has been addressed in previous studies, a systematic analysis of inter-species variability for different test types, modes of action and species is as of yet lacking. Hence, the aim of the present study was to identify similarities and differences in contaminant levels affecting cold-blooded and warm-blooded species administered via different routes. To that end, data on lethal water concentrations LC50, tissue residues LR50 and oral doses LD50 were collected from databases, each representing the largest of its kind. LC50 data were multiplied by a bioconcentration factor (BCF) to convert them to internal concentrations that allow for comparison among species. For each endpoint data set, we calculated the mean and standard deviation of species' lethal level per compound. Next, the means and standard deviations were averaged by mode of action. Both the means and standard deviations calculated depended on the number of species tested, which is at odds with quality standard setting procedures. Means calculated from (BCF) LC50, LR50 and LD50 were largely similar, suggesting that different administration routes roughly yield similar internal levels. Levels for compounds interfering biochemically with elementary life processes were about one order of magnitude below that of narcotics disturbing membranes, and neurotoxic pesticides and dioxins induced death in even lower amounts. Standard deviations for LD50 data were similar across modes of action, while variability of LC50 values was lower for narcotics than for substances with a specific mode of action. The study indicates several directions to go for efficient use of available data in risk assessment and reduction of species testing. PMID:23932508

  3. Antidiarrheal activity and acute oral toxicity of Mentha longifolia L. essential oil

    PubMed Central

    Jalilzadeh-Amin, Ghader; Maham, Massoud

    2015-01-01

    Objectives: Mentha longifolia L. (Lamiaceae) is an annual herb that is used in the Iranian traditional medicine for treating stomach and intestinal disorders. The purpose of this study was to determine the protective effect of M. longifolia on experimental diarrhea in a rat model. Materials and Methods: The antidiarrheal activity of essential oil of M. longifolia (20-80 mg/kg) was investigated against castor oil-induced diarrhea in rats using loperamide as the standard reference drug. In acute toxicity evaluation, rats were orally administrated with single dose of EOML at doses ranging from 10 to 1000 mg/kg. Results: EOML caused a significant (p<0.05) and dose-dependent decrease of gastrointestinal transit, nevertheless, it could not block the inhibitory effect of atropine (0.1 mg/kg). EOML at oral doses of 20 and 80 mg/kg protected the animals against castor oil-induced diarrhea significantly (p<0.05). EOML decreased the intestinal fluid accumulation as indicated by the significantly (p<0.05 to p<0.001) decrease compared to control. The oral LD50 of EOML was found to be 470 mg/kg in rat. Conclusion: Since the inhibition of intestinal hyperactivity and hypersecretory are the bases of the treatment of diarrhea, results obtained in the present study suggest that EOML is endowed with antidiarrheal activity. EOML is moderately toxic for oral medication. PMID:25949954

  4. Acute oral toxicity of chemicals in terrestrial life stages of amphibians: Comparisons to birds and mammals.

    PubMed

    Crane, Mark; Finnegan, Meaghean; Weltje, Lennart; Kosmala-Grzechnik, Sylwia; Gross, Melanie; Wheeler, James R

    2016-10-01

    Amphibians are currently the most threatened and rapidly declining group of vertebrates and this has raised concerns about their potential sensitivity and exposure to plant protection products and other chemicals. Current environmental risk assessment procedures rely on surrogate species (e.g. fish and birds) to cover the risk to aquatic and terrestrial life stages of amphibians, respectively. Whilst a recent meta-analysis has shown that in most cases amphibian aquatic life stages are less sensitive to chemicals than fish, little research has been conducted on the comparative sensitivity of terrestrial amphibian life stages. Therefore, in this paper we address the questions "What is the relative sensitivity of terrestrial amphibian life stages to acute chemical oral exposure when compared with mammals and birds?" and "Are there correlations between oral toxicity data for amphibians and data for mammals or birds?" Identifying a relationship between these data may help to avoid additional vertebrate testing. Acute oral amphibian toxicity data collected from the scientific literature and ecotoxicological databases were compared with toxicity data for mammals and birds. Toxicity data for terrestrial amphibian life stages are generally sparse, as noted in previous reviews. Single-dose oral toxicity data for terrestrial amphibian life stages were available for 26 chemicals and these were positively correlated with LD50 values for mammals, while no correlation was found for birds. Further, the data suggest that oral toxicity to terrestrial amphibian life stages is similar to or lower than that for mammals and birds, with a few exceptions. Thus, mammals or birds are considered adequate toxicity surrogates for use in the assessment of the oral exposure route in amphibians. However, there is a need for further data on a wider range of chemicals to explore the wider applicability of the current analyses and recommendations.

  5. Hypoglycemic activity and acute oral toxicity of chromium methionine complexes in mice.

    PubMed

    Tang, Hai-yan; Xiao, Qing-gui; Xu, Hong-bin; Zhang, Yi

    2015-01-01

    The hypoglycemic activity of chromium methionine (CrMet) in alloxan-induced diabetic (AID) mice was investigated and compared with those of chromium trichloride hexahydrate (CrCl3·6H2O) and chromium nicotinate (CrNic) through a 15-day feeding experiment. The acute oral toxicity of CrMet was also investigated in ICR (Institute for Cancer Research) mice by a single oral gavage. The anti-diabetic activity of CrMet was explored in detail from the aspects of body weight (BW), blood glucose, triglyceride, total cholesterol, liver glycogen levels, aspartate transaminase (AST) and alanine transaminase (ALT) levels. The obtained results showed that CrMet had beneficial effects on glucose and lipid metabolism, and might possess hepatoprotective efficacy for diabetes. Daily treatment with 500 and 1000μg Cr/kg BW of CrMet in AID mice for 15 days indicated that this low-molecular-weight organic chromium complex had better bioavailability and more beneficial effects on diabetics than CrCl3·6H2O. CrMet also had advantage over CrNic in the control of AST and ALT activities. Acute toxicity studies revealed that CrMet had low toxicity potential and relatively high safety margins in mice with the LD50 value higher than 10.0g/kg BW. These findings suggest that CrMet might be of potential value in the therapy and protection of diabetes.

  6. Estimation of acute oral toxicity in rat using local lazy learning

    PubMed Central

    2014-01-01

    Background Acute toxicity means the ability of a substance to cause adverse effects within a short period following dosing or exposure, which is usually the first step in the toxicological investigations of unknown substances. The median lethal dose, LD50, is frequently used as a general indicator of a substance’s acute toxicity, and there is a high demand on developing non-animal-based prediction of LD50. Unfortunately, it is difficult to accurately predict compound LD50 using a single QSAR model, because the acute toxicity may involve complex mechanisms and multiple biochemical processes. Results In this study, we reported the use of local lazy learning (LLL) methods, which could capture subtle local structure-toxicity relationships around each query compound, to develop LD50 prediction models: (a) local lazy regression (LLR): a linear regression model built using k neighbors; (b) SA: the arithmetical mean of the activities of k nearest neighbors; (c) SR: the weighted mean of the activities of k nearest neighbors; (d) GP: the projection point of the compound on the line defined by its two nearest neighbors. We defined the applicability domain (AD) to decide to what an extent and under what circumstances the prediction is reliable. In the end, we developed a consensus model based on the predicted values of individual LLL models, yielding correlation coefficients R2 of 0.712 on a test set containing 2,896 compounds. Conclusion Encouraged by the promising results, we expect that our consensus LLL model of LD50 would become a useful tool for predicting acute toxicity. All models developed in this study are available via http://www.dddc.ac.cn/admetus. PMID:24959207

  7. Refinement and reduction of acute oral toxicity testing: a critical review of the use of cytotoxicity data.

    PubMed

    Schrage, Arnhild; Hempel, Katja; Schulz, Markus; Kolle, Susanne N; van Ravenzwaay, Bennard; Landsiedel, Robert

    2011-07-01

    Acute oral toxicity testing is still required for the classification and labelling of chemicals, agrochemicals and related formulations. There have been increasing efforts over the last two decades to reduce the number of animals needed for this testing, according to the Three Rs concept. To evaluate the utility of an in vitro cytotoxicity test in our routine testing for acute oral toxicity, we have implemented in our laboratory the neutral red uptake (NRU) method, with Balb/c 3T3 fibroblasts after a 48-hour exposure, which was recommended in ICCVAM Report 07-4519, 2006. Initially, we tested 16 substances that had existing in vivo and in vitro data available, to prove our technical proficiency with the in vitro test. Then, testing was performed with 187 test substances, including a broad variety of chemicals, agrochemicals and formulations. The starting dose for acute oral systemic toxicity assays in rats (LD50) was estimated by using the prediction model presented in the ICCVAM validation study, and subsequently compared to the results obtained by in vivo testing performed according to, or similar to, OECD Test Guideline 423. Comparison of all of the 203 predicted LD50 values that were deduced from the in vitro IC50 values, with the in vivo results from oral toxicity studies in rats, resulted in a low overall concordance of 35%. The in vitro cytotoxicity assay achieved a good concordance of 74%, only for the weakly toxic substances (EU-GHS Cat. 4). However, it must be noted that 71% of the substances tested (i.e. 145/203) were classified as being weakly toxic in vitro. We further analysed the utility of the in vitro test for predicting the starting dose for an in vivo study, and the potential reduction in animal usage that this would engender. In this regard, the prediction by the cytotoxicity test was useful for 59% of the substances. However, the use of a standard starting dose of 300 mg/kg bw by default (without previous cytotoxicity testing) would have been

  8. Acute, mutagenicity, teratogenicity and subchronic oral toxicity studies of diaveridine in rodents.

    PubMed

    Wang, Jianzhong; Sun, Feifei; Tang, Shusheng; Zhang, Suxia; Cao, Xingyuan

    2015-09-01

    Diaveridine (DVD) is a member of the 2,4-pyrimidinediamine class of dihydrofolate reductase inhibitors. It is used in combination with sulfaquinoxaline as an antiprotozoal agent in animals for the prophylaxis and treatment of coccidiosis and leucocytozoonosis. Herein, we report a complete toxicological safety assessment of DVD for clinical use. The study of toxicity, genetic toxicity (mammalian erythrocyte micronucleus assay, mice sperm abnormality test and in vivo chromosome aberration test of mammalian bone marrow), 90-day sub-chronic toxicity and teratogenicity test were performed. In the acute oral toxicity tests, median lethal dose, LD50, was more than 2378mg/kg body weight in Sprague Dawley rats (1025mg/kg body weight in ICR mice). The testing results for three terms of mutagenicity toxicity (mouse chromosome aberration, erythrocyte micronucleus and sperm abnormality) were all negative at 128-512mg/kg body weight. For 90-day feeding of DVD at the dosage of 10mg/kg body weight in both male and female SD rats, no signs of toxicological effects were detected. Meanwhile, for teratogenicity test in female SD rats at the dosage of 37mg/kg body weight, there were no toxicological signs observed. Thus, our results suggested that the DVD is safe when administered orally in rats at 10mg/kg body weight per day. PMID:26397222

  9. Photoprotective effect and acute oral systemic toxicity evaluation of the novel heterocyclic compound LQFM048.

    PubMed

    Vinhal, Daniela C; de Ávila, Renato Ivan; Vieira, Marcelo S; Luzin, Rangel M; Quintino, Michelle P; Nunes, Liliane M; Ribeiro, Antonio Carlos Chaves; de Camargo, Henrique Santiago; Pinto, Angelo C; Dos Santos Júnior, Helvécio M; Chiari, Bruna G; Isaac, Vera; Valadares, Marize C; Martins, Tatiana Duque; Lião, Luciano M; de S Gil, Eric; Menegatti, Ricardo

    2016-08-01

    The new heterocyclic derivative LQFM048 (3) (2,4,6-tris ((E)-ethyl 2-cyano-3-(4-hydroxy-3-methoxyphenyl)acrylate)-1,3,5-triazine) was originally designed through the molecular hybridization strategy from Uvinul® T 150 (1) and (E)-ethyl 2-cyano-3-(4hydroxy-3-methoxyphenyl)acrylate (2) sunscreens, using green chemistry approach. This compound was obtained in global yields (80%) and showed an interesting redox potential. In addition, it is thermally stable up to temperatures around 250°C. It was observed that LQFM048 (3) showed a low degradation after 150min of sunlight exposure at 39°C, whereas the extreme radiation conditions induced a considerable photodegradation of the LQFM048 (3), especially when irradiated by VIS and VIS+UVA. During the determination of sun protection factor, LQFM048 (3) showed interesting results, specially as in association with other photoprotective compounds and commercial sunscreen. Additionally, the compound (3) did not promote cytotoxicity for 3T3 fibroblasts. Moreover, it was not able to trigger acute oral systemic toxicity in mice, being classified as a compound with low acute toxicity hazard (2.000mg/kg>LD50<5.000mg/kg). Therefore, this compound synthesized using green chemistry approach is promising showing potential to development of a new sunscreen product with advantage of presenting redox potential, indicating antioxidant properties.

  10. Photoprotective effect and acute oral systemic toxicity evaluation of the novel heterocyclic compound LQFM048.

    PubMed

    Vinhal, Daniela C; de Ávila, Renato Ivan; Vieira, Marcelo S; Luzin, Rangel M; Quintino, Michelle P; Nunes, Liliane M; Ribeiro, Antonio Carlos Chaves; de Camargo, Henrique Santiago; Pinto, Angelo C; Dos Santos Júnior, Helvécio M; Chiari, Bruna G; Isaac, Vera; Valadares, Marize C; Martins, Tatiana Duque; Lião, Luciano M; de S Gil, Eric; Menegatti, Ricardo

    2016-08-01

    The new heterocyclic derivative LQFM048 (3) (2,4,6-tris ((E)-ethyl 2-cyano-3-(4-hydroxy-3-methoxyphenyl)acrylate)-1,3,5-triazine) was originally designed through the molecular hybridization strategy from Uvinul® T 150 (1) and (E)-ethyl 2-cyano-3-(4hydroxy-3-methoxyphenyl)acrylate (2) sunscreens, using green chemistry approach. This compound was obtained in global yields (80%) and showed an interesting redox potential. In addition, it is thermally stable up to temperatures around 250°C. It was observed that LQFM048 (3) showed a low degradation after 150min of sunlight exposure at 39°C, whereas the extreme radiation conditions induced a considerable photodegradation of the LQFM048 (3), especially when irradiated by VIS and VIS+UVA. During the determination of sun protection factor, LQFM048 (3) showed interesting results, specially as in association with other photoprotective compounds and commercial sunscreen. Additionally, the compound (3) did not promote cytotoxicity for 3T3 fibroblasts. Moreover, it was not able to trigger acute oral systemic toxicity in mice, being classified as a compound with low acute toxicity hazard (2.000mg/kg>LD50<5.000mg/kg). Therefore, this compound synthesized using green chemistry approach is promising showing potential to development of a new sunscreen product with advantage of presenting redox potential, indicating antioxidant properties. PMID:27208746

  11. Extensive review of fish embryo acute toxicities for the prediction of GHS acute systemic toxicity categories.

    PubMed

    Scholz, Stefan; Ortmann, Julia; Klüver, Nils; Léonard, Marc

    2014-08-01

    Distribution and marketing of chemicals require appropriate labelling of health, physical and environmental hazards according to the United Nations global harmonisation system (GHS). Labelling for (human) acute toxicity categories is based on experimental findings usually obtained by oral, dermal or inhalative exposure of rodents. There is a strong societal demand for replacing animal experiments conducted for safety assessment of chemicals. Fish embryos are considered as alternative to animal testing and are proposed as predictive model both for environmental and human health effects. Therefore, we tested whether LC50s of the fish embryo acute toxicity test would allow effectively predicting of acute mammalian toxicity categories. A database of published fish embryo LC50 containing 641 compounds was established. For these compounds corresponding rat oral LD50 were identified resulting in 364 compounds for which both fish embryo LC50 and rat LD50 was available. Only a weak correlation of fish embryo LC50 and rat oral LD50 was obtained. Fish embryos were also not able to effectively predict GHS oral acute toxicity categories. We concluded that due to fundamental exposure protocol differences (single oral dose versus water-borne exposure) a reverse dosimetry approach is needed to explore the predictive capacity of fish embryos.

  12. Extensive review of fish embryo acute toxicities for the prediction of GHS acute systemic toxicity categories.

    PubMed

    Scholz, Stefan; Ortmann, Julia; Klüver, Nils; Léonard, Marc

    2014-08-01

    Distribution and marketing of chemicals require appropriate labelling of health, physical and environmental hazards according to the United Nations global harmonisation system (GHS). Labelling for (human) acute toxicity categories is based on experimental findings usually obtained by oral, dermal or inhalative exposure of rodents. There is a strong societal demand for replacing animal experiments conducted for safety assessment of chemicals. Fish embryos are considered as alternative to animal testing and are proposed as predictive model both for environmental and human health effects. Therefore, we tested whether LC50s of the fish embryo acute toxicity test would allow effectively predicting of acute mammalian toxicity categories. A database of published fish embryo LC50 containing 641 compounds was established. For these compounds corresponding rat oral LD50 were identified resulting in 364 compounds for which both fish embryo LC50 and rat LD50 was available. Only a weak correlation of fish embryo LC50 and rat oral LD50 was obtained. Fish embryos were also not able to effectively predict GHS oral acute toxicity categories. We concluded that due to fundamental exposure protocol differences (single oral dose versus water-borne exposure) a reverse dosimetry approach is needed to explore the predictive capacity of fish embryos. PMID:24929227

  13. The value of selected in vitro and in silico methods to predict acute oral toxicity in a regulatory context: results from the European Project ACuteTox.

    PubMed

    Prieto, P; Kinsner-Ovaskainen, A; Stanzel, S; Albella, B; Artursson, P; Campillo, N; Cecchelli, R; Cerrato, L; Díaz, L; Di Consiglio, E; Guerra, A; Gombau, L; Herrera, G; Honegger, P; Landry, C; O'Connor, J E; Páez, J A; Quintas, G; Svensson, R; Turco, L; Zurich, M G; Zurbano, M J; Kopp-Schneider, A

    2013-06-01

    ACuteTox is a project within the 6th European Framework Programme which had as one of its goals to develop, optimise and prevalidate a non-animal testing strategy for predicting human acute oral toxicity. In its last 6 months, a challenging exercise was conducted to assess the predictive capacity of the developed testing strategies and final identification of the most promising ones. Thirty-two chemicals were tested blind in the battery of in vitro and in silico methods selected during the first phase of the project. This paper describes the classification approaches studied: single step procedures and two step tiered testing strategies. In summary, four in vitro testing strategies were proposed as best performing in terms of predictive capacity with respect to the European acute oral toxicity classification. In addition, a heuristic testing strategy is suggested that combines the prediction results gained from the neutral red uptake assay performed in 3T3 cells, with information on neurotoxicity alerts identified by the primary rat brain aggregates test method. Octanol-water partition coefficients and in silico prediction of intestinal absorption and blood-brain barrier passage are also considered. This approach allows to reduce the number of chemicals wrongly predicted as not classified (LD50>2000 mg/kg b.w.).

  14. Acute and 28-day sub-acute oral toxicity evaluation of two dietary bamboo charcoal powders in Sprague-Dawley rats.

    PubMed

    Jia, Zhen-chao; Luo, Sha; Zhong, Yu-ting; Li, Xiao; Chen, Jin-yao; Zhang, Li-shi

    2015-04-01

    No data were available on the acute oral toxicity, short-term oral toxicity of vegetable carbon in animals. This study was designed to evaluate the safety of two commercially available dietary bamboo charcoal powders (BCP1 and BCP2). The size distribution of the two powders was determined by a Mastersizer 2000 laser particle size analyzer prior to the in vivo safety studies. For the acute toxicity study, a single dose of 11.24 g/kg body weight of BCP1 and BCP2 was given once orally to healthy Sprague-Dawley (SD) rats. Mortality and clinical symptoms were observed and recorded for the first 30 min after treatment, at 4 h post-administration, and then at least once daily for 14 days after administration. In the repeated dose 28-day oral toxicity study, BCP1 and BCP2 were administered orally at doses of 2.81, 5.62, and 11.24 g/kg body weight for 28 days to SD rats. Animals were sacrificed and organs and blood samples were analyzed. Results showed that both BCP1 and BCP2 were micro-sized and various in size. In the acute toxicity and the repeated dose 28-day oral toxicity studies, BCP caused neither mortality nor visible signs of toxicity in rats. No significant differences were found in the relative organ weights or in biochemical parameters in BCP treated groups compared to a control group. No treatment-related histological changes were observed in the organs of these animals. Based on these data, it is concluded that the median lethal dose (LD50) of BCP for both male and female rats is more than 11.24 g/kg body weight and the no-observed-adverse-effect level (NOAEL) is >11.24 g/kg body weight for 28 days.

  15. Acute and Subchronic Oral Toxicity Evaluation of Aqueous Root Extract of Dicoma anomala Sond. in Wistar Rats

    PubMed Central

    Balogun, Fatai Oladunni; Tom Ashafa, Anofi Omotayo

    2016-01-01

    The present study evaluated the safety of aqueous root extract of Dicoma anomala (AQRED) through acute and subchronic toxicity studies. Single oral dose of AQRED at the concentration of 0, 5, 300, and 2000 mg/kg as well as 125, 250, and 500 mg/kg/day was administered to rats for 14-day acute and 90-day subchronic oral toxicity studies. The results revealed no mortalities or observed clinical signs of toxicity in all the rats during both investigation periods. In subchronic toxicity testing, administration of AQRED also did not cause any changes in body weight as well as food and water consumption patterns. The haematological parameters and blood chemistry revealed no significant difference (p > 0.05) between the treatment and the control except in platelet count, alkaline phosphatase, and sodium levels where there was a significant increase (p < 0.05), although there was also a significant reduction (p < 0.05) in alanine transaminase, aspartate transaminase, and creatinine when compared to control. However, these changes were not reflecting the results from histology. Conclusively, the obtained results suggested that the LD50 of AQRED is in excess of 2000 mg/kg and its oral administration for 90 days revealed that it is unlikely to be toxic, hence, safe. PMID:27200099

  16. Biochemical and histopathological effects on liver due to acute oral toxicity of aqueous leaf extract of Ecliptaalba on female Swiss albino mice

    PubMed Central

    Singh, Tanuja; Sinha, Nivedita; Singh, Anjali

    2013-01-01

    Background: Limited data is available about the toxicity of herbal remedies used for self-medication. Since a popular medicinal plant Ecliptaalba contains various bioactive molecules, the present study aimed to observe the biochemical and histological changes in liver associated with acute oral toxicity (LD50) of aqueous extract of E. alba (L.) Hassk. in female Swiss albino mice. Materials and Methods: For the acute oral toxicity study, the animals were divided into six groups of 6 mice each. Group– I was normal control and the treatment groups were administered aqueous leaf extract of E. alba orally at different doses of 500 mg (group – I),1750 mg (group–III), 2000 mg (group- IV), 2500 mg (group- V) and 3000 mg/ kg/b.wt.(group- VI) for seven consecutive days. The mice were sacrificed on the eighth day and blood was collected for the analysis of ALP (alkaline phosphatase), SGPT (serum glutamic pyruvic transferase), total protein and albumin. The liver was dissected, weighed, and processed for histopathological analysis. Results: The LD50 was found to be 2316.626 mg/kg /body weight in female mice. Serum SGPT, total protein and albumin increased in treated group- IV (P < 0.05), V (P < 0.01), and VI (P < 0.01) as compared to the control (group- I). ALP level significantly decreased in the treated group- IV (P < 0.05), V (P < 0.01) and VI (P < 0.01). Histopathological changes were observed at dose of 2000 mg (group- IV), 2500 mg (group- V) and 3000 mg (group- VI). Conclusion: It was concluded that oral administration of aqueous leaf extract of E. alba had detrimental effects on biochemical parameters and induced histopathological alterations in liver of female Swiss albino mice at doses higher than 2000 mg/kg/day indicating that its indiscriminate use should be avoided. PMID:23543876

  17. A Quantitative Structure Activity Relationship for acute oral toxicity of pesticides on rats: Validation, domain of application and prediction.

    PubMed

    Hamadache, Mabrouk; Benkortbi, Othmane; Hanini, Salah; Amrane, Abdeltif; Khaouane, Latifa; Si Moussa, Cherif

    2016-02-13

    Quantitative Structure Activity Relationship (QSAR) models are expected to play an important role in the risk assessment of chemicals on humans and the environment. In this study, we developed a validated QSAR model to predict acute oral toxicity of 329 pesticides to rats because a few QSAR models have been devoted to predict the Lethal Dose 50 (LD50) of pesticides on rats. This QSAR model is based on 17 molecular descriptors, and is robust, externally predictive and characterized by a good applicability domain. The best results were obtained with a 17/9/1 Artificial Neural Network model trained with the Quasi Newton back propagation (BFGS) algorithm. The prediction accuracy for the external validation set was estimated by the Q(2)ext and the root mean square error (RMS) which are equal to 0.948 and 0.201, respectively. 98.6% of external validation set is correctly predicted and the present model proved to be superior to models previously published. Accordingly, the model developed in this study provides excellent predictions and can be used to predict the acute oral toxicity of pesticides, particularly for those that have not been tested as well as new pesticides.

  18. Acute, sub-chronic oral toxicity studies and evaluation of antiulcer activity of Sooktyn in experimental animals

    PubMed Central

    Chandra, Phool; Sachan, Neetu; Kishore, Kamal; Ghosh, Ashoke Kumar

    2012-01-01

    Sooktyn (SKN), mineralo-herbal drug which is being used largely by the patients for its extremely good therapeutic value to treat the gastric ulcers. The present study was undertaken to evaluate the toxicity studies and antiulcer activity of SKN. Acute and sub-chronic toxicities were studied in male and female Wistar rats. A single acute SKN of 2 000 mg/kg was administered by oral gavage for acute toxicity. Sub-chronic doses were 400 and 800 mg/kg/day. The major toxicological end points examined included animal body weight and food intake, selected tissue weights, and detailed gross necropsy. In addition, we examined blood elements: hematocrit, hemoglobin concentration, erythrocyte count, total leukocyte count and MCH, MCHC and platelets as well as biochemical parameters: urea, sugar, alanine transaminase, aspartate transaminase, alkaline phosphatase, total proteins, and creatinine. Also, anti-ulcer activity was carried out by employing indomethacin, ethanol, pylorus ligation, and hypothermic-stress-induced ulcer models. LD50 may be greater than 2 000 mg/kg (orally) for SKN and there were no signs of toxicity on 28 days sub-chronic oral administration of 400 and 800 mg/kg of SKN in rats on the basis of blood elements and biochemical parameters. The ulcer indices decrease in all ulcer models with 66.62%, 61.24%, 80.18%, and 74.76% in indomethacin, ethanol, pylorus ligation, and hypothermic-stress-induced ulcer models, respectively. The results suggest that SKN has no signs of toxicity at 2 000 mg/kg body weight of rats orally; sub-chronically. The drug is safe and has antiulcer activity. PMID:22837960

  19. Acute Oral Poisoning Due to Chloracetanilide Herbicides

    PubMed Central

    Seok, Su-Jin; Choi, Sang-Cheon; Yang, Jong-Oh; Lee, Eun-Young; Song, Ho-Yeon; Hong, Sae-Yong

    2012-01-01

    Chloracetanilide herbicides (alachlor, butachlor, metachlor) are used widely. Although there are much data about chronic low dose exposure to chloracetanilide in humans and animals, there are few data about acute chloracetanilide poisoning in humans. This study investigated the clinical feature of patients following acute oral exposure to chloracetanilide. We retrospectively reviewed the data on the patients who were admitted to two university hospitals from January 2006 to December 2010. Thirty-five patients were enrolled. Among them, 28, 5, and 2 cases of acute alachlor, metachlor, butachlor poisoning were included. The mean age was 49.8 ± 15.4 yr. The poison severity score (PSS) was 17 (48.6%), 10 (28.6%), 5 (14.3%), 2 (5.7%), and 1 (2.9%) patients with a PSS of 0, 1, 2, 3, and 4, respectively. The age was higher for the symptomatic patients (1-4 PSS) than that for the asymptomatic patients (0 PSS) (43.6 ± 15.2 vs 55.7 ± 13.5). The arterial blood HCO3 ¯ was lower in the symptomatic patients (1-4 PSS) than that in the asymptomatic patients (0 PSS). Three patients were a comatous. One patient died 24 hr after the exposure. In conclusion, although chloracetanilide poisoning is usually of low toxicity, elder patients with central nervous system symptoms should be closely monitored and cared after oral exposure. PMID:22323855

  20. Acute oral poisoning due to chloracetanilide herbicides.

    PubMed

    Seok, Su-Jin; Choi, Sang-Cheon; Gil, Hyo-Wook; Yang, Jong-Oh; Lee, Eun-Young; Song, Ho-Yeon; Hong, Sae-Yong

    2012-02-01

    Chloracetanilide herbicides (alachlor, butachlor, metachlor) are used widely. Although there are much data about chronic low dose exposure to chloracetanilide in humans and animals, there are few data about acute chloracetanilide poisoning in humans. This study investigated the clinical feature of patients following acute oral exposure to chloracetanilide. We retrospectively reviewed the data on the patients who were admitted to two university hospitals from January 2006 to December 2010. Thirty-five patients were enrolled. Among them, 28, 5, and 2 cases of acute alachlor, metachlor, butachlor poisoning were included. The mean age was 49.8 ± 15.4 yr. The poison severity score (PSS) was 17 (48.6%), 10 (28.6%), 5 (14.3%), 2 (5.7%), and 1 (2.9%) patients with a PSS of 0, 1, 2, 3, and 4, respectively. The age was higher for the symptomatic patients (1-4 PSS) than that for the asymptomatic patients (0 PSS) (43.6 ± 15.2 vs 55.7 ± 13.5). The arterial blood HCO₃⁻ was lower in the symptomatic patients (1-4 PSS) than that in the asymptomatic patients (0 PSS). Three patients were a comatous. One patient died 24 hr after the exposure. In conclusion, although chloracetanilide poisoning is usually of low toxicity, elder patients with central nervous system symptoms should be closely monitored and cared after oral exposure.

  1. Toxicological assessment of enzyme-treated asparagus extract in rat acute and subchronic oral toxicity studies and genotoxicity tests.

    PubMed

    Ito, Tomohiro; Ono, Tomoko; Sato, Atsuya; Goto, Kazunori; Miura, Takehito; Wakame, Koji; Nishioka, Hiroshi; Maeda, Takahiro

    2014-03-01

    The safety of enzyme-treated asparagus extract (ETAS) developed as a novel anti-stress functional material was assessed in acute and subchronic studies and genotoxicity assays. In the acute oral dose toxicity study, all rats survived during the test period and ETAS did not influence clinical appearance, body weight gain and necropsy findings at a dosage of 2000mg/kg body weight. Thus, the 50% lethal dose (LD50) of ETAS was determined to be greater than 2000mg/kg. The 90-day subchronic study (500, 1000 and 2000mg/kg body weight, delivered by gavage) in rats reported no significant adverse effects in food consumption, body weight, mortality, urinalysis, hematology, biochemistry, necropsy, organ weight and histopathology. In the micronucleus test of mice, the incidence of micronuclei in ETAS-administered groups (500, 1000 and 2000mg/kg/day, injected twice) was equivalent to that of the negative control group, while the positive control group receiving mitomycin C showed a high incidence. The potential of ETAS to induce gene mutation was tested using four Salmonella typhimurium strains and Escherichia coli WP2uvrA. The test sample was not mutagenic to the test strains. These results support the safety of ETAS as food and dietary supplement.

  2. [Acute conditions of the oral cavity].

    PubMed

    Bindslev, Preben Hørsted; Schou, Søren

    2010-11-01

    Acute conditions are mainly caused by inflammatory and infectious reactions in the dental pulp, periodontal tissues, periapical bone and the tissues around partially impacted teeth. Pain may also be related to traumatic injuries to the teeth and jaws as well as sequelae after oral surgery. Emergency treatment involves incision of abscesses, root canal treatment, irrigation with antiseptics, immobilisation of teeth or fractured bones, and prescription of analgetics. Antibiotics are only indicated in cases in which there is a risk that an infection spreads to adjacent regions or a risk of fever and malaise.

  3. Effects of oral acute administration and subchronic feeding of several levels of D-psicose in rats.

    PubMed

    Matsuo, Tatsuhiro; Tanaka, Tomohiro; Hashiguchi, Mineo; Izumori, Ken; Suzuki, Hiroo

    2002-12-01

    The effects of oral acute administration and subchronic (34 d) feeding of several levels of D-psicose, a C3-epimer of D-fructose, were studied in rats. In the acute administration test, five groups of eight male Wistar rats (3 wk old) were orally given D-psicose in doses of 8, 11, 14, 17, and 20 g/kg. Three rats receiving 14 g/kg, three rats receiving 17 g/kg and eight rats receiving 20 g/kg of D-psicose died within 2 d after administration. The calculated LD50 values were 16.3 g/kg by the Behrens-Karber method and 15.8 g/kg by the Litchfield-Wilcoxon method. In the subcronic feeding test, eight groups of seven male Wistar rats (3 wk old) were fed diets containing 0 (control), 10, 20, 30, and 40% for 34 d. One rat fed 30% D-psicose diet and five rats fed 40% D-psicose diet died during the experimental period. Body weight gain, food intake and food efficiency were more extensively suppressed by the higher D-psicose diets. The weights of heart, spleen and abdominal adipose tissue were smaller in the order of dietary D-psicose concentration. Cecal weight increased with increasing D-psicose concentration in the diets. Cecal hypertrophy was observed in rats fed 10-40% D-psicose diets. These results suggest that D-psicose differs in nutritional characteristics from D-glucose or D-fructose. The feeding of diets extremely high in D-psicose seems to be harmful to the intestinal tract.

  4. Biochemical, oxidative and histological changes caused by sub-acute oral exposure of some synthetic cyanogens in rats: ameliorative effect of α-ketoglutarate.

    PubMed

    Bhattacharya, Rahul; Rao, Pooja; Singh, Poonam; Yadav, Shiv Kumar; Upadhyay, Preeti; Malla, Sandhya; Gujar, Niranjan Laxman; Lomash, Vinay; Pant, Satish Chandra

    2014-05-01

    Time-dependent cyanide generation and acute toxicity of six different cyanogens were reported earlier, out of which malononitrile (MCN), propionitrile (PCN), and sodium nitroprusside (SNP) were found to be very toxic. We report here 14 d sub-acute toxicity of MCN, PCN, and SNP (oral; 1/10 LD50 daily) in female rats, and its amelioration by α-ketoglutarate (α-KG; oral; 5.26 mmol/kg; +5 min), a potential cyanide antidote. Significant decrease in white blood cells (PCN, SNP), platelets count (PCN), and blood glucose levels (MCN, PCN, SNP) was accompanied by elevated levels of alanine aminotransferase, lactate dehydrogenase (MCN, PCN, SNP), and aspartate aminotransferase (PCN, SNP). Oxidative damage was evidenced by diminished total antioxidant status in plasma and enhanced malondialdehyde levels in liver and kidney. This was accompanied by diminished levels of reduced glutathione, glutathione peroxidase, glutathione reductase, superoxide dismutase, and catalase in the brain, liver and kidney. We also observed increased levels of blood cyanide and thiocyanate, together with inhibition of cytochrome c oxidase and thiosulfate-sulfur transferase activities in total brain and liver homogenate, respectively. Cyanogens also produced several histological changes in all the organs studied. Post-treatment with α-KG significantly abrogated the toxicity of cyanogens, indicating its utility as an antidote for long-term cyanogen exposure.

  5. 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

  6. 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

  7. Oral flora of elderly patients following acute medical admission.

    PubMed

    Preston, A J; Gosney, M A; Noon, S; Martin, M V

    1999-01-01

    The human oral microflora is diverse and is usually predominately composed of Gram-positive bacteria. It is uncommon to find Gram-negative bacilli (GNB) in healthy mouths. The incidence of infection with GNB rises in institutionalised, frail elderly subjects. There is also evidence of an association between intra-oral GNB presence and denture wearing. There have been few studies which have investigated intra-oral GNB carriage in acutely ill elderly patients. The aim of this study was to evaluate the oral flora of a group of elderly patients during an acute medical admission and to investigate any associations between the oral microflora and existing medical or oral factors. A total of 28 patients (17 females and 11 males; age: 74-93 years) on a care for the elderly ward were studied. Epidemiological data, detailed medical histories and oral examinations were undertaken. In addition, oral swabs of the palate area were taken to determine their oral flora. Twelve (43%) of the patients had GNB in their oral cavities. These patients were suffering from a variety of medical conditions and were on various drug regimes. There was a correlation between oral GNB presence and denture use. There was no association between GNB presence and denture hygiene. As oropharyngeal GNB colonisation can be associated with infections such as aspiration pneumonia, it is important in patients at risk that intra-oral organisms are identified and managed.

  8. The Acute Toxicity of Tannic Acid Administered Intragastrically

    PubMed Central

    Boyd, Eldon M.

    1965-01-01

    The LD50 ± S.E. of tannic acid given orally to albino rats was found to be 2.26±0.083 g. per kg. body weight, which is higher than its apparent LD50 when given per rectum. The immediate cause of death was respiratory failure preceded by convulsions when death occurred early and by hypothermic cachexia when death was delayed. Death was associated with a progressively developing hepatic necrosis and nephritis and a temporary acute gastroenteritis. It was accompanied by loss of weight and edema in many organs, evidence of stimulation of the spleen, adrenal cortex and testes, and atrophy of the thymus. Recovery in survivors was associated with a temporary increase in weight of the spleen and testes and persistence of loss of weight in the adrenal, pyloric stomach, and skin. PMID:14291458

  9. 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.

  10. Oral toxicity of fipronil insecticide against the stingless bee Melipona scutellaris (Latreille, 1811).

    PubMed

    Lourenço, Clara Tavares; Carvalho, Stephan Malfitano; Malaspina, Osmar; Nocelli, Roberta Cornélio Ferreira

    2012-10-01

    For a better evaluation of the model using Apis mellifera in toxicology studies with insecticides, the oral acute toxicity of the insecticide fipronil against the stingless bee Melipona scutellaris was determined. The results showed that fipronil was highly toxic to M. scutellaris, with a calculated LC(50) (48 h) value of 0.011 ng a.i./μL of sucrose solution and an estimated oral LD(50) (48 h) of 0.6 ng a.i./bee. Our results showed that M. scutellaris bee is more sensitive to fipronil than the model specie A. mellifera.

  11. Acute toxicity of diazinon is similar for eight stocks of bobwhite

    USGS Publications Warehouse

    Hill, E.F.; Camardese, M.B.; Heinz, G.H.; Spann, J.W.; DeBevec, A.B.

    1984-01-01

    Nine-week-old bobwhite (Colinus virginianus) from eight different game farms were tested for their sensitivity to an acute oral exposure of technical-grade diazinon (phosphorothioic acid O, O-diethyl-O-[6-methyl- 2-(1 -methylethy 1)-4-pyrimidinyl]ester). Extraneous variables associated with interlaboratory differences in husbandry were eliminated by incubating eggs and rearing chicks to test age for all stocks simultaneously in the same facilities at the Patuxent Wildlife Research Center. Under this single set of conditions, the responses of the eight stocks of bobwhite to diazinon were statistically inseparable, with LD50 values varying from 13 mg/kg (95% confidence interval, 8-21 mg/kg) to 17 mg/kg (95% confidence interval, 11-25 mg/kg). The pooled LD50 for the eight stocks was 14.7 mg/kg (95% confidence interval,13.1-16.5 mg/kg).

  12. Antagonists for acute oral cadmium chloride intoxication

    SciTech Connect

    Basinger, M.A.; Jones, M.M.; Holscher, M.A.; Vaughn, W.K.

    1988-01-01

    An examination has been carried out on the relative efficacy of a number of chelating agents when acting as antagonists for oral cadmium chloride intoxication in mice. The compounds were administered orally after the oral administration of cadmium chloride at 1 mmol/kg. Of the compounds examined, several were useful in terms of enhancing survival, but by far the most effective in both enhancing survival and leaving minimal residual levels of cadmium in the liver and the kidney, was meso-2,3-dimercaptosuccinic acid (DMSA). Several polyaminocarboxylic acids also enhanced survival. The most effective of these in reducing liver and kidney levels of cadmium were diethylenetriaminepentaacetic acid (DTPA), trans-1,2-diaminocyclohexane-N,N,N'N'-tetraacetic acid (CDTA), and triethylenetetraminehexaacetic acid (TTHA). D-Penicillamine (DPA) was found to promote survival but also led to kidney cadmium levels higher than those found in the controls. Sodium 2,3-dimercaptopropane-1-sulfonate (DMPS) was as effective in promoting survival as DMSA but left levels of cadmium in the kidney and liver that were approximately four times greater than those found with DMSA.

  13. Oral rehydration of children with acute diarrhoea.

    PubMed

    Hirschhorn, N; Westley, T A

    1972-09-01

    A simple, reproducible method for preparing glucose-electrolyte solution for oral rehydration of infantile diarrhea victims is presented briefly in this letter. Using reagent-grade materials and a nested set of measuring spoons labeled as to content, the following measurements are made: sodium chloride, 1/2 teaspoon; sodium bicarbonate, 1/2 teaspoon; potassium chloride, 1/4 teaspoon; and glucose, 2 tablespoons. Combine these powders in a plastic vial and cap; when ready for use, dissolve in 1 liter of solution. This method was tested 10 times with a range of error of only +/-5% of the mean.

  14. Acute and sub-acute toxicological assessment of the aqueous seed extract of Persea americana mill (Lauraceae) in rats.

    PubMed

    Ozolua, Raymond I; Anaka, Ogochukwu N; Okpo, Stephen O; Idogun, Sylvester E

    2009-07-03

    The aqueous seed extract of Persea americana Mill (Lauraceae) is used by herbalists in Nigeria for the management of hypertension. As part of our on-going scientific evaluation of the extract, we designed the present study to assess its acute and sub-acute toxicity profiles in rats. Experiments were conducted to determine the oral median lethal dose (LD(50)) and other gross toxicological manifestations on acute basis. In the sub-acute experiments, the animals were administered 2.5 g/kg (p.o) per day of the extract for 28 consecutive days. Animal weight and fluid intake were recorded during the 28 days period. Terminally, kidneys, hearts, blood/sera were obtained for weight, haematological and biochemical markers of toxicity. Results show that the LD(50) could not be determined after a maximum dose of 10 g/kg. Sub-acute treatment with the extract neither affected whole body weight nor organ-to-body weight ratios but significantly increased the fluid intake (P < 0.0001). Haematological parameters and the levels of ALT, AST, albumin and creatinine were not significantly altered. However, the concentration of total proteins was significantly increased in the treated group. In conclusion, the aqueous seed extract of P. americana is safe on sub-acute basis but extremely high doses may not be advisable.

  15. Oral and intramuscular toxicity or inorganic and organic mercury chloride to growing quail

    SciTech Connect

    Hill, E.F.; Soares, J.H. Jr.

    1987-01-01

    The lethal toxicity of inorganic (HgCl/sub 2/) and organic (CH/sub 3/HgCl) mercury chloride was compared for Coturnix (Japanese quail, Coturnix japonica) of different ages from hatch through adulthood by single-dose acute oral and intramuscular injections and by a 5-d dietary trial. Sublethal mercury toxicity was studied by evaluation of plasma and brain cholinesterase activity. CH/sub 3/HgCl was more toxic than HgCl/sub 2/ in all tests at each age tested. LD50s consistently increased over the first 4 wk for both acute methods and both mercurials and then stabilized. The striking difference between single-dose acute and 5-d dietary tests was that CH/sub 3/HgCl averaged about twice as toxic as HgCl/sub 2/ by both acute methods, compared to 100 times as toxic by the dietary method. For example, at 2 wk of age, the oral LD50s for CH/sub 3/HgCl and HgCl/sub 2/ were 18 and 42 mg/kg and the dietary LC50s were 47 and 5086 ppm. When birds were fed HgCl/sub 2/ developed clinical signs of intoxication, they could recover once treatment was withdrawn; however, on CH/sub 3/HgCl, clinical signs often commenced after treatment was withdrawn, and then actually intensified for several days and culminated in death.

  16. Oral and intramuscular toxicity of inorganic and organic mercury chloride to growing quail

    USGS Publications Warehouse

    Hill, E.F.; Soares, J.H.

    1987-01-01

    The lethal toxicity of inorganic (HgCl2) and organic (CH3HgCl) mercury chloride was compared for Coturnix (Japanese quail, Coturnix japonica) of different ages from hatch through adulthood by single-dose acute oral and intramuscular injections and by a 5-d dietary trial. Sublethal mercury toxicity was studied by evaluation of plasma and brain cholinesterase activity. CH3HgCl was more toxic than HgCl2 in all tests at each age tested. LD50s consistently increased over the first 4 wk for both acute methods and both mercurials and then stabilized. The striking difference between single-dose acute and 5-d dietary tests was that CH3HgCl averaged about twice as toxic as HgCl2 by both acute methods, compared to 100 times as toxic by the dietary method. For example, at 2 wk of age, the oral LD50s for CH3HgCl and HgCl2 were 18 and 42 mg/kg and the dietary LC50s were 47 and 5086 ppm. When birds were fed HgCl2 and developed clinical signs of intoxication, they could recover once treatment was withdrawn; however, on CH3HgCl, clinical signs often commenced after treatment was withdrawn, and then actually intensified for several days and culminated in death.

  17. Antioxidant Capacity, Cytotoxicity, and Acute Oral Toxicity of Gynura bicolor.

    PubMed

    Teoh, Wuen Yew; Sim, Kae Shin; Moses Richardson, Jaime Stella; Abdul Wahab, Norhanom; Hoe, See Ziau

    2013-01-01

    Gynura bicolor (Compositae) which is widely used by the locals as natural remedies in folk medicine has limited scientific studies to ensure its efficacy and nontoxicity. The current study reports the total phenolic content, antioxidant capacity, cytotoxicity, and acute oral toxicity of crude methanol and its fractionated extracts (hexane, ethyl acetate, and water) of G. bicolor leaves. Five human colon cancer cell lines (HT-29, HCT-15, SW480, Caco-2, and HCT 116), one human breast adenocarcinoma cell line (MCF7), and one human normal colon cell line (CCD-18Co) were used to evaluate the cytotoxicity of G. bicolor. The present findings had clearly demonstrated that ethyl acetate extract of G. bicolor with the highest total phenolic content among the extracts showed the strongest antioxidant activity (DPPH radical scavenging assay and metal chelating assay), possessed cytotoxicity, and induced apoptotic and necrotic cell death, especially towards the HCT 116 and HCT-15 colon cancer cells. The acute oral toxicity study indicated that methanol extract of G. bicolor has negligible level of toxicity when administered orally and has been regarded as safe in experimental rats. The findings of the current study clearly established the chemoprevention potential of G. bicolor and thus provide scientific validation on the therapeutic claims of G. bicolor. PMID:24369485

  18. Antioxidant Capacity, Cytotoxicity, and Acute Oral Toxicity of Gynura bicolor

    PubMed Central

    Sim, Kae Shin; Abdul Wahab, Norhanom

    2013-01-01

    Gynura bicolor (Compositae) which is widely used by the locals as natural remedies in folk medicine has limited scientific studies to ensure its efficacy and nontoxicity. The current study reports the total phenolic content, antioxidant capacity, cytotoxicity, and acute oral toxicity of crude methanol and its fractionated extracts (hexane, ethyl acetate, and water) of G. bicolor leaves. Five human colon cancer cell lines (HT-29, HCT-15, SW480, Caco-2, and HCT 116), one human breast adenocarcinoma cell line (MCF7), and one human normal colon cell line (CCD-18Co) were used to evaluate the cytotoxicity of G. bicolor. The present findings had clearly demonstrated that ethyl acetate extract of G. bicolor with the highest total phenolic content among the extracts showed the strongest antioxidant activity (DPPH radical scavenging assay and metal chelating assay), possessed cytotoxicity, and induced apoptotic and necrotic cell death, especially towards the HCT 116 and HCT-15 colon cancer cells. The acute oral toxicity study indicated that methanol extract of G. bicolor has negligible level of toxicity when administered orally and has been regarded as safe in experimental rats. The findings of the current study clearly established the chemoprevention potential of G. bicolor and thus provide scientific validation on the therapeutic claims of G. bicolor. PMID:24369485

  19. Acute and chronic toxicity of the aqueous extract of Artemisia afra in rodents.

    PubMed

    Mukinda, J T; Syce, J A

    2007-05-30

    Artemisia afra (Jacq. Ex. Willd), "African Wormwood" is widely used traditionally in South Africa with no literature evidence substantiating its safety. The aim of this study was to investigate the safety of the aqueous extract of Artemisia afra by determining its pharmaco-toxicological effects after acute and chronic administration in mice and rats, respectively. The aqueous extract mimicked the traditional decoction dosage form of Artemisia afra. In mice, single intraperitoneal injections of Artemisia afra-extract (1.5-5.5g/kg) induced a regular dose-dependent increase in the death rate and incidence of general behaviour adverse effects, while with single oral doses (2-24g/kg) the increases in incidence of general behaviour adverse effects and mortality rate were dose-independent. The LD(50s) after acute intraperitoneal and oral doses were 2.45 and 8.96g/kg, respectively. Rats given oral doses of Artemisia afra-extract (0.1 or 1g/kg/day) survived the 3 months of dosing (i.e. LD(50) much higher than 1g/kg), experienced no significant changes in general behaviour and haematological and biochemical parameters, except for transient decrease in AST activity. No significant changes were observed in organ weights, and histopathological results showed normal profile suggesting no morphological alterations. Collectively, the results indicate that Artemisia afra-extract is non-toxic when given acutely, has low chronic toxicity potential and, in high doses, may have a hepatoprotective effect.

  20. Oral microbiota species in acute apical endodontic abscesses

    PubMed Central

    George, Noelle; Flamiatos, Erin; Kawasaki, Kellie; Kim, Namgu; Carriere, Charles; Phan, Brian; Joseph, Raphael; Strauss, Shay; Kohli, Richie; Choi, Dongseok; Craig Baumgartner, J.; Sedgley, Christine; Maier, Tom; Machida, Curtis A.

    2016-01-01

    Background and objectives Acute apical abscesses are serious endodontic diseases resulting from pulpal infection with opportunistic oral microorganisms. The objective of this study was to identify and compare the oral microbiota in patients (N=18) exhibiting acute apical abscesses, originating from the demographic region in Portland, Oregon. The study hypothesis is that abscesses obtained from this demographic region may contain unique microorganisms not identified in specimens from other regions. Design Endodontic abscesses were sampled from patients at the Oregon Health & Science University (OHSU) School of Dentistry. DNA from abscess specimens was subjected to polymerase chain reaction amplification using 16S rRNA gene-specific primers and Cy3-dCTP labeling. Labeled DNA was then applied to microbial microarrays (280 species) generated by the Human Oral Microbial Identification Microarray Laboratory (Forsyth Institute, Cambridge, MA). Results The most prevalent microorganisms, found across multiple abscess specimens, include Fusobacterium nucleatum, Parvimonas micra, Megasphaera species clone CS025, Prevotella multisaccharivorax, Atopobium rimae, and Porphyromonas endodontalis. The most abundant microorganisms, found in highest numbers within individual abscesses, include F. nucleatum, P. micra, Streptococcus Cluster III, Solobacterium moorei, Streptococcus constellatus, and Porphyromonas endodontalis. Strong bacterial associations were identified between Prevotella multisaccharivorax, Acidaminococcaceae species clone DM071, Megasphaera species clone CS025, Actinomyces species clone EP053, and Streptococcus cristatus (all with Spearman coefficients >0.9). Conclusions Cultivable and uncultivable bacterial species have been identified in endodontic abscesses obtained from the Portland, Oregon demographic region, and taxa identifications correlated well with other published studies, with the exception of Treponema and Streptococcus cristae, which were not commonly

  1. Single dose oral flurbiprofen for acute postoperative pain in adults

    PubMed Central

    Sultan, Asquad; McQuay, Henry J; Moore, R Andrew; Derry, Sheena

    2014-01-01

    Background Flurbiprofen is a non-selective non-steroidal anti-inflammatory drug (NSAID), related to ibuprofen and naproxen, used to treat acute and chronic painful conditions. There is no systematic review of its use in acute postoperative pain. Objectives To assess efficacy, duration of action, and associated adverse events of single dose oral flurbiprofen in acute postoperative pain in adults. Search methods We searched Cochrane CENTRAL, MEDLINE, EMBASE and the Oxford Pain Relief Database for studies to January 2009. Selection criteria Randomised, double blind, placebo-controlled trials of single dose orally administered flurbiprofen in adults with moderate to severe acute postoperative pain. Data collection and analysis Two review authors independently assessed trial quality and extracted data. Pain relief or pain intensity data were extracted and converted into the dichotomous outcome of number of participants with at least 50% pain relief over 4 to 6 hours, from which relative risk (RR) and number needed to treat to benefit (NNT) were calculated. Numbers of participants using rescue medication over specified time periods, and time to use of rescue medication, were sought as additional measures of efficacy. Information on adverse events and withdrawals were collected. Main results Eleven studies compared flurbiprofen (699 participants) with placebo (362 participants) in studies lasting 6 to 12 hours. Studies were of adequate reporting quality, and most participants had pain following dental extractions. The dose of flurbiprofen used was 25 mg to 100 mg, with most information for 50 mg and 100 mg. The NNT for at least 50% pain relief over 4 to 6 hours for flurbiprofen 50 mg compared with placebo (692 participants) was 2.7 (2.3 to 3.3) and for 100 mg (416 participants) it was 2.5 (2.0 to 3.1). With flurbiprofen 50 mg and 100 mg 65% to 70% of participants experienced at least 50% pain relief, compared with 25% to 30% with placebo. Rescue medication was used by 25

  2. Acute and neurotoxicity of two structurally related acetylenic compounds: 5,7,11-dodecatriyn-1-ol and 5,7,11,13-octadecatetrayne-1,18-diol.

    PubMed

    Gad, S C; Dunn, B J; Gavigan, F A; Reilly, C; Peckham, J C

    1988-02-01

    Two structurally related acetylenic compounds, 5,7,11-Dodecatriyn-1-ol, (Compound A), and 5,7,11,13-Octadecatetrayne-1,18-Diol (Compound B), were evaluated in a tier I toxicology testing program as part of an ongoing research and development program. This battery of acute tests included acute oral, guinea pig maximization, photosensitization, dermal irritation, Ames and multiple genetic endpoint and a 2 week oral fetotoxicity study. Compound A was found to have an oral LD50 of 0.25 ml/kg, be an extreme dermal sensitizer, a mild dermal irritant (PDII of 1.7), and not mutagenic or fetotoxic in the tests employed. Compound B had an oral LD50 greater than 4 g/kg, was a moderate dermal sensitizer and mild dermal irritant (PDII of 1.4), was not mutagenic in the Ames test but weakly increased the incidence of SCEs and gene mutations in Chinese Hamster Ovary cells, and was not fetotoxic. Neither compound was found to be a photosensitizer, but during the course of the photosensitization study Compound A was found to cause neuromuscular signs (including hind limb paralysis) and a bilateral necrosis of the medulla oblongata in female guinea pigs. A similar lesion was found in female rats receiving a single oral dose of 0.25 ml/kg and in nonpregnant females dosed daily for two weeks at 0.03 ml/kg. Compound B was not found to produce any of these neurologic effects.

  3. Acute toxicity of pinnatoxins E, F and G to mice.

    PubMed

    Munday, Rex; Selwood, Andrew I; Rhodes, Lesley

    2012-11-01

    The acute toxicities to mice of pinnatoxins E, F and G, members of the cyclic imine group of phycotoxins, by intraperitoneal injection and/or oral administration, have been determined. These substances were all very toxic by intraperitoneal injection, with LD(50) values between 12.7 and 57 μg/kg. Pinnatoxin E was much less toxic by oral administration than by intraperitoneal injection, but this was not the case for pinnatoxin F. The median lethal doses of the latter substance by gavage and by voluntary intake were only 2 and 4 times higher than that by injection. The high oral toxicity of pinnatoxin F raises concerns as to the possibility of adverse effects of this substance in shellfish consumers, although it should be noted that no toxic effects in humans have been recorded with pinnatoxins or with any other compound of the cyclic imine group. PMID:22813782

  4. Infection in acute leukemia patients receiving oral nonabsorable antibiotics.

    PubMed

    Hahn, D M; Schimpff, S C; Fortner, C L; Smyth, A C; Young, V M; Wiernik, P H

    1978-06-01

    During a 20-month period all acute nonlymphocytic patients (87 patient trials) receiving cytotoxic chemotherapy were placed on an oral nonabsorbable antibiotic regimen consisting of gentamicin, vancomycin, and nystatin in addition to an intensive program of infection prevention aimed at reducing exogenously acquired and body-surface potential pathogens. Although side effects of anorexia, diarrhea, and nausea were common, gentamicin-vancomycin-nystatin was ingested 80% of the study time. Microbial growth in gingival and rectal cultures was substantially reduced. The incidence of bacteremias and other serious infections was low. Pseudomonas aeruginosa, other gram-negative bacilli, and Candida species caused few infections along the alimentary canal, whereas infections of the skin (especially Staphylococcus aureus) were not reduced compared with those occurring in former years. A total of the 104 acquired gram-negative bacilli were gentamicin resistant; 5 subsequently caused infection. Thus, despite certain definite drawbacks, the use of oral nonabsorbable antibiotics to suppress alimentary tract microbial flora in combination with other infection prevention techniques in granulocytopenic cancer patients has proven feasible and tolerable and has been associated with a low order of life-threatening infections. PMID:98107

  5. Acute arsenic exposure treated with oral D-penicillamine

    SciTech Connect

    Watson, W.A.; Veltri, J.C.; Metcalf, T.J.

    1981-06-01

    Arsenic trioxide (As2O3) is the arsenic compound most commonly implicated in acute toxic exposures. The toxicity of As2O3 is a function of the preparation's particle size and solubility. A 16-month-old female presented at a local emergency room with a history of acute ingestion of As2O3 obtained from a commonly available pesticide. Classic gastrointestinal symptoms of arsenic toxicity were exhibited shortly after ingestion; however, aggressive decontamination followed by early chelation therapy resulted in the cessation of toxic manifestations and an uneventful recovery. Oral chelation therapy with D-penicillamine has rarely been reported as an effective agent in the treatment of arsenic poisoning. The case reported herein is further documentation that D-penicillamine is effective in increasing the mobilization of arsenic. The authors also recommend that products containing arsenic compounds should not be used where children may come in contact with them until the Environmental Protection Agency's child resistant packaging regulations become effective.

  6. Exploring waiving opportunities for mammalian acute systemic toxicity tests.

    PubMed

    Graepel, Rabea; Asturiol, David; Prieto, Pilar; Worth, Andrew P

    2016-07-01

    A survey was carried out to explore opportunities for waiving mammalian acute systemic toxicity tests. We were interested in finding out whether data from a sub-acute toxicity test could be used to predict the outcome of an acute systemic toxicity test. The survey was directed at experts in the field of toxicity testing, and was carried out in the context of the upcoming 2018 final registration deadline for chemicals under the EU REACH Regulation. In addition to the survey, a retrospective data analysis of chemicals that had already been registered with the European Chemicals Agency, and for which both acute and sub-acute toxicity data were available, was carried out. This data analysis was focused on chemicals that were administered via the oral route. The answers to the questionnaire showed a willingness to adopt waiving opportunities. In addition, the responses showed that data from a sub-acute toxicity test or dose-range finding study might be useful for predicting chemicals that do not require classification for acute oral toxicity (LD50 > 2000mg/kg body weight). However, with the exception of substances that fall into the non-classified category, it is difficult to predict current acute oral toxicity categories. PMID:27494626

  7. Effects of oral montelukast on airway function in acute asthma.

    PubMed

    Cýllý, A; Kara, A; Ozdemir, T; Oğüş, C; Gülkesen, K H

    2003-05-01

    Montelukast, a specific cysteinyl leukotriene receptor antagonist, has been shown to improve pulmonary function within 1 h of ingestion. This study was undertaken to compare the effects on peak expiratory flow rate (PEFR) of oral montelukast added to intravenous steroid, intravenous steroid alone and placebo during the 24 h period following administration. Seventy asthmatic patients (FEV1 40-80% predicted and > or = 15% improvement after inhaled beta agonist) were enrolled in a single blind study to receive oral montelukast (10 mg) plus intravenous prednisolone (1 mg/kg), intravenous prednisolone (1 mg/kg) or placebo in a randomised fashion. The patients received one ofthe above three groups of medication before any other treatments. This was immediately followed by the aerosol treatments of 100 mcg of terbutaline sulphate divided into three doses during 1 h as described in the consensus statement. Thereafter, patients were observed for 24 h to document the effects on PEFR, Borg dyspnoea score and need for rescue medication. The primary end point was percentage change at different time points. Secondary end points were Borg dyspnoea score and use of rescue medication. Compared with placebo, montelukast added to the prednisolone group and the prednisolone alone group had significant percentage change from baseline in PEFR in the entire 24 h period (P<0.05). The difference in PEFR between montelukast plus prednisolone group and prednisolone group favoured the montelukast plus prednisolone group but did not reach statistical significance. Furthermore, montelukast plus prednisolone group required less inhaled short-acting beta agonistthan other two groups. The results of this study indicate that adding montelukast to steroid in acute asthma may have some additive improvement in lung functions. PMID:12735671

  8. Neutral red uptake cytotoxicity tests for estimating starting doses for acute oral toxicity tests.

    PubMed

    Stokes, William S; Casati, Silvia; Strickland, Judy; Paris, Michael

    2008-05-01

    In vitro cytotoxicity assays can be used as alternative toxicity tests to reduce the total number of animals needed for acute oral toxicity tests. This unit describes two methods for determining the in vitro cytotoxicity of test substances using neutral red uptake (NRU) and using the in vitro data to determine starting doses for in vivo acute oral systemic toxicity tests, e.g., the up-and-down procedure or the acute toxic class method. The use of the NRU methods to determine starting doses for acute oral toxicity tests may reduce the number of animals required, and for relatively toxic substances, this approach may also reduce the number of animals that die or require humane euthanasia due to severe toxicity. An interlaboratory validation study has demonstrated that the methods are useful and reproducible for these purposes. Two standardized protocols provide details for performing NRU tests with rodent and human cells.

  9. Acute oral toxicity and liver oxidant/antioxidant stress of halogenated benzene, phenol, and diphenyl ether in mice: a comparative and mechanism exploration.

    PubMed

    Shi, Jiaqi; Feng, Mingbao; Zhang, Xuesheng; Wei, Zhongbo; Wang, Zunyao

    2013-09-01

    The lethal doses (LD50s) of fluorinated, chlorinated, brominated, and iodinated benzene, phenol, and diphenyl ether in mice were ascertained respectively under the consistent condition. The acute toxicity of four benzenes orders in fluorobenzene (FB) < iodobenzene < chlorobenzene≈bromobenzene, that of four phenols orders in 4-iodophenol≈4-bromophenol < 4-chlorophenol (4-MCP) < 4-fluorophenol (4-MFP), and that of four diphenyl ethers orders in 4,4'-iododiphenyl ether < 4,4'-difluorodiphenyl ether < 4,4'-dichlorodiphenyl ether≈4,4'-dibromodiphenyl ether. General behavior adverse effects were observed, and poisoned mouse were dissected to observe visceral lesions. FB, 4-MCP, and 4-MFP produced toxic faster than other halogenated benzenes and phenols, as they had lower octanol-water partition coefficients. Pathological changes in liver and liver/kidney weight changes were also observed. Hepatic superoxide dismutase, catalase activities, and malondialdehyde level were tested after a 28-day exposure, which reflects a toxicity order basically consistent with that reflected by the LD50s. By theoretical calculation and building models, the toxicity of benzene, phenol, and diphenyl ether were influenced by different structural properties.

  10. Correlation of oral health of children with acute leukemia during the induction phase

    PubMed Central

    Dholam, Kanchan P.; Gurav, Sandeep; Dugad, Jinesh; Banavli, Shripad

    2014-01-01

    Background: Treatment of acute leukemia's- a common childhood malignancy, involves intensive and powerful multi-drug chemotherapeutic regime. Oral lesions are a common complication in these patients affecting oral health status. Aim: This study was conducted to evaluate and assess the oral health status of newly diagnosed leukemic pediatric patients during induction phase and its correlation to outcome of induction therapy. Material Methods: Oral examinations was done in 33 children between the age group of 5-15 years with acute lymphoblastic leukemia (ALL) and acute myloblastic leukemia (AML), who were undergoing chemotherapy. Oral Hygiene Index- Simplified, (OHI-S) decayed missing filled teeth index (def/DMFT), Loe and Sillness index for gingiva, and complete blood count at first and fourth week of induction phase were recorded for each patient. The changes in the oral health status were analyzed with Wilcoxon signed rank test. Results: During an induction phase it was observed that level of OHI-S (P = 0.002), Loe and Sillness index (P = 0.003), def/DMFT index (P = 0.076), platelet count (P = 0.00) increased significantly and no significant difference was noted in hemoglobin (P = 0.4) and total leucocytes count (P = 0.11). Conclusion: It was observed that, although oral health status had significantly worsened, the induction outcome was not affected. PMID:25006282

  11. The ability of filgrastim to mitigate mortality following LD50/60 total-body irradiation is administration time-dependent.

    PubMed

    Farese, Ann M; Brown, Cassandra R; Smith, Cassandra P; Gibbs, Allison M; Katz, Barry P; Johnson, Cynthia S; Prado, Karl L; MacVittie, Thomas J

    2014-01-01

    The identification of the optimal administration schedule for an effective medical countermeasure is critical for the effective treatment of individuals exposed to potentially lethal doses of radiation. The efficacy of filgrastim (Neupogen®), a potential medical countermeasure, to improve survival when initiated at 48 h following total body irradiation in a non-human primate model of the hematopoietic syndrome of the acute radiation syndrome was investigated. Animals were exposed to total body irradiation, antero-posterior exposure, total midline tissue dose of 7.5 Gy, (target lethal dose 50/60) delivered at 0.80 Gy min, using linear accelerator-derived 6 MV photons. All animals were administered medical management. Following irradiation on day 0, filgrastim (10 μg kg d) or the control (5% dextrose in water) was administered subcutaneously daily through effect (absolute neutrophil count ≥ 1,000 cells μL for three consecutive days). The study (n = 80) was powered to demonstrate a 25% improvement in survival following the administration of filgrastim or control beginning at 48 ± 4 h post-irradiation. Survival analysis was conducted on the intention-to-treat population using a two-tailed null hypothesis at a 5% significance level. Filgrastim, initiated 48 h after irradiation, did not improve survival (2.5% increase, p = 0.8230). These data demonstrate that efficacy of a countermeasure to mitigate lethality in the hematopoietic syndrome of the acute radiation syndrome can be dependent on the interval between irradiation and administration of the medical countermeasure.

  12. Oral manifestations as an early clinical sign of acute myeloid leukaemia: a case report.

    PubMed

    Guan, G; Firth, N

    2015-03-01

    Leukaemia is the most common malignancy in children and one of the most common malignancies in young adults. Acute myeloid leukaemia is often associated with early oral manifestations. The purpose of this study is to report the case of a 49-year-old male with spontaneous gingival bleeding for over two years with undiagnosed leukaemia. Haematological investigation was instigated and on referral to the Haematology Department at Dunedin Public Hospital, the diagnosis of an acute myeloid leukaemia was confirmed. Since oral lesions can be one of the early events of acute myeloid leukaemia, they may be considered as an important diagnostic indicator for oral health practitioners, and their roles in diagnosing and treating such patients.

  13. Oral complications and dental care in children with acute lymphoblastic leukaemia.

    PubMed

    Valéra, Marie-Cécile; Noirrit-Esclassan, Emmanuelle; Pasquet, Marléne; Vaysse, Fréderic

    2015-08-01

    Acute leukaemia is the most common type of childhood cancer, the acute lymphoblastic type accounting for the majority of cases. Children affected by leukaemia receive various forms of treatments including chemotherapeutic agents and stem cell transplants. Leukaemia and its treatment can directly or indirectly affect oral health and further dental treatments. The oral complications include mucositis, opportunistic infections, gingival inflammation and bleeding, xerostomia and carious lesions. An additional consideration in children is the impact of the treatments on the developing dentition and on orofacial growth. The aim of this review is to describe the oral complications in children with acute lymphoblastic leukaemia and the methods of prevention and management before, during and after the cancer treatment.

  14. Acute oral toxicity of Pereskia bleo and Pereskia grandifolia in mice

    PubMed Central

    Sim, K. S.; Sri Nurestri, A. M.; Sinniah, S. K.; Kim, K. H.; Norhanom, A. W.

    2010-01-01

    Pereskia bleo and Pereskia grandifolia, belonging to the botanical family Cactaceae, have been traditionally used by the locals in Malaysia for treatment of various ailments. The current study reports the outcome of acute oral toxicity investigation of Pereskia bleo and Pereskia grandifolia, on ICR mice. No mortalities or evidence of adverse effects have been observed in ICR mice following acute oral administration at the highest dose of 2500 mg/ kg crude extracts of Pereskia bleo and Pereskia grandifolia. This is the first report on the acute oral toxicity of Pereskia bleo and Pereskia grandifolia and the findings of this study are in agreement with those of in vitro experiments and thus provide scientific validation on the use of the leaves of Pereskia bleo and Pereskia grandifolia. PMID:20548939

  15. [Acute poisoning due to oral intake of an organic solvent].

    PubMed

    Holtz, J; Nicole, A; Regamey, C

    1992-11-21

    We report a case of paint thinner intoxication by oral intake, with loss of consciousness, upper gastrointestinal injuries, renal failure, rhabdomyolysis and cervical plexus injury. The clinical picture was similar to other cases reported in the literature. PMID:1448688

  16. Acute and sub-acute oral toxicity assessment of the hydroalcoholic extract of Withania somnifera roots in Wistar rats.

    PubMed

    Prabu, P C; Panchapakesan, S; Raj, C David

    2013-08-01

    Withania somnifera is a widely used medicinal plant for several disorders. Toxicity studies on Withania somnifera are not available. Acute and sub-acute oral toxicities of Withania somnifera root extract in Wistar rats were evaluated in the present study. In the acute toxicity study, WSR extract was administered to five rats at 2000 mg/kg, once orally and were observed for 14 days. No toxic signs/mortality were observed. In the sub-acute study, WSR extract was administered once daily for 28 days to rats at 500, 1000 and 2000 mg/kg, orally. No toxic signs/mortality were observed. There were no significant changes (P < 0.05) in the body weights, organ weights and haemato-biochemical parameters in any of the dose levels. No treatment related gross/histopathological lesions were observed. The present investigation demonstrated that the no observed adverse effect level was 2000 mg/kg body weight per day of hydroalcoholic extract of W. somnifera in rats and hence may be considered as non-toxic.

  17. Quantitative structure-activity relationship modelling of oral acute toxicity and cytotoxic activity of fragrance materials in rodents.

    PubMed

    Papa, E; Luini, M; Gramatica, P

    2009-10-01

    Fragrance materials are used as ingredients in many consumer and personal care products. The wide and daily use of these substances, as well as their mainly uncontrolled discharge through domestic sewage, make fragrance materials both potential indoor and outdoor air pollutants which are also connected to possible toxic effects on humans (asthma, allergies, headaches). Unfortunately, little is known about the environmental fate and toxicity of these substances. However, the use of alternative, predictive approaches, such as quantitative structure-activity relationships (QSARs), can help in filling the data gap and in the characterization of the environmental and toxicological profile of these substances. In the proposed study, ordinary least squares regression-based QSAR models were developed for three toxicological endpoints: mouse oral LD(50), inhibition of NADH-oxidase (EC(50) NADH-Ox) and the effect on mitochondrial membrane potential (EC(50) DeltaPsim). Theoretical molecular descriptors were calculated by using DRAGON software, and the best QSAR models were developed according to the principles defined by the Organization for Economic Co-operation and Development.

  18. Improving reptile ecological risk assessment: oral and dermal toxicity of pesticides to a common lizard species (Sceloporus occidentalis).

    PubMed

    Weir, Scott M; Yu, Shuangying; Talent, Larry G; Maul, Jonathan D; Anderson, Todd A; Salice, Christopher J

    2015-08-01

    Reptiles have been understudied in ecotoxicology, which limits consideration in ecological risk assessments. The goals of the present study were 3-fold: to improve oral and dermal dosing methodologies for reptiles, to generate reptile toxicity data for pesticides, and to correlate reptile and avian toxicity. The authors first assessed the toxicity of different dosing vehicles: 100 μL of water, propylene glycol, and acetone were not toxic. The authors then assessed the oral and dermal toxicity of 4 pesticides following the up-and-down procedure. Neither brodifacoum nor chlorothalonil caused mortality at doses ≤ 1750 μg/g. Under the "neat pesticide" oral exposure, endosulfan (median lethal dose [LD50] = 9.8 μg/g) was more toxic than λ-cyhalothrin (LD50 = 916.5 μg/g). Neither chemical was toxic via dermal exposure. An acetone dosing vehicle increased λ-cyhalothrin toxicity (oral LD50 = 9.8 μg/g; dermal LD50 = 17.5 μg/g), but not endosulfan. Finally, changes in dosing method and husbandry significantly increased dermal λ-cyhalothrin LD50s, which highlights the importance of standardized methods. The authors combined data from the present study with other reptile LD50s to correlate with available avian data. When only definitive LD50s were used in the analysis, a strong correlation was found between avian and reptile toxicity. The results suggest it is possible to build predictive relationships between avian and reptile LD50s. More research is needed, however, to understand trends associated with chemical classes and modes of action. PMID:25760295

  19. Improving reptile ecological risk assessment: oral and dermal toxicity of pesticides to a common lizard species (Sceloporus occidentalis).

    PubMed

    Weir, Scott M; Yu, Shuangying; Talent, Larry G; Maul, Jonathan D; Anderson, Todd A; Salice, Christopher J

    2015-08-01

    Reptiles have been understudied in ecotoxicology, which limits consideration in ecological risk assessments. The goals of the present study were 3-fold: to improve oral and dermal dosing methodologies for reptiles, to generate reptile toxicity data for pesticides, and to correlate reptile and avian toxicity. The authors first assessed the toxicity of different dosing vehicles: 100 μL of water, propylene glycol, and acetone were not toxic. The authors then assessed the oral and dermal toxicity of 4 pesticides following the up-and-down procedure. Neither brodifacoum nor chlorothalonil caused mortality at doses ≤ 1750 μg/g. Under the "neat pesticide" oral exposure, endosulfan (median lethal dose [LD50] = 9.8 μg/g) was more toxic than λ-cyhalothrin (LD50 = 916.5 μg/g). Neither chemical was toxic via dermal exposure. An acetone dosing vehicle increased λ-cyhalothrin toxicity (oral LD50 = 9.8 μg/g; dermal LD50 = 17.5 μg/g), but not endosulfan. Finally, changes in dosing method and husbandry significantly increased dermal λ-cyhalothrin LD50s, which highlights the importance of standardized methods. The authors combined data from the present study with other reptile LD50s to correlate with available avian data. When only definitive LD50s were used in the analysis, a strong correlation was found between avian and reptile toxicity. The results suggest it is possible to build predictive relationships between avian and reptile LD50s. More research is needed, however, to understand trends associated with chemical classes and modes of action.

  20. The use of noninvasive ventilation in acute respiratory failure associated with oral contrast aspiration pneumonitis.

    PubMed

    Keddissi, J I; Metcalf, J P

    2000-05-01

    Noninvasive ventilation (NIV) has been used to treat patients with acute respiratory failure, including cases of pneumonia. We used this technique in the management of an 83-year-old patient with acute respiratory failure secondary to inadvertent administration of oral contrast material into the lung, and who did not want to be intubated. NIV resulted in immediate improvement of respiratory status. The patient was weaned from NIV over the next 24 hours and eventually discharged from the hospital.

  1. Acute and Chronic Toxicity of an Aqueous Fraction of the Stem Bark of Stryphnodendron adstringens (Barbatimão) in Rodents.

    PubMed

    Costa, Marco Antonio; Palazzo de Mello, João Carlos; Kaneshima, Edílson Nobuyoshi; Ueda-Nakamura, Tânia; Dias Filho, Benedito Prado; Audi, Elisabeth Aparecida; Nakamura, Celso Vataru

    2013-01-01

    Stryphnodendron adstringens has a high tannin content and is used as an antiseptic and antimicrobial and in the treatment of leucorrhea, gonorrhea, wound healing, and gastritis. The present study evaluated the toxic effects of the heptamer prodelphinidin (F2) from the stem bark of S. adstringens in rodents. In the acute toxicity test, the mice that received oral doses exhibited reversible effects, with an LD50 of 3.015 mg · kg(-1). In the chronic toxicity test at 90 days, Wistar rats were treated with different doses of F2 (10, 100, and 200 mg · kg(-1)). In the biochemical, hematological, and histopathological examinations and open-field test, the different dose groups did not exhibit significant differences compared with controls. The present results indicate that F2 from the stem bark of S. adstringens caused no toxicity with acute and chronic oral treatment in rodents at the doses administered.

  2. Acute and Chronic Toxicity of an Aqueous Fraction of the Stem Bark of Stryphnodendron adstringens (Barbatimão) in Rodents

    PubMed Central

    Costa, Marco Antonio; Palazzo de Mello, João Carlos; Kaneshima, Edílson Nobuyoshi; Ueda-Nakamura, Tânia; Dias Filho, Benedito Prado; Audi, Elisabeth Aparecida

    2013-01-01

    Stryphnodendron adstringens has a high tannin content and is used as an antiseptic and antimicrobial and in the treatment of leucorrhea, gonorrhea, wound healing, and gastritis. The present study evaluated the toxic effects of the heptamer prodelphinidin (F2) from the stem bark of S. adstringens in rodents. In the acute toxicity test, the mice that received oral doses exhibited reversible effects, with an LD50 of 3.015 mg · kg−1. In the chronic toxicity test at 90 days, Wistar rats were treated with different doses of F2 (10, 100, and 200 mg · kg−1). In the biochemical, hematological, and histopathological examinations and open-field test, the different dose groups did not exhibit significant differences compared with controls. The present results indicate that F2 from the stem bark of S. adstringens caused no toxicity with acute and chronic oral treatment in rodents at the doses administered. PMID:23970938

  3. Acute toxicity study of the oil from Azadirachta indica seed (neem oil).

    PubMed

    Gandhi, M; Lal, R; Sankaranarayanan, A; Banerjee, C K; Sharma, P L

    1988-01-01

    The seed oil of Azadirachta indica (neem oil) is well known for its medicinal properties in the indigenous Indian system of medicine. Its acute toxicity was documented in rats and rabbits by the oral route. Dose-related pharmacotoxic symptoms were noted along with a number of biochemical and histopathological indices of toxicity. The 24-h LD50 was established as 14 ml/kg in rats and 24 ml/kg in rabbits. Prior to death, animals of both species exhibited comparable pharmacotoxic symptoms in order and severity, with lungs and central nervous system as the target organs of toxicity. Edible mustard seed oil (80 ml/kg) was tested in the same manner to document the degree to which the physical characteristics of an oil could contribute to the oral toxicity of neem oil. PMID:3419203

  4. Serum and salivary cardiac analytes in acute myocardial infarction related to oral health status

    NASA Astrophysics Data System (ADS)

    Ebersole, Jeffrey L.; Kryscio, Richard J.; Campbell, Charles; Kinane, Denis F.; McDevitt, John T.; Christodoulides, Nicolaos; Floriano, Pierre N.; Miller, Craig S.

    2014-06-01

    With the advent of an increased emphasis on the potential to utilize biomarkers in saliva for systemic diseases, the issue of existing oral disease is an important consideration that could adversely affect the interpretation of diagnostic results obtained from saliva. We addressed the question does a patient's oral inflammation status confound biomarker levels used in diagnosis of acute myocardial infarction (AMI). The results demonstrated that multiple serum biomarkers and a few salivary biomarkers reflected the cardiac event. Importantly, oral health of the individual had minimal impact on the validity of the serum or salivary biomarker effectiveness.

  5. Neuroanatomical Correlates of Oral Reading in Acute Left Hemispheric Stroke

    ERIC Educational Resources Information Center

    Cloutman, Lauren L.; Newhart, Melisssa; Davis, Cameron L.; Heidler-Gary, Jennifer; Hillis, Argye E.

    2011-01-01

    Oral reading is a complex skill involving the interaction of orthographic, phonological, and semantic processes. Functional imaging studies with nonimpaired adult readers have identified a widely distributed network of frontal, inferior parietal, posterior temporal, and occipital brain regions involved in the task. However, while functional…

  6. Estimation of maximum tolerated dose for long-term bioassays from acute lethal dose and structure by QSAR

    SciTech Connect

    Gombar, V.K.; Enslein, K.; Hart, J.B.; Blake, B.W.; Borgstedt, H.H.

    1991-09-01

    A quantitative structure-activity relationship (QSAR) model has been developed to estimate maximum tolerated doses (MTD) from structural features of chemicals and the corresponding oral acute lethal doses (LD50) as determined in male rats. The model is based on a set of 269 diverse chemicals which have been tested under the National Cancer Institute/National Toxicology Program (NCI/NTP) protocols. The rat oral LD50 value was the strongest predictor. Additionally, 22 structural descriptors comprising nine substructural MOLSTAC(c) keys, three molecular connectivity indices, and sigma charges on 10 molecular fragments were identified as endpoint predictors. The model explains 76% of the variance and is significant (F = 35.7) at p less than 0.0001 with a standard error of the estimate of 0.40 in the log (1/mol) units used in Hansch-type equations. Cross-validation showed that the difference between the average deleted residual square (0.179) and the model residual square (0.160) was not significant (t = 0.98).

  7. TISSUE DISPOSITION OF DIMETHYLARSINIC ACID IN THE MOUSE AFTER ACUTE ORAL ADMINISTRATION

    EPA Science Inventory

    TISSUE DISPOSITION OF DIMETHYLARSINIC ACID IN THE MOUSE
    AFTER ACUTE ORAL ADMINISTRATION

    Michael F. Hughes, Ph.D., Brenda C. Edwards, Carol T. Mitchell and Elaina M. Kenyon, Ph.D. United States Environmental Protection Agency, Office of Research and Development, Nation...

  8. 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.

  9. Minimally differentiated acute myelogenous leukemia (AML-M0) granulocytic sarcoma presenting in the oral cavity.

    PubMed

    Amin, Kay S; Ehsan, Aamir; McGuff, H Stan; Albright, Steven C

    2002-07-01

    Acute myelogenous leukemia with minimal differentiation (AML-M0) is a rare subtype of acute leukemia in which blasts fail to show morphologic differentiation and conventional cytochemical stains and myeloid markers are negative. Acute myelogenous leukemia (AML) presents primarily with peripheral blood and/or bone marrow involvement. Presentation in extramedullary sites, including the head and neck region, is not uncommon. Acute myelomonocytic leukemia (AML-M4) and acute monocytic leukemia (AML-M5) have had the highest incidence of associated oral infiltrates. We report a case of a 58-year-old gentleman, with no prior history of acute leukemia, presenting with a solitary palatal swelling. Initial morphologic examination favored high-grade non-Hodgkin's lymphoma (NHL). Conventional cytochemical and immunohistochemical stains were negative for lymphoid and myeloid markers. Subsequent immunophenotyping via flow cytometry performed on peripheral blood and bone marrow aspirate demonstrated myeloid lineage without lymphoid differentiation, confirming the diagnosis of AML-M0.To our knowledge, this subtype of AML-M0 has not been previously reported involving the oral cavity. With absence of morphologic differentiation, and negative findings on conventional cytochemical and immunohistochemical stains, this subtype of leukemia may be misdiagnosed as non-Hodgkin's lymphoma (NHL). Flow cytometry is useful in detecting the myeloid lineage of this leukemia. PMID:12110349

  10. Oral bisphosphonate use in the elderly is not associated with acute kidney injury.

    PubMed

    Shih, Andrew W Y; Weir, Matthew A; Clemens, Kristin K; Yao, Zhan; Gomes, Tara; Mamdani, Muhammad M; Juurlink, David N; Hird, Amanda; Hodsman, Anthony; Parikh, Chirag R; Wald, Ron; Cadarette, Suzanne M; Garg, Amit X

    2012-10-01

    Intravenous bisphosphonates can cause acute kidney injury; however, this risk was not found with oral bisphosphonates in randomized clinical trials with restrictive eligibility criteria. In order to provide complementary safety data, we studied the risk of acute kidney injury in a population-based cohort of 122,727 patients aged 66 years and older discharged from hospital following a new fragility fracture and no history of bisphosphonate use in the prior year. Bisphosphonate treatment was identified within 120 days after discharge and event rates were measured from 90 days of therapy initiation. The primary outcome was hospitalization with acute kidney injury with secondary outcomes of new nephrology consultation and, in a subset of patients with laboratory values, acute kidney injury was defined as an increase in serum creatinine. We identified 18,286 bisphosphonate users and 104,441 non-users with a mean age of 81 years. Of 5772 patients with laboratory values, 40% had chronic kidney disease (eGFR <60 ml/min per 1.73 m(2)). Overall, there was no statistically significant difference in the risk of acute kidney injury among bisphosphonate users compared to non-users (adjusted odds ratio 1.03), and no significant differences in other outcomes or in subgroups of patients with baseline chronic kidney disease. Thus, in this older population-based cohort, oral bisphosphonate use was not associated with acute kidney injury.

  11. Oral iron acutely elevates bacterial growth in human serum.

    PubMed

    Cross, James H; Bradbury, Richard S; Fulford, Anthony J; Jallow, Amadou T; Wegmüller, Rita; Prentice, Andrew M; Cerami, Carla

    2015-11-23

    Iron deficiency is the most common nutrient deficiency worldwide and routine supplementation is standard policy for pregnant mothers and children in most low-income countries. However, iron lies at the center of host-pathogen competition for nutritional resources and recent trials of iron administration in African and Asian children have resulted in significant excesses of serious adverse events including hospitalizations and deaths. Increased rates of malaria, respiratory infections, severe diarrhea and febrile illnesses of unknown origin have all been reported, but the mechanisms are unclear. We here investigated the ex vivo growth characteristics of exemplar sentinel bacteria in adult sera collected before and 4 h after oral supplementation with 2 mg/kg iron as ferrous sulfate. Escherichia coli, Yersinia enterocolitica and Salmonella enterica serovar Typhimurium (all gram-negative bacteria) and Staphylococcus epidermidis (gram-positive) showed markedly elevated growth in serum collected after iron supplementation. Growth rates were very strongly correlated with transferrin saturation (p < 0.0001 in all cases). Growth of Staphylococcus aureus, which preferentially scavenges heme iron, was unaffected. These data suggest that even modest oral supplements with highly soluble (non-physiological) iron, as typically used in low-income settings, could promote bacteremia by accelerating early phase bacterial growth prior to the induction of immune defenses.

  12. Oral iron acutely elevates bacterial growth in human serum

    PubMed Central

    Cross, James H.; Bradbury, Richard S.; Fulford, Anthony J.; Jallow, Amadou T.; Wegmüller, Rita; Prentice, Andrew M.; Cerami, Carla

    2015-01-01

    Iron deficiency is the most common nutrient deficiency worldwide and routine supplementation is standard policy for pregnant mothers and children in most low-income countries. However, iron lies at the center of host-pathogen competition for nutritional resources and recent trials of iron administration in African and Asian children have resulted in significant excesses of serious adverse events including hospitalizations and deaths. Increased rates of malaria, respiratory infections, severe diarrhea and febrile illnesses of unknown origin have all been reported, but the mechanisms are unclear. We here investigated the ex vivo growth characteristics of exemplar sentinel bacteria in adult sera collected before and 4 h after oral supplementation with 2 mg/kg iron as ferrous sulfate. Escherichia coli, Yersinia enterocolitica and Salmonella enterica serovar Typhimurium (all gram-negative bacteria) and Staphylococcus epidermidis (gram-positive) showed markedly elevated growth in serum collected after iron supplementation. Growth rates were very strongly correlated with transferrin saturation (p < 0.0001 in all cases). Growth of Staphylococcus aureus, which preferentially scavenges heme iron, was unaffected. These data suggest that even modest oral supplements with highly soluble (non-physiological) iron, as typically used in low-income settings, could promote bacteremia by accelerating early phase bacterial growth prior to the induction of immune defenses. PMID:26593732

  13. Oral iron acutely elevates bacterial growth in human serum.

    PubMed

    Cross, James H; Bradbury, Richard S; Fulford, Anthony J; Jallow, Amadou T; Wegmüller, Rita; Prentice, Andrew M; Cerami, Carla

    2015-01-01

    Iron deficiency is the most common nutrient deficiency worldwide and routine supplementation is standard policy for pregnant mothers and children in most low-income countries. However, iron lies at the center of host-pathogen competition for nutritional resources and recent trials of iron administration in African and Asian children have resulted in significant excesses of serious adverse events including hospitalizations and deaths. Increased rates of malaria, respiratory infections, severe diarrhea and febrile illnesses of unknown origin have all been reported, but the mechanisms are unclear. We here investigated the ex vivo growth characteristics of exemplar sentinel bacteria in adult sera collected before and 4 h after oral supplementation with 2 mg/kg iron as ferrous sulfate. Escherichia coli, Yersinia enterocolitica and Salmonella enterica serovar Typhimurium (all gram-negative bacteria) and Staphylococcus epidermidis (gram-positive) showed markedly elevated growth in serum collected after iron supplementation. Growth rates were very strongly correlated with transferrin saturation (p < 0.0001 in all cases). Growth of Staphylococcus aureus, which preferentially scavenges heme iron, was unaffected. These data suggest that even modest oral supplements with highly soluble (non-physiological) iron, as typically used in low-income settings, could promote bacteremia by accelerating early phase bacterial growth prior to the induction of immune defenses. PMID:26593732

  14. Evaluation of Caenorhabditis elegans as an acute lethality and a neurotoxicity screening model

    SciTech Connect

    Williams, P.L.

    1988-01-01

    This investigation evaluated C. elegans as a lethality and neurotoxicity screening model. The lethality experiments were performed in both agar and an aquatic medium. The salts of 8 metals (Hg, Be, Al, Cu, Zn, Pb, Cd, and Sr) were used in the agar studies and the salts of 14 metals (Ag, Hg, Cu, Be, Al, Pb, Cr, As, Tl, Zn, Cd, Ni, Sr, and Sb) were used in the aquatic tests. In each of these tests an LC50 value was determined. The data from the agar plates were compared to the published mammalian oral LD50 values for salts of the same metals. Within this set of chemicals C. elegans was found to be a predictor of mammalian acute lethality, generating LC50 values parallel to the rat and mouse LD50 values. The aquatic data were compared to data from EPA Ambient Water Quality Criteria documents. C. elegans was found to be less sensitive than Daphnia but generally more sensitive than the other invertebrate organisms that are presently used. The neurotoxicity testing also was performed in both agar and an aquatic media. The testing in agar was conducted with the salts of 4 metals (Cu, Be, Pb, and Hg) and 2 organophosphate pesticides (malathion and vapona). The studies in an aquatic medium tested the salts of 4 metals (Cu, Be, Pb, and Hg).

  15. Transitioning antimicrobials from intravenous to oral in pediatric acute uncomplicated osteomyelitis

    PubMed Central

    Batchelder, Nathan; So, Tsz-Yin

    2016-01-01

    Osteomyelitis is a bone infection that requires prolonged antibiotic treatment and potential surgical intervention. If left untreated, acute osteomyelitis can lead to chronic osteomyelitis and overwhelming sepsis. Early treatment is necessary to prevent complications, and the standard of care is progressing to a shorter duration of intravenous (IV) antibiotics and transitioning to oral therapy for the rest of the treatment course. We systematically reviewed the current literature on pediatric patients with acute osteomyelitis to determine when and how to transition to oral antibiotics from a short IV course. Studies have shown that switching to oral after a short course (i.e., 3-7 d) of IV therapy has similar cure rates to continuing long-term IV therapy. Prolonged IV use is also associated with increased risk of complications. Parameters that help guide clinicians on making the switch include a downward trend in fever, improvement in local tenderness, and a normalization in C-reactive protein concentration. Based on the available literature, we recommend transitioning antibiotics to oral after 3-7 d of IV therapy for pediatric patients (except neonates) with acute uncomplicated osteomyelitis if there are signs of clinical improvement, and such regimen should be continued for a total antibiotic duration of four to six weeks. PMID:27610339

  16. [Acute oral suicidal intoxication with captan--a case report].

    PubMed

    Chodorowski, Zygmunt; Sein Anand, Jacek; Waldman, Wojciech

    2004-01-01

    According to the best of our knowledge the second case of acute intoxication with captan was described. In this paper a 22-year old female was admitted to the Department of Toxicology with a nausea, weakness, numbness of upper limbs and substernal pain. She said that these symptoms began two hours after suicidal ingestion of 5.0 g of captan. At admission the patient was alert. Temperature was 37 degrees C, heart rate 100-120 b/min., BP 100-120/60-70 mm Hg and breathing rate 17/min. WBC were slightly elevated 12.4 x 10(3)/microl as well as the creatine kinase activity 329 U/L. ECG showed inversion of a T segment in V1-V4 leads. ECHO-sound made in 4th and 120th day after the onset of intoxication showed no changes, with EF--70%. Temporary increase of creatine kinase activity as well as the presence of inverted T segment in V1-V4 leads may suggest cardiotoxic effects of captan during acute intoxication.

  17. Acute ischaemic colitis associated with oral phenylephrine decongestant use.

    PubMed

    Ward, Paul W; Shaneyfelt, Terrence M; Roan, Ronald M

    2014-01-01

    In this case, the authors have presented for the first time that ischaemic colitis may be associated with phenylephrine use. Since phenylephrine is the more common active ingredient in over-the-counter (OTC) cold medications, other presentations may follow this case. A MEDLINE search was performed for all case reports or case series of ischaemic colitis secondary to pseudoephedrine or phenylephrine use published between 1966 and 2013. The search resulted in four case reports and one case series describing patients with acute onset ischaemic colitis with exposure to pseudoephedrine immediately prior to onset. However, we found no case reports of ischaemic colitis associated with phenylephrine use. We present this case as an unexpected clinical outcome of phenylephrine, which has not been associated with ischaemic colitis in the literature. Also, this case serves as a reminder of the important clinical lesson to question all patients' use of OTC and prescribed medications.

  18. Acute and subchronic oral toxicities of Calendula officinalis extract in Wistar rats.

    PubMed

    Lagarto, Alicia; Bueno, Viviana; Guerra, Isbel; Valdés, Odalys; Vega, Yamile; Torres, Leonid

    2011-05-01

    We have studied the acute and subchronic oral toxicities of Calendula officinalis extract in male and female Wistar rats. A single acute C. officinalis extract dose of 2000 mg/kg dissolved in distilled water was administered by oral gavage for acute toxicity. Subchronic doses of 50, 250 and 1000 mg/kg/day were administered in drinking water. The major toxicological endpoints examined included animal body weight, water and food intake, selected tissue weights, and histopathological examinations. In addition, we examined blood elements: hematocrit, hemoglobin concentration, erythrocyte count, total and differential leukocyte count and blood clotting time and blood chemistry: glucose, total cholesterol, urea, total proteins, alkaline phosphatase, alanine aminotransferase (ALT) and aspartate aminotransferase (AST). In the acute study, there were no mortality and signs of toxicity. In the subchronic study, several of the blood elements were significantly affected in males and females after 90 days; hemoglobin, erythrocytes, leukocytes and blood clotting time. For blood chemistry parameters, ALT, AST and alkaline phosphatase were affected. Histopathological examination of tissues showed slight abnormalities in hepatic parenchyma that were consistent with biochemical variations observed. These studies indicate that the acute and subchronic toxicities of C. officinalis extract are low. PMID:20335011

  19. Acute and subchronic oral toxicities of Calendula officinalis extract in Wistar rats.

    PubMed

    Lagarto, Alicia; Bueno, Viviana; Guerra, Isbel; Valdés, Odalys; Vega, Yamile; Torres, Leonid

    2011-05-01

    We have studied the acute and subchronic oral toxicities of Calendula officinalis extract in male and female Wistar rats. A single acute C. officinalis extract dose of 2000 mg/kg dissolved in distilled water was administered by oral gavage for acute toxicity. Subchronic doses of 50, 250 and 1000 mg/kg/day were administered in drinking water. The major toxicological endpoints examined included animal body weight, water and food intake, selected tissue weights, and histopathological examinations. In addition, we examined blood elements: hematocrit, hemoglobin concentration, erythrocyte count, total and differential leukocyte count and blood clotting time and blood chemistry: glucose, total cholesterol, urea, total proteins, alkaline phosphatase, alanine aminotransferase (ALT) and aspartate aminotransferase (AST). In the acute study, there were no mortality and signs of toxicity. In the subchronic study, several of the blood elements were significantly affected in males and females after 90 days; hemoglobin, erythrocytes, leukocytes and blood clotting time. For blood chemistry parameters, ALT, AST and alkaline phosphatase were affected. Histopathological examination of tissues showed slight abnormalities in hepatic parenchyma that were consistent with biochemical variations observed. These studies indicate that the acute and subchronic toxicities of C. officinalis extract are low.

  20. Acute oral toxicity and biodistribution study of zinc-aluminium-levodopa nanocomposite

    NASA Astrophysics Data System (ADS)

    Kura, Aminu Umar; Saifullah, Bullo; Cheah, Pike-See; Hussein, Mohd Zobir; Azmi, Norazrina; Fakurazi, Sharida

    2015-03-01

    Layered double hydroxide (LDH) is an inorganic-organic nano-layered material that harbours drug between its two-layered sheets, forming a sandwich-like structure. It is attracting a great deal of attention as an alternative drug delivery (nanodelivery) system in the field of pharmacology due to their relative low toxic potential. The production of these nanodelivery systems, aimed at improving human health through decrease toxicity, targeted delivery of the active compound to areas of interest with sustained release ability. In this study, we administered zinc-aluminium-LDH-levodopa nanocomposite (ZAL) and zinc-aluminium nanocomposite (ZA) to Sprague Dawley rats to evaluate for acute oral toxicity following OECD guidelines. The oral administration of ZAL and ZA at a limit dose of 2,000 mg/kg produced neither mortality nor acute toxic signs throughout 14 days of the observation. The percentage of body weight gain of the animals showed no significant difference between control and treatment groups. Animal from the two treated groups gained weight continuously over the study period, which was shown to be significantly higher than the weight at the beginning of the study ( P < 0.05). Biochemical analysis of animal serum showed no significant difference between rats treated with ZAL, ZA and controls. There was no gross lesion or histopathological changes observed in vital organs of the rats. The results suggested that ZAL and ZA at 2,000 mg/kg body weight in rats do not induce acute toxicity in the animals. Elemental analysis of tissues of treated animals demonstrated the wider distribution of the nanocomposite including the brain. In summary, findings of acute toxicity tests in this study suggest that zinc-aluminium nanocomposite intercalated with and the un-intercalated were safe when administered orally in animal models for short periods of time. It also highlighted the potential distribution ability of Tween-80 coated nanocomposite after oral administration.

  1. Effective management of acute deep vein thrombosis: direct oral anticoagulants.

    PubMed

    Roussin, A

    2015-02-01

    Deep vein thrombosis (DVT) is a manifestation of venous thromboembolism (VTE) and accounts for most venous thromboembolic events. Although DVT is not directly life-threatening, thrombi in the proximal veins of the leg can embolize to the lungs to form a pulmonary embolism, which may prove rapidly fatal. If untreated, DVT can also lead to significant morbidity, including development of post-thrombotic syndrome. Among many risk factors, surgery, hospitalization, older age and active cancer increase the risk of VTE, and a previous event increases the risk of recurrence. Early detection and effective clot resolution are vital in managing DVT. Conventional approaches to acute treatment of VTE involve initial fast-acting parenteral heparin overlapping with and followed by vitamin K antagonist therapy. However, vitamin K antagonists have a narrow therapeutic window, require regular monitoring, and have multiple food and drug interactions. Results from phase III clinical studies involving direct Factor Xa and IIa inhibitors suggest that these agents provide an alternative therapeutic option that overcomes some of the complications associated with conventional treatment with predictable pharmacological properties and convenient dosing schedules. Analysis of data from the rivaroxaban EINSTEIN studies also suggests that these agents have the potential to improve patient-reported treatment satisfaction and reduce the length of hospital stay compared with conventional therapy. This review considers these treatment options, suitable treatment durations to prevent recurrence, and the management of DVT treatment in challenging patient groups. PMID:24927023

  2. Critique on the use of the standardized avian acute oral toxicity test for first generation anticoagulant rodenticides

    USGS Publications Warehouse

    Vyas, Nimish B.; Rattner, Barnett A.

    2012-01-01

    Avian risk assessments for rodenticides are often driven by the results of standardized acute oral toxicity tests without regards to a toxicant's mode of action and time course of adverse effects. First generation anticoagulant rodenticides (FGARs) generally require multiple feedings over several days to achieve a threshold concentration in tissue and cause adverse effects. This exposure regimen is much different than that used in the standardized acute oral toxicity test methodology. Median lethal dose values derived from standardized acute oral toxicity tests underestimate the environmental hazard and risk of FGARs. Caution is warranted when FGAR toxicity, physiological effects, and pharmacokinetics derived from standardized acute oral toxicity testing are used for forensic confirmation of the cause of death in avian mortality incidents and when characterizing FGARs' risks to free-ranging birds.

  3. Help Desk Answers: Are IV fluids better than oral rehydration for children with acute diarrhea and vomiting?

    PubMed

    Patnaik, Suvag; Nanda, Mitali; Tiburicio, Jose

    2016-04-01

    Intravenous fluid therapy (IVF) has a slightly lower failure rate than oral replacement therapy (ORT) in children with acute gastroenteritis, but the clinical significance is questionable. IVF takes longer to initiate than ORT and lengthens the hospital stay. PMID:27262252

  4. Development of an Orientia tsutsugamushi Lc-1 Murine Intraperitoneal Challenge Model for Scrub Typhus: Determination of Murine Lethal Dose (MuLD50), Tissue Bacterial Loads, and Clinical Outcomes.

    PubMed

    Lurchachaiwong, Woradee; McCardle, Wesley; Chan, Teik-Chye; Schuster, Anthony L; Richards, Allen L

    2015-09-01

    Currently, no vaccine has been developed to protect humans from naturally acquired heterologous Orientia tsutsugamushi infections. To enhance the validity of vaccine candidates, we are developing a murine chigger challenge model with the O. tsutsugamushi Lc-1-infected Leptotrombidium chiangraiensis Line-1. To this end, an intraperitoneal (i.p.) murine challenge model using an O. tsutsugamushi Lc-1 isolate was developed for eventual validation of the chigger challenge model. We have determined that the murine lethal dose that kills 50% of the challenged mice (MuLD50) of a liver/spleen homogenate developed from O. tsutsugamushi Lc-1-infected ICR Swiss mice to be 10(-6.9). Employing different inoculum doses of this homogenate, the bacterial load using quantitative real-time PCR (qPCR) was determined to range from 60 to 1.6 × 10(5) genome equivalent copies (GEC)/μL of liver and 33.4 to 2.2 × 10(5) GEC/μL of spleen tissue. The clinical outcomes relative to homogenate dose levels followed a dose-dependent pattern. The successful development and characterization of the O. tsutsugamushi Lc-1 i.p. challenge model will assist in the development and validation of a mouse chigger challenge scrub typhus model.

  5. Acute Myeloid Leukaemia Diagnosed by Intra-Oral Myeloid Sarcoma. A Case Report

    PubMed Central

    Papamanthos, Mattheos K.; Skulakis, Haralampos E.; Fericean, Angela-Monika A.; Zorba, Matina T.; Matiakis, Apostolos T.

    2010-01-01

    Myeloid sarcoma (MS) is a rare extramedullary malignant tumor composed of immature myeloid cells. It is strongly associated with a well known or covert acute myeloid leukaemia, chronic myeloproliferative diseases or myelodysplastic syndromes. Intraoral MS scarcely occurs. An unusual case of acute myeloid leukaemia, which was diagnosed by mandibular MS that was developed in the alveolar socket after a dental extraction, is reported. The histological examination (including immunohistochemical analysis) of a subsequent biopsy showed infiltration of the oral mucosa by neoplastic cells. This lesion was therefore classified as acute myeloid leukaemia. The patient was referred to oncologists that confirmed the initial diagnosis. The patient underwent chemotherapy and the mandibular tumor disappeared. Forty days later, a relapse of the disease, which appeared as a great-ulcerated lesion, was developed in the hard palate. Thirty days after the second chemotherapy had finished, a new intraoral tumor was developed in the vestibular maxillary gingiva. Review of the literature shows no report of intraoral relapse and particularly multiple relapse of a MS that involves the oral cavity. Even though MS is encountered infrequently in the oral cavity, it should be considered in the differential diagnosis of conditions (especially tumors) with a similar clinical appearance. PMID:20512638

  6. Genetic and acute toxicological evaluation of an algal oil containing eicosapentaenoic acid (EPA) and palmitoleic acid.

    PubMed

    Collins, M L; Lynch, B; Barfield, W; Bull, A; Ryan, A S; Astwood, J D

    2014-10-01

    Algal strains of Nannochloropsis sp. were developed, optimized, cultivated and harvested to produce a unique composition of algal oil ethyl esters (Algal-EE) that are naturally high in eicosapentaenoic acid (EPA, 23-30%) and palmitoleic acid (20-25%), and contain no docosahexaenoic acid (DHA). Algal-EE was evaluated for mutagenic activity (Ames bacterial reverse mutation, in vitro mammalian chromosome aberration, in vivo micronucleus test) and for acute oral toxicity in Sprague-Dawley rats. In the acute toxicity study, rats received a single oral gavaged dose of Algal-EE (2000 mg/kg body weight). Clinical observations were made for 14 days before sacrifice on Day 15. Macroscopic evaluation involved the examination of all organs in the cranial, thoracic, and abdominal cavities. Algal-EE showed no evidence of mutagenicity, did not produce an increase in the frequency of structural chromosome aberrations, and did not cause an increase in the induction of micronucleated polychromatic erythrocytes. There were no macroscopic abnormalities. Algal-EE up to 2000 mg/kg body weight did not affect body weight, organ appearance or produce any toxic-related signs of morbidity. The acute median lethal dose (LD50) of Algal-EE was >2000 mg/kg body weight. Based on these assays, Algal-EE does not appear to have any genetic or acute oral toxicity. PMID:25057807

  7. Comparison of oral montelukast with oral zileuton in acute asthma: A randomized, double-blind, placebo-controlled study

    PubMed Central

    Magazine, Rahul; Shahul, Hameed Aboobackar; Chogtu, Bharti; Kamath, Asha

    2016-01-01

    Background: Leukotriene modifiers have an established role in the management of chronic asthma but their role in acute asthma is still under evaluation. Objective: To study and compare the effects of oral montelukast with oral zileuton in acute asthma. Materials and Methods: This study included 120 asthmatics and was conducted from September 2012 to March 2014. Patients were randomized into three different groups to receive montelukast or zileuton or placebo in addition to standard treatment for asthma exacerbation. Peak expiratory flow rate (PEFR) values, details of rescue medication and vital signs were recorded at 6 h, 12 h, 24 h, and 48 h of drug or placebo administration and at discharge. Additional recording was done in the morning (8–10 am) following admission. The primary endpoint was the mean PEFR of each group at these time points; the secondary end point being the need for rescue medications. Results: The mean PEFR recordings of the three study groups – placebo, montelukast, and zileuton – respectively, at various time points were as follows: at 6 h (223.25 ± 90.40, 199.00 ± 82.52, 233.75 ± 84.05; P = 0.240); at 12 h (271.00 ± 109.38, 251.50 ± 101.44, 309.50 ± 129.63; P = 0.048); at 24 h (288.25 ± 114.26, 269.00 ± 107.51, 324.50 ± 127.88; P = 0.080); and at 48 h (295.00 ± 114.80, 293.50 ± 113.24, 344.75 ± 119.91; P = 0.015); discharge (305.00 ± 118.56, 305.25 ± 119.51, 361.25 ± 119.70; P = 0.010). The mean PEFR for the three study groups at 8–10 am on the morning following admission was 268.75 ± 111.43, 252.50 ± 99.99, 306.75 ± 114.44; P = 0.047. Total rescue doses needed were 10, 1, and 0, respectively (P = 0.049). Conclusion: Zileuton is better than montelukast as an additional drug in acute asthma and results in significant improvement in lung function, and reduction in the need for rescue medications. PMID:27185992

  8. Oral N-acetylcysteine has a deleterious effect in acute iron intoxication in rats.

    PubMed

    Abu-Kishk, Ibrahim; Kozer, Eran; Goldstein, Lee H; Weinbaum, Sarit; Bar-Haim, Adina; Alkan, Yoav; Petrov, Irena; Evans, Sandra; Siman-Tov, Yariv; Berkovitch, Matitiahu

    2010-01-01

    Acute iron intoxication is associated with depletion of reduced glutathione in hepatocytes and changes in the glutathione system enzymes. We hypothesized that treatment with N-acetylcysteine (NAC), a glutathione reducing agent and an antioxidant, would reduce mortality in acute iron intoxication. We used a rat model to test this hypothesis. Male rats were assigned to 4 groups. Group 1 received 400 mg/kg elemental iron by oral gavage, group 2 received the same dose of iron followed by NAC, group 3 received NAC only, whereas group 4 received distilled water. Iron and liver transaminases in the blood, and glutathione system enzymes in the liver and erythrocytes were measured. Mortality in group 2 was significantly higher after 2, 6, and 24 hours compared with group 1 (P < .001). No deaths were observed in groups 3 and 4. Serum iron levels were significantly higher in group 2 rats compared to group 1 rats (P < .001). Hepatic and erythrocyte glutathione system enzymes were significantly lower among rats in group 2 compared to rats in group 1. The administration of NAC probably increased the absorption of iron through the gastrointestinal tract, causing higher serum iron levels with significant hepatic damage. These results indicate that in a rat model of acute iron intoxication, orally administered NAC may increase mortality. PMID:20006194

  9. Effects of chelating agents on oral uptake and renal deposition and excretion of cadmium.

    PubMed Central

    Engström, B

    1984-01-01

    The gastrointestinal absorption, transport, tissue deposition and excretion of cadmium was studied in adult male mice given a single oral LD50 dose of 109Cd-labeled CdCl2 alone or in combination with nitrilotriacetic acid (NTA), sodium tripolyphosphate (STPP) or ethylenediaminetetraacetic acid (EDTA). Blood, intestinal mucosa, liver and kidneys were analyzed for 109Cd at different times after exposure and the influence of the chelating agents on Cd binding to metallothionein and other tissue ligands was also studied. Acute toxicity was noted. Complex formation between Cd and EDTA was studied in solutions containing Cd:EDTA at 1:04 and 1:4 molar ratios. Adult male mice were exposed orally or by direct infusion into the stomach to either of the two solutions (containing an LD50 dose of Cd). Body retention and tissue deposition of Cd was recorded after 4 (direct infusion) or 21 days (oral exposure), and the mortality in different exposure groups observed. Adult male were also exposed to a low oral dose of 109Cd-labeled cadmium (0.5 mg/kg), followed by 18 months continuous administration of NTA, (500 ppm) STPP (500 ppm) or EDTA (50 ppm) in the drinking water or the chelating agent in combination with Cd (50 ppm), Cd alone (50 ppm) or deionized water. Whole-body retention of 109Cd, tissue deposition of 109Cd and total Cd and development of proteinuria were observed. When cadmium was given with an excess of EDTA, all Cd ions were bound in a 1:1 Cd-EDTA complex. Decreased acute toxicity was observed which was related to increased body elimination of cadmium. The Cd passes though the body still bound to EDTA and is excreted via the kidneys in this form. Similar results were found in mice exposed to Cd + NTA, while gavage of CD + STPP led to an initially decreased systemic uptake of Cd and thereafter to a prolongation of the biological half-time and thus a comparatively higher body retention of the metal. Cd may form a 2:1 complex with EDTA in the presence of excess cadmium

  10. Toxicity of oral exposure to 2,4,6-trinitrotoluene in the western fence lizard (Sceloporus occidentalis).

    PubMed

    McFarland, Craig A; Quinn, Michael J; Bazar, Matthew A; Remick, Amera K; Talent, Larry G; Johnson, Mark S

    2008-05-01

    Contamination of the soil with the explosive 2,4,6-trinitrotoluene (TNT) has been found at military sites, many of which are habitats used by reptiles. To provide data useful in assessing ecological risk for reptilian species, acute, subacute, and subchronic oral toxicity studies were conducted with the western fence lizard (Sceloporus occidentalis). Oral median lethal dose (LD50) values for TNT in corn oil were 1,038 and 1,579 mg/kg of body weight for male and female lizards, respectively. Overt signs of toxicity included chromaturia, abdominal enlargement, and tremors. A 14-d subacute study followed in which male lizards were orally dosed with TNT (corn oil) at 0, 33, 66, 132, 263, 525, and 1,050 mg/kg of body weight each day. Clinical signs of toxicity, while similar to the LD50 study, were more subtle and noted in lizards receiving TNT amounts of at least 66 mg/kg/d. Chromaturia was an early consistent sign, often preceding the onset of adverse effects. Male lizards in the 60-d subchronic study were dosed at 0, 3, 15, 25, 35, and 45 mg/kg/d with nearly complete survival (>90%) for lizards in all treatments. Changes in food consumption and body weight were observed at 35 and 45 mg/kg/d. Alterations in hematological end points; blood chemistries (albumin, total protein, alkaline phosphatase, calcium); kidney, spleen, and liver weights; and adverse histopathology were observed in lizards exposed at 25 to 45 mg/kg/d. Testosterone concentration, sperm count, and motility were variable between treatments. Although not significant, incidences of hypospermia and testicular atrophy were observed in some individuals. Together, these data suggest a lowest-observed-adverse effect level of 25 mg/kg/d and a no-observed-adverse effect level of 15 mg/kg/d in S. occidentalis. PMID:18419183

  11. Toxicity of oral exposure to 2,4,6-trinitrotoluene in the western fence lizard (Sceloporus occidentalis).

    PubMed

    McFarland, Craig A; Quinn, Michael J; Bazar, Matthew A; Remick, Amera K; Talent, Larry G; Johnson, Mark S

    2008-05-01

    Contamination of the soil with the explosive 2,4,6-trinitrotoluene (TNT) has been found at military sites, many of which are habitats used by reptiles. To provide data useful in assessing ecological risk for reptilian species, acute, subacute, and subchronic oral toxicity studies were conducted with the western fence lizard (Sceloporus occidentalis). Oral median lethal dose (LD50) values for TNT in corn oil were 1,038 and 1,579 mg/kg of body weight for male and female lizards, respectively. Overt signs of toxicity included chromaturia, abdominal enlargement, and tremors. A 14-d subacute study followed in which male lizards were orally dosed with TNT (corn oil) at 0, 33, 66, 132, 263, 525, and 1,050 mg/kg of body weight each day. Clinical signs of toxicity, while similar to the LD50 study, were more subtle and noted in lizards receiving TNT amounts of at least 66 mg/kg/d. Chromaturia was an early consistent sign, often preceding the onset of adverse effects. Male lizards in the 60-d subchronic study were dosed at 0, 3, 15, 25, 35, and 45 mg/kg/d with nearly complete survival (>90%) for lizards in all treatments. Changes in food consumption and body weight were observed at 35 and 45 mg/kg/d. Alterations in hematological end points; blood chemistries (albumin, total protein, alkaline phosphatase, calcium); kidney, spleen, and liver weights; and adverse histopathology were observed in lizards exposed at 25 to 45 mg/kg/d. Testosterone concentration, sperm count, and motility were variable between treatments. Although not significant, incidences of hypospermia and testicular atrophy were observed in some individuals. Together, these data suggest a lowest-observed-adverse effect level of 25 mg/kg/d and a no-observed-adverse effect level of 15 mg/kg/d in S. occidentalis.

  12. Orally Administered Enoxaparin Ameliorates Acute Colitis by Reducing Macrophage-Associated Inflammatory Responses

    PubMed Central

    Lean, Qi Ying; Eri, Rajaraman D.; Randall-Demllo, Sarron; Sohal, Sukhwinder Singh; Stewart, Niall; Peterson, Gregory M.; Gueven, Nuri; Patel, Rahul P.

    2015-01-01

    Inflammatory bowel diseases, such as ulcerative colitis, cause significant morbidity and decreased quality of life. The currently available treatments are not effective in all patients, can be expensive and have potential to cause severe side effects. This prompts the need for new treatment modalities. Enoxaparin, a widely used antithrombotic agent, is reported to possess anti-inflammatory properties and therefore we evaluated its therapeutic potential in a mouse model of colitis. Acute colitis was induced in male C57BL/6 mice by administration of dextran sulfate sodium (DSS). Mice were treated once daily with enoxaparin via oral or intraperitoneal administration and monitored for colitis activities. On termination (day 8), colons were collected for macroscopic evaluation and cytokine measurement, and processed for histology and immunohistochemistry. Oral but not intraperitoneal administration of enoxaparin significantly ameliorated DSS-induced colitis. Oral enoxaparin-treated mice retained their body weight and displayed less diarrhea and fecal blood loss compared to the untreated colitis group. Colon weight in enoxaparin-treated mice was significantly lower, indicating reduced inflammation and edema. Histological examination of untreated colitis mice showed a massive loss of crypt architecture and goblet cells, infiltration of immune cells and the presence of edema, while all aspects of this pathology were alleviated by oral enoxaparin. Reduced number of macrophages in the colon of oral enoxaparin-treated mice was accompanied by decreased levels of pro-inflammatory cytokines. Oral enoxaparin significantly reduces the inflammatory pathology associated with DSS-induced colitis in mice and could therefore represent a novel therapeutic option for the management of ulcerative colitis. PMID:26218284

  13. Acute, reproductive toxicity and two-generation teratology studies of a standardized quassinoid-rich extract of Eurycoma longifolia Jack in Sprague-Dawley rats.

    PubMed

    Low, Bin-Seng; Das, Prashanta Kumar; Chan, Kit-Lam

    2014-07-01

    The roots of Eurycoma longifolia Jack are popularly sought as herbal medicinal supplements to improve libido and general health amongst the local ethnic population. The major quassinoids of E. longifolia improved spermatogenesis and fertility but toxicity studies have not been well documented. The reproductive toxicity, two generation of foetus teratology and the up-and-down acute toxicity were investigated in Sprague-Dawley rats orally treated with quassinoid-rich E. longifolia extract (TAF273). The results showed that the median lethal dose (LD50 ) of TAF273 for female and male rats was 1293 and >2000 mg/kg, respectively. Fertility index and litter size of the TAF273 treated were significantly increased when compared with those of the non-treated animals. The TAF273-treated dams decreased in percentage of pre-implantation loss, post-implantation loss and late resorption. No toxic symptoms were observed on the TAF273-treated pregnant female rats and their foetuses were normal. The no-observed adverse effect level (NOAEL) obtained from reproductive toxicity and teratology studies of TAF273 in rats was 100 mg/kg body weight/day, being more than 10-fold lower than the LD50 value. Thus, any human dose derived from converting the rat doses of 100 mg/kg and below may be considered as safe for further clinical studies. PMID:24318772

  14. Acute, reproductive toxicity and two-generation teratology studies of a standardized quassinoid-rich extract of Eurycoma longifolia Jack in Sprague-Dawley rats.

    PubMed

    Low, Bin-Seng; Das, Prashanta Kumar; Chan, Kit-Lam

    2014-07-01

    The roots of Eurycoma longifolia Jack are popularly sought as herbal medicinal supplements to improve libido and general health amongst the local ethnic population. The major quassinoids of E. longifolia improved spermatogenesis and fertility but toxicity studies have not been well documented. The reproductive toxicity, two generation of foetus teratology and the up-and-down acute toxicity were investigated in Sprague-Dawley rats orally treated with quassinoid-rich E. longifolia extract (TAF273). The results showed that the median lethal dose (LD50 ) of TAF273 for female and male rats was 1293 and >2000 mg/kg, respectively. Fertility index and litter size of the TAF273 treated were significantly increased when compared with those of the non-treated animals. The TAF273-treated dams decreased in percentage of pre-implantation loss, post-implantation loss and late resorption. No toxic symptoms were observed on the TAF273-treated pregnant female rats and their foetuses were normal. The no-observed adverse effect level (NOAEL) obtained from reproductive toxicity and teratology studies of TAF273 in rats was 100 mg/kg body weight/day, being more than 10-fold lower than the LD50 value. Thus, any human dose derived from converting the rat doses of 100 mg/kg and below may be considered as safe for further clinical studies.

  15. Acute and subchronic toxicity of naturally weathered Exxon Valdez crude oil in mallards and ferrets

    SciTech Connect

    Stubblefield, W.A.; Hancock, G.A.; Ford, W.H.; Ringer, R.K.

    1995-11-01

    The toxic properties of naturally weathered Exxon Valdez crude oil (WEVC) were assessed in a battery of acute and subchronic toxicity tests using mallards, Anas platyrhynchos, and European ferrets, Mustela putorius. Adult mallard acute oral toxicity study results indicated no mortalities or signs o toxicity, i.e., no-observed-adverse-effect level (NOAEL) and median lethal dose (LD50) > 5,000 mg/kg. Acute oral feeding and food avoidance tests with ducklings also indicated no toxicity (NOAEL and LC50 > 50,000 mg/kg diet) with no evidence of food avoidance (FAC50 > 20,000 mg/kg diet). No mortalities or toxic signs were noted in a 14-d feeding study with adult birds at dietary concentrations up to 100,000 mg WEVC/kg diet. Among clinical and physiological end points evaluated, the only significant difference noted was an increase in liver: body weight ratios in the 100,000-mg WEVC/kg diet dose group. No differences in clinical chemistry or hematological parameters were noted, and there were no consistent differences in histological evaluations of organ tissues. Daily oral doses of up to 5,000 mg/kg of WEVC over 5 d resulted in minimal effects on ferrets. Increased serum albumin concentrations were observed in the 5,000-mg/kg dose group females and decreased spleen weights were noted in females of all WEVC treatment groups. No other significant observations were noted.

  16. Toxicological assessment of combined lead and cadmium: acute and sub-chronic toxicity study in rats.

    PubMed

    Yuan, Guiping; Dai, Shujun; Yin, Zhongqiong; Lu, Hongke; Jia, Renyong; Xu, Jiao; Song, Xu; Li, Li; Shu, Yang; Zhao, Xinghong

    2014-03-01

    The exposure to chemical mixtures is a common and important determinant of toxicity and receives concern for their introduction by inhalation and ingestion. However, few in vivo mixture studies have been conducted to understand the health effects of chemical mixtures compared with single chemicals. In this study, the acute and 90day sub-chronic toxicity tests of combined Pb and Cd were conducted. In the acute toxicity test, the LD50 value of Pb(NO3)2 and CdCl2 mixture by the oral route was 2696.54mg/kg by Bliss method. The sub-chronic treatment revealed that the low-dose combination of Pb and Cd exposures can significantly change the physiological and biochemical parameters of the blood of Sprague-Dawley (SD) rats with dose-response relationship and causes microcytic hypochromic anemia and the damages of liver and kidney of the SD rats to various degrees. Histopathological exams showed that the target organs of Pb and Cd were testicle, liver, and kidneys. These observations suggest that Pb and Cd are practically additive-toxic for the SD rats in oral acute toxicity studies. The lowest observed adverse-effect level in rats may be lower than a dose of 29.96mg/(kgbwday) when administered orally for 90 consecutive days.

  17. [Oral rehydration in acute gastroenteritis in infants and children--advantages of a standardized protocol].

    PubMed

    Weizman, Z; Weizman, A; Alsheikh, A; Herzog, L; Tal, A; Gorodischer, R

    2000-11-01

    Oral rehydration (OR) for acute gastroenteritis in infants and children has been shown to be as effective as IV therapy, with less discomfort and lower costs. In this retrospective study we compared 2 pediatric wards, in 1 of which only a standardized, simplified, bedside protocol, based on American Academy of Pediatrics guidelines, was used. There were no significant clinical characteristics in the 208 patients. In the ward which used the above protocol, OR utilization was significantly more frequent than in the other ward (48% versus 15%), thus saving equipment costs of nearly $1,000/3 months. There were no significant differences in outcome between the wards. We conclude that introducing a standardized management protocol may increase OR utilization in hospitalized children with acute diarrhea. PMID:11341212

  18. Evaluation of acute and sub-acute toxicity of Pinus eldarica bark extract in Wistar rats

    PubMed Central

    Ghadirkhomi, Akram; Safaeian, Leila; Zolfaghari, Behzad; Agha Ghazvini, Mohammad Reza; Rezaei, Parisa

    2016-01-01

    Objective: Pinus eldarica (P. eldarica) is one of the most common pines in Iran which has various bioactive constituents and different uses in traditional medicine. Since there is no documented evidence for P. eldarica safety, the acute and sub-acute oral toxicities of hydroalcoholic extract of P. eldarica bark were investigated in male and female Wistar rats in this study. Materials and Methods: In the acute study, a single dose of extract (2000 mg/kg) was orally administered and animals were monitored for 7 days. In the sub-acute study, repeated doses (125, 250 and 500 mg/kg/day) of the extract were administered for 28 days and biochemical, hematological and histopathological parameters were evaluated. Results: Our results showed no sign of toxicity and no mortality after single or repeated administration of P. eldarica. The median lethal dose (LD50) of P. eldarica was determined to be higher than 2000 mg/kg. The mean body weight and most of the biochemical and hematological parameters showed normal levels. There were only significant decreases in serum triglyceride levels at the doses of 250 and 500 mg/kg of the extract in male rats (p<0.05 and p<0.01, respectively) and in monocyte counts at the highest dose of the extract in both male and female rats (p<0.05). Mild inflammation was also found in histological examination of kidney and liver tissues at the highest dose of extract. Conclusion: Oral administration of the hydroalcoholic extract of P. eldarica bark may be considered as relatively non-toxic particularly at the doses of 125 and 250 mg/kg. PMID:27761426

  19. Safety evaluation of turmeric polysaccharide extract: assessment of mutagenicity and acute oral toxicity.

    PubMed

    Velusami, Chandrasekaran Chinampudur; Boddapati, Srinivasa Rao; Hongasandra Srinivasa, Srikanth; Richard, Edwin Jothie; Joseph, Joshua Allan; Balasubramanian, Murali; Agarwal, Amit

    2013-01-01

    Curcuma longa Linn. (Zingiberaceae) commonly known as turmeric has long been used for centuries as a spice and household remedy. The present study was carried out to assess the possible mutagenic potential and acute oral toxicity of polysaccharide extract of turmeric rhizome (NR-INF-02) using standard tests. The standard battery of in vitro genotoxicity tests, bacterial reverse mutation test (BRMT), chromosome aberration (CA), and micronucleus (MN) tests were employed to assess the possible mutagenic activity of NR-INF-02 (Turmacin). The results showed no mutagenic effect with NR-INF-02 up to a dose of 5000 µg/mL in BRMT. The results on CA and MN tests revealed the non clastogenic activity of NR-INF-02 in a dose range of 250.36 to 2500 µg/mL with and without metabolic activation (S9). In acute oral toxicity study, NR-INF-02 was found to be safe up to 5 g/kg body weight in Wistar rats. Overall, results indicated that polysaccharide extract of C. longa was found to be genotoxically safe and also exhibited maximum tolerable dose of more than 5 g/kg rat body weight. PMID:24455673

  20. Central nervous system toxicity after acute oral formaldehyde exposure in rabbits: An experimental study.

    PubMed

    Arici, S; Karaman, S; Dogru, S; Cayli, S; Arici, A; Suren, M; Karaman, T; Kaya, Z

    2014-11-01

    Formaldehyde (FA) is one of the most widely used chemical compounds in industrial field. It is described as toxic, particularly to the nervous system, the urogenital system, and the respiratory tracts. In this study, we determined the effects of acute oral exposure to FA in rabbit brain tissue. A total of 16 rabbits were selected and divided into 2 groups: formaldehyde group (group F) and control group (group C). FA was administered to group F at a rate of 40 mg/kg/day via a nasogastric tube for 5 days. Saline was similarly administered to the eight controls. All the animals were euthanized after 5 days of exposure, and brain tissue samples were collected in 10% neutral formalin and embedded in paraffin. To investigate the effects of FA on the apoptotic process, we examined active caspase-3, Bax, and Bcl-2 immunohistochemical expression and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate -biotin nick-end labeling (TUNEL) reactivity in the rabbit brains. In addition, glial fibrillary acidic protein (GFAP) was biochemically assessed in brain tissue samples for neurotoxicity. We found that FA treatment caused a significant decrease in Bcl-2 expression and an increase in active caspase-3 and Bax expressions as well as an increase in the number of TUNEL-positive apoptotic cells. The GFAP level was found to be significantly higher in group F. In conclusion, acute oral exposure to FA caused DNA damage, apoptosis, and neuronal injury in the rabbit brains.

  1. Safety Evaluation of Turmeric Polysaccharide Extract: Assessment of Mutagenicity and Acute Oral Toxicity

    PubMed Central

    Velusami, Chandrasekaran Chinampudur; Boddapati, Srinivasa Rao; Hongasandra Srinivasa, Srikanth; Richard, Edwin Jothie; Balasubramanian, Murali

    2013-01-01

    Curcuma longa Linn. (Zingiberaceae) commonly known as turmeric has long been used for centuries as a spice and household remedy. The present study was carried out to assess the possible mutagenic potential and acute oral toxicity of polysaccharide extract of turmeric rhizome (NR-INF-02) using standard tests. The standard battery of in vitro genotoxicity tests, bacterial reverse mutation test (BRMT), chromosome aberration (CA), and micronucleus (MN) tests were employed to assess the possible mutagenic activity of NR-INF-02 (Turmacin). The results showed no mutagenic effect with NR-INF-02 up to a dose of 5000 µg/mL in BRMT. The results on CA and MN tests revealed the non clastogenic activity of NR-INF-02 in a dose range of 250.36 to 2500 µg/mL with and without metabolic activation (S9). In acute oral toxicity study, NR-INF-02 was found to be safe up to 5 g/kg body weight in Wistar rats. Overall, results indicated that polysaccharide extract of C. longa was found to be genotoxically safe and also exhibited maximum tolerable dose of more than 5 g/kg rat body weight. PMID:24455673

  2. Investigation of intestine function during acute viral hepatitis using combined sugar oral loads.

    PubMed Central

    Parrilli, G; Cuomo, R; Nardone, G; Maio, G; Izzo, C M; Budillon, G

    1987-01-01

    One fifth of all cases of A virus hepatitis (AVH) have symptoms of gastroenteritis at the onset. This study investigated the mediated intestinal absorption of D-xylose (D-xyl) and 3-o-methyl-D-glucose (3-omG) and the non-mediated permeation of lactulose (Lacl, mol wt 342) and L-rhamnose (L-rh, mol wt 164) during acute and remission phases of AVH. Ten patients with AVH were given an oral load containing these sugars (5 g D-xyl: 2.5 g 3-omG, 1 g L-rh, 5 g lacl in 250 ml water) once during the acute phase and again during remission. The same load was given once to a group of 22 healthy controls. The mean concentration of D-xyl in urine and the ratio of D-xyl to 3-omG in plasma and urine were normal in both the AVH phases, ruling out intestinal malabsorption even in the acute phase. This study showed a significant increase in non-mediated permeation to Lacl, but not to L-rh, during the acute phase. These data indicate that the barrier function of the intestine is compromised in AVH infection while the absorptive function is not. An abnormally low concentration of D-xyl and 3-omG in plasma at one hour was found in all patients during the acute phase. This finding cannot be explained by alterations in intestinal absorption, but could be accounted for by increased space distribution of the sugars because of increased diffusion into tissue cells and/or expansion of the extracellular space by fluid retention. PMID:3428669

  3. Acute oral candidiasis during febrile episodes in immunocompromised patients with haematologic malignancies.

    PubMed

    Bergmann, O J; Andersen, P L

    1990-01-01

    To estimate clinical, pathogenic and serological aspects of acute oral candidiasis (AOC) during febril episodes in patients with haematologic malignancies, 23 consecutive patients who developed AOC within 7 days from start of fever were compared with 23 consecutive patients who did not develop AOC. The duration of fever and severe granulocytopenia (less than 0.5 x 10(9)/l) was significantly longer in patients with AOC than in patients without AOC, the median differences between the patients with and without AOC being 4 and 3 days, respectively. Development of AOC could not be correlated to a change in the qualitative composition of the oral microflora. The thrombocyte count was lower in patients with AOC on day 4, whereas no differences were found in leukocyte counts. The prevalences of Candida albicans agglutinin titres greater than or equal to 5 were similar in patients with (24%) and without AOC (33%), and in controls (29%). Seroconversion or a significant increase in the agglutinin titre occurred in 4 patients with AOC and long-lasting fever, who became afebrile after systemic antifungal therapy. It is concluded that AOC is associated with long-lasting fever and decreased bone marrow function as judged by low thrombocyte counts, but not related to specific bacteria in the oral cavity or to an increased occurrence of C. albicans antibodies in the serum.

  4. Oral administration of sodium butyrate attenuates inflammation and mucosal lesion in experimental acute ulcerative colitis.

    PubMed

    Vieira, Erica L M; Leonel, Alda J; Sad, Alexandre P; Beltrão, Nathália R M; Costa, Thaís F; Ferreira, Talita M R; Gomes-Santos, Ana C; Faria, Ana M C; Peluzio, Maria C G; Cara, Denise C; Alvarez-Leite, Jacqueline I

    2012-05-01

    Butyrate is a four-carbon short-chain fatty acid that improves colonic trophism. Although several studies have shown the benefits of butyrate enemas in ulcerative colitis (UC), studies using the oral route are rare in the literature. In the present study, we evaluated the effect of butyrate intake in the immune response associated to UC. For that, mice were fed control or butyrate (0.5% sodium butyrate) diets for 14 days. Acute UC was induced by dextran sulphate sodium (DSS, 2.5%), replacing drinking water. The results showed that, in UC animals, oral butyrate significantly improved trophism and reduced leukocyte (eosinophil and neutrophil) infiltration in the colon mucosa and improved the inflammatory profile (activated macrophage, B and T lymphocytes) in cecal lymph nodes. In the small intestine, although mucosa histology was similar among groups, DSS treatment reduced duodenal transforming growth factor-β, increased interleukin-10 concentrations and increased memory T lymphocytes and dendritic cells in Peyer's patches. Butyrate supplementation was able to revert these alterations. When cecal butyrate concentration was analyzed in cecal content, it was still higher in the healthy animals receiving butyrate than in the UC+butyrate and control groups. In conclusion, our results show that oral administration of sodium butyrate improves mucosa lesion and attenuates the inflammatory profile of intestinal mucosa, local draining lymph nodes and Peyer's patches of DSS-induced UC. Our results also highlight the potential use of butyrate supplements as adjuvant in UC treatment.

  5. Beryllium metal I. experimental results on acute oral toxicity, local skin and eye effects, and genotoxicity.

    PubMed

    Strupp, Christian

    2011-01-01

    The toxicity of soluble metal compounds is often different from that of the parent metal. Since no reliable data on acute toxicity, local effects, and mutagenicity of beryllium metal have ever been generated, beryllium metal powder was tested according to the respective Organisation for Economical Co-Operation and Development (OECD) guidelines. Acute oral toxicity of beryllium metal was investigated in rats and local effects on skin and eye in rabbits. Skin-sensitizing properties were investigated in guinea pigs (maximization method). Basic knowledge about systemic bioavailability is important for the design of genotoxicity tests on poorly soluble substances. Therefore, it was necessary to experimentally compare the capacities of beryllium chloride and beryllium metal to form ions under simulated human lung conditions. Solubility of beryllium metal in artificial lung fluid was low, while solubility in artificial lysosomal fluid was moderate. Beryllium chloride dissolution kinetics were largely different, and thus, metal extracts were used in the in vitro genotoxicity tests. Genotoxicity was investigated in vitro in a bacterial reverse mutagenicity assay, a mammalian cell gene mutation assay, a mammalian cell chromosome aberration assay, and an unscheduled DNA synthesis (UDS) assay. In addition, cell transformation was tested in a Syrian hamster embryo cell assay, and potential inhibition of DNA repair was tested by modification of the UDS assay. Beryllium metal was found not to be mutagenic or clastogenic based on the experimental in vitro results. Furthermore, treatment with beryllium metal extracts did not induce DNA repair synthesis, indicative of no DNA-damaging potential of beryllium metal. A cell-transforming potential and a tendency to inhibit DNA repair when the cell is severely damaged by an external stimulus were observed. Beryllium metal was also found not to be a skin or eye irritant, not to be a skin sensitizer, and not to have relevant acute oral

  6. Beryllium Metal I. Experimental Results on Acute Oral Toxicity, Local Skin and Eye Effects, and Genotoxicity

    PubMed Central

    Strupp, Christian

    2011-01-01

    The toxicity of soluble metal compounds is often different from that of the parent metal. Since no reliable data on acute toxicity, local effects, and mutagenicity of beryllium metal have ever been generated, beryllium metal powder was tested according to the respective Organisation for Economical Co-Operation and Development (OECD) guidelines. Acute oral toxicity of beryllium metal was investigated in rats and local effects on skin and eye in rabbits. Skin-sensitizing properties were investigated in guinea pigs (maximization method). Basic knowledge about systemic bioavailability is important for the design of genotoxicity tests on poorly soluble substances. Therefore, it was necessary to experimentally compare the capacities of beryllium chloride and beryllium metal to form ions under simulated human lung conditions. Solubility of beryllium metal in artificial lung fluid was low, while solubility in artificial lysosomal fluid was moderate. Beryllium chloride dissolution kinetics were largely different, and thus, metal extracts were used in the in vitro genotoxicity tests. Genotoxicity was investigated in vitro in a bacterial reverse mutagenicity assay, a mammalian cell gene mutation assay, a mammalian cell chromosome aberration assay, and an unscheduled DNA synthesis (UDS) assay. In addition, cell transformation was tested in a Syrian hamster embryo cell assay, and potential inhibition of DNA repair was tested by modification of the UDS assay. Beryllium metal was found not to be mutagenic or clastogenic based on the experimental in vitro results. Furthermore, treatment with beryllium metal extracts did not induce DNA repair synthesis, indicative of no DNA-damaging potential of beryllium metal. A cell-transforming potential and a tendency to inhibit DNA repair when the cell is severely damaged by an external stimulus were observed. Beryllium metal was also found not to be a skin or eye irritant, not to be a skin sensitizer, and not to have relevant acute oral

  7. Oral administration of lactulose: a novel therapy for acute carbon monoxide poisoning via increasing intestinal hydrogen production.

    PubMed

    Fan, Dan-Feng; Hu, Hui-Jun; Sun, Xue-Jun; Meng, Xiang-En; Zhang, Yu; Pan, Shu-Yi

    2016-01-01

    It has been known that the pathophysiology of carbon monoxide (CO) poisoning is related to hypoxia, the increased production of reactive oxygen species (ROS) and oxidative stress. Studies have shown that the novel, safe and effective free radical scavenger, hydrogen, has neuroprotective effects in both acute CO poisoning and delayed neuropsychological sequelae in CO poisoning. Orally administered lactulose, which may be used by some intestinal bacteria as a food source to produce endogenous hydrogen, can ameliorate oxidative stress. Based on the available findings, we hypothesize that oral administration of lactulose may be a novel therapy for acute CO poisoning via increasing intestinal hydrogen production.

  8. Oral Supplementation of Glucosamine Fails to Alleviate Acute Kidney Injury in Renal Ischemia-Reperfusion Damage.

    PubMed

    Johnsen, Marc; Späth, Martin Richard; Denzel, Martin S; Göbel, Heike; Kubacki, Torsten; Hoyer, Karla Johanna Ruth; Hinze, Yvonne; Benzing, Thomas; Schermer, Bernhard; Antebi, Adam; Burst, Volker; Müller, Roman-Ulrich

    2016-01-01

    Acute kidney injury is a leading contributor to morbidity and mortality in the ageing population. Proteotoxic stress response pathways have been suggested to contribute to the development of acute renal injury. Recent evidence suggests that increased synthesis of N-glycan precursors in the hexosamine pathway as well as feeding of animals with aminosugars produced in the hexosamine pathway may increase stress resistance through reducing proteotoxic stress and alleviate pathology in model organisms. As feeding of the hexosamine pathway metabolite glucosamine to aged mice increased their life expectancy we tested whether supplementation of this aminosugar may also protect mice from acute kidney injury after renal ischemia and reperfusion. Animals were fed for 4 weeks ad libitum with standard chow or standard chow supplemented with 0.5% N-acetylglucosamine. Preconditioning with caloric restriction for four weeks prior to surgery served as a positive control for protective dietary effects. Whereas caloric restriction demonstrated the known protective effect both on renal function as well as survival in the treated animals, glucosamine supplementation failed to promote any protection from ischemia-reperfusion injury. These data show that although hexosamine pathway metabolites have a proven role in enhancing protein quality control and survival in model organisms oral glucosamine supplementation at moderate doses that would be amenable to humans does not promote protection from ischemia-reperfusion injury of the kidney. PMID:27557097

  9. Oral Supplementation of Glucosamine Fails to Alleviate Acute Kidney Injury in Renal Ischemia-Reperfusion Damage

    PubMed Central

    Johnsen, Marc; Späth, Martin Richard; Denzel, Martin S.; Göbel, Heike; Kubacki, Torsten; Hoyer, Karla Johanna Ruth; Hinze, Yvonne; Benzing, Thomas; Schermer, Bernhard; Antebi, Adam; Burst, Volker; Müller, Roman-Ulrich

    2016-01-01

    Acute kidney injury is a leading contributor to morbidity and mortality in the ageing population. Proteotoxic stress response pathways have been suggested to contribute to the development of acute renal injury. Recent evidence suggests that increased synthesis of N-glycan precursors in the hexosamine pathway as well as feeding of animals with aminosugars produced in the hexosamine pathway may increase stress resistance through reducing proteotoxic stress and alleviate pathology in model organisms. As feeding of the hexosamine pathway metabolite glucosamine to aged mice increased their life expectancy we tested whether supplementation of this aminosugar may also protect mice from acute kidney injury after renal ischemia and reperfusion. Animals were fed for 4 weeks ad libitum with standard chow or standard chow supplemented with 0.5% N-acetylglucosamine. Preconditioning with caloric restriction for four weeks prior to surgery served as a positive control for protective dietary effects. Whereas caloric restriction demonstrated the known protective effect both on renal function as well as survival in the treated animals, glucosamine supplementation failed to promote any protection from ischemia-reperfusion injury. These data show that although hexosamine pathway metabolites have a proven role in enhancing protein quality control and survival in model organisms oral glucosamine supplementation at moderate doses that would be amenable to humans does not promote protection from ischemia-reperfusion injury of the kidney. PMID:27557097

  10. Analgesic activity and acute toxicity study of Semecarpus anacardium stem bark extracts using mice

    PubMed Central

    Lingaraju, G. M.; Hoskeri, H. Joy; Krishna, V.; Babu, P. Suresh

    2011-01-01

    Background: The analgesic activity of petroleum ether, chloroform and methanol extracts of Semecarpus anacardium was investigated by tail flicking and writhing method using acetyl salicylic acid as the standard reference. Materials and Methods: The staircase method was adopted for the determination of the acute toxicity. LD50 of the petroleum ether extract and the chloroform extract was 700 mg/kg; however, the LD50 for the methanol extract was 500 mg/kg. After 1 h of oral administration of the extracts, 0.6% acetic acid was administered intraperitoneally and the analgesic activity was evaluated. Results: The number of writhing observed in the control group was 73.33 writhes. The methanol extract showed a significant analgesic activity, with 28.33 writhes, than the petroleum ether extract and the chloroform extract. But, all the extracts showed proved to be less potent than the standard drug which showed 2.33 writhes. Animals pretreated with saline did not show a signify cant effect on the latent period of tail-flick response. The analgesic effect of the petroleum ether extract was comparatively less evident. The maximum possible analgesia (MPA) increased up to 9.1% which remained elevated above the basal levels throughout the observation period. The MPA calculated for the chloroform extract increased to 14.03%. However, the analgesic effect of the methanol extract was also observed at 0.5 h following oral administration and the effect remained significant throughout the 3 h observation period, and was increased to 20.43%. Conclusion: Consistent analgesic activity of all the three S. anacardium extracts was observed by both the methods. The methanol extract was more potent than the petroleum ether and chloroform extracts but was less effective than the standard drug. This investigation supported the ethnomedicinal claims of S. anacardium. PMID:21731397

  11. Medical Research and Evaluation Facility (MREF) and studies supporting the medical chemical defense program. Determination of the minimum effective pyridostigmine pretreatment dose in monkeys challenged with 5 x LD50 Soman and treated with atropine/2-PAM. Final report, 22 October 1992-31 August 1993

    SciTech Connect

    Olson, C.T.; Menton, R.G.; Kiser, R.C.; Hayes, T.L.; Matthews, M.C.

    1995-08-01

    This task was conducted to determine the minimum dose of pyridostigmine (PYR), and the associated level of erythrocyte acetycholinesterase inhibition (AChE-I), that provides protection from 5 X 48-br GD LD50 of untreated monkeys. Monkeys were injected im with GD and treated with 0.4 mg atropine (ATR) free base and 25.7 mg pralidoxime (2-PAM) per kg BW.

  12. Analysis of public oral toxicity data from REACH registrations 2008-2014.

    PubMed

    Luechtefeld, Thomas; Maertens, Alexandra; Russo, Daniel P; Rovida, Costanza; Zhu, Hao; Hartung, Thomas

    2016-01-01

    The European Chemicals Agency, ECHA, made available a total of 13,832 oral toxicity studies for 8,568 substances up to December 2014. 75% of studies were from the retired OECD Test Guideline 401 (11% TG 420, 11% TG 423 and 1.5% TG 425). Concordance across guidelines, evaluated by comparing LD50 values ≥ 2000 or < 2000 mg/kg body weight from chemicals tested multiple times between different guidelines, was at least 75% and for their own repetition more than 90%. In 2009, Bulgheroni et al. created a simple model for predicting acute oral toxicity using no observed adverse effect levels (NOAEL) from 28-day repeated dose toxicity studies in rats. This was reproduced here for 1,625 substances. In 2014, Taylor et al. suggested no added value of the 90-day repeated dose oral toxicity test given the availability of a low 28-day study with some constraints. We confirm that the 28-day NOAEL is predictive (albeit imperfectly) of 90-day NOAELs, however, the suggested constraints did not affect predictivity. 1,059 substances with acute oral toxicity data (268 positives, 791 negatives, all Klimisch score 1) were used for modeling: The Chemical Development Kit was used to generate 27 molecular descriptors and a similarity-informed multilayer perceptron showing 71% sensitivity and 72% specificity. Additionally, the k-nearest neighbors (KNN) algorithm indicated that similarity-based approaches alone may be poor predictors of acute oral toxicity, but can be used to inform the multilayer perceptron model, where this was the feature with highest information value. PMID:26863198

  13. Acute toxicity of diphacinone in Northern bobwhite: Effects on survival and blood clotting

    USGS Publications Warehouse

    Rattner, Barnett A.; Horak, Katherine E.; Warner, Sarah E.; Johnston, John J.

    2010-01-01

    The anticoagulant rodenticide diphacinone was slightly toxic (acute oral LD50 2014 mg/kg) to Northern bobwhite (Colinus virginianus) in a 14-day acute toxicity trial. Precise and sensitive assays of blood clotting (prothrombin time, Russell?s Viper venom time, and thrombin clotting time) were adapted for use in quail, and this combination of assays is recommended to measure the effects of anticoagulant rodenticides. A single oral sublethal dose of diphacinone (434 mg/kg body weight) prolonged clotting time at 48 h post-dose compared to controls. At 783 mg/kg (approximate LD02), clotting time was prolonged at both 24 and 48 h post-dose. Prolongation of in vitro clotting time reflects impaired coagulation complex activity, and was detected before overt signs of toxicity were apparent at the greatest dosages (2868 and 3666 mg/kg) in the acute toxicity trial. These clotting time assays and toxicity data will assist in the development of a pharmacodynamic model to predict toxicity, and also facilitate rodenticide hazard and risk assessments in avian species.

  14. Single dose oral naproxen and naproxen sodium for acute postoperative pain (Review)

    PubMed Central

    Mason, L; Edwards, JE; Moore, RA; McQuay, HJ

    2014-01-01

    Background Postoperative pain is often poorly managed. Treatment options include a range of drug therapies such as non-steroidal anti-inflammatory drugs (NSAIDs) of which naproxen is one. Naproxen is used to treat a variety of painful conditions including acute postoperative pain, and is often combined with sodium to improve its solubility for oral administration. Naproxen sodium 550 mg (equivalent to 500 mg of naproxen) is considered to be an effective dose for treating postoperative pain but to date no systematic review of the effectiveness of naproxen/naproxen sodium at different doses has been published. Objectives To assess the efficacy, safety and duration of action of a single oral dose of naproxen or naproxen sodium for acute postoperative pain in adults. Search strategy We searched The Cochrane Library, MEDLINE, EMBASE and the Oxford Pain Relief Database for relevant studies. Additional studies were identified from the reference list of retrieved reports. The most recent search was undertaken in July 2004. Selection criteria Included studies were randomised, double blind, placebo-controlled trials of a single dose of orally administered naproxen or naproxen sodium in adults with moderate to severe acute postoperative pain. Data collection and analysis Pain relief or pain intensity data were extracted and converted into dichotomous information to give the number of patients with at least 50% pain relief over four to six hours. Relative risk estimates (RR) and the number-needed-to-treat (NNT) for at least 50% pain relief were then calculated. Information was sought on the percentage of patients experiencing any adverse event, and the number-needed-to-harm was derived. Time to remedication was also estimated. Main results Ten trials (996 patients) met the inclusion criteria: nine assessed naproxen sodium; one combined the results from two small trials of naproxen alone. Included studies scored well for methodological quality. Meta-analysis of six trials (500

  15. Effect of surgical castration with or without oral meloxicam on the acute inflammatory response in yearling beef bulls

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Pain management and welfare are increasingly prevalent concerns within animal agriculture and oral analgesics may alleviate the pain associated with castration. This study was conducted to elucidate the effects of surgical castration on the acute inflammatory response and immunomodulation and whethe...

  16. [Investigation of vectors and reservoirs in an acute Chagas outbreak due to possible oral transmission in Aguachica, Cesar, Colombia].

    PubMed

    Soto, Hugo; Tibaduiza, Tania; Montilla, Marleny; Triana, Omar; Suárez, Diana Carolina; Torres Torres, Mariela; Arias, María Teresa; Lugo, Ligia

    2014-04-01

    Colombia recorded 11 cases of acute Chagas disease and 80 cases of oral contamination with Trypanosoma cruzi. The current study analyzes the entomological and parasitological characteristics of the outbreak in Aguachica, Cesar Department, in 2010. An interdisciplinary group of health professionals and regional university personnel conducted the laboratory tests in the patients and the investigation of the transmission focus. Eleven cases of acute Chagas diseases were detected in a single family in a dwelling with domiciliated triatomines and Rhodnius pallescens, Pantrongylus geniculatus, Eratyrus cuspidatus, and two Didelphis marsupialis opossums infected with T. cruzi in Attalea butyracea and Elaeis oleifera palm trees in the urban area of Aguachica. The study analyzes the role of R. pallescens and palm trees in the wild cycle of T. cruzi and in oral transmission of Chagas disease. Sporadic incursions by wild R. pallescens, P. geniculatus, and E. cuspidatus from the nearby palm trees into human dwellings may cause increasingly frequent outbreaks of oral Chagas disease.

  17. Acute Oral Ethanol Exposure Triggers Asthma In Cockroach Allergen–Sensitized Mice

    PubMed Central

    Bouchard, Jacqueline C.; Kim, Jiyoun; Beal, Dominic R.; Vaickus, Louis J.; Craciun, Florin L.; Remick, Daniel G.

    2013-01-01

    Asthma may be triggered by multiple mediators, including allergen-IgE cross-linking and non-IgE mechanisms. Several clinical studies have shown acute ethanol consumption exacerbates asthma, yet no animal model exists to study this process. We developed a model of ethanol-triggered asthma in allergen-sensitized mice to evaluate the mechanisms of ethanol inducing asthma-like responses. Outbred mice were exposed to cockroach allergens on Days 0 and 14; and on Day 21, mice received ethanol by oral gavage. Tracer studies confirmed alcohol aspiration did not occur. Within 30 minutes, alcohol induced degranulation of over 74% of mast cells, and multiple parameters of asthma-like pulmonary inflammation were triggered. Ethanol-gavaged mice had a fivefold increased production of eotaxin-2 (534 pg/mL) and a sevenfold increase in bronchoalveolar eosinophils (70,080 cells). Ethanol induced a 10-fold increase in IL-13, from 84 pg/mL in sensitized mice to 845 pg/mL in ethanol-gavaged sensitized mice. In cockroach allergen–sensitized mice, ethanol triggered asthma-like changes in respiratory physiology and a significant fivefold increase in airway mucin production. Importantly, none of these asthmatic exacerbations were observed in normal mice gavaged with ethanol. Cromolyn sodium effectively stabilized mast cells, yet increased mucin production and bronchoalveolar eosinophil recruitment. Together, these data show a single oral alcohol exposure will trigger asthma-like pulmonary inflammation in allergen-sensitized mice, providing a novel asthma model. PMID:22796441

  18. Phytochemical Screening and Acute Oral Toxicity Study of Java Tea Leaf Extracts.

    PubMed

    Pariyani, Raghunath; Ismail, Intan Safinar; Azam, Amalina Ahmad; Abas, Faridah; Shaari, Khozirah; Sulaiman, Mohd Roslan

    2015-01-01

    The term Java tea refers to the decoction of Orthosiphon stamineus (OS) Benth (Lamiaceae) leaves, which are widely consumed by the people in Europe and South East Asian countries. The OS leaves are known for their use in traditional medicinal systems as a prophylactic and curative agent for urinary stone, diabetes, and hypertension and also as a diuretic agent. The present study was aimed at evaluating its possible toxicity. Herein, the major phytochemical constituents of microwave dried OS leaf, which is the common drying process for tea sachets in the market, were also identified. The acute oral toxicity test of aqueous, 50% aqueous ethanolic, and ethanolic extracts of OS was performed at a dose of 5000 mg/Kg body weight of Sprague-Dawley rats. During the 14-day study, the animals were observed for any mortality, behavioral, motor-neuronal abnormalities, body weight, and feed-water consumption pattern. The hematological and serum biochemical parameters to assess the kidney and liver functions were carried out, along with the histological analysis of these organs. It was found that all microwave dried OS leaf extracts did not cause any toxic effects or mortality at the administered dose. No abnormality was noticed in all selected parameters in rats of both sexes as compared with their respective control groups. Thus, the possible oral lethal dose for microwave dried Java tea leaves is more than 5000 mg/Kg body weight.

  19. Acute oral toxicity and brine shrimp lethality of Elaeis guineensis Jacq., (oil palm leaf) methanol extract.

    PubMed

    Syahmi, Abdul Rani Muhamad; Vijayarathna, Soundararajan; Sasidharan, Sreenivasan; Latha, Lachimanan Yoga; Kwan, Yuet Ping; Lau, Yee Ling; Shin, Lai Ngit; Chen, Yeng

    2010-11-01

    Elaeis guineensis (Arecaceae) is widely used in West African traditional medicine for treating various ailments. An evaluation on the toxicity of extracts of this plant is crucial to support the therapeutic claims. The acute oral toxicity and brine shrimp lethality of a methanolic extract of this plant was tested. Oral administration of crude extract at the highest dose of 5,000 mg/kg resulted in no mortalities or evidence of adverse effects, implying that E. guineensis is nontoxic. Normal behavioral pattern, clinical signs and histology of vital organs confirm this evidence. The E. guineensis extracts screened for toxicity against brine shrimp had 50% lethal concentration (LC₅₀) values of more than 1.0 mg/mL (9.00 and 3.87 mg/mL, at 6 and 24 h, respectively), confirming that the extract was not toxic. Maximum mortalities occurred at 100 mg/mL concentration while the least mortalities happened to be at 0.195 mg/mL concentration. The results of both tests confirm that E. guineensis is nontoxic and hence safe for commercial utilization. PMID:21072022

  20. Phytochemical Screening and Acute Oral Toxicity Study of Java Tea Leaf Extracts.

    PubMed

    Pariyani, Raghunath; Ismail, Intan Safinar; Azam, Amalina Ahmad; Abas, Faridah; Shaari, Khozirah; Sulaiman, Mohd Roslan

    2015-01-01

    The term Java tea refers to the decoction of Orthosiphon stamineus (OS) Benth (Lamiaceae) leaves, which are widely consumed by the people in Europe and South East Asian countries. The OS leaves are known for their use in traditional medicinal systems as a prophylactic and curative agent for urinary stone, diabetes, and hypertension and also as a diuretic agent. The present study was aimed at evaluating its possible toxicity. Herein, the major phytochemical constituents of microwave dried OS leaf, which is the common drying process for tea sachets in the market, were also identified. The acute oral toxicity test of aqueous, 50% aqueous ethanolic, and ethanolic extracts of OS was performed at a dose of 5000 mg/Kg body weight of Sprague-Dawley rats. During the 14-day study, the animals were observed for any mortality, behavioral, motor-neuronal abnormalities, body weight, and feed-water consumption pattern. The hematological and serum biochemical parameters to assess the kidney and liver functions were carried out, along with the histological analysis of these organs. It was found that all microwave dried OS leaf extracts did not cause any toxic effects or mortality at the administered dose. No abnormality was noticed in all selected parameters in rats of both sexes as compared with their respective control groups. Thus, the possible oral lethal dose for microwave dried Java tea leaves is more than 5000 mg/Kg body weight. PMID:26819955

  1. No change in spontaneous behavior of rats after acute oral doses of aspartame, phenylalanine, and tyrosine.

    PubMed

    Mullenix, P J; Tassinari, M S; Schunior, A; Kernan, W J

    1991-04-01

    Spontaneous behavior subsequent to acute oral administration of high doses of aspartame, phenylalanine, or tyrosine was analyzed using a computer pattern recognition system. Sprague-Dawley male rats (250-300 g) were dosed orally with aspartame (500 or 1000 mg/kg), phenylalanine (281 or 562 mg/kg), or tyrosine (309 or 618 mg/kg), and their behavior was analyzed 1 hr after dosing. The computer pattern recognition system recorded and classified 13 different behavioral acts performed by the animals during the first 15-min exploration of a novel environment. Three measures that provide independent information concerning motor output from the central nervous system were taken: the number of behavioral initiations, total time, and time structure. These results were compared with the effects induced by d-amphetamine. Plasma concentrations of phenylalanine and tyrosine were determined from blood samples taken immediately after behavioral examination. Data analysis revealed that these doses of aspartame, phenylalanine, and tyrosine did not induce any significant changes in spontaneous behavior. Unlike low doses of amphetamine and despite high plasma concentrations of phenylalanine and tyrosine, no behavioral alteration was detected by the computer pattern recognition system. Absence of behavioral changes in this study using an objective analysis of behavior raises questions concerning the relationship between amino acid precursor loading and purported anecdotal changes in behavior following aspartame administration.

  2. Acute oral toxicity and brine shrimp lethality of Elaeis guineensis Jacq., (oil palm leaf) methanol extract.

    PubMed

    Syahmi, Abdul Rani Muhamad; Vijayarathna, Soundararajan; Sasidharan, Sreenivasan; Latha, Lachimanan Yoga; Kwan, Yuet Ping; Lau, Yee Ling; Shin, Lai Ngit; Chen, Yeng

    2010-11-10

    Elaeis guineensis (Arecaceae) is widely used in West African traditional medicine for treating various ailments. An evaluation on the toxicity of extracts of this plant is crucial to support the therapeutic claims. The acute oral toxicity and brine shrimp lethality of a methanolic extract of this plant was tested. Oral administration of crude extract at the highest dose of 5,000 mg/kg resulted in no mortalities or evidence of adverse effects, implying that E. guineensis is nontoxic. Normal behavioral pattern, clinical signs and histology of vital organs confirm this evidence. The E. guineensis extracts screened for toxicity against brine shrimp had 50% lethal concentration (LC₅₀) values of more than 1.0 mg/mL (9.00 and 3.87 mg/mL, at 6 and 24 h, respectively), confirming that the extract was not toxic. Maximum mortalities occurred at 100 mg/mL concentration while the least mortalities happened to be at 0.195 mg/mL concentration. The results of both tests confirm that E. guineensis is nontoxic and hence safe for commercial utilization.

  3. Phytochemical Screening and Acute Oral Toxicity Study of Java Tea Leaf Extracts

    PubMed Central

    Safinar Ismail, Intan; Azam, Amalina Ahmad; Abas, Faridah; Shaari, Khozirah; Sulaiman, Mohd Roslan

    2015-01-01

    The term Java tea refers to the decoction of Orthosiphon stamineus (OS) Benth (Lamiaceae) leaves, which are widely consumed by the people in Europe and South East Asian countries. The OS leaves are known for their use in traditional medicinal systems as a prophylactic and curative agent for urinary stone, diabetes, and hypertension and also as a diuretic agent. The present study was aimed at evaluating its possible toxicity. Herein, the major phytochemical constituents of microwave dried OS leaf, which is the common drying process for tea sachets in the market, were also identified. The acute oral toxicity test of aqueous, 50% aqueous ethanolic, and ethanolic extracts of OS was performed at a dose of 5000 mg/Kg body weight of Sprague-Dawley rats. During the 14-day study, the animals were observed for any mortality, behavioral, motor-neuronal abnormalities, body weight, and feed-water consumption pattern. The hematological and serum biochemical parameters to assess the kidney and liver functions were carried out, along with the histological analysis of these organs. It was found that all microwave dried OS leaf extracts did not cause any toxic effects or mortality at the administered dose. No abnormality was noticed in all selected parameters in rats of both sexes as compared with their respective control groups. Thus, the possible oral lethal dose for microwave dried Java tea leaves is more than 5000 mg/Kg body weight. PMID:26819955

  4. Acute supra-therapeutic oral terbutaline administration has no ergogenic effect in non-asthmatic athletes.

    PubMed

    Sanchez, Anthony M J; Borrani, Fabio; Le Fur, Marie Amélie; Le Mieux, Anais; Lecoultre, Virgile; Py, Guillaume; Gernigon, Christophe; Collomp, Katia; Candau, Robin

    2013-02-01

    This study aimed to investigate the effects on a possible improvement in aerobic and anaerobic performance of oral terbutaline (TER) at a supra-therapeutic dose in 7 healthy competitive male athletes. On day 1, ventilatory threshold, maximum oxygen uptake [Formula: see text] and corresponding power output were measured and used to determine the exercise load on days 2 and 3. On days 2 and 3, 8 mg of TER or placebo were orally administered in a double-blind process to athletes who rested for 3 h, and then performed a battery of tests including a force-velocity exercise test, running sprint and a maximal endurance cycling test at Δ50 % (50 % between VT and [Formula: see text]). Lactatemia, anaerobic parameters and endurance performance ([Formula: see text] and time until exhaustion) were raised during the corresponding tests. We found that TER administration did not improve any of the parameters of aerobic performance (p > 0.05). In addition, no change in [Formula: see text] kinetic parameters was found with TER compared to placebo (p > 0.05). Moreover, no enhancement of the force-velocity relationship was observed during sprint exercises after TER intake (p > 0.05) and, on the contrary, maximal strength decreased significantly after TER intake (p < 0.05) but maximal power remained unchanged (p > 0.05). In conclusion, oral acute administration of TER at a supra-therapeutic dose seems to be without any relevant ergogenic effect on anaerobic and aerobic performances in healthy athletes. However, all participants experienced adverse side effects such as tremors. PMID:22767151

  5. Optimal Oral Antithrombotic Regimes for Patients with Acute Coronary Syndrome: A Network Meta-Analysis

    PubMed Central

    Ye, Yicong; Xie, Hongzhi; Zeng, Yong; Zhao, Xiliang; Tian, Zhuang; Zhang, Shuyang

    2014-01-01

    Objective We performed a network meta-analysis to investigate the optimal antithrombotic regime by indirectly comparing new antithrombotic regimes (new P2Y12 inhibitors plus aspirin or novel oral anticoagulants on top of traditional dual antiplatelet therapy [DAPT]) in patients with acute coronary syndrome (ACS). Methods A systematic search of MEDLINE, EMBASE, and the Cochrane databases was performed to identify all phase 3 randomized controlled trials (RCTs) involving novel oral anticoagulants or oral P2Y12 inhibitors in patients with ACS. Major adverse cardiac events (MACE) were regarded as the efficacy endpoint, and thrombolysis in myocardial infarction (TIMI) major bleeding events were used as the safety endpoint. The net clinical benefit was calculated as the sum of MACE and TIMI major bleeding events. Results Five phase 3 RCTs with 64,476 ACS patients were included. Although there were no significant differences among new antithrombotic regimes, rivaroxaban 5 mg twice daily plus traditional DAPT might be the most effective in reducing the incidence of MACE, accompanying the highest risk of TIMI major bleeding. Ticagrelor plus aspirin presented slight advantage on the net clinical benefit over other new antithrombotic regimes, with the highest probability of being the best regimes for net clinical benefit (35.0%), followed by prasugrel plus aspirin (28.0%), and rivaroxaban 2.5 mg twice daily plus traditional DAPT (19.5%). Conclusion Novel antithrombotic regime with ticagrelor plus aspirin brings a larger clinical benefit in comparison with other regimes, suggesting that it may be the optimal antithrombotic regime for patients with ACS. PMID:24614630

  6. Acute phase treatment of VTE: Anticoagulation, including non-vitamin K antagonist oral anticoagulants.

    PubMed

    Hillis, Christopher M; Crowther, Mark A

    2015-06-01

    The acute phase of venous thromboembolism (VTE) treatment focuses on the prompt and safe initiation of full-dose anticoagulation to decrease morbidity and mortality. Immediate management consists of resuscitation, supportive care, and thrombolysis for patients with haemodynamically significant pulmonary embolism (PE) or limb-threatening deep-vein thrombosis (DVT). Patients with contraindications to anticoagulants are considered for vena cava filters. Disposition for the acute treatment of VTE is then considered based on published risk scores and the patient's social status, as the first seven days carries the highest risk for VTE recurrence, extension and bleeding due to anticoagulation. Next, a review of: immediate and long-term bleeding risk, comorbidities (i. e. active cancer, renal failure, obesity, thrombophilia), medications, patient preference, VTE location and potential for pregnancy should be undertaken. This will help determine the most suitable anticoagulant for immediate treatment. The non-vitamin K antagonist oral anticoagulants (NOACs), including the factor Xa inhibitors apixaban, edoxaban and rivaroxaban as well as the direct-thrombin inhibitor dabigatran, are increasing the convenience of and options available for VTE treatment. Current options for immediate treatment include low-molecular-weight heparin (LMWH), unfractionated heparin (UFH), fondaparinux, apixaban, or rivaroxaban. LMWH or UFH may be continued as monotherapy or transitioned to treatment with a VKA, dabigatran or edoxaban. This review describes the upfront treatment of VTE and the evolving role of NOACs in the contemporary management of VTE.

  7. Evaluation of a low-dose CT protocol with oral contrast for assessment of acute appendicitis.

    PubMed

    Platon, Alexandra; Jlassi, Helmi; Rutschmann, Olivier T; Becker, Christoph D; Verdun, Francis R; Gervaz, Pascal; Poletti, Pierre-Alexandre

    2009-02-01

    The aim of this study was to evaluate a low-dose CT with oral contrast medium (LDCT) for the diagnosis of acute appendicitis and compare its performance with standard-dose i.v. contrast-enhanced CT (standard CT) according to patients' BMIs. Eighty-six consecutive patients admitted with suspicion of acute appendicitis underwent LDCT (30 mAs), followed by standard CT (180 mAs). Both examinations were reviewed by two experienced radiologists for direct and indirect signs of appendicitis. Clinical and surgical follow-up was considered as the reference standard. Appendicitis was confirmed by surgery in 37 (43%) of the 86 patients. Twenty-nine (34%) patients eventually had an alternative discharge diagnosis to explain their abdominal pain. Clinical and biological follow-up was uneventful in 20 (23%) patients. LDCT and standard CT had the same sensitivity (100%, 33/33) and specificity (98%, 45/46) to diagnose appendicitis in patients with a body mass index (BMI) >or= 18.5. In slim patients (BMI<18.5), sensitivity to diagnose appendicitis was 50% (2/4) for LDCT and 100% (4/4) for standard CT, while specificity was identical for both techniques (67%, 2/3). LDCT may play a role in the diagnostic workup of patients with a BMI >or= 18.5.

  8. Saving two birds with one stone: using active substance avian acute toxicity data to predict formulated plant protection product toxicity.

    PubMed

    Maynard, Samuel K; Edwards, Peter; Wheeler, James R

    2014-07-01

    Environmental safety assessments for exposure of birds require the provision of acute avian toxicity data for both the pesticidal active substance and formulated products. As an example, testing on the formulated product is waived in Europe using an assessment of data for the constituent active substance(s). This is often not the case globally, because some countries require acute toxicity tests with every formulated product, thereby triggering animal welfare concerns through unnecessary testing. A database of 383 formulated products was compiled from acute toxicity studies conducted with northern bobwhite (Colinus virginianus) or Japanese quail (Coturnix japonica) (unpublished regulatory literature). Of the 383 formulated products studied, 159 contained only active substances considered functionally nontoxic (median lethal dose [LD50] > highest dose tested). Of these, 97% had formulated product LD50 values of >2000 mg formulated product/kg (limit dose), indicating that no new information was obtained in the formulated product study. Furthermore, defined (point estimated) LD50 values for formulated products were compared with LD50 values predicted from toxicity of the active substance(s). This demonstrated that predicted LD50 values were within 2-fold and 5-fold of the measured formulated product LD50 values in 90% and 98% of cases, respectively. This analysis demonstrates that avian acute toxicity testing of formulated products is largely unnecessary and should not be routinely required to assess avian acute toxicity. In particular, when active substances are known to be functionally nontoxic, further formulated product testing adds no further information and unnecessarily increases bird usage in testing. A further analysis highlights the fact that significant reductions (61% in this dataset) could be achieved by using a sequential testing design (Organisation for Economic Co-operation and Development test guideline 223), as opposed to established single

  9. Single dose oral indometacin for the treatment of acute postoperative pain

    PubMed Central

    Moore, R Andrew; Derry, Sheena; Mason, Lorna; McQuay, Henry J; Edwards, Jayne

    2014-01-01

    Background This is an updated version of the original Cochrane review published in Issue 4, 2004. Indometacin is a non-steroidal anti-inflammatory drug (NSAID) used most commonly for the treatment of inflammation and pain resulting from rheumatic disease (arthritis), and less commonly in postoperative pain management. When taken for chronic pain conditions, indometacin has been associated with a high incidence of adverse events. The benefits and harms of orally-administered indometacin for postoperative pain are not clear. Objectives To determine the efficacy of a single dose of oral indometacin compared with placebo in treating acute postoperative pain in adults, and to analyse information relating to adverse events. Search methods We searched the Cochrane CENTRAL Register of Controlled Trials in The Cochrane Library, MEDLINE, EMBASE and the Oxford Pain Relief Database for relevant studies in January 2002 and for the updated search in December 2007. Additional studies were sought from the reference lists of retrieved studies. Selection criteria Studies were included in the review if they were randomised, double blind, placebo-controlled clinical trials using a single oral dose of indometacin in adults with acute postoperative pain. Data collection and analysis Studies were assessed independently by two review authors. Pain relief or pain intensity data were extracted and converted into dichotomous information to give the number of participants with at least 50% pain relief over four to six hours. The relative benefit for at least 50% pain relief was calculated. Main results In the original review one study of 59 women with post-episiotomy pain met the inclusion criteria. The dose of indometacin assessed against placebo was 50 mg, and the results concluded that indometacin was not significantly better than placebo for relieving postoperative pain at four to six hours. There was insufficient information to conduct further efficacy analyses or assess adverse events

  10. Single dose oral mefenamic acid for acute postoperative pain in adults

    PubMed Central

    Moll, Rachel; Derry, Sheena; Moore, R Andrew; McQuay, Henry J

    2014-01-01

    Background Mefenamic acid is a non-steroidal anti-inflammatory drug (NSAID). It is most often used for treating pain of dysmenorrhoea in the short term (seven days or less), as well as mild to moderate pain including headache, dental pain, postoperative and postpartum pain. It is widely available in many countries worldwide. Objectives To assess the efficacy of single dose oral mefenamic acid in acute postoperative pain, and any associated adverse events. Search methods We searched Cochrane CENTRAL, MEDLINE, EMBASE and the Oxford Pain Relief Database for studies to December 2010. Selection criteria Single oral dose, randomised, double-blind, placebo-controlled trials of mefenamic acid for relief of established moderate to severe postoperative pain in adults. Data collection and analysis Studies were assessed for methodological quality and the data extracted by two review authors independently. Summed total pain relief (TOTPAR) or pain intensity difference (SPID) over 4 to 6 hours was used to calculate the number of participants achieving at least 50% pain relief. These derived results were used to calculate, with 95% confidence intervals, the relative benefit compared to placebo, and the number needed to treat (NNT) for one participant to experience at least 50% pain relief over 4 to 6 hours. Numbers of participants using rescue medication over specified time periods, and time to use of rescue medication, were sought as additional measures of efficacy. Information on adverse events and withdrawals was collected. Main results Four studies with 842 participants met the inclusion criteria; 126 participants were treated with mefenamic acid 500 mg, 67 with mefenamic acid 250 mg, 197 with placebo, and 452 with lignocaine, aspirin, zomepirac or nimesulide. Participants had pain following third molar extraction, episiotomy and orthopaedic surgery. The NNT for at least 50% pain relief over 6 hours with a single dose of mefenamic acid 500 mg compared to placebo was 4.0 (2

  11. Mitigation of the Hematopoietic and Gastrointestinal Acute Radiation Syndrome by Octadecenyl Thiophosphate, a Small Molecule Mimic of Lysophosphatidic Acid

    PubMed Central

    Deng, Wenlin; Kimura, Yasuhiro; Gududuru, Veeresh; Wu, Wenjie; Balogh, Andrea; Szabo, Erzsebet; Thompson, Karin Emmons; Yates, C. Ryan; Balazs, Louisa; Johnson, Leonard R.; Miller, Duane D.; Strobos, Jur; McCool, W. Shannon; Tigyi, Gabor J.

    2015-01-01

    We have previously demonstrated that the small molecule octadecenyl thiophosphate (OTP), a synthetic mimic of the growth factor-like mediator lysophosphatidic acid (LPA), showed radioprotective activity in a mouse model of total-body irradiation (TBI) when given orally or intraperitoneally 30 min before exposure to 9 Gy γ radiation. In the current study, we evaluated the effects of OTP, delivered subcutaneously, for radioprotection or radiomitigation from −24 h before to up to +72 h postirradiation using a mouse TBI model with therapeutic doses at around 1 mg/kg. OTP was injected at 10 mg/kg without observable toxic side effects in mice, providing a comfortable safety margin. Treatment of C57BL/6 mice with a single dose of OTP over the time period from −12 h before to +26 h after a lethal dose of TBI reduced mortality by 50%. When administered at +48 h to +72 h postirradiation (LD50/30 to LD100/30), OTP reduced mortality by ≥34%. OTP administered at +24 h postirradiation significantly elevated peripheral white blood cell and platelet counts, increased crypt survival in the jejunum, enhanced intestinal glucose absorption and reduced endotoxin seepage into the blood. In the 6.4–8.6 Gy TBI range using LD50/10 as the end point, OTP yielded a dose modification factor of 1.2. The current data indicate that OTP is a potent radioprotector and radiomitigator ameliorating the mortality and tissue injury of acute hematopoietic as well as acute gastrointestinal radiation syndrome. PMID:25807318

  12. Laboratory Evaluation of Acute Toxicity of the Essential Oil of Allium tuberosum Leaves and Its Selected Major Constituents Against Apolygus lucorum (Hemiptera: Miridae)

    PubMed Central

    Shi, Jizhe; Liu, Xinchao; Li, Zhen; Zheng, Yuanyuan; Zhang, Qingwen; Liu, Xiaoxia

    2015-01-01

    The aim of this research was to evaluate acute toxicity of the essential oil of leaves of Chinese chives, Allium tuberosum Rottler ex Spreng (Asparagales: Alliaceae) and its major constituents against Apolygus lucorum Meyer-Dür (Hemiptera: Miridae). The essential oil of A. tuberosum leaves was obtained by hydrodistillation and analyzed by gas chromatography and gas chromatography-mass spectrometry. The major constituents of the oil were sulfur-containing compounds, including allyl methyl trisulfide (36.24%), diallyl disulfide (27.26%), diallyl trisulfide (18.68%), and dimethyl trisulfide (9.23%). The essential oil of A. tuberosum leaves exhibited acute toxicity against Ap. lucorum with an LD50 value of 20.03 μg per adult. Among the main compounds, diallyl trisulfide (LD50 = 10.13 μg per adult) showed stronger acute toxicity than allyl methyl trisulfide (LD50 = 21.10 μg per adult) and dimethyl trisulfide (LD50 = 21.65 μg per adult). The LD50 value of diallyl disulfide against Ap. lucorum was 28.10 μg per adult. The results indicated that the essential oil of A. tuberosum and its major constituents may have a potential to be developed as botanical insecticides against Ap. lucorum. PMID:26254289

  13. Quantitative comparisons of acute toxicity of organic chemicals to rat and fish

    SciTech Connect

    Janardan, S.K.; Olson, C.S.; Schaeffer, D.J.

    1984-12-01

    Relationships between the acute toxicity of chemicals to fish (LC50) and rat (LD50) were analyzed using a Model II regression analysis after logarithmic transformation. (Model II regression assumes errors in both variables.) Significant correlations were found among bluegill and fathead minnow LC50S and rat LD50 values for the priority pollutants. Fathead minnow and bluegill LC50S for 48 pesticides were highly correlated. No correlations were found between fishes and rats for carbamate plus organophosphate pesticides. Correlations were obtained among all species for the combined priority pollutant plus pesticide data and for chlorinated pesticides.

  14. Multivariate correlations between properties of metal ions and their acute toxicity in mice

    SciTech Connect

    Turner, J.E.; Williams, M.W.; Hingerty, B.E.; Hayden, T.L.

    1986-01-01

    This paper extends our earlier study of correlations of acute metal-ion toxicity (14-day LD50) in mice and physicochemical properties of the ions. Here we put metal ions into two main groups as defined by Kaiser. Using most of the metals in the periodic system, we find the least redundant linear combinations W/sub i/ of the ionic radius, sum of ionization potentials, atomic weight, Williams softness parameter, and electronegativity for each of Kaiser's two groups. Information is provided so that the W/sub i/ can be evaluated for any metal from these five quantities. For the two groups of metals we then tested for multivariate correlations between the S/sub i/ having the highest sample variance and our mouse LD50. For our LD50 involving the five metal ions in Kaiser's group (1) the correlation is poor, whereas a good correlation is found for the 14 ions in group (2). 10 refs., 3 tabs.

  15. Fosfomycin: A First-Line Oral Therapy for Acute Uncomplicated Cystitis

    PubMed Central

    Zhanel, George G.; Walkty, Andrew J.; Karlowsky, James A.

    2016-01-01

    Fosfomycin is a new agent to Canada approved for the treatment of acute uncomplicated cystitis (AUC) in adult women infected with susceptible isolates of E. coli and Enterococcus faecalis. We reviewed the literature regarding the use of oral fosfomycin for the treatment of AUC. All English-language references from 1975 to October 2015 were reviewed. In Canada, fosfomycin tromethamine is manufactured as Monurol® and is available as a 3-gram single dose sachet. Fosfomycin has a unique chemical structure, inhibiting peptidoglycan synthesis at an earlier site compared to β-lactams with no cross-resistance with other agents. Fosfomycin displays broad-spectrum activity against ESBL-producing, AmpC-producing, carbapenem-non-susceptible, and multidrug-resistant (MDR) E. coli. Resistance to fosfomycin in E. coli is rare (<1%). Fosfomycin is excreted unchanged in the urine by glomerular filtration with peak urinary concentration ~4000 µg/mL and remains at concentrations >100 µg/mL for 48 hours after a single 3-gram oral dose. No dosage adjustments are required in elderly patients, in pregnant patients, or in either renal or hepatic impairment. Fosfomycin demonstrates a favorable safety profile, and clinical trials have demonstrated efficacy in AUC that is comparable to ciprofloxacin, nitrofurantoin, and trimethoprim-sulfamethoxazole. Fosfomycin's in vitro activity against common uropathogens, including MDR isolates, its favorable safety profile including pregnancy patients, drug interactions, and clinical trials data demonstrating efficacy in AUC, has resulted in Canadian, US, and European guidelines/authorities recommending fosfomycin as a first line agent for the treatment of AUC. PMID:27366158

  16. Oral processing effort, appetite and acute energy intake in lean and obese adults.

    PubMed

    Mattes, Richard D; Considine, Robert V

    2013-08-15

    Chewing reportedly contributes to satiation and satiety signals. Attempts to document and quantify this have led to small and inconsistent effects. The present trial manipulated oral processing effort though required chewing of gums of different hardness and measured appetitive sensations, energy intake, gastric emptying, GI transit time, and concentrations of glucose, insulin, GLP-1, ghrelin and pancreatic polypeptide. Sixty adults classified by sex and BMI (15 each of lean females, obese females, lean males and obese males) were tested in a randomized, controlled, cross-over trial with three arms. They chewed nothing, soft gum or hard gum for 15 min while sipping grape juice (10% of individual energy needs) containing acetaminophen and lactulose on one day each separated by 7 days. Electromyographic recordings and self-reports were obtained during and after chewing to quantify oral processing effort. Blood was sampled through an indwelling catheter and appetite ratings were obtained at baseline and at 0, 15, 30, 45, 60, 90, 120, 180 and 240 min after chewing initiation. Breath samples were collected at 10 min intervals for the first 2h and at 30 min intervals for the next 2h. No effects of chewing were observed for appetitive sensations or gut peptide concentrations. Energy intake tended to decline in lean and increase in obese participants so that daily energy intake differed significantly between the two groups when chewing either gum, while no difference was observed on the non-chewing day. Serum glucose and insulin were significantly lower at selected time points 90-240 min after chewing compared to baseline and the non-chewing day. These data indicate chewing effort does not affect appetitive sensations or gut peptide secretion, but may exert a small differential effect on acute energy intake in lean and obese individuals and lead to greater post-prandial declines of serum glucose and insulin. The efficacy of gum chewing as a substitute for eating for weight

  17. WEB-BASED INTERSPECIES CORRELATION ESTIMATION (WEB-ICE) FOR ACUTE TOXICITY: USER MANUAL V2

    EPA Science Inventory

    Predictive toxicological models are integral to environmental risk Assessment where data for most species are limited. Web-based Interspecies Correlation Estimation (Web-ICE) models are least square regressions that predict acute toxicity (LC50/LD50) of a chemical to a species, ...

  18. Oral sapropterin acutely augments reflex vasodilation in aged human skin through nitric oxide-dependent mechanisms.

    PubMed

    Stanhewicz, Anna E; Alexander, Lacy M; Kenney, W Larry

    2013-10-01

    Functional constitutive nitric oxide synthase (NOS) and its cofactor tetrahydrobiopterin (BH4) are required for full reflex cutaneous vasodilation and are attenuated in primary aging. Acute, locally administered BH4 increases reflex vasodilation through NO-dependent mechanisms in aged skin. We hypothesized that oral sapropterin (Kuvan, shelf-stable pharmaceutical formulation of BH4) would augment reflex vasodilation in aged human skin during hyperthermia. Nine healthy human subjects (76 ± 1 yr) ingested sapropterin (10 mg/kg) or placebo in a randomized double-blind crossover design. Venous blood samples were collected prior to, and 3 h following, ingestion of sapropterin for measurement of plasma BH4. Three intradermal microdialysis fibers were placed in the forearm skin for local delivery of 1) lactated Ringer's solution, 2) 10 mM BH4, and 3) 20 mM N(G)-nitro-l-arginine methyl ester (l-NAME) to inhibit NOS. Red cell flux was measured at each site by laser-Doppler flowmetry (LDF) as reflex vasodilation was induced using a water-perfused suit. At 1°C rise in oral temperature, mean body temperature was clamped and 20 mM l-NAME was perfused at each site. Cutaneous vascular conductance was calculated (CVC = LDF/MAP) and expressed as a percentage of maximum (%CVCmax 28 mM sodium nitroprusside and local heat 43°C). Plasma concentrations of BH4 were significantly elevated 3 h after ingestion of sapropterin (0 h: 19.1 ± 2 pmol/ml vs. 3 h: 43.8 ± 3 pmol/ml; P < 0.001). Sapropterin increased NO-dependent vasodilation at control site (placebo: 14 ± 1 %CVCmax vs. sapropterin: 25 ± 4 %CVCmax; P = 0.004). Local BH4 administration increased NO-dependent vasodilation compared with control in placebo trials only (control: 14 ± 1 %CVCmax vs. BH4-treated: 24 ± 3 %CVCmax; P = 0.02). These data suggest oral sapropterin increases bioavailable BH4 in aged skin microvasculature sufficiently to increase NO synthesis through NOS and that sapropterin may be a viable intervention to

  19. Acute Disseminated Encephalomyelitis after Oral Therapy with Herbal Extracts: A Case Report

    PubMed Central

    Kaymakamzade, Bahar; Karabudak, Rana; Kurne, Aslı Tuncer; Nurlu, Gülay

    2016-01-01

    Background: Acute disseminated encephalomyelitis (ADEM) is a rare demyelinating disease of the central nervous system, commonly attributed to infections or vaccinations. Toxic or allergenic compounds can also trigger a response in the immune system and may cause demyelination. We present a case with ADEM after using oral herbal medications. Case Report: A 25 year-old male developed bilateral central facial palsy and severe quadriparesis after taking herbal drugs (containing echinacea and many other herbal ingredients) for two weeks. He had used the extract to increase his potency and reproductivity. He had no past history of recent immunization or viral infection. The clinical findings, cerebrospinal fluid (CSF) analysis and brain magnetic resonance imaging (MRI) were compatible with ADEM. The neurological findings were improved after seven doses of pulse methylprednisolone treatment. To our knowledge, this is the third report in the literature that links herbal therapy and demyelinating disease. Conclusion: Most of the ADEM cases related to herbal therapy in the literature similarly used echinacea. It is our opinion that other ingredients of the herbal extract used by our case, besides echinacea, could have the potential to cause a trigger in the immune system. Further studies are needed to clarify the immunological effects of different kinds of herbal compounds, as well as the effects of different parts of the plants and the results of various dosages. Moreover, ingredients should also be tested for toxicity, adverse effects and drug interactions. PMID:27308086

  20. Premedication With Oral Pregabalin for the Prevention of Acute Postsurgical Pain in Coronary Artery Bypass Surgery

    PubMed Central

    Ziyaeifard, Mohsen; Mehrabanian, Mohammad Javad; Faritus, Seyedeh Zahra; Khazaei Koohpar, Mehrdad; Ferasatkish, Rasool; Hosseinnejad, Heidar; Mehrabanian, Mohammadreza

    2015-01-01

    Background: For coronary artery bypass grafting (CABG) sternotomy should be performed. The pain after surgery is severe and requires medical intervention. Use of the analgesics is limited by their side effects and studies suggest that prevention with some medications before surgery is effective in controlling the postoperative pain. Objectives: We investigated the efficacy of pregabalin administration before surgery in the treatment of acute postoperative pain after CABG surgery. Patients and Methods: Sixty patients indicated for elective CABG surgery were randomly allocated to two groups. One group received placebo and the other received 150 mg of oral pregabalin before surgery. Heart rates, blood pressure, respiratory rate, intensive care unit (ICU) stay duration, morphine consumption, and pain score according to the visual analog scale (VAS) were measured and recorded at 4, 12, and 24 hours of surgery. Results: Pregabalin consumption did not alter hemodynamic parameters and was safe in patients after CABG. Its consumption was associated with significant reduction in the pain score (P values were 0.035, 0.026, and 0.047 respectively at 4, 12, and 24 hours of surgery). Its use was not associated with changes in the morphine consumption at 4, 12, and 24 hours of surgery (P > 0.05). Conclusions: Premedication with studied dose of pregabalin is effective for the prevention of postoperative pain in patients after CABG and has no adverse effects. Trials with other treating schedule and doses of the drug should be performed to determine the best treatment plan. PMID:25830118

  1. Adverse Effects of Oral Nonselective and cyclooxygenase-2-Selective NSAIDs on Hospitalization for Acute Kidney Injury

    PubMed Central

    Chou, Chia-I.; Shih, Chia-Jen; Chen, Yung-Tai; Ou, Shuo-Ming; Yang, Chih-Yu; Kuo, Shu-Chen; Chu, Dachen

    2016-01-01

    Abstract To investigate the association between the use of nonselective or cyclooxygenase (COX)-2-selective nonsteroidal antiinflammatory drugs (NSAIDs) and risk of acute kidney injury (AKI) in a general Asian population. We conducted an observational, nationwide, nested case–control cohort study using Taiwan's National Health Insurance Research Database between 2010 and 2012. AKI cases were defined as hospitalization with a principle diagnosis of AKI. Each case was matched to 4 randomly selected controls based on age, sex, and the month and year of cohort entry. Odds ratios (ORs) were used to demonstrate the association between hospitalization for AKI and current, recent, or past use of an oral NSAID. During the study period, we identified 6199 patients with AKI and 24,796 matched controls. Overall, current users (adjusted OR 2.73, 95% confidence interval [CI] 2.28–3.28) and recent users (adjusted OR 1.17, 95% CI 1.01–1.35) were associated with increased risk of hospitalization for AKI. The risk was also similar for nonselective NSAIDs. However, neither current nor recent use of COX-2 inhibitors was significantly associated with AKI events. Our study supported that the initiation of nonselective NSAIDs rather than COX-2 inhibitors is associated with an increased risk of AKI requiring hospitalization. Future randomized trials are needed to elucidate these findings. PMID:26945352

  2. Dose-response relationship of an environmental mixture of pyrethroids following an acute oral administration in the rat

    EPA Science Inventory

    Dose-response relationship of an environmental mixture of pyrethroids following an acute oral administration in the rat M.F. Hughes1, D.G. Ross1, J.M. Starr1, E.J. Scollon1,2, M.J. Wolansky1,3, K.M. Crofton1, M.J. DeVito1,4 1U.S. EPA, ORD, Research Triangle Park, NC, 2U.S. EPA,...

  3. Acute and Subchronic Toxicity Study of Euphorbia hirta L. Methanol Extract in Rats

    PubMed Central

    Yuet Ping, Kwan; Darah, Ibrahim; Chen, Yeng; Sreeramanan, Subramaniam

    2013-01-01

    Despite Euphorbia hirta L. ethnomedicinal benefits, very few studies have described the potential toxicity. The aim of the present study was to evaluate the in vivo toxicity of methanolic extracts of E. hirta. The acute and subchronic oral toxicity of E. hirta was evaluated in Sprague Dawley rats. The extract at a single dose of 5000 mg/kg did not produce treatment related signs of toxicity or mortality in any of the animals tested during the 14-day observation period. Therefore, the LD 50 of this plant was estimated to be more than 5000 mg/kg. In the repeated dose 90-day oral toxicity study, the administration of 50 mg/kg, 250 mg/kg, and 1000 mg/kg/day of E. hirta extract per body weight revealed no significant difference (P > 0.05) in food and water consumptions, body weight change, haematological and biochemical parameters, relative organ weights, and gross findings compared to the control group. Macropathology and histopathology examinations of all organs including the liver did not reveal morphological alteration. Analyses of these results with the information of signs, behaviour, and health monitoring could lead to the conclusion that the long-term oral administration of E. hirta extract for 90 days does not cause sub-chronic toxicity. PMID:24386634

  4. Acute Toxicity Study of Zerumbone-Loaded Nanostructured Lipid Carrier on BALB/c Mice Model

    PubMed Central

    Rahman, Heshu Sulaiman; Rasedee, Abdullah; Othman, Hemn Hassan; Chartrand, Max Stanley; Namvar, Farideh; Abdul Samad, Nozlena; Andas, Reena Joys; Ng, Kuan Beng; How, Chee Wun

    2014-01-01

    Zerumbone- (ZER-) loaded nanostructure lipid carrier (NLC) (ZER-NLC) prepared for its antileukemia effect in vitro was evaluated for its toxicological effects by observing changes in the liver, kidney, spleen, lung, heart, and brain tissues, serum biochemical parameters, total haemogram, and bone marrow stem cells. The acute toxicity study for ZER-NLC was conducted by orally treating BALB/c mice with a single dose with either water, olive oil, ZER, NLC, or ZER-NLC for 14 days. The animals were observed for clinical and behavioral abnormalities, toxicological symptoms, feed consumption, and gross appearance. The liver, kidney, heart, lung, spleen, and brain tissues were assessed histologically. Total haemogram was counted by hemocytometry and microhematocrit reader. Bone marrow examination in terms of cellular morphology was done by Wright staining with bone marrow smear. Furthermore, serum biochemical parameters were determined spectrophotometrically. Grossly all treated mice, their investigated tissues, serum biochemical parameters, total haemogram, and bone marrow were normal. At oral doses of 100 and 200 mg/kg ZER-NLC there was no sign of toxicity or mortality in BALB/c mice. This study suggests that the 50% lethal dose (LD50) of ZER-NLC is higher than 200 mg/kg, thus, safe by oral administration. PMID:25276798

  5. 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

  6. [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. PMID:16277953

  7. [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.

  8. Antibody blockade of IL-17 family cytokines in immunity to acute murine oral mucosal candidiasis.

    PubMed

    Whibley, Natasha; Tritto, Elaine; Traggiai, Elisabetta; Kolbinger, Frank; Moulin, Pierre; Brees, Dominique; Coleman, Bianca M; Mamo, Anna J; Garg, Abhishek V; Jaycox, Jillian R; Siebenlist, Ulrich; Kammüller, Michael; Gaffen, Sarah L

    2016-06-01

    Antibodies targeting IL-17A or its receptor, IL-17RA, are approved to treat psoriasis and are being evaluated for other autoimmune conditions. Conversely, IL-17 signaling is critical for immunity to opportunistic mucosal infections caused by the commensal fungus Candida albicans, as mice and humans lacking the IL-17R experience chronic mucosal candidiasis. IL-17A, IL-17F, and IL-17AF bind the IL-17RA-IL-17RC heterodimeric complex and deliver qualitatively similar signals through the adaptor Act1. Here, we used a mouse model of acute oropharyngeal candidiasis to assess the impact of blocking IL-17 family cytokines compared with specific IL-17 cytokine gene knockout mice. Anti-IL-17A antibodies, which neutralize IL-17A and IL-17AF, caused elevated oral fungal loads, whereas anti-IL-17AF and anti-IL-17F antibodies did not. Notably, there was a cooperative effect of blocking IL-17A, IL-17AF, and IL-17F together. Termination of anti-IL-17A treatment was associated with rapid C. albicans clearance. IL-17F-deficient mice were fully resistant to oropharyngeal candidiasis, consistent with antibody blockade. However, IL-17A-deficient mice had lower fungal burdens than anti-IL-17A-treated mice. Act1-deficient mice were much more susceptible to oropharyngeal candidiasis than anti-IL-17A antibody-treated mice, yet anti-IL-17A and anti-IL-17RA treatment caused equivalent susceptibilities. Based on microarray analyses of the oral mucosa during infection, only a limited number of genes were associated with oropharyngeal candidiasis susceptibility. In sum, we conclude that IL-17A is the main cytokine mediator of immunity in murine oropharyngeal candidiasis, but a cooperative relationship among IL-17A, IL-17AF, and IL-17F exists in vivo. Susceptibility displays the following hierarchy: IL-17RA- or Act1-deficiency > anti-IL-17A + anti-IL-17F antibodies > anti-IL-17A or anti-IL-17RA antibodies > IL-17A deficiency.

  9. Effect of Preoperative Oral Amantadine on Acute and Chronic Postoperative Pain After Mandibular Fracture Surgery

    PubMed Central

    Yazdani, Javad; Aghamohamadi, Davood; Amani, Masoomeh; Mesgarzadeh, Ali Hossein; Maghbooli Asl, Davood; Pourlak, Tannaz

    2016-01-01

    Background Postoperative pain from open reduction and internal fixation of mandibular fracture is a serious issue. Amantadine is an N-methyl-D-aspartic acid or N-methyl-D-aspartate (NMDA) receptor antagonist that can be effective against postoperative pain. Objectives The present study examined the efficacy of amantadine in alleviating the postoperative pain of mandibular fracture surgery. Patients and Methods In this double-blind study, 60 patients (ASA physical status I–II) were randomly divided into two groups. The mean ages of the participants were 31.2 ± 13.1 years and 32.3 ± 18.1 years, respectively. The male/female ratios were 24/6 and 26/4, respectively, in the case and control groups. Randomization was based on a single sequence of random assignments using computer-generated random numbers. Group I was given oral amantadine 100 mg 1 hour before surgery, and group II received a placebo at the identical time. Through PCA pumps, patients received a bolus dose of morphine at 0.02 mg/kg body weight, to a maximum of 1.5 mg. PCA pumps were set at 6 minutes lockout intervals and a maximum dose of 0.15 mg/kg/h, to a maximum of 10 mg/h. Pain was assessed using a visual analog scale (VAS) at 0, 2, 4, 6, 12, and 24 hours and 1, 2, 3, 4, 5, and 6 months after surgery. The amounts of analgesic consumed were recorded for the first 24 hours, and for 6 months after surgery. Results There were no significant differences between the two groups with respect to age, gender, nausea and vomiting, sleep quality, blood pressure, and heart rate. No significant differences were observed between the two groups in pain scores (P = 0.39) and analgesic consumption (P = 0.78). Conclusions The results suggest that a single dose of preoperative oral amantadine did not reduce acute or chronic postoperative pain, nor analgesic consumption. PMID:27642581

  10. Improvement of banana cv. Rasthali (Silk, AAB) against Fusarium oxysporum f.sp. cubense (VCG 0124/5) through induced mutagenesis: Determination of LD50 specific to mutagen, explants, toxins and in vitro and in vivo screening for Fusarium wilt resistance.

    PubMed

    Saraswathi, M S; Kannan, G; Uma, S; Thangavelu, R; Backiyarani, S

    2016-05-01

    Shoot tips and in vitro grown proliferating buds of banana cv. Rasthali (Silk, AAB) were treated with various concentrations and durations of chemical mutagens viz., EMS, NaN3 and DES. LD50 for shoot tips based on 50% reduction in fresh weight was determined as 2% for 3 h, 0.02% for 5 h and 0.15% for 5 h, while for proliferating buds, they were 0.6% for 30 min, 0.01% for 2 h and 0.06% for 2 h for the mutagens EMS, NaN3 and DES, respectively. Subsequently, the mutated explants were screened in vitro against fusarium wilt using selection agents like fusaric acid and culture filtrate. LD50 for in vitro selection agents calculated based on 50% survival of explants was 0.050 mM and 7% for fusaric acid and culture filtrate, respectively and beyond which a rapid decline in growth was observed. This was followed by pot screening which led to the identification of three putative resistant mutants with an internal disease score of 1 (corm completely clean, no vascular discolouration). The putative mutants identified in the present study have also been mass multiplied in vitro.

  11. Improvement of banana cv. Rasthali (Silk, AAB) against Fusarium oxysporum f.sp. cubense (VCG 0124/5) through induced mutagenesis: Determination of LD50 specific to mutagen, explants, toxins and in vitro and in vivo screening for Fusarium wilt resistance.

    PubMed

    Saraswathi, M S; Kannan, G; Uma, S; Thangavelu, R; Backiyarani, S

    2016-05-01

    Shoot tips and in vitro grown proliferating buds of banana cv. Rasthali (Silk, AAB) were treated with various concentrations and durations of chemical mutagens viz., EMS, NaN3 and DES. LD50 for shoot tips based on 50% reduction in fresh weight was determined as 2% for 3 h, 0.02% for 5 h and 0.15% for 5 h, while for proliferating buds, they were 0.6% for 30 min, 0.01% for 2 h and 0.06% for 2 h for the mutagens EMS, NaN3 and DES, respectively. Subsequently, the mutated explants were screened in vitro against fusarium wilt using selection agents like fusaric acid and culture filtrate. LD50 for in vitro selection agents calculated based on 50% survival of explants was 0.050 mM and 7% for fusaric acid and culture filtrate, respectively and beyond which a rapid decline in growth was observed. This was followed by pot screening which led to the identification of three putative resistant mutants with an internal disease score of 1 (corm completely clean, no vascular discolouration). The putative mutants identified in the present study have also been mass multiplied in vitro. PMID:27319054

  12. Lipase inhibition attenuates the acute inhibitory effects of oral fat on food intake in healthy subjects.

    PubMed

    O'Donovan, Deirdre; Feinle-Bisset, Christine; Wishart, Judith; Horowitz, Michael

    2003-11-01

    The lipase inhibitor, orlistat, is used in the treatment of obesity and reduces fat absorption by about 30%. However, the mean weight loss induced by orlistat is less than expected for the degree of fat malabsorption. It was hypothesised that lipase inhibition with orlistat attenuates the suppressive effects of oral fat on subsequent energy intake in normal-weight subjects. Fourteen healthy, lean subjects (nine males, five females; aged 25 +/- 1.3 years) were studied twice, in a double-blind fashion. The subjects received a high-fat yoghurt 'preload' (males 400 g (2562 kJ); females 300 g (1923 kJ)), containing orlistat (120 mg) on one study day (and no orlistat on the other 'control' day), 30 min before ad libitum access to food and drinks; energy intake was assessed during the following 8 h. Blood samples were taken at regular intervals for the measurement of plasma cholecystokinin (CCK). Each subject performed a 3 d faecal fat collection following each study. Energy intake during the day was greater following orlistat (10,220 (SEM 928) kJ) v. control (9405 (SEM 824) kJ) (P=0.02). On both days plasma CCK increased (P<0.05) after the preload. Plasma CCK 20 min following ingestion of the preload was less after orlistat (4.1 (SEM 0.9) pmol/l) v. control (5.3 (SEM 0.9) pmol/l (P=0.028); however there was no difference in the area under the curve 0-510 min between the two study days. Fat excretion was greater following orlistat (1017 (SEM 168) kJ) v. control (484 (SEM 90) kJ) (P=0.004). In conclusion, in healthy, lean subjects the acute inhibitory effect of fat on subsequent energy intake is attenuated by orlistat and the increase in energy intake approximates the energy lost due to fat malabsorption. PMID:14667178

  13. Web-based Interspecies Correlation Estimation (Web-ICE) for Acute Toxicity: User Manual Version 3.1

    EPA Science Inventory

    Predictive toxicological models are integral to ecological risk assessment because data for most species are limited. Web-based Interspecies Correlation Estimation (Web-ICE) models are least square regressions that predict acute toxicity (LC50/LD50) of a chemical to a species, ge...

  14. Evaluation of the antinociceptive activity and acute oral toxicity of standardized ethanolic extract of the rhizome of Curcuma xanthorrhiza Roxb.

    PubMed

    Devaraj, Sutha; Esfahani, Azadeh Sabetghadam; Ismail, Sabariah; Ramanathan, Surash; Yam, Mun Fei

    2010-04-22

    Ethanolic extract of Curcuma xanthorrhiza was used to evaluate the analgesic and toxicity effects in vivo. The extract was standardized using GC-MS, which showed that 1 mg of Curcuma xanthorrhiza ethanolic extract contains 0.1238 mg of xanthorrhizol. The analgesic activity was studied in rats using three different models, namely the hot plate test, tail flick test and formalin-induced pain test. The acute oral toxicity was examined by the oral administration of standardized Curcuma xanthorrhiza ethanolic extract in mice at doses ranging from 300-5,000 mg/kg and observation for 14 days. Standardized Curcuma xanthorrhiza ethanolic extract did not show significant analgesic effect in the hot plate and tail flick tests. However, in the formalin-induced pain test, Curcuma xanthorrhiza ethanolic extract significantly (P < 0.05) suppressed the paw licking time of rats in both early and late phases at doses 200 and 400 mg/kg of the extract, respectively. In the acute oral toxicity study, Curcuma xanthorrhiza ethanolic extract did not show any toxic effects in mice at 5 g/kg. These experimental results suggest that the standardized Curcuma xanthorrhiza ethanolic extract showed peripheral and central antinociceptive activity associated with neurogenic pain as well as a relative absence of toxic effects which could compromise the medicinal use of this plant in folk medicine.

  15. Safety Evaluation of Chrysanthemum indicum L. Flower Oil by Assessing Acute Oral Toxicity, Micronucleus Abnormalities, and Mutagenicity

    PubMed Central

    Hwang, Eun-Sun; Kim, Gun-Hee

    2013-01-01

    Chrysanthemum indicum is widely used to treat immune-related and infectious disorders in East Asia. C. indicum flower oil contains 1,8-cineole, germacrene D, camphor, α-cadinol, camphene, pinocarvone, β-caryophyllene, 3-cyclohexen-1-ol, and γ-curcumene. We evaluated the safety of C. indicum flower oil by conducting acute oral toxicity, bone marrow micronucleus, and bacterial reverse mutation tests. Mortality, clinical signs and gross findings of mice were measured for 15 days after the oral single gavage administration of C. indicum flower oil. There were no mortality and clinical signs of toxicity at 2,000 mg/kg body weight/day of C. indicum flower oil throughout the 15 day period. Micronucleated erythrocyte cell counts for all treated groups were not significantly different between test and control groups. Levels of 15.63~500 μg C. indicum flower oil/plate did not induce mutagenicity in S. Typhimurium and E. coli, with or without the introduction of a metabolic activation system. These results indicate that ingesting C. indicum flower oil produces no acute oral toxicity, bone marrow micronucleus, and bacterial reverse mutation. PMID:24471119

  16. Acute effects of an oral nitric oxide supplement on blood pressure, endothelial function, and vascular compliance in hypertensive patients.

    PubMed

    Houston, Mark; Hays, Laurie

    2014-07-01

    This blinded placebo-controlled crossover study evaluated the acute effects of an orally disintegrating lozenge that generates nitric oxide (NO) in the oral cavity on blood pressure (BP) response, endothelial function, and vascular compliance in unmedicated hypertensive patients. Thirty patients with clinical hypertension were recruited and enrolled in a blinded placebo-controlled clinical trial in an outpatient setting. Average baseline BP in 30 patients was 144±3/91±1 mm Hg. NO supplementation resulted in a significant decrease of 4 mm Hg in resting systolic BP (P<.003) and a significant decrease of 5 mm Hg in diastolic BP (P<.002) from baseline and placebo after 20 minutes. In addition, there was a further statistically significant reduction by 6 mm Hg in both systolic and diastolic pressure after 60 minutes (P<.0001 vs baseline). After a half hour of a single dose, there was a significant improvement in vascular compliance as measured by augmentation index and, after 4 hours, a statistically significant improvement in endothelial function as measured by the EndoPAT (Itamar Medical, Franklin, MA). A single administration of an oral active NO supplement appears to acutely lower BP, improve vascular compliance, and restore endothelial function in patients with hypertension. PMID:24962851

  17. Acute phase proteins, C9, factor B, and lysozyme in recurrent oral ulceration and Behçet's syndrome.

    PubMed Central

    Lehner, T; Adinolfi, M

    1980-01-01

    The concentrations and sequential changes of some acute phase proteins, factor B, and lysozyme have been assayed in recurrent oral ulceration and Behçet's syndrome. C9 was elevated in both groups of patients and was the sensitive index of disease activity; however, it failed to discriminate between the three types of recurrent oral ulcers and four types of Behçet's syndrome. The level of alpha 1 acid glycoprotein and lysozyme were significantly increased predominantly in the ocular type, whereas factor B was significantly increased especially in the neurological type of Behçet's syndrome. It is suggested that the changes in the concentrations of some plasma proteins may help our understanding of tissue involvement in Behçet's syndrome, as well as in the selection of therapeutic agents in this disease. PMID:6900632

  18. Acute and subchronic toxicity as well as evaluation of safety pharmacology of eucalyptus oil-water emulsions.

    PubMed

    Hu, Zhiqiang; Feng, Ruizhang; Xiang, Fa; Song, Xu; Yin, Zhongqiong; Zhang, Chao; Zhao, Xinghong; Jia, Renyong; Chen, Zhenzhen; Li, Li; Yin, Lizi; Liang, Xiaoxia; He, Changliang; Shu, Gang; Lv, Cheng; Zhao, Ling; Ye, Gang; Shi, Fei

    2014-01-01

    Essential oil has performed a variety of indirect services used as insect/pest repellent. The present study investigated the acute and subchronic toxicity of eucalyptus oil emulsion in water (EOE). In addition, we conduct safety pharmacology evaluation of EOE to supplement the toxicity tests and provide a basis for a comprehensive understanding of the toxicity of EOE. Acute administration of EOE was done as single dose from 2772 mg to 5742 mg of EOE per kg/bodyweight (b.wt.) and subchronic toxicity study for thirty days was done by daily oral administration of EOE at doses of 396, 792 and 1188 mg/kg b.wt. In SPF SD rats. The acute toxicity study showed the LD50 of EOE was 3811.5 mg/kg. The subchronic toxicity study suggested the high-dose and middle-dose EOE slowed down the growth of male rats. The clinical pathology showed the high-dose and middle-dose EOE could cause damage to liver and kidney. The safety pharmacology indicated that EOE had no side effects on rats. These results suggest that EOE is a safe veterinary medicine for external use.

  19. Acute and subchronic toxicity as well as evaluation of safety pharmacology of eucalyptus oil-water emulsions.

    PubMed

    Hu, Zhiqiang; Feng, Ruizhang; Xiang, Fa; Song, Xu; Yin, Zhongqiong; Zhang, Chao; Zhao, Xinghong; Jia, Renyong; Chen, Zhenzhen; Li, Li; Yin, Lizi; Liang, Xiaoxia; He, Changliang; Shu, Gang; Lv, Cheng; Zhao, Ling; Ye, Gang; Shi, Fei

    2014-01-01

    Essential oil has performed a variety of indirect services used as insect/pest repellent. The present study investigated the acute and subchronic toxicity of eucalyptus oil emulsion in water (EOE). In addition, we conduct safety pharmacology evaluation of EOE to supplement the toxicity tests and provide a basis for a comprehensive understanding of the toxicity of EOE. Acute administration of EOE was done as single dose from 2772 mg to 5742 mg of EOE per kg/bodyweight (b.wt.) and subchronic toxicity study for thirty days was done by daily oral administration of EOE at doses of 396, 792 and 1188 mg/kg b.wt. In SPF SD rats. The acute toxicity study showed the LD50 of EOE was 3811.5 mg/kg. The subchronic toxicity study suggested the high-dose and middle-dose EOE slowed down the growth of male rats. The clinical pathology showed the high-dose and middle-dose EOE could cause damage to liver and kidney. The safety pharmacology indicated that EOE had no side effects on rats. These results suggest that EOE is a safe veterinary medicine for external use. PMID:25663980

  20. Acute and subchronic toxicity as well as evaluation of safety pharmacology of eucalyptus oil-water emulsions

    PubMed Central

    Hu, Zhiqiang; Feng, Ruizhang; Xiang, Fa; Song, Xu; Yin, Zhongqiong; Zhang, Chao; Zhao, Xinghong; Jia, Renyong; Chen, Zhenzhen; Li, Li; Yin, Lizi; Liang, Xiaoxia; He, Changliang; Shu, Gang; Lv, Cheng; Zhao, Ling; Ye, Gang; Shi, Fei

    2014-01-01

    Essential oil has performed a variety of indirect services used as insect/pest repellent. The present study investigated the acute and subchronic toxicity of eucalyptus oil emulsion in water (EOE). In addition, we conduct safety pharmacology evaluation of EOE to supplement the toxicity tests and provide a basis for a comprehensive understanding of the toxicity of EOE. Acute administration of EOE was done as single dose from 2772 mg to 5742 mg of EOE per kg/bodyweight (b.wt.) and subchronic toxicity study for thirty days was done by daily oral administration of EOE at doses of 396, 792 and 1188 mg/kg b.wt. In SPF SD rats. The acute toxicity study showed the LD50 of EOE was 3811.5 mg/kg. The subchronic toxicity study suggested the high-dose and middle-dose EOE slowed down the growth of male rats. The clinical pathology showed the high-dose and middle-dose EOE could cause damage to liver and kidney. The safety pharmacology indicated that EOE had no side effects on rats. These results suggest that EOE is a safe veterinary medicine for external use. PMID:25663980

  1. Acute and sub-chronic toxicity of glucose-cysteine Maillard reaction products in Sprague-Dawley rats.

    PubMed

    Li, Yixing; Su, Linliang; Li, Fenfang; Wang, Chaozheng; Yuan, Debao; Chen, Jiao; Tan, Lin; Jin, Zhiqiang; Ma, Weihong

    2015-06-01

    Maillard reaction products (MRPs) derived from glucose-cysteine reactions have excellent anti-browning ability. However, there is a lack of information about their acute and sub-chronic toxicities. To our knowledge, the present study is the first to evaluate the acute and sub-chronic toxicities of MRPs in experimental animals. Acute toxicity testing and analysis by Horn's method showed that the median lethal oral dose (LD50) of MRPs in rats was 6.81 g/kg body weight. The sub-chronic toxicity test involved feeding rats with diet containing 0, 0.43, 0.85, or 1.70% (w/w) MRPs for 90 days. These treatments did not affect mortality, gross pathology, histology, hematology, or blood chemistry, and there were no dose-dependent changes in feed consumption. Based on these results, the dietary no-observed-adverse-effect level (NOAEL) for 90-day exposure was 1.29 and 1.51 g MRPs/kg body weight/day for male and female rats, respectively. PMID:25817020

  2. Managing a Rivaroxaban Bleed: Understanding the Difficulties in Acute Reversal of the New Oral Anticoagulants through a Case Report

    PubMed Central

    Singh, Robby; Mckay, Paulina

    2014-01-01

    With the arrival of a new generation of oral anticoagulants significant burdens associated with warfarin's use on both the patient and the healthcare system have been alleviated. Nevertheless, a shortfall exists in regard to an agent or protocol for reversal of these new anticoagulants in the setting of an acute bleed. Our case of a patient presenting to the hospital with a vaginal bleed while on rivaroxaban highlights the difficulty in management without a clear protocol or agent for reversal of anticoagulation. PMID:25478253

  3. Acute and subacute toxicity assessment of lutein in lutein-deficient mice.

    PubMed

    Nidhi, Bhatiwada; Baskaran, Vallikannan

    2013-10-01

    Dietary lutein consumption is lower than the actual recommended allowances to prevent macular degeneration; thus dietary lutein supplements have been recommended. This study aimed to investigate potential adverse effect of lutein from Tagetes erecta in lutein-deficient (LD) male mice. Preliminary acute toxicity study revealed that the LD50 exceeded the highest dose of 10000 mg/kg BW. In a subacute study, male mice were gavaged with 0, 100, 1000 mg/kg BW/day for a period of 4 wk. Plasma lutein levels increased dose dependently (P < 0.01) after acute and subacute feeding of lutein in LD mice. Compared to the control (peanut oil without lutein) group, no treatment-related toxicologically significant effects of lutein were prominent in clinical observation, ophthalmic examinations, body, and organ weights. Further, no toxicologically significant findings were eminent in hematological, histopathological, and other clinical chemistry parameters. In the oral subacute toxicity study, the no-observed-adverse-effect level (NOAEL) for lutein in LD mice was determined as 1000 mg/kg/day, the highest dose tested.

  4. Efficacy and effects of palifermin for the treatment of oral mucositis in patients affected by acute lymphoblastic leukemia.

    PubMed

    Lucchese, Alessandra; Matarese, Giovanni; Ghislanzoni, Luis Huanca; Gastaldi, Giorgio; Manuelli, Maurizio; Gherlone, Enrico

    2016-01-01

    This randomized-controlled trial studied the efficacy of palifermin, administered as a dose during hematopoietic stem cell transplant (HSCT) therapy, as primary prophylaxis on pediatric patients with acute lymphoblastic leukemia in order to reduce oral mucositis (OM). Patients in the palifermin group were randomly assigned to receive palifermin, 60 μg/kg, intravenously as a single dose 3 days before and 0, +1, and +2 post autologous HSCT infusion. The patients in the control group received only a placebo treatment. OM-related assessments were the WHO oral-toxicity scale and the patient-reported outcomes. There was a statistically significant reduction in the incidence of OM grade 3 and 4 in the palifermin group compared to the control group. There was also a reduction in the degree of severity of OM in the palifermin group (1.65 grade respect to 2.33 in the control group). Palifermin could prevent the recurrence of severe OM and improve the quality of life in patients with acute lymphoblastic leukemia (ALL). PMID:26428409

  5. Evaluation of the mutagenic potential and acute oral toxicity of standardized extract of Ocimum sanctum (OciBest™).

    PubMed

    Chandrasekaran, C V; Srikanth, H S; Anand, M S; Allan, J Joshua; Viji, M M Hipolith; Amit, A

    2013-09-01

    Ocimum sanctum L. (Lamiaceae) is found throughout India and in many parts of world. O. sanctum is used for the treatment of various health indications. In this lieu, it is of prime importance to investigate the safety aspects of the plant. Hence, the present study was conducted to investigate the possible genotoxic potential and acute oral toxicity of the extract of O. sanctum (OciBest™). The standard battery of in vitro genotoxicity tests, namely bacterial reverse mutation, chromosome aberration and micronucleus (MN) tests were employed to assess the possible mutagenic activity. The results showed that OciBest™ (7.9-2500.0 µg/mL) did not increase the number of histidine revertant colonies in Salmonella typhimurium strains (TA98 and TAMix) with and without exogenous metabolic activation (S9). OciBest™ (10.0-100.0 µg/mL) did not show structural chromosomal aberrations or increase in MN induction, with and without S9, at the tested dose range in both 4-h and 18-h exposure cell cultures. Thus, OciBest™ is not genotoxic in bacterial reverse mutation, chromosomal aberration and MN tests. In an acute oral toxicity test, rats were treated with 5 g/kg of OciBest™ and observed for signs of toxicity for 14 days and the results did not show any treatment-related toxic effects to Wistar rats. PMID:23424203

  6. In vitro anti oxidant activity and acute oral toxicity of Terminalia paniculata bark ethanolic extract on Sprague Dawley rats

    PubMed Central

    Mopuri, Ramgopal; Meriga, Balaji

    2014-01-01

    Objective To ensure the safety and evaluate the anti oxidant activity of Terminalia paniculata (T. paniculata) ethanolic extract in Sprague Dawley rats. Methods The solvent extracts (hexane, ethyl acetate and ethanol) of T. paniculata were subjected to phytochemical analysis and their DPPH radical scavenging activity was assayed. The oral acute toxicity was evaluated using ethanolic extract of T. paniculata. Results Ethyl acetate and ethanolic extracts showed more phytochemicals, whereas highest DPPH scavenging activity was found in ethanolic extract. In an acute toxicity study, T. paniculata ethanolic extract was orally administered (1 000 mg/kg body weight) to rats and observed for 72 h for any toxic symptoms and the dose was continued up to 14 d. On the 15th day rats were sacrificed and blood samples were collected from control and test animals and analyzed for some biochemical parameters. We did not observe any behavioral changes in test groups in comparison with their controls. Also, there were no significant alterations in biochemical, hematological (hemoglobin content and blood cells count) and liver function parameters such as serum glutamate pyruvate transaminase, serum glutamate oxaloacetate transaminase, alkaline phosphatase, total proteins, albumin and bilirubin levels between T. paniculata ethanolic extract treated and normal control groups. Conclusions Together our results demonstrated that T. paniculata ethanolic possessed potent antioxidant activity and it was safer and non toxic to rats even at higher doses and therefore could be well considered for further investigation for its medicinal and therapeutic efficacy. PMID:25182554

  7. Safety of Pochonia chlamydosporia var catenulata in acute oral and dermal toxicity/pathogenicity evaluations in rats and rabbits.

    PubMed

    García, Liseth; Bulnes, Carlos; Melchor, Gleiby; Vega, Ernesto; Ileana, Miranda; de Oca, Nivian Montes; Hidalgo, Leopoldo; Marrero, Eva

    2004-10-01

    The nematophagous fungus, Pochonia chlamydosporia var. catenulata (Kamyschlco ex Barron & Onions) Zare & W-Gams, was investigated as a potential biocontrol agent in integrated pest management strategy for Meloidogyne incognita (Kofoid and White) Chitwood in vegetable crops in Cuba. An acute oral and dermal toxicity/patogenicity study was performed to determine the safety of this fungus in non-target organisms. In the first study, a 1-dose level of 5 x 10(8) units of the microbial pest control agent/treated rat was used. Mortality or clinical signs were not evident and no adverse effects on body weight, hematology, microbiology and gross or microscopic pathology were observed. Food and water consumption was not significantly different between control and treated groups. In the acute dermal toxicity study, there was neither mortality nor clinical signs of toxicity, and no toxic effects in gross and microscopic pathology were detected. Thus, Pochonia chlamydosporia var. catenulate (Vcc-108, IMI SD 187), administered oral and dermally to rats and rabbits respectively, was safe in toxicity/pathogenicity studies. PMID:15487645

  8. Signal Words

    MedlinePlus

    ... Signal Words? Signal words are found on pesticide product labels, and they describe the acute (short-term) toxicity ... red letters on the front panel of the product label. 2,4 Acute Oral LD 50 Inhalation LC ...

  9. Oral glutamine supplementation improves intestinal permeability dysfunction in a murine acute graft-vs.-host disease model.

    PubMed

    Noth, Rainer; Häsler, Robert; Stüber, Eckhard; Ellrichmann, Mark; Schäfer, Heiner; Geismann, Claudia; Hampe, Jochen; Bewig, Burkhard; Wedel, Thilo; Böttner, Martina; Schreiber, Stefan; Rosenstiel, Philip; Arlt, Alexander

    2013-04-01

    Although a profound barrier dysfunction has been reported, little is known about the pathophysiological mechanism evoking gastrointestinal graft-vs.-host disease (GI-GvHD) and apparent therapeutic options. The aim of this study was to evaluate the influence of oral glutamine on the course of GI-GvHD in an acute semiallogenic graft-vs.-host disease (GvHD) in irradiated B6D2F1 mice. An acute semiallogenic GvHD was induced by intraperitoneal injection of lymphocytes from C57BL/6 mice to irradiated B6D2F1 mice. Half of the GvHD animals received oral glutamine supplementation for 6 days started at the time of lymphocyte transfer. Six days after induction of the semiallogenic GvHD, jejunum specimens were prepared. The expression of the proinflammatory cytokine TNF-α and the tight junction protein occludin was investigated by PCR. Histological changes along with the apoptotic response were evaluated and intestinal permeability was assessed. Animals with GvHD showed a strong increase in paracellular permeability as a sign of the disturbed barrier function. TNF-α expression was significantly increased and the expression of the tight junction protein occludin decreased. GvHD led to mucosal atrophy, crypt hyperplasia, crypt apoptosis, and a disintegration of the tight junctions. Glutamine-treated mice showed reduced expression of TNF-α, increased occludin expression, fewer histological changes in the jejunum, smaller number of apoptotic cells in the crypt, and reduced gastrointestinal permeability. In conclusion, oral glutamine seems to have beneficial effects on the severity of inflammatory changes in the course of GvHD and might be a therapeutic option.

  10. Oral Maintenance Chemotherapy with 6-Mercaptopurine and Methotrexate in Patients with Acute Myeloid Leukemia Ineligible for Transplantation.

    PubMed

    Choi, Yong Won; Jeong, Seong Hyun; Ahn, Mi Sun; Lee, Hyun Woo; Kang, Seok Yun; Choi, Jin-Hyuk; Park, Joon Seong

    2015-10-01

    For decades, maintenance chemotherapy has failed to improve the cure rate or prolong the survival of patients with acute myeloid leukemia (AML), other than those with acute promyelocytic leukemia. Immediately after the first complete remission following consolidation therapy was obtained, oral maintenance chemotherapy (daily 6-mercaptopurine and weekly methotrexate) was given and continued for two years in transplant-ineligible AML patients. Leukemia-free survival (LFS) and overall survival (OS) were studied and compared between these patients and the historical control group who did not receive maintenance therapy. Consecutive 52 transplant-ineligible AML patients were analyzed. Among these patients, 27 received oral maintenance chemotherapy. No significant difference was found in the patients' characteristics between the maintenance and the control groups. The median OS was 43 (95% CI, 19-67) and 19 (95% CI, 8-30) months in the maintenance and the control groups, respectively (P = 0.202). In the multivariate analysis, the presence of maintenance therapy was an independent prognostic factor for better OS (P = 0.021) and LFS (P = 0.024). Clinical benefit from maintenance chemotherapy was remarkable in older patients (≥ 60 yr) (P = 0.035), those with intermediate or unfavorable cytogenetics (P = 0.006), those with initial low blast count in peripheral blood (P = 0.044), and those receiving less than two cycles of consolidation therapy (P = 0.017). Maintenance oral chemotherapy as a post-remission therapy can prolong the survival of patients with AML who are not eligible for transplantation, particularly older patients, those with intermediate or unfavorable cytogenetics, those with initial low blast count, and those receiving less than two cycles of consolidation therapy.

  11. [Improving the solubility of fraxinellone to increase its oral bioavailability and hepatoprotective action against acute liver injury in mice].

    PubMed

    Ran, Qi-Qiong; Ruan, Li-Ping; Zhu, Dan-Ni; Yu, Bo-Yang

    2007-06-01

    Fraxinellone, the major component of Cortex Dictamni, is naturally degraded limonids compound. Fraxinellone has significant anti-inflammatory activity in acute liver injury model. However, the low solubility and permeability of fraxinellone limited its potential application and even therapeutic effects. The aim of the paper is to increase oral bioavailability of fraxinellone, thus improving its hepatoprotection effect in vivo. We evaluated the effects of different pH values and different solubilizer (PEG 6000, PVP K30, HP-beta-CD, F68 and SDS) on the solubility of fraxinellone. The results showed that HP-beta-CD increased solubility of fraxinellone up to 155 times compared to that of water. More than 2. 1 mg mL1 fraxinellone can be resolved when adding 20% HP-beta-CD. Mouse acute liver injury model induced hy CCl4 was used to evaluate in vivo activity of fraxinellone with or without HP-beta-CD. The result shows that the hepatoprotective activity of fraxinellone in 20% HP-beta-CD solution has been significantly improved compared with that of fraxinellone solution without HP-beta-CD: the former inhibited 59 percent the increase of enzyme activity of ALT in liver, while the latter only inhibited 20 percent. A LC-MS/MS method was also developed to determine the oral bioavailability of fraxinellone. Fraxinellone solution with or without HP-betaCD were administered intra-gastrically to rats, and it was found that the bioavailahility of fraxinellone with HP-beta-CD was 23%, while only 5% without HP-beta-CD. The result showed that HP-beta-CD can significantly increase the solubility and permeability of fraxinellone, and improve bioavailability 3. 5 fold in vivo acute liver injury model as well as administration.

  12. Quantitative Structure--Activity Relationship Modeling of Rat Acute Toxicity by Oral Exposure

    EPA Science Inventory

    Background: Few Quantitative Structure-Activity Relationship (QSAR) studies have successfully modeled large, diverse rodent toxicity endpoints. Objective: In this study, a combinatorial QSAR approach has been employed for the creation of robust and predictive models of acute toxi...

  13. Should a Preschool Child with Acute Episodic Wheeze be Treated with Oral Corticosteroids? A Pro/Con Debate.

    PubMed

    Beigelman, Avraham; Durrani, Sandy; Guilbert, Theresa W

    2016-01-01

    Traditionally, preschool-aged children with an acute wheezing episode have been treated with oral corticosteroids (OCSs) based on the efficacy of OCSs in older children and adolescents. However, this practice has been recently challenged based on the results of recent studies. The argument supporting the use of OCSs underscores the observation that many children with recurrent preschool wheezing develop atopic disease in early life which predicts both an increased risk to develop asthma in later life and response to OCS therapy. Further, review of the literature demonstrates heterogeneity of study designs, OCS dosage, interventions, study medication adherence, and settings and overall lack of predefined preschool wheezing phenotypes. The heterogeneity of these studies does not allow a definitive recommendation discouraging OCS use. Advocates against the use of OCSs in this population argue that most of studies investigating the efficacy of OCSs in acute episodic wheeze in preschool-aged children have not demonstrated beneficial effects. Moreover, repeated OCS bursts may be associated with adverse effects. Finally, both sides can agree that there is a significant need to conduct efficacy trials evaluating OCS treatment in preschool-aged children with recurrent wheezing targeted at phenotypes that would be expected to respond to OCSs. This article presents a summary of recent literature regarding the use of OCSs for acute episodic wheezing in preschool-aged children and a "pro" and "con" debate for such use.

  14. Chick embryo chorioallantoic membrane (CAM): an alternative predictive model in acute toxicological studies for anti-cancer drugs

    PubMed Central

    KUE, Chin Siang; TAN, Kae Yi; LAM, May Lynn; LEE, Hong Boon

    2015-01-01

    The chick embryo chorioallantoic membrane (CAM) is a preclinical model widely used for vascular and anti-vascular effects of therapeutic agents in vivo. In this study, we examine the suitability of CAM as a predictive model for acute toxicology studies of drugs by comparing it to conventional mouse and rat models for 10 FDA-approved anticancer drugs (paclitaxel, carmustine, camptothecin, cyclophosphamide, vincristine, cisplatin, aloin, mitomycin C, actinomycin-D, melphalan). Suitable formulations for intravenous administration were determined before the average of median lethal dose (LD50) and median survival dose (SD50) in the CAM were measured and calculated for these drugs. The resultant ideal LD50 values were correlated to those reported in the literature using Pearson’s correlation test for both intravenous and intraperitoneal routes of injection in rodents. Our results showed moderate correlations (r2=0.42 − 0.68, P<0.005–0.05) between the ideal LD50 values obtained using the CAM model with LD50 values from mice and rats models for both intravenous and intraperitoneal administrations, suggesting that the chick embryo may be a suitable alternative model for acute drug toxicity screening before embarking on full toxicological investigations in rodents in development of anticancer drugs. PMID:25736707

  15. Chick embryo chorioallantoic membrane (CAM): an alternative predictive model in acute toxicological studies for anti-cancer drugs.

    PubMed

    Kue, Chin Siang; Tan, Kae Yi; Lam, May Lynn; Lee, Hong Boon

    2015-01-01

    The chick embryo chorioallantoic membrane (CAM) is a preclinical model widely used for vascular and anti-vascular effects of therapeutic agents in vivo. In this study, we examine the suitability of CAM as a predictive model for acute toxicology studies of drugs by comparing it to conventional mouse and rat models for 10 FDA-approved anticancer drugs (paclitaxel, carmustine, camptothecin, cyclophosphamide, vincristine, cisplatin, aloin, mitomycin C, actinomycin-D, melphalan). Suitable formulations for intravenous administration were determined before the average of median lethal dose (LD50) and median survival dose (SD(50)) in the CAM were measured and calculated for these drugs. The resultant ideal LD(50) values were correlated to those reported in the literature using Pearson's correlation test for both intravenous and intraperitoneal routes of injection in rodents. Our results showed moderate correlations (r(2)=0.42 - 0.68, P<0.005-0.05) between the ideal LD(50) values obtained using the CAM model with LD(50) values from mice and rats models for both intravenous and intraperitoneal administrations, suggesting that the chick embryo may be a suitable alternative model for acute drug toxicity screening before embarking on full toxicological investigations in rodents in development of anticancer drugs. PMID:25736707

  16. Oral intoxication of mice with Shiga toxin type 2a (Stx2a) and protection by anti-Stx2a monoclonal antibody 11E10.

    PubMed

    Russo, L M; Melton-Celsa, A R; Smith, M A; Smith, M J; O'Brien, A D

    2014-03-01

    Shiga toxin (Stx)-producing Escherichia coli (STEC) strains cause food-borne outbreaks of hemorrhagic colitis and, less commonly, a serious kidney-damaging sequela called the hemolytic uremic syndrome (HUS). Stx, the primary virulence factor expressed by STEC, is an AB5 toxin with two antigenically distinct forms, Stx1a and Stx2a. Although both toxins have similar biological activities, Stx2a is more frequently produced by STEC strains that cause HUS than is Stx1a. Here we asked whether Stx1a and Stx2a act differently when delivered orally by gavage. We found that Stx2a had a 50% lethal dose (LD50) of 2.9 μg, but no morbidity occurred after oral intoxication with up to 157 μg of Stx1a. We also compared several biochemical and histological parameters in mice intoxicated orally versus intraperitoneally with Stx2a. We discovered that both intoxication routes caused similar increases in serum creatinine and blood urea nitrogen, indicative of kidney damage, as well as electrolyte imbalances and weight loss in the animals. Furthermore, kidney sections from Stx2a-intoxicated mice revealed multifocal, acute tubular necrosis (ATN). Of particular note, we detected Stx2a in kidney sections from orally intoxicated mice in the same region as the epithelial cell type in which ATN was detected. Lastly, we showed reduced renal damage, as determined by renal biomarkers and histopathology, and full protection of orally intoxicated mice with monoclonal antibody (MAb) 11E10 directed against the toxin A subunit; conversely, an irrelevant MAb had no therapeutic effect. Orally intoxicated mice could be rescued by MAb 11E10 6 h but not 24 h after Stx2a delivery.

  17. Acute and subchronic toxicological evaluation of the semipurified extract of seeds of guaraná (Paullinia cupana) in rodents.

    PubMed

    Antonelli-Ushirobira, T M; Kaneshima, E N; Gabriel, M; Audi, E A; Marques, L C; Mello, J C P

    2010-07-01

    We evaluated the toxicity of a semipurified extract (EPA fraction, containing caffeine and several flavan-3-ols and proanthocyanidins) of seeds of the native Amazon plant Paullinia cupana (guaraná) in rodents. Acute toxicity was tested in male Swiss mice, which received different doses orally (OR) and intraperitoneally (ip); control groups received water. These tests produced acute mortality, with LD(50) of 1.825 g/kg (OR) and 0.827 g/kg (ip), and a significant weight decrease in lungs of mice receiving a dose of 0.1g/kg. In the repeated-dose toxicity test, the EPA was administered OR daily to male and female Wistar rats at doses of 30, 150, and 300 mg/kg/day/90 days. Their behavior, mortality, weight changes, laboratory tests, and the weights and histopathology of organs were evaluated. No rats died during the tests. Males dosed at 150 or 300 mg/kg gained weight more slowly and lost kidney weight (absolute and relative weights, compared to the control group). Hematological and biochemical tests showed few changes, differing somewhat between males and females; the histopathological evaluation indicated no significant changes. These results indicate that the EPA fraction of guaraná caused no toxicity in rats at the smallest dose evaluated (30 mg/kg). No other species was evaluated.

  18. 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.

  19. Evaluation of temporal artery and disposable digital oral thermometers in acutely ill patients.

    PubMed

    Counts, Diane; Acosta, Mary; Holbrook, Holly; Foos, Eileen; Hays-Ponder, Kimberly; Macairan, Olga; Thomas, Linda; Whitsett, Maryse; Williams, Lori; Twiss, Elizabeth J

    2014-01-01

    Accurate measurement of temperature is essential for timely and appropriate patient management. In this study, both the digital, disposable oral and temporal artery thermometers had precision values that exceeded expert recommendations for use of the devices as equivalent to a reference standard device.

  20. New oral anticoagulants: clinical indications, monitoring and treatment of acute bleeding complications.

    PubMed

    Fenger-Eriksen, C; Münster, A-M; Grove, E L

    2014-07-01

    New oral anticoagulants like the direct thrombin inhibitor, dabigatran (Pradaxa®), and factor Xa-inhibitors, rivaroxaban (Xarelto®) and apixaban (Eliquis®) are available for prophylaxis and treatment of thromboembolic disease. They are emerging alternatives to warfarin and provide equal or better clinical outcome together with reduced need for routine monitoring. Methods for measuring drug concentrations are available, although a correlation between plasma drug concentrations and the risk of bleeding has not been firmly established. Standard laboratory measures like prothrombin time and activated partial thromboplastin time are not sensitive enough to detect thrombin or factor Xa inhibition provided by new oral anticoagulants. Thus, these standard tests may only be used as a crude estimation of the actual anticoagulation status. Further challenges regarding patients receiving new oral anticoagulants who presents with major bleeding or need for emergency surgery pose a unique problem. No established agents are clinically available to reverse the anticoagulant effect, although preclinical data report prothrombin complex concentrate as more efficient than fresh frozen plasma or other prohaemostatic agents. This review summaries current knowledge on approved new oral anticoagulants and discusses clinical aspects of monitoring, with particular focus on the management of the bleeding patient.

  1. Pain‑relieving effect of a compound isolated from white peony root oral liquid on acute radiation‑induced esophagitis.

    PubMed

    Wang, Zhiyu; Shen, Li; Li, Xing; Shu, Xin; Shan, Baoen; Zhang, Li; Gong, Yanjun; Dong, Zhiming

    2013-06-01

    Acute radiation‑induced esophagitis (ARIE) is a common complication of radiotherapy. The aim of this study was to clarify the molecular mechanism of pain relief by the compound of white peony root oral liquid (cWPROL) in ARIE. An animal model of ARIE was established and either cWPROL or a mixture of lidocaine, dexamethasone and gentamycin (mLDG) was administered. We indirectly observed rat symptoms of pain by recording the weight of food and the volume of water consumed by the rats, along with changes in body weight. Additionally, the expression levels of substance P (SP) in the esophageal tissues were detected by immunohistochemistry. It was demonstrated that cWPROL was able to release the pain of ARIE by decreasing the expression of SP; this may be one of the molecular mechanisms via which cWPROL induces pain relief.

  2. Comparative acute and subchronic toxicity of ethylene glycol monopropyl ether and ethylene glycol monopropyl ether acetate.

    PubMed Central

    Katz, G V; Krasavage, W J; Terhaar, C J

    1984-01-01

    The acute toxicity of ethylene glycol monopropyl ether (EGPE) and ethylene glycol monopropyl ether acetate (EGPEA) was determined in a series of standardized tests. The oral LD50 in rats was 3089 and 9456 mg/kg EGPE and EGPEA, respectively. Skin irritation was slight following an occluded single dose application of either compound to the guinea pig abdomen. The dermal LD50 for guinea pigs was 1 to 5 mL/kg and greater than 20 mL/kg EGPE and EGPEA, respectively. EGPE produced a very weak positive sensitization response in one of five guinea pigs. No positive response was elicited when 10 guinea pigs were similarly challenged with EGPEA. EGPE produced transient moderate to severe eye irritation in rabbits while EGPEA produced slight eye irritation. Subchronic toxicity was determined in a series of oral and inhalation studies. Groups of 10 male rats were dosed with 15, 7.5, 3.75 or 1.88 mmole/kg EGPE and 30, 15 or 7.5 mmole/kg EGPEA by gavage 5 days/week for 6 weeks. Hemoglobinuria was seen at least once at all dose levels of both compounds. EGPE had little effect on feed consumption or body weight gain, while body weight gain was reduced in the two high dose groups exposed to EGPEA and feed consumption was reduced at all dose levels. Hematologic changes were seen at all dose levels of both compounds. Absolute and/or relative spleen weights were increased at all but the lowest EGPE dose level and at all EGPEA dose levels. Gross and histopathologic examinations revealed significant effects on the spleen of animals exposed to EGPE and on the spleen, liver, kidney and testes of animals exposed to EGPEA. The no-observed effect level (NOEL) for splenic changes was 1.88 mmole/kg EGPE. A NOEL for hematology was not established. The NOEL for liver and testicular changes were 15 and 7.5 mmole/kg EGPEA, respectively while a NOEL for hematologic, splenic and renal changes was not established. Groups of 10 rats (5M, 5F) were exposed to 800, 400, 200 or 100 ppm EGPE or EGPEA 6 hr

  3. Preparation of five 3-MCPD fatty acid esters and the effects of their chemical structures on acute oral toxicity in Swiss mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fatty acid esters of 3-monochloro-1, 2-propanediol (3-MCPDEs), including 1-stearic, 1-oleic, 1-linoleic, 1-linoleic-2-palmitic and 1-palmitic-2-linoleic acid esters, were synthetized and examined for their acute oral toxicities in Swiss mice. 3-MCPDEs were obtained through the reaction of 3-MCPD and...

  4. Effect of oral infection with Kashmir bee virus and Israeli acute paralysis virus on bumblebee (Bombus terrestris) reproductive success.

    PubMed

    Meeus, Ivan; de Miranda, Joachim R; de Graaf, Dirk C; Wäckers, Felix; Smagghe, Guy

    2014-09-01

    Israeli acute paralysis virus (IAPV) together with Acute bee paralysis virus (ABPV) and Kashmir bee virus (KBV) constitute a complex of closely related dicistroviruses. They are infamous for their high mortality after injection in honeybees. These viruses have also been reported in non-Apis hymenopteran pollinators such as bumblebees, which got infected with IAPV when placed in the same greenhouse with IAPV infected honeybee hives. Here we orally infected Bombus terrestris workers with different doses of either IAPV or KBV viral particles. The success of the infection was established by analysis of the bumblebees after the impact studies: 50days after infection. Doses of 0.5×10(7) and 1×10(7) virus particles per bee were infectious over this period, for IAPV and KBV respectively, while a dose of 0.5×10(6) IAPV particles per bee was not infectious. The impact of virus infection was studied in micro-colonies consisting of 5 bumblebees, one of which becomes a pseudo-queen which proceeds to lay unfertilized (drone) eggs. The impact parameters studied were: the establishment of a laying pseudo-queen, the timing of egg-laying, the number of drones produced, the weight of these drones and worker mortality. In this setup KBV infection resulted in a significant slower colony startup and offspring production, while only the latter can be reported for IAPV. Neither virus increased worker mortality, at the oral doses used. We recommend further studies on how these viruses transmit between different pollinator species. It is also vital to understand how viral prevalence can affect wild bee populations because disturbance of the natural host-virus association may deteriorate the already critically endangered status of many bumblebee species.

  5. Effect of oral infection with Kashmir bee virus and Israeli acute paralysis virus on bumblebee (Bombus terrestris) reproductive success.

    PubMed

    Meeus, Ivan; de Miranda, Joachim R; de Graaf, Dirk C; Wäckers, Felix; Smagghe, Guy

    2014-09-01

    Israeli acute paralysis virus (IAPV) together with Acute bee paralysis virus (ABPV) and Kashmir bee virus (KBV) constitute a complex of closely related dicistroviruses. They are infamous for their high mortality after injection in honeybees. These viruses have also been reported in non-Apis hymenopteran pollinators such as bumblebees, which got infected with IAPV when placed in the same greenhouse with IAPV infected honeybee hives. Here we orally infected Bombus terrestris workers with different doses of either IAPV or KBV viral particles. The success of the infection was established by analysis of the bumblebees after the impact studies: 50days after infection. Doses of 0.5×10(7) and 1×10(7) virus particles per bee were infectious over this period, for IAPV and KBV respectively, while a dose of 0.5×10(6) IAPV particles per bee was not infectious. The impact of virus infection was studied in micro-colonies consisting of 5 bumblebees, one of which becomes a pseudo-queen which proceeds to lay unfertilized (drone) eggs. The impact parameters studied were: the establishment of a laying pseudo-queen, the timing of egg-laying, the number of drones produced, the weight of these drones and worker mortality. In this setup KBV infection resulted in a significant slower colony startup and offspring production, while only the latter can be reported for IAPV. Neither virus increased worker mortality, at the oral doses used. We recommend further studies on how these viruses transmit between different pollinator species. It is also vital to understand how viral prevalence can affect wild bee populations because disturbance of the natural host-virus association may deteriorate the already critically endangered status of many bumblebee species. PMID:25004171

  6. Oral Phage Therapy of Acute Bacterial Diarrhea With Two Coliphage Preparations: A Randomized Trial in Children From Bangladesh

    PubMed Central

    Sarker, Shafiqul Alam; Sultana, Shamima; Reuteler, Gloria; Moine, Deborah; Descombes, Patrick; Charton, Florence; Bourdin, Gilles; McCallin, Shawna; Ngom-Bru, Catherine; Neville, Tara; Akter, Mahmuda; Huq, Sayeeda; Qadri, Firdausi; Talukdar, Kaisar; Kassam, Mohamed; Delley, Michèle; Loiseau, Chloe; Deng, Ying; El Aidy, Sahar; Berger, Bernard; Brüssow, Harald

    2016-01-01

    Background Antibiotic resistance is rising in important bacterial pathogens. Phage therapy (PT), the use of bacterial viruses infecting the pathogen in a species-specific way, is a potential alternative. Method T4-like coliphages or a commercial Russian coliphage product or placebo was orally given over 4 days to Bangladeshi children hospitalized with acute bacterial diarrhea. Safety of oral phage was assessed clinically and by functional tests; coliphage and Escherichia coli titers and enteropathogens were determined in stool and quantitative diarrhea parameters (stool output, stool frequency) were measured. Stool microbiota was studied by 16S rRNA gene sequencing; the genomes of four fecal Streptococcus isolates were sequenced. Findings No adverse events attributable to oral phage application were observed (primary safety outcome). Fecal coliphage was increased in treated over control children, but the titers did not show substantial intestinal phage replication (secondary microbiology outcome). 60% of the children suffered from a microbiologically proven E. coli diarrhea; the most frequent diagnosis was ETEC infections. Bacterial co-pathogens were also detected. Half of the patients contained phage-susceptible E. coli colonies in the stool. E. coli represented less than 5% of fecal bacteria. Stool ETEC titers showed only a short-lived peak and were otherwise close to the replication threshold determined for T4 phage in vitro. An interim analysis after the enrollment of 120 patients showed no amelioration in quantitative diarrhea parameter by PT over standard care (tertiary clinical outcome). Stool microbiota was characterized by an overgrowth with Streptococcus belonging to the Streptococcus gallolyticus and Streptococcus salivarius species groups, their abundance correlated with quantitative diarrhea outcome, but genome sequencing did not identify virulence genes. Interpretation Oral coliphages showed a safe gut transit in children, but failed to achieve

  7. In vivo uptake and acute immune response to orally administered chitosan and PEG coated PLGA nanoparticles

    SciTech Connect

    Semete, B.; Booysen, L.I.J.; Kalombo, L.; Venter, J.D.; Katata, L.; Ramalapa, B.; Verschoor, J.A.; Swai, H.

    2010-12-01

    Nanoparticulate drug delivery systems offer great promise in addressing challenges of drug toxicity, poor bioavailability and non-specificity for a number of drugs. Much progress has been reported for nano drug delivery systems for intravenous administration, however very little is known about the effects of orally administered nanoparticles. Furthermore, the development of nanoparticulate systems necessitates a thorough understanding of the biological response post exposure. This study aimed to elucidate the in vivo uptake of chitosan and polyethylene glycol (PEG) coated Poly, DL, lactic-co-glycolic Acid (PLGA) nanoparticles and the immunological response within 24 h of oral and peritoneal administration. These PLGA nanoparticles were administered orally and peritoneally to female Balb/C mice, they were taken up by macrophages of the peritoneum. When these particles were fluorescently labelled, intracellular localisation was observed. The expression of pro-inflammatory cytokines IL-2, IL-6, IL-12p70 and TNF-{alpha} in plasma and peritoneal lavage was found to remain at low concentration in PLGA nanoparticles treated mice as well as ZnO nanoparticles during the 24 hour period. However, these were significantly increased in lipopolysaccharide (LPS) treated mice. Of these pro-inflammatory cytokines, IL-6 and IL-12p70 were produced at the highest concentration in the positive control group. The anti-inflammatory cytokines IL-10 and chemokines INF-{gamma}, IL-4, IL-5 remained at normal levels in PLGA treated mice. IL-10 and INF-{gamma} were significantly increased in LPS treated mice. MCP-1 was found to be significantly produced in all groups in the first hours, except the saline treated mice. These results provide the first report to detail the induction of cytokine production by PLGA nanoparticles engineered for oral applications.

  8. Oral inflammation and bacteremia: implications for chronic and acute systemic diseases involving major organs.

    PubMed

    Hirschfeld, Josefine; Kawai, Toshihisa

    2015-01-01

    Gingivitis and periodontitis are both highly prevalent gum diseases characterized by an accumulation of a polymicrobial biofilm (dental plaque) around teeth and inflammation in adjacent soft tissues. During dental procedures, even tooth brushing, these bacteria and their components, such as endotoxin, can easily disseminate into the systemic circulation through minor or major gingival injuries. Particularly in immuno-compromised subjects or patients with preexisting pathologic conditions, bacteremia may lead to bacterial infection of distant organs, which may cause immunological reactions. Oral bacteria and endotoxins have been found in sepsis, infective endocarditis, lung infection, liver disease and many other potentially lethal disorders. This article presents a review of the possible pathologic consequences of bacteremia originating in the oral cavity and points out the most commonly affected organs as well as preventive and treatment measures. At the present time, plaque control by subjects and/or dental professionals is one of the most effective means to prevent the onset and progression of oral bacteremia-induced systemic diseases. PMID:25567334

  9. Urinary dopamine and noradrenaline outputs during large acute changes in oral salt intake in healthy Chinese subjects.

    PubMed

    Chan, T Y; Critchley, J A; Ho, C S; Chan, J C; Wong, W K; Swaminathan, R; Tomlinson, B

    1994-10-01

    1. In order to investigate the role of renal dopamine and sympathetic activity in the natriuretic response to oral sodium loading in Chinese subjects, we studied the effects of two different sodium intakes (20 followed by 220 mmol day-1 each given for 5 days) on mean arterial pressure (MAP) and the urinary excretion of sodium, dopamine (DA) and noradrenaline (NA) in eight healthy subjects. 2. MAP did not change. There was an eight- to ninefold increase in sodium excretion (P < 0.01). An 8-17% increase in urinary DA (P < 0.05) over the first 3 days, and a 22% decrease in urine NA (P < 0.05) on the last day of the high sodium intake were seen. 3. The relatively small increase in urinary DA, despite an eleven-fold increase in sodium intake from a state of marked sodium deprivation, may suggest that, in healthy Chinese subjects, the renal DA mechanism only contributes partly to the acute natriuretic response. Furthermore, the renal DA response appeared to be attenuated during the period of high sodium intake. 4. There is no evidence from the present study that a reduction in sympathetic activity plays an important role in the acute natriuretic response to sodium loading in this group of subjects.

  10. Clinical Outcomes of Thirteen Patients with Acute Chagas Disease Acquired through Oral Transmission from Two Urban Outbreaks in Northeastern Brazil

    PubMed Central

    Bastos, Claudilson J. C.; Aras, Roque; Mota, Gildo; Reis, Francisco; Dias, Juarez Pereira; de Jesus, Robson Silva; Freire, Miralba Silva; de Araújo, Eline G.; Prazeres, Juliana; Grassi, Maria Fernanda Rios

    2010-01-01

    Background Outbreaks of orally transmitted Trypanosoma cruzi continue to be reported in Brazil and are associated with a high mortality rate, mainly due to myocarditis. Methods This study is a detailed report on the disease progression of acute Chagas disease in 13 patients who were infected during two micro-outbreaks in two northeastern Brazilian towns. Clinical outcomes as well as EKG and ECHO results are described, both before and after benznidazole treatment. Results Fever and dyspnea were the most frequent symptoms observed. Other clinical findings included myalgia, periorbital edema, headache and systolic murmur. Two patients died of cardiac failure before receiving benznidazole treatment. EKG and ECHO findings frequently showed a disturbance in ventricular repolarization and pericardial effusion. Ventricular dysfunction (ejection fraction <55%) was present in 27.3% of patients. After treatment, EKG readings normalized in 91.7% of patients. Ventricular repolarization abnormalities persisted in 50% of the patients, while sinus bradycardia was observed in 18%. The systolic ejection fraction normalized in two out of three patients with initially depressed ventricular function, while pericardial effusion disappeared. Conclusions Myocarditis is frequently found and potentially severe in patients with acute Chagas disease. Benznidazole treatment may improve clinical symptoms, as well as EKG and ECHO findings. PMID:20559542

  11. Oral toxicity of 1,2-dichloropropane: Acute, short-term, and long-term studies in rats

    SciTech Connect

    Bruckner, J.V.; MacKenzie, W.F.; Ramanathan, R.; Muralidhara, S.; Kim, H.J.

    1989-01-01

    The investigation characterized the acute and short- and long-term toxic potency of orally administered 1,2-dichloropropane (DCP). In the acute and short-term studies, male rats of 250-300 g were gavaged with 0, 100, 250, 500, or 1000 mg DCP/kg in corn oil once daily for up to 10 consecutive days. Although ingestion of DCP caused body weight loss and CNS depression, few other toxic effects were manifest 24 hr after a single dose of the chemical. Morphological changes were limited to liver centrilobular cells in 500 and 1000 mg/kg rats. Similarly, elevated activity of some serum enzymes occurred only at these two highest dose levels. Hepatic nonprotein sulfhydryl (NPS) levels were decreased and renal NPS levels increased at 24 hr. In the short-term study resistance developed to DCP hepatotoxicity over the 10 consecutive days of exposure, as reflected by progressively lower serum enzyme levels and by decreases in the severity and incidence of toxic hepatitis and periportal vacuolization. Nucleolar enlargement in hepatocytes, however, was observed at all dosage levels at 5 and 10 days. There were a number of manifestations of hemolytic anemia, including erythrophagocytosis in the liver, splenic hemosiderosis and hyperplasia of erythropoietic elements of the red pulp, renal tubular cell hemosiderosis, and hyperbilirubinemia.

  12. Oral disopyramide after admission to hospital with suspected acute myocardial infarction. U. K. Rythmodan Multicentre Study Group.

    PubMed Central

    1984-01-01

    A multi-centre double-blind randomized study is reported in which the effect on mortality of oral disopyramide (300 mg loading dose, then 100 mg qds) was compared with placebo in 1985 patients entering hospital with suspected acute myocardial infarction. Treatment was commenced with 24 hr of onset of symptoms (mean time to first dose 9 hr) and continued until discharge from hospital or 14 days, whichever came first. Nine-hundred and ninety-five patients were allocated to disopyramide and 990 to placebo. The overall mortality, calculated on an intention-to-treat basis, was 7.2% for the disopyramide and 5.6% for the placebo patients. Among those patients with proven infarction mortality was 9.5% of 687 on disopyramide and 7.4% of 716 on placebo. These differences are not statistically significant. Patients with cardiac failure or hypotension at entry did not fare worse on disopyramide, but those with a conduction defect did. Reinfarction was not significantly influenced by disopyramide. The prophylactic use of disopyramide in patients with suspected acute myocardial infarction does not reduce mortality or the incidence of early reinfarction. PMID:6369290

  13. Use of butterflies as nontarget insect test species and the acute toxicity and hazard of mosquito control insecticides.

    PubMed

    Hoang, Tham C; Pryor, Rachel L; Rand, Gary M; Frakes, Robert A

    2011-04-01

    Honeybees are the standard insect test species used for toxicity testing of pesticides on nontarget insects for the U.S. Environmental Protection Agency (U.S. EPA) under the Federal Insecticide Fungicide and Rodenticide Act (FIFRA). Butterflies are another important insect order and a valued ecological resource in pollination. The current study conducted acute toxicity tests with naled, permethrin, and dichlorvos on fifth larval instar (caterpillars) and adults of different native Florida, USA, butterfly species to determine median lethal doses (24-h LD50), because limited acute toxicity data are available with this major insect group. Thorax- and wing-only applications of each insecticide were conducted. Based on LD50s, thorax and wing application exposures were acutely toxic to both caterpillars and adults. Permethrin was the most acutely toxic insecticide after thorax exposure to fifth instars and adult butterflies. However, no generalization on acute toxicity (sensitivity) of the insecticides could be concluded based on exposures to fifth instars versus adult butterflies or on thorax versus wing exposures of adult butterflies. A comparison of LD50s of the butterflies from this study (caterpillars and adults) with honeybee LD50s for the adult mosquito insecticides on a µg/organism or µg/g basis indicates that several butterfly species are more sensitive to these insecticides than are honeybees. A comparison of species sensitivity distributions for all three insecticides shows that permethrin had the lowest 10th percentile. Using a hazard quotient approach indicates that both permethrin and naled applications in the field may present potential acute hazards to butterflies, whereas no acute hazard of dichlorvos is apparent in butterflies. Butterflies should be considered as potential test organisms when nontarget insect testing of pesticides is suggested under FIFRA. PMID:21309017

  14. Use of butterflies as nontarget insect test species and the acute toxicity and hazard of mosquito control insecticides.

    PubMed

    Hoang, Tham C; Pryor, Rachel L; Rand, Gary M; Frakes, Robert A

    2011-04-01

    Honeybees are the standard insect test species used for toxicity testing of pesticides on nontarget insects for the U.S. Environmental Protection Agency (U.S. EPA) under the Federal Insecticide Fungicide and Rodenticide Act (FIFRA). Butterflies are another important insect order and a valued ecological resource in pollination. The current study conducted acute toxicity tests with naled, permethrin, and dichlorvos on fifth larval instar (caterpillars) and adults of different native Florida, USA, butterfly species to determine median lethal doses (24-h LD50), because limited acute toxicity data are available with this major insect group. Thorax- and wing-only applications of each insecticide were conducted. Based on LD50s, thorax and wing application exposures were acutely toxic to both caterpillars and adults. Permethrin was the most acutely toxic insecticide after thorax exposure to fifth instars and adult butterflies. However, no generalization on acute toxicity (sensitivity) of the insecticides could be concluded based on exposures to fifth instars versus adult butterflies or on thorax versus wing exposures of adult butterflies. A comparison of LD50s of the butterflies from this study (caterpillars and adults) with honeybee LD50s for the adult mosquito insecticides on a µg/organism or µg/g basis indicates that several butterfly species are more sensitive to these insecticides than are honeybees. A comparison of species sensitivity distributions for all three insecticides shows that permethrin had the lowest 10th percentile. Using a hazard quotient approach indicates that both permethrin and naled applications in the field may present potential acute hazards to butterflies, whereas no acute hazard of dichlorvos is apparent in butterflies. Butterflies should be considered as potential test organisms when nontarget insect testing of pesticides is suggested under FIFRA.

  15. Citrus peel extract attenuates acute cyanide poisoning-induced seizures and oxidative stress in rats.

    PubMed

    Abdel Moneim, Ahmed E

    2014-01-01

    The primary aimed of this study was to investigate the potential protective effects of methanolic extract of citrus peel (MECP) on acute cyanide (KCN) poisoning-induced seizures and oxidative stress in rats. The intraperitoneal LD50 value of KCN (6.3 mg/Kg bwt), based on 24 hrs mortality, was significantly increased by 9, 52 or 113% by oral administration of MECP (500 mg/Kg bwt) pre-administered for 1, 2 and 3 days, respectively, in rats in a time-dependent manner. Intraperitoneal injection of the sublethal dose of KCN (3 mg/Kg bwt) into rats increased, 24 hrs later, lipid peroxidation (LPO), nitric oxide (NO), glutamate levels and acetylcholinesterase (AChE) activity in hippocampus, striatum and cerebral cortex. KCN also decreased brain glutathione (GSH) level and superoxide dismutase (SOD) and catalase (CAT) activities in these animals. Pre-treatment of rats with MECP inhibited KCN-induced increases in LPO, NO, and glutamate levels and AChE activity as well as decreases in brain GSH level and SOD and CAT activities. In addition, KCN significantly decreased norepinephrine, dopamine and serotonin levels in different brain regions which were resolved by MECP. From the present results, it can be concluded that the neuroprotective effects of MECP against KCN-induced seizures and oxidative stress may be due to the inhibition of oxidative stress overproduction and maintenance of antioxidant defense mechanisms.

  16. Acute oral toxicity studies of Swietenia macrophylla seeds in Sprague Dawley rats

    PubMed Central

    Balijepalli, Madhu Katyayani; Suppaiah, Velan; Chin, An-me; Buru, Ayuba Sunday; Sagineedu, Sreenivasa Rao; Pichika, Mallikarjuna Rao

    2015-01-01

    Background: Swietenia macrophylla King. (Meliaceae) seeds (SMS); commonly known as sky fruit and locally known in Malaysia as Tunjuk Langit; have been used in traditional Malay medicine for the treatment of diabetes and hypertension. The people eat only a tiny amount of raw seed, weighing not more than 5 mg. Aim: To evaluate the safety of Swietenia macrophylla seeds (SMS) at a single-dose oral administration of 2 g/kg body weight (bw) in sprague dawley (SD) rats. Materials and Methods: Eight-week old male and female SD rats were administered a single-oral dose of 2g/kg bw. The rats’ general behavior, and toxic signs were observed throughout the 14-day study period. The food and water intake by rats and their body weight were monitored during the study period. At the end of the study period, the relative weights of the organs (lung, liver, spleen, heart, kidney, testis, stomach); the hematological and biochemical parameters were measured; the architecture and histology of the organs (liver, kidney and lungs) were observed. Results: Oral administration of SMS to rats did not affect, either food or water intake; relative organ weight of vital organs; the hematological and biochemical parameters; did not show significant changes in the architecture and histology of vital organs. Overall, there were neither signs of toxicity nor deaths recorded during the study period. Conclusion: The rat dose of 2 g/kg bw is equivalent to the human dose of 325 mg/kg bw, which is well below the usual amount consumed by people, did not show any signs of toxicity in rats. PMID:25598633

  17. Oral sildenafil as a rescue therapy in presumed acute pulmonary hypertensive crisis.

    PubMed

    Maxted, Andrew Peter; Hill, Abigail; Davies, Patrick

    2013-02-01

    A 23-week-old baby, born at 26(+2) weeks, presented to the hospital with critical respiratory failure, which was impossible to stabilize. She had unstable oxygen saturations between 35% and 95%. A presumptive diagnosis of bronchopulmonary dysplasia with associated pulmonary hypertensive crisis was made. In the absence of inhaled nitric oxide, 2 oral doses of 1 mg/kg sildenafil were given, with a dramatic improvement 30 to 45 minutes later. Her oxygenation index fell from 43 to 14. She made a full recovery and was discharged from the hospital 2 weeks later.

  18. Acute effects of sono-activated photocatalytic titanium dioxide nanoparticles on oral squamous cell carcinoma.

    PubMed

    Moosavi Nejad, S; Takahashi, Hiromasa; Hosseini, Hamid; Watanabe, Akiko; Endo, Hitomi; Narihira, Kyoichi; Kikuta, Toshihiro; Tachibana, Katsuro

    2016-09-01

    Sonodynamic therapy (SDT) is a new treatment modality using ultrasound to activate certain chemical sensitizers for cancer therapy. In this study, effects of high intensity focused ultrasound (HIFU) combined with photocatalytic titanium dioxide (TiO2) nanoparticles on human oral squamous cell line HSC-2 were investigated. Viability of HSC-2 cells after 0, 0.1, 1, or 3s of HIFU irradiation with 20, 32, 55 and 73Wcm(-2) intensities in the presence or absence of TiO2 was measured immediately after the exposures in vitro. Immediate effects of HIFU (3s, 73Wcm(-2)) combined with TiO2 on solid tumors were also examined by histological study. Cytotoxic effect of HIFU+TiO2in vitro was significantly higher than that of TiO2 or HIFU alone with the tendency to increase for higher HIFU intensity, duration, and TiO2 concentration in the suspension. In vivo results showed significant necrosis and tissue damage in HIFU and HIFU+TiO2 treated samples. However, penetration of TiO2 nanoparticles into the cell cytoplasm was only observed in HIFU+TiO2 treated tissues. In this study, our findings provide a rational basis for the development of an effective HIFU based sonodynamic activation method. This approach offers an attractive non-invasive therapy technique for oral cancer in future.

  19. Acute effects of oral or parenteral aspartame on catecholamine metabolism in various regions of rat brain.

    PubMed

    Yokogoshi, H; Wurtman, R J

    1986-03-01

    Hypertensive (SHR) and nonhypertensive [Wistar-Kyoto (WKY); Sprague-Dawley (SD)] strains of rats received the dipeptide sweetener aspartame (200 mg/kg) or, as a positive control, tyrosine (200 mg/kg) by gavage or parenterally, after a brief (2-h) fast. Two hours later, compared with those of saline controls brain levels of the norepinephrine metabolite 3-methoxy-4-hydroxyphenylethylethyleneglycol (MHPG) sulfate were significantly higher in the hypothalamus (WKY), locus coeruleus (SD and SHR) and brain stem (SHR) in tyrosine-treated animals, and in the locus coeruleus (SD) of those given aspartame. Brain norepinephrine levels were also higher, compared with those of saline-treated control rats, in the cerebral cortex (SD and SHR), amygdala (SD) and locus coeruleus (WKY) after tyrosine administration, and in the amygdala (SD) and cerebral cortex (SHR) after aspartame administration. In another study, oral aspartame was found to be at least as effective as the parenterally administered sweetener in raising regional brain levels of tyrosine or MHPG sulfate (i.e., compared with corresponding levels in saline-treated rats). Animals receiving oral aspartame also exhibited higher plasma tyrosine and phenylalanine ratios (i.e., the ratios of their plasma concentrations to the summed concentrations of other large neutral amino acids that compete with them for uptake into the brain), than animals receiving saline.

  20. Increased uptake of guideline-recommended oral antiplatelet therapy: insights from the Canadian acute coronary syndrome reflective.

    PubMed

    Gandhi, Sumeet; Zile, Brigita; Tan, Mary K; Saranu, Jhansi; Bucci, Claudia; Yan, Andrew T; Robertson, Patrick; Quantz, Mackenzie A; Letovsky, Eric; Tanguay, Jean-Francois; Dery, Jean-Pierre; Fitchett, David; Madan, Mina; Cantor, Warren J; Heffernan, Michael; Natarajan, Madhu K; Wong, Graham C; Welsh, Robert C; Goodman, Shaun G

    2014-12-01

    Current guideline-based recommendations for oral dual-antiplatelet therapy in an acute coronary syndrome (ACS) include the use of newer adenosine diphosphate receptor inhibitor (ADPri) regimens and agents. The Canadian ACS Reflective Program is a multicenter observational quality-enhancement project that compared the use of ADPri therapy in 2 phases (November 2011-March 2013 and April 2013-November 2013) and also compared ADPri use with previous national data from the Canadian Global Registry of Acute Coronary Events (2000-2008). Of 3099 patients with ACS, 30.6% had ST-segment elevation myocardial infarction (STEMI), 52.3% had non-STEMI, and 17% had unstable angina. There was high use of dual-antiplatelet therapy for ≤ 24 hours, with important increases noted when compared with previous national experience (P for trend, < 0.0001). Clopidogrel was the most commonly used ADPri (82.2%), with lower use of the newer agents ticagrelor (9.0%) and prasugrel (3.1%). Ticagrelor and prasugrel use was most frequent in patients with STEMI undergoing percutaneous coronary intervention PCI (34.3%). There was relatively lower use of ADPri therapy at discharge; it was given mainly to patients who did not undergo PCI (68.2%) and to those with non-ST-elevation ACS (82%). When comparing the 2 consecutive phases of data collection in the ACS Reflective, there was an approximate 3- and 2-fold increase in the early and discharge use of the newer ADPri agents, respectively. In conclusion, there has been a temporal increase in ADPri use compared with previous national experience and an increased uptake of newer ADPri agents. Additional work is needed to identify and address barriers limiting optimal implementation of these newer guideline-recommended agents into routine Canadian practice. PMID:25475475

  1. Evidence for effects on thermoregulation after acute oral exposure to type I and type II pyrethroids in infant rats.

    PubMed

    Bardullas, Ulises; Sosa-Holt, Carla Solange; Pato, Alejandro Martín; Nemirovsky, Sergio Iván; Wolansky, Marcelo Javier

    2015-01-01

    Most pyrethroid (PYR) insecticides may be classified either as type-I compounds, which produce whole body tremors and hyperthermia, or type-II compounds, which produce salivation, choreoathetosis, and hypothermia (i.e., producing T and CS neurobehavioral syndromes, respectively). This classification is based on clinical observations in adult rats and mice after intracerebroventricular or intravascular administration of highly effective acute (bolus) doses. PYR neurotoxicity in infant animals is not characterized as much as in adult animals. Endpoints informing on vital determinants of mammal's maturation, such as body temperature may help recognizing age-related differences in susceptibility to PYRs. In this work, body temperature (Tb) was monitored at 30-min intervals after acute oral exposure to T-syndrome PYR bifenthrin (BIF), CS-syndrome PYR cypermethrin (CYPM), and a BIF–CYPM mixture in weanling rats by using a subcutaneous temperature monitoring system. In both single-compound assays, a time- and dose-related decline of Tb was the most evident impact on thermoregulation observed starting at ~2–3 h after dosing.Moreover, 15–18 mg/kg BIF induced a mild increase in Tb before the hypothermic action was apparent. The lowest effective dose for temperature perturbation was 15mg/kg for BIF and 10mg/kg for CYPM, and moderate neurobehavioral alterations were evident at 12 and 10mg/kg, respectively. When low effective doses of BIF and CYPM were co-administered mild behavioral effects and a transient increase in Tb (p=0.02) were observed at 1–2 h, and no Tb decline was apparent afterwards compared to control animals. Noteworthy, the hypothermic action of BIF in infant rats was quite different from the hyperthermia consistently reported in studies using mature animals. Our results suggest that body temperature monitoring may be useful as a complementary assessment to reveal qualitative age-specific pesticide effects in rats.

  2. [Alteration of the acute toxicity and various pharmacologic effects of streptomycin sulfate by calcium 4'-phosphopantothenate].

    PubMed

    Dorofeev, B F; Korablev, M V; Kopelevich, V M

    1983-10-01

    The effect of calcium 4'-phosphopantothenate (CPP) on acute toxicity of streptomycin and the decrease by the antibiotic of the muscle working capacity, "holes" reflex, body temperature and oxygen intake was studied on 258 albino mice weighing 22-26 g. Medical calcium pantothenate (CPA) was used for control purposes. CPP is an antagonist of streptomycin sulfate. In a dose of 1/10 or 1/5 of the LD50 injected intraperitoneally CPP lowered acute toxicity of streptomycin and prevented its effect in a dose of 0.11--1.1 g/kg injected subcutaneously on the muscle working capacity, "holes" reflex and body temperature. The spectrum index of the CPP antitoxic effect was equal to 22.5. By its acute toxicity CPP (LD50 1.18 +/- 0.07 g/kg) did not differ from CPA (LD50 1.25 +/- 0.08 g/kg). The efficacy of CPP, by its antitoxic spectrum, was 1.8 times higher than that of CPA. CPA lowered the streptomycin effect on the "holes" reflex and body temperature, while CPP prevented it. Both the drugs did not influence the decrease in the oxygen consumption induced by streptomycin. PMID:6651265

  3. Detection of neutral sugars in purified type G botulinum progenitor toxin and the effects of some glycolytic enzymes on its molecular dissociation and oral toxicity.

    PubMed

    Nukina, M; Miyata, T; Sakaguchi, S; Sakaguchi, G

    1991-04-15

    Arabinose and galactose were detected in purified type G botulinum toxin (Mr about 500,000) of Clostridium argentinense. The i.p. LD50/mg N of type G progenitor toxin was one-tenth, but the oral LD50/mg N twice that of type A-L toxin. The lysozyme-, endo-beta-galactosidase-, and N-glucanase-treated toxins each had a molecular mass of about 300,000. The oral toxicity of the endo-beta-galactosidase or N-glucanase-treated toxin was one-fifth that of untreated progenitor toxin. On DEAE-Sephadex chromatography, the N-glucanase-treated toxin dissociated into two fractions, nontoxic and toxic. SDS-PAGE of the toxic fraction showed a single band with a Mr of about 150,000, and after dithiothreitol treatment, two bands with Mr of 100,000 and 50,000.

  4. [Effect of a new amino acid solution in the oral hydration of nursing infants with acute diarrhea. A prospective study].

    PubMed

    Velásquez-Jones, L; Mota-Hernández, F

    1990-01-01

    Thirty-two one- to 12-month-old male infants with diarrheal dehydration treated with either the oral rehydration solution recommended by the World Health Organization (WHO), or the same solution modified by the addition of glycerine (60 mmol/L) and glycil-glycine (30 mmol/L), with a total osmolality of 379 mOsm/kg. The patients belonging to the latter group exhibited greater stool losses (10.3 +/- 8.3 vs 8.0 +/- 6.4 mL/kg/hour) and a greater urine volume (10.4 +/- 14.2 vs 4.6 +/- 4.0 mL/kg/6 hours), during the first four to six hours of the rehydration period. The results of this study show, that in contrast with those of other series, the addition of glycine and glycil-glycine to the WHO solution, at the concentrations used in the study, produces greater fecal water losses in children with dehydration due to acute diarrhea.

  5. 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

  6. Acute allergic skin response as a new tool to evaluate the allergenicity of whey hydrolysates in a mouse model of orally induced cow's milk allergy.

    PubMed

    van Esch, Betty C A M; Schouten, Bastiaan; Hofman, Gerard A; van Baalen, Ton; Nijkamp, Frans P; Knippels, Léon M J; Willemsen, Linette E M; Garssen, Johan

    2010-06-01

    Hypoallergenic milk formulae are used for cow's milk allergic infants and may be a good option for infants at risk. Clinical studies have shown that the protein source or the hydrolysis methodology used may influence the effectiveness in infants stressing the importance of adequate pre-clinical testing of hypoallergenic formulae in an in vivo model of orally induced cow's milk allergy. This study was undertaken to introduce a new read-out system to measure the residual allergenicity of whey hydrolysates on both the sensitization and challenge phase of orally induced cow's milk allergy in mice. Mice were sensitized orally to whey or a partial whey hydrolysate (pWH) to measure the residual sensitizing capacity. To predict the residual allergenicity of hydrolysates, whey allergic mice were challenged in the ear with pWH, extensive whey hydrolysate or an amino acid-based formula. An acute allergic skin response (ear swelling at 1 h), whey-specific serum antibodies, and local MCP-1 concentrations were measured. In contrast to whey, oral sensitization with pWH did not result in the induction of whey-specific antibodies, although a minor residual skin response to whey was observed after challenge. Skin exposure to whey hydrolysates showed a hydrolysation dependent reduction of the acute allergic skin response in whey allergic mice. In contrast to whey, skin exposure to pWH did not enhance tissue MCP-1 levels. The acute allergic skin response in mice orally sensitized to cow's milk proteins reveals a new pre-clinical tool which might provide information about the residual sensitizing capacity of hydrolysates supporting the discussion on the use of hypoallergenic formulae in high risk children. This mouse model might be a relevant model for the screening of new hypoallergenic formulae aimed to prevent or treat cow's milk allergy.

  7. Evaluation of Acute 13-Week Subchronic Toxicity and Genotoxicity of the Powdered Root of Tongkat Ali (Eurycoma longifolia Jack)

    PubMed Central

    Liao, Jiunn-Wang; Liao, Po-Lin; Huang, Wei-Kuang; Tse, Ling-Shan; Lin, Cheng-Hui; Kang, Jaw-Jou; Cheng, Yu-Wen

    2013-01-01

    Tongkat Ali (Eurycoma longifolia) is an indigenous traditional herb in Southern Asia. Its powdered root has been processed to produce health supplements, but no detailed toxicology report is available. In this study, neither mutagenicity nor clastogenicity was noted, and acute oral LD50 was more than 6 g/kg b.w. After 4-week subacute and 13-week subchronic exposure paradigms (0, 0.6, 1.2, and 2 g/kg b.w./day), adverse effects attributable to test compound were not observed with respect to body weight, hematology, serum biochemistry, urinalysis, macropathology, or histopathology. However, the treatment significantly reduced prothrombin time, partial thromboplastin time, blood urea nitrogen, creatinine, aspartate aminotransferase, creatine phosphate kinase, lactate dehydrogenase, and cholesterol levels, especially in males (P < 0.05). These changes were judged as pharmacological effects, and they are beneficial to health. The calculated acceptable daily intake (ADI) was up to 1.2 g/adult/day. This information will be useful for product development and safety management. PMID:24062779

  8. Evaluation of Acute 13-Week Subchronic Toxicity and Genotoxicity of the Powdered Root of Tongkat Ali (Eurycoma longifolia Jack).

    PubMed

    Li, Ching-Hao; Liao, Jiunn-Wang; Liao, Po-Lin; Huang, Wei-Kuang; Tse, Ling-Shan; Lin, Cheng-Hui; Kang, Jaw-Jou; Cheng, Yu-Wen

    2013-01-01

    Tongkat Ali (Eurycoma longifolia) is an indigenous traditional herb in Southern Asia. Its powdered root has been processed to produce health supplements, but no detailed toxicology report is available. In this study, neither mutagenicity nor clastogenicity was noted, and acute oral LD50 was more than 6 g/kg b.w. After 4-week subacute and 13-week subchronic exposure paradigms (0, 0.6, 1.2, and 2 g/kg b.w./day), adverse effects attributable to test compound were not observed with respect to body weight, hematology, serum biochemistry, urinalysis, macropathology, or histopathology. However, the treatment significantly reduced prothrombin time, partial thromboplastin time, blood urea nitrogen, creatinine, aspartate aminotransferase, creatine phosphate kinase, lactate dehydrogenase, and cholesterol levels, especially in males (P < 0.05). These changes were judged as pharmacological effects, and they are beneficial to health. The calculated acceptable daily intake (ADI) was up to 1.2 g/adult/day. This information will be useful for product development and safety management. PMID:24062779

  9. Comparative acute systemic toxicity of several quinoxaline 1,4-di-N-oxides in Wistar rats.

    PubMed

    Azqueta, Amaya; Gil, Ana Gloria; García-Rodríguez, Alba; García-Jalón, Jose Antonio; Cia, Felipe; Zarranz, Belén; Monge, Antonio; de Cerain, Adela López

    2007-01-01

    The acute toxicity of six quinoxaline 1,4-di-N-oxides has been evaluated in an attempt to determine: a) the feasibility of testing systemic toxicity of these compounds in a very preliminary phase without an adequate formulation for in vivo administration, b) the LD50 range and the toxic target organ of these compounds in order to have an approximation of the structure-activity relationship. Quinoxaline 1,4-di-N-oxides have shown a great variety of biological activities with potential therapeutic application in cancer, malaria, etc. Problems of toxicity hinder the progression of these compounds to clinical phases. The compounds dissolved in DMSO at their solubility limit were administered i.v. to female Wistar rats (8 weeks, 160 g), using an infusion pump (300 microL; 20 microl/min). Animals were observed for a period of 14 days. This dose of the vehicle (1.7 ml/kg) was well tolerated by the animals. The LD50 could not be determined, but a marked hypoactivity was induced by the treatment. The same compounds were also injected intraperitoneally, suspended in 0.01% Tween 80/0.09 % saline, and the animals that did not die were observed for a period of 14 days. The LD50 could be estimated to be in a range between 30 and 120 mg/kg, except for one of the compounds. A decrease in the evolution of body weight and hypoactivity were the principal symptoms induced by the treatment. In both assays, histopathologic study of heart, liver, kidney, lung, spleen and ovaries indicated that the target organs may be heart and spleen. In conclusion, the i.v. route is not adequate for estimating the LD50 of these compounds due to solubility problems; by i.p. route, the LD50 interval is between 30 and 120 mg/kg. The data did not permit the deduction of any specific structure-activity relationship.

  10. Acute metabolic responses of postpartal dairy cows to subcutaneous glucagon injections, oral glycerol, or both.

    PubMed

    Osman, M A; Allen, P S; Mehyar, N A; Bobe, G; Coetzee, J F; Koehler, K J; Beitz, D C

    2008-09-01

    This study examined the effects of multiple subcutaneous glucagon injections with or without co-administration of oral glycerol on energy status-related blood metabolites and hormones of Holstein dairy cows in the first 2 wk postpartum. Twenty multiparous cows were fed a dry cow ration supplemented with 6 kg of cracked corn during the dry period to increase the likelihood of developing postpartal fatty liver syndrome. Cows with a body condition score of >or=3.5 points (1- to 5-point scale) were assigned randomly to 1 of 4 treatment groups: saline, glucagon, glycerol, or glucagon plus glycerol. Following treatment, serial blood samples were collected over an 8-h period to determine the effects of glucagon and glycerol on blood metabolites and hormones. Treatment effects were determined by comparing the concentrations of metabolites and hormones during the first 4-h period and the entire 8-h period after treatment administration (time 0) with the concentration of the same compounds at time 0 on d 1, 7, and 13 postpartum. Administration of glucagon alone increased concentrations of plasma glucagon and insulin on d 1, 7, and 13 and increased plasma glucose and decreased plasma nonesterified fatty acids (NEFA) on d 7 and 13 postpartum relative to the saline group. Administration of glycerol alone increased plasma glucose on d 7 and plasma triacylglycerols on d 1 postpartum. Glycerol administration also decreased plasma glucagon and NEFA on d 1, 7, and 13 and plasma beta-hydroxybutyrate (BHBA) on d 1 postpartum relative to the saline group. Administration of glucagon plus glycerol increased and sustained concentrations of plasma glucagon, glucose, and insulin on d 1, 7, and 13 and decreased plasma NEFA on d 1, 7, and 13 and BHBA on d 1 and 7. Early postpartal treatment of dairy cows with glucagon plus glycerol increased plasma glucose and insulin, decreased plasma NEFA and BHBA, and increased secretion of liver NEFA as plasma triacylglycerols. This suggests that glucagon

  11. Growth performance and oxidative damage in kidney induced by oral administration of Cr(III) in chicken.

    PubMed

    Liu, Yanhan; Liu, Cun; Cheng, Jia; Fan, Wentao; Zhang, Xiao; Liu, Jianzhu

    2015-11-01

    This study aimed to evaluate the effects of adding chromic chloride (CrCl3) in the drinking water of chickens. Hyland brown male chickens were randomly divided into four groups. Three groups orally received 1/2 LD50, 1/4 LD50, and 1/8 LD50 CrCl3mgkg(-1) body weight daily for 42d. The fourth group was treated with water. The chickens were sacrificed at 14, 28, and 42d post-treatment. The renal injury was examined through histological analysis, and kidney mass was determined. The effects on growth performance were assessed by measuring the weight of the body, chest muscles, and leg muscles. Oxidative damage was evaluated by determining the antioxidant defense levels in kidney homogenates. The body weight and the weight of tissues gained time-dependently, but significantly decreased compared with those in the control group (P<0.05) at the same exposure time. Administering Cr(3+) significantly increased the levels of malondialdehyde, glutathione, and hydrogen peroxide in the kidney compared with those in the control groups. Whereas, administering Cr(3+) reduced the activities of superoxide dismutase, catalase, glutathione peroxidase, and total an-tioxidant capacity compared with those in the control group (P<0.05) in a dose- and time-dependent manner. In conclusion, oral administration of CrCl3 decreases the growth performance of chickens, leads to the pathological lesions and affects nephritic antioxidant capacity in the kidney dose- and time-dependently.

  12. [The effect of immunofan on the immunity system characteristics and lipid peroxidation parameters upon acute chemical poisoning].

    PubMed

    Zabrodskiĭ, P F; Germanchuk, V G; Nodel', M L; Vasilenko, O A; Aredakov, A N

    2004-01-01

    The results of experiments on Wistar rats under conditions of acute poisoning with 0.75 LD50 of zarin (isopropylmethyl fluorophosphonate), luisite (beta-chlorovinyl dichloroarsine), arsenic chloride, and dichloroethane showed that a four-day treatment with immunofan in a dose of 10 microg/kg restored the immune status characteristics (antibody formation to T-dependent antigen, antibody-dependent cell-mediated cytotoxicity, natural killer cell activity, and delayed type hypersensitivity) and the related LPO parameters.

  13. Direct effects of Facio-Oral Tract Therapy® on swallowing frequency of non-tracheotomised patients with acute neurogenic dysphagia

    PubMed Central

    Lerch, Annekatrin; Cataldo, Marilena; Kerz, Thomas

    2015-01-01

    Objectives: The aim of this study was to investigate the direct effect of Facio-Oral Tract Therapy® on swallowing frequency of non-tracheotomised patients with acute neurogenic dysphagia. Methods: Within a pre-, post-/during and follow-up study design, 19 non-tracheotomised dysphagic patients were included consecutively and treated according to three specific preselected Facio-Oral Tract Therapy stimulation techniques. Results: The primary outcome was the direct effect of the three different Facio-Oral Tract Therapy stimulation techniques on the number of swallows. We found a significant effect of Facio-Oral Tract Therapy on swallowing frequency as compared to baseline with an increase by 65.63% and medium effect size of D = 0.62. No significant difference could be demonstrated when comparing baseline to follow-up. Conclusion: For the first time, this positive therapy effect could be demonstrated on a population of non-tracheotomised patients. Facio-Oral Tract Therapy seems to be an appropriate means for improving effectiveness and safety of swallowing. Since improvement was not long lasting, it appears to be reasonable to apply therapy frequently during the day with the plausible result of minimising the amount of aspirated saliva and thereby reducing the risk of aspiration pneumonia. Further studies may consider choosing a randomised controlled trial design to demonstrate that change in swallow frequency is related to the target intervention only. PMID:26770778

  14. Evidence for efficacy of acute treatment of episodic tension-type headache: methodological critique of randomised trials for oral treatments.

    PubMed

    Moore, R Andrew; Derry, Sheena; Wiffen, Philip J; Straube, Sebastian; Bendtsen, Lars

    2014-11-01

    The International Headache Society (IHS) provides guidance on the conduct of trials for acute treatment of episodic tension-type headache (TTH), a common disorder with considerable disability. Electronic and other searches identified randomised, double-blind trials of oral drugs treating episodic TTH with moderate or severe pain at baseline, or that tested drugs at first pain onset. The aims were to review methods, quality, and outcomes reported (in particular the IHS-recommended primary efficacy parameter pain-free after 2 hours), and to assess efficacy by meta-analysis. We identified 58 reports: 55 from previous reviews and searches, 2 unpublished reports, and 1 clinical trial report with results. We included 40 reports of 55 randomised trials involving 12,143 patients. Reporting quality was generally good, with potential risk of bias from incomplete outcome reporting and small size; the 23 largest trials involved 82% of patients. Few trials reported IHS outcomes. The number needed to treat values for being pain-free at 2 hours compared with placebo were 8.7 (95% confidence interval [CI] 6.2 to 15) for paracetamol 1000 mg, 8.9 (95% CI 5.9 to 18) for ibuprofen 400mg, and 9.8 (95% CI 5.1 to 146) for ketoprofen 25mg. Lower (better) number needed to treat values were calculated for outcomes of mild or no pain at 2 hours, and patient global assessment. These were similar to values for these drugs in migraine. No other drugs had evaluable results for these patient-centred outcomes. There was no evidence that any one outcome was better than others. The evidence available for treatment efficacy is small in comparison to the size of the clinical problem.

  15. Phase 2 study of TAK-442, an oral factor Xa inhibitor, in patients following acute coronary syndrome.

    PubMed

    Goldstein, Sidney; Bates, Eric R; Bhatt, Deepak L; Cao, Charlie; Holmes, David; Kupfer, Stuart; Martinez, Felipe; Spaeder, Jeffrey; Weitz, Jeffrey I; Ye, Zhan; Zannad, Faiez

    2014-06-01

    TAK-442 is an oral direct factor Xa inhibitor. We sought to determine the dose-dependent effect of TAK-442 on major bleeding when added to standard treatment in stabilised patients with acute coronary syndrome (ACS). In this phase II double-blind study, 2,753 ACS patients were randomised to TAK-442 or placebo in addition to usual care using a three-stage adaptive design. Patients were randomised to placebo in all stages, but doses of TAK-442 escalated from 10 mg BID, 20 mg twice-daily (BID), or 40 mg once-daily (QD) in stage 1; to 40 mg BID, 80 mg QD, or 80 mg BID in stage 2; and to 160 mg QD or 120 mg BID in stage 3. Study drug was started 36 hours after emergent treatment of ACS and within seven days of admission, and continued for 24 weeks. The primary endpoint was incidence of TIMI (thrombolysis in myocardial infarction) major bleeding. TIMI major bleeding incidence was low, but higher with the pooled TAK-442 doses than with placebo (17 [0.9%] vs 4 [0.5%]; p=0.47), although the difference was neither significant nor dose-dependent. However, a dose response was evident when using the modified ISTH scale. The incidence of cardiovascular events was similar among TAK-442 dose groups and placebo. When administered over a wide range of doses after an ACS event, TAK-442 treatment did not result in a dose-dependent increase in TIMI major bleeding, but increased bleeding was observed when a more sensitive bleeding scale was used. There was no evidence for efficacy.

  16. Comparison of coronary angiography and early oral dipyridamole thallium-201 scintigraphy in patients receiving thrombolytic therapy for acute myocardial infarction

    SciTech Connect

    Jain, A.; Hicks, R.R.; Myers, G.H.; McCarthy, J.J.; Perry, J.R.; Adams, K.F. )

    1990-10-01

    We evaluated 50 consecutive patients who received thrombolytic therapy for acute myocardial infarction using thallium-201 single photon emission computed tomography in combination with oral dipyridamole to assess the frequency of residual myocardial ischemia. Thallium studies were performed early after myocardial infarction at a mean of 4.6 days. The time from the onset of chest pain to the administration of thrombolytic therapy was 2.6 hours (range 0.5 to 5.5). Q wave myocardial infarction was evident in 46 patients; four patients had a non-Q wave infarction (anterior infarction in 31 patients and inferior infarction in 19 patients). The serum mean peak creatinine kinase was 1503 IU/L (range 127 to 6500). Coronary angiography was performed in all patients at a mean of 3.1 days (range 2 to 10) and revealed the infarct-related vessel to be patent in 36 patients (72%). The ejection fraction was 48% (range 26% to 67%). After dipyridamole administration, 13 patients (26%) developed angina that was easily reversed with the administration of intravenous aminophylline. Systolic blood pressure decreased from 122 to 115 mm Hg (p less than 0.05) and the heart rate increased from 76 to 85 beats/min (p less than 0.05). None of the patients had significant hypotension, arrhythmias, or evidence of infarct extension. Perfusion abnormalities were present on the initial thallium images in 48 patients. Redistribution suggestive of ischemia was present in 36 patients (72%). Ischemia confined to the vascular distribution of the infarct vessel was evident in 22 patients. Seven patients had ischemia in the infarct zone as well as in a remote myocardial segment. Thus 29 patients (58%) had ischemia in the distribution of the infarct vessel. Ischemia in the infarct zone was evident in 19 of 36 patients with open infarct vessels and in 10 of 14 patients with occluded infarct vessels.

  17. 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.

  18. Acute and sub-chronic (28 days) oral toxicity evaluation of tincture Baccharis trimera (Less) Backer in male and female rodent animals.

    PubMed

    da Silva, Andreia R H; Reginato, Fernanda Z; Guex, Camille G; Figueredo, Kássia C; da C Araldi, Isabel C; de Freitas, Robson B; Boligon, Aline A; Athayde, Margareth L; Mazzanti, Cinthia Melazzo de Andrade; Hübscher, Gilberti H; de F Bauermann, Liliane

    2016-02-01

    The infusion of Baccharis trimera (Less) DC, popularly known as "carqueja" (broom), is popularly used in the treatment of hepatic and digestive problems. In this study, we evaluated the acute and sub-chronic oral toxicities of B. trimera tincture on male and female Wistar rats according to Organization for Economic Cooperation and Development (OECD, guidelines 423 e 407, respectively). The B. trimera tincture was administered by oral gavage in a single dose (2000 mg/kg) in doses of 100, 200 and 400 mg/kg daily for 28 days. Blood was collected to analyze hematological and biochemical parameters. Kidneys and liver were homogenized to determine lipid peroxidation and δ-aminolevulinate dehydratase (δ-ALA-D) and catalase (CAT) enzyme activities. In acute treatment, tincture did not induce any signs of toxicity or mortality. Daily oral administration produced no significant changes in the hematological and biochemical parameters, except for the hepatic enzymes alanine aminotransferase (ALAT) and aspartate aminotransferase (ASAT) that showed a reduction in both sexes. Moreover, the B. trimera tincture did not increase lipid peroxidation or affected ALA-D and CAT activities. In conclusion, the tincture of B. trimera may be considered relatively safe in this protocol.

  19. Acute toxicity of some synthetic cyanogens in rats: time-dependent cyanide generation and cytochrome oxidase inhibition in soft tissues after sub-lethal oral intoxication.

    PubMed

    Rao, Pooja; Singh, Poonam; Yadav, Shiv Kumar; Gujar, Niranjan L; Bhattacharya, Rahul

    2013-09-01

    Cyanogens include complex nitrile-containing compounds that can generate free cyanide of toxicological significance. Acute toxicity, time-dependent cyanide generation and cytochrome oxidase (CYTOX) inhibition in soft tissues, and urinary thiocyanate levels were measured after acute cyanogen intoxication in rats. Order of cyanogens in terms of LD₅₀ was: malononitrile (MCN)>propionitrile (PCN)≈sodium nitroprusside (SNP)>acrylonitrile (ACN)>succinonitrile (SCN)>acetonitrile (ATCN) for oral, and SNP>MCN>ACN>PCN>SCN>ATCN for intraperitoneal and subcutaneous routes. MCN was most toxic by oral (LD₅₀=66.4 mg/kg) and SNP by intraperitoneal (LD₅₀=16.7 mg/kg) and subcutaneous (LD₅₀=11.9 mg/kg) routes. Minimum survival time (25 min) was recorded after 4.0 LD₅₀ ATCN. Order of cyanogens (0.75 LD₅₀; oral) on the basis of maximum blood cyanide and time of peak cyanide generation were: ATCN>SNP>SCN>PCN>MCN>ACN, and MCN (30 min)

  20. Food-based solutions are a viable alternative to glucose-electrolyte solutions for oral hydration in acute diarrhoea--studies in a rat model of secretory diarrhoea.

    PubMed

    Rolston, D D; Mathew, P; Mathan, V I

    1990-01-01

    A survey of acute diarrhoea and its treatment, in 3 groups of villages in south India, revealed that use of the World Health Organization oral rehydration solution (WHO-ORS) was poor or virtually non-existent and that several liquid foods were given to children during acute diarrhoea. The effects of the most commonly used, boiled and cooled supernatants of these liquid foods [rice (Oryza sativa)-water, ragi (Eleusine coracana)-water, arrowroot (Maranta arundinacea)-water], and tender coconut-water, and of the bicarbonate- and citrate-WHO-ORS on intestinal water transport were evaluated using a rat model of secretory diarrhoea. All solutions either decreased cholera toxin-induced net water secretion (arrowroot-water) or reversed it to net absorption. Ragi-water produced maximum net water absorption, significantly greater than the WHO oral rehydration solutions. WHO-ORS utilization is poor in some developing countries, and locally used food-based solutions could be used for maintaining hydration or correcting the dehydration due to acute diarrhoea once their effectiveness has been proved by clinical trials. PMID:2345922

  1. Food-based solutions are a viable alternative to glucose-electrolyte solutions for oral hydration in acute diarrhoea--studies in a rat model of secretory diarrhoea.

    PubMed

    Rolston, D D; Mathew, P; Mathan, V I

    1990-01-01

    A survey of acute diarrhoea and its treatment, in 3 groups of villages in south India, revealed that use of the World Health Organization oral rehydration solution (WHO-ORS) was poor or virtually non-existent and that several liquid foods were given to children during acute diarrhoea. The effects of the most commonly used, boiled and cooled supernatants of these liquid foods [rice (Oryza sativa)-water, ragi (Eleusine coracana)-water, arrowroot (Maranta arundinacea)-water], and tender coconut-water, and of the bicarbonate- and citrate-WHO-ORS on intestinal water transport were evaluated using a rat model of secretory diarrhoea. All solutions either decreased cholera toxin-induced net water secretion (arrowroot-water) or reversed it to net absorption. Ragi-water produced maximum net water absorption, significantly greater than the WHO oral rehydration solutions. WHO-ORS utilization is poor in some developing countries, and locally used food-based solutions could be used for maintaining hydration or correcting the dehydration due to acute diarrhoea once their effectiveness has been proved by clinical trials.

  2. Genotoxicity and acute and subchronic toxicity studies of a standardized methanolic extract of Ficus deltoidea leaves

    PubMed Central

    Farsi, Elham; Shafaei, Armaghan; Hor, Sook Yee; Khadeer Ahamed, Mohamed B.; Yam, Mun Fei; Asmawi, Mohd Z.; Ismail, Zhari

    2013-01-01

    OBJECTIVE: Ficus deltoidea leaves have been used in traditional medicine in Southeast Asia to treat diabetes, inflammation, diarrhea, and infections. The present study was conducted to assess the genotoxicity and acute and subchronic toxicity of a standardized methanol extract of F. deltoidea leaves. METHODS: Sprague Dawley rats were orally treated with five different single doses of the extract and screened for signs of toxicity for two weeks after administration. In the subchronic study, three different doses of the extract were administered for 28 days. Mortality, clinical signs, body weight changes, hematological and biochemical parameters, gross findings, organ weights, and histological parameters were monitored during the study. Genotoxicity was assessed using the Ames test with the TA98 and TA100 Salmonella typhimurium strains. Phytochemical standardization was performed using a colorimeter and high-performance liquid chromatography. Heavy metal detection was performed using an atomic absorption spectrometer. RESULTS: The acute toxicity study showed that the LD50 of the extract was greater than 5000 mg/kg. In the subchronic toxicity study, there were no significant adverse effects on food consumption, body weight, organ weights, mortality, clinical chemistry, hematology, gross pathology, or histopathology. However, a dose-dependent increase in the serum urea level was observed. The Ames test revealed that the extract did not have any potential to induce gene mutations in S. typhimurium, either in the presence or absence of S9 activation. Phytochemical analysis of the extract revealed high contents of phenolics, flavonoids, and tannins. High-performance liquid chromatography analysis revealed high levels of vitexin and isovitexin in the extract, and the levels of heavy metals were below the toxic levels. CONCLUSION: The no-observed adverse effect level of F. deltoidea in rats was determined to be 2500 mg/kg. PMID:23778480

  3. “Doing Our Part” (Taking Responsibility): A Grounded Theory of the Process of Adherence to Oral Chemotherapy in Children and Adolescents with Acute Lymphoblastic Leukemia

    PubMed Central

    Landier, Wendy; Hughes, Cynthia B.; Calvillo, Evelyn R.; Anderson, Nancy L.R.; Briseño-Toomey, Deborah; Dominguez, Leticia; Martinez, Alex M.; Hanby, Cara; Bhatia, Smita

    2011-01-01

    Children and adolescents with acute lymphoblastic leukemia (A.L.L.) receive treatment that relies on daily self- or parent/caregiver-administered oral chemotherapy for approximately two years. Despite the fact that pediatric A.L.L. is uniformly fatal without adequate treatment, non-adherence to oral chemotherapy has been observed in up to one-third of patients. Little is known about the reasons for non-adherence in these patients. This study employed Straussian grounded theory methodology to develop and validate a model to explain the process of adherence to oral chemotherapy in children and adolescents with A.L.L. Thirty-eight semi-structured interviews (with 17 patients and 21 parents/caregivers) and four focused group discussions were conducted. Three stages were identified in the process of adherence: (1) Recognizing the Threat, (2) Taking Control, and (3) Managing for the Duration. Doing Our Part was identified as the core theme explaining the process of adherence, and involves the parent (or patient) taking responsibility for assuring that medications are taken as prescribed. Understanding the association between taking oral chemotherapy and control/cure of leukemia (Making the Connection) appeared to mediate adherence behaviors. PMID:21653911

  4. Phase III trials of new oral anticoagulants in the acute treatment and secondary prevention of VTE: comparison and critique of study methodology and results.

    PubMed

    Cohen, Alexander T; Imfeld, Stephan; Rider, Thomas

    2014-05-01

    The traditional treatment of venous thromboembolism (VTE) has been use of heparin and vitamin K antagonists (VKA), and although shown to be effective, they have numerous limitations. New oral anticoagulants (NOACs) including direct thrombin (factor IIa) inhibitors (dabigatran) and selective factor Xa inhibitors (rivaroxaban, apixaban and edoxaban) have emerged as promising alternatives with the potential to overcome the limitations of traditional treatments. Clinical trials have been performed with a view to making significant changes to the acute, long-term and extended treatment of VTE. Data are now available on the efficacy and safety, including bleeding rates, of the NOACs in comparison with VKA in the acute treatment and secondary prevention of VTE as well as in comparison with placebo extended VTE treatment. This review compares and contrasts the design and results of the Phase III trials of NOACs in VTE and discusses the implications of the NOACs in terms of treatment strategies in VTE patients.

  5. Antinociception induced by acute oral administration of sweet substance in young and adult rodents: the role of endogenous opioid peptides chemical mediators and μ(1)-opioid receptors.

    PubMed

    de Freitas, Renato Leonardo; Kübler, João Marcus Lopes; Elias-Filho, Daoud Hibraim; Coimbra, Norberto Cysne

    2012-04-01

    The present work aimed to investigate the effects of acute sucrose treatment on the perception of painful stimuli. Specifically, we sought to determine the involvement of the endogenous opioid peptide-mediated system as well as the role of the μ(1)-opioid receptor in antinociception organisation induced by acute sucrose intake. Nociception was assessed with the tail-flick test in rats (75, 150 and 250 g) of different ages acutely pre-treated with 500 μL of a sucrose solution (25, 50, 150 and 250 g/L) or tap water. Young and Adult rats (250 g) showed antinociception after treatment with 50 g/L (during 5 min) and 150 g/L and 250 g/L (during 20 min) sucrose solutions. Surprisingly, this antinociception was more consistent in mature adult rodents than in pups. To evaluate the role of opioid systems, mature adult rodents were pre-treated with different doses (0.25, 1 or 4 mg/kg) of the non-selective opioid receptor antagonist naloxone, the selective μ(1)-opioid receptor antagonist naloxonazine or vehicle followed by 250 g/L sucrose solution treatment. Sucrose-induced antinociception was reduced by pre-treatment with both naloxone and naloxonazine. The present findings suggest that sweet substance-induced hypo-analgesia is augmented by increasing sucrose concentrations in young and adult rodents. Acute oral sucrose treatment inhibits pain in laboratory animal by mediating endogenous opioid peptide and μ(1)-opioid receptor actions.

  6. Acute and Cytotoxicity Studies of Aqueous and Ethanolic Leaf Extracts of Chromolaena odorata.

    PubMed

    Asomugha, R N; Ezejiofor, A N; Okafor, P N; Ijeh, I I

    2015-01-01

    Chromolaena odorata, a commonly used traditional remedy for different ailments, believed to be quite safe in terms of toxicity was evaluated for acute toxicity and cytotoxic potentials. Acute toxicity was done on albino Wistar rats using the Lorke method while brine shrimps were used to test for cytotoxicity. The results showed that the estimated LD50 for the aqueous and ethanolic extracts was 2154 and > 5000 mg kg(-1) body weight, respectively. Cytotoxicity to brine shrimps showed LC50 values of 324 and 392 ppm for aqueous and ethanolic extracts, respectively. These results indicate the relative non toxic nature of Chromolaena odorata extracts.

  7. Normal tissue complication probability (NTCP) modelling using spatial dose metrics and machine learning methods for severe acute oral mucositis resulting from head and neck radiotherapy

    PubMed Central

    Dean, Jamie A; Wong, Kee H; Welsh, Liam C; Jones, Ann-Britt; Schick, Ulrike; Newbold, Kate L; Bhide, Shreerang A; Harrington, Kevin J; Nutting, Christopher M; Gulliford, Sarah L

    2016-01-01

    Background and Purpose Severe acute mucositis commonly results from head and neck (chemo)radiotherapy. A predictive model of mucositis could guide clinical decision-making and inform treatment planning. We aimed to generate such a model using spatial dose metrics and machine learning. Material and Methods Predictive models of severe acute mucositis were generated using radiotherapy dose (dose-volume and spatial dose metrics) and clinical data. Penalised logistic regression, support vector classification and random forest classification (RFC) models were generated and compared. Internal validation was performed (with 100-iteration cross-validation), using multiple metrics, including area under the receiver operating characteristic curve (AUC) and calibration slope, to assess performance. Associations between covariates and severe mucositis were explored using the models. Results The dose-volume-based models (standard) performed equally to those incorporating spatial information. Discrimination was similar between models, but the RFCstandard had the best calibration. The mean AUC and calibration slope for this model were 0.71 (s.d.=0.09) and 3.9 (s.d.=2.2), respectively. The volumes of oral cavity receiving intermediate and high doses were associated with severe mucositis. Conclusions The RFCstandard model performance is modest-to-good, but should be improved, and requires external validation. Reducing the volumes of oral cavity receiving intermediate and high doses may reduce mucositis incidence. PMID:27240717

  8. Oral contrast for CT in patients with acute non-traumatic abdominal and pelvic pain: what should be its current role?

    PubMed

    Kielar, Ania Z; Patlas, Michael N; Katz, Douglas S

    2016-10-01

    Positive oral contrast agents, including barium suspensions and water-soluble iodinated solutions, have traditionally been used in conjunction with the CT evaluation of patients with abdominal and pelvic pain. Due to continued advancements in CT technology, and due to increasing obesity and correspondingly a general increase in the intra-abdominal and intra-pelvic fat separating bowel loops in North American patients and in patients in other parts of the world over the past few decades, the ability of radiologists to accurately evaluate the cause of acute symptoms has substantially improved. Recent research and evolving imaging society guidelines/systematic reviews increasingly support performing CT scans of the abdomen and pelvis without the need for positive oral contrast in these types of adult patient populations, in most clinical situations. Increased patient throughput, patient preference, patient safety, and most importantly, retention of high diagnostic accuracy, are reasons for this recent change in practice to routinely omit the use of enteric contrast agents for the majority of patients presenting with acute abdominal and pelvic pain whom are undergoing emergency CT. PMID:27166963

  9. Acute and subacute toxicity of 10B-paraboronophenylalanine

    SciTech Connect

    Taniyama, K.; Fujiwara, H.; Kuno, T.; Saito, N.; Shuntoh, H.; Sakaue, M.; Tanaka, C. )

    1989-07-01

    The acute and subacute toxicities of 10B-paraboronophenylalanine (10B-BPA) were investigated in the rat, according to the Good Laboratory Practice Standard for safety studies on drugs in Japan. In the acute toxicity test of 10B-BPA, LD50 values of acidic 10B-BPA for intraperitoneal and subcutaneous injections were 640 mg/kg for male and 710 mg/kg for female rats, and more than 1,000 mg/kg for male and female rats, respectively. The LD50 values of neutral 10B-BPA for intraperitoneal and subcutaneous injections were more than 3,000 mg/kg for male and female rats. The difference in LD50 values between acidic and neutral 10B-BPA may be attributed to the acidity of material. From the subacute toxicity test, in which the rats were injected daily subcutaneously for 28 days, the following toxic effects of 10B-BPA were observed. Increase in ketone level in the urine was induced in all rats treated with 10B-BPA. High dose of 10B-BPA (1,500 mg/kg) induced increase in spleen weight and reticulocyte count, and decrease in hemoglobin count, thereby suggesting that 10B-BPA causes hemolysis. Increases in the leukocyte count and the ratio of neutrophils and lymphocytes were also observed in rats treated with a high dose of 10B-BPA. This may be attributed to local reactions at the injection site. There were no significant differences in the findings between control rats and rats treated with a low dose of 10B-BPA (300 mg/kg). Thus, low doses of neutral 10B-BPA may be available for use as a drug.

  10. Comparative studies of oral administration of marine collagen peptides from Chum Salmon (Oncorhynchus keta) pre- and post-acute ethanol intoxication in female Sprague-Dawley rats.

    PubMed

    Liang, Jiang; Li, Qiong; Lin, Bing; Yu, Yongchao; Ding, Ye; Dai, Xiaoqian; Li, Yong

    2014-09-01

    The present study aimed to evaluate the effect of an oral administration of marine collagen peptides (MCPs) pre- and post-acute ethanol intoxication in female Sprague-Dawley (SD) rats. MCPs were orally administered to rats at doses of 0 g per kg bw, 2.25 g per kg bw, 4.5 g per kg bw and 9.0 g per kg bw, prior to or after the oral administration of ethanol. Thirty minutes after ethanol treatment, the effect of MCPs on motor incoordination and hypnosis induced by ethanol were investigated using a screen test, fixed speed rotarod test (5 g per kg bw ethanol) and loss of righting reflex (7 g per kg bw ethanol). In addition, the blood ethanol concentrations at 30, 60, 90, and 120 minutes after ethanol administration (5 g per kg bw ethanol) were measured. The results of the screen test and fixed speed rotarod test suggested that treatment with MCPs at 4.5 g per kg bw and 9.0 g per kg bw prior to ethanol could attenuate ethanol-induced loss of motor coordination. Moreover, MCP administered both pre- and post-ethanol treatment had significant potency to alleviate the acute ethanol induced hypnotic states in the loss of righting reflex test. At 30, 60, 90 and 120 minutes after ethanol ingestion at 5 g per kg bw, the blood ethanol concentration (BEC) of control rats significantly increased compared with that in the 4.5 g per kg bw and 9.0 g per kg bw MCP pre-treated groups. However, post-treatment with MCPs did not exert a significant inhibitory effect on the BEC of the post-treated groups until 120 minutes after ethanol administration. Therefore, the anti-inebriation effect of MCPs was verified in SD rats with the possible mechanisms related to inhibiting ethanol absorption and facilitating ethanol metabolism. Moreover, the efficiency was better when MCPs were administered prior to ethanol.

  11. Influence of body habitus and use of oral contrast on reader confidence in patients with suspected acute appendicitis using 64 MDCT.

    PubMed

    Anderson, Stephan W; Rhea, James T; Milch, Holly N; Ozonoff, Al; Lucey, Brian C; Soto, Jorge A

    2010-11-01

    The purpose of this study is to evaluate how body habitus affects reader confidence in diagnosing acute appendicitis and appendiceal visualization using 64 MDCT technology with and without oral contrast. We conducted a HIPAA compliant, IRB approved study of adult patients presenting to the Emergency Department with nontraumatic abdominal pain. Subjects were randomized to two groups: 64 MDCT scans performed with oral and intravenous contrast or scans performed solely with intravenous contrast. Three radiologists established their confidence about the presence of appendicitis as well as recording whether the appendix was visualized. Reader confidence in diagnosing acute appendicitis was compared between the two groups for the three readers. The impact of patient BMI and estimated intra-abdominal fat on reader confidence in diagnosing appendicitis was determined. Finally, a comparison of the effect of BMI and intra-abdominal fat on appendiceal visualization between the two groups was carried out. Three hundred three patients were enrolled in this study. There was a statistically significant difference in confidence based on BMI for reader 2, group 1 in diagnosing appendicitis. No further statistically significant differences in reader confidence for diagnosing appendicitis based on BMI or intra-abdominal fat were identified. There was no influence of BMI or intra-abdominal fat on appendiceal visualization. Increasing BMI was seen to improve reader confidence for one of three readers in patients that received both oral and intravenous contrast. No further effects of BMI or intra-abdominal fat on confidence in diagnosing or excluding appendicitis were seen. Neither BMI nor intra-abdominal fat were seen to influence appendiceal visualization.

  12. Acute toxicity and vascular properties of seed of Parkia biglobosa (JACQ) R. Br Gift (Mimosaceae) on rat aorta.

    PubMed

    Ouédraogo, Sylvin; Somé, Noya; Ouattara, Sounkalo; Kini, Félix B; Traore, Aristide; Bucher, Bernard; Guissou, I Pierre

    2012-01-01

    The authors report here the results of study on Parkia biglobosa seeds used in Burkina Faso for arterial hypertension treatment. Investigations were done on acute toxicity and vascular properties of fermented and roasted seeds. Acute toxicity test using mice, revealed by the intraperitoneal route a lethal dose 50 (LD50) of 1800 mg/kg and 1600 mg/kg of body weight for aqueous extract from roasted and fermented seeds respectively. According to the scale of Hodge and Sterner and that of the World Health Organization, such drugs would be classified lightly toxic. Oral administration (up to 3000 mg/kg) did not induce any death of animal. For the vascular properties, the effects of these products were tested on the aorta isolated from rats. The cumulative administration of extract from roasted and fermented seeds (0.1-10 mg/mL) in an organ bath induced a concentration-dependent relaxation of the aorta pre contracted by phenylephrine, with or without functional endothelium. The extracts (10 mg/mL) inhibited for 100% the contraction induced by phenylephrine. The EC50 values in presence and absence of endothelium were respectively of 5.37 ± 0.12 and 4.19 ± 1.02 mg/mL for fermented seeds; for roasted seeds these values were respectively, 5.39 ± 1.12 and 5.93 ± 0.95 mg/mL. Nevertheless, low concentration of roasted seeds (1-4 mg/mL) induced endothelium-dependent relaxation and this effect was inhibited by indomethacin (10⁻⁵M), and not by L-NAME (310⁻⁴M). These experimental results revealed a vasorelaxant effect of P. biglobosa seeds. P. biglobosa seems to act directly on the smooth muscle and via endothelium involving the generation of vasodilatating prostaglandins. This vasodilator effect would be in favor of an anti hypertensive property of P. biglobosa seeds.

  13. Preliminary acute and subchronic toxicity studies of GLG-V-13, a novel class III antiarrhythmic agent, in mice.

    PubMed

    Chen, C L; Chandra, S A; Kim, S; Sangiah, S; Chen, H; Roder, J D; Qualls, C W; Garrison, G L; Cowell, R L; Berlin, K D; Scherlag, B J; Lazzara, R

    2000-01-01

    The acute and subchronic toxic effects of GLG-V-13 (3-[4-(1H-imidazol-1-yl)benzoyl]-7-isopropyl-3,7-diazabicyclo[3.3.1]nona ne dihydroperchlorate, CAS 155029-33-7), a novel class III with some class Ib antiarrhythmic activity, were investigated in mice. The estimated LD50 for GLG-V-13 given orally were 419 mg/kg for male mice and 383 mg/kg for female mice, respectively. The acute toxic signs appeared to be of the central nervous system in origin. Four groups of mice (15 per sex, group and dose) were fed daily with diets containing GLG-V-13 for 90 consecutive days. The equivalent daily doses were 0, 22, 50 and 121 mg/kg/day and 0, 27, 60 and 136 mg/kg/day for male and female mice, respectively. All of the mice survived. Food consumption was decreased. However, mean body weight and body weight gain were not significantly changed. Gross pathological changes, especially in the lungs and liver, were found in the middle and high dose groups. Consistent increased mean corpuscular hemoglobin concentration and decreased mean corpuscular hemoglobin were observed in all dose groups. Hepatocellular necrosis was found in both male and female mice treated with the drug and was dose-dependent. Marked vacuolation of the X zone in the adrenal gland with mild to moderate deposition of ceroid pigments (brown degeneration) was observed in female mice. Lesions in the kidneys and adrenal glands may be a possible reason for changes in serum sodium and potassium ions concentrations leading to an increase in water intake. A significant reduction in cholesterol in the high dose group may be a favorable pharmacological effect of GLG-V-13. The data from the 90-day subchronic toxicity studies indicate that GLG-V-13 appears to have limited systemic toxicity potential.

  14. Acute systemic toxicity.

    PubMed

    Botham, Philip A

    2002-01-01

    Use of the test that aimed to identify the single lethal dose of a substance that kills half the animals in a test group (the LD50 test) should finally be discontinued by the end of 2002, after many years of controversy and debate. In its stead are three recently developed alternative animal tests that significantly improve animal welfare: the fixed dose procedure, the acute toxic class method, and the up and down procedure. These tests have already undergone revision, both to improve their scientific performance and, importantly, to increase their regulatory acceptance. They can now be used within a strategy of acute toxicity testing for all types of test substances and for all regulatory and in-house purposes. In vitro cytotoxicity tests could be used (perhaps by mid-2002) as adjuncts to these alternative animal tests to improve dose level selection and reduce (at least modestly) the number of animals used. However, the total replacement of animal tests requires a considerable amount of further test development, followed by validation, which will require at least 10 yr.

  15. [Oral viral infections].

    PubMed

    Parent, Dominique

    2016-02-01

    Exclude herpes infection in the presence of acute oral ulcers of unknown origin, particularly in patients in poor general condition. Remember that asymptomatic HSV-1 shedding in saliva may result in an oral-genital transmission. Perform an anogenital examination and a screening for other sexually transmitted diseases when oral warts are diagnosed. Search for immunosuppression and monitor the patient (screening for a potential associated carcinoma) when there is rapid growth of oral warts. Consider all the clinical signs (systemic, skin, other mucosa, immunity...) when a patient has an enanthem or oral ulcerations. Ask for a HIV test when an oral Kaposi's sarcoma, a hairy leukoplakia or major aphthae are diagnosed. PMID:26854091

  16. Acute physical exercise is safe in patients with primary antiphospholipid syndrome with exclusive venous thrombosis and under oral anticoagulation with warfarin.

    PubMed

    Garcia, Carolina Borges; Seguro, Luciana Parente Costa; Perandini, Luiz Augusto; de Sá Pinto, Ana Lúcia; Lima, Fernanda Rodrigues; Negrão, Carlos Eduardo; Bonfa, Eloisa; Borba, Eduardo Ferreira

    2014-12-01

    The purpose of present study was to evaluate the effects of maximal acute physical exercise on prothrombin time/international normalized ratio (PT/INR) in patients with primary antiphospholipid syndrome (PAPS) under oral anticoagulation with warfarin and the safety of acute exercise in regard to thrombosis and bleeding risk. Eighteen physically inactive women with PAPS (Sydney criteria) with exclusive venous events and without thrombocytopenia were included. All patients were under stable warfarin therapy (PT/INR target: 2.0-3.0). Eighteen age-matched healthy sedentary women without thrombosis/bleeding disorders were selected as controls. All subjects performed a maximal exercise test, and capillary blood samples were obtained pre-, post- and at 1-h post-exercise (recovery time) for PT/INR analysis using a portable CoaguCheck. PAPS patients and controls had similar mean age (31.50 ± 8.06 vs. 29.61 ± 7.05 years, p = 0.46) and body mass index (24.16 ± 3.67 vs. 24.66 ± 2.71 kg/m(2), p = 0.65). PAPS had a mild but significant increase in PT/INR value at 1-h post-exercise (recovery) compared with pre- (2.33 ± 0.34 vs. 2.26 ± 0.29, p = 0.001) and post-exercise (2.33 ± 0.34 vs. 2.26 ± 0.32, p = 0.001) that was observed in 61.11 % of these patients. None of the subjects had thrombotic or bleeding complications related to the acute exercise. Acute exercise in patients with PAPS with exclusive venous thrombosis was safe with a minor increase in PT/INR. This is an important step to introduce regular exercise training as a therapeutic tool in the management of these patients.

  17. Patterns of Return to Oral Intake and Decannulation Post-tracheostomy across Clinical Populations in an Acute Inpatient Setting

    ERIC Educational Resources Information Center

    Pryor, Lee; Ward, Elizabeth; Cornwell, Petrea; O'Connor, Stephanie; Chapman, Marianne

    2016-01-01

    Background: Dysphagia is often a comorbidity in patients who require a tracheostomy, yet little is known about patterns of oral intake commencement in tracheostomized patients, or how patterns may vary depending on the clinical population and/or reason for tracheostomy insertion. Aims: To document patterns of clinical management around the…

  18. Acute Toxicity-Supported Chronic Toxicity Prediction: A k-Nearest Neighbor Coupled Read-Across Strategy

    PubMed Central

    Chavan, Swapnil; Friedman, Ran; Nicholls, Ian A.

    2015-01-01

    A k-nearest neighbor (k-NN) classification model was constructed for 118 RDT NEDO (Repeated Dose Toxicity New Energy and industrial technology Development Organization; currently known as the Hazard Evaluation Support System (HESS)) database chemicals, employing two acute toxicity (LD50)-based classes as a response and using a series of eight PaDEL software-derived fingerprints as predictor variables. A model developed using Estate type fingerprints correctly predicted the LD50 classes for 70 of 94 training set chemicals and 19 of 24 test set chemicals. An individual category was formed for each of the chemicals by extracting its corresponding k-analogs that were identified by k-NN classification. These categories were used to perform the read-across study for prediction of the chronic toxicity, i.e., Lowest Observed Effect Levels (LOEL). We have successfully predicted the LOELs of 54 of 70 training set chemicals (77%) and 14 of 19 test set chemicals (74%) to within an order of magnitude from their experimental LOEL values. Given the success thus far, we conclude that if the k-NN model predicts LD50 classes correctly for a certain chemical, then the k-analogs of such a chemical can be successfully used for data gap filling for the LOEL. This model should support the in silico prediction of repeated dose toxicity. PMID:26006240

  19. 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.

  20. The evolution of arsenic in the treatment of acute promyelocytic leukemia and other myeloid neoplasms: Moving toward an effective oral, outpatient therapy.

    PubMed

    Falchi, Lorenzo; Verstovsek, Srdan; Ravandi-Kashani, Farhad; Kantarjian, Hagop M

    2016-04-15

    The therapeutic potential of arsenic derivatives has long been recognized and was recently rediscovered in modern literature. Early studies demonstrated impressive activity of this compound in patients with relapsed acute promyelocytic leukemia (APL). Over the last 2 decades, intravenous arsenic trioxide has been used successfully, both alone and in combination with other agents, for the treatment of APL and, with some success, of other myeloid neoplasms. Arsenic trioxide is currently part the standard of care for patients with APL. More recently, oral formulations of this compound have been developed and are entering clinical practice. In this review, the authors discuss the evolution of arsenic in the treatment of APL and other myeloid neoplasms. PMID:26716387

  1. Oral or parenteral administration of curcumin does not prevent the growth of high-risk t(4;11) acute lymphoblastic leukemia cells engrafted into a NOD/SCID mouse model

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The efficacy of orally and parenterally administered curcumin was evaluated in NOD.CB17-Prkdcscid/J mice engrafted with the human t(4;11) acute lymphoblastic leukemia line SEM. SEM cells were injected into the tail vein and engraftment was monitored by flow cytometry. Once engraftment was observed...

  2. Effect of surgical castration with or without oral meloxicam on the acute inflammatory response in yearling beef bulls

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Pain management and welfare are increasingly prevalent concerns within animal agriculture. Analgesics may alleviate pain and inflammation associated with castration of beef cattle. This study was conducted to elucidate the effects of surgical castration on the acute inflammatory response and immunom...

  3. Toxicological investigations in the semiconductor industry: I. Studies on the acute oral toxicity of a complex mixture of waste products from the aluminium plasma etching process.

    PubMed

    Bauer, S; Wolff, I; Werner, N; Hoffmann, P; Herzschuh, R; Oemus, K; Rath, F W; Voigt, R

    1992-01-01

    In dry etching processes--one of the sources of potential exposure to toxic wastes in the semiconductor industry--complex mixtures of inorganic and organic compounds arise from reactions between feed stock gases (BCl3/Cl2), top layers (aluminium photoresist), and the carrier gas (N2). Two different fractions of the complex mixture--one an ethanolic solution (ES) and the other an insoluble liquid residue (LR)--were examined for acute oral toxicity in rats. Analytical data showed that the ethanol soluble fraction contained mainly inorganic compounds, whereas the residue contained various halogenated hydrocarbons. Neither death nor behavioral changes occurred after oral administration and observation up to 23 days. ES caused a lower mean arterial blood pressure in both sexes, increased P-R-intervals in male rats, and caused some mild biochemical and hematological alterations and changes in relative organ weights compared to the control groups. Exposure to LR influenced food and water intake, and caused a significant decrease in body weights, signs of polyurie, as well as changes in various relative organ weights and biochemical and hematological parameters. The blood pressure of the male animals fell and the heart rates of both sexes decreased. PMID:1386950

  4. Toxicological investigations in the semiconductor industry: I. Studies on the acute oral toxicity of a complex mixture of waste products from the aluminium plasma etching process

    SciTech Connect

    Bauer, S.; Wolff, I.; Werner, N.; Hoffmann, P.; Herzschuh, R.; Oemus, K.; Rath, F.W.; Voigt, R. )

    1992-05-01

    In dry etching processes--one of the sources of potential exposure to toxic wastes in the semiconductor industry--complex mixtures of inorganic and organic compounds arise from reactions between feed stock gases (BCl3/Cl2), top layers (aluminium photoresist), and the carrier gas (N2). Two different fractions of the complex mixture--one an ethanolic solution (ES) and the other an insoluble liquid residue (LR)--were examined for acute oral toxicity in rats. Analytical data showed that the ethanol soluble fraction contained mainly inorganic compounds, whereas the residue contained various halogenated hydrocarbons. Neither death nor behavioral changes occurred after oral administration and observation up to 23 days. ES caused a lower mean arterial blood pressure in both sexes, increased P-R-intervals in male rats, and caused some mild biochemical and hematological alterations and changes in relative organ weights compared to the control groups. Exposure to LR influenced food and water intake, and caused a significant decrease in body weights, signs of polyurie, as well as changes in various relative organ weights and biochemical and hematological parameters. The blood pressure of the male animals fell and the heart rates of both sexes decreased.

  5. Selection of orally active antifungal agents from 3,5-substituted isoxazolidine derivatives based on acute efficacy-safety profiles.

    PubMed

    Palmer, G C; Ordy, M J; Simmons, R D; Strand, J C; Radov, L A; Mullen, G B; Kinsolving, C R; St Georgiev, V; Mitchell, J T; Allen, S D

    1989-06-01

    Routine in vitro screening of a new synthetic series of 3,5-substituted 2-methylisoxazolidines revealed that three imidazole analogs (PR 967-248, PR 967-234, and PR 969-566) and, to a lesser extent, a triazole analog (PR 988-399) exerted rather potent antifungal activity against three systemic and four dermatophytic classes of fungi. When tested in vivo for ability to eradicate Candida vaginitis in the rat, the triazole derivative, PR 988-399, was effective after oral administration. In this in vivo test for efficacy, PR 967-234 and PR 969-566 reduced but did not eradicate the infection, while PR 967-248 was inactive. PR 988-399 was, moreover, 4- to 13-fold less potent than the three imidazoles in inhibiting testosterone synthesis in isolated rat Leydig cells. After oral or intravenous administration, PR 988-399 and PR 969-566 elicited the fewest cardiovascular and behavioural side effects in conscious dogs. The rat safety study consisted of oral dosing followed by evaluation of the exploratory motor activity of the naive animals in a novel environment. Motor activity was suppressed least by PR 988-399 and most by PR 969-566. In a battery of mouse behavioural-neuromuscular-drug interaction tests, PR 988-399 and PR 969-566 produced the fewest central-behavioural-neuromuscular signs. These efficacy-safety evaluations were performed with ketoconazole as a positive reference standard. The sequence of drug testing with respect to efficacy-safety considerations appears to be a suitable approach for early detection of orally active antifungal agents such as PR 988-399 for more advanced development.

  6. Oral infection with enteropathogenic Escherichia coli triggers immune response and intestinal histological alterations in mice selected for their minimal acute inflammatory responses.

    PubMed

    Vulcano, Amanda Bardella; Tino-De-Franco, Milene; Amaral, José Araujo; Ribeiro, Orlando Garcia; Cabrera, Wafa Hanna Koury; Bordenalli, Marcela Aparecida; Carbonare, Cristiane Barros; Álvares, Eliana Parisi; Carbonare, Solange Barros

    2014-06-01

    Enteropathogenic Escherichia coli (EPEC), a leading cause of infant diarrhea, is an important public health problem in Brazil and other developing countries. In vitro assays of bacterial adhesion to cultured cells are important tools for studying bacterial pathogenicity but do not reproduce all the events that occur in natural infections. In this study, the effects of oral infection with EPEC on mice selected for their minimal acute inflammatory response (AIR min) were evaluated. Mice were orally infected with EPEC and variations in body weight, bacterial shedding and antibody production observed. The infected animals developed seric and secretory anti-EPEC antibodies; however, neither mortality nor diarrhea was observed. Light microscopy of their intestines demonstrated histological modifications that were not present in controls. However, electron microscopy did not show bacteria attached to the intestinal epithelia to form attaching and effacing lesions, characteristic of EPEC in humans. The bacteria were detected in Peyer's patches and intestinal contents up to 5 hr post-infection. When human anti-EPEC secretory immunoglobulin A or avian immunoglobulin Y antibodies were administered to infected animals, they developed minor histological alterations compared with non-treated animals. In summary, it was found that EPEC triggers immune responses and intestinal histological alterations but does not produce evidence of diarrheal disease in mice infected by the oral route. This study of EPEC experimental infection provides a better understanding of the effects of antibodies on bacterial infections and may provide a suitable model for the design and testing of immunobiological products for active or passive immunization. PMID:24750489

  7. Preliminary pediatric clinical evaluation of the oral probiotic Streptococcus salivarius K12 in preventing recurrent pharyngitis and/or tonsillitis caused by Streptococcus pyogenes and recurrent acute otitis media

    PubMed Central

    Di Pierro, Francesco; Donato, Guido; Fomia, Federico; Adami, Teresa; Careddu, Domenico; Cassandro, Claudia; Albera, Roberto

    2012-01-01

    Background The oral probiotic Streptococcus salivarius K12 has been shown clearly to antagonize the growth of Streptococcus pyogenes, the most important bacterial cause of pharyngeal infections in humans, by releasing two bacteriocins named salivaricin A2 and salivaricin B. Unpublished observations indicate that it can also antagonize the growth of other bacteria involved in acute otitis media. Because of its ability to colonize the oral cavity and its safety profile, we have tested its efficacy in reducing the incidence of streptococcal pharyngitis and/or tonsillitis and episodes of acute otitis media. Methods We enrolled 82 children, including 65 with and 17 without a recent diagnosis of recurrent oral streptococcal pathology. Of those with recurrent pathology, 45 were treated daily for 90 days with an oral slow-release tablet containing five billion colony-forming units of S. salivarius K12 (Bactoblis®), and the remaining 20 served as an untreated control group. The 17 children without a recent diagnosis of recurrent oral pathology were used as an additional control group. After 90 days of treatment, a 6-month follow-up period without treatment was included to evaluate a possible persistent protective role for the previously administered product. Results The 41 children who completed the 90-day course of Bactoblis showed a reduction in their episodes of streptococcal pharyngeal infection (about 90%) and/or acute otitis media (about 40%), calculated by comparing infection rates in the previous year. The 90-day treatment also reduced the reported incidence of pharyngeal and ear infections by about 65% in the 6-month follow-up period during which the product was not administered. Subjects tolerated the product well, with no side effects or dropouts reported. Conclusion Prophylactic administration of S. salivarius K12 to children with a history of recurrent oral streptococcal pathology reduced episodes of streptococcal pharyngeal infections and/or tonsillitis as

  8. Safety assessment of the fermented Phylloporia ribis (Lonicera japonica Thunb.) mycelia by oral acute toxicity study in mice and 90-day feeding study in rats.

    PubMed

    Lu, Lianhua; Fan, Yiou; Yao, Wenhuan; Xie, Wei; Guo, Jie; Yan, Yan; Yang, Fei; Xu, Lingchuan

    2014-07-01

    Phylloporia ribis is an edible fungus in China. Its fermented mycelia have been approved by the National Health and Family Planning Commission (NHFPC) of PR China for use as a novel food material, but little information on its safety is available. The present research was the first to evaluate acute and subchronic toxicity in experimental animals of fermented Phylloporia ribis mycelia (FPM) following standard procedures. In acute toxicity study, FPM was orally administered to male and female mice twice a day at single dose of 10 g/kg bw. The Maximum Tolerated Dose (MTD) of FPM for mice of both sexes was over 10 g/kg bw. No death and abnormal behaviors occurred during 14 days study except for an increased locomotor activity in three animals. In 90-day feeding study, male and female Sprague-Dawley rats were fed diets containing 10.0%, 5.0%, 2.5%, 1.25% and 0% (control) FPM for 90 days. The treatment caused no effects on mortality, gross pathology, histology, hematology, and blood chemistry, no dose-dependent changes in food consumption, but caused effect on body weight gain compared with control group. The No Observed Adverse-Effect Level (NOAEL) of FPM was greater than 8.7 g/kg bw/day in both sexes of rats.

  9. Comparative acute toxicity and primary irritancy of the ethylidene and vinyl isomers of norbornene.

    PubMed

    Ballantyne, B; Myers, R C; Klonne, D R

    1997-01-01

    The acute toxicity and primary irritancy of the industrial chemicals 5-ethylidene-2-norbornene (ENB) and 5-vinyl-2-norbornene (VNB) were studied. They are of moderate acute peroral toxicity in the rat, with LD50 values for ENB of 2.54 (male) and 5.66 (female) ml kg(-1), and for VNB of 5.90 (male) and 11.9 (female) ml kg(-1). Percutaneous toxicity is slight in the rabbit by 24-h occluded contact, with no mortalities for ENB up to 8.0 ml kg(-1) and only one mortality (male) at 16.0 ml kg(-1) VNB. Dynamically generated saturated vapor atmosphere LT50 values for ENB in the rat were 75 (male) and 125 (female) min, and for VNB they were 28 (male) and 37 (female) min. The 4-h LC50 values for ENB were 2717 (male) and 3015 (female) ppm, and for VNB they were 2231 (male) and 2518 (female) ppm. Intravenously, the ENB LD50 ranged from 0.09 (male rabbit) to 0.11 ml kg(-1) (female); corresponding LD50 values for VNB were 0.10-0.05 mg kg(-1). Acute neurotoxic signs were seen by the intravenous and inhalation routes of exposure, including tremors, ataxia and convulsions; the latter were sufficient to cause vertebral column luxation or fracture, producing spinal cord compression and resultant hindlimb paralysis. Both ENB and VNB are moderately irritating to the skin (rabbit), causing erythema and edema, but not necrosis. Both materials cause slight conjunctival hyperemia and chemosis in rabbits, but not corneal injury. PMID:9285533

  10. Spodoptera frugiperda resistance to oral infection by Autographa californica multiple nucleopolyhedrovirus linked to aberrant occlusion-derived virus binding in the midgut.

    PubMed

    Haas-Stapleton, Eric J; Washburn, Jan O; Volkman, Loy E

    2005-05-01

    Spodoptera frugiperda larvae are highly resistant to oral infection by Autographa californica multiple nucleopolyhedrovirus (AcMNPV) (LD(50), approximately 9200 occlusions), but extremely susceptible to budded virus within the haemocoel (LD(50), <1 p.f.u.). The inability of AcMNPV occlusion-derived virus (ODV) to establish primary infections readily within midgut cells accounts for a major proportion of oral resistance. To determine whether inappropriate binding of AcMNPV ODV to S. frugiperda midgut cells contributes to lack of oral infectivity, the binding and fusion properties of AcMNPV ODV were compared with those of the ODV of a new isolate of Spodoptera frugiperda multiple nucleopolyhedrovirus (SfMNPV) obtained from a field-collected larva (oral LD(50), 12 occlusions). By using a fluorescence-dequenching assay conducted in vivo, it was found that AcMNPV ODV bound to the midgut epithelia of S. frugiperda larvae at approximately 15 % of the level of SfMNPV ODV, but that, once bound, the efficiencies of fusion for the two ODVs were similar: 60 % for AcMNPV and 53 % for SfMNPV. Whilst the difference in binding efficiencies was significant, it could not account entirely for the observed differences in infectivity. Competition experiments, however, revealed that, in S. frugiperda larvae, SfMNPV ODV bound to a midgut cell receptor that was not bound by AcMNPV ODV, indicating that ODV interaction with a specific receptor(s) was necessary for productive infection of midgut columnar epithelial cells. Fusion in the absence of this ligand-receptor interaction did not result in productive infections. PMID:15831946

  11. Acute effects of oral low doses of pyridostigmine on simple visual discrimination and unconditioned consummatory acts in rats.

    PubMed

    Liu, W F

    1992-01-01

    Pyridostigmine bromide (Pyr), a reversible cholinesterase inhibitor, is currently suggested to be the most effective pretreatment drug against intoxication with potent organophosphates (OP). This investigation was conducted to determine if oral low doses of Pyr would affect performance of a simple visual discrimination task, and further to assess the alterations of motor or motivational function that might underlie the performance deficits in the water-deprived rats. Rats were trained extensively on a successive light-intensity discrimination implemented with the use of a multiple schedule. The multiple schedule consisted of one fixed-ratio (FR-10) and one differential reinforcement of low rates (DRL-10 s) component, which were signalled by the 10-s discriminative stimuli of bright (S+) and dim (S-) houselights, respectively, in simple alternation. The light intensity difference (S-/S+) was about 0.6. Pyr, at doses (3-12 mg/kg), which did not cause overt symptoms, moderately decreased S+ respondings but did not affect S- respondings. The ratio of S+/S- respondings, an index of discrimination performance, was moderately decreased. Over the range of doses evaluated, Pyr also attenuated the corresponding water intake in a dose-dependent manner, but it did not significantly affect locomotor activity. The lowest effective doses of the above affected behaviors were virtually identical (6 mg/kg). These results suggest that the disruptive effects of a single oral low dose of Pyr on the rat operant performance involve motivational dysfunction rather than motor impairment.

  12. Differential cytotoxicity of long-chain bases for human oral gingival epithelial keratinocytes, oral fibroblasts, and dendritic cells.

    PubMed

    Mehalick, Leslie A; Poulsen, Christopher; Fischer, Carol L; Lanzel, Emily A; Bates, Amber M; Walters, Katherine S; Cavanaugh, Joseph E; Guthmiller, Janet M; Johnson, Georgia K; Wertz, Philip W; Brogden, Kim A

    2015-12-01

    Long-chain bases, found in the oral cavity, have potent antimicrobial activity against oral pathogens. In an article associated with this dataset, Poulson and colleagues determined the cytotoxicities of long-chain bases (sphingosine, dihydrosphingosine, and phytosphingosine) for human oral gingival epithelial (GE) keratinocytes, oral gingival fibroblasts (GF), dendritic cells (DC), and squamous cell carcinoma (SCC) cell lines [1]. Poulson and colleagues found that GE keratinocytes were more resistant to long-chain bases as compared to GF, DC, and SCC cell lines [1]. In this study, we assess the susceptibility of DC to lower concentrations of long chain bases. 0.2-10.0 µM long-chain bases and GML were not cytotoxic to DC; 40.0-80.0 µM long-chain bases, but not GML, were cytotoxic for DC; and 80.0 µM long-chain bases were cytotoxic to DC and induced cellular damage and death in less than 20 mins. Overall, the LD50 of long-chain bases for GE keratinocytes, GF, and DC were considerably higher than their minimal inhibitory concentrations for oral pathogens, a finding important to pursuing their future potential in treating periodontal and oral infections.

  13. A critical role of acute bronchoconstriction in the mortality associated with high-dose sarin inhalation: effects of epinephrine and oxygen therapies.

    PubMed

    Gundavarapu, Sravanthi; Zhuang, Jianguo; Barrett, Edward G; Xu, Fadi; Russell, Robert G; Sopori, Mohan L

    2014-01-15

    Sarin is an organophosphate nerve agent that is among the most lethal chemical toxins known to mankind. Because of its vaporization properties and ease and low cost of production, sarin is the nerve agent with a strong potential for use by terrorists and rouge nations. The primary route of sarin exposure is through inhalation and, depending on the dose, sarin leads to acute respiratory failure and death. The mechanism(s) of sarin-induced respiratory failure is poorly understood. Sarin irreversibly inhibits acetylcholine esterase, leading to excessive synaptic levels of acetylcholine and, we have previously shown that sarin causes marked ventilatory changes including weakened response to hypoxia. We now show that LD50 sarin inhalation causes severe bronchoconstriction in rats, leading to airway resistance, increased hypoxia-induced factor-1α, and severe lung epithelium injury. Transferring animals into 60% oxygen chambers after sarin exposure improved the survival from about 50% to 75% at 24h; however, many animals died within hours after removal from the oxygen chambers. On the other hand, if LD50 sarin-exposed animals were administered the bronchodilator epinephrine, >90% of the animals survived. Moreover, while both epinephrine and oxygen treatments moderated cardiorespiratory parameters, the proinflammatory cytokine surge, and elevated expression of hypoxia-induced factor-1α, only epinephrine consistently reduced the sarin-induced bronchoconstriction. These data suggest that severe bronchoconstriction is a critical factor in the mortality induced by LD50 sarin inhalation, and epinephrine may limit the ventilatory, inflammatory, and lethal effects of sarin.

  14. The absorption, distribution, excretion, and metabolism of a single oral dose of O-ethyl O-4-nitrophenyl phenylphosphonothioate in hens

    SciTech Connect

    Abou-Donia, M.B.; Reichert, B.L.; Ashry, M.A.

    1983-08-01

    The disposition and metabolism of a single oral 10 mg/kg (LD50) of uniformly phenyl-labeled (/sup 14/C)EPN (O-ethyl O-4-nitrophenyl (/sup 14/C)phenylphosphonothioate) were studied in adult hens. The birds were protected from acute toxicity with atropine sulfate. Three treated hens were killed at each time interval (days): 0.5, 2, 4, 8, 12. Radioactivity was adsorbed from the gastrointestinal tract and distributed in all tissues. Most of the dose was excreted in the combined urinary-fecal excreta (74%). Only traces of the radioactivity (0.2%) were detected in expired CO/sub 2/. Most of the excreted radioactive materials were identified as phenylphosphonic acid (PPA), O-ethyl phenylphosphonic acid (EPPA), and O-ethyl phenylphosphonothioc acid (EPPTA). Radioactivity in tissues reached a peak of 11.8% in 12 days. The highest concentration of radioactivity was present in the liver followed by bile, kidney, adipose tissue, and muscle. EPN was the major compound identified in brain, spinal cord, sciatic nerve, kidney, and plasma. Most of the radioactivity in the liver was identified as EPPA followed by EPPTA and PPA. Kinetic studies showed that EPN disappeared exponentially from tissues. The half-life of the elimination of EPN from plasma was 16.5 days corresponding to a constant rate value of 0.04 day-1. Relative residence (RR) of EPN relative to plasma was shortest in liver and longest in adipose tissue followed by sciatic nerve and spinal cord.

  15. Effectiveness of Donepezil, Rivastigmine, and (±)Huperzine A in Counteracting the Acute Toxicity of Organophosphorus Nerve Agents: Comparison with Galantamine

    PubMed Central

    Aracava, Yasco; Pereira, Edna F. R.; Akkerman, Miriam; Adler, Michael

    2009-01-01

    Galantamine, a centrally acting cholinesterase (ChE) inhibitor and a nicotinic allosteric potentiating ligand used to treat Alzheimer's disease, is an effective and safe antidote against poisoning with nerve agents, including soman. Here, the effectiveness of galantamine was compared with that of the centrally active ChE inhibitors donepezil, rivastigmine, and (±)huperzine A as a pre- and/or post-treatment to counteract the acute toxicity of soman. In the first set of experiments, male prepubertal guinea pigs were treated intramuscularly with one of the test drugs and 30 min later challenged with 1.5 × LD50 soman (42 μg/kg s.c.). All animals that were pretreated with galantamine (6–8 mg/kg), 3 mg/kg donepezil, 6 mg/kg rivastigmine, or 0.3 mg/kg (±)huperzine A survived the soman challenge, provided that they were also post-treated with atropine (10 mg/kg i.m.). However, only galantamine was well tolerated. In subsequent experiments, the effectiveness of specific treatment regimens using 8 mg/kg galantamine, 3 mg/kg donepezil, 6 mg/kg rivastigmine, or 0.3 mg/kg (±)huperzine A was compared in guinea pigs challenged with soman. In the absence of atropine, only galantamine worked as an effective and safe pretreatment in animals challenged with 1.0 × LD50 soman. Galantamine was also the only drug to afford significant protection when given to guinea pigs after 1.0 × LD50 soman. Finally, all test drugs except galantamine reduced the survival of the animals when administered 1 or 3 h after the challenge with 0.6 or 0.7 × LD50 soman. Thus, galantamine emerges as a superior antidotal therapy against the toxicity of soman. PMID:19741148

  16. Acute changes in serum calcium and parathyroid hormone circulating levels induced by the oral intake of five currently available calcium salts in healthy male volunteers.

    PubMed

    Deroisy, R; Zartarian, M; Meurmans, L; Nelissenne, N; Micheletti, M C; Albert, A; Reginster, J Y

    1997-05-01

    Several calcium supplements are currently available and many of them are marketed without proper comparison of the bioavailability of the actual preparations. The aim of the present trial was to evaluate and compare the acute changes in serum calcium (Ca) and parathyroid hormone (PTH) levels following the oral administration of a vehicle and of five calcium salts currently prescribed in Western Europe. No significant changes in serum Ca or PTH levels were observed after administration of the vehicle. All calcium salts induced significant increases in serum Ca and decreases in serum PTH compared to baseline values. Comparison of the six response curves revealed a significantly greater increase in serum Ca and a greater decrease in serum PTH after each of the calcium salts than observed after the vehicle. However, no statistically significant differences were observed between the different calcium salts for serum Ca increments. The decrease in serum PTH observed after administration of an ossein-hydroxyapatite complex was significantly less important than after the four other calcium salts, even if statistically different than after vehicle. When assessing the area under the curve (AUC) of PTH values, we observed that calcium carbonate and citrate induce a significantly greater decrease in serum PTH than the other calcium salts which are, however, statistically more active than the vehicle. Serum PTH is decreased under the lower limit of the normal range (10 pg/ml), between t60 and t120 for calcium carbonate and citrate and between t60 and t90 for calcium gluconolactate while the mean PTH values remain within the normal range throughout the study with calcium pidolate, the ossein-hydroxyapatite complex and the vehicle. In conclusion, all calcium preparations significantly increase serum calcium and decrease serum parathormone, compared to what is observed after oral intake of a vehicle. However, significant differences in suppression of parathormone are observed

  17. The effects of acute oral glutamine supplementation on exercise-induced gastrointestinal permeability and heat shock protein expression in peripheral blood mononuclear cells.

    PubMed

    Zuhl, Micah; Dokladny, Karol; Mermier, Christine; Schneider, Suzanne; Salgado, Roy; Moseley, Pope

    2015-01-01

    Chronic glutamine supplementation reduces exercise-induced intestinal permeability and inhibits the NF-κB pro-inflammatory pathway in human peripheral blood mononuclear cells. These effects were correlated with activation of HSP70. The purpose of this paper is to test if an acute dose of oral glutamine prior to exercise reduces intestinal permeability along with activation of the heat shock response leading to inhibition of pro-inflammatory markers. Physically active subjects (N = 7) completed baseline and exercise intestinal permeability tests, determined by the percent ratio of urinary lactulose (5 g) to rhamnose (2 g). Exercise included two 60-min treadmill runs at 70 % of VO2max at 30 °C after ingestion of glutamine (Gln) or placebo (Pla). Plasma levels of endotoxin and TNF-α, along with peripheral blood mononuclear cell (PBMC) protein expression of HSP70 and IκBα, were measured pre- and post-exercise and 2 and 4 h post-exercise. Permeability increased in the Pla trial compared to that at rest (0.06 ± 0.01 vs. 0.02 ± 0.018) and did not increase in the Gln trial. Plasma endotoxin was lower at the 4-h time point in the Gln vs. 4 h in the Pla (6.715 ± 0.046 pg/ml vs. 7.952 ± 1.11 pg/ml). TNF-α was lower 4 h post-exercise in the Gln vs. Pla (1.64 ± 0.09 pg/ml vs. 1.87 ± 0.12 pg/ml). PBMC expression of IkBα was higher 4 h post-exercise in the Gln vs. 4 h in the Pla (1.29 ± 0.43 vs. 0.8892 ± 0.040). HSP70 was higher pre-exercise and 2 h post-exercise in the Gln vs. Pla (1.35 ± 0.21 vs. 1.000 ± 0.000 and 1.65 ± 0.21 vs. 1.27 ± 0.40). Acute oral glutamine supplementation prevents an exercise-induced rise in intestinal permeability and suppresses NF-κB activation in peripheral blood mononuclear cells. PMID:25062931

  18. The effects of acute oral glutamine supplementation on exercise-induced gastrointestinal permeability and heat shock protein expression in peripheral blood mononuclear cells.

    PubMed

    Zuhl, Micah; Dokladny, Karol; Mermier, Christine; Schneider, Suzanne; Salgado, Roy; Moseley, Pope

    2015-01-01

    Chronic glutamine supplementation reduces exercise-induced intestinal permeability and inhibits the NF-κB pro-inflammatory pathway in human peripheral blood mononuclear cells. These effects were correlated with activation of HSP70. The purpose of this paper is to test if an acute dose of oral glutamine prior to exercise reduces intestinal permeability along with activation of the heat shock response leading to inhibition of pro-inflammatory markers. Physically active subjects (N = 7) completed baseline and exercise intestinal permeability tests, determined by the percent ratio of urinary lactulose (5 g) to rhamnose (2 g). Exercise included two 60-min treadmill runs at 70 % of VO2max at 30 °C after ingestion of glutamine (Gln) or placebo (Pla). Plasma levels of endotoxin and TNF-α, along with peripheral blood mononuclear cell (PBMC) protein expression of HSP70 and IκBα, were measured pre- and post-exercise and 2 and 4 h post-exercise. Permeability increased in the Pla trial compared to that at rest (0.06 ± 0.01 vs. 0.02 ± 0.018) and did not increase in the Gln trial. Plasma endotoxin was lower at the 4-h time point in the Gln vs. 4 h in the Pla (6.715 ± 0.046 pg/ml vs. 7.952 ± 1.11 pg/ml). TNF-α was lower 4 h post-exercise in the Gln vs. Pla (1.64 ± 0.09 pg/ml vs. 1.87 ± 0.12 pg/ml). PBMC expression of IkBα was higher 4 h post-exercise in the Gln vs. 4 h in the Pla (1.29 ± 0.43 vs. 0.8892 ± 0.040). HSP70 was higher pre-exercise and 2 h post-exercise in the Gln vs. Pla (1.35 ± 0.21 vs. 1.000 ± 0.000 and 1.65 ± 0.21 vs. 1.27 ± 0.40). Acute oral glutamine supplementation prevents an exercise-induced rise in intestinal permeability and suppresses NF-κB activation in peripheral blood mononuclear cells.

  19. Postmarketing cohort study to assess the safety profile of oral dexketoprofen trometamol for mild to moderate acute pain treatment in primary care.

    PubMed

    Carne, Xavier; Rios, Jose; Torres, Ferran

    2009-10-01

    Recently, new concerns on the safety profile of nonsteroidal anti-inflammatory drugs (NSAIDs) have been raised by the European Medicines Agency (EMEA) and other regulatory authorities. The safety profile of oral dexketoprofen trometamol for the treatment of acute mild to moderate pain of different causes in actual conditions of use in the primary care setting was assessed. A prospective cohort study was designed to evaluate the tolerability of dexketoprofen compared with other commonly prescribed analgesics. Medications were given according to specifications in the summary of product characteristics. The intensity of pain was assessed at baseline and at days 1 and 7 of drug treatment using a 100-mm visual analog scale (VAS). Adverse events (AEs) were recorded. A total of 7,337 patients (median age [IQR] = 46 [33-61] years) were included in the study comparing dexketoprofen (n = 5,429), diclofenac (n = 485), ibuprofen (n = 479), paracetamol (n = 459), metamizole (n = 207), aceclofenac (n = 103), naproxen (n = 74), piroxicam (n = 69) and dexibuprofen (n = 32). The reasons for use were: musculoskeletal disorders, headache, dysmenorrhea and odontalgia. Treatment compliance was very high. Metamizole-paracetamol and dexketoprofen showed the lowest prevalence of AEs (2.7% and 3.6%, respectively), while aceclofenac-diclofenac showed the highest prevalence (8.2%) (P < 0.0001). AEs most frequently observed during NSAID treatment were those related to the gastrointestinal tract (3.5% of subjects, 84% of all AEs), followed by AEs related to the nervous system (0.4%) and skin (0.1%). Most of the reported AEs (91.3%) were of mild to moderate intensity (303 of 332) and only 3.3% of them were considered severe (11 of 332). Risks for gastrointestinal AEs were adjusted for age, gender, history of previous NSAID intake, gastroprotective drugs and reason for prescription. Taking metamizole-paracetamol as the reference group, the odds ratios (OR, 95%) were: 1.30 (0.77-2.19) for

  20. Acute oral administration of a tyrosine and phenylalanine-free amino acid mixture reduces exercise capacity in the heat.

    PubMed

    Tumilty, Les; Davison, Glen; Beckmann, Manfred; Thatcher, Rhys

    2013-06-01

    Acute tyrosine administration is associated with increased exercise capacity in the heat. To explore whether reduced plasma tyrosine and phenylalanine (tyrosine precursor) is associated with impaired exercise capacity in the heat, eight healthy, moderately trained male volunteers, unacclimated to exercise in the heat, performed two tests in a crossover design separated by at least 7 days. In a randomised, double-blind fashion, subjects ingested 500 mL flavoured, sugar-free water containing amino acids [(TYR-free; isoleucine 15 g, leucine 22.5 g, valine 17.5 g, lysine 17.5 g, methionine 5 g, threonine 10 g, tryptophan 2.5 g)] to lower the ratio of plasma tyrosine plus phenylalanine:amino acids competing for blood-brain barrier uptake (CAA), a key determinant of brain uptake, or a balanced mixture (BAL; TYR-free plus 12.5 g tyrosine and 12.5 g phenylalanine). One hour later, subjects cycled to exhaustion at 63 ± 5 % [Formula: see text]O2peak in 30 °C and 60 % relative humidity. Pre-exercise ratio of plasma tyrosine plus phenylalanine:ΣCAA declined 75 ± 5 % from rest in TYR-free (P < 0.001), but was unchanged in BAL (P = 0.061). Exercise time was shorter in TYR-free (59.8 ± 19.0 min vs. 66.2 ± 16.9 min in TYR-free and BAL respectively; P = 0.036). Heart rate (P = 0.298), core (P = 0.134) and skin (P = 0.384) temperature, RPE (P > 0.05) and thermal sensation (P > 0.05) were similar at exhaustion in both trials. These data indicate that acutely depleting plasma catecholamine precursors:ΣCAA is associated with reduced submaximal exercise capacity in the heat.

  1. Toxicity of white phosphorus to waterfowl: acute exposure in mallards

    USGS Publications Warehouse

    Sparling, D.W.; Gustafson, M.; Klein, P.; Karouna-Renier, N.

    1997-01-01

    As part of an effort to understand extensive, white phosphorus (P4)-induced waterfowl mortality at Eagle River Flats, Fort Richardson, Alaska, we conducted a number of acute toxicity tests using penned mallards (Anas platyrhynchos) in 1993 and 1994. The 24-hr median lethal dose (LD50) for P4 dissolved in oil was 6.46 mg/kg in adult males and 6.96 mg/kg in adult females. Although the median lethal doses were not statistically different, the female dose-response curve had a statistically shallower slope than that of males. The LD50 for the ecologically more relevant pelletized form of P4 in adult males was 4.05 mg/kg. In mallards, one mechanism of P4 toxicity caused rapid (3 to 10 hr) mortality and had signs consistent with anoxia. A second, slower acting mechanism resulted in hepatic and renal pathology including extensive fat deposition in the liver and cellular necrosis. White phosphorus accumulated in adipose tissues, but only for a few days.

  2. The prolonged gastrointestinal syndrome in rhesus macaques: the relationship between gastrointestinal, hematopoietic, and delayed multi-organ sequelae following acute, potentially lethal, partial-body irradiation.

    PubMed

    MacVittie, Thomas J; Bennett, Alexander; Booth, Catherine; Garofalo, Michael; Tudor, Gregory; Ward, Amanda; Shea-Donohue, Terez; Gelfond, Daniel; McFarland, Emylee; Jackson, William; Lu, Wei; Farese, Ann M

    2012-10-01

    The dose response relationship for the acute gastrointestinal syndrome following total-body irradiation prevents analysis of the full recovery and damage to the gastrointestinal system, since all animals succumb to the subsequent 100% lethal hematopoietic syndrome. A partial-body irradiation model with 5% bone marrow sparing was established to investigate the prolonged effects of high-dose radiation on the gastrointestinal system, as well as the concomitant hematopoietic syndrome and other multi-organ injury including the lung. Herein, cellular and clinical parameters link acute and delayed coincident sequelae to radiation dose and time course post-exposure. Male rhesus Macaca mulatta were exposed to partial-body irradiation with 5% bone marrow (tibiae, ankles, feet) sparing using 6 MV linear accelerator photons at a dose rate of 0.80 Gy min(-1) to midline tissue (thorax) doses in the exposure range of 9.0 to 12.5 Gy. Following irradiation, all animals were monitored for multiple organ-specific parameters for 180 d. Animals were administered medical management including administration of intravenous fluids, antiemetics, prophylactic antibiotics, blood transfusions, antidiarrheals, supplemental nutrition, and analgesics. The primary endpoint was survival at 15, 60, or 180 d post-exposure. Secondary endpoints included evaluation of dehydration, diarrhea, hematologic parameters, respiratory distress, histology of small and large intestine, lung radiographs, and mean survival time of decedents. Dose- and time-dependent mortality defined several organ-specific sequelae, with LD50/15 of 11.95 Gy, LD50/60 of 11.01 Gy, and LD50/180 of 9.73 Gy for respective acute gastrointestinal, combined hematopoietic and gastrointestinal, and multi-organ delayed injury to include the lung. This model allows analysis of concomitant multi-organ sequelae, thus providing a link between acute and delayed radiation effects. Specific and multi-organ medical countermeasures can be assessed for

  3. Acute systemic toxicity--prospects for tiered testing strategies.

    PubMed

    Botham, P A

    2004-04-01

    After many years of controversy and debate, the LD50 test was finally deleted by the end of 2002. Three alternative animal tests, the Fixed Dose Procedure, the Acute Toxic Class Method and the Up and Down Procedure have been developed which give rise to significant improvements in animal welfare. They have recently undergone revision to improve their scientific performance but more importantly to increase their regulatory acceptance. They can now be used within a strategy for acute toxicity testing for all types of test substances and for all regulatory and in-house purposes. In vitro cytotoxicity tests could be used as adjuncts to these alternative animal tests within the next year or so to improve dose level selection and thus give further modest improvements in the numbers of animals used. However, the total replacement of animal tests requires a considerable amount of further test development, followed by validation, and is at least 10 years away.

  4. Acute D-psicose administration decreases the glycemic responses to an oral maltodextrin tolerance test in normal adults.

    PubMed

    Iida, Tetsuo; Kishimoto, Yuka; Yoshikawa, Yuko; Hayashi, Noriko; Okuma, Kazuhiro; Tohi, Mikiko; Yagi, Kanako; Matsuo, Tatsuhiro; Izumori, Ken

    2008-12-01

    An examination was conducted to verify D-psicose suppressed the elevation of blood glucose and insulin concentration in a dose-dependent manner under the concurrent administration of maltodextrin and D-psicose to healthy humans. Twenty subjects aged 20-39 y, 11 males and 9 females were recruited. A load test of oral maltodextrin was conducted as a randomized single blind study. The subjects took one of five test beverages (7.5 g D-psicose alone, 75 g maltodextrin alone, 75 g maltodextrin +2.5, 5 or 7.5 g D-psicose). Blood was collected before an intake and at 30, 60, 90 and 120 min after an intake. Intervals of administration were at least 1 wk. The load test with 75 g maltodextrin showed significant suppressions of the elevation of blood glucose and insulin concentration under the doses of 5 g or more D-psicose with dose dependency. An independent administration of 7.5 g D-psicose had no influence on blood glucose or insulin concentration. D-Psicose is considered efficacious in the suppression of the elevation of blood glucose concentration after eating in humans.

  5. 'She's manipulative and he's right off': a critical analysis of psychiatric nurses' oral and written language in the acute inpatient setting.

    PubMed

    Hamilton, Bridget; Manias, Elizabeth

    2006-06-01

    Remarks such as 'she's manipulative' and 'he's right off' are familiar to psychiatric nurses. This paper critiques the language nurses use in acute inpatient psychiatry services, highlighting the diverse discourses implicated in nurses' writing and speaking about patients. Based on a review of the literature, this paper examines ethnographic studies and discourse analyses of psychiatric nurses' oral and written language. A prominent debate in the literature surrounds nurses' use of standardized language, which is the use of set terms for symptoms and nursing activities. This review of spoken descriptions of patients highlights nurses' use of informal and local descriptions, incorporating elements of moral judgement, common sense language and empathy. Research into written accounts in patient files and records show nurses' use of objectifying language, the dominance of medicine and the emergence of the language of bureaucracy in health services. Challenges to the language of psychiatry and psychiatric nursing arise from fields as diverse as bioscience, humanism and social theory. Authors who focus on the relationship between language, power and the discipline of nursing disagree in regard to their analysis of particular language as a constructive exercise of power by nurses. Thus, particular language is in some instances endorsed and in other instances censured, by nurses in research and practice. In this paper, a Foucauldian analysis provides further critique of taken-for-granted practices of speech and writing. Rather than censoring language, we recommend that nurses, researchers and educators attend to nurses' everyday language and explore what it produces for nurses, patients and society.

  6. Adverse Effects of Oral Nonselective and cyclooxygenase-2-Selective NSAIDs on Hospitalization for Acute Kidney Injury: A Nested Case-Control Cohort Study.

    PubMed

    Chou, Chia-I; Shih, Chia-Jen; Chen, Yung-Tai; Ou, Shuo-Ming; Yang, Chih-Yu; Kuo, Shu-Chen; Chu, Dachen

    2016-03-01

    To investigate the association between the use of nonselective or cyclooxygenase (COX)-2-selective nonsteroidal antiinflammatory drugs (NSAIDs) and risk of acute kidney injury (AKI) in a general Asian population. We conducted an observational, nationwide, nested case-control cohort study using Taiwan's National Health Insurance Research Database between 2010 and 2012. AKI cases were defined as hospitalization with a principle diagnosis of AKI. Each case was matched to 4 randomly selected controls based on age, sex, and the month and year of cohort entry. Odds ratios (ORs) were used to demonstrate the association between hospitalization for AKI and current, recent, or past use of an oral NSAID. During the study period, we identified 6199 patients with AKI and 24,796 matched controls. Overall, current users (adjusted OR 2.73, 95% confidence interval [CI] 2.28-3.28) and recent users (adjusted OR 1.17, 95% CI 1.01-1.35) were associated with increased risk of hospitalization for AKI. The risk was also similar for nonselective NSAIDs. However, neither current nor recent use of COX-2 inhibitors was significantly associated with AKI events. Our study supported that the initiation of nonselective NSAIDs rather than COX-2 inhibitors is associated with an increased risk of AKI requiring hospitalization. Future randomized trials are needed to elucidate these findings. PMID:26945352

  7. A tutorial for analysing the cost-effectiveness of alternative methods for assessing chemical toxicity: the case of acute oral toxicity prediction.

    PubMed

    Norlen, Hedvig; Worth, Andrew P; Gabbert, Silke

    2014-05-01

    Compared with traditional animal methods for toxicity testing, in vitro and in silico methods are widely considered to permit a more cost-effective assessment of chemicals. However, how to assess the cost-effectiveness of alternative methods has remained unclear. This paper offers a user-oriented tutorial for applying cost-effectiveness analysis (CEA) to alternative (non-animal) methods. The purpose is to illustrate how CEA facilitates the identification of the alternative method, or the combination of methods, that offers the highest information gain per unit of cost. We illustrate how information gains and costs of single methods and method combinations can be assessed. By using acute oral toxicity as an example, we apply CEA to a set of four in silico methods (ToxSuite, TOPKAT, TEST, ADMET Predictor), one in vitro method (the 3T3 Neutral Red Uptake cytotoxicity assay), and various combinations of these methods. Our results underline that in silico tools are more cost-effective than the in vitro test. Battery combinations of alternative methods, however, do not necessarily outperform single methods, because additional information gains from the battery are easily outweighed by additional costs. PMID:24901905

  8. 'She's manipulative and he's right off': a critical analysis of psychiatric nurses' oral and written language in the acute inpatient setting.

    PubMed

    Hamilton, Bridget; Manias, Elizabeth

    2006-06-01

    Remarks such as 'she's manipulative' and 'he's right off' are familiar to psychiatric nurses. This paper critiques the language nurses use in acute inpatient psychiatry services, highlighting the diverse discourses implicated in nurses' writing and speaking about patients. Based on a review of the literature, this paper examines ethnographic studies and discourse analyses of psychiatric nurses' oral and written language. A prominent debate in the literature surrounds nurses' use of standardized language, which is the use of set terms for symptoms and nursing activities. This review of spoken descriptions of patients highlights nurses' use of informal and local descriptions, incorporating elements of moral judgement, common sense language and empathy. Research into written accounts in patient files and records show nurses' use of objectifying language, the dominance of medicine and the emergence of the language of bureaucracy in health services. Challenges to the language of psychiatry and psychiatric nursing arise from fields as diverse as bioscience, humanism and social theory. Authors who focus on the relationship between language, power and the discipline of nursing disagree in regard to their analysis of particular language as a constructive exercise of power by nurses. Thus, particular language is in some instances endorsed and in other instances censured, by nurses in research and practice. In this paper, a Foucauldian analysis provides further critique of taken-for-granted practices of speech and writing. Rather than censoring language, we recommend that nurses, researchers and educators attend to nurses' everyday language and explore what it produces for nurses, patients and society. PMID:16643343

  9. In vitro growth-inhibitory effect of plant-derived extracts and compounds against Paenibacillus larvae and their acute oral toxicity to adult honey bees.

    PubMed

    Flesar, Jaroslav; Havlik, Jaroslav; Kloucek, Pavel; Rada, Vojtech; Titera, Dalibor; Bednar, Michal; Stropnicky, Michal; Kokoska, Ladislav

    2010-09-28

    In total, 26 natural compounds of various chemical classes (flavonoids, alkaloids, terpenoids) and 19 crude extracts from selected plants were tested in vitro for antibacterial activity against three strains of P. larvae, the causal agent of American Foulbrood Disease of honey bees (AFB) by the broth microdilution method. Among the individual substances, sanguinarine (MIC 4 microg/ml), followed by thymoquinone, capsaicin, trans-2-hexenal and nordihydroguaiaretic acid (MIC 4-32 microg/ml) possessed the strongest antibacterial effect. In case of extracts, common hop (Humulus lupulus L.) and myrtle (Myrtus communis L.) methanolic-dichloromethane extracts exhibited the highest growth-inhibitory effect with MICs ranging from 2 to 8 microg/ml. Acute oral toxicity of the most active natural products was determined on adult honey bees, showing them as non-toxic at concentrations as high as 100 microg peer bee. Our study leads to identification of highly potent natural products effective against AFB in vitro with very low MICs compared to those reported in literature, low toxicity to adult honey bees and commercial availability suggesting them as perspective, low cost and consumer-acceptable agents for control of AFB.

  10. Prediction of Acute Radiation Mucositis using an Oral Mucosal Dose Surface Model in Carbon Ion Radiotherapy for Head and Neck Tumors

    PubMed Central

    Musha, Atsushi; Shimada, Hirofumi; Shirai, Katsuyuki; Saitoh, Jun-ichi; Yokoo, Satoshi; Chikamatsu, Kazuaki; Ohno, Tatsuya; Nakano, Takashi

    2015-01-01

    Purpose To evaluate the dose-response relationship for development of acute radiation mucositis (ARM) using an oral mucosal dose surface model (OMDS-model) in carbon ion radiotherapy (C-ion RT) for head and neck tumors. Methods Thirty-nine patients receiving C-ion RT for head and neck cancer were evaluated for ARM (once per week for 6 weeks) according to the Common Terminology Criteria for Adverse Events (CTCAE), version 4.0, and the Radiation Therapy Oncology Group (RTOG) scoring systems. The irradiation schedule typically used was 64 Gy [relative biological effectiveness (RBE)] in 16 fractions for 4 weeks. Maximum point doses in the palate and tongue were compared with ARM in each patient. Results The location of the ARM coincided with the high-dose area in the OMDS-model. There was a clear dose-response relationship between maximum point dose and ARM grade assessed using the RTOG criteria but not the CTCAE. The threshold doses for grade 2–3 ARM in the palate and tongue were 43.0 Gy(RBE) and 54.3 Gy(RBE), respectively. Conclusions The OMDS-model was useful for predicting the location and severity of ARM. Maximum point doses in the model correlated well with grade 2–3 ARM. PMID:26512725

  11. Efficacy of a Solution Composed by Verbascoside, Polyvinylpyrrolidone (PVP) and Sodium Hyaluronate in the Treatment of Chemotherapy-induced Oral Mucositis in Children With Acute Lymphoblastic Leukemia.

    PubMed

    Bardellini, Elena; Amadori, Francesca; Schumacher, Richard Fabian; D'Ippolito, Carmelita; Porta, Fulvio; Majorana, Alessandra

    2016-10-01

    The aim of this study was to assess the efficacy of a solution composed by verbascoside, polyvinylpyrrolidone, and sodium hyaluronate (Mucosyte) in the treatment of chemotherapy-induced oral mucositi (OM). Patients between 5 and 18 years receiving chemotherapy for acute lymphoblastic leukemia and with OM grade 1 or 2 were randomized in group A (treated with Mucosyte, 3 mouthwashes/d per 8 d) and group B (treated with placebo, ie, an inert water-based solution, 3 mouthwashes/d per 8 d). The OM scoring was performed at day 1 (diagnosis of OM-T0), after 3 days of treatment (T1), and at day 8 (T2). Pain was evaluated through the visual analog scale with the same timing of OM measurement. A total of 56 patients were included (28 patients per group). Group A experienced a statistically significant decline of OM at T2 (P=0.0038); a statistically significant difference in pain reduction between 2 groups both at T1 and at T2 (P<0.005) was observed. The use of Mucosyte mouthwashes in children with chemotherapy-induced OM may be recommended as supportive therapy. PMID:27571124

  12. Comparative study of genotoxicity and tissue distribution of nano and micron sized iron oxide in rats after acute oral treatment

    SciTech Connect

    Singh, Shailendra Pratap; Rahman, M.F.; Murty, U.S.N.; Mahboob, M.; Grover, Paramjit

    2013-01-01

    Though nanomaterials (NMs) are being utilized worldwide, increasing use of NMs have raised concerns over their safety to human health and environment. Iron oxide (Fe{sub 2}O{sub 3}) NMs have important applications. The aim of this study was to assess the genotoxicity of Fe{sub 2}O{sub 3}-30 nm and Fe{sub 2}O{sub 3}-bulk in female Wistar rats. Fe{sub 2}O{sub 3}-30 nm was characterized by using transmission electron microscopy, dynamic light scattering, laser Doppler velocimetry and surface area analysis. The rats were treated orally with the single doses of 500, 1000, 2000 mg/kg bw of Fe{sub 2}O{sub 3}-30 nm and Fe{sub 2}O{sub 3} –bulk. The genotoxicity was evaluated at 6, 24, 48 and 72 h by the comet assay in leucocytes, 48 and 72 h by micronucleus test (MNT) in peripheral blood cells, 18 and 24 h by chromosomal aberration (CA) assay and 24 and 48 h by MNT in bone marrow cells. The biodistribution of iron (Fe) was carried out at 6, 24, 48 and 72 h after treatment in liver, spleen, kidney, heart, brain, bone marrow, urine and feces by using atomic absorption spectrophotometry. The % tail DNA, frequencies of micronuclei and CAs were statistically insignificant (p > 0.05) at all doses. These results suggest that Fe{sub 2}O{sub 3}-30 nm and Fe{sub 2}O{sub 3}-bulk was not genotoxic at the doses tested. Bioavailability of Fe was size and dose dependent in all the tissues from the groups exposed to Fe{sub 2}O{sub 3}-30 nm. Fe{sub 2}O{sub 3} NMs were able to enter in the organs and the rats are biocompatible with much higher concentration of Fe. However, the accumulated Fe did not cause significant genotoxicity. This study provides additional knowledge about the toxicology of Fe{sub 2}O{sub 3} NMs. -- Highlights: ► Fe{sub 2}O{sub 3}-30 nm and Fe{sub 2}O{sub 3}-bulk were orally administered to rats with single doses. ► The nano and bulk Fe{sub 2}O{sub 3} showed insignificant results with MNT, comet and CA assays. ► The bulk was excreted via feces whereas the NMs

  13. Fusidic Acid: A Bacterial Elongation Factor Inhibitor for the Oral Treatment of Acute and Chronic Staphylococcal Infections.

    PubMed

    Fernandes, Prabhavathi

    2016-01-01

    Fusidic acid is an oral antistaphylococcal antibiotic that has been used in Europe for more than 40 years to treat skin infections as well as chronic bone and joint infections. It is a steroidal antibiotic and the only marketed member of the fusidane class. Fusidic acid inhibits protein synthesis by binding EF-G-GDP, which results in the inhibition of both peptide translocation and ribosome disassembly. It has a novel structure and novel mode of action and, therefore, there is little cross-resistance with other known antibiotics. Many mutations can occur in the FusA gene that codes for EF-G, and some of these mutations can result in high-level resistance (minimum inhibitory concentration [MIC] > 64 mg/L), whereas others result in biologically unfit staphylococci that require compensatory mutations to survive. Low-level resistance (<8 mg/L) is more common and is mediated by fusB, fusC, and fusD genes that code for small proteins that protect EF-G-GDP from binding fusidic acid. The genes for these proteins are spread by plasmids and can be selected mostly by topical antibiotic use. Reports of resistance have led to combination use of fusidic acid with rifampin, which is superseded by the development of a new dosing regimen for fusidic acid that can be used in monotherapy. It consists of a front-loading dose to decrease the potential for resistance development followed by a maintenance dose. This dosing regimen is now being used in clinical trials in the United States for skin and refractory bone and joint infections. PMID:26729758

  14. NMR-based metabonomic study of the sub-acute toxicity of titanium dioxide nanoparticles in rats after oral administration

    NASA Astrophysics Data System (ADS)

    Bu, Qian; Yan, Guangyan; Deng, Pengchi; Peng, Feng; Lin, Hongjun; Xu, Youzhi; Cao, Zhixing; Zhou, Tian; Xue, Aiqin; Wang, Yanli; Cen, Xiaobo; Zhao, Ying-Lan

    2010-03-01

    As titanium dioxide nanoparticles (TiO2 NPs) are widely used commercially, their potential toxicity on human health has attracted particular attention. In the present study, the oral toxicological effects of TiO2 NPs (dosed at 0.16, 0.4 and 1 g kg - 1, respectively) were investigated using conventional approaches and metabonomic analysis in Wistar rats. Serum chemistry, hematology and histopathology examinations were performed. The urine and serum were investigated by 1H nuclear magnetic resonance (NMR) using principal components and partial least squares discriminant analysis. The metabolic signature of urinalysis in TiO2 NP-treated rats showed increases in the levels of taurine, citrate, hippurate, histidine, trimethylamine-N-oxide (TMAO), citrulline, α-ketoglutarate, phenylacetylglycine (PAG) and acetate; moreover, decreases in the levels of lactate, betaine, methionine, threonine, pyruvate, 3-D-hydroxybutyrate (3-D-HB), choline and leucine were observed. The metabonomics analysis of serum showed increases in TMAO, choline, creatine, phosphocholine and 3-D-HB as well as decreases in glutamine, pyruvate, glutamate, acetoacetate, glutathione and methionine after TiO2 NP treatment. Aspartate aminotransferase (AST), creatine kinase (CK) and lactate dehydrogenase (LDH) were elevated and mitochondrial swelling in heart tissue was observed in TiO2 NP-treated rats. These findings indicate that disturbances in energy and amino acid metabolism and the gut microflora environment may be attributable to the slight injury to the liver and heart caused by TiO2 NPs. Moreover, the NMR-based metabolomic approach is a reliable and sensitive method to study the biochemical effects of nanomaterials.

  15. Oral caffeine administration ameliorates acute colitis by suppressing chitinase 3-like 1 expression in intestinal epithelial cells

    PubMed Central

    Lee, In-Ah; Low, Daren; Kamba, Alan; Llado, Victoria; Mizoguchi, Emiko

    2013-01-01

    Background The initial trigger of inflammatory bowel disease (IBD) can be partly attributed towards the interaction and invasion of intestinal epithelial cells (IECs) and submucosal compartments. Identifying safe and economical methods to block these interactions may help prevent the onset of early colitis. Chitinase 3-like 1 is an inducible host protein that facilitates bacterial attachment and invasion on/into IECs. Therefore, we test the hypothesis of inhibiting CHI3L1 using the pan-chitinase inhibitor caffeine to reduce the likelihood of early colitis onset. Methods IEC lines were treated with caffeine (2.5 mM or 5 mM) and analyzed for CHI3L1 expression and the impact on bacterial invasion. In vivo, mice were treated with 2.5 mM caffeine and induced with 3.5% dextran sulfate sodium (DSS)-mediated colitis and subsequently analyzed colitis development. Results In vitro, caffeine treatment in IEC lines down-regulated CHI3L1 mRNA expression, which resulted in the reduction of bacterial invasion in a caffeine dose-dependent manner. In vivo, mice treated with caffeine displayed delayed response towards DSS-induced colitis, characterized by lower body weight loss, clinical and histological scores. Bacterial translocation into other organs and pro-inflammatory cytokines production were also reduced in the caffeine-treated mice with DSS-induced colitis. Caffeine treatment also resulted in the loss of CHI3L1-associated AKT signaling pathway activation both in vitro and in vivo. Conclusion Development of acute colitis is reduced upon caffeine treatment. The mechanism involves the down-regulation of CHI3L1 expression and its associated bacterial interaction effect. Therefore caffeine is proposed as a safe and economical candidate for successful IBD management. PMID:23925589

  16. Hydroethanolic extract of Baccharis trimera promotes gastroprotection and healing of acute and chronic gastric ulcers induced by ethanol and acetic acid.

    PubMed

    Dos Reis Lívero, Francislaine Aparecida; da Silva, Luisa Mota; Ferreira, Daniele Maria; Galuppo, Larissa Favaretto; Borato, Debora Gasparin; Prando, Thiago Bruno Lima; Lourenço, Emerson Luiz Botelho; Strapasson, Regiane Lauriano Batista; Stefanello, Maria Élida Alves; Werner, Maria Fernanda de Paula; Acco, Alexandra

    2016-09-01

    Ethanol is a psychoactive substance highly consumed around the world whose health problems include gastric lesions. Baccharis trimera is used in folk medicine for the treatment of gastrointestinal disorders. However, few studies have evaluated its biological and toxic effects. To validate the popular use of B. trimera and elucidate its possible antiulcerogenic and cytotoxic mechanisms, a hydroethanolic extract of B. trimera (HEBT) was evaluated in models of gastric lesions. Rats and mice were used to evaluate the protective and antiulcerogenic effects of HEBT on gastric lesions induced by ethanol, acetic acid, and chronic ethanol consumption. The effects of HEBT were also evaluated in a pylorus ligature model and on gastrointestinal motility. The LD50 of HEBT in mice was additionally estimated. HEBT was analyzed by nuclear magnetic resonance, and a high-performance liquid chromatography fingerprint analysis was performed. Oral HEBT administration significantly reduced the lesion area and the oxidative stress induced by acute and chronic ethanol consumption. However, HEBT did not protect against gastric wall mucus depletion and did not alter gastric secretory volume, pH, or total acidity in the pylorus ligature model. Histologically, HEBT accelerated the healing of chronic gastric ulcers in rats, reflected by contractions of the ulcer base. Flavonoids and caffeoylquinic acids were detected in HEBT, which likely contributed to the therapeutic efficacy of HEBT, preventing or reversing ethanol- and acetic acid-induced ulcers, respectively. HEBT antiulcerogenic activity may be partially attributable to the inhibition of free radical generation and subsequent prevention of lipid peroxidation. Our results indicate that HEBT has both gastroprotective and curative activity in animal models, with no toxicity. PMID:27314669

  17. Complete Protection against Pneumonic and Bubonic Plague after a Single Oral Vaccination

    PubMed Central

    Derbise, Anne; Hanada, Yuri; Khalifé, Manal; Carniel, Elisabeth; Demeure, Christian E.

    2015-01-01

    Background No efficient vaccine against plague is currently available. We previously showed that a genetically attenuated Yersinia pseudotuberculosis producing the Yersinia pestis F1 antigen was an efficient live oral vaccine against pneumonic plague. This candidate vaccine however failed to confer full protection against bubonic plague and did not produce F1 stably. Methodology/Principal Findings The caf operon encoding F1 was inserted into the chromosome of a genetically attenuated Y. pseudotuberculosis, yielding the VTnF1 strain, which stably produced the F1 capsule. Given orally to mice, VTnF1 persisted two weeks in the mouse gut and induced a high humoral response targeting both F1 and other Y. pestis antigens. The strong cellular response elicited was directed mostly against targets other than F1, but also against F1. It involved cells with a Th1—Th17 effector profile, producing IFNγ, IL-17, and IL-10. A single oral dose (108 CFU) of VTnF1 conferred 100% protection against pneumonic plague using a high-dose challenge (3,300 LD50) caused by the fully virulent Y. pestis CO92. Moreover, vaccination protected 100% of mice from bubonic plague caused by a challenge with 100 LD50 Y. pestis and 93% against a high-dose infection (10,000 LD50). Protection involved fast-acting mechanisms controlling Y. pestis spread out of the injection site, and the protection provided was long-lasting, with 93% and 50% of mice surviving bubonic and pneumonic plague respectively, six months after vaccination. Vaccinated mice also survived bubonic and pneumonic plague caused by a high-dose of non-encapsulated (F1-) Y. pestis. Significance VTnF1 is an easy-to-produce, genetically stable plague vaccine candidate, providing a highly efficient and long-lasting protection against both bubonic and pneumonic plague caused by wild type or un-encapsulated (F1-negative) Y. pestis. To our knowledge, VTnF1 is the only plague vaccine ever reported that could provide high and durable protection

  18. Nonadherence to Oral Mercaptopurine and Risk of Relapse in Hispanic and Non-Hispanic White Children With Acute Lymphoblastic Leukemia: A Report From the Children's Oncology Group

    PubMed Central

    Bhatia, Smita; Landier, Wendy; Shangguan, Muyun; Hageman, Lindsey; Schaible, Alexandra N.; Carter, Andrea R.; Hanby, Cara L.; Leisenring, Wendy; Yasui, Yutaka; Kornegay, Nancy M.; Mascarenhas, Leo; Ritchey, A. Kim; Casillas, Jacqueline N.; Dickens, David S.; Meza, Jane; Carroll, William L.; Relling, Mary V.; Wong, F. Lennie

    2012-01-01

    Purpose Systemic exposure to mercaptopurine (MP) is critical for durable remissions in children with acute lymphoblastic leukemia (ALL). Nonadherence to oral MP could increase relapse risk and also contribute to inferior outcome in Hispanics. This study identified determinants of adherence and described impact of adherence on relapse, both overall and by ethnicity. Patients and Methods A total of 327 children with ALL (169 Hispanic; 158 non-Hispanic white) participated. Medication event-monitoring system caps recorded date and time of MP bottle openings. Adherence rate, calculated monthly, was defined as ratio of days of MP bottle opening to days when MP was prescribed. Results After 53,394 person-days of monitoring, adherence declined from 94.7% (month 1) to 90.2% (month 6; P < .001). Mean adherence over 6 months was significantly lower among Hispanics (88.4% v 94.8%; P < .001), patients age ≥ 12 years (85.8% v 93.1%; P < .001), and patients from single-mother households (80.6% v 93.1%; P = .001). A progressive increase in relapse was observed with decreasing adherence (reference: adherence ≥ 95%; 94.9% to 90%: hazard ratio [HR], 4.1; 95% CI,1.2 to 13.5; P = .02; 89.9% to 85%: HR, 4.0; 95% CI, 1.0 to 15.5; P = .04; < 85%: HR. 5.7; 95% CI, 1.9 to 16.8; P = .002). Cumulative incidence of relapse (± standard deviation) was higher among Hispanics (16.5% ± 4.0% v 6.3% ± 2.2%; P = .02). Association between Hispanic ethnicity and relapse (HR, 2.6; 95% CI, 1.1 to 6.1; P = .02) became nonsignificant (HR, 1.8; 95% CI, 0.6 to 5.2; P = .26) after adjusting for adherence and socioeconomic status. At adherence rates ≥ 90%, Hispanics continued to demonstrate higher relapse, whereas at rates < 90%, relapse risk was comparable to that of non-Hispanic whites. Conclusion Lower adherence to oral MP increases relapse risk. Ethnic difference in relapse risk differs by level of adherence—an observation currently under investigation. PMID:22564992

  19. Towards Global QSAR Model Building for Acute Toxicity: Munro Database Case Study

    PubMed Central

    Chavan, Swapnil; Nicholls, Ian A.; Karlsson, Björn C. G.; Rosengren, Annika M.; Ballabio, Davide; Consonni, Viviana; Todeschini, Roberto

    2014-01-01

    A series of 436 Munro database chemicals were studied with respect to their corresponding experimental LD50 values to investigate the possibility of establishing a global QSAR model for acute toxicity. Dragon molecular descriptors were used for the QSAR model development and genetic algorithms were used to select descriptors better correlated with toxicity data. Toxic values were discretized in a qualitative class on the basis of the Globally Harmonized Scheme: the 436 chemicals were divided into 3 classes based on their experimental LD50 values: highly toxic, intermediate toxic and low to non-toxic. The k-nearest neighbor (k-NN) classification method was calibrated on 25 molecular descriptors and gave a non-error rate (NER) equal to 0.66 and 0.57 for internal and external prediction sets, respectively. Even if the classification performances are not optimal, the subsequent analysis of the selected descriptors and their relationship with toxicity levels constitute a step towards the development of a global QSAR model for acute toxicity. PMID:25302621

  20. Comparison of early exercise treadmill test and oral dipyridamole thallium-201 tomography for the identification of jeopardized myocardium in patients receiving thrombolytic therapy for acute Q-wave myocardial infarction

    SciTech Connect

    Jain, A.; Hicks, R.R.; Frantz, D.M.; Myers, G.H.; Rowe, M.W. )

    1990-09-01

    Thrombolytic therapy has become the treatment of choice for patients with acute myocardial infarction. Researchers are not yet able to identify patients with salvage of myocardium who are at risk for recurrent coronary events. Thus, a prospective trial was performed in 46 patients with myocardial infarction (28 anterior and 18 inferior) who received thrombolytic therapy to determine if early thallium tomography (4.7 days) using oral dipyridamole would identify more patients with residual ischemia than early symptom-limited exercise treadmill tests (5.5 days). There were no complications during the exercise treadmill tests or oral dipyridamole thallium tomography. Mean duration of exercise was 11 +/- 3 minutes and the peak heart rate was 126 beats/min. Thirteen patients had positive test results. After oral dipyridamole all patients had abnormal thallium uptake on the early images. Positive scans with partial filling in of the initial perfusion defects were evident in 34 patients. Angina developed in 13 patients and was easily reversed with intravenous aminophylline. Both symptom-limited exercise treadmill tests and thallium tomography using oral dipyridamole were safely performed early after myocardial infarction in patients receiving thrombolytic therapy. Thallium tomography identified more patients with residual ischemia than exercise treadmill tests (74 vs 28%). Further studies are required to determine whether the results of thallium tomography after oral dipyridamole can be used to optimize patient management and eliminate the need for coronary angiography in some patients.

  1. Treponema parvum sp. nov., a small, glucoronic or galacturonic acid-dependent oral spirochaete from lesions of human periodontitis and acute necrotizing ulcerative gingivitis.

    PubMed

    Wyss, C; Dewhirst, F E; Gmür, R; Thurnheer, T; Xue, Y; Schüpbach, P; Guggenheim, B; Paster, B J

    2001-05-01

    Small oral spirochaetes with a strict dependence on either glucuronic acid (GluA) or galacturonic acid (GalA) were isolated from European patients with periodontitis and from Chinese patients with either gingivitis or acute necrotizing ulcerative gingivitis (ANUG). Thirteen such isolates were similar phenotypically to Treponema pectinovorum ATCC 33768T and this classification was confirmed by 16S rRNA sequencing. However, four isolates differed from T. pectinovorum by their small cell size, by a prominent beta-glucuronidase activity, by a distinct protein and antigen profile, by an inability to grow on pectin as sole source of carbohydrate and by a markedly enhanced growth rate when supplied with a second carbohydrate (L-arabinose, D-galactose, D-glucose, D-fructose, D-mannitol, D-mannose, pectin, D-ribose or D-xylose) in addition to the essential GluA/GalA. By 16S rRNA sequencing these four isolates clustered in the recently described phylotype 'Smibert-2'. T. pectinovorum (14 strains) and 'Smibert-2' (four isolates with beta-glucuronidase activity) could each be subdivided into two serotypes based on immunoblot reactivity with two mAbs. Representatives of the two groups, including T. pectinovorum ATCC 33768T, showed a 1:2:1-type periplasmic flagellar arrangement. 'Smibert-2' is described as a novel species, Treponema parvum sp. nov., with isolate OMZ 833T (= ATCC 700770T) proposed as the type strain and OMZ 842 (= ATCC 700773) as reference strain for a second serotype.

  2. The oral glucose tolerance test for the diagnosis of diabetes mellitus in patients during acute coronary syndrome hospitalization: a meta-analysis of diagnostic test accuracy

    PubMed Central

    2012-01-01

    Background The appropriateness of the routine performance of an oral glucose tolerance test (OGTT) to screen for diabetes mellitus (DM) during acute coronary syndrome hospitalization is still under debate. Methods A systematic search of databases (MEDLINE [1985 to March 2012], EMBASE [1985 to March 2012]) was conducted. All prospective cohort studies assessing the accuracy or reproducibility of an OGTT in ACS or non-ACS individuals were included. A bivariate model was used to calculate the pooled sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR). Heterogeneity was explored using subgroup analysis and meta-regression. Results Fifteen studies with 8,027 participants were included (10 ACS and 5 non-ACS studies). The pooled results on SEN, SPE, PLR, NLR, and DOR were 0.70 (95% CI, 0.60-0.78), 0.91 (95% CI, 0.86-0.94), 7.6 (95% CI, 4.9-11.7), 0.33 (95% CI, 0.25-0.45), and 23 (95% CI, 12–41), respectively. The OGTT has a slightly lower SPE in diagnosing DM in ACS than in non-ACS patients (0.86 [95% CI 0.81-0.92] versus 0.95 [95% CI 0.93-0.98], p<0.01), while the SEN values are comparable (0.71 [95% CI 0.60-0.82] versus 0.67 [95% CI 0.54-0.81], p=0.43). After adjusting the interval between repeated tests and age, the meta-regression did not show a difference in DOR between ACS and non-ACS studies. Conclusions Despite the discrepancy in the interval between the two OGTTs, performing an OGTT in patients with ACS provides accuracy that is similar to that in in non-ACS patients. It is reasonable to screen patients hospitalized for ACS for previously undiagnosed DM using an OGTT. PMID:23270530

  3. Posaconazole oral suspension primary prophylaxis in acute leukemia and allogeneic stem cell transplant patients: can it be used without measurement of plasma concentration?

    PubMed

    Girmenia, Corrado; Annino, Luciana; Mariotti, Benedetta; Fanci, Rosa; Minotti, Clara; Spadea, Antonio; Carotti, Alessandra; Piedimonte, Monica; Chierichini, Anna; Cerchiara, Elisabetta; Caselli, Desiree; Cupelli, Luca; Arcioni, Francesco; Bertaina, Alice; Ribersani, Michela; Proia, Anna; Mengarelli, Andrea; Perriello, Vincenzo; Torelli, Giovanni Fernando; Di Gioia, Massimo; Del Principe, Maria Ilaria; Cassetta, Maria Iris; Fallani, Stefania; Novelli, Andrea

    2016-07-01

    Posaconazole oral suspension (PCZ-susp) can display a variable degree of inter and intra-individual absorption. However, there is no agreement on the need of plasma-posaconazole-concentration (PPC) monitoring as a routine practice in patients receiving PCZ-susp. In this prospective, multicenter study we evaluated the variability of PPCs in hematologic patients receiving PCZ-susp prophylaxis with the aim to define conditions at different risk of subtherapeutic PPCs. Overall, 103 acute leukemia (AL) patients submitted to intensive chemotherapy (115 courses) and 46 allogeneic stem cell transplant (allo-SCT) recipients (47 courses) receiving PCZ-susp prophylaxis were considered. The adequacy of PPC pattern after the steady state (≥day 7 of treatment) in courses with two or more PPC measurements was defined as follows: inadequate pattern: PPC < 0.5 mcg/ml at least once; borderline pattern: PPC always ≥0.5mcg/ml but < 0.7 mcg/ml at least once; adequate pattern: PPC always ≥0.7 mcg/ml. The PPC pattern was evaluable in 83 and 37 AL and allo-SCT patients, respectively. It was adequate, borderline and inadequate in 63.9%, 14.5%, and 21.7% of courses, respectively, in AL, and in 62.2%, 10.8%, and 27.0% of courses, respectively, in allo-SCT. In both groups, an inadequate PPC pattern was associated with the development of diarrhea. In absence of diarrhea, the probability of an inadequate PPC pattern was 11.9% in AL and 17.2% in allo-SCT patients. PCZ-susp might be used without stringent need of PPC monitoring in patients without diarrhea.

  4. The Hematopoietic Syndrome of the Acute Radiation Syndrome in Rhesus Macaques: A Systematic Review of the Lethal Dose Response Relationship.

    PubMed

    MacVittie, Thomas J; Farese, Ann M; Jackson, William

    2015-11-01

    Well characterized animal models that mimic the human response to potentially lethal doses of radiation are required to assess the efficacy of medical countermeasures under the criteria of the U.S. Food and Drug Administration "animal rule." Development of a model requires the determination of the radiation dose response relationship and time course of mortality and morbidity across the hematopoietic acute radiation syndrome. The nonhuman primate, rhesus macaque, is a relevant animal model that may be used to determine the efficacy of medical countermeasures to mitigate major signs of morbidity and mortality at selected lethal doses of total body irradiation. A systematic review of relevant studies that determined the dose response relationship for the hematopoietic acute radiation syndrome in the rhesus macaque relative to radiation quality, dose rate, and exposure uniformity has never been performed. The selection of data cohorts was made from the following sources: Ovid Medline (1957-present), PubMed (1954-present), AGRICOLA (1976-present), Web of Science (1954-present), and U.S. HHS REPORT (2002 to present). The following terms were used: Rhesus, total body-irradiation, total body x irradiation, TBI, irradiation, gamma radiation, hematopoiesis, LD50/60, Macaca mulatta, whole-body irradiation, nonhuman primate, NHP, monkey, primates, hematopoietic radiation syndrome, mortality, and nuclear radiation. The reference lists of all studies, published and unpublished, were reviewed for additional studies. The total number of hits across all search sites was 3,001. There were a number of referenced, unpublished, non-peer reviewed government reports that were unavailable for review. Fifteen studies, 11 primary (n = 863) and four secondary (n = 153) studies [n = 1,016 total nonhuman primates (NHP), rhesus Macaca mulatta] were evaluated to provide an informative and consistent review. The dose response relationships (DRRs) were determined for uniform or non-uniform total

  5. Differential cytotoxicity of long-chain bases for human oral gingival epithelial keratinocytes, oral fibroblasts, and dendritic cells

    PubMed Central

    Poulsen, Christopher; Mehalick, Leslie A.; Fischer, Carol L.; Lanzel, Emily A.; Bates, Amber M.; Walters, Katherine S.; Cavanaugh, Joseph E.; Guthmiller, Janet M.; Johnson, Georgia K.; Wertz, Philip W.; Brogden, Kim A.

    2015-01-01

    Long-chain bases are present in the oral cavity. Previously we determined that sphingosine, dihydrosphingosine, and phytosphingosine have potent antimicrobial activity against oral pathogens. Here, we determined the cytotoxicities of long-chain bases for oral cells, an important step in considering their potential as antimicrobial agents for oral infections. This information would clearly help in establishing prophylactic or therapeutic doses. To assess this, human oral gingival epithelial (GE) keratinocytes, oral gingival fibroblasts (GF), and dendritic cells (DC) were exposed to 10.0-640.0 µM long-chain bases and glycerol monolaurate (GML). The effects of long-chain bases on cell metabolism (conversion of resazurin to resorufin), membrane permeability (uptake of propridium iodide or SYTOX-Green), release of cellular contents (LDH), and cell morphology (confocal microscopy) were all determined. GE keratinocytes were more resistant to long-chain bases as compared to GF and DC, which were more susceptible. For DC, 0.2 to 10.0 µM long-chain bases and GML were not cytotoxic; 40.0 to 80.0 µM long-chain bases, but not GML, were cytotoxic; and 80.0 µM long-chain bases induced cellular damage and death in less than 20 minutes. The LD50 of long-chain bases for GE keratinocytes, GF, and DC were considerably higher than their minimal inhibitory concentrations for oral pathogens, a finding important to pursuing their future potential in treating periodontal and oral infections. PMID:26005054

  6. Evaluation of Acute toxicity of Lambda Cyhalothrin in Mus musculus L.

    PubMed

    Tomar, Monika; Kumar, Ajay; Kataria, Sudhir Kumar

    2015-08-01

    Lambda Cyhalothrin (LCT) is a type II synthetic pyrethroid widely used in agriculture, home pest control and protection of food stuff. Here, we evaluated its toxicity on biochemical parameters (Total protein, Acetyl cholinesterase, RNA and DNA) and liver histological alteration in mice after 24 h of oral administration @ 25, 50 and 75% of LD50 i.e.; 26.49 mg/kg/body wt. Distilled water (DW) and Cyclophosphamide (CP @ 40 mg/kg/body wt.) were used as negative and positive control; respectively. LCT treated mice showed significant decrease in total protein (P < 0.01), acetyl cholinesterase (P < 0.001) and DNA (P < 0.001) in a dose dependent manner. On the contrary, RNA content showed significant increase (P < 0.01) at 50% of LD50 of LCT. Histological observations of the mice liver showed vascular congestion and hepatocyte degeneration with 6.63 mg/kg/body wt. of LCT; and accumulation of RBCs with sinusoid degeneration and wide necrotic area with pyknosis with 13.25 and 19.88 mg/kg/body wt., respectively. The results demonstrated LCT induced biochemical changes and hepatotoxicity in female mice. PMID:26349319

  7. In vitro cytotoxicity testing of 30 reference chemicals to predict acute human and animal toxicity

    SciTech Connect

    Barile, F.A.; Arjun, S.; Borges, L. )

    1991-03-11

    This study was conducted in cooperation with the Scandinavian Society of Cell Toxicology, as part of the Multicenter Evaluation for In Vitro Cytotoxicity (MEIC), and was designed to develop an in vitro model for predicting acute human and animal toxicity. The technique relies on the ability of cultured transformed rat lung epithelial cells (L2) to incorporate radiolabled amino acids into newly synthesized proteins in the absence or presence of increasing doses of the test chemical, during a 24-hr incubation. IC50 values were extrapolated from the dose-response curves after linear regression analysis. Human toxic blood concentrations estimated from rodent LD50 values suggest that our experimental IC50's are in close correlation with the former. Validation of the data by the MEIC committee shows that our IC50 values predicted human lethal dosage as efficient as rodent LD50's. It is anticipated that this and related procedures may supplement or replace currently used animal protocols for predicting human toxicity.

  8. Sprague-Dawley rats display metabolism-mediated sex differences in the acute toxicity of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy)

    SciTech Connect

    Fonsart, Julien ||; Menet, Marie-Claude |; Decleves, Xavier ||; Galons, Herve |; Crete, Dominique; Debray, Marcel; Scherrmann, Jean-Michel ||; Noble, Florence ||

    2008-07-01

    The use of the amphetamine derivative 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) has been associated with unexplained deaths. Male humans and rodents are more sensitive to acute toxicity than are females, including a potentially lethal hyperthermia. MDMA is highly metabolized to five main metabolites, by the enzymes CYP1A2 and CYP2D. The major metabolite in rats, 3,4-methylenedioxyamphetamine (MDA), also causes hyperthermia. We postulated that the reported sex difference in rats is due to a sexual dimorphism(s). We therefore determined (1) the LD50 of MDMA and MDA, (2) their hyperthermic effects, (3) the activities of liver CYP1A2 and CYP2D, (4) the liver microsomal metabolism of MDMA and MDA, (5) and the plasma concentrations of MDMA and its metabolites 3 h after giving male and female Sprague-Dawley (SD) rats MDMA (5 mg.kg{sup -1} sc). The LD50 of MDMA was 2.4-times lower in males than in females. MDMA induced greater hyperthermia (0.9 deg. C) in males. The plasma MDA concentration was 1.3-fold higher in males, as were CYP1A2 activity (twice) and N-demethylation to MDA (3.3-fold), but the plasma MDMA concentration (1.4-fold) and CYP2D activity (1.3-fold) were higher in females. These results suggest that male SD rats are more sensitive to MDMA acute toxicity than are females, probably because their CYP1A2 is more active, leading to higher N-demethylation and plasma MDA concentration. This metabolic pathway could be responsible for the lethality of MDMA, as the LD50 of MDA is the same in both sexes. These data strongly suggest that the toxicity of amphetamine-related drugs largely depends on metabolic differences.

  9. Toxicological evaluation of neem (Azadirachta indica) oil: acute and subacute toxicity.

    PubMed

    Deng, Yun-xia; Cao, Mei; Shi, Dong-xia; Yin, Zhong-qiong; Jia, Ren-yong; Xu, Jiao; Wang, Chuan; Lv, Cheng; Liang, Xiao-xia; He, Chang-liang; Yang, Zhi-rong; Zhao, Jian

    2013-03-01

    Neem (Azadirachta indica), popularly known as traditional medicine is a native plant in India. Neem oil is a vegetable oil derived from seeds or fruits of the neem tree through pressing or solvent extraction, and largely used in popular medicine to have antifungal, antibacterial, antimalarial, antiparasitic, anti-inflammatory, as well as immunemodulatory properties in different animal species. In the present study, acute and 28-day subacute toxicity tests were carried out. In the acute toxicity test, the LD50 values of neem oil were found to be 31.95g/kg. The subacute treatment with neem oil failed to change body weight gain, food and water consumption. Serum biochemistry analysis showed no significant differences in any of the parameters examined under the dose of 1600mg/kg/day. Histopathological exams showed that the target organs of neem oil were testicle, liver and kidneys up to the dose of 1600mg/kg/day.

  10. Toxicological evaluation of neem (Azadirachta indica) oil: acute and subacute toxicity.

    PubMed

    Deng, Yun-xia; Cao, Mei; Shi, Dong-xia; Yin, Zhong-qiong; Jia, Ren-yong; Xu, Jiao; Wang, Chuan; Lv, Cheng; Liang, Xiao-xia; He, Chang-liang; Yang, Zhi-rong; Zhao, Jian

    2013-03-01

    Neem (Azadirachta indica), popularly known as traditional medicine is a native plant in India. Neem oil is a vegetable oil derived from seeds or fruits of the neem tree through pressing or solvent extraction, and largely used in popular medicine to have antifungal, antibacterial, antimalarial, antiparasitic, anti-inflammatory, as well as immunemodulatory properties in different animal species. In the present study, acute and 28-day subacute toxicity tests were carried out. In the acute toxicity test, the LD50 values of neem oil were found to be 31.95g/kg. The subacute treatment with neem oil failed to change body weight gain, food and water consumption. Serum biochemistry analysis showed no significant differences in any of the parameters examined under the dose of 1600mg/kg/day. Histopathological exams showed that the target organs of neem oil were testicle, liver and kidneys up to the dose of 1600mg/kg/day. PMID:23353547

  11. Length of mechanical restraint following haloperidol injections versus oral atypical antipsychotics for the initial treatment of acute schizophrenia: a propensity-matched analysis from the Japanese diagnosis procedure combination database.

    PubMed

    Nakamura, Mitsuhiro; Yasunaga, Hideo; Haraguchi, Tadashi; Ando, Shuntaro; Sugihara, Toru; Horiguchi, Hiromasa; Ohe, Kazuhiko; Matsuda, Shinya; Fushimi, Kiyohide

    2013-10-30

    Differences in effectiveness between haloperidol injection and oral atypical antipsychotics in the acute-phase treatment of schizophrenia are not well examined. We retrospectively investigated whether these treatment options affected the length of mechanical restraint. We used the Japanese Diagnosis Procedure Combination Database to identify schizophrenia patients who were involuntarily hospitalized and receiving mechanical restraint between July and December, 2006-2009. Data included patient demographics, use of antipsychotics, and number of days on which patients underwent mechanical restraint. Propensity score matching was performed to compare the number of days of mechanical restraint between the haloperidol injection group and the oral atypical antipsychotics group. We used survival analysis to examine whether the initial difference in treatment affected the number of days of mechanical restraint. Cox regression was performed to compare the concurrent effects of various factors. Among 1731 eligible patients, 574 were treated with haloperidol injections and 420 with atypical antipsychotics. Matching produced 274 patients in each group. Cox regression analysis showed that the initial therapeutic agents did not significantly affect the number of days of mechanical restraint. The results indicate that atypical antipsychotics were as effective as haloperidol injections in the acute-phase treatment of schizophrenia.

  12. Tremorgenic toxin from Penicillium veruculosum.

    PubMed

    Cole, R J; Kirksey, J W; Moore, J H; Blankenship, B R; Diener, U L; Davis, N D

    1972-08-01

    A new mycotoxin that produces severe tremors and acute toxicity when administered orally or intraperitoneally (ip) to mice and 1-day-old cockerels was obtained from a strain of Penicillium verruculosum Peyronel isolated from peanuts. The ip 50% lethal dose (LD(50)) of this tremorgen was 2.4 mg/kg in mice and 15.2 mg/kg in chickens. Orally administered LD(50) values for the toxin were 126.7 mg/kg in mice and 365.5 mg/kg in chickens. The trivial name "verruculogen" is proposed for this tremorgenic mycotoxin. Physical and chemical characteristics of the mycotoxin are described. PMID:4341967

  13. Tremorgenic Toxin from Penicillium verruculosum

    PubMed Central

    Cole, R. J.; Kirksey, J. W.; Moore, J. H.; Blankenship, B. R.; Diener, U. L.; Davis, N. D.

    1972-01-01

    A new mycotoxin that produces severe tremors and acute toxicity when administered orally or intraperitoneally (ip) to mice and 1-day-old cockerels was obtained from a strain of Penicillium verruculosum Peyronel isolated from peanuts. The ip 50% lethal dose (LD50) of this tremorgen was 2.4 mg/kg in mice and 15.2 mg/kg in chickens. Orally administered LD50 values for the toxin were 126.7 mg/kg in mice and 365.5 mg/kg in chickens. The trivial name „verruculogen” is proposed for this tremorgenic mycotoxin. Physical and chemical characteristics of the mycotoxin are described. PMID:4341967

  14. Short-term toxicity studies of sanguinarine and of two alkaloid extracts of Sanguinaria canadensis L.

    PubMed

    Becci, P J; Schwartz, H; Barnes, H H; Southard, G L

    1987-01-01

    The short-term toxicity of sanguinarine, a benzophenanthridine alkaloid, and of two alkaloid extracts of Sanguinaria canadensis L. are presented. The acute oral LD50 in rats of sanguinarine was calculated to be 1658 mg/kg, and of the two alkaloid extracts, 1440 and 1250 mg/kg. The acute iv LD50 in rats of sanguinarine was found to be 29 mg/kg. No toxic effects were observed in rats fed up to 150 ppm sanguinarine in the diet for 14 d and in rats treated by gavage with up to 0.6 mg/kg body weight for 30 d. The acute dermal LD50 in rabbits was found to be greater than 200 mg/kg.

  15. A Community-based Survey of the Awareness and Acceptability of Oral Rehydration Therapy (ORT) as a Treatment for Acute Diarrhoea in Children.

    ERIC Educational Resources Information Center

    Ekanem, E. E.; Benebo, N. S.

    1988-01-01

    A total of 267 Nigerian mothers with children under the age of five years were investigated regarding the degree of their awareness and acceptance of oral rehydration therapy in the treatment of childhood diarrhea. Results indicate that only 39 percent of the mothers had heard of ORT in treating diarrhea. (RJC)

  16. 49 CFR 173.132 - Class 6, Division 6.1-Definitions.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... it falls within any one of the following categories when tested on laboratory animals (whenever possible, animal test data that has been reported in the chemical literature should be used): (i) Oral... substance per mass of test animal (mg/kg). (2) LD50 for acute dermal toxicity means that dose of...

  17. Toxicity of Pesticides. Agrichemical Fact Sheet 2.

    ERIC Educational Resources Information Center

    Hock, Winand K.

    This fact sheet gives the acute oral and dermal toxicity (LD 50) of over 250 pesticides in lab animals. The chemicals are categorized as fungicides, herbicides, insecticides, or miscellaneous compounds. One or more trade names are given for each pesticide. In addition, a brief explanation of toxicity determination is given. (BB)

  18. 49 CFR 173.132 - Class 6, Division 6.1-Definitions.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... Toxicity. A liquid or solid with an LD50 for acute oral toxicity of not more than 300 mg/kg. (ii) Dermal... inhalation of vapors of not more than 5000 mL/m3; or (2) Is an irritating material, with properties similar... aerodynamic diameter of that particle-fraction is 10 microns or less. A liquid substance should be tested if...

  19. 49 CFR 173.132 - Class 6, Division 6.1-Definitions.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Toxicity. A liquid or solid with an LD50 for acute oral toxicity of not more than 300 mg/kg. (ii) Dermal... inhalation of vapors of not more than 5000 mL/m3; or (2) Is an irritating material, with properties similar... aerodynamic diameter of that particle-fraction is 10 microns or less. A liquid substance should be tested if...

  20. 49 CFR 173.132 - Class 6, Division 6.1-Definitions.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... Toxicity. A liquid or solid with an LD50 for acute oral toxicity of not more than 300 mg/kg. (ii) Dermal... inhalation of vapors of not more than 5000 mL/m3; or (2) Is an irritating material, with properties similar... aerodynamic diameter of that particle-fraction is 10 microns or less. A liquid substance should be tested if...

  1. Toxicological evaluation of ferrous N-carbamylglycinate chelate: Acute, Sub-acute toxicity and mutagenicity.

    PubMed

    Wan, Dan; Zhou, Xihong; Xie, Chunyan; Shu, Xugang; Wu, Xin; Yin, Yulong

    2015-11-01

    Iron is an essential trace element that is vital important in various biological process. A deficiency in iron could induce public health problem e.g. anaemia, while an overload could induce ROS production, lipid peroxidation and DNA bases modifications. In the present study, a new iron fortifier was synthesized, and its acute/sub-acute toxicity was investigated. According to the improved Karber's method, the median lethal dose (LD50) of the ferrous N-carbamylglycinate in SD rat was 3.02 g/kg and the 95% confidence intervals were between 2.78 and 3.31 g/kg. No biologically significant or test substance-related differences were observed in body weights, feed consumption, clinical signs, organ weights, histopathology, ophthalmology, hematology, and clinical chemistry parameters in any of the treatment groups of ferrous N-carbamylglycinate at target concentrations corresponding to 150, 300, and 600 mg/kg/day for 28 days. The no observed adverse effect level (NOAEL) for ferrous N-carbamylglycinate was at least 600 mg/kg b.w. day in rats. In addition, no evidence of mutagenicity was found, either in vitro in bacterial reverse mutation assay or in vivo in mice bone marrow micronucleus assay and sperm shape abnormality assay. On the basis of our findings, we conclude that ferrous N-carbamylglycinate is a low-toxic substance with no genotoxicity.

  2. [Safety Evaluation of Rare Sugar Syrup: Single-dose Oral Toxicity in Rats, Reverse Mutation Assay, Chromosome Aberration Assay, and Acute Non-Effect Level for Diarrhea of a Single Dose in Humans].

    PubMed

    Yamada, Takako; Iida, Tetsuo; Takamine, Satoshi; Hayashi, Noriko; Okuma, Kazuhiro

    2015-01-01

    The safety of rare sugar syrup obtained from high-fructose corn syrup under slightly alkaline conditions was studied. Mutagenicity of rare sugar syrup was assessed by a reverse mutation assay using Salmonella typhimurium and Escherichia coli, and an in vitro chromosomal aberration assay using Chinese hamster lung cell line (CHL/IU). No mutagenicity of rare sugar syrup was detected under these experimental conditions. Oral administration of single dose (15,000 mg/kg) of rare sugar syrup to rats caused no abnormalities, suggesting no adverse effect of rare sugar syrup. In humans, the acute non-effect level of rare sugar syrup for causing diarrhea was estimated as 0.9 g/kg body weight as dry solid base in both males and females. PMID:26537651

  3. AVP-825 Breath-Powered Intranasal Delivery System Containing 22 mg Sumatriptan Powder vs 100 mg Oral Sumatriptan in the Acute Treatment of Migraines (The COMPASS Study): A Comparative Randomized Clinical Trial Across Multiple Attacks

    PubMed Central

    Tepper, Stewart J; Cady, Roger K; Silberstein, Stephen; Messina, John; Mahmoud, Ramy A; Djupesland, Per G; Shin, Paul; Siffert, Joao

    2015-01-01

    Objective The objective of this study was to compare the efficacy, tolerability, and safety of AVP-825, an investigational bi-directional breath-powered intranasal delivery system containing low-dose (22 mg) sumatriptan powder, vs 100 mg oral sumatriptan for acute treatment of migraine in a double-dummy, randomized comparative efficacy clinical trial allowing treatment across multiple migraine attacks. Background In phases 2 and 3, randomized, placebo-controlled trials, AVP-825 provided early and sustained relief of moderate or severe migraine headache in adults, with a low incidence of triptan-related adverse effects. Methods This was a randomized, active-comparator, double-dummy, cross-over, multi-attack study (COMPASS; NCT01667679) with two ≤12-week double-blind periods. Subjects experiencing 2-8 migraines/month in the past year were randomized 1:1 using computer-generated sequences to AVP-825 plus oral placebo tablet or an identical placebo delivery system plus 100 mg oral sumatriptan tablet for the first period; patients switched treatment for the second period in this controlled comparative design. Subjects treated ≤5 qualifying migraines per period within 1 hour of onset, even if pain was mild. The primary end-point was the mean value of the summed pain intensity differences through 30 minutes post-dose (SPID-30) using Headache Severity scores. Secondary outcomes included pain relief, pain freedom, pain reduction, consistency of response across multiple migraines, migraine-associated symptoms, and atypical sensations. Safety was also assessed. Results A total of 275 adults were randomized, 174 (63.3%) completed the study (ie, completed the second treatment period), and 185 (67.3%) treated at least one migraine in both periods (1531 migraines assessed). There was significantly greater reduction in migraine pain intensity with AVP-825 vs oral sumatriptan in the first 30 minutes post-dose (least squares mean SPID-30 = 10.80 vs 7.41, adjusted mean

  4. Safety and efficacy of non-vitamin K oral anticoagulant treatment compared with warfarin in patients with non-valvular atrial fibrillation who develop acute ischemic stroke or transient ischemic attack: a multicenter prospective cohort study (daVinci study).

    PubMed

    Saji, Naoki; Kimura, Kazumi; Tateishi, Yohei; Fujimoto, Shigeru; Kaneko, Nobuyuki; Urabe, Takao; Tsujino, Akira; Iguchi, Yasuyuki

    2016-11-01

    The safety and efficacy of non-vitamin K oral anticoagulant (NOAC) compared with warfarin in treating patients with non-valvular atrial fibrillation (NVAF) who developed acute ischemic stroke or transient ischemic attack (AIS/TIA), particularly those receiving tissue-plasminogen activator (tPA) therapy, remains unclear. Between April 2012 and December 2014, we conducted a multicenter prospective cohort study to assess the current clinical practice for treating such patients. We divided the patients into two groups according to the administration of oral anticoagulants (warfarin or NOACs) and tPA therapy. The risk of any hemorrhagic or ischemic event was compared within 1 month after the onset of stroke. We analyzed 235 patients with AIS/TIA including 73 who received tPA therapy. Oral anticoagulants were initiated within 2-4 inpatient days. NOACs were administered to 49.8 % of patients, who were predominantly male, younger, had small infarcts, lower NIHSS scores, and had a lower all-cause mortality rate (0 vs. 4.2 %, P = 0.06) and a lower risk of any ischemic events (6.0 vs. 7.6 %, P = 0.797) compared with warfarin users. The prevalence of all hemorrhagic events was equivalent between the two groups. Early initiation of NOACs after tPA therapy appeared to lower the risk of hemorrhagic events, although there was no significant difference (0 vs. 5.6 %, P = 0.240). Although more clinicians are apt to prescribe NOACs in minor ischemic stroke, NOAC treatment may provide a potential benefit in such cases. Early initiation of NOACs after tPA therapy may reduce the risk of hemorrhagic events compared with warfarin.

  5. Oral administration of a recombinant attenuated Yersinia pseudotuberculosis strain elicits protective immunity against plague.

    PubMed

    Sun, Wei; Sanapala, Shilpa; Rahav, Hannah; Curtiss, Roy

    2015-11-27

    A Yersinia pseudotuberculosis PB1+ (Yptb PB1+) mutant strain combined with chromosome insertion of the caf1R-caf1A-caf1M-caf1 operon and deletions of yopJ and yopK, χ10068 [pYV-ω2 (ΔyopJ315 ΔyopK108) ΔlacZ044::caf1R-caf1M-caf1A-caf1] was constructed. Results indicated that gene insertion and deletion did not affect the growth rate of χ10068 compared to wild-type Yptb cultured at 26 °C. In addition, the F1 antigen in χ10068 was synthesized and secreted on the surface of bacteria at 37 °C (mammalian body temperature), not at ambient culture temperature (26 °C). Immunization with χ10068 primed antibody responses and specific T-cell responses to F1 and YpL (Y. pestis whole cell lysate). Oral immunization with a single dose of χ10068 provided 70% protection against a subcutaneous (s.c.) challenge with ∼ 2.6 × 10(5) LD50 of Y. pestis KIM6+ (pCD1Ap) (KIM6+Ap) and 90% protection against an intranasal (i.n.) challenge with ∼ 500 LD50 of KIM6+Ap in mice. Our results suggest that χ10068 can be used as an effective precursor to make a safe vaccine to prevent plague in humans and to eliminate plague circulation among humans and animals.

  6. Acute effects of bright light and caffeine on nighttime melatonin and temperature levels in women taking and not taking oral contraceptives

    NASA Technical Reports Server (NTRS)

    Wright, K. P. Jr; Myers, B. L.; Plenzler, S. C.; Drake, C. L.; Badia, P.; Czeisler, C. A. (Principal Investigator)

    2000-01-01

    Caffeine and bright light effects on nighttime melatonin and temperature levels in women were tested during the luteal phase of the menstrual cycle (n=30) or the pseudo luteal phase for oral contraceptive users (n=32). Participants were randomly assigned to receive either bright (5000 lux) or dim room light (<88 lux) between 20:00 and 08:00 h under a modified constant routine protocol. Half the subjects in each lighting condition were administered either caffeine (100 mg) or placebo in a double-blind manner at 20:00, 23:00, 02:00 and 05:00 h. Results showed that the combination of bright light and caffeine enhanced nighttime temperature levels to a greater extent than did either caffeine or bright light alone. Both of the latter groups had higher temperature levels relative to the dim light placebo condition and the two groups did not differ. Temperature levels in the bright light caffeine condition were maintained at near peak circadian levels the entire night in the luteal and pseudo luteal phase. Melatonin levels were reduced throughout the duration of bright light exposure for all women. Caffeine reduced the onset of melatonin levels for women in the luteal phase, but it had little effect on melatonin levels for oral contraceptive users. The results for women in the luteal phase of the menstrual cycle are consistent with our previous findings in men. The results also suggest that oral contraceptives may alter the effects of caffeine on nighttime melatonin levels.

  7. Does an L-glutamine-containing, Glucose-free, Oral Rehydration Solution Reduce Stool Output and Time to Rehydrate in Children with Acute Diarrhoea? A Double-blind Randomized Clinical Trial

    PubMed Central

    Gutiérrez, Claudia; Villa, Sofía; Mota, Felipe R.; Calva, Juan J.

    2007-01-01

    This study assessed whether an oral rehydration solution (ORS) in which glucose is replaced by L-glutamine (L-glutamine ORS) is more effective than the standard glucose-based rehydration solution recommended by the World Health Organization (WHO-ORS) in reducing the stool volume and time to rehydrate in acute diarrhoea. In a double-blind, randomized controlled trial in a Mexican hospital, 147 dehydrated children, aged 1–60 month(s), were assigned either to the WHO-ORS (74 children), or to the L-glutamine ORS (73 children) and followed until successful rehydration. There were no significant differences between the groups in stool output during the first four hours, time to successful rehydration, volume of ORS required for rehydration, urinary output, and vomiting. This was independent of rotavirus-associated infection. An L-glutamine-containing glucose-free ORS seems not to offer greater clinical benefit than the standard WHO-ORS in mildly-to-moderately-dehydrated children with acute non-cholera diarrhoea. PMID:18330060

  8. Acute toxicity of T2 mycotoxin to the guinea-pig by inhalation and subcutaneous routes.

    PubMed Central

    Marrs, T. C.; Edginton, J. A.; Price, P. N.; Upshall, D. G.

    1986-01-01

    The acute inhalation and subcutaneous toxicity of T2 mycotoxin has been investigated in guinea-pigs. The toxicity by the two routes was quantitatively and qualitatively similar. The LCt50 was 5749 mg min m-3 and the subcutaneous LD50 1-2 mg kg-1. Histological changes in the decedents which were similar by both routes of administration were most marked in the lymphoreticular system but also occurred in the gut. Lymphocytolysis and phagocytosis occurred in both the cortex of the thymus and of the lymph nodes. Lymph nodes were more severely affected in the decedents among the animals dosed with T2 by the subcutaneous route. The small intestine exhibited dead and dying cells throughout the lamina propria after T2 by either route. Images Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 2 Fig. 3 PMID:3707855

  9. Actions and interactions of cholinolytics and cholinesterase reactivators in the treatment of acute organophosphorus toxicity.

    PubMed

    Das Gupta, S; Ghosh, A K; Chowdhri, B L; Asthana, S N; Batra, B S

    1991-01-01

    Different drug combinations consisting of cholinolytic and a cholinesterase (ChE) reactivator provide greater therapeutic efficacy in acute organophosphorus (OP) poisoning in mice than when used alone. Maximum protection, as determined by a shift of the LD50 for the two OP agents, was observed with the cholinolytic benactyzine. A protection index (P.I.) of 42 was obtained when benactyzine was given along with obidoxime in diisopropylphosphorofluoridate (DFP) intoxication. With the more toxic OP agent soman (o-pinacolylmethylphosphonofluoridate), the same cholinolytic only offered a maximum P.I. of 3.2 when administered with HS-6, another bispyridinium ChE reactivator. This beneficial effect of benactyzine is possibly due to its greater antimuscarinic effect in the central nervous system than atropine or dexetimide. PMID:1935707

  10. The pharmacological profile and clinical prospects of the oral 5-HT1F receptor agonist lasmiditan in the acute treatment of migraine

    PubMed Central

    Israel, Heike; Neeb, Lars

    2015-01-01

    More than 20 years have passed without the launch of a new substance class for acute migraine therapy. Triptans were the latest class of substances which successfully passed all developmental stages with a significant antimigraine efficacy and a sufficient safety profile. New drugs with a better adverse event profile and at least similar efficacy are needed for migraine subjects who cannot tolerate triptans for attack treatment. Lasmiditan is a novel highly specific 5-HT1F receptor agonist currently in clinical trials for acute migraine therapy and devoid of vasoconstriction in coronary arteries as determined in a surrogate assay. In both phase II randomized, placebo-controlled trials in acute migraine the primary endpoint was met. For the intravenous formulation a clear dose-dependent effect on headaches could be determined. Lasmiditan tablets in doses of 50–400 mg show significant headache relief after 2 hours compared with placebo and improved accompanying symptoms. This substance is chemically clearly different from other antimigraine drugs, which is also reflected by its dose-dependent adverse event profile chiefly including dizziness, vertigo, paresthesia and fatigue. Adverse events are usually linked to the central nervous system. Future phase III clinical trials with an active triptan comparator or in a preferential trial design will allow a better comparison of lasmiditan and triptans. They will also determine whether lasmiditan will become available to the migraine patient. PMID:25584073

  11. The efficacy of oxymetazoline administered with a nasal bellows container and combined with oral phenoxymethyl-penicillin in the treatment of acute maxillary sinusitis.

    PubMed

    Wiklund, L; Stierna, P; Berglund, R; Westrin, K M; Tönnesson, M

    1994-01-01

    The efficacy of a new administration form of oxymetazoline, a nasal bellows container, was investigated in two separate studies by means of a combined treatment with phenoxymethyl-penicillin for acute maxillary sinusitis. In the first study (study 1), oxymetazoline administered with a bellows (OXBE) was compared both with a placebo belows (PLBE) as well as with oxymetazoline and placebo administered with a conventional nasal spray (OXSP respective PLSP) in 73 patients. In the second study (study 2), OXBE was compared only with PLBE in 48 patients. Objective evaluation was made by comparing the radiographical improvement in conventional plain sinus X-ray images. A scoring system corresponding to the outcome of antral irrigation was used for evaluating the X-ray pictures. Subjective symptoms; nasal stuffiness and pain, were assessed by registrations on visual analogue scales. Neither with regard to radiographical improvement nor to decrease in subjective symptoms could any significant differences be found between the different treatment modes. Oxymetazoline administered with a nasal bellows thus did not accelerate the rate of healing of acute maxillary sinusitis in these two studies. It is inferred from these results that decongestion of the sinus ostia is not of primary importance for the course of healing of a manifest acute sinusitis.

  12. 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 ...

  13. A Consistent Orally-Infected Hamster Model for Enterovirus A71 Encephalomyelitis Demonstrates Squamous Lesions in the Paws, Skin and Oral Cavity Reminiscent of Hand-Foot-and-Mouth Disease.

    PubMed

    Phyu, Win Kyaw; Ong, Kien Chai; Wong, Kum Thong

    2016-01-01

    Enterovirus A71 (EV-A71) causes self-limiting, hand-foot-and-mouth disease (HFMD) that may rarely be complicated by encephalomyelitis. Person-to-person transmission is usually by fecal-oral or oral-oral routes. To study viral replication sites in the oral cavity and other tissues, and to gain further insights into virus shedding and neuropathogenesis, we developed a consistent, orally-infected, 2-week-old hamster model of HFMD and EV-A71 encephalomyelitis. Tissues from orally-infected, 2-week-old hamsters were studied by light microscopy, immunohistochemistry and in situ hybridization to detect viral antigens and RNA, respectively, and by virus titration. Hamsters developed the disease and died after 4-8 days post infection; LD50 was 25 CCID50. Macroscopic cutaneous lesions around the oral cavity and paws were observed. Squamous epithelium in the lip, oral cavity, paw, skin, and esophagus, showed multiple small inflammatory foci around squamous cells that demonstrated viral antigens/RNA. Neurons (brainstem, spinal cord, sensory ganglia), acinar cells (salivary gland, lacrimal gland), lymphoid cells (lymph node, spleen), and muscle fibres (skeletal, cardiac and smooth muscles), liver and gastric epithelium also showed varying amounts of viral antigens/RNA. Intestinal epithelium, Peyer's patches, thymus, pancreas, lung and kidney were negative. Virus was isolated from oral washes, feces, brain, spinal cord, skeletal muscle, serum, and other tissues. Our animal model should be useful to study squamous epitheliotropism, neuropathogenesis, oral/fecal shedding in EV-A71 infection, person-to-person transmission, and to test anti-viral drugs and vaccines.

  14. A Consistent Orally-Infected Hamster Model for Enterovirus A71 Encephalomyelitis Demonstrates Squamous Lesions in the Paws, Skin and Oral Cavity Reminiscent of Hand-Foot-and-Mouth Disease.

    PubMed

    Phyu, Win Kyaw; Ong, Kien Chai; Wong, Kum Thong

    2016-01-01

    Enterovirus A71 (EV-A71) causes self-limiting, hand-foot-and-mouth disease (HFMD) that may rarely be complicated by encephalomyelitis. Person-to-person transmission is usually by fecal-oral or oral-oral routes. To study viral replication sites in the oral cavity and other tissues, and to gain further insights into virus shedding and neuropathogenesis, we developed a consistent, orally-infected, 2-week-old hamster model of HFMD and EV-A71 encephalomyelitis. Tissues from orally-infected, 2-week-old hamsters were studied by light microscopy, immunohistochemistry and in situ hybridization to detect viral antigens and RNA, respectively, and by virus titration. Hamsters developed the disease and died after 4-8 days post infection; LD50 was 25 CCID50. Macroscopic cutaneous lesions around the oral cavity and paws were observed. Squamous epithelium in the lip, oral cavity, paw, skin, and esophagus, showed multiple small inflammatory foci around squamous cells that demonstrated viral antigens/RNA. Neurons (brainstem, spinal cord, sensory ganglia), acinar cells (salivary gland, lacrimal gland), lymphoid cells (lymph node, spleen), and muscle fibres (skeletal, cardiac and smooth muscles), liver and gastric epithelium also showed varying amounts of viral antigens/RNA. Intestinal epithelium, Peyer's patches, thymus, pancreas, lung and kidney were negative. Virus was isolated from oral washes, feces, brain, spinal cord, skeletal muscle, serum, and other tissues. Our animal model should be useful to study squamous epitheliotropism, neuropathogenesis, oral/fecal shedding in EV-A71 infection, person-to-person transmission, and to test anti-viral drugs and vaccines. PMID:26815859

  15. A Consistent Orally-Infected Hamster Model for Enterovirus A71 Encephalomyelitis Demonstrates Squamous Lesions in the Paws, Skin and Oral Cavity Reminiscent of Hand-Foot-and-Mouth Disease

    PubMed Central

    Phyu, Win Kyaw; Ong, Kien Chai; Wong, Kum Thong

    2016-01-01

    Enterovirus A71 (EV-A71) causes self-limiting, hand-foot-and-mouth disease (HFMD) that may rarely be complicated by encephalomyelitis. Person-to-person transmission is usually by fecal-oral or oral-oral routes. To study viral replication sites in the oral cavity and other tissues, and to gain further insights into virus shedding and neuropathogenesis, we developed a consistent, orally-infected, 2-week-old hamster model of HFMD and EV-A71 encephalomyelitis. Tissues from orally-infected, 2-week-old hamsters were studied by light microscopy, immunohistochemistry and in situ hybridization to detect viral antigens and RNA, respectively, and by virus titration. Hamsters developed the disease and died after 4–8 days post infection; LD50 was 25 CCID50. Macroscopic cutaneous lesions around the oral cavity and paws were observed. Squamous epithelium in the lip, oral cavity, paw, skin, and esophagus, showed multiple small inflammatory foci around squamous cells that demonstrated viral antigens/RNA. Neurons (brainstem, spinal cord, sensory ganglia), acinar cells (salivary gland, lacrimal gland), lymphoid cells (lymph node, spleen), and muscle fibres (skeletal, cardiac and smooth muscles), liver and gastric epithelium also showed varying amounts of viral antigens/RNA. Intestinal epithelium, Peyer’s patches, thymus, pancreas, lung and kidney were negative. Virus was isolated from oral washes, feces, brain, spinal cord, skeletal muscle, serum, and other tissues. Our animal model should be useful to study squamous epitheliotropism, neuropathogenesis, oral/fecal shedding in EV-A71 infection, person-to-person transmission, and to test anti-viral drugs and vaccines. PMID:26815859

  16. The acute effects of experimental short-term evening and night shifts on human circadian rhythm: the oral temperature, heart rate, serum cortisol and urinary catecholamines levels.

    PubMed

    Fujiwara, S; Shinkai, S; Kurokawa, Y; Watanabe, T

    1992-01-01

    This study was designed to examine the temporal changes in circadian rhythm of oral temperature, heart rate, serum cortisol and urinary catecholamines levels due to experimental short-term shifts. The six subjects were assigned to consecutive day (work 0800-1600 hours; sleep 0000-0800 hours), evening (1600-2400 hours; 0400-1200 hours), and night (0000-0800 hours; 1200-2000 hours) shifts of 2 days each scheduled as hospital shiftwork by nurses, in random order, during which data were collected every 4 h throughout the experimental periods. According to acrophases of a fitted cosine curve and visual inspection on chronograms, the phases of circadian rhythms were delayed to different degrees in the evening shifts with a minimum of about 1 h for oral temperature and a maximum of about 4 h for urinary free noradrenaline. The corresponding phase delays were larger in the night shift for oral temperature (about 3 h), resting heart rate (about 5 h) and urinary free noradrenaline (about 13 h); the diurnal variations of serum cortisol and urinary free adrenaline were greatly modified, and their circadian rhythmicities disappeared, indicating that the normal circadian phase relations of these variables were disrupted more by the night shift. The comparison of chronograms and correlation analyses revealed that the 4-h mean heart rate and urinary free noradrenaline were largely affected by rest-activity level in connection with shifts, while the resting heart rate and urinary free adrenaline were less affected. On the other hand, the sleep factor (time of onset and/or period) seemed to be more potent in modifying the circadian rhythm of serum cortisol, especially with the night shifts.

  17. THE PROLONGED GASTROINTESTINAL SYNDROME IN RHESUS MACAQUES: THE RELATIONSHIP BETWEEN GASTROINTESTINAL, HEMATOPOIETIC, AND DELAYED MULTI-ORGAN SEQUELAE FOLLOWING ACUTE, POTENTIALLY LETHAL, PARTIAL-BODY IRRADIATION

    PubMed Central

    MacVittie, Thomas J.; Bennett, Alexander; Booth, Catherine; Garofalo, Michael; Tudor, Gregory; Ward, Amanda; Shea-Donohue, Terez; Gelfond, Daniel; McFarland, Emylee; Jackson, William; Lu, Wei; Farese, Ann M.

    2014-01-01

    The dose response relationship for the acute gastrointestinal syndrome following total-body irradiation prevents analysis of the full recovery and damage to the gastrointestinal system, since all animals succumb to the subsequent 100% lethal hematopoietic syndrome. A partial-body irradiation model with 5% bone marrow sparing was established to investigate the prolonged effects of high-dose radiation on the gastrointestinal system, as well as the concomitant hematopoietic syndrome and other multi-organ injury including the lung. Herein, cellular and clinical parameters link acute and delayed coincident sequelae to radiation dose and time course post-exposure. Male rhesus Macaca mulatta were exposed to partial-body irradiation with 5% bone marrow (tibiae, ankles, feet) sparing using 6 MV linear accelerator photons at a dose rate of 0.80 Gy min−1 to midline tissue (thorax) doses in the exposure range of 9.0 to 12.5 Gy. Following irradiation, all animals were monitored for multiple organ-specific parameters for 180 d. Animals were administered medical management including administration of intravenous fluids, antiemetics, prophylactic antibiotics, blood transfusions, antidiarrheals, supplemental nutrition, and analgesics. The primary endpoint was survival at 15, 60, or 180 d post-exposure. Secondary endpoints included evaluation of dehydration, diarrhea, hematologic parameters, respiratory distress, histology of small and large intestine, lung radiographs, and mean survival time of decedents. Dose- and time-dependent mortality defined several organ-specific sequelae, with LD50/15 of 11.95 Gy, LD50/60 of 11.01 Gy, and LD50/180 of 9.73 Gy for respective acute gastrointestinal, combined hematopoietic and gastrointestinal, and multi-organ delayed injury to include the lung. This model allows analysis of concomitant multi-organ sequelae, thus providing a link between acute and delayed radiation effects. Specific and multi-organ medical countermeasures can be assessed for

  18. Oral candidiasis and angular cheilitis.

    PubMed

    Sharon, Victoria; Fazel, Nasim

    2010-01-01

    Candidiasis, an often encountered oral disease, has been increasing in frequency. Most commonly caused by the overgrowth of Candida albicans, oral candidiasis can be divided into several categories including acute and chronic forms, and angular cheilitis. Risk factors for the development of oral candidiasis include immunosuppression, wearing of dentures, pharmacotherapeutics, smoking, infancy and old age, endocrine dysfunction, and decreased salivation. Oral candidiasis may be asymptomatic. More frequently, however, it is physically uncomfortable, and the patient may complain of burning mouth, dysgeusia, dysphagia, anorexia, and weight loss, leading to nutritional deficiency and impaired quality of life. A plethora of antifungal treatments are available. The overall prognosis of oral candidiasis is good, and rarely is the condition life threatening with invasive or recalcitrant disease.

  19. Oral administration of fermented wild ginseng ameliorates DSS-induced acute colitis by inhibiting NF-κB signaling and protects intestinal epithelial barrier.

    PubMed

    Seong, Myeong A; Woo, Jong Kyu; Kang, Ju-Hee; Jang, Yeong Su; Choi, Seungho; Jang, Young Saeng; Lee, Taek Hwan; Jung, Kyung Hoon; Kang, Dong Kyu; Hurh, Byung Seok; Kim, Dae Eung; Kim, Sun Yeou; Oh, Seung Hyun

    2015-07-01

    Ginseng has been widely used for therapeutic and preventive purposes for thousands of years. However, orally administered ginseng has very low bioavailability and absorption in the intestine. Therefore, fermented ginseng was developed to enhance the beneficial effects of ginseng in the intestine. In this study, we investigated the molecular mechanisms underlying the anti-inflammatory activity of fermented wild ginseng (FWG). We found that FWG significantly alleviated the severity of colitis in a dextran sodium sulfate (DSS)-induced colitis mouse model, and decreased expression level of pro-inflammatory cytokines in colonic tissue. Moreover, we observed that FWG suppressed the infiltration of macrophages in DSS-induced colitis. FWG also attenuated the transcriptional activity of nuclear factor-κB (NF-κB) by reducing the translocation of NF-κB into the nucleus. Our data indicate that FWG contains anti-inflammatory activity via NF-κB inactivation and could be useful for treating colitis.

  20. [EFFECT OF 4-METHYLPYRAZOLE ON IMMUNE RESPONSE, FUNCTION OF Th1 AND Th2 LYMPHOCYTES, AND CYTOKINE CONCENTRATION IN RAT BLOOD AFTER ACUTE METHANOL POISONING].

    PubMed

    Zabrodskii, P F; Maslyakov, V V; Gromov, M S

    2016-01-01

    It was established in experiments on noninbred albino rats that the acute intoxication with methanol (1.0 LD50) decreased cellular and humoral immune responses, Th2-lymphocyte activity (to a greater extent as compared to the function of Th1 cells), reduced the blood concentration of immunoregulatory (IFN-g, IL-2, IL-4) and proinflammatory (TNF, IL-1b, IL-6) cytokines on the average by 36.5% (p < 0.05), and did not affect the content of anti-inflammatory cytokines (IL-10, IL-13). Methanol antidote 4-methylpyrazole (non-competitive inhibitor of alcohol dehydrogenase) administered upon acute intoxication with methanol at a dose of 1.0 DL50 partially reduces the intoxication-induced suppression of humoral and cellular immune response, activity of T-helper cells, and production of IL-4 and restores blood levels of TNF, IL-1b, IFN-γ, IL-4, IL-2, IL-6 to the control values.

  1. [Oral candidiasis: clinical features and control].

    PubMed

    Yamamoto, Tetsuya

    2010-10-01

    Candidiasis is the most commonly encountered fungal infection, and oral candidiasis is often observed as a local opportunistic infection. Oral candidiasis is clinically divided into three types: acute forms, chronic forms, and Candida-associated lesions. Candida adhesion and multiplication are largely regulated by the local and systemic factors of the host. The local factors include impairment of the oral mucosal integrity, which is usually impaired by hyposalivation, anticancer drugs/radiation for head and neck cancers, denture wearing, a decrease in the oral bacterial population, and poor oral hygiene. Among Candida species, oral candidiasis is mostly caused by Candida albicans (C. albicans), C. glabrata, or C. tropicalis. Oral Candida induces a variety of symptoms, such as oral mucosal inflammation manifesting as an uncomfortable feeling, pain, erythema, erosion, taste abnormalities, and hyperplasia of the oral mucosa. Candida overgrowth in the oral cavity may disseminate to distant organs. Therefore, in order to avoid the sequelae of systemic candidiasis, oral candidiasis should be rapidly controlled. Oral candidiasis is usually treated by the local application of antifungal drugs. However, oral candidiasis occasionally escapes the control of such local treatment due to the development of multi-drug resistant Candida strains and species or due to the suppression of salivation or cellular immune activity. When drug-resistant strains are suspected as the pathogens and when the host is generally compromised, the oral administration of combinations of antifungal drugs, enhancement of cellular immune activity, and improvement of the nutritional condition are recommended.

  2. Acute, short- and long-term efficacy of oral bevantolol in patients with coronary artery disease: a placebo-controlled, randomized, double-blind study.

    PubMed

    Gimeno, J V; Ferrer, J; Olague, J; Bordes, P; Serra, J; Estruch, G; Mainer, V; Algarra, F J

    1986-09-01

    The efficacy and safety of bevantolol (new cardioselective beta-blocking agent without intrinsic sympathetic activity) were evaluated in chronic stable angina pectoris. Acute effects on heart rate (HR) and pulmonary function (forced expiratory volume in the first second, FEV1, and vital capacity, VC) (double-blind placebo, propranolol, 80 mg, and bevantolol, 150 mg) and the antianginal efficacy during early (double-blind placebo period) and chronic bevantolol therapy (long-term follow-up for 52 weeks) were studied. Bevantolol reduces HR in the same way as propranolol (both p less than 0.01). Pulmonary function is modified significantly only by propranolol (decreasing FEV1, p less than 0.05). Bevantolol reduces antianginal attacks and nitroglycerin consumption (p less than 0.01) and improves exercise tolerance (p less than 0.01) during early and chronic therapy.

  3. Acute, short- and long-term efficacy of oral bevantolol in patients with coronary artery disease: a placebo-controlled, randomized, double-blind study.

    PubMed

    Gimeno, J V; Ferrer, J; Olague, J; Bordes, P; Serra, J; Estruch, G; Mainer, V; Algarra, F J

    1986-09-01

    The efficacy and safety of bevantolol (new cardioselective beta-blocking agent without intrinsic sympathetic activity) were evaluated in chronic stable angina pectoris. Acute effects on heart rate (HR) and pulmonary function (forced expiratory volume in the first second, FEV1, and vital capacity, VC) (double-blind placebo, propranolol, 80 mg, and bevantolol, 150 mg) and the antianginal efficacy during early (double-blind placebo period) and chronic bevantolol therapy (long-term follow-up for 52 weeks) were studied. Bevantolol reduces HR in the same way as propranolol (both p less than 0.01). Pulmonary function is modified significantly only by propranolol (decreasing FEV1, p less than 0.05). Bevantolol reduces antianginal attacks and nitroglycerin consumption (p less than 0.01) and improves exercise tolerance (p less than 0.01) during early and chronic therapy. PMID:3530572

  4. Effect of Admission Oral Diuretic Dose on Response to Continuous versus Bolus Intravenous Diuretics in Acute Heart Failure: An Analysis from DOSE-AHF

    PubMed Central

    Shah, Ravi V.; McNulty, Steven; O'Connor, Christopher M.; Felker, G. Michael; Braunwald, Eugene; Givertz, Michael M.

    2014-01-01

    Background Results from the Diuretic Optimization Strategies in Acute Heart Failure (DOSE-AHF) study suggest that an initial continuous infusion of loop diuretics is not superior to bolus dosing with regard to clinical endpoints in AHF. We hypothesized that outpatient furosemide dose was associated with congestion and poorer renal function, and explored the hypothesis that a continuous infusion may be more effective in patients on higher outpatient diuretic doses. Methods DOSE-AHF randomized 308 patients within 24 hours of admission to high vs. low initial intravenous diuretic dose given as either a continuous infusion or bolus. We compared baseline characteristics and assessed associations between mode of administration (bolus vs. continuous) and outcomes in patients receiving high-dose (≥120 mg furosemide equivalent, n=177) versus low-dose (<120 mg furosemide equivalent, n=131) outpatient diuretics. Results Patients on higher doses of furosemide were less frequently on renin-angiotensin system inhibitors (P=.01), and had worse renal function and more advanced symptoms. There was a significant interaction between outpatient dose and mode of therapy (P=0.01) with respect to net fluid loss at 72 hours after adjusting for creatinine and intensification strategy. Admission diuretic dose was associated with an increased risk of death or rehospitalization at 60 days (adjusted HR=1.08 per 20-mg increment in dose, 95% CI 1.01–1.16, P=.03). Conclusions In acute HF, patients on higher diuretic doses have greater disease severity, and may benefit from an initial bolus strategy. PMID:23194486

  5. Acute contact toxicity test of insecticides (Cipermetrina 25, Lorsban 48E, Thionex 35) on honeybees in the southwestern zone of Uruguay.

    PubMed

    Carrasco-Letelier, Leonidas; Mendoza-Spina, Yamandú; Branchiccela, María Belén

    2012-07-01

    Glyphosate-resistant soybean cultivation is expanding rapidly in Uruguay, with its land area having increased by 95 times during the past 10 years. Because of the region's Neotropical conditions, insecticide use is required to ensure adequate soybean productivity. However, in areas shared by soybean crops and beekeepers - such as the southwestern zone of Uruguay (SWZU) - the use of insecticides can increase the risks of honeybee death and honey contamination. Uruguayan commercial and legal guidelines set out practices and field doses designed to prevent acute intoxication with insecticides. However, honeybees in the SWZU are predominantly a polyhybrid subspecies different from that used to set international reference values, and hence they may have a different acute toxicity response, thus rendering such precautions ineffective. The aim of this work was to assess the acute toxicity response of polyhybrid honeybees in the SWZU to cypermethrin (commercial formulation: Cipermetrina 25 Agrin®), chlorpyrifos (commercial formulation: Lorsban 48E®), and endosulfan (commercial formulation: Thionex 35®). Acute toxicity bioassays were conducted to determine the median lethal dose (LD(50)) of each insecticide for the honeybees. The results indicate that, compared with EU reference values, SWZU honeybees have a higher toxicological sensitivity to chlorpyrifos and endosulfan, and a lower toxicological sensitivity to cypermethrin, based on the commercial formulations tested. However, when these results were adjusted according to their field dose equivalents, only chlorpyrifos emerged as a potential problem for beekeeping, as the maximum recommended field dose of Lorsban 48E® for soybean crops in Uruguay is 23 times the corresponding LD(50) for honeybees in the SWZU. PMID:22440636

  6. Acute contact toxicity test of insecticides (Cipermetrina 25, Lorsban 48E, Thionex 35) on honeybees in the southwestern zone of Uruguay.

    PubMed

    Carrasco-Letelier, Leonidas; Mendoza-Spina, Yamandú; Branchiccela, María Belén

    2012-07-01

    Glyphosate-resistant soybean cultivation is expanding rapidly in Uruguay, with its land area having increased by 95 times during the past 10 years. Because of the region's Neotropical conditions, insecticide use is required to ensure adequate soybean productivity. However, in areas shared by soybean crops and beekeepers - such as the southwestern zone of Uruguay (SWZU) - the use of insecticides can increase the risks of honeybee death and honey contamination. Uruguayan commercial and legal guidelines set out practices and field doses designed to prevent acute intoxication with insecticides. However, honeybees in the SWZU are predominantly a polyhybrid subspecies different from that used to set international reference values, and hence they may have a different acute toxicity response, thus rendering such precautions ineffective. The aim of this work was to assess the acute toxicity response of polyhybrid honeybees in the SWZU to cypermethrin (commercial formulation: Cipermetrina 25 Agrin®), chlorpyrifos (commercial formulation: Lorsban 48E®), and endosulfan (commercial formulation: Thionex 35®). Acute toxicity bioassays were conducted to determine the median lethal dose (LD(50)) of each insecticide for the honeybees. The results indicate that, compared with EU reference values, SWZU honeybees have a higher toxicological sensitivity to chlorpyrifos and endosulfan, and a lower toxicological sensitivity to cypermethrin, based on the commercial formulations tested. However, when these results were adjusted according to their field dose equivalents, only chlorpyrifos emerged as a potential problem for beekeeping, as the maximum recommended field dose of Lorsban 48E® for soybean crops in Uruguay is 23 times the corresponding LD(50) for honeybees in the SWZU.

  7. Effectiveness of chelation therapy with time after acute uranium intoxication

    SciTech Connect

    Domingo, J.L.; Ortega, A.; Llobet, J.M.; Corbella, J. )

    1990-01-01

    The effect of increasing the time interval between acute uranium exposure and chelation therapy was studied in male Swiss mice. Gallic acid, 4,5-dihydroxy-1,3- benzenedisulfonic acid (Tiron), diethylenetriaminepentaacetic acid (DTPA), and 5-aminosalicylic acid (5-AS) were administered ip at 0, 0.25, 1, 4, and 24 hr after sc injection of 10 mg/kg of uranyl acetate dihydrate. Chelating agents were given at doses equal to one-fourth of their respective LD50 values. Daily elimination of uranium into urine and feces was determined for 4 days after which time the mice were killed, and the concentration of uranium was measured in kidney, spleen, and bone. The excretion of uranium was especially rapid in the first 24 hr. Treatment with Tiron or gallic acid at 0, 0.25, or 1 hr after uranium exposure significantly increased the total excretion of the metal. In kidney and bone, only administration of Tiron at 0, 0.25, or 1 hr after uranium injection, or gallic acid at 1 hr after uranium exposure significantly reduced tissue uranium concentrations. Treatment at later times (4 to 24 hr) did not increase the total excretion of the metal and did not decrease the tissue uranium concentrations 4 days after uranyl acetate administration. The results show that the length of time before initiating chelation therapy for acute uranium intoxication greatly influences the effectiveness of this therapy.

  8. Isolation of an orally active insecticidal toxin from the venom of an Australian tarantula.

    PubMed

    Hardy, Margaret C; Daly, Norelle L; Mobli, Mehdi; Morales, Rodrigo A V; King, Glenn F

    2013-01-01

    Many insect pests have developed resistance to existing chemical insecticides and consequently there is much interest in the development of new insecticidal compounds with novel modes of action. Although spiders have deployed insecticidal toxins in their venoms for over 250 million years, there is no evolutionary selection pressure on these toxins to possess oral activity since they are injected into prey and predators via a hypodermic needle-like fang. Thus, it has been assumed that spider-venom peptides are not orally active and are therefore unlikely to be useful insecticides. Contrary to this dogma, we show that it is possible to isolate spider-venom peptides with high levels of oral insecticidal activity by directly screening for per os toxicity. Using this approach, we isolated a 34-residue orally active insecticidal peptide (OAIP-1) from venom of the Australian tarantula Selenotypus plumipes. The oral LD50 for OAIP-1 in the agronomically important cotton bollworm Helicoverpa armigera was 104.2±0.6 pmol/g, which is the highest per os activity reported to date for an insecticidal venom peptide. OAIP-1 is equipotent with synthetic pyrethroids and it acts synergistically with neonicotinoid insecticides. The three-dimensional structure of OAIP-1 determined using NMR spectroscopy revealed that the three disulfide bonds form an inhibitor cystine knot motif; this structural motif provides the peptide with a high level of biological stability that probably contributes to its oral activity. OAIP-1 is likely to be synergized by the gut-lytic activity of the Bacillus thuringiensis Cry toxin (Bt) expressed in insect-resistant transgenic crops, and consequently it might be a good candidate for trait stacking with Bt. PMID:24039872

  9. Isolation of an Orally Active Insecticidal Toxin from the Venom of an Australian Tarantula

    PubMed Central

    Hardy, Margaret C.; Daly, Norelle L.; Mobli, Mehdi; Morales, Rodrigo A. V.; King, Glenn F.

    2013-01-01

    Many insect pests have developed resistance to existing chemical insecticides and consequently there is much interest in the development of new insecticidal compounds with novel modes of action. Although spiders have deployed insecticidal toxins in their venoms for over 250 million years, there is no evolutionary selection pressure on these toxins to possess oral activity since they are injected into prey and predators via a hypodermic needle-like fang. Thus, it has been assumed that spider-venom peptides are not orally active and are therefore unlikely to be useful insecticides. Contrary to this dogma, we show that it is possible to isolate spider-venom peptides with high levels of oral insecticidal activity by directly screening for per os toxicity. Using this approach, we isolated a 34-residue orally active insecticidal peptide (OAIP-1) from venom of the Australian tarantula Selenotypus plumipes. The oral LD50 for OAIP-1 in the agronomically important cotton bollworm Helicoverpa armigera was 104.2±0.6 pmol/g, which is the highest per os activity reported to date for an insecticidal venom peptide. OAIP-1 is equipotent with synthetic pyrethroids and it acts synergistically with neonicotinoid insecticides. The three-dimensional structure of OAIP-1 determined using NMR spectroscopy revealed that the three disulfide bonds form an inhibitor cystine knot motif; this structural motif provides the peptide with a high level of biological stability that probably contributes to its oral activity. OAIP-1 is likely to be synergized by the gut-lytic activity of the Bacillus thuringiensis Cry toxin (Bt) expressed in insect-resistant transgenic crops, and consequently it might be a good candidate for trait stacking with Bt. PMID:24039872

  10. Acute oral gallium arsenide exposure and changes in certain hematological, hepatic, renal and immunological indices at different time intervals in male Wistar rats.

    PubMed

    Flora, S J; Kumar, P; Kannan, G M; Rai, G P

    1998-01-31

    Male albino rats were given a single oral dose of gallium arsenide (GaAs) (100, 200 or 500 mg/kg). Erythrocyte delta-aminolevulinic acid dehydratase (ALAD) activity was inhibited in all the three GaAs-exposed groups accompanied by elevated urinary excretion of ALA. A significant increase in serum aspartate aminotransferase (AST) activity, and gamma-glutamyltranspeptidase (gamma-GT) was observed. A significant increase in hepatic malondialdehyde (MDA) and a decrease in hepatic glutathione contents were also noted. Renal alkaline phosphatase activity, urinary ALA and protein excretion increased significantly on GaAs exposure. These changes were accompanied by significant alterations in almost all the immunological variables, with an increase in gallium and arsenic concentration in blood and soft tissues. While most of the above biochemical alterations were prominent at day 7 following single exposure to 200 and 500 mg/kg GaAs, most of the immunological indices altered with all the three doses and remained high even at day 21. The results suggest only a moderate effect of GaAs on renal and hepatic tissues. By contrast, immunological and haematological systems are the most vulnerable to the toxic effects of GaAs.

  11. Oral administration of fermented wild ginseng ameliorates DSS-induced acute colitis by inhibiting NF-κB signaling and protects intestinal epithelial barrier

    PubMed Central

    Seong, Myeong A; Woo, Jong Kyu; Kang, Ju-Hee; Jang, Yeong Su; Choi, Seungho; Jang, Young Saeng; Lee, Taek Hwan; Jung, Kyung Hoon; Kang, Dong Kyu; Hurh, Byung Seok; Kim, Dae Eung; Kim, Sun Yeou; Oh, Seung Hyun

    2015-01-01

    Ginseng has been widely used for therapeutic and preventive purposes for thousands of years. However, orally administered ginseng has very low bioavailability and absorption in the intestine. Therefore, fermented ginseng was developed to enhance the beneficial effects of ginseng in the intestine. In this study, we investigated the molecular mechanisms underlying the anti-inflammatory activity of fermented wild ginseng (FWG). We found that FWG significantly alleviated the severity of colitis in a dextran sodium sulfate (DSS)-induced colitis mouse model, and decreased expression level of pro-inflammatory cytokines in colonic tissue. Moreover, we observed that FWG suppressed the infiltration of macrophages in DSS-induced colitis. FWG also attenuated the transcriptional activity of nuclear factor-κB (NF-κB) by reducing the translocation of NF-κB into the nucleus. Our data indicate that FWG contains anti-inflammatory activity via NF-κB inactivation and could be useful for treating colitis. [BMB Reports 2015; 48(7): 419-425] PMID:25936779

  12. Dose-dependent antioxidant responses and pathological changes in tenca (Tinca tinca) after acute oral exposure to Microcystis under laboratory conditions.

    PubMed

    Atencio, L; Moreno, I; Jos, A; Pichardo, S; Moyano, R; Blanco, A; Cameán, A M

    2008-07-01

    The effects of cyanobacterial cells containing microcystins (MCs), toxins from cyanobacteria, on oxidative stress biomarkers from liver and kidney of Tenca fish (Tinca tinca) were investigated under laboratory conditions. Moreover, a histopathological study of liver, kidney, heart and intestine tissues was performed. Fish were orally exposed to cyanobacterial cells dosing 0, 5, 11, 25 and 55 microg MC-LR/fish mixed with the food. Results showed a dose-dependent decrease of superoxide dismutase (SOD) activity, and also of catalase (CAT) in the liver. Glutathione levels and protein oxidation, however, were not altered by the exposure to the cyanobacterial material. The microscopic study revealed tissue alterations even at the lower cyanobacterial cells doses. Onion-like hepatocytes in the liver, glomerulopathy in the kidney, loss of myofibrils in the heart and vacuolated enterocytes in the gastrointestinal tract were the main changes observed. These findings suggest that this fresh water fish can be adversely affected by cyanobacterial blooms in their natural habitats. PMID:18588906

  13. [Immune homeostasis impairment in acute carbon tetrachloride intoxicated rats corrected by administration of tocopherol acetate and unithiol].

    PubMed

    Zabrodskiĭ, P F; Gromov, M S; Masliakov, V V

    2015-01-01

    The results of experiments on noninbred albino rats showed that the acute intoxication with carbon tetrachloride (CT) at a dose of 1 LD50 reduced the parameters of cellular immune response and function of Th1 cells more significantly than the levels of humoral immune response and Th2-lymphocyte function, decreases the blood content of immunoregulatory cytokines IFN-g, IL-2, IL-4 and anti-inflammatory cytokine IL-13, while not changing the concentration of anti-inflammatory cytokine IL-10 and increasing the concentration of pro-inflammatory cytokine IL-6. The application of unithiol, tocopherol acetate, and combinations partially restores the parameters examined. The combined effects of drugs during intoxication with CT does not exceed their separate action.

  14. Diarrhoea in adults (acute)

    PubMed Central

    2008-01-01

    Introduction An estimated 4000 million cases of diarrhoea occurred worldwide in 1996, resulting in 2.5 million deaths. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatments for acute diarrhoea in adults living in resource-rich countries? What are the effects of treatments for acute mild-to-moderate diarrhoea in adults from resource-rich countries traveling to resource-poor countries? What are the effects of treatments for acute mild-to-moderate diarrhoea in adults living in resource-poor countries? What are the effects of treatments for acute severe diarrhoea in adults living in resource-poor countries? We searched: Medline, Embase, The Cochrane Library and other important databases up to January 2007 (BMJ Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 71 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review we present information relating to the effectiveness and safety of the following interventions: antibiotics, antimotility agents, antisecretory agents, bismuth subsalicylate, diet, intravenous rehydration, nasogastric tube rehydration, and oral rehydration solutions (amino acid oral rehydration solution, bicarbonate oral rehydration solution, reduced osmolarity oral rehydration solution, rice-based oral rehydration solution, standard oral rehydration solution). PMID:19450323

  15. Diarrhoea in adults (acute)

    PubMed Central

    2011-01-01

    Introduction An estimated 4.6 billion cases of diarrhoea occurred worldwide in 2004, resulting in 2.2 million deaths. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatments for acute diarrhoea in adults living in resource-rich countries? What are the effects of treatments for acute mild-to-moderate diarrhoea in adults from resource-rich countries travelling to resource-poor countries? What are the effects of treatments for acute mild-to-moderate diarrhoea in adults living in resource-poor countries? What are the effects of treatments for acute severe diarrhoea in adults living in resource-poor countries? We searched: Medline, Embase, The Cochrane Library, and other important databases up to January 2010 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 72 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review we present information relating to the effectiveness and safety of the following interventions: antibiotics, antimotility agents, antisecretory agents, bismuth subsalicylate, diet, intravenous rehydration, nasogastric tube rehydration, oral rehydration solutions (amino acid oral rehydration solution, bicarbonate oral rehydration solution, reduced osmolarity oral rehydration solution, rice-based oral rehydration solution, standard oral rehydration solution), vitamin A supplementation, and zinc supplementation. PMID:21718555

  16. Health Impacts from Acute Radiation Exposure

    SciTech Connect

    Strom, Daniel J.

    2003-09-30

    Absorbed doses above1-2 Gy (100-200 rads) received over a period of a day or less lead to one or another of the acute radiation syndromes. These are the hematopoietic syndrome, the gastrointestinal (GI) syndrome, the cerebrovascular (CV) syndrome, the pulmonary syndrome, or the cutaneous syndrome. The dose that will kill about 50% of the exposed people within 60 days with minimal medical care, LD50-60, is around 4.5 Gy (450 rads) of low-LET radiation measured free in air. The GI syndrome may not be fatal with supportive medical care and growth factors below about 10 Gy (1000 rads), but above this is likely to be fatal. Pulmonary and cutaneous syndromes may or may not be fatal, depending on many factors. The CV syndrome is invariably fatal. Lower acute doses, or protracted doses delivered over days or weeks, may lead to many other health outcomes than death. These include loss of pregnancy, cataract, impaired fertility or temporary or permanent sterility, hair loss, skin ulceration, local tissue necrosis, developmental abnormalities including mental and growth retardation in persons irradiated as children or fetuses, radiation dermatitis, and other symptoms listed in Table 2 on page 12. Children of parents irradiated prior to conception may experience heritable ill-health, that is, genetic changes from their parents. These effects are less strongly expressed than previously thought. Populations irradiated to high doses at high dose rates have increased risk of cancer incidence and mortality, taken as about 10-20% incidence and perhaps 5-10% mortality per sievert of effective dose of any radiation or per gray of whole-body absorbed dose low-LET radiation. Cancer risks for non-uniform irradiation will be less.

  17. Chronic oral administration of low-dose combination of fenofibrate and rosuvastatin protects the rat heart against experimentally induced acute myocardial infarction.

    PubMed

    Garg, Monika; Khanna, Deepa; Kalra, Sanjeev; Balakumar, Pitchai

    2016-10-01

    Fenofibrate and rosuvastatin at low doses might have experimental pleiotropic benefits. This study investigated the combined effect of low doses of fenofibrate and rosuvastatin in isoproterenol-induced experimental myocardial infarction. Rats administered isoproterenol (85 mg/kg/day, s.c.) for 2 days (day 29 and day 30) of 30 days experimental protocol developed significant myocardial infarction that was accompanied with high myocardial oxidative stress and lipid peroxidation, elevated serum markers of cardiac injury, lipid abnormalities, and elevated circulatory levels of C-reactive protein. Pretreatment with low doses of fenofibrate (30 mg/kg/day p.o., 30 days) and rosuvastatin (2 mg/kg/day p.o., 30 days) both alone or in combination markedly prevented isoproterenol-induced myocardial infarction and associated abnormalities while the low-dose combination of fenofibrate and rosuvastatin was more effective. Histopathological study in isoproterenol control rat heart showed necrosis with edema and acute inflammation at the margins of necrotic area. The rat heart from low-dose fenofibrate and rosuvastatin pretreated group showed scanty inflammation and no ischemia. In conclusion, fenofibrate and rosuvastatin pretreatment in low doses might have a therapeutic potential to prevent the pathogenesis of myocardial infarction. Moreover, their combined treatment option might offer superior therapeutic benefits via a marked reduction in myocardial infarct size and oxidative stress, suggesting a possibility of their pleiotropic cardioprotective action at low doses. PMID:27148865

  18. Comparison of sesion severity, distribution, and colonic mucin expression in pigs with acute swine dysentery following oral inoculation with "Brachyspira hampsonii" or Brachyspira hyodysenteriae.

    PubMed

    Wilberts, B L; Arruda, P H; Kinyon, J M; Madson, D M; Frana, T S; Burrough, E R

    2014-11-01

    Swine dysentery is classically associated with infection by Brachyspira hyodysenteriae, the only current officially recognized Brachyspira sp. that consistently imparts strong beta-hemolysis on blood agar. Recently, several strongly beta-hemolytic Brachyspira have been isolated from swine with clinical dysentery that are not identified as B. hyodysenteriae by PCR including the recently proposed species "Brachyspira hampsonii." In this study, 6-week-old pigs were inoculated with either a clinical isolate of "B. hampsonii" (EB107; n = 10) clade II or a classic strain of B. hyodysenteriae (B204; n = 10) to compare gross and microscopic lesions and alterations in colonic mucin expression in pigs with clinical disease versus controls (n = 6). Gross lesions were similar between infected groups. No histologic difference was observed between infected groups with regard to neutrophilic inflammation, colonic crypt depth, mucosal ulceration, or hemorrhage. Histochemical and immunohistochemical evaluation of the apex of the spiral colon revealed decreased expression of sulphated mucins, decreased expression of MUC4, and increased expression of MUC5AC in diseased pigs compared to controls. No difference was observed between diseased pigs in inoculated groups. This study reveals significant alterations in colonic mucin expression in pigs with acute swine dysentery and further reveals that these and other microscopic changes are similar following infection with "B. hampsonii" clade II or B. hyodysenteriae.

  19. Oral cysticercosis.

    PubMed

    Chunduri, Nagendra S; Goteki, Venkateswarulu; Gelli, Vamsi; Madasu, Krishnaveni

    2013-03-01

    Cysticercosis is a common disease in developing countries, but oral lesions caused by this parasitic infestation are rare. We report here a rare case of oral cysticercosis in a 17 year old male who sought treatment for an asymptomatic nodule of the lower lip that had previously been diagnosed as a mucocele. PMID:23691623

  20. [Aphthous ulcers and oral ulcerations].

    PubMed

    Vaillant, Loïc; Samimi, Mahtab

    2016-02-01

    Aphthous ulcers are painful ulcerations located on the mucous membrane, generally in the mouth, less often in the genital area. Three clinical forms of aphthous ulcers have been described: minor aphthous ulcers, herpetiform aphthous ulcers and major aphthous ulcers. Many other conditions presenting with oral bullous or vesiculous lesions orulcerations and erosions can be mistaken for aphthous ulcers. Currently, treatment of aphthous ulcers is palliative and symptomatic. Topical treatments (topical anesthetics, topical steroids and sucralfate) are the first line therapy. Recurrent aphthous stomatitis (RAS) is defined by the recurrence of oral aphthous ulcers at least 4 times per year. RAS is often idiopathic but can be associated with gastro-intestinal diseases (i.e. celiac disease, inflammatory bowel diseases), nutritional deficiencies (iron, folates...), immune disorders (HIV infection, neutropenia) and rare syndromes. Behçet's disease is a chronic, inflammatory, disease whose main clinical feature is recurrent bipolar aphthosis. Colchicine associated with topical treatments constitutes a suitable treatment of most RAS. Thalidomide is the most effective treatment of RAS but its use is limited by frequent adverse effects. Oral ulcers can be related to a wide range of conditions that constitute the differential diagnoses of aphthous ulcers. Oral ulcers are classified into three main groups: acute ulcers with abrupt onset and short duration, recurrent ulcers (mainly due to postherpetic erythema multiforme) and chronic ulcers (with slow onset and insidious progression). Acute oral ulcers are due to trauma, bacterial infections (including acute necrotizing ulcerative gingivitis), deep fungal infection, gastro-intestinal (namely inflammatory bowel disease) or systemic diseases. Chronic oral ulcers may be drug-induced, or due to benign or malignant tumors. Every oral solitary chronic ulcer should be biopsied to rule out squamous cell carcinoma. A solitary palatal ulcer

  1. Dose-related effects following oral exposure of 2,4-dinitrotoluene on the Western fence lizard, Sceloporus occidentalis.

    PubMed

    Suski, Jamie G; Salice, Christopher; Houpt, John T; Bazar, Matthew A; Talent, Larry G

    2008-02-01

    2,4-dintitrotoluene (2,4-DNT) is an explosive frequently found in the soil of military installations. Because reptiles can be common on these sites, ecological risk assessments for compounds such as 2,4-DNT could be improved with toxicity data specific to reptiles. Western fence lizards, Sceloporus occidentalis, were used to develop a laboratory toxicity model for reptiles. A hierarchical approach was used; acute to subchronic studies were conducted to provide toxicity data relevant to short- and long-term exposures. First, a modified median lethal dose (LD50) study was conducted on male and female lizards using a stage-wise probit model. The LD50 was 577 mg/kg for female and 380 mg/kg for male lizards. Subsequently, a subacute experiment was conducted to further assess 2,4-DNT toxicity to male lizards and to define exposure levels for a longer term, subchronic study. The subchronic study was conducted for 60 consecutive days; male lizards were exposed to 0, 9, 15, 25, 42, 70 mg/kg/d. Dose-dependent mortality was observed in the three highest dose groups (25, 42, and 70 mg/kg/d); all other animals survived the study duration. Benchmark dose model calculations based on mortality indicated a 5% effect level of 15.8 mg/kg/d. At study termination, a gross necropsy was performed, organ weights were taken, and blood was collected for clinical and hematological analysis. Body weight, kidney weight, food consumption, postdose observations, and blood chemistries all were found to be significantly different from controls at doses above 9 mg/kg/d. Also, preliminary results suggest behavioral observations, and reduced food consumption may be a sensitive indicator of toxicity. The present study indicates Sceloporus occidentalis is suitable for evaluating toxicity of compounds to reptilian species. PMID:18348623

  2. Oral cenesthopathy.

    PubMed

    Umezaki, Yojiro; Miura, Anna; Watanabe, Motoko; Takenoshita, Miho; Uezato, Akihito; Toriihara, Akira; Nishikawa, Toru; Toyofuku, Akira

    2016-01-01

    Cenesthopathy is characterized by abnormal and strange bodily sensations and is classified as a 'delusional disorder, somatic type' or 'somatoform disorder' according to the DSM 5. The oral cavity is one of the frequent sites of cenesthopathy, thus the term 'oral cenesthopathy.' Patients with oral cenesthopathy complain of unusual sensations without corresponding abnormal findings in the oral area, such as excessive mucus secretion, a slimy sensation, or a feeling of coils or wires being present within the oral region. They usually visit multiple dentists rather than psychiatrists. Without a proper diagnosis, they repeatedly pursue unnecessary surgical procedures to remove their 'foreign body'. This sometimes creates a dilemma between the dentists and patients. The nosography of oral cenesthopathy has been discussed in some case reports and reviews but is overlooked in mainstream medicine. This review focuses on the various aspects of oral cenesthopathy. The estimated prevalence of cenesthopathy was 0.2 to 1.9 % in a study done at a Japanese university psychiatry clinic and 27 % in a study done at a Japanese psychosomatic dentistry clinic. Oral cenesthopathy do not have clear disposition, while some studies reported that elderly women were most commonly affected. Its pathophysiology has not been fully elucidated. However, recent studies have suggested a right > left asymmetrical pattern of the cerebral blood flow of patients with oral cenesthopathy. Antidepressants, antipsychotic drugs, electroconvulsive therapy, and psychotherapy might be effective in some cases, though it is known to be intractable. To date, the epidemiology, pathophysiology, etiology, classification and treatment of oral cenesthopathy are unknown due to the few reports on the disorder, though there are a few case reports. To overcome this difficult medical condition, clinico-statistical and case-control studies done under rigorous criteria and with a large sample size are required. PMID

  3. Risk of Acute Liver Injury Associated with the Use of Moxifloxacin and Other Oral Antimicrobials: A Retrospective, Population-Based Cohort Study

    PubMed Central

    Kaye, James A; Castellsague, Jordi; Bui, Christine L; Calingaert, Brian; McQuay, Lisa J; Riera-Guardia, Nuria; Saltus, Catherine W; Quinlan, Scott; Holick, Crystal N; Wahl, Peter M; Suzart, Kiliana; Rothman, Kenneth J; Wallander, Mari-Ann; Perez-Gutthann, Susana

    2014-01-01

    Study Objective To estimate the incidence and relative risk of a hospitalization or emergency visit for noninfectious liver injury in users of eight oral antimicrobials—amoxicillin, amoxicillin-clavulanic acid, clarithromycin, cefuroxime, doxycycline, levofloxacin, moxifloxacin, telithromycin—compared with nonusers of these antimicrobials. Design Retrospective, observational cohort study with a nested case-control analysis. Data Source HealthCore Integrated Research Database. Patients Adults with continuous health plan enrollment for at least 6 months before study entry who had a new dispensing of a study antimicrobial between July 1, 2001, and March 31, 2009. Cases had diagnoses indicating noninfectious liver injury during follow-up. To control for potentially confounding risk factors, 10 controls at risk for liver injury during follow-up were matched to each case by age, sex, and event date (liver injury date of the case), and analyses were adjusted for medical history, concomitant drugs, and health care service use. Measurements and Main Results Two physician reviewers (blind to exposure) validated the cases. Among 1.3 million antimicrobial users, we identified 607 cases of liver injury, including 82 cases of severe hepatocellular injury and 11 cases of liver failure. Liver injury incidence in nonusers of study antimicrobials was 35/100,000 person-years (95% confidence interval [CI] 29–42/100,000 person-years). For valid cases, the adjusted relative risk among current users of multiple antimicrobials was 3.2 (95% CI 1.6–6.7). Levofloxacin had the highest relative risk for current single use (3.2, 95% CI 1.8–5.8). Relative risks were also elevated for amoxicillin-clavulanic acid (2.5, 95% CI 1.3–5.0), doxycycline (2.5, 95% CI 1.2–5.2), moxifloxacin (2.3, 95% CI 1.1–4.7), and amoxicillin (2.3, 95% CI 1.1–4.7). Conclusion The results support a comparatively high adjusted relative risk of liver injury among patients exposed concurrently to

  4. Cystitis - acute

    MedlinePlus

    Uncomplicated urinary tract infection; UTI - acute; Acute bladder infection; Acute bacterial cystitis ... International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: A 2010 ...

  5. Oral complications of cancer therapies. Oral complications in the pediatric population

    SciTech Connect

    Leggott, P.J. )

    1990-01-01

    A number of acute oral complications may be associated with cancer therapy in children, but the extent and duration of these complications, and the most effective management techniques. have not been well described. The few studies differ in design, making comparisons difficult. Well-controlled, prospective clinical studies are needed to define the most effective strategies for the management of acute oral complications in children. However, it is clear that dental intervention prior to cancer therapy is an important factor in the optimal preparation of the patient. During cancer therapy, intensive supervised oral preventive protocols appear to be of benefit to the child's oral health, overall comfort, and well-being. Furthermore, the prevention of oral infection may significantly reduce the morbidity associated with cancer therapy. Long-term preventive oral care may help prevent dental disease and infection in medically compromised children and contribute to improving the quality of life. 41 references.

  6. Novel Oral P2Y12 Inhibitor Prasugrel vs. Clopidogrel in Patients with Acute Coronary Syndrome: Evidence Based on 6 Studies

    PubMed Central

    Jia, Min; Li, Zaibo; Chu, Hongtao; Li, Lin; Chen, Keyong

    2015-01-01

    Background Whether prasugrel can take the place of clopidogrel for patients with acute coronary syndrome (ACS) is not clear. The aim of this study was to perform a meta-analysis for systematically reviewing the evidence on prasugrel in comparison to clopidogrel in patients with ACS. Material/Methods Relevant prospective and retrospective studies were searched in databases. Six studies were finally included. Pooled risk ratios (RRs) and 95% confidence intervals (CIs) were calculated to assess all causes of death, myocardial infarction (MI), stroke, major bleeding, major/minor bleeding, and stent thrombosis (for PCI performed). Results Compared with clopidogrel, prasugrel had similar risks of all cause of death (Pooled RR: 0.83; 95% CI: 0.64–1.06, p=0.14, I2=55%), MI (Pooled RR: 0.86; 95% CI: 0.71–1.04, p=0.12) and stroke (pooled RR: 0.88; 95% CI: 0.70–1.10, p=0.25). However, prasugrel was associated with significantly higher risk of both major bleeding (Pooled RR: 1.19; 95% CI: 0.99–1.44, p=0.06, I2=0%) and the risk of total major and minor bleeding (Pooled RR: 1.30; 95% CI: 1.15–1.48, p<0.0001, I2=0%). For the patients who underwent percutaneous coronary intervention (PCI), prasugrel was associated with significantly lower risk of stent thrombosis (Pooled RR: 0.47; 95% CI: 0.34–0.61, p<0.00001, I2=0%). Conclusions Prasugrel has similar effects as clopidogrel in terms of all causes of death, MI, and stroke in ACS patients. For the patients who underwent PCI, prasugrel contributes to lower risk of stent thrombosis. However, prasugrel is associated with significantly higher risk of bleeding. For the patients with active pathological bleeding or a history of stroke and/or TIA, prasugrel should not be recommended. PMID:25893318

  7. Formulated Beta-Cyfluthrin Shows Wide Divergence in Toxicity among Bird Species

    PubMed Central

    Addy-Orduna, Laura M.; Zaccagnini, María-Elena; Canavelli, Sonia B.; Mineau, Pierre

    2011-01-01

    It is generally assumed that the toxicity of pyrethroid insecticides to birds is negligible, though few species have been tested. The oral acute toxicity of formulated beta-cyfluthrin was determined for canaries (Serinus sp.), shiny cowbirds (Molothrus bonariensis), and eared doves (Zenaida auriculata). Single doses were administered to adults by gavage. Approximate lethal doses 50 (LD50) and their confidence intervals were determined by approximate D-optimal design. Canaries were found to be substantially more sensitive to formulated beta-cyfluthrin (LD50 = (170 ± 41) mg/kg) than the other two species tested (LD50 = (2234 ± 544) mg/kg and LD50 = (2271 ± 433) mg/kg, resp.). The LD50 obtained for canaries was also considerably lower than typical toxicity values available in the literature for pyrethroids. This study emphasizes the need for testing a broader range of species with potentially toxic insecticides, using modern up and down test designs with minimal numbers of birds. PMID:21584255

  8. Pharmacokinetics of eight anticoagulant rodenticides in mice after single oral administration.

    PubMed

    Vandenbroucke, V; Bousquet-Melou, A; De Backer, P; Croubels, S

    2008-10-01

    The first aim of the study was to investigate the pharmacokinetics of eight anticoagulant rodenticides (brodifacoum, bromadiolone, chlorophacinone, coumatetralyl, difenacoum, difethialone, flocoumafen and warfarin) in plasma and liver of the mouse after single oral administration. Eight groups of mice dosed orally with a different anticoagulant rodenticide in a dose equal to one-half the lethal dose 50 (LD(50)), were killed at various times up to 21 days after administration. The eight anticoagulant rodenticides were assayed in plasma and liver by an LC-ESI-MS/MS method. Depending on the compound, the limit of quantification was set at 1 or 5 ng/mL in plasma. In liver, the limit of quantification was set at 250 ng/g for coumatetralyl and warfarin and at 100 ng/g for the other compounds. The elimination half-lives in plasma for first-generation rodenticides were shorter than those for second-generation rodenticides. Coumatetralyl, a first-generation product, had a plasma elimination half-life of 0.52 days. Brodifacoum, a second-generation product, showed a plasma elimination half-life of 91.7 days. The elimination half-lives in liver varied from 15.8 days for coumatetralyl to 307.4 days for brodifacoum. The second aim of the study was to illustrate the applicability of the developed method in a clinical case of a dog suspected of rodenticide poisoning. PMID:19000263

  9. Mouse Model of Oral Infection with Virulent Type A Francisella tularensis▿

    PubMed Central

    KuoLee, R.; Zhao, X.; Austin, J.; Harris, G.; Conlan, J. W.; Chen, W.

    2007-01-01

    Francisella tularensis is a gram-negative facultative intracellular pathogen and the causative agent of tularemia. Little is known about the immunopathogenesis of oral infection with this pathogen. Here, for the first time, we examined the susceptibility of mice to intragastric inoculation with virulent type A F. tularensis and characterized the course of infection and the associated host responses. Both immunocompetent and immunodeficient mice were relatively susceptible to intragastric inoculation of type A F. tularensis with a 50% lethal dose (LD50) of 106 organisms, which was 100,000-fold higher than the LD100 for intradermal or respiratory routes of infection. Mice deficient in gamma interferon or tumor necrosis factor receptors 1 and 2 were more susceptible than wild-type controls to oral infection with a high dose of the pathogen. After oral inoculation, F. tularensis appeared first in the mesenteric lymph nodes (MLN) and then rapidly spread to the livers and spleens, where the organism multiplied to high numbers and induced marked neutrophilic infiltration and severe tissue necrosis. Infected mice showed rapid increases in tissue cytokine mRNA expression, which peaked in the MLN at 2 days postinfection (dpi) and in the liver and spleen at 3 dpi. The levels of gamma interferon, interleukin-1β (IL-1β), IL-6, tumor necrosis factor alpha, macrophage inflammatory protein 1α, KC, interferon-inducible protein 10, and monocyte chemotactic protein 1 were elevated from day 2 postinoculation onward. Moreover, mice intradermally immunized with the live vaccine strain of F. tularensis showed little survival advantage over naive mice after oral challenge with type A F. tularensis. These results suggest that type A F. tularensis is an effective oral pathogen that can cause fatal systemic infection and could pose a public health concern, particularly to immunocompromised individuals, if ingested in contaminated water and food. PMID:17242058

  10. Ampicillin Oral

    MedlinePlus

    ... capsule, liquid, and pediatric drops to take by mouth. It is usually taken every 6 hours (four ... blood thinners') such as warfarin (Coumadin), atenolol (Tenormin), oral contraceptives, probenecid (Benemid), rifampin, sulfasalazine, and vitamins.tell ...

  11. 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.

  12. Oral Cancer

    MedlinePlus

    ... swallowing A lump in your neck An earache Oral cancer treatments may include surgery, radiation therapy or chemotherapy. Some patients have a combination of treatments. NIH: National Cancer Institute

  13. Oral Health

    MedlinePlus

    ... its box has the American Dental Association's (ADA) seal of acceptance, it is good for your oral ... dispensed solutions have the American Dental Association (ADA) seal. Other over-the-counter whitening products include whitening ...

  14. Oral Cancer

    MedlinePlus

    ... use. Some oral cancers are linked to human papilloma virus (HPV) infections of the mouth and throat. ... The number of oropharyngeal cancers linked to human papilloma virus (HPV) has risen dramatically over the past ...

  15. Acute toxicity and risk assessment of permethrin, naled, and dichlorvos to larval butterflies via ingestion of contaminated foliage.

    PubMed

    Hoang, Tham C; Rand, Gary M

    2015-02-01

    Three Florida native larval butterflies (Junonia coenia, Anartia jatrophae, Eumaeus atala) were used in the present study to determine the acute toxicity, hazard, and risk of a 24h ingestion of leaves contaminated with the adult mosquito control insecticides permethrin, naled, and dichlorvos to late 4th and early 5th in-star caterpillars. Based on 24-h LD50s for ingestion, naled was more acutely toxic than permethrin and dichlorvos to caterpillars. Hazard quotients using the ratio of the highest doses and the 90th percentile doses from field measurements in host plant foliage following actual mosquito control applications to the toxicological benchmarks from laboratory toxicity tests indicate potential high acute hazard for naled compared to permethrin and dichlorvos. Based on probabilistic ecological risk methods, naled exposure doses in the environment also presented a higher acute risk to caterpillars than permethrin and dichlorvos. The acute toxicity laboratory results and ecological risk assessment are based only on dietary ingestion and single chemical doses. It does not include other typical exposure scenarios that may occur in the environment. It is thus plausible to state that the ecological risk assessment presented here underestimates the potential risks in the field to caterpillars. However, one assumption that is scientifically feasible and certainly real from the results - if the environmental exposure doses of mosquito control operations are similar or higher to those presented here in leaves from the field, after applications, there will likely be significant mortalities and other adverse effects on caterpillar populations. PMID:25462317

  16. Acute toxicity of vipoxin and its components: is the acidic component an "inhibitor" of PLA2 toxicity?

    PubMed

    Atanasov, Vasil N; Stoykova, Silviya; Goranova, Yana; Mitewa, Mariana; Petrova, Svetla

    2012-12-01

    Vipoxin is a heterodimeric neurotoxin isolated from the venom of the Bulgarian long-nosed viper Vipera ammodytes meridionalis. Vipoxin represents a noncovalent association of two subunits - a basic and toxic phospholipase A2 enzyme, and an acidic non-enzymatic component (vipoxin's acidic component). It was postulated that the phospholipase A2 subunit was more toxic than the whole vipoxin complex and the function of the acidic component was to reduce the enzymatic and toxic activities of the basic phospholipase A2. In the present study, we report new data on the acute toxicity (LD50) of vipoxin and its individual separated components. Vipoxin LD50 (mice, i.p. and i.v.) values were found to be 0.7-1.2 mg/kg b.w. (i.p.) and 0.9-1.3 mg/kg b.w. (i.v.). The established LD50 values for the separated pure phospholipase A2 subunit are higher - 10.0-13.0 mg/kg b.w (i.p.) and 2.2-3.0 mg/kg b.w. (i.v.), i.e. the individual phospholipase A2 subunit displays less toxic activity than vipoxin, contrary to the data published in the literature. The reconstituted vipoxin complex (obtained after preliminary incubation of pure separated phospholipase A2 and acidic component showed enzyme activity and toxicity comparable to that of the native vipoxin complex. Addition of acidic component to the phospholipase A2 subunit showed a positive effect on the enzymatic activity, reaching maximal enzyme reaction rate of acidic component to phospholipase A2 molar ratio of 0.8:1 on using 4-nitro-3-octanoyloxy-benzoic acid as substrate. For the first time we showed that the acidic subunit was absolutely required for the toxic activity of vipoxin. Based on the obtained results, we assume that the function of the acidic component is to stabilize the neurotoxin's quaternary structure, required for its toxic and enzymatic activities, similarly to the role of the acidic component of crotoxin. PMID:23554559

  17. Oral Debio1143 (AT406), an antagonist of inhibitor of apoptosis proteins, in combination with daunorubicin and cytarabine in patients with poor-risk acute myeloid leukemia - results of a phase I dose escalation study

    PubMed Central

    Erba, Harry P.; Larson, Richard A.; Luger, Selina M.; Tallman, Martin S.; Brill, Jeffrey M.; Vuagniaux, Gregoire; Rouits, Elisabeth; Sorensen, J. Mel; Zanna, Claudio

    2016-01-01

    Background Treatment of acute myeloid leukemia (AML) remains difficult due to the development of treatment resistance which might be overcome through antagonists of inhibitors of apoptosis proteins (IAPs). Patients and methods This multi-center, open-label, dose escalation study aimed to evaluate tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and efficacy of Debio1143 (formerly AT-406), a new IAP antagonist, when given along with a standard "7 plus 3 regimen" of daunorubicin and cytarabine to poor-risk patients with AML during the induction cycle. Consecutive patient cohorts received once daily 100, 200, 300, or 400 mg of oral Debio1143 on treatment days 1–5. Blood samples were collected regularly until hematological recovery or response; bone marrow samples on day 0, 14, and 29; and PK and PD samples on days 1, 3, 5, 8, 10 and 1, 2, 8, respectively. Results Of 29 enrolled patients, 23 completed the study. Most common adverse events of any grade deemed related to treatment were nausea (31% of patients), diarrhea (14%), and febrile neutropenia (14%). Exposure exceeded dose-proportionality, without accumulation over 5 days. Inhibition of cIAP-1 was detectable in CD34/CD117+ cells and blasts. A total of 11 (38%) patients achieved complete remission, the majority in the 100 mg dose cohort. Of these, 6 (56%) relapsed still within the study period. Responders more frequently showed plasma increases of TNFα and IL-8 post-first dose of Debio1143. Conclusion Debio1143 up to 400 mg/day showed good tolerability in combination with daunorubicin and cytarabine; further studies in subsets of patients with AML are warranted. PMID:25842225

  18. Oral biopsy: oral pathologist's perspective.

    PubMed

    Kumaraswamy, K L; Vidhya, M; Rao, Prasanna Kumar; Mukunda, Archana

    2012-01-01

    Many oral lesions may need to be diagnosed by removing a sample of tissue from the oral cavity. Biopsy is widely used in the medical field, but the practice is not quite widespread in dental practice. As oral pathologists, we have found many artifacts in the tissue specimen because of poor biopsy technique or handling, which has led to diagnostic pitfalls and misery to both the patient and the clinician. This article aims at alerting the clinicians about the clinical faults arising preoperatively, intraoperatively and postoperatively while dealing with oral biopsy that may affect the histological assessment of the tissue and, therefore, the diagnosis. It also reviews the different techniques, precautions and special considerations necessary for specific lesions.

  19. The neonicotinoid pesticide, imidacloprid, affects Bombus impatiens (bumblebee) sonication behavior when consumed at doses below the LD50.

    PubMed

    Switzer, Callin M; Combes, Stacey A

    2016-08-01

    We investigated changes in sonication (or buzz-pollination) behavior of Bombus impatiens bumblebees, after consumption of the neonicotinoid pesticide, imidacloprid. We measured sonication frequency, sonication length, and flight (wing beat) frequency of marked bees collecting pollen from Solanum lycopsersicum (tomato), and then randomly assigned bees to consume 0, 0.0515, 0.515, or 5.15 ng of imidacloprid. We recorded the number of bees in each treatment group that resumed sonication behavior after consuming imidacloprid, and re-measured sonication and flight behavior for these bees. We did not find evidence that consuming 0.0515 ng imidacloprid affected the sonication length, sonication frequency, or flight frequency for bees that sonicated after consuming imidacloprid; we were unable to test changes in these variables for bees that consumed 0.515 or 5.15 ng because we did not observe enough of these bees sonicating after treatment. We performed Cox proportional hazard regression to determine whether consuming imidacloprid affected the probability of engaging in further sonication behavior on S. lycopersicum and found that bumblebees who consumed 0.515 or 5.15 ng of imidacloprid were significantly less likely to sonicate after treatment than bees who consumed no imidacloprid. At the end of the experiment, we classified bees as dead or alive; our data suggest a trend of increasing mortality with higher doses of imidacloprid. Our results show that even modest doses of imidacloprid can significantly affect the likelihood of bumblebees engaging in sonication, a behavior critical for the pollination of a variety of crops and other plants.

  20. Comparison of brain mitochondrial cytochrome c oxidase activity with cyanide LD(50) yields insight into the efficacy of prophylactics.

    PubMed

    Marziaz, Mandy L; Frazier, Kathryn; Guidry, Paul B; Ruiz, Robyn A; Petrikovics, Ilona; Haines, Donovan C

    2013-01-01

    Cyanide inhibits cytochrome c oxidase, the terminal oxidase of the mitochondrial respiratory pathway, therefore inhibiting the cell oxygen utilization and resulting in the condition of histotoxic anoxia. The enzyme rhodanese detoxifies cyanide by utilizing sulfur donors to convert cyanide to thiocyanate, and new and improved sulfur donors are actively sought as researchers seek to improve cyanide prophylactics. We have determined brain cytochrome c oxidase activity as a marker for cyanide exposure for mice pre-treated with various cyanide poisoning prophylactics, including sulfur donors thiosulfate (TS) and thiotaurine (TT3). Brain mitochondria were isolated by differential centrifugation, the outer mitochondrial membrane was disrupted by a maltoside detergent, and the decrease in absorbance at 550 nm as horse heart ferrocytochrome c (generated by the dithiothreitol reduction of ferricytochrome c) was oxidized was monitored. Overall, the TS control prophylactic treatment provided significant protection of the cytochrome c oxidase activity. The TT3-treated mice showed reduced cytochrome c oxidase activity even in the absence of cyanide. In both treatment series, addition of exogenous Rh did not significantly enhance the prevention of cytochrome c oxidase inhibition, but the addition of sodium nitrite did. These findings can lead to a better understanding of the protection mechanism by various cyanide antidotal systems.

  1. A functional dual-coated (FDC) microtiter plate method to replace the botulinum toxin LD50 test.

    PubMed

    Liu, Yvonne Y B; Rigsby, Peter; Sesardic, Dorothea; Marks, James D; Jones, Russell G A

    2012-06-01

    Conventional capture ("Sandwich") ELISAs equally detect denatured inactive and native active botulinum type A toxin. Light chain endoprotease activity assays also fail to distinguish between various inactive molecules including partially denatured and fragmented material still retaining this protease activity. By co-coating microtiter plates with SNAP25 substrate and a monoclonal antibody specific for a conformational epitope of the toxin's Hc domain, it was possible to develop a highly sensitive (130 aM LoD), precise (1.4% GCV) new assay specific for the biologically active toxin molecule. Capture was performed in phosphate buffer with a fixed optimal concentration of chaotropic agent (e.g., 1.2 M urea) to differentially isolate functional toxin molecules. Addition of enzymatically favorable buffer containing zinc and DTT reduced the interchain disulfide bond releasing and activating the captured L-chain with subsequent specific cleavage of the SNAP25(1-206) substrate. A neoepitope antibody specific for the newly exposed Q(197) epitope was used to quantify the cleaved SNAP25(1-197). The assay's requirement for the intact toxin molecule was demonstrated with pre-reduced toxin (heavy and light chains), recombinant LHn fragments, and stressed samples containing partially or fully denatured material. This is the first known immunobiochemical assay that correlates with in vivo potency and provides a realistic alternative. PMID:22406430

  2. The neonicotinoid pesticide, imidacloprid, affects Bombus impatiens (bumblebee) sonication behavior when consumed at doses below the LD50.

    PubMed

    Switzer, Callin M; Combes, Stacey A

    2016-08-01

    We investigated changes in sonication (or buzz-pollination) behavior of Bombus impatiens bumblebees, after consumption of the neonicotinoid pesticide, imidacloprid. We measured sonication frequency, sonication length, and flight (wing beat) frequency of marked bees collecting pollen from Solanum lycopsersicum (tomato), and then randomly assigned bees to consume 0, 0.0515, 0.515, or 5.15 ng of imidacloprid. We recorded the number of bees in each treatment group that resumed sonication behavior after consuming imidacloprid, and re-measured sonication and flight behavior for these bees. We did not find evidence that consuming 0.0515 ng imidacloprid affected the sonication length, sonication frequency, or flight frequency for bees that sonicated after consuming imidacloprid; we were unable to test changes in these variables for bees that consumed 0.515 or 5.15 ng because we did not observe enough of these bees sonicating after treatment. We performed Cox proportional hazard regression to determine whether consuming imidacloprid affected the probability of engaging in further sonication behavior on S. lycopersicum and found that bumblebees who consumed 0.515 or 5.15 ng of imidacloprid were significantly less likely to sonicate after treatment than bees who consumed no imidacloprid. At the end of the experiment, we classified bees as dead or alive; our data suggest a trend of increasing mortality with higher doses of imidacloprid. Our results show that even modest doses of imidacloprid can significantly affect the likelihood of bumblebees engaging in sonication, a behavior critical for the pollination of a variety of crops and other plants. PMID:27189613

  3. Current Therapy in Acute Mouth Infections

    ERIC Educational Resources Information Center

    Goldfarb, George; Burnstein, Irwin L.

    1970-01-01

    Until a dental department is added to a college health service, a physician or nurse can give treatment for acute oral infections. Treatment excludes the use of caustic, escharotic chemicals in favor of more benign agents. (Author)

  4. Oral candidiasis.

    PubMed

    Millsop, Jillian W; Fazel, Nasim

    2016-01-01

    Oral candidiasis (OC) is a common fungal disease encountered in dermatology, most commonly caused by an overgrowth of Candida albicans in the mouth. Although thrush is a well-recognized presentation of OC, it behooves clinicians to be aware of the many other presentations of this disease and how to accurately diagnose and manage these cases. The clinical presentations of OC can be broadly classified as white or erythematous candidiasis, with various subtypes in each category. The treatments include appropriate oral hygiene, topical agents, and systemic medications. This review focuses on the various clinical presentations of OC and treatment options.

  5. Research on acute toxicity and the behavioral effects of methanolic extract from psilocybin mushrooms and psilocin in mice.

    PubMed

    Zhuk, Olga; Jasicka-Misiak, Izabela; Poliwoda, Anna; Kazakova, Anastasia; Godovan, Vladlena V; Halama, Marek; Wieczorek, Piotr P

    2015-04-01

    The pharmacological activities and acute toxicity of the psilocin (PC) and dried residues of the crude extracts of psychotropic mushrooms were investigated in mice. The hallucinogenic substances were effectively isolated, by using methanol, from the species of Psilocybe semilanceata and Pholiotina cyanopus, that were collected in the north-east region of Poland. The chemical analysis of these extracts, which was performed by liquid chromatography with mass spectrometry detection (LC-MS), indicated the presence of psilocin and other hallucinogenic substances, including indolealkylamines and their phosphorylated analogues. When the pure psilocin or fungal extracts were used, slight differences in determined LD50 values were observed. However, the application of PC evoked the highest level of toxicity (293.07 mg/kg) compared to the activity of extracts from Ph. cyanopus and P. semilanceata, where the level of LD50 was 316.87 mg/kg and 324.37 mg/kg, respectively. Furthermore, the behavioral test, which considered the head-twitching response (HTR), was used to assess the effects of the studied psychotropic factors on the serotonergic system. Both, the fungal extracts and psilocin evoked characteristic serotoninergic effects depending on the dose administered to mice, acting as an agonist/partial agonist on the serotonergic system. A dose of 200 mg/kg 5-hydroxytryptophan (5-HTP) induced spontaneous head-twitching in mice (100% effect), as a result of the formation of 5-hydroxytryptamine (5-HT) in the brain. Compared to the activity of 5-HTP, the intraperitoneal administration of 1mg/kg of psilocin or hallucinogenic extracts of studied mushrooms (Ph. cyanopus and P. semilanceata) reduced the number of head-twitch responses of about 46% and 30%, respectively. In contrast, the administration of PC exhibited a reduction of about 60% in HTR numbers. PMID:25826052

  6. Research on acute toxicity and the behavioral effects of methanolic extract from psilocybin mushrooms and psilocin in mice.

    PubMed

    Zhuk, Olga; Jasicka-Misiak, Izabela; Poliwoda, Anna; Kazakova, Anastasia; Godovan, Vladlena V; Halama, Marek; Wieczorek, Piotr P

    2015-03-27

    The pharmacological activities and acute toxicity of the psilocin (PC) and dried residues of the crude extracts of psychotropic mushrooms were investigated in mice. The hallucinogenic substances were effectively isolated, by using methanol, from the species of Psilocybe semilanceata and Pholiotina cyanopus, that were collected in the north-east region of Poland. The chemical analysis of these extracts, which was performed by liquid chromatography with mass spectrometry detection (LC-MS), indicated the presence of psilocin and other hallucinogenic substances, including indolealkylamines and their phosphorylated analogues. When the pure psilocin or fungal extracts were used, slight differences in determined LD50 values were observed. However, the application of PC evoked the highest level of toxicity (293.07 mg/kg) compared to the activity of extracts from Ph. cyanopus and P. semilanceata, where the level of LD50 was 316.87 mg/kg and 324.37 mg/kg, respectively. Furthermore, the behavioral test, which considered the head-twitching response (HTR), was used to assess the effects of the studied psychotropic factors on the serotonergic system. Both, the fungal extracts and psilocin evoked characteristic serotoninergic effects depending on the dose administered to mice, acting as an agonist/partial agonist on the serotonergic system. A dose of 200 mg/kg 5-hydroxytryptophan (5-HTP) induced spontaneous head-twitching in mice (100% effect), as a result of the formation of 5-hydroxytryptamine (5-HT) in the brain. Compared to the activity of 5-HTP, the intraperitoneal administration of 1mg/kg of psilocin or hallucinogenic extracts of studied mushrooms (Ph. cyanopus and P. semilanceata) reduced the number of head-twitch responses of about 46% and 30%, respectively. In contrast, the administration of PC exhibited a reduction of about 60% in HTR numbers.

  7. Research on Acute Toxicity and the Behavioral Effects of Methanolic Extract from Psilocybin Mushrooms and Psilocin in Mice

    PubMed Central

    Zhuk, Olga; Jasicka-Misiak, Izabela; Poliwoda, Anna; Kazakova, Anastasia; Godovan, Vladlena V.; Halama, Marek; Wieczorek, Piotr P.

    2015-01-01

    The pharmacological activities and acute toxicity of the psilocin (PC) and dried residues of the crude extracts of psychotropic mushrooms were investigated in mice. The hallucinogenic substances were effectively isolated, by using methanol, from the species of Psilocybe semilanceata and Pholiotina cyanopus, that were collected in the north-east region of Poland. The chemical analysis of these extracts, which was performed by liquid chromatography with mass spectrometry detection (LC-MS), indicated the presence of psilocin and other hallucinogenic substances, including indolealkylamines and their phosphorylated analogues. When the pure psilocin or fungal extracts were used, slight differences in determined LD50 values were observed. However, the application of PC evoked the highest level of toxicity (293.07 mg/kg) compared to the activity of extracts from Ph. cyanopus and P. semilanceata, where the level of LD50 was 316.87 mg/kg and 324.37 mg/kg, respectively. Furthermore, the behavioral test, which considered the head-twitching response (HTR), was used to assess the effects of the studied psychotropic factors on the serotonergic system. Both, the fungal extracts and psilocin evoked characteristic serotoninergic effects depending on the dose administered to mice, acting as an agonist/partial agonist on the serotonergic system. A dose of 200 mg/kg 5-hydroxytryptophan (5-HTP) induced spontaneous head-twitching in mice (100% effect), as a result of the formation of 5-hydroxytryptamine (5-HT) in the brain. Compared to the activity of 5-HTP, the intraperitoneal administration of 1mg/kg of psilocin or hallucinogenic extracts of studied mushrooms (Ph. cyanopus and P. semilanceata) reduced the number of head-twitch responses of about 46% and 30%, respectively. In contrast, the administration of PC exhibited a reduction of about 60% in HTR numbers. PMID:25826052

  8. Acute Bronchitis

    MedlinePlus

    ... tightness. There are two main types of bronchitis: acute and chronic. Most cases of acute bronchitis get better within several days. But your ... that cause colds and the flu often cause acute bronchitis. These viruses spread through the air when ...

  9. Non-animal Replacements for Acute Toxicity Testing.

    PubMed

    Barker-Treasure, Carol; Coll, Kevin; Belot, Nathalie; Longmore, Chris; Bygrave, Karl; Avey, Suzanne; Clothier, Richard

    2015-07-01

    Current approaches to predicting adverse effects in humans from acute toxic exposure to cosmetic ingredients still heavily necessitate the use of animals under EU legislation, particularly in the context of the REACH system, when cosmetic ingredients are also destined for use in other industries. These include the LD50 test, the Up-and-Down Procedure and the Fixed Dose Procedure, which are regarded as having notable scientific deficiencies and low transferability to humans. By expanding on previous in vitro tests, such as the animal cell-based 3T3 Neutral Red Uptake (NRU) assay, this project aims to develop a truly animal-free predictive test for the acute toxicity of cosmetic ingredients in humans, by using human-derived cells and a prediction model that does not rely on animal data. The project, funded by Innovate UK, will incorporate the NRU assay with human dermal fibroblasts in animal product-free culture, to generate an in vitro protocol that can be validated as an accepted replacement for the currently available in vivo tests. To date, the project has successfully completed an assessment of the robustness and reproducibility of the method, by using sodium lauryl sulphate (SLS) as a positive control, and displaying analogous results to those of the original studies with mouse 3T3 cells. Currently, the testing of five known ingredients from key groups (a surfactant, a preservative, a fragrance, a colour and an emulsifier) is under way. The testing consists of initial range-finding runs followed by three valid runs of a main experiment with the appropriate concentration ranges, to generate IC50 values. Expanded blind trials of 20 ingredients will follow. Early results indicate that this human cell-based test holds the potential to replace aspects of in vivo animal acute toxicity testing, particularly with reference to cosmetic ingredients.

  10. Non-animal Replacements for Acute Toxicity Testing.

    PubMed

    Barker-Treasure, Carol; Coll, Kevin; Belot, Nathalie; Longmore, Chris; Bygrave, Karl; Avey, Suzanne; Clothier, Richard

    2015-07-01

    Current approaches to predicting adverse effects in humans from acute toxic exposure to cosmetic ingredients still heavily necessitate the use of animals under EU legislation, particularly in the context of the REACH system, when cosmetic ingredients are also destined for use in other industries. These include the LD50 test, the Up-and-Down Procedure and the Fixed Dose Procedure, which are regarded as having notable scientific deficiencies and low transferability to humans. By expanding on previous in vitro tests, such as the animal cell-based 3T3 Neutral Red Uptake (NRU) assay, this project aims to develop a truly animal-free predictive test for the acute toxicity of cosmetic ingredients in humans, by using human-derived cells and a prediction model that does not rely on animal data. The project, funded by Innovate UK, will incorporate the NRU assay with human dermal fibroblasts in animal product-free culture, to generate an in vitro protocol that can be validated as an accepted replacement for the currently available in vivo tests. To date, the project has successfully completed an assessment of the robustness and reproducibility of the method, by using sodium lauryl sulphate (SLS) as a positive control, and displaying analogous results to those of the original studies with mouse 3T3 cells. Currently, the testing of five known ingredients from key groups (a surfactant, a preservative, a fragrance, a colour and an emulsifier) is under way. The testing consists of initial range-finding runs followed by three valid runs of a main experiment with the appropriate concentration ranges, to generate IC50 values. Expanded blind trials of 20 ingredients will follow. Early results indicate that this human cell-based test holds the potential to replace aspects of in vivo animal acute toxicity testing, particularly with reference to cosmetic ingredients. PMID:26256397

  11. Phytochemical Screening and Acute Toxicity of Aqueous Extract of Leaves of Conocarpus erectus Linnaeus in Swiss Albino Mice.

    PubMed

    Nascimento, Dayane K D; Souza, Ivone A DE; Oliveira, Antônio F M DE; Barbosa, Mariana O; Santana, Marllon A N; Pereira, Daniel F; Lira, Eduardo C; Vieira, Jeymesson R C

    2016-09-01

    Mangroves represent areas of high biological productivity and it is a region rich in bioactive substances used in medicine production. Conocarpus erectus (Combretaceae) known as button mangrove is one of the species found in mangroves and it is used in folk medicine in the treatment of anemia, catarrh, conjunctivitis, diabetes, diarrhea, fever, gonorrhea, headache, hemorrhage, orchitis, rash, bumps and syphilis. The present study aimed to investigate the acute toxicity of aqueous extract of leaves of C. erectus in Swiss albino mice. The plant material was collected in Vila Velha mangroves, located in Itamaracá (PE). The material was subjected to a phytochemical screening where extractive protocols to identify majority molecules present in leaves were used. The evaluation of acute toxicity of aqueous extract of C. erectus followed the model of Acute Toxicity Class based on OECD 423 Guideline, 2001. The majority molecules were identified: flavonoids, tannins and saponins. The LD50 was estimated at 2,000 mg/kg bw. Therefore, the aqueous extract showed low acute toxicity classified in category 5.

  12. Phytochemical Screening and Acute Toxicity of Aqueous Extract of Leaves of Conocarpus erectus Linnaeus in Swiss Albino Mice.

    PubMed

    Nascimento, Dayane K D; Souza, Ivone A DE; Oliveira, Antônio F M DE; Barbosa, Mariana O; Santana, Marllon A N; Pereira, Daniel F; Lira, Eduardo C; Vieira, Jeymesson R C

    2016-09-01

    Mangroves represent areas of high biological productivity and it is a region rich in bioactive substances used in medicine production. Conocarpus erectus (Combretaceae) known as button mangrove is one of the species found in mangroves and it is used in folk medicine in the treatment of anemia, catarrh, conjunctivitis, diabetes, diarrhea, fever, gonorrhea, headache, hemorrhage, orchitis, rash, bumps and syphilis. The present study aimed to investigate the acute toxicity of aqueous extract of leaves of C. erectus in Swiss albino mice. The plant material was collected in Vila Velha mangroves, located in Itamaracá (PE). The material was subjected to a phytochemical screening where extractive protocols to identify majority molecules present in leaves were used. The evaluation of acute toxicity of aqueous extract of C. erectus followed the model of Acute Toxicity Class based on OECD 423 Guideline, 2001. The majority molecules were identified: flavonoids, tannins and saponins. The LD50 was estimated at 2,000 mg/kg bw. Therefore, the aqueous extract showed low acute toxicity classified in category 5. PMID:27508993

  13. Oral Cancer

    MedlinePlus

    ... What are the effects of oral cancer on speech and swallowing? The effects of cancer on speech and swallowing depend on the location and size ... movement. This could result in unclear production of speech sounds made with the lips such as /p/, / ...

  14. Oral Warts

    MedlinePlus

    ... Title: Oral Warts Description: Warts are small, white, gray, or pinkish rough bumps that look like cauliflower. They can appear inside the lips and on other parts of the mouth. Credit: NIDCR publication: Mouth Problems + HIV Download: Low-Resolution Image High- ...

  15. Treatment methods for oral mucous chemical burns

    NASA Astrophysics Data System (ADS)

    Mosesyants, Elvira N.

    1994-12-01

    A constantly growing number of patients turning to toxicological centers with oral mucous chemical burns after acute poisoning made us take up the research of this problem. A high level of fatalities made it necessary to work out new more effective methods of treatment. The aim of this research was to study the peculiarities of the clinical picture of the oral mucous chemical burns and work out more affective methods of treatment and their tests.

  16. Controlled trial of Penfluridol in Acute Psychosis

    PubMed Central

    van Praag, H. M.; Schut, T.; Dols, L.; van Schilfgaarden, R.

    1971-01-01

    A controlled study was made of penfluridol medication consisting of a single weekly oral dose of 30 mg in 30 patients with acute psychoses of varying type and origin. This medication was found to be effective. No significant side effects occurred. Several long-acting neuroleptics for injection are now available. The development of an oral compound of this type is an asset because of the manageability of the oral drug in the hands of family doctors and social psychiatrists. PMID:4943034

  17. Uncomplicated acute bronchitis.

    PubMed

    Gonzales, R; Sande, M A

    2000-12-19

    Acute bronchitis is an acute cough illness in otherwise healthy adults that usually lasts 1 to 3 weeks. This review describes the pathophysiology of the condition and provides a practical approach to the evaluation and treatment of adults with uncomplicated acute bronchitis. Practical points to be made are:1. Respiratory viruses appear to cause the large majority of cases of uncomplicated acute bronchitis.2. Pertussis infection is present in up to 10% to 20% of adults with cough illness of more than 2 to 3 weeks' duration. No clinical features distinguish pertussis from nonpertussis infection in adults who were immunized against pertussis as children.3. Transient bronchial hyperresponsiveness appears to be the predominant mechanism of the bothersome cough of acute bronchitis.4. Ruling out pneumonia is the primary objective in evaluating adults with acute cough illness in whom comorbid conditions and occult asthma are absent or unlikely. In the absence of abnormalities in vital signs (heart rate > 100 beats/min, respiratory rate > 24 breaths/min, and oral body temperature > 38 degrees C), the likelihood of pneumonia is very low.5. Randomized, placebo-controlled trials do not support routine antibiotic treatment of uncomplicated acute bronchitis.6. Randomized, placebo-controlled trials have shown that inhaled albuterol decreases the duration of cough in adults with uncomplicated acute bronchitis.7. Intervention studies suggest that antibiotic treatment of acute bronchitis can be reduced by using a combination of patient and physician education. Decreased rates of antibiotic treatment are not associated with increased utilization, return visits, or dissatisfaction with care.

  18. Oral care.

    PubMed

    Hitz Lindenmüller, Irène; Lambrecht, J Thomas

    2011-01-01

    Adequate dental and oral hygiene may become a challenge for all users and especially for elderly people and young children because of their limited motor skills. The same holds true for patients undergoing/recovering from chemo-/radiotherapy with accompanying sensitive mucosal conditions. Poor dental hygiene can result in tooth decay, gingivitis, periodontitis, tooth loss, bad breath (halitosis), fungal infection and gum diseases. The use of a toothbrush is the most important measure for oral hygiene. Toothbrushes with soft bristles operated carefully by hand or via an electric device help to remove plaque and to avoid mucosal trauma. A handlebar with a grip cover can be helpful for manually disabled patients or for those with reduced motor skills. In case of oral hygiene at the bedside or of patients during/after chemo-/radiotherapy a gauze pad can be helpful for gently cleaning the teeth, gums and tongue. The use of fluoride toothpaste is imperative for the daily oral hygiene. Detergents such as sodium lauryl sulphate improve the cleaning action but may also dehydrate and irritate the mucous membrane. The use of products containing detergents and flavouring agents (peppermint, menthol, cinnamon) should therefore be avoided by bedridden patients or those with dry mouth and sensitive mucosa. Aids for suitable interdental cleaning, such as dental floss, interdental brushes or dental sticks, are often complicated to operate. Their correct use should be instructed by healthcare professionals. To support dental care, additional fluoridation with a fluoride gel or rinse can be useful. Products further containing antiseptics such as chlorhexidine or triclosan reduce the quantity of bacteria in the mouth. For patients undergoing or having undergone radio-/chemotherapy, a mouthwash that concomitantly moisturizes the oral mucosa is advisable. PMID:21325845

  19. Oral care.

    PubMed

    Hitz Lindenmüller, Irène; Lambrecht, J Thomas

    2011-01-01

    Adequate dental and oral hygiene may become a challenge for all users and especially for elderly people and young children because of their limited motor skills. The same holds true for patients undergoing/recovering from chemo-/radiotherapy with accompanying sensitive mucosal conditions. Poor dental hygiene can result in tooth decay, gingivitis, periodontitis, tooth loss, bad breath (halitosis), fungal infection and gum diseases. The use of a toothbrush is the most important measure for oral hygiene. Toothbrushes with soft bristles operated carefully by hand or via an electric device help to remove plaque and to avoid mucosal trauma. A handlebar with a grip cover can be helpful for manually disabled patients or for those with reduced motor skills. In case of oral hygiene at the bedside or of patients during/after chemo-/radiotherapy a gauze pad can be helpful for gently cleaning the teeth, gums and tongue. The use of fluoride toothpaste is imperative for the daily oral hygiene. Detergents such as sodium lauryl sulphate improve the cleaning action but may also dehydrate and irritate the mucous membrane. The use of products containing detergents and flavouring agents (peppermint, menthol, cinnamon) should therefore be avoided by bedridden patients or those with dry mouth and sensitive mucosa. Aids for suitable interdental cleaning, such as dental floss, interdental brushes or dental sticks, are often complicated to operate. Their correct use should be instructed by healthcare professionals. To support dental care, additional fluoridation with a fluoride gel or rinse can be useful. Products further containing antiseptics such as chlorhexidine or triclosan reduce the quantity of bacteria in the mouth. For patients undergoing or having undergone radio-/chemotherapy, a mouthwash that concomitantly moisturizes the oral mucosa is advisable.

  20. Subacute toxicity of orally applied alpha-cypermethrin in Swiss mice.

    PubMed

    Luty, S; Latuszynska, J; Obuchowska-Przebirowska, D; Tokarska, M; Haratym-Maj, A

    2000-01-01

    The effect of a synthetic pyrethroid - alpha-cypermethrin administered per os for 28 days to Swiss mice was examined on phagocytic and bactericidal activity of neutrophils, and leukocytic image, IL-12 p70 level in blood plasma, as well as histologic and ultrastructural picture of the liver, heart, kidneys, lung and spleen. A synthetic pyrethroid alpha-cypermethrin, [(R,S)-alpha-cyano-3-phenoxybenzyl (R,S)-cis,trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylate], produced by the Chemical Plant in Jaworzno was used in the study. The preparation for the application per os was used in doses 1/2 LD(50) (25 mg/kg body mass) and 1/5 LD(50) (10 mg/kg body mass). The results were presented as mean (x) +/- standard error (SEM) and subjected to statistical analysis by the parametric t-Student test. Subacute poisoning of mice with alpha-cypermethrin in doses 1/2 LD(50) and 1/5 LD(50) resulted in decreased bactericidal activity of neutrophils. The dose 10 mg/kg body mass had a stronger stimulatory effect on phagocytic activity than 25 mg/kg body mass. Significantly higher numbers of monocytes and lymphocytes were observed in the blood of male mice poisoned with 1/5 LD(50) alpha-cypermethrin. The administration of alpha-cypermethrin resulted for both doses in the decrease in IL-12 p70 serum secretion. The lowest IL-12 p70 level (pg/ml) was noted among female mice administered 1/2 LD(50) of the preparation. The results of the study may indicate that the pyrethroid in the study had a suppressive effect on Il-12 p70 production. In mice administered 1/5 LD(50) or 1/2 LD(50) of the preparation examined, histopathologic and ultrastructural changes were observed in the liver and kidneys.

  1. RUBY-1: a randomized, double-blind, placebo-controlled trial of the safety and tolerability of the novel oral factor Xa inhibitor darexaban (YM150) following acute coronary syndrome

    PubMed Central

    Steg, Ph. Gabriel; Mehta, Shamir R.; Jukema, J. Wouter; Lip, Gregory Y.H.; Gibson, C. Michael; Kovar, Frantisek; Kala, Petr; Garcia-Hernandez, Alberto; Renfurm, Ronny W.; Granger, Christopher B.

    2011-01-01

    Aims To establish the safety, tolerability and most promising regimen of darexaban (YM150), a novel, oral, direct factor Xa inhibitor, for prevention of ischaemic events in acute coronary syndrome (ACS). Methods In a 26-week, multi-centre, double-blind, randomized, parallel-group study, 1279 patients with recent high-risk non-ST-segment or ST-segment elevation ACS received one of six darexaban regimens: 5 mg b.i.d., 10 mg o.d., 15 mg b.i.d., 30 mg o.d., 30 mg b.i.d., or 60 mg o.d. or placebo, on top of dual antiplatelet treatment. Primary outcome was incidence of major or clinically relevant non-major bleeding events. The main efficacy outcome was a composite of death, stroke, myocardial infarction, systemic thromboembolism, and severe recurrent ischaemia. Results Bleeding rates were numerically higher in all darexaban arms vs. placebo (pooled HR: 2.275; 95% CI: 1.13–4.60, P = 0.022). Using placebo as reference (bleeding rate 3.1%), there was a dose–response relationship (P = 0.009) for increased bleeding with increasing darexaban dose (6.2, 6.5, and 9.3% for 10, 30, and 60 mg daily, respectively), which was statistically significant for 30 mg b.i.d. (P = 0.002). There was no decrease (indeed a numerical increase in the 30 and 60 mg dose arms) in efficacy event rates with darexaban, but the study was underpowered for efficacy. Darexaban showed good tolerability without signs of liver toxicity. Conclusions Darexaban when added to dual antiplatelet therapy after ACS produces an expected dose-related two- to four-fold increase in bleeding, with no other safety concerns but no signal of efficacy. Establishing the potential of low-dose darexaban in preventing major cardiac events after ACS requires a large phase III trial. ClinicalTrials.gov Identifier: NCT00994292 PMID:21878434

  2. Oral Cancer Screening

    MedlinePlus

    ... Prevention Oral Cavity and Oropharyngeal Cancer Screening Research Oral Cavity and Oropharyngeal Cancer Screening (PDQ®)–Patient Version What ... These are called diagnostic tests . General Information About Oral Cavity and Oropharyngeal Cancer Key Points Oral cavity and ...

  3. Toxic effects of oral 2-amino-4,6-dinitrotoluene in the Western fence lizard (Sceloporus occidentalis).

    PubMed

    McFarland, Craig A; Quinn, Michael J; Boyce, John; LaFiandra, Emily M; Bazar, Matthew A; Talent, Larry G; Johnson, Mark S

    2011-02-01

    The compound 2-amino-4,6-dinitrotoluene (2A-DNT) was evaluated under laboratory conditions in the Western fence lizard (Sceloporus occidentalis) to assess the potential for reptile toxicity. Oral LD(50) values were 1406 and 1867 mg/kg for male and female lizards, respectively. Based on responses from a 14-day subacute study, a 60-day subchronic experiment followed where lizards were orally dosed at 0, 5, 15, 20, 25, 30 mg/kg-d. At day 60, number of days and survivors, food consumption, and change in body weight were inversely related to dose. Signs of toxicity were characterized by anorexia and generalized cachexia. Significant adverse histopathology was observed in hepatic tissue at ≥ 15 mg/kg-d, consistent with hepatocellular transdifferentiation. Based on survival, loss of body weight, diminished food intake, changes in liver, kidney, and testes, and increased blood urea nitrogen, these data suggest a LOAEL of 15 mg/kg-d and a NOAEL of 5 mg/kg-d in S. occidentalis. PMID:21067851

  4. Chitosan-glycolipid nanogels loaded with anti-obese marine carotenoid fucoxanthin: Acute and sub-acute toxicity evaluation in rodent model.

    PubMed

    Ravi, Hindupur; Arunkumar, Ranganathan; Baskaran, Vallikannan

    2015-10-01

    Fucoxanthin (FUCO) is a light- and heat-sensitive marine xanthophyll carotenoid, present in brown algae that render physiological properties as anti-oxidants. In this study, nanoencapsulation is an approach adopted to improve bioavailability of FUCO by using ionic-gelation method with polymeric chitosan (CS) dispersed in glycolipid (GL), as a carrier. Further, the aim was to investigate adverse effect of acute and sub-acute toxicity of chitosan nanogels (CS-NGs) loaded with FUCO+GL in rats. In the acute toxicity study, FUCO was fed to rats at doses of 0.1, 1, 10 and 100 mg/kg body weight (BW). In the sub-acute toxicity study, FUCO was fed at doses of 1 and 10 mg/kg BW for 28 days. In both the studies, no mortality and abnormalities in gross morphology were observed. Acute toxicity study revealed that the LD50 of FUCO in CS-NGs is higher than 100 mg/kg BW. No postprandial plasma levels of FUCO were detected. However, fucoxanthinol (FUOH), a hydrolytic metabolite of FUCO was detected in a dose dependent manner (P < 0.01). Compared to the control group(s), no dose-related toxic effects of CS-NGs with FUCO + GL were found in haematological, histopathological, plasma biochemical indices, etc. The no-observed-adverse-effect level (NOAEL) for CS-NGs with FUCO + GL in rats was 10 mg/kg/day. To conclude, no apparent adverse effect of CS-NGs with FUCO + GL demonstrating CS could be a promising polymer matrix for safe delivery of FUCO. This is the first study to demonstrate the safety assessment of CS-NGs with FUCO + GL.

  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. 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

    2016-01-01

    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. PMID:26760987

  7. Amphiphilic poly-N-vynilpyrrolidone nanoparticles: Cytotoxicity and acute toxicity study.

    PubMed

    Kuskov, A N; Kulikov, P P; Shtilman, M I; Rakitskii, V N; Tsatsakis, A M

    2016-10-01

    The aim of the present study was to evaluate the cytotoxicity against MCF-7 cells and acute intraperitoneal toxicity of amphiphilic poly-N-vinylpyrrolidone nanoparticles to confirm possibility of their application for creation of novel drug delivery systems. The effect of cellular uptake of polymeric nanoparticles on human cancer cell line MCF-7 cells was investigated by MTT assay. MTT analysis showed that tested amphiphilic polymers were essentially non-toxic. In acute toxicity studies, LD50 and other toxicity indexes were evaluated, under which no deaths or treatment related complications were observed even in high concentration treatment for 14 days of experiment. For histological analysis, organs of the animals were weighed and examined. No animal died during the study and no significant changes have been observed regarding body weight, feed consumption, organ weight or histological data. Obtained results show that amphiphilic poly-N-vinylpyrrolidone nanoparticles possessed no toxicity against cells and in animals after intraperitoneal administration. Thus, amphiphilic PVP nanoparticles demonstrate high potential as carriers for novel high-effective drug delivery systems. PMID:27539747

  8. Chemical composition, protoscolicidal effects and acute toxicity of Pistacia atlantica Desf. fruit extract.

    PubMed

    Mahmoudvand, Hossein; Kheirandish, Farnaz; Ghasemi Kia, Mehdi; Tavakoli Kareshk, Amir; Yarahmadi, Mohammad

    2016-01-01

    The present study was designed to evaluate the chemical composition and scolicidal effects of Pistacia atlantica Desf. extract against protoscoleces of hydatid cysts and its acute toxicity in mice model. Various concentrations of the methanolic extract (5-50 mg/mL) were used for 10-60 min. Viability of protoscoleces was confirmed using eosin exclusion test (0.1%). Acute toxicity was also determined in mice model. The main components were β-myrcene (41.4%), α-pinene (32.48%) and limonene (4.66%). Findings demonstrated that P. atlantica extract at the concentrations of 25 and 50 mg/mL after 20 and 10 min of exposure killed 100% protoscoleces. The LD50 of the intraperitoneal injection of the P. atlantica methanolic extract was 2.43 g/kg and the maximum non-fatal dose was 1.66 g/kg. Obtained results showed the potential of P. atlantica extract as a natural source with no significant toxicity for the production of new scolicidal agent to use in hydatid cyst surgery. PMID:26252652

  9. Amphiphilic poly-N-vynilpyrrolidone nanoparticles: Cytotoxicity and acute toxicity study.

    PubMed

    Kuskov, A N; Kulikov, P P; Shtilman, M I; Rakitskii, V N; Tsatsakis, A M

    2016-10-01

    The aim of the present study was to evaluate the cytotoxicity against MCF-7 cells and acute intraperitoneal toxicity of amphiphilic poly-N-vinylpyrrolidone nanoparticles to confirm possibility of their application for creation of novel drug delivery systems. The effect of cellular uptake of polymeric nanoparticles on human cancer cell line MCF-7 cells was investigated by MTT assay. MTT analysis showed that tested amphiphilic polymers were essentially non-toxic. In acute toxicity studies, LD50 and other toxicity indexes were evaluated, under which no deaths or treatment related complications were observed even in high concentration treatment for 14 days of experiment. For histological analysis, organs of the animals were weighed and examined. No animal died during the study and no significant changes have been observed regarding body weight, feed consumption, organ weight or histological data. Obtained results show that amphiphilic poly-N-vinylpyrrolidone nanoparticles possessed no toxicity against cells and in animals after intraperitoneal administration. Thus, amphiphilic PVP nanoparticles demonstrate high potential as carriers for novel high-effective drug delivery systems.

  10. Interactions between methaqualone and ethanol in rats and mice during acute and chronic states.

    PubMed

    Ho, C C; Ho, A K

    1978-01-01

    1. The effects of acute and chronic treatment of methaqualone on ethanol preference, the rate of disappearance of ethanol and on toxicity were studied in mice and rats. 2. Acute treatment with methaqualone showed a dose-dependent suppression in the voluntary intake of ethanol in C57Bl/6J mice in rats. No significant change in ethanol intake was observed during chronic methaqualone treatment and withdrawal. 3. Methaqualone pretreatment significantly (P less than 0.005) delayed the disappearance of ethanol in the blood and brain over a period of 50 and 200 min after a loading dose of 2.0 g/kg, i.p., of ethanol. 4. Methaqualone pretreatment at doses of 140 and 200 mg/kg significantly increased ethanol toxicity by 11% and 28%, respectively. Co-administration of ethanol using 6.0, 7.0 and 8.0 g/kg also reduced the LD50 of methaqualone by 19%, 24% and 40%, respectively. 5. Chronic administration with ethanol decreased the toxicity due to methaqualone. Potentiation of ethanol toxicity by methaqualone may be of clinical importance in view of the narrow range of safety margin of ethanol.

  11. Acute toxicity and in vivo biodistribution of monodispersed mesoporous bioactive glass spheres in intravenously exposed mice.

    PubMed

    Mao, Cong; Chen, Xiaofeng; Hu, Qing; Miao, Guohou; Lin, Cai

    2016-01-01

    The use of biomaterials from laboratories to clinics requires exhaustive and elaborate studies involving the biodistribution, clearance, and biocompatibility of biomaterials for in vivo biomedical applications. This study aimed to evaluate the acute toxicity and biodistribution of intravenously administrated sub-micrometer mesoporous bioactive glass spheres (SMBGs) in mice. The lethal dose 50 (LD50) of SMBGs was higher than 250 mg/kg. The acute toxicity was evaluated at 14 days after intravenous injection of SMBGs at 20, 100 and 180 mg/kg in ICR mice. The mortality, coefficients of major organs, hematology data and blood biochemical indexes revealed the low in vivo toxicity of SMBGs at all doses. However, the histological examination showed lymphocytic infiltration and granuloma formation in hepatocyte and megakaryocyte hyperplasia in the spleen at high dose. The silicon content analysis using ICP-OES and TEM results indicated that SMBGs mainly distributed in the resident macrophages of the liver and spleen, and could be cleared from the body more than 2 weeks. These findings can be important for the toxicity assessment of sub-micrometer particles and the development of bioactive glass based drug delivery system for biomedical applications.

  12. The 90-day oral toxicity of d-psicose in male Wistar rats

    PubMed Central

    Matsuo, Tatsuhiro; Ishii, Reika; Shirai, Yoko

    2012-01-01

    d-Psicose is a rare sugar present in small quantities in natural products. In a previous study, we showed that d-psicose suppresses increase in plasma glucose and reduces body fat accumulation in rats. Based on acute toxicity testing in rats, d-psicose is classified as an ordinary substance (LD50 = 16 g/kg). Elucidating the effects of sub-chronic feeding of d-psicose in rats is essential before it can be utilized as a physiologically functional food. In this study, male Wistar rats (3 weeks old) were fed diets containing 3% d-psicose or sucrose for 90 days. The body weight gain and intra-abdominal adipose tissue weight did not differ between the sucrose and the d-psicose groups. The weights of the liver and kidneys were significantly higher in the d-psicose group than in the sucrose group. However, no gross pathological findings were evident at dietary doses of 3% d-psicose or were correlated with hypertrophy of the liver and kidney. In a clinical chemistry analysis, the erythrocyte and leukocyte courts were significantly higher in the d-psicose group, but that was not considered to be toxicologically significant. Therefore, the present study found no adverse effects of d-psicose in rats fed a diet containing 3% d-psicosefor 90 days. PMID:22448098

  13. The 90-day oral toxicity of d-psicose in male Wistar rats.

    PubMed

    Matsuo, Tatsuhiro; Ishii, Reika; Shirai, Yoko

    2012-03-01

    d-Psicose is a rare sugar present in small quantities in natural products. In a previous study, we showed that d-psicose suppresses increase in plasma glucose and reduces body fat accumulation in rats. Based on acute toxicity testing in rats, d-psicose is classified as an ordinary substance (LD(50) = 16 g/kg). Elucidating the effects of sub-chronic feeding of d-psicose in rats is essential before it can be utilized as a physiologically functional food. In this study, male Wistar rats (3 weeks old) were fed diets containing 3% d-psicose or sucrose for 90 days. The body weight gain and intra-abdominal adipose tissue weight did not differ between the sucrose and the d-psicose groups. The weights of the liver and kidneys were significantly higher in the d-psicose group than in the sucrose group. However, no gross pathological findings were evident at dietary doses of 3% d-psicose or were correlated with hypertrophy of the liver and kidney. In a clinical chemistry analysis, the erythrocyte and leukocyte courts were significantly higher in the d-psicose group, but that was not considered to be toxicologically significant. Therefore, the present study found no adverse effects of d-psicose in rats fed a diet containing 3% d-psicosefor 90 days.

  14. Oral exposure to polystyrene nanoparticles effects iron absorption

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The use of engineered nanoparticles in food and pharmaceuticals is expected to increase, but the impact of chronic oral exposure to nanoparticles on human health remains unknown. Here, we show that chronic and acute oral exposure to polystyrene nanoparticles can influence iron uptake and iron trans...

  15. The Acute Toxicity and Hematological Characterization of the Effects of Tentacle-Only Extract from the Jellyfish Cyanea capillata

    PubMed Central

    Xiao, Liang; Liu, Sihua; He, Qian; Wang, Qianqian; Ye, Xuting; Liu, Guoyan; Nie, Fei; Zhao, Jie; Zhang, Liming

    2011-01-01

    To investigate the hematologic changes and the activities of jellyfish venoms other than hemolytic and cardiovascular toxicities, the acute toxicity of tentacle-only extract (TOE) from the jellyfish Cyanea capillata was observed in mice, and hematological indexes were examined in rats. The median lethal dose (LD50) of TOE was 4.25 mg/kg, and the acute toxicity involved both heart- and nervous system-related symptoms. Arterial blood gas indexes, including pH, PCO2, HCO3−, HCO3std, TCO2, BEecf and BE (B), decreased significantly. PO2 showed a slight increase, while SO2c (%) had no change at any time. Na+ and Ca2+ decreased, but K+ increased. Biochemical indexes, including LDH, CK, CK-MB, ALT, AST and sCr, significantly increased. Other biochemical indexes, including BUN and hemodiastase, remained normal. Lactic acid significantly increased, while glucose, Hct% and THbc showed slight temporary increases and then returned to normal. These results on the acute toxicity and hematological changes should improve our understanding of the in vivo pathophysiological effects of TOE from C. capillata and indicate that it may also have neurotoxicity, liver toxicity and muscular toxicity in addition to hemolytic and cardiovascular toxicities, but no kidney or pancreatic toxicity. PMID:21731547

  16. [Oral pain].

    PubMed

    Benslama, Lotfi

    2002-02-15

    Pain, a major symptom of stomatological disease, usually leads to a specialist consultation. Most commonly it is caused by dental caries and differs in nature and in intensity according to the stage of disease: dentinitis, pulpitis, desmodontitis and dental abscess. Added to this is peridental pain and the pre- and post-operative pains related to these diseases. Almost all oral-maxillary pathology is painful, be it boney such as in osteomyelitis and fractures, mucosal in gingivo-stomatitis and aphthous ulcers, or tumourous. However, besides the "multidisciplinary" facial pains such as facial neuralgia and vascular pain, two pain syndromes are specific to stomatology: pain of the tempero-mandibular joint associated with problems of the bite and glossodynia, a very common somatic expression of psychological problems.

  17. [Oral contraception].

    PubMed

    Guillat, J C

    1980-04-20

    OC (oral contraception) includes the combined and sequential methods, postcoital and progestin only contraception, mini pills, and macro pills. The mechanism of action of OC modifies the hypothalamo-hypophysary secretion, the uterine mucosa, and the cervical mucus. Effectiveness of OC is nearly 100%; prescription of OC requires a complete clinical and biological evaluation of the patient. Contraindications to OC are any form of cancer, hypertension, vascular or thrombotic antecedents, obesity, tabagism, diabetes. OC users must be checked at least every 6 months, and treatment can last, if there are no evident signs of side effects, until about age 40. The most commonly known side effects of OC are menstruation disorders, cardio- and cerebrovascular effects, hepatic and metabolic effects; there is no evidence that OC can cause carcinogenic effects, but it can increase teratogenic risk. The association of OC with such drugs as Rifampicine, anticonvulsants and/or tranquillizers, can nullify contraceptive effectiveness. PMID:6900393

  18. Efficacy and safety of catnip (Nepeta cataria) as a novel filth fly repellent.

    PubMed

    Zhu, J J; Zeng, X-P; Berkebile, D; DU, H-J; Tong, Y; Qian, K

    2009-09-01

    Catnip (Nepeta cataria) is known for its pseudo-narcotic effects on cats. Recently, it has been reported as an effective mosquito repellent against several Aedes and Culex species, both topically and spatially. Our laboratory bioassays showed that catnip essential oil (at a dosage of 20 mg) resulted in average repellency rates of 96% against stable flies, Stomoxys calcitrans (L.) and 79% against houseflies, Musca domestica (L.), respectively. This finding suggested that the application of repellent could be used as part of filth fly management. Further evaluations of catnip oil toxicity were conducted to provide a broad-spectrum safety profile of catnip oil use as a potential biting and nuisance insect repellent in urban settings. Acute oral, dermal, inhalation, primary dermal and eye irritation toxicity tests were performed. The acute oral LD(50) of catnip oil was found to be 3160 mg/kg body weight (BW) and 2710 mg/kg BW in female and male rats, respectively. The acute dermal LD50 was > 5000 mg/kg BW. The acute inhalation LD50 was observed to be > 10,000 mg/m3. Primary skin irritation tested on New Zealand white rabbits showed that catnip oil is a moderate irritant. Catnip oil was classified as practically non-irritating to the eye. In comparison with other U.S. Environmental Protection Agency-approved mosquito repellents (DEET, picaridin and p-menthane-3,8-diol), catnip oil can be considered as a relatively safe repellent, which may cause minor skin irritation.

  19. [Treatment and prevention of acute radiation dermatitis].

    PubMed

    Benomar, S; Boutayeb, S; Lalya, I; Errihani, H; Hassam, B; El Gueddari, B K

    2010-06-01

    Acute radiation dermatitis is a common side-effect of radiotherapy which often necessitates interruption of the therapy. Currently, there is no general consensus about its prevention or about the treatment of choice. The goal of this work was to focus on optimal methods to prevent and manage acute skin reactions related to radiation therapy and to determine if there are specific topical or oral agents for the prevention of this acute skin reaction. The prevention and the early treatment are the two focus points of the management of the acute radiation dermatitis.

  20. Oral Immunotherapy for Food Allergy.

    PubMed

    Burbank, Allison J; Sood, Puja; Vickery, Brian P; Wood, Robert A

    2016-02-01

    Food allergy is a potentially life-threatening condition with no approved therapies, apart from avoidance and injectable epinephrine for acute allergic reactions. Oral immunotherapy (OIT) is an experimental treatment in which food-allergic patients consume gradually increasing quantities of the food to increase their threshold for allergic reaction. This therapy carries significant risk of allergic reactions. The ability of OIT to desensitize patients to particular foods is well-documented, although the ability to induce tolerance has not been established. This review focuses on recent studies for the treatment of food allergies such as cow's milk, hen's egg, and peanut.

  1. Oral Immunotherapy for Food Allergy.

    PubMed

    Burbank, Allison J; Sood, Puja; Vickery, Brian P; Wood, Robert A

    2016-02-01

    Food allergy is a potentially life-threatening condition with no approved therapies, apart from avoidance and injectable epinephrine for acute allergic reactions. Oral immunotherapy (OIT) is an experimental treatment in which food-allergic patients consume gradually increasing quantities of the food to increase their threshold for allergic reaction. This therapy carries significant risk of allergic reactions. The ability of OIT to desensitize patients to particular foods is well-documented, although the ability to induce tolerance has not been established. This review focuses on recent studies for the treatment of food allergies such as cow's milk, hen's egg, and peanut. PMID:26617227

  2. Studies on combined effects of organophosphates and heavy metals in birds. I. Plasma and brain cholinesterase in Coturnix quail fed methyl mercury and orally dosed with parathion

    USGS Publications Warehouse

    Dieter, M.P.; Ludke, J.L.

    1975-01-01

    We found that mercury potentiated the toxicity and biochemical effects of parathion. Male Coturnix quail (Coturnix coturnix japonica) were fed a sublethal concentration of morsodren (4 ppm as methyl mercury) for 18 weeks. This resulted in an accumulation of 21.0 ppm of mercury in the liver and 8.4 ppm in the carcass. Birds fed clean feed and those fed morsodren-treated feed were orally dosed with 2, 4, 6, 8,and 10 mg/kg parathion, and their 48-h survival times compared. The computed LD50 was 5.86mg/kg in birds not fed morsodren and 4.24 in those fed the heavy metal. When challenged with a sublethal, oral dose of parathion (1.0 mg/kg), morsodren-fed birds exhibited significantly greater inhibition of plasma and brain cholinesterase activity than controls dosed with parathion. Brain cholinesterase activity was inhibited 41% in morsodren-fed birds and 26in clean-fed birds dosed with parathion, which suggested that the increase in parathion toxicity in the presence of morsodren was directly related to the inhibitation of brain cholinesterase.

  3. Long-term oral complications of allogeneic haematopoietic SCT.

    PubMed

    Hull, K M; Kerridge, I; Schifter, M

    2012-02-01

    This study assessed the incidence of long-term oral complications in 88 survivors of allogeneic haematopoietic cell transplantation (HCT). Patients examined were between 6 months and 6 years post-HCT and aged from 19 to 65 years. Subjects were investigated for both the subjective and objective features of long-term adverse oral effects of HCT. The most common oral symptoms reported were xerostomia (44%, n=39) and reduction in taste (20%, n=18). Only a minority of patients (15%) reported that oral disease had a significant adverse impact upon their quality of life. The majority of patients (53%) had clinical markers of oral chronic GVHD (cGVHD). The most frequently identified feature was salivary hypofunction, with 34% of subjects demonstrating a reduction in stimulated saliva. Oral mucosal changes consistent with cGVHD affected 21% of subjects. Oral cGVHD commonly occurs after allogeneic HCT, often coexists with cutaneous, hepatic or ocular cGVHD and may lead to debilitating symptoms. Transplant type and pre-existing acute GVHD are the major risk factors for oral cGVHD. The identification of risk factors specific for oral cGVHD may allow clinicians some foresight into identifying patients at high risk of developing oral cGVHD and encourage attention to education, regular oral surveillance and rigorous preventative oral health strategies both pre- and post-transplant. PMID:21441960

  4. Bone marrow-derived cells participate in stromal remodeling of the lung following acute bacterial pneumonia in mice.

    PubMed

    Serikov, Vladimir B; Mikhaylov, Viatcheslav M; Krasnodembskay, Anna D; Matthay, Michael A

    2008-01-01

    Bone marrow-derived cells (BMDC) have been shown to graft injured tissues, differentiate in specialized cells, and participate in repair. The importance of these processes in acute lung bacterial inflammation and development of fibrosis is unknown. The goal of this study was to investigate the temporal sequence and lineage commitment of BMDC in mouse lungs injured by bacterial pneumonia. We transplanted GFP-tagged BMDC into 5-Gy-irradiated C57BL/6 mice. After 3 months of recovery, mice were subjected to LD(50) intratracheal instillation of live E. coli (controls received saline) which produced pneumonia and subsequent areas of fibrosis. Lungs were investigated by immunohistology for up to 6 months. At the peak of lung inflammation, the predominant influx of BMDC were GFP(+) leukocytes. Postinflammatory foci of lung fibrosis were evident after 1-2 months. The fibrotic foci in lung stroma contained clusters of GFP(+) CD45(+) cells, GFP(+) vimentin-positive cells, and GFP(+) collagen I-positive fibroblasts. GFP(+) endothelial or epithelial cells were not identified. These data suggest that following 5-Gy irradiation and acute bacterial pneumonia, BMDC may temporarily participate in lung postinflammatory repair and stromal remodeling without long-term engraftment as specialized endothelial or epithelial cells.

  5. Comparative toxicity of diphacinone to northern bobwhite (Colinus virginianus) and American kestrels (Falco sparverius)

    USGS Publications Warehouse

    Rattner, Barnett A.; Horak, Katherine E.; Warner, Sarah E.; Day, Daniel D.; Johnston, John J.

    2010-01-01

    The acute oral toxicity of the anticoagulant rodenticide diphacinone was found to be about 20 times greater to American kestrels (LD50=97 mg/kg) than to northern bobwhite (LD50=2,014 mg/kg). Several precise and sensitive clotting assays (prothrombin time, Russell's Viper venom time, thrombin clotting time) were adapted for use in these species, and this combination of assays is recommended to detect effects of diphacinone and other rodenticides on coagulation. Oral administration of diphacinone over a range of doses (sublethal to the extrapolated LD15) prolonged prothrombin time and Russell's Viper venom time within 24 to 48 hrs post-exposure. Prolongation of in vitro clotting time reflects impaired coagulation complex activity and was detected before or at the onset of overt signs of toxicity and lethality. These data will assist in the development of a pharmacodynamic model to assess and predict rodenticide toxicity to non-target avian species.

  6. Acute toxicity of dietary polybrominated biphenyls in Bobwhite Quail

    SciTech Connect

    Cottrell, W.O.; Ringer, R.K.; Babish, J.G.

    1984-09-01

    This investigation was undertaken to study the acute oral toxicity of PBB to Bobwhite Quail (Colinus virginianus). The median lethal dietary concentration (LC/sub 56/) of PBB was determined over 8 days and clinical signs of intoxication are described.

  7. Evaluation of the Salmonella enterica Serovar Pullorum Pathogenicity Island 2 Mutant as a Candidate Live Attenuated Oral Vaccine.

    PubMed

    Yin, Junlei; Cheng, Zhao; Wang, Xiaochun; Xu, Lijuan; Li, Qiuchun; Geng, Shizhong; Jiao, Xinan

    2015-07-01

    Salmonella enterica serovar Pullorum (S. Pullorum) is a highly adapted pathogen that causes pullorum disease (PD), an important systemic disease of poultry that causes severe economic losses in developing countries. In the interests of developing a safe and immunogenic oral vaccine, the efficacy of a Salmonella pathogenicity island 2 (SPI2)-deleted mutant of S. Pullorum (S06004ΔSPI2) was evaluated in chickens. S06004ΔSPI2 was severely less virulent than the parental wild-type strain S06004 as determined by the 50% lethal dose (LD50) for 3-day-old chickens when injected intramuscularly. Two-day-old chickens immunized with a single oral dose of S06004ΔSPI2 showed no differences in body weight or clinical symptoms compared with those in the negative-control group. S06004ΔSPI2 bacteria were not isolated from livers or spleens of immunized chickens after a short period of time, and specific humoral and cellular immune responses were significantly induced. Immunized chickens were challenged with S. Pullorum strain S06004 and Salmonella enterica serovar Gallinarum (S. Gallinarum) strain SG9 at 10 days postimmunization (dpi), and efficient protection against the challenges was observed. None of the immunized chickens died, the clinical symptoms were slight and temporary following challenge in immunized chickens compared with those in the control group, and these chickens recovered by 3 to 5 dpi. Overall, these results demonstrate that S06004ΔSPI2 can be used as a live attenuated oral vaccine.

  8. Evaluation of the Salmonella enterica Serovar Pullorum Pathogenicity Island 2 Mutant as a Candidate Live Attenuated Oral Vaccine

    PubMed Central

    Yin, Junlei; Cheng, Zhao; Wang, Xiaochun; Xu, Lijuan; Li, Qiuchun; Geng, Shizhong

    2015-01-01

    Salmonella enterica serovar Pullorum (S. Pullorum) is a highly adapted pathogen that causes pullorum disease (PD), an important systemic disease of poultry that causes severe economic losses in developing countries. In the interests of developing a safe and immunogenic oral vaccine, the efficacy of a Salmonella pathogenicity island 2 (SPI2)-deleted mutant of S. Pullorum (S06004ΔSPI2) was evaluated in chickens. S06004ΔSPI2 was severely less virulent than the parental wild-type strain S06004 as determined by the 50% lethal dose (LD50) for 3-day-old chickens when injected intramuscularly. Two-day-old chickens immunized with a single oral dose of S06004ΔSPI2 showed no differences in body weight or clinical symptoms compared with those in the negative-control group. S06004ΔSPI2 bacteria were not isolated from livers or spleens of immunized chickens after a short period of time, and specific humoral and cellular immune responses were significantly induced. Immunized chickens were challenged with S. Pullorum strain S06004 and Salmonella enterica serovar Gallinarum (S. Gallinarum) strain SG9 at 10 days postimmunization (dpi), and efficient protection against the challenges was observed. None of the immunized chickens died, the clinical symptoms were slight and temporary following challenge in immunized chickens compared with those in the control group, and these chickens recovered by 3 to 5 dpi. Overall, these results demonstrate that S06004ΔSPI2 can be used as a live attenuated oral vaccine. PMID:25924763

  9. [Latest advances in acute pancreatitis].

    PubMed

    de-Madaria, Enrique

    2015-09-01

    The present article analyses the main presentations on acute pancreatitis at Digestive Disease Week 2015. Arterial pseudoaneurysm is an uncommon complication of acute pancreatitis (incidence 0.7%) and mortality from this cause is currently anecdotal. Diabetes mellitus has little impact on the clinical course of acute pancreatitis, unlike cirrhosis, which doubles the risk of mortality. Intake of unsaturated fat could be associated with an increased severity of acute pancreatitis and is a confounding factor in studies evaluating the relationship between obesity and morbidity and mortality. PET-CT (positron emission tomography-computed tomography) could be a non-invasive tool to detect infection of collections in acute pancreatitis. Peripancreatic fat necrosis is less frequent than pancreatic fat necrosis and is associated with a better clinical course. If the clinical course is poor, increasing the calibre of the percutaneous drains used in the treatment of infected necrosis can avoid surgery in 20% of patients. The use of low molecular-weight heparin in moderate or severe pancreatitis could be associated with a better clinical course, specifically with a lower incidence of necrosis. In acute recurrent pancreatitis, simvastatin is a promising drug for prophylaxis of new episodes of acute pancreatitis. Nutritional support through a nasogastric tube does not improve clinical course compared with oral nutrition.

  10. Assessment of Antioxidant Potential and Acute Toxicity Studies of Whole Plant Extract of Pergularia Daemia (Forsk)

    PubMed Central

    Vaithiyanathan, Veluchamy; Mirunalini, Sankaran

    2015-01-01

    Background: Pergularia daemia (Asclepiadacea) is a fetid- smelling perennial herb growing well along the river bang and road sides of India. Naturally the plant has powerful antioxidants including polyphenols, flavanoids, steroids and terpenoids. Objective: The aim of this study is to evaluate the in vitro antioxidant potential and to determine the median lethal dose (LD50) of crude ethyl acetate and methanol extracts of Pergularia daemia. The plant Pergularia daemia possess effective scavenging activity against 2, 2' azino bis (3 ethylbenzothiazoline 6 sulfonic acid (ABTS), nitric oxide and reducing power radicals at different concentrations (100, 200, 300, 400 & 500 µg/mL) of both extracts. Results: From the above in vitro assay we have exposed that the methanolic extract exert higher antioxidant activity at 400 µg/mL than ethyl acetate extract. Acute toxicity study revealed that the extracts showed no signs of toxicity upto a dose level of 2500 mg/kg b.wt. Conclusion: Thus our findings provide that both extracts of Pergularia daemia possess a strong antioxidant capacity and are relatively has high margin of safety. PMID:26862261

  11. Clinical & pathological features of acute toxicity due to Cassia occidentalis in vertebrates.

    PubMed

    Vashishtha, V M; John, T J; Kumar, Amod

    2009-07-01

    Cassia occidentalis is an annual shrub found in many countries including India. Although bovines and ovines do not eat it, parts of the plant are used in some traditional herbal medicines. Several animal studies have documented that fresh or dried beans are toxic. Ingestion of large amounts by grazing animals has caused serious illness and death. The toxic effects in large animals, rodents and chicken are on skeletal muscles, liver, kidney and heart. The predominant systems involved depend upon the animal species and the dose of the beans consumed. Brain functions are often affected. Gross lesions at necropsy consist of necrosis of skeletal muscle fibres and hepatic centrilobular necrosis; renal tubular necrosis is less frequent. Muscle and liver cell necrosis is reflected in biochemical abnormalities. The median lethal dose (LD(50)) is 1 g/kg for mice and rats. Toxicity is attributed to various anthraquinones and their derivatives and alkaloids, but the specific toxins have not been identified. Data on human toxicity are extremely scarce. This review summarizes information available on Cassia toxicity in animals and compares it with toxic features reported in children. The clinical spectrum and histopathology of C. occidentalis poisoning in children resemble those of animal toxicity, affecting mainly hepatic, skeletal muscle and brain tissues. The case-fatality rate in acute severe poisoning is 75-80 per cent in children. PMID:19700797

  12. [Acute diazepam poisoning in experimental animals and the effect of centrophenoxine on it].

    PubMed

    Mirchev, N

    1976-01-01

    The author carried out studies on 20 white rats (weight of 150 gm) and 40 white mice (weight of 20 gm), equal number of both sexes administering oraly respective doses of diazepam in a dose of 650 mg/body weight and 620 mg/body weight, having in mind the LD50 determined by him (730 mg/body weight for rats and 535 mg/body weight for mice). In this way he induced acute intoxication especially gravely manifested in mice. After two hours, when the rats were in a comatous state, he introduced oraly centrophenoxine in a dose of 50 mg/body weight in half of the animals, but the other animals remained as controls. Mice succumed to coma after two and a half hours. In half of them he administered oraly centrophenoxine in a boose of 50 mg/body weight, which dose was repeated after two hours, but the remaining animals remained as controls. All rats, treated with centrophenoxine, remained alive and recovered quickly from the intoxication while four of the control animals died, but in the remaining alive animals the recovery was very slow. Only four of the mice treated with centrophenoxine died, but in the remaining alive mice the signs of intoxication disappeared quickly. Twelve of the control animals died, but the remaining animals recovered very quickly. The obtained results corresponded to the favourable effect of centophenoxine, observed by us, in treatment of persons, intoxicated by diazepam.

  13. Oral Health in Pregnancy.

    PubMed

    Hartnett, Erin; Haber, Judith; Krainovich-Miller, Barbara; Bella, Abigail; Vasilyeva, Anna; Lange Kessler, Julia

    2016-01-01

    Oral health is crucial to overall health. Because of normal physiologic changes, pregnancy is a time of particular vulnerability in terms of oral health. Pregnant women and their providers need more knowledge about the many changes that occur in the oral cavity during pregnancy. In this article we describe the importance of the recognition, prevention, and treatment of oral health problems in pregnant women. We offer educational strategies that integrate interprofessional oral health competencies. PMID:27281467

  14. Illumina sequencing of the V4 hypervariable region 16S rRNA gene reveals extensive changes in bacterial communities in the cecum following carbohydrate oral infusion and development of early-stage acute laminitis in the horse.

    PubMed

    Moreau, Michael M; Eades, Susan C; Reinemeyer, Craig R; Fugaro, Michael N; Onishi, Janet C

    2014-01-31

    In the equine carbohydrate overload model of acute laminitis, disease progression is associated with changes in bacteria found in the cecum. To date, research has focused on changes in specific Gram-positive bacteria in this portion of the intestinal tract. Metagenomic methods are now available making it possible to interrogate microbial communities using animal protocols that sufficiently power a study. In this study, the microbiota in cecal fluid collected from control, non-laminitic horses (n=8) and from horses with early-stage acute laminitis induced with either oligofructan (n=6) or cornstarch (n=6) were profiled. The microbiota were identified based on sequencing the V4 hypervariable region of the 16S rRNA gene. The results of the study show that the relative abundance of Lactobacillus sp. and Streptococcus sp. increased significantly (p<0.05) following OF and CS infusion. Other significant changes included an increase (p<0.05) in relative abundance of Veillonella sp. and Serratia sp., two potentially pathogenic, Gram-negative bacteria. Significant decreases in the relative abundance of presumptive normal flora were detected as well. Although changes in cecal microbiota described in this communication are from a pilot study, it is hypothesized that an overgrowth of pathogenic Gram-negative bacteria develops and contributes to enterocolitis, pyrexia and lameness in the carbohydrate overload model of acute laminitis. PMID:24355533

  15. Poliomyelitis in transgenic mice expressing CD155 under the control of the Tage4 promoter after oral and parenteral poliovirus inoculation.

    PubMed

    Khan, Shaukat; Toyoda, Hidemi; Linehan, Melissa; Iwasaki, Akiko; Nomoto, Akio; Bernhardt, Günter; Cello, Jeronimo; Wimmer, Eckard

    2014-08-01

    An important step in poliovirus (PV) infection by the oral route in humans is replication of the virus in lymphatic tissues of the gastrointestinal (GI) tract, thought to be mainly in the Peyer's patches of the small intestine. No immunocompetent transgenic (tg) mice that express human PV receptor (CD155) under the control of different promoters can be infected orally. The mouse orthologue of human CD155 is Tage4, a protein expressed at the surface of enterocytes and in the Peyer's patches. We describe here the generation of a tg mouse model in which the Tage4 promoter was used to drive expression of the human PV receptor-coding region (Tage4-CD155tg mice). In this model, CD155 expression was observed by immunostaining in different regions in the Peyer's patches but not in their germinal centres. Although a similar pattern of staining was observed between 3- and 6-week-old Tage4-CD155tg mice, poliomyelitis was only seen in the younger mice after PV infection by the oral route. When compared with TgPVR21 mice that expressed CD155 driven by its human promoter, 3-week-old Tage4-CD155tg mice were more susceptible to gut infection and paralysis following feeding with PV. Also, Tage4-CD155tg mice exhibited higher susceptibility to poliomyelitis after parenteral inoculation of PV. Remarkably, the LD50 after intracerebral inoculation of PV was similar in both CD155 tg mouse strains. The CD155 tg mouse model reported here, although moderately susceptible to oral infection, may be suitable to study mechanisms of PV replication in the gastrointestinal tract and to dissect important aspects of PV neuroinvasiveness.

  16. Acute gastroenteritis.

    PubMed

    Graves, Nancy S

    2013-09-01

    Acute gastroenteritis is a common infectious disease syndrome, causing a combination of nausea, vomiting, diarrhea, and abdominal pain. There are more than 350 million cases of acute gastroenteritis in the United States annually and 48 million of these cases are caused by foodborne bacteria. Traveler's diarrhea affects more than half of people traveling from developed countries to developing countries. In adult and pediatric patients, the prevalence of Clostridium difficile is increasing. Contact precautions, public health education, and prudent use of antibiotics are necessary goals in decreasing the prevalence of Clostridium difficle. Preventing dehydration or providing appropriate rehydration is the primary supportive treatment of acute gastroenteritis.

  17. Oral Cancer Foundation

    MedlinePlus

    ... Famous People Famous historical Arts & Entertainment Sports figures ... The Oral Cancer Foundation The Oral Cancer Foundation is a national public service, non-profit entity designed to reduce suffering ...

  18. 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.

  19. 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.

  20. 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. PMID:26125159

  1. Acute Bronchitis

    MedlinePlus

    ... bronchitis? Acute bronchitis is almost always caused by viruses that attack the lining of the bronchial tree ... infection. As your body fights back against these viruses, more swelling occurs and more mucus is produced. ...

  2. Acute Pericarditis

    MedlinePlus

    ... large pericardial effusions). Acute pericarditis usually responds to colchicine or NSAIDs (such as aspirin and ibuprofen ) taken ... reduce pain but relieves it by reducing inflammation. Colchicine also decreases the chance of pericarditis returning later. ...

  3. Developing Oral Communication Skills.

    ERIC Educational Resources Information Center

    Washington Office of the State Superintendent of Public Instruction, Olympia.

    Intended for use by both elementary and secondary school teachers, the two papers in this report stress the importance of developing students' oral and written communication skills. The first paper, "Relationship of Oral Communication to Reading," by Phil Backlund and John Johnson, argues that ability in oral communication is a prerequisite to the…

  4. Bibliography on Oral History.

    ERIC Educational Resources Information Center

    Waserman, Manfred J., Comp.

    This annotated bibliography covers articles and books dealing with oral history published between 1950 and 1970. In addition to works treating oral history as a methodology for historical discovery, the guide includes a separate annotated list of twenty selected books that use oral history material in the development of their themes and…

  5. Oral Contraceptives and Cancer Risk

    MedlinePlus

    ... oral contraceptives are available in the United States today? How could oral contraceptives influence cancer risk? How ... oral contraceptives are available in the United States today? Two types of oral contraceptives (birth control pills) ...

  6. Head, Neck, and Oral Cancer

    MedlinePlus

    ... Neck and Oral Pathology Head, Neck and Oral Pathology Close to 42,000 Americans will be diagnosed ... Neck and Oral Pathology Head, Neck and Oral Pathology Close to 42,000 Americans will be diagnosed ...

  7. Tissue, Dosimetry, Metabolism and Excretion of Pentavalent and Trivalent Dimethylated Arsenic in Mice after Oral Administration

    EPA Science Inventory

    Dimethylarsinic acid (DMA(V)) is a rat bladder carcinogen and the major urinary metabolite of administered inorganic arsenic in most mammals. This study examined the disposition of pentavalent and trivalent dimethylated arsenic inmice after acute oral administration. Adult fema...

  8. State of the art: Oral antiplatelet therapy

    PubMed Central

    Myat, Aung; Kubica, Jacek; Tantry, Udaya S

    2016-01-01

    Platelet adhesion, activation, and aggregation are central to the propagation of coronary thrombosis following rupture, fissure, or erosion of an atherosclerotic plaque. This chain of deleterious events underlies the pathophysiological process leading to an acute coronary syndrome. Therefore, oral antiplatelet therapy has become the cornerstone of therapy for the management of acute coronary syndrome and the prevention of ischemic complications associated with percutaneous coronary intervention. Landmark trials have established aspirin, and the addition of clopidogrel to aspirin, as key therapeutic agents in the context of acute coronary syndrome and percutaneous coronary intervention. Dual antiplatelet therapy has been the guideline-mandated standard of care in acute coronary syndrome and percutaneous coronary intervention. Despite the proven efficacy of dual antiplatelet therapy, adverse ischemic events continue to occur and this has stimulated the development of novel, more potent antiplatelet agents. We focus this state-of-the-art review on the most recent advances in oral antiplatelet therapy, treading the tightrope of potency versus bleeding risk, the quest to determine the optimal duration of dual antiplatelet therapy and future of personalized antiplatelet therapy. PMID:27298725

  9. Doxepin Rinse Versus Placebo in the Treatment of Acute Oral Mucositis Pain in Patients Receiving Head and Neck Radiotherapy With or Without Chemotherapy: A Phase III, Randomized, Double-Blind Trial (NCCTG-N09C6 [Alliance])

    PubMed Central

    Leenstra, James L.; Miller, Robert C.; Qin, Rui; Martenson, James A.; Dornfeld, Kenneth J.; Bearden, James D.; Puri, Dev R.; Stella, Philip J.; Mazurczak, Miroslaw A.; Klish, Marie D.; Novotny, Paul J.; Foote, Robert L.; Loprinzi, Charles L.

    2014-01-01

    Purpose Painful oral mucositis (OM) is a significant toxicity during radiotherapy for head and neck cancers. The aim of this randomized, double-blind, placebo-controlled trial was to test the efficacy of doxepin hydrochloride in the reduction of radiotherapy-induced OM pain. Patients and Methods In all, 155 patients were randomly allocated to a doxepin oral rinse or a placebo for the treatment of radiotherapy-related OM pain. Patients received a single dose of doxepin or placebo on day 1 and then crossed over to receive the opposite agent on a subsequent day. Pain questionnaires were administered at baseline and at 5, 15, 30, 60, 120, and 240 minutes. Patients were then given the option to continue doxepin. The primary end point was pain reduction as measured by the area under the curve (AUC) of the pain scale using data from day 1. Results Primary end point analysis revealed that the AUC for mouth and throat pain reduction was greater for doxepin (−9.1) than for placebo (−4.7; P < .001). Crossover analysis of patients completing both phases confirmed that patients experienced greater mouth and throat pain reduction with doxepin (intrapatient changes of 4.1 for doxepin-placebo arm and −2.8 for placebo-doxepin arm; P < .001). Doxepin was associated with more stinging or burning, unpleasant taste, and greater drowsiness than the placebo rinse. More patients receiving doxepin expressed a desire to continue treatment than did patients with placebo after completion of each of the randomized phases of the study. Conclusion A doxepin rinse diminishes OM pain. Further studies are warranted to determine its role in the management of OM. PMID:24733799

  10. Acute toxicity and synergistic and antagonistic effects of the aromatic compounds of some essential oils against Culex quinquefasciatus Say larvae.

    PubMed

    Pavela, Roman

    2015-10-01

    The efficacy of 30 aromatic compounds and their mutual binary combinations was assessed for acute toxicity against the larvae Culex quinquefasciatus. Based on comparison of the lethal doses, thymol and p-cymene were selected as the most effective (LD50 = 18 and 21 mg L(-1), respectively, and LD90 = 25 and 30 mg L(-1), respectively). Although the LD50 for terpinolene and trans-anethole was also estimated at 21 mg L(-1), their LD90 was significantly higher compared to the substances above (245 and 34 mg L(-1), respectively). In total, 435 binary combinations were tested, of which 249 combinations showed a significant synergistic effect, while 74 combinations showed a significant antagonistic effect on mortality. Only nine substances were identified as being able to create a synergistic effect with more than 20 substances: limonene, trans-anethole, 4-allylanisole, carvacrol, isoeugenol, menthone, carvone, borneol, and camphor. The highest synergistic effect on larval mortality was achieved for the combinations: eugenol and isoeugenol, carvone and carvacrol, carvone and 4-allylanisole, carvone and α-terpineol, carvone and menthone, limonene and trans-anethole, limonene and menthone, α-pinene and menthone, β-citronellol and menthone, carvacrol and 4-allylanisole, carvacrol and terpineol, α-terpinene and trans-anethole, camphor and menthone, camphene and menthone, and 4-allylanisole and menthone. Significant differences between achieved mortality and the mutual mixing ratio were found for the five selected binary mixtures that had shown the most significant synergistic effect in the previous tests. The mixture of limonene and trans-anethole showed the highest mortality, with the mixing ratio 1:1; the mixture of eugenol and isoeugenol caused 90.2% mortality, with the mixing ratio 1:3. One hundred percent mortality was achieved if carvacrol was contained in a mixture with carvone in a ratio >2. After a comparison of all our results, based on our experiments, we

  11. [EFFECT OF 4-METHYLPYRAZOLE ON IMMUNE RESPONSE, FUNCTION OF Th1 AND Th2 LYMPHOCYTES, AND CYTOKINE CONCENTRATION IN RAT BLOOD AFTER ACUTE METHANOL POISONING].

    PubMed

    Zabrodskii, P F; Maslyakov, V V; Gromov, M S

    2016-01-01

    It was established in experiments on noninbred albino rats that the acute intoxication with methanol (1.0 LD50) decreased cellular and humoral immune responses, Th2-lymphocyte activity (to a greater extent as compared to the function of Th1 cells), reduced the blood concentration of immunoregulatory (IFN-g, IL-2, IL-4) and proinflammatory (TNF, IL-1b, IL-6) cytokines on the average by 36.5% (p < 0.05), and did not affect the content of anti-inflammatory cytokines (IL-10, IL-13). Methanol antidote 4-methylpyrazole (non-competitive inhibitor of alcohol dehydrogenase) administered upon acute intoxication with methanol at a dose of 1.0 DL50 partially reduces the intoxication-induced suppression of humoral and cellular immune response, activity of T-helper cells, and production of IL-4 and restores blood levels of TNF, IL-1b, IFN-γ, IL-4, IL-2, IL-6 to the control values. PMID:27455577

  12. Recombinant expression of Bacillus anthracis lethal toxin components of Indian isolate in Escherichia coli and determination of its acute toxicity level in mouse model.

    PubMed

    Nagendra, Suryanarayana; Vanlalhmuaka; Verma, Sarika; Tuteja, Urmil; Thavachelvam, Kulanthaivel

    2015-12-15

    Bacillus anthracis lethal toxin (LeTx) is the principle factor responsible for toxaemia and anthrax related death. Lethal toxin consist of two proteins viz protective antigen (PA) and lethal factor which combines in a typical fashion similar to other toxins belonging to A-B toxin super family. The amount of LeTx required to kill a particular organism generally differs among strains owing to their geographical distributions and genetic variation. In the present study, we have cloned PA and LF genes from B. anthracis clinical isolate of Indian origin and expressed them in soluble form employing Escherichia coli expression system. Both the proteins were purified to near homogeneity level using Immobilized metal ion affinity chromatography (IMAC). Further we have used equal ratio of both the proteins to form LeTx and determined its acute toxicity level in Balb/c mice by graphical method of Miller and Tainter. The LD50 value of LeTx by intravenous (i.v) route was found to be 0.97 ± 0.634 mg kg(-1) Balb/c mice. This study highlights the expression of recombinant LeTx from E. coli and assessing its acute toxicity level in experimental mouse model.

  13. Acute toxicity from baking soda ingestion.

    PubMed

    Thomas, S H; Stone, C K

    1994-01-01

    Sodium bicarbonate is an extremely well-known agent that historically has been used for a variety of medical conditions. Despite the widespread use of oral bicarbonate, little documented toxicity has occurred, and the emergency medicine literature contains no reports of toxicity caused by the ingestion of baking soda. Risks of acute and chronic oral bicarbonate ingestion include metabolic alkalosis, hypernatremia, hypertension, gastric rupture, hyporeninemia, hypokalemia, hypochloremia, intravascular volume depletion, and urinary alkalinization. Abrupt cessation of chronic excessive bicarbonate ingestion may result in hyperkalemia, hypoaldosteronism, volume contraction, and disruption of calcium and phosphorus metabolism. The case of a patient with three hospital admissions in 4 months, all the result of excessive oral intake of bicarbonate for symptomatic relief of dyspepsia is reported. Evaluation and treatment of patients with acute bicarbonate ingestion is discussed.

  14. 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

  15. 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. PMID:26617944

  16. Infant oral health and oral habits.

    PubMed

    Nowak, A J; Warren, J J

    2000-10-01

    Many oral diseases and conditions, including dental caries (cavities) and malocclusions, have their origins early in life. Prudent anticipatory guidance by the medical and dental professions can help prevent many of the more common oral health problems. This article provides information on the rationale for early dental examination and instructions for pediatric and family practitioners in scheduling and conducting an early oral intervention appointment. In addition, feeding practices, non-nutritive sucking, mouth breathing, and bruxing are discussed, including their effects on orofacial growth and development.

  17. Optimal timing of initiation of oral P2Y12-receptor antagonist therapy in patients with non-ST elevation acute coronary syndromes. Lessons learnt from the ACCOAST-trial.

    PubMed

    Zeymer, Uwe; Montalescot, Gilles; Ardissino, Diego; Bolognese, Leonardo; Clemmensen, Peter; Collet, Jean-Philippe; Lopez-Sendon, Jose; Widimsky, Petr

    2016-06-01

    The optimal time-point of the initiation of P2Y12 antagonist therapy in patients with non-ST elevation acute coronary syndromes (NTSE-ACS) is still a matter of debate. European guidelines recommend P2Y12 as soon as possible after first medical contact. However, the only trial which compared the two strategies did not demonstrate any benefit of pre-treatment with prasugrel before angiography compared to starting therapy after angiography and just prior to percutaneous coronary intervention (PCI). This paper summarizes the results of pharmacodynamic and previous studies, and gives recommendations for the initiation of P2Y12 antagonist therapy in NSTE-ACS in different clinical situations. PMID:25921481

  18. [Acute epiglottitis in adults].

    PubMed

    Castillo, A

    1992-09-01

    The author presents the clinical history of 14 patients, from 21 to 48 years of age, 10 men and 4 women, with a final diagnosis of acute epiglottitis who were hospitalized at Gorgas Army Hospital or at the San Fernando Clinic. All the patients had pharyngitis and dysphagia, a few with nasal voice, stridor and difficulty breathing, as the chief complaint. All the patients were initially intubated orally for diagnostic purposes and immediately after nasotracheal intubation was done until the patient improved in 2 or 3 days (one patient remained intubated for 5 days). All patients were kept in the Intensive Care Unit and were treated with Ampicillin and Chloramphenicol IV and lately with a second generation cephalosporin (Cefamandole). The patients allergic to Penicillin were treated with Clindamycin and Chloramphenicol. Corticosteroids were not used in any of the patients. There were no sequelae and none of the patients expired. PMID:1439005

  19. Assessment of antidiabetic activity and acute toxicity of leaf extracts from Physalis peruviana L. in guinea-pig

    PubMed Central

    Kasali, Félicien Mushagalusa; Kadima, Justin Ntokamunda; Mpiana, Pius Tshimankinda; Ngbolua, Koto-te-Nyiwa; Tshibangu, Damien Sha-Tshibey

    2013-01-01

    Objective To verify the antidiabetic activity of leaf extracts from Physalis peruviana L. popularly used in the Eastern part of the Democratic Republic of the Congo and to point out the possible toxicity. Method Aqueous decoctions prepared from dried leaves powder were administrated to guinea pigs at the dose range of 100 mg/kg to 3.2 g/kg of body weight. The hypoglycemic activity was evaluated by glucose tolerance test, loading animals with glucose 4 g/kg and measuring blood glucose concentrations at various times. The effect was compared to the control and glibenclamide as antidiabetic reference drug. Acute toxicity was evaluated by recording mortality rate, changes on blood biomarkers and damage caused to vital organs. Results At a dose of 100 mg/kg, the aqueous extract induced a significant reduction of peak concentration at 30 min after glucose loading as compared with control or reference (P<0.05). At doses greater than 400 mg, some alterations on blood, kidney and liver markers were observed. Upper 800 mg/kg, mortality was observed with LD50 estimated at about 1 280 mg/kg. At the autopsy, vital organs were in haemorrhage and swelling state. Conclusion The crude aqueous extracts from the leaves of Physalis peruviana L. present hypoglycemic activity in animal model, but at high doses the plant may cause severe intoxication.

  20. In vivo titration of white spot syndrome virus (WSSV) in specific pathogen-free Litopenaeus vannamei by intramuscular and oral routes.

    PubMed

    Escobedo-Bonilla, C M; Wille, M; Sanz, V Alday; Sorgeloos, P; Pensaert, M B; Nauwynck, H J

    2005-09-01

    White spot syndrome virus (WSSV) is a devastating pathogen in shrimp aquaculture. Standardized challenge procedures using a known amount of infectious virus would assist in evaluating strategies to reduce its impact. In this study, the shrimp infectious dose 50% endpoint (SID50 ml(-1)) of a Thai isolate of WSSV was determined by intramuscular inoculation (i.m.) in 60 and 135 d old specific pathogen-free (SPF) Litopenaeus vannamei using indirect immunofluorescence (IIF) and 1-step polymerase chain reaction (PCR). Also, the lethal dose 50% endpoint (LD50 ml(-1)) was determined from the proportion of dead shrimp. The median virus infection titers in 60 and 135 d old juveniles were 10(6.8) and 10(6.5) SID50 ml(-1), respectively. These titers were not significantly different (p > or = 0.05). The titration of the WSSV stock by oral intubation in 80 d old juveniles resulted in approximately 10-fold reduction in virus titer compared to i.m. inoculation. This lower titer is probably the result of physical and chemical barriers in the digestive tract of shrimp that hinder WSSV infectivity. The titers determined by infection were identical to the titers determined by mortality in all experiments using both i.m. and oral routes at 120 h post inoculation (hpi), indicating that every infected shrimp died. The determination of WSSV titers for dilutions administered by i.m. and oral routes constitutes the first step towards the standardization of challenge procedures to evaluate strategies to reduce WSSV infection.

  1. Clinical signs, pathology and dose-dependent survival of adult wood frogs, Rana sylvatica, inoculated orally with frog virus 3 Ranavirus sp., Iridoviridae.

    PubMed

    Forzn, Mara J; Jones, Kathleen M; Vanderstichel, Raphal V; Wood, John; Kibenge, Frederick S B; Kuiken, Thijs; Wirth, Wytamma; Ariel, Ellen; Daoust, Pierre-Yves

    2015-05-01

    Amphibian populations suffer massive mortalities from infection with frog virus 3 FV3, genus Ranavirus, family Iridoviridae, a pathogen also involved in mortalities of fish and reptiles. Experimental oral infection with FV3 in captive-raised adult wood frogs, Rana sylvatica Lithobates sylvaticus, was performed as the first step in establishing a native North American animal model of ranaviral disease to study pathogenesis and host response. Oral dosing was successful LD50 was 10(2.93 2.423.44) p.f.u. for frogs averaging 35mm in length. Onset of clinical signs occurred 614days post-infection p.i. median 11 days p.i. and time to death was 1014 days p.i. median 12 days p.i.. Each tenfold increase in virus dose increased the odds of dying by 23-fold and accelerated onset of clinical signs and death by approximately 15. Ranavirus DNA was demonstrated in skin and liver of all frogs that died or were euthanized because of severe clinical signs. Shedding of virus occurred in faeces 710 days p.i. 34.5days before death and skin sheds 10 days p.i. 01.5days before death of some frogs dead from infection. Most common lesions were dermal erosion and haemorrhages haematopoietic necrosis in bone marrow, kidney, spleen and liver and necrosis in renal glomeruli, tongue, gastrointestinal tract and urinary bladder mucosa. Presence of ranavirus in lesions was confirmed by immunohistochemistry. Intracytoplasmic inclusion bodies probably viral were present in the bone marrow and the epithelia of the oral cavity, gastrointestinal tract, renal tubules and urinary bladder. Our work describes a ranaviruswood frog model and provides estimates that can be incorporated into ranavirus disease ecology models.

  2. Ageing, dementia and oral health.

    PubMed

    Foltyn, P

    2015-03-01

    Neurocognitive decline and delirium, frailty, incontinence, falls, hearing and vision impairment, medication compliance and pharmacokinetics, skin breakdown, impaired sleep and rest are regarded as geriatric giants by gerontologists, geriatricians and nursing home staff. As these are all interrelated in the elderly, failure to act on one can impact on the others. However, the implications of poor oral health have for too long been ignored and deserve equal status. Mouth pain can be devastating for the elderly, compound psychosocial problems, frustrate carers and nursing home staff and disrupt family dynamics. As appearance, function and comfort suffer, so may a person's self-esteem and confidence. The contributing factors for poor oral health such as rapid dental decay, acute and chronic periodontal infections and compromised systemic health on a background of a dry mouth, coupled with xerostomia-inducing medications, reduced fine motor function, declining cognition and motivation will not only lead to an increase in both morbidity and mortality but also impact on quality of life. PMID:25762045

  3. Advances in Oral Coagulants

    PubMed Central

    2013-01-01

    This article reviews current and future treatment practices concerning oral anticoagulants. In the second decade of the 21st millennium clinicians can finally treat thrombotic disease with long-awaited new oral anticoagulant medications. In addition, improvements have been made in managing warfarin, the traditional but far from obsolete medication. The first part of this review will cover current advances with warfarin treatment. The second portion will discuss specific active coagulation factor inhibitors, the new oral anticoagulants.

  4. Fucoidan Extracts Ameliorate Acute Colitis.

    PubMed

    Lean, Qi Ying; Eri, Rajaraman D; Fitton, J Helen; Patel, Rahul P; Gueven, Nuri

    2015-01-01

    Inflammatory bowel diseases (IBD), such as ulcerative colitis and Crohn's disease, are an important cause of morbidity and impact significantly on quality of life. Overall, current treatments do not sustain a long-term clinical remission and are associated with adverse effects, which highlight the need for new treatment options. Fucoidans are complex sulphated, fucose-rich polysaccharides, found in edible brown algae and are described as having multiple bioactivities including potent anti-inflammatory effects. Therefore, the therapeutic potential of two different fucoidan preparations, fucoidan-polyphenol complex (Maritech Synergy) and depyrogenated fucoidan (DPF) was evaluated in the dextran sulphate sodium (DSS) mouse model of acute colitis. Mice were treated once daily over 7 days with fucoidans via oral (Synergy or DPF) or intraperitoneal administration (DPF). Signs and severity of colitis were monitored daily before colons and spleens were collected for macroscopic evaluation, cytokine measurements and histology. Orally administered Synergy and DPF, but not intraperitoneal DPF treatment, significantly ameliorated symptoms of colitis based on retention of body weight, as well as reduced diarrhoea and faecal blood loss, compared to the untreated colitis group. Colon and spleen weight in mice treated with oral fucoidan was also significantly lower, indicating reduced inflammation and oedema. Histological examination of untreated colitis mice confirmed a massive loss of crypt architecture and goblet cells, infiltration of immune cells and oedema, while all aspects of this pathology were alleviated by oral fucoidan. Importantly, in this model, the macroscopic changes induced by oral fucoidan correlated significantly with substantially decreased production of at least 15 pro-inflammatory cytokines by the colon tissue. Overall, oral fucoidan preparations significantly reduce the inflammatory pathology associated with DSS-induced colitis and could therefore represent

  5. Acute Pancreatitis

    PubMed Central

    Geokas, Michael C.

    1972-01-01

    For many decades two types of acute pancreatitis have been recognized: the edematous or interstitial and the hemorrhagic or necrotic. In most cases acute pancreatitis is associated with alcoholism or biliary tract disease. Elevated serum or urinary α-amylase is the most important finding in diagnosis. The presence of methemalbumin in serum and in peritoneal or pleural fluid supports the diagnosis of the hemorrhagic form of the disease in patients with a history and enzyme studies suggestive of pancreatitis. There is no characteristic clinical picture in acute pancreatitis, and its complications are legion. Pancreatic pseudocyst is probably the most common and pancreatic abscess is the most serious complication. The pathogenetic principle is autodigestion, but the precise sequence of biochemical events is unclear, especially the mode of trypsinogen activation and the role of lysosomal hydrolases. A host of metabolic derangements have been identified in acute pancreatitis, involving lipid, glucose, calcium and magnesium metabolism and changes of the blood clotting mechanism, to name but a few. Medical treatment includes intestinal decompression, analgesics, correction of hypovolemia and other supportive and protective measures. Surgical exploration is advisable in selected cases, when the diagnosis is in doubt, and is considered imperative in the presence of certain complications, especially pancreatic abscess. PMID:4559467

  6. 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. PMID:25871419

  7. Oral microbiota and cancer

    PubMed Central

    Meurman, Jukka H.

    2010-01-01

    Inflammation caused by infections may be the most important preventable cause of cancer in general. However, in the oral cavity the role of microbiota in carcinogenesis is not known. Microbial populations on mouth mucosa differ between healthy and malignant sites and certain oral bacterial species have been linked with malignancies but the evidence is still weak in this respect. Nevertheless, oral microorganisms inevitably up-regulate cytokines and other inflammatory mediators that affect the complex metabolic pathways and may thus be involved in carcinogenesis. Poor oral health associates statistically with prevalence of many types of cancer, such as pancreatic and gastrointestinal cancer. Furthermore, several oral micro-organisms are capable of converting alcohol to carcinogenic acetaldehyde which also may partly explain the known association between heavy drinking, smoking, poor oral health and the prevalence of oral and upper gastrointestinal cancer. A different problem is the cancer treatment-caused alterations in oral microbiota which may lead to the emergence of potential pathogens and subsequent other systemic health problems to the patients. Hence clinical guidelines and recommendations have been presented to control oral microbiota in patients with malignant disease, but also in this area the scientific evidence is weak. More controlled studies are needed for further conclusion. PMID:21523227

  8. Oral therapy for Peyronie’s disease, does it work?

    PubMed Central

    Barrett-Harlow, Brittani

    2016-01-01

    Peyronie’s disease (PD) is a localized, wound-healing, connective tissue disorder of the penis characterized by scarring of the tunica albuginea. This fibrous inelastic scar leads to penile pain, penile deformity and erectile dysfunction (ED), and a difficulty performing coitus. Over the past several decades, a myriad of oral agents for the treatment of PD have been studied and suggested. While the gold standard of care remains surgical therapy, many physicians continue to prescribe oral and intralesional injections for treatment during the acute phase of the disease. This article seeks to summarize the different oral therapy agents for PD and the research associated with each medication. While the American Urological Association has not recommended most of the mentioned medications for the treatment of PD, two newer therapies have shown success and have the potential of becoming baseline treatments for the acute phase of PD. PMID:27298776

  9. 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. PMID:27482300

  10. 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…

  11. Oral Transliterating. NETAC Tipsheet

    ERIC Educational Resources Information Center

    Troiano, Claire A.

    2005-01-01

    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 deaf person, inaudibly repeats the spoken message for the deaf person, making it as speechreadable as possible. This is called…

  12. Acute Vestibulopathy

    PubMed Central

    Cha, Yoon-Hee

    2011-01-01

    The presentation of acute vertigo may represent both a common benign disorder or a life threatening but rare one. Familiarity with the common peripheral vestibular disorders will allow the clinician to rapidly “rule-in” a benign disorder and recognize when further testing is required. Key features of vertigo required to make an accurate diagnosis are duration, chronicity, associated symptoms, and triggers. Bedside tests that are critical to the diagnosis of acute vertigo include the Dix-Hallpike maneuver and canalith repositioning manuever, occlusive ophthalmoscopy, and the head impulse test. The goal of this review is to provide the clinician with the clinical and pathophysiologic background of the most common disorders that present with vertigo to develop a logical differential diagnosis and management plan. PMID:23983835

  13. [Acute diarrhea].

    PubMed

    Burgmann, Konstantin; Schoepfer, Alain

    2014-09-01

    Diarrhea, defined as three or more loose or watery stools per day, represents a frequent problem in outpatients as well as inpatients. As most of the patients with acute diarrhea show a self-limiting disease course, the main challenge for the physician is to discriminate patients for whom symptomatic therapy is sufficient from those with severe disease course and threatening complications. This review aims to provide a practical guidance for such decisions.

  14. Curricular Guidelines for Oral Biology.

    ERIC Educational Resources Information Center

    Journal of Dental Education, 1984

    1984-01-01

    The American Association of Dental Schools' guidelines for oral biology curriculum cover its scope, primary educational goals, prerequisites, sequencing, faculty, course content in each subarea (oral tissues and systems and oral diagnostic methodology), and specific behavioral objectives. (MSE)

  15. Thrush (Oral Candidiasis) in Children

    MedlinePlus

    ... A A A In oral candidiasis, normal mouth yeast overgrows, causing white, slightly elevated lesions. Overview Thrush ( ... candidiasis), also known as oral moniliasis, is a yeast infection of the mouth or throat (the oral ...

  16. 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 ...

  17. Acute Toxic Neuropathy Mimicking Guillain Barre Syndrome

    PubMed Central

    Jalal, Muhammed Jasim Abdul; Fernandez, Shirley Joan; Menon, Murali Krishna

    2015-01-01

    Case: A 30 year old male presented with numbness of palms and soles followed by weakness of upper limbs and lower limbs of 5 days duration, which was ascending and progressive. Three months back he was treated for oral and genital ulcers with oral steroids. His ulcers improved and shifted to indigenous medication. His clinical examination showed polyneuropathy. CSF study did not show albuminocytological dissociation. Nerve conduction study showed demyelinating polyneuropathy. His blood samples and the ayurvedic drug samples were sent for toxicological analysis. Inference: Acute toxic neuropathy - Arsenic PMID:25811007

  18. 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 "chistes" (jokes), 1…

  19. Comparative study on toxic effects induced by oral or intravascular administration of commonly used disinfectants and surfactants in rats.

    PubMed

    Xue, Yuying; Zhang, Shanshan; Tang, Meng; Zhang, Ting; Wang, Yiqing; Hieda, Yoko; Takeshita, Haruo

    2012-07-01

    Accidental ingestion or injection of household products sometimes occurs due to their accessibility, but the toxic manifestations have not been well characterized when they are internally administered. The aim of this study was to investigate the toxic effects induced by ingestion or injection of different ionic surfactants and disinfectants in rats. The test drugs involved benzalkonium and benzethonium (BZK and BZT, both cationic surfactants used as disinfectants), alkyldiaminoethylglycine (AEG, an amphoteric surfactant used as a disinfectant), linear alkylbenzenesulfonate (LAS, an anionic surfactant), polyoxyethylene cetylether (PEC, a nonionic surfactant), chlorhexidine (CHX, not a surfactant but a disinfectant) and saline (control). Male Sprague-Dawley rats were administered one of the test drugs orally (p.o.), intravenously (i.v.) or intraarterially (i.a.). The fatal effects appeared rapidly (<30 min) in i.v.-administered rats, while taking hours (>5 h) in i.a./p.o.-administered rats after a dose of around LD(50) , although the progress and degree of toxic effects varied among the drugs tested. In intravascular administration, BZK and BZT were fatal at doses of 15-20 mg kg(-1) . Higher concentrations in lung and kidney than in blood were determined. CHX showed a high toxic effect compared with cationic surfactants. The rats administered anionic (LAS) or amphoteric (AEG) surfactant died in less than 24 h at doses over 100 mg kg(-1) . In p.o. administration, the toxic effects were concentration/dose-dependent, and all rats administered high doses of surfactants except for PEC died at 5-20 h. The overall toxic ranks could be: cationic surfactant/CHX> anionic/amphoteric surfactant > nonionic surfactant.

  20. Acute Bacterial Prostatitis: Diagnosis and Management.

    PubMed

    Coker, Timothy J; Dierfeldt, Daniel M

    2016-01-15

    Acute bacterial prostatitis is an acute infection of the prostate gland that causes pelvic pain and urinary tract symptoms, such as dysuria, urinary frequency, and urinary retention, and may lead to systemic symptoms, such as fevers, chills, nausea, emesis, and malaise. Although the true incidence is unknown, acute bacterial prostatitis is estimated to comprise approximately 10% of all cases of prostatitis. Most acute bacterial prostatitis infections are community acquired, but some occur after transurethral manipulation procedures, such as urethral catheterization and cystoscopy, or after transrectal prostate biopsy. The physical examination should include abdominal, genital, and digital rectal examination to assess for a tender, enlarged, or boggy prostate. Diagnosis is predominantly made based on history and physical examination, but may be aided by urinalysis. Urine cultures should be obtained in all patients who are suspected of having acute bacterial prostatitis to determine the responsible bacteria and its antibiotic sensitivity pattern. Additional laboratory studies can be obtained based on risk factors and severity of illness. Radiography is typically unnecessary. Most patients can be treated as outpatients with oral antibiotics and supportive measures. Hospitalization and broad-spectrum intravenous antibiotics should be considered in patients who are systemically ill, unable to voluntarily urinate, unable to tolerate oral intake, or have risk factors for antibiotic resistance. Typical antibiotic regimens include ceftriaxone and doxycycline, ciprofloxacin, and piperacillin/tazobactam. The risk of nosocomial bacterial prostatitis can be reduced by using antibiotics, such as ciprofloxacin, before transrectal prostate biopsy. PMID:26926407

  1. 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.

  2. Acute toxicity of fipronil to the stingless bee Scaptotrigona postica Latreille.

    PubMed

    Jacob, Cynthia Renata Oliveira; Soares, Hellen Maria; Carvalho, Stephan Malfitano; Nocelli, Roberta Cornélio Ferreira; Malaspina, Osmar

    2013-01-01

    Fipronil is an insecticide widely used to control a great number of pests, thus the aim of this study was to determine the lethal dose and lethal concentration (LD(50) and LC(50)) of this insecticide to the stingless bees Scaptotrigona postica Latreille, 1807. The LD(50) and LC(50) values obtained after 24 h of exposition were of 0.54 ng a.i./bee and 0.24 ng a.i./μL diet, respectively. These values were considered highly toxic to stingless bees.

  3. Thymic necrosis following oral inoculation of mouse thymic virus.

    PubMed

    Morse, S S

    1989-11-01

    Mouse thymic virus (MTLV;ICTV designation murid herpesvirus 3) infects developing T lymphocytes of neonatal mice, causing thymic necrosis and acute immunosuppression. Infected animals shed virus indefinitely. However, although transmission in nature is presumably by contact and is likely to involve the oral-nasal route, virtually all experimental studies with MTLV have used systemic (intraperitoneal) inoculation. In order to determine whether systemic inoculation causes artifacts in pathogenesis of the infection, effects of intraperitoneal and oral-nasal inoculation were compared in newborn mice. Thymic necrosis occurred with either route of inoculation, although rate of infection was lower with oral inoculation, varying from about 20% to 67%. There were no gross differences in pathogenesis. Orally infected animals seroconverted and shed virus. These data indicate that the apparent lymphotropism of thymic virus, and induction of thymic necrosis, are not dependent on route of inoculation.

  4. [Acute pancreatitis: an overview of the management].

    PubMed

    Rebours, V

    2014-10-01

    Over the past decades, the incidence and the number of hospital admissions for acute pancreatitis have increased in the Western countries. The two most common etiological factors of acute pancreatitis are gallstones (including small gallstones or microlithiasis) and alcohol abuse. Acute pancreatitis is associated with a significant mortality (4-10%) and 25% in case of pancreatic necrosis, especially. Edematous pancreatitis is benign and oral feeding can be restarted once abdominal pain is decreasing and inflammatory markers are improving. Enteral tube feeding should be the primary therapy in patients with predicted severe acute pancreatitis who require nutritional support. Enteral nutrition in acute pancreatitis can be administered via either the nasojejunal or nasogastric route. In case of necrosis, preventive antibiotics are not recommended. The single indication is infected necrosis confirmed by fine needle aspiration. The incidence trends of acute pancreatitis possibly reflect a change in the prevalence of main etiological factors (e.g. gallstones and alcohol consumption) and cofactors such as tobacco, obesity and genetic susceptibility. Priority is to search for associated causes, especially in cases with atypical symptoms. In case of first acute pancreatitis in patients older than 50 years, the presence of a tumor (benign or malignant) has to be specifically ruled out, using CT-scan, MRI and endoscopic ultrasound.

  5. Acute toxicity, brine shrimp cytotoxicity, anthelmintic and relaxant potentials of fruits of Rubus fruticosus Agg

    PubMed Central

    2013-01-01

    Background Rubus fruticosus is used in tribal medicine as anthelmintic and an antispasmodic. In the current work, we investigated the anthelmintic and antispasmodic activities of crude methanol extract of fruits of R. fruticosus on scientific grounds. Acute toxicity and brine shrimp cytotoxicity activity of the extract were also performed. Methods Acute toxicity study of crude methanol extract of R. fruticosus was performed on mice. In vitro Brine shrimp cytotoxicity assay was performed on shrimps of Artemia salina. In vitro Anthelmintic activity was tested against Raillietina spiralis and Ascaridia galli. Relaxant activities were tested on spontaneous rabbits’ jejunal preparations. Calcium chloride curves were constructed to elucidate possible mode of action of the extract. Results LD 50 of the extract for acute toxicity studies was 887.75 ± 9.22 mg/ml. While CC 50 of the extract for Brine shrimps cytotoxicity assay was 13.28 ± 2.47 μg/ml. Test samples of crude methanolic extract of R. fruticosus (Rf.Cr) at concentration 20 mg/ml showed excellent anthelmintic activity against Raillietina spiralis. Anthelmintic activity was 1.37 times of albendazole against the Raillietina spiralis at concentration 40 mg/ml. At higher concentration (40 mg/ml), Rf.Cr has 89. 83% parasiticidal activity. The mean EC50 relaxation activity for spontaneous and KCl-induced contractions was 7.96 ± 0.1 and 6.45 ± 0.29 mg/ml, respectively. EC 50 (Log[Ca++]M) for control calcium chloride curves was −1.75 ± 0.01 vs. EC 50 −1.78 ± 0.06 in the presence of 3.0 mg/ml of Rf.Cr. Similarly, EC 50(Log[Ca++]M) in the absence and presence of verapamil (0.1 μM) were −2.46 ± 0.01 and −1.72 ± 0.02, respectively. Conclusions The anthelmintic and relaxant activities explained traditional uses of R. fruticosus on scientific grounds. Relaxant activity follows the inhibition of voltage gated channels. Although the plant extract has cytotoxic effects, yet it is

  6. Synthesis, expression and purification of a type of chlorotoxin-like peptide from the scorpion, Buthus martensii Karsch, and its acute toxicity analysis.

    PubMed

    Fu, Yue-jun; Yin, Li-tian; Wang, Wei; Chai, Bao-feng; Liang, Ai-hua

    2005-10-01

    A gene, rBmK Cta, encoding a chlorotoxin-like peptide from the scorpion, Buthus martensii Karsch, was synthesized according to the sequence optimized for codon usage in Escherichia coli and was expressed in E. coli BL21 (DE3) using a pExSecI expression system in which the IgG-binding domain-ZZ of protein A is fused to the N-terminal of rBmK CTa. The fusion protein, ZZ-rBmK CTa, was expressed in soluble form (7.8 mg l(-1)) and was purified to give a single band on SDS-PAGE. The domain-ZZ of fusion protein ZZ-rBmK CTa was removed by cleavage of an Asn-Gly peptide bond with hydroxylamine. The rBmK CTa was separated from the IgG-binding moiety by a second passage through the IgG affinity column. Western blot analysis demonstrated that this protein was rBmK CTa. Acute toxicity assay in mice demonstrated that the rBmK CTa had an LD(50) value of 4.3 mg kg(-1).

  7. Chemical composition, acute toxicity, and antinociceptive activity of the essential oil of a plant breeding cultivar of basil (Ocimum basilicum L.).

    PubMed

    Venâncio, Antônio Medeiros; Onofre, Alexandre Sherlley; Lira, Amintas Figueiredo; Alves, Péricles Barreto; Blank, Arie Fitzgerald; Antoniolli, Angelo Roberto; Marchioro, Murilo; Estevam, Charles dos Santos; de Araujo, Brancilene Santos

    2011-05-01

    Ocimum basilicum L. is an aromatic herb used in Brazil to treat illnesses such as respiratory and rheumatic problems, vomiting, and pain. In the present study, the chemical composition, acute toxicity, and antinociceptive effects of the essential oil (EO) of the cultivar "Maria Bonita" obtained from O. basilicum L. PI 197442 genotype were evaluated in Swiss mice (20-35 g each). Lethal dose to cause 50 % death (LD50) was calculated from a dose-response curve (100-5000 mg/kg body wt.; n = 6) as 532 mg/kg body wt. In the acetic acid-induced writhing test (0.6 % i. p.), EO (50, 100, and 200 mg/kg body wt., n = 8, s. c.) was effective in reducing the abdominal contractions at all doses (48-78 %). In the hot-plate test, EO significantly increased the latency at 50 mg/kg body wt. at all times (37-52 %, n = 8, s. c.). However, the effects of morphine and EO at 50 mg/kg were reverted in the presence of naloxone, an opioid antagonist. In the formalin test, EO significantly reduced paw licking time in the first and second phases of pain at 200 mg/kg body wt. (38 and 75 %, respectively, n = 8, s. c.). The results suggested that the peripheral and central antinociceptive effects of EO are related to the inhibition of the biosynthesis of pain mediators, such as prostaglandins and prostacyclins, and its ability to interact with opioid receptors.

  8. 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.

  9. 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

  10. Establishing a murine model of the Hematopoietic Syndrome of the Acute Radiation Syndrome

    PubMed Central

    Plett, P. Artur; Sampson, Carol H.; Chua, Hui Lin; Joshi, Mandar; Booth, Catherine; Gough, Alec; Johnson, Cynthia S.; Katz, Barry P.; Farese, Ann M.; Parker, Jeffrey; MacVittie, Thomas J.; Orschell, Christie M.

    2012-01-01

    We have developed a murine model of the Hematopoietic Syndrome of the Acute Radiation Syndrome (H-ARS) for efficacy testing of medical countermeasures (MCM) against radiation according to the FDA Animal Rule. Ten to 12 week old male and female C57BL/6 mice were exposed to the LD50/30-LD70/30 dose of total body irradiation (TBI, 137Cs, 0.62-0.67 Gy min-1) in the morning hours when mice were determined to be most radiosensitive, and assessed for 30 day survival and mean survival time (MST). Antibiotics were delivered in the drinking water on days 4-30 post-TBI at a concentration based on the amount of water that lethally-irradiated mice were found to consume. The fluoroquinolones, ciprofloxacin and levofloxacin, and the tetracycline doxycycline and aminoglycoside neomycin, all significantly increased MST of decedent mice, while ciprofloxacin (p=0.061) and doxycycline + neomycin (p=0.005) showed at least some efficacy to increase 30 day survival. Blood sampling (30uL/mouse every 5th day) was found to negatively impact 30 day survival. Histopathology of tissues harvested from non-moribund mice showed expected effects of lethal irradiation, while moribund mice were largely septicemic with a preponderance of enteric organisms. Kinetics of loss and recovery of peripheral blood cells in untreated mice and those treated with two MCM, granulocyte-colony stimulating factor and Amifostine, further characterized and validated our model for use in screening studies and pivotal efficacy studies of candidate MCM for licensure to treat irradiated individuals suffering from H-ARS. PMID:22929467

  11. Acute and sub-chronic toxicity study of diaveridine in Wistar rats.

    PubMed

    Wang, Xu; Su, Shijia; Ihsan, Awais; Huang, Qin; Chen, Dongmei; Cheng, Guyue; Liu, Zhenli; Wang, Yulian; Yuan, Zonghui

    2015-10-01

    Diaveridine, a developed dihydrofolate reductase inhibitor, has been widely used as anticoccidial drug and antibacterial synergist. However, few studies have been performed to investigate its toxicity. To provide detailed toxicity with a wide spectrum of doses for diaveridine, acute and sub-chronic toxicity studies were conducted. Calculated LD50 was 2330 mg/kg b.w. in females and 3100 mg/kg b.w. in males, and chromodacryorrhea was noted in some females before their death. In the sub-chronic study, diaveridine was fed to Wistar rats during 90 days at dietary levels of 0, 23, 230, 1150 and 2000 mg/kg, which were about 0, 2.0-2.3, 21.0-23.5, 115.2-126.9 and 212.4-217.9 mg/kg b.w., respectively. Significant decrease in body weights in both genders at 1150 and 2000 mg/kg groups and significant increases in relative weights of brain in both genders, liver in females, kidneys and testis in males, alkaline phosphatase and potassium in both genders at 2000 mg/kg diet were noted. Significant decrease in absolute weights of several